miladalsh/processed_scinews_dataset · Datasets at Hugging Face

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Carrier multiplication (CM) is a process in which high-energy free carriers relax by generation of additional electron-hole pairs rather than by heat dissipation. CM is promising disruptive improvements in photovoltaic energy conversion and light detection technologies. Current state-of-the-art nanomaterials including quantum dots and carbon nanotubes have demonstrated CM, but are not satisfactory owing to high-energy-loss and inherent difficulties with carrier extraction. Here, we report CM in van der Waals (vdW) MoTe 2 and WSe 2 films, and find characteristics, commencing close to the energy conservation limit and reaching up to 99% CM conversion efficiency with the standard model. This is demonstrated by ultrafast optical spectroscopy with independent approaches, photo-induced absorption, photo-induced bleach, and carrier population dynamics. Combined with a high lateral conductivity and an optimal bandgap below 1 eV, these superior CM characteristics identify vdW materials as an attractive candidate material for highly efficient and mechanically flexible solar cells in the future. Introduction Atomically thin van der Waals (vdW) layered materials are intensively investigated owing to their fascinating properties. These include exceptional mechanical flexibility and a large range of available band structures and band gaps, from true insulators (hexagonal boron nitride) down to semiconductors (transition metal dichalcogenides, TMDs) and metals (graphene). The TMD-based vdW-layered materials can also have excellent optoelectronic properties, including high in-plane charge carrier mobility. In addition, the very weak vdW bonding between individual layers allows for easy formation of multi-layered structures using the same or different materials, as the lattice matching is not important and a heterostructure with a near-perfect interface may be formed. This new dimension of nanomaterial engineering offers the possibility for a new generation of highly efficient and mechanically flexible optoelectronics. These also include thin-film, mechanically flexible solar cells, owing to band gap tunability by composition and layer thickness, high mobility and a possibility of an ultrahigh internal radiative efficiency of >99% 1 , promoted by good surface passivation and large exciton binding energy. Moreover, absorption of sunlight in semiconducting TMDs monolayers reaches typically 5–10% 2 , 3 , which is an order of magnitude larger than that in most common photovoltaic materials of Si, CdTe, and GaAs 4 . Accordingly, prototype ultrathin photovoltaic devices, a few atomic layers in thickness, have been realized using MoS 2 and WSe 2 5 . For a single photon absorption in a semiconductor, one photoexcited electron–hole pair is created and yields initial nonthermal distribution of a photoexcited carrier. The photoexcited carrier then interacts with phonon, losing energy to the lattice as heat, which is responsible for intervalley scattering of the carrier. Carrier–carrier scattering mediated by Coulomb interaction redistributes the electron energy to form a quasi-equilibrium state, which follows Fermi–Dirac distribution, responsible for intravalley scattering of the photoexcited carrier. When the excess energy of photoexcited carrier increases above the bandgap energy with strong Coulomb interaction, the photoexcited carrier obtains sufficient energy to scatter with an electron in the valence band, consequently exciting an additional electron across the bandgap to the conduction band, which is known as carrier multiplication (CM, see Fig. 1 ). CM owing to this inverse Auger process has been suggested to enhance the efficiency of a solar cell above the Shockley−Queisser limit 6 up to ~46% 7 , 8 . In bulk semiconductors, the CM process is rather inefficient and has a high threshold energy—typically exceeding 4–5 times the bandgap ( E g ) 9 , 10 . This is due to the low density of final states, limited by the momentum conservation rule, and the rapid carrier cooling by phonon scattering. The situation is different in nanostructures, where quantum confinement relaxes strict momentum conservation and could also affect carrier thermalization 10 , 11 , 12 , 13 , which competes with CM 14 . Fig. 1 Pump-probe spectroscopy of carrier multiplication (CM). a The CM process (left), and two different Auger processes identified in vdW materials. b Schematic of the differential transmittance experiment. c Steady-state absorption spectrum of the investigated 2H-MoTe 2 thin film, featuring multiple peaks, including the primary A and B excitons. An indirect bandgap ( E g ) is also marked. In the inset, the smooth background absorption has been subtracted, to better reveal the peaks at excitonic transitions. d Band structure and density of states for 2H-MoTe 2 thin-film. Full size image In general, the conversion efficiency and the threshold energy of CM in a particular material are influenced by (i) Coulomb interactions, which can be promoted by spatial confinement and dielectric screening, (ii) carrier cooling by phonon scattering, (iii) initial/final density of states, and possibly also (especially for thin films), and (iv) surface/defect trapping. The CM conversion efficiency can be promoted by (i) strong Coulomb interaction within spatially confined atomically thin (3–4 Å) layers, (ii) large exciton-binding energies of several hundred meV, much larger than those in quantum wells, and (iii) predominant lower carrier cooling rates by less electron–phonon coupling efficiency due to predominant high exciton binding energies 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 . Therefore TMDs, featuring bandgaps in the 0.7–1 eV 8 range, optimal for CM, could open a possibility by way of increasing the power conversion efficiency of solar cells above the Shockley–Queisser limit. Here, we report on the observation of the CM phenomenon in thin TMD films of 2H-MoTe 2 and 2H-WSe 2 . We demonstrate a small CM threshold energy, as low as twice the bandgap, and a high CM conversion efficiency of nearly 93%, when using the usual modeling 11 . These characteristics are superior to those obtained previously for CM in nanostructures and in bulk materials 9 , 10 , 12 , 13 , 14 , 27 . We introduced ultrafast transient absorption spectroscopy with three independent approaches: (i) photo-induced bleaching of the band-to-band absorption at the direct bandgap, (ii) photo-induced intraband absorption of free carriers, and (iii) carrier population dynamics as a function of pump photon energy. These three independent approaches yield consistent", "role": "user" }, { "content": "Physicists at the Center for Integrated Nanostructure Physics (CINAP), within the Institute for Basic Science (IBS, South Korea), have discovered an intriguing phenomenon, known as carrier multiplication (CM), in a class of semiconductors with incredible thinness, outstanding properties, and possible applications in electronics and optics. Published in Nature Communications, these new findings have the potential to boost the photovoltaics and photodetector fields, and could improve the efficiency of solar cells produced with these ultrathin materials to up to 46%. An interesting class of 2-D materials, the van der Waals layered transition metal dichalcogenides (2-D TMDs), are expected to create the next-generation of optoelectronic devices, such as solar cells, transistors, light emitting diodes (LED), etc. They consist of individual thin layers separated by very weak chemical bonds (van der Waals bonds), and have unique optical properties, high light absorption, and high carrier (electron and hole) mobility. Beyond allowing the option to tune their band gap by changing composition and layer thickness, these materials also offer an ultrahigh internal radiative efficiency of > 99%, promoted by the elimination of surface imperfections and large binding energy between carriers. Absorption of sunlight in semiconducting 2-D TMD monolayers reaches 5-10% typically, which is an order of magnitude larger than that in most common photovoltaic materials, like silicon, cadmium telluride, and gallium arsenide. Despite these ideal characteristics, however, the maximum power conversion efficiency of 2-D-TMDs solar cells has remained below 5% due to losses at the metal electrodes. The IBS team in collaboration with researchers at the University of Amsterdam aimed to overcome this drawback by exploring the CM process in these materials. CM is a very efficient way to convert light into electricity. A single photon usually excites a single electron, leaving behind an 'empty space' (hole). However, it is possible to generate two or more electron-hole pairs in particular semiconductors if the energy of the incident light is sufficiently large, more specifically, if the photon energy is twice the material's bandgap energy. While the CM phenomenon is rather inefficient in bulk semiconductors, it was expected to be very efficient in 2-D materials, but was not proved experimentally due to some technical limitations, like proper 2-D TMD synthesis and ultrafast optical measurement. In this study, the team observed CM in 2-D TMDs, namely 2H-MoTe2 and 2H-WSe2 films, for the first time; a finding that is expected to improve the current efficiency of 2-D TMD solar cells, even going beyond the Shockley-Queisser limit of 33.7%. \"Our new results contribute to the fundamental understanding of the CM phenomenon in 2-D-TMD. If one overcomes the contact losses and succeeds in developing photovoltaics with CM, their maximum power conversion efficiency could be increased up to 46%,\" says Young Hee Lee, CINAP director. \"This new nanomaterial engineering offers the possibility for a new generation of efficient, durable, and flexible solar cells.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Carrier multiplication (CM) is a process in which high-energy free carriers relax by generation of additional electron-hole pairs rather than by heat dissipation. CM is promising disruptive improvements in photovoltaic energy conversion and light detection technologies. Current state-of-the-art nanomaterials including quantum dots and carbon nanotubes have demonstrated CM, but are not satisfactory owing to high-energy-loss and inherent difficulties with carrier extraction. Here, we report CM in van der Waals (vdW) MoTe 2 and WSe 2 films, and find characteristics, commencing close to the energy conservation limit and reaching up to 99% CM conversion efficiency with the standard model. This is demonstrated by ultrafast optical spectroscopy with independent approaches, photo-induced absorption, photo-induced bleach, and carrier population dynamics. Combined with a high lateral conductivity and an optimal bandgap below 1 eV, these superior CM characteristics identify vdW materials as an attractive candidate material for highly efficient and mechanically flexible solar cells in the future. Introduction Atomically thin van der Waals (vdW) layered materials are intensively investigated owing to their fascinating properties. These include exceptional mechanical flexibility and a large range of available band structures and band gaps, from true insulators (hexagonal boron nitride) down to semiconductors (transition metal dichalcogenides, TMDs) and metals (graphene). The TMD-based vdW-layered materials can also have excellent optoelectronic properties, including high in-plane charge carrier mobility. In addition, the very weak vdW bonding between individual layers allows for easy formation of multi-layered structures using the same or different materials, as the lattice matching is not important and a heterostructure with a near-perfect interface may be formed. This new dimension of nanomaterial engineering offers the possibility for a new generation of highly efficient and mechanically flexible optoelectronics. These also include thin-film, mechanically flexible solar cells, owing to band gap tunability by composition and layer thickness, high mobility and a possibility of an ultrahigh internal radiative efficiency of >99% 1 , promoted by good surface passivation and large exciton binding energy. Moreover, absorption of sunlight in semiconducting TMDs monolayers reaches typically 5–10% 2 , 3 , which is an order of magnitude larger than that in most common photovoltaic materials of Si, CdTe, and GaAs 4 . Accordingly, prototype ultrathin photovoltaic devices, a few atomic layers in thickness, have been realized using MoS 2 and WSe 2 5 . For a single photon absorption in a semiconductor, one photoexcited electron–hole pair is created and yields initial nonthermal distribution of a photoexcited carrier. The photoexcited carrier then interacts with phonon, losing energy to the lattice as heat, which is responsible for intervalley scattering of the carrier. Carrier–carrier scattering mediated by Coulomb interaction redistributes the electron energy to form a quasi-equilibrium state, which follows Fermi–Dirac distribution, responsible for intravalley scattering of the photoexcited carrier. When the excess energy of photoexcited carrier increases above the bandgap energy with strong Coulomb interaction, the photoexcited carrier obtains sufficient energy to scatter with an electron in the valence band, consequently exciting an additional electron across the bandgap to the conduction band, which is known as carrier multiplication (CM, see Fig. 1 ). CM owing to this inverse Auger process has been suggested to enhance the efficiency of a solar cell above the Shockley−Queisser limit 6 up to ~46% 7 , 8 . In bulk semiconductors, the CM process is rather inefficient and has a high threshold energy—typically exceeding 4–5 times the bandgap ( E g ) 9 , 10 . This is due to the low density of final states, limited by the momentum conservation rule, and the rapid carrier cooling by phonon scattering. The situation is different in nanostructures, where quantum confinement relaxes strict momentum conservation and could also affect carrier thermalization 10 , 11 , 12 , 13 , which competes with CM 14 . Fig. 1 Pump-probe spectroscopy of carrier multiplication (CM). a The CM process (left), and two different Auger processes identified in vdW materials. b Schematic of the differential transmittance experiment. c Steady-state absorption spectrum of the investigated 2H-MoTe 2 thin film, featuring multiple peaks, including the primary A and B excitons. An indirect bandgap ( E g ) is also marked. In the inset, the smooth background absorption has been subtracted, to better reveal the peaks at excitonic transitions. d Band structure and density of states for 2H-MoTe 2 thin-film. Full size image In general, the conversion efficiency and the threshold energy of CM in a particular material are influenced by (i) Coulomb interactions, which can be promoted by spatial confinement and dielectric screening, (ii) carrier cooling by phonon scattering, (iii) initial/final density of states, and possibly also (especially for thin films), and (iv) surface/defect trapping. The CM conversion efficiency can be promoted by (i) strong Coulomb interaction within spatially confined atomically thin (3–4 Å) layers, (ii) large exciton-binding energies of several hundred meV, much larger than those in quantum wells, and (iii) predominant lower carrier cooling rates by less electron–phonon coupling efficiency due to predominant high exciton binding energies 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 . Therefore TMDs, featuring bandgaps in the 0.7–1 eV 8 range, optimal for CM, could open a possibility by way of increasing the power conversion efficiency of solar cells above the Shockley–Queisser limit. Here, we report on the observation of the CM phenomenon in thin TMD films of 2H-MoTe 2 and 2H-WSe 2 . We demonstrate a small CM threshold energy, as low as twice the bandgap, and a high CM conversion efficiency of nearly 93%, when using the usual modeling 11 . These characteristics are superior to those obtained previously for CM in nanostructures and in bulk materials 9 , 10 , 12 , 13 , 14 , 27 . We introduced ultrafast transient absorption spectroscopy with three independent approaches: (i) photo-induced bleaching of the band-to-band absorption at the direct bandgap, (ii) photo-induced intraband absorption of free carriers, and (iii) carrier population dynamics as a function of pump photon energy. These three independent approaches yield consistent<|im_end|> <|im_start|>assistant Physicists at the Center for Integrated Nanostructure Physics (CINAP), within the Institute for Basic Science (IBS, South Korea), have discovered an intriguing phenomenon, known as carrier multiplication (CM), in a class of semiconductors with incredible thinness, outstanding properties, and possible applications in electronics and optics. Published in Nature Communications, these new findings have the potential to boost the photovoltaics and photodetector fields, and could improve the efficiency of solar cells produced with these ultrathin materials to up to 46%. An interesting class of 2-D materials, the van der Waals layered transition metal dichalcogenides (2-D TMDs), are expected to create the next-generation of optoelectronic devices, such as solar cells, transistors, light emitting diodes (LED), etc. They consist of individual thin layers separated by very weak chemical bonds (van der Waals bonds), and have unique optical properties, high light absorption, and high carrier (electron and hole) mobility. Beyond allowing the option to tune their band gap by changing composition and layer thickness, these materials also offer an ultrahigh internal radiative efficiency of > 99%, promoted by the elimination of surface imperfections and large binding energy between carriers. Absorption of sunlight in semiconducting 2-D TMD monolayers reaches 5-10% typically, which is an order of magnitude larger than that in most common photovoltaic materials, like silicon, cadmium telluride, and gallium arsenide. Despite these ideal characteristics, however, the maximum power conversion efficiency of 2-D-TMDs solar cells has remained below 5% due to losses at the metal electrodes. The IBS team in collaboration with researchers at the University of Amsterdam aimed to overcome this drawback by exploring the CM process in these materials. CM is a very efficient way to convert light into electricity. A single photon usually excites a single electron, leaving behind an 'empty space' (hole). However, it is possible to generate two or more electron-hole pairs in particular semiconductors if the energy of the incident light is sufficiently large, more specifically, if the photon energy is twice the material's bandgap energy. While the CM phenomenon is rather inefficient in bulk semiconductors, it was expected to be very efficient in 2-D materials, but was not proved experimentally due to some technical limitations, like proper 2-D TMD synthesis and ultrafast optical measurement. In this study, the team observed CM in 2-D TMDs, namely 2H-MoTe2 and 2H-WSe2 films, for the first time; a finding that is expected to improve the current efficiency of 2-D TMD solar cells, even going beyond the Shockley-Queisser limit of 33.7%. "Our new results contribute to the fundamental understanding of the CM phenomenon in 2-D-TMD. If one overcomes the contact losses and succeeds in developing photovoltaics with CM, their maximum power conversion efficiency could be increased up to 46%," says Young Hee Lee, CINAP director. "This new nanomaterial engineering offers the possibility for a new generation of efficient, durable, and flexible solar cells." <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 51961, 47544, 320, 10190, 8, 374, 264, 1920, 304, 902, 1579, 65487, 1949, 35991, 12234, 555, 9659, 315, 5217, 17130, 87693, 13840, 4856, 1109, 555, 8798, 14091, 49686, 13, 18582, 374, 26455, 62642, 18637, 304, 4604, 93591, 292, 4907, 14747, 323, 3177, 18468, 14645, 13, 9303, 1614, 8838, 10826, 38921, 20622, 316, 2229, 82, 2737, 31228, 32094, 323, 12782, 20622, 354, 51725, 617, 21091, 18582, 11, 719, 527, 539, 58831, 56612, 311, 1579, 65487, 77401, 323, 38088, 27129, 449, 19115, 33289, 13, 5810, 11, 584, 1934, 18582, 304, 5355, 2761, 29614, 1147, 320, 17008, 54, 8, 6178, 6777, 220, 17, 323, 468, 1542, 220, 17, 12631, 11, 323, 1505, 17910, 11, 1081, 11627, 3345, 311, 279, 4907, 29711, 4017, 323, 19261, 709, 311, 220, 1484, 4, 18582, 14747, 15374, 449, 279, 5410, 1646, 13, 1115, 374, 21091, 555, 24955, 9533, 29393, 66425, 51856, 449, 9678, 20414, 11, 6685, 38973, 44225, 11, 6685, 38973, 83451, 11, 323, 19115, 7187, 30295, 13, 58752, 449, 264, 1579, 45569, 98971, 323, 459, 23669, 7200, 42510, 3770, 220, 16, 384, 53, 11, 1521, 16757, 18582, 17910, 10765, 62627, 54, 7384, 439, 459, 19411, 9322, 3769, 369, 7701, 11297, 323, 99097, 19303, 13238, 7917, 304, 279, 3938, 13, 29438, 40616, 2740, 15792, 5355, 2761, 29614, 1147, 320, 17008, 54, 8, 64241, 7384, 527, 25228, 3210, 27313, 56612, 311, 872, 27387, 6012, 13, 4314, 2997, 25363, 22936, 25152, 323, 264, 3544, 2134, 315, 2561, 7200, 14726, 323, 7200, 33251, 11, 505, 837, 1672, 42391, 320, 17757, 24346, 32732, 263, 25719, 1425, 8, 1523, 311, 5347, 1965, 1076, 1105, 320, 21086, 9501, 29953, 17356, 11968, 3422, 11, 350, 6204, 82, 8, 323, 37182, 320, 4539, 1994, 570, 578, 350, 6204, 6108, 62627, 54, 48435, 291, 7384, 649, 1101, 617, 9250, 3469, 4748, 772, 8535, 6012, 11, 2737, 1579, 304, 90649, 6900, 19115, 31139, 13, 763, 5369, 11, 279, 1633, 7621, 62627, 54, 64186, 1990, 3927, 13931, 6276, 369, 4228, 18488, 315, 7447, 48435, 291, 14726, 1701, 279, 1890, 477, 2204, 7384, 11, 439, 279, 55372, 12864, 374, 539, 3062, 323, 264, 30548, 78, 7993, 449, 264, 3221, 17453, 3836, 3834, 1253, 387, 14454, 13, 1115, 502, 13167, 315, 20622, 316, 2229, 15009, 6209, 279, 13336, 369, 264, 502, 9659, 315, 7701, 11297, 323, 99097, 19303, 3469, 4748, 772, 28429, 13, 4314, 1101, 2997, 15792, 2269, 9672, 11, 99097, 19303, 13238, 7917, 11, 56612, 311, 7200, 13225, 11716, 2968, 555, 18528, 323, 6324, 26839, 11, 1579, 31139, 323, 264, 13336, 315, 459, 37232, 1494, 1108, 5419, 12164, 1413, 15374, 315, 871, 1484, 4, 220, 16, 1174, 30026, 555, 1695, 7479, 1522, 40227, 323, 3544, 25435, 263, 11212, 4907, 13, 23674, 11, 44225, 315, 40120, 304, 5347, 1965, 1076, 287, 350, 6204, 82, 1647, 337, 5184, 25501, 11383, 220, 20, 4235, 605, 4, 220, 17, 1174, 220, 18, 1174, 902, 374, 459, 2015, 315, 26703, 8294, 1109, 430, 304, 1455, 4279, 4604, 93591, 292, 7384, 315, 12095, 11, 85090, 6777, 11, 323, 18879, 2170, 220, 19, 662, 63909, 11, 25018, 37232, 589, 258, 4604, 93591, 292, 7766, 11, 264, 2478, 25524, 13931, 304, 26839, 11, 617, 1027, 15393, 1701, 6178, 50, 220, 17, 323, 468, 1542, 220, 17, 220, 20, 662, 1789, 264, 3254, 69010, 44225, 304, 264, 87836, 11, 832, 6685, 40541, 1639, 17130, 4235, 31520, 6857, 374, 3549, 323, 36508, 2926, 2536, 69218, 8141, 315, 264, 6685, 40541, 1639, 19115, 13, 578, 6685, 40541, 1639, 19115, 1243, 84261, 449, 51923, 263, 11, 13490, 4907, 311, 279, 55372, 439, 8798, 11, 902, 374, 8647, 369, 10074, 3258, 72916, 315, 279, 19115, 13, 51961, 4235, 67085, 72916, 78926, 555, 67948, 2925, 16628, 8873, 2142, 279, 17130, 4907, 311, 1376, 264, 48844, 63359, 46780, 1614, 11, 902, 11263, 99362, 72, 4235, 6315, 582, 8141, 11, 8647, 369, 10805, 22510, 3258, 72916, 315, 279, 6685, 40541, 1639, 19115, 13, 3277, 279, 13937, 4907, 315, 6685, 40541, 1639, 19115, 12992, 3485, 279, 7200, 42510, 4907, 449, 3831, 67948, 2925, 16628, 11, 279, 6685, 40541, 1639, 19115, 94663, 14343, 4907, 311, 45577, 449, 459, 17130, 304, 279, 1062, 768, 7200, 11, 52394, 13548, 459, 5217, 17130, 4028, 279, 7200, 42510, 311, 279, 390, 23985, 7200, 11, 902, 374, 3967, 439, 19115, 47544, 320, 10190, 11, 1518, 23966, 13, 220, 16, 7609, 18582, 56612, 311, 420, 29049, 5033, 261, 1920, 706, 1027, 12090, 311, 18885, 279, 15374, 315, 264, 13238, 2849, 3485, 279, 48083, 3258, 34363, 26860, 74333, 4017, 220, 21, 709, 311, 4056, 2790, 4, 220, 22, 1174, 220, 23, 662, 763, 20155, 5347, 1965, 1076, 1105, 11, 279, 18582, 1920, 374, 4856, 64481, 323, 706, 264, 1579, 12447, 4907, 2345, 87184, 49005, 220, 19, 4235, 20, 3115, 279, 7200, 42510, 320, 469, 342, 883, 220, 24, 1174, 220, 605, 662, 1115, 374, 4245, 311, 279, 3428, 17915, 315, 1620, 5415, 11, 7347, 555, 279, 24151, 29711, 6037, 11, 323, 279, 11295, 19115, 28015, 555, 51923, 263, 72916, 13, 578, 6671, 374, 2204, 304, 51593, 47194, 11, 1405, 31228, 66678, 12234, 288, 7452, 24151, 29711, 323, 1436, 1101, 7958, 19115, 29487, 2065, 220, 605, 1174, 220, 806, 1174, 220, 717, 1174, 220, 1032, 1174, 902, 4634, 288, 449, 18582, 220, 975, 662, 23966, 13, 220, 16, 34826, 10039, 1395, 66425, 51856, 315, 19115, 47544, 320, 10190, 570, 264, 578, 18582, 1920, 320, 2414, 705, 323, 1403, 2204, 5033, 261, 11618, 11054, 304, 62627, 54, 7384, 13, 293, 328, 82149, 315, 279, 41264, 1380, 24621, 685, 9526, 13, 272, 3441, 7759, 21395, 44225, 20326, 315, 279, 27313, 220, 17, 39, 5364, 78, 6777, 220, 17, 15792, 4632, 11, 16850, 5361, 40035, 11, 2737, 279, 6156, 362, 323, 426, 25435, 2439, 13, 1556, 25636, 7200, 42510, 320, 469, 342, 883, 374, 1101, 13160, 13, 763, 279, 55959, 11, 279, 11113, 4092, 44225, 706, 1027, 33356, 291, 11, 311, 2731, 16805, 279, 40035, 520, 25435, 14338, 34692, 13, 294, 17366, 6070, 323, 17915, 315, 5415, 369, 220, 17, 39, 5364, 78, 6777, 220, 17, 15792, 2269, 9672, 13, 8797, 1404, 2217, 763, 4689, 11, 279, 14747, 15374, 323, 279, 12447, 4907, 315, 18582, 304, 264, 4040, 3769, 527, 28160, 555, 320, 72, 8, 67948, 2925, 22639, 11, 902, 649, 387, 30026, 555, 29079, 66678, 323, 2815, 47262, 23061, 11, 320, 3893, 8, 19115, 28015, 555, 51923, 263, 72916, 11, 320, 35694, 8, 2926, 6801, 992, 17915, 315, 5415, 11, 323, 11000, 1101, 320, 36046, 369, 15792, 12631, 705, 323, 320, 344, 8, 7479, 14, 755, 440, 93669, 13, 578, 18582, 14747, 15374, 649, 387, 30026, 555, 320, 72, 8, 3831, 67948, 2925, 16628, 2949, 29079, 398, 45408, 19670, 2740, 15792, 320, 18, 4235, 19, 80352, 8, 13931, 11, 320, 3893, 8, 3544, 25435, 263, 65500, 49969, 315, 3892, 7895, 757, 53, 11, 1790, 8294, 1109, 1884, 304, 31228, 48396, 11, 323, 320, 35694, 8, 96531, 4827, 19115, 28015, 7969, 555, 2753, 17130, 4235, 52801, 263, 59086, 15374, 4245, 311, 96531, 1579, 25435, 263, 11212, 49969, 220, 868, 1174, 220, 845, 1174, 220, 1114, 1174, 220, 972, 1174, 220, 777, 1174, 220, 508, 1174, 220, 1691, 1174, 220, 1313, 1174, 220, 1419, 1174, 220, 1187, 1174, 220, 914, 1174, 220, 1627, 662, 15636, 350, 6204, 82, 11, 16850, 7200, 70, 2690, 304, 279, 220, 15, 13, 22, 4235, 16, 384, 53, 220, 23, 2134, 11, 23669, 369, 18582, 11, 1436, 1825, 264, 13336, 555, 1648, 315, 7859, 279, 2410, 14747, 15374, 315, 13238, 7917, 3485, 279, 48083, 3258, 4235, 26860, 74333, 4017, 13, 5810, 11, 584, 1934, 389, 279, 22695, 315, 279, 18582, 25885, 304, 15792, 350, 6204, 12631, 315, 220, 17, 39, 5364, 78, 6777, 220, 17, 323, 220, 17, 39, 13299, 1542, 220, 17, 662, 1226, 20461, 264, 2678, 18582, 12447, 4907, 11, 439, 3428, 439, 11157, 279, 7200, 42510, 11, 323, 264, 1579, 18582, 14747, 15374, 315, 7154, 220, 6365, 13689, 994, 1701, 279, 13783, 34579, 220, 806, 662, 4314, 17910, 527, 16757, 311, 1884, 12457, 8767, 369, 18582, 304, 51593, 47194, 323, 304, 20155, 7384, 220, 24, 1174, 220, 605, 1174, 220, 717, 1174, 220, 1032, 1174, 220, 975, 1174, 220, 1544, 662, 1226, 11784, 24955, 9533, 41658, 44225, 66425, 51856, 449, 2380, 9678, 20414, 25, 320, 72, 8, 6685, 38973, 12704, 12092, 315, 279, 7200, 4791, 68775, 44225, 520, 279, 2167, 7200, 42510, 11, 320, 3893, 8, 6685, 38973, 10805, 370, 438, 44225, 315, 1949, 35991, 11, 323, 320, 35694, 8, 19115, 7187, 30295, 439, 264, 734, 315, 14155, 69010, 4907, 13, 4314, 2380, 9678, 20414, 7692, 13263, 128257, 198, 128256, 78191, 198, 67171, 292, 1705, 520, 279, 5955, 369, 50521, 64051, 7993, 28415, 320, 34, 691, 2599, 705, 2949, 279, 10181, 369, 14967, 10170, 320, 3336, 50, 11, 4987, 12126, 705, 617, 11352, 459, 41765, 25885, 11, 3967, 439, 19115, 47544, 320, 10190, 705, 304, 264, 538, 315, 5347, 1965, 1076, 1105, 449, 15400, 15792, 2136, 11, 19310, 6012, 11, 323, 3284, 8522, 304, 31591, 323, 70985, 13, 30114, 304, 22037, 26545, 11, 1521, 502, 14955, 617, 279, 4754, 311, 7916, 279, 4604, 93591, 1233, 323, 4604, 347, 295, 1279, 5151, 11, 323, 1436, 7417, 279, 15374, 315, 13238, 7917, 9124, 449, 1521, 37232, 589, 258, 7384, 311, 709, 311, 220, 2790, 14697, 1556, 7185, 538, 315, 220, 17, 9607, 7384, 11, 279, 5355, 2761, 29614, 1147, 64241, 9320, 9501, 29953, 17356, 11968, 3422, 320, 17, 9607, 350, 6204, 82, 705, 527, 3685, 311, 1893, 279, 1828, 43927, 315, 3469, 4748, 772, 8535, 7766, 11, 1778, 439, 13238, 7917, 11, 1380, 380, 1105, 11, 3177, 90556, 1891, 2601, 320, 13953, 705, 5099, 13, 2435, 6824, 315, 3927, 15792, 13931, 19180, 555, 1633, 7621, 11742, 27460, 320, 16023, 2761, 29614, 1147, 27460, 705, 323, 617, 5016, 29393, 6012, 11, 1579, 3177, 44225, 11, 323, 1579, 19115, 320, 75603, 323, 14512, 8, 31139, 13, 31886, 10923, 279, 3072, 311, 26306, 872, 7200, 13225, 555, 10223, 18528, 323, 6324, 26839, 11, 1521, 7384, 1101, 3085, 459, 37232, 1494, 1108, 5419, 12164, 1413, 15374, 315, 871, 220, 1484, 13689, 30026, 555, 279, 44032, 315, 7479, 17190, 25384, 323, 3544, 11212, 4907, 1990, 35991, 13, 22855, 66181, 315, 40120, 304, 5347, 1965, 1076, 287, 220, 17, 9607, 350, 6204, 1647, 337, 5184, 25501, 220, 20, 12, 605, 4, 11383, 11, 902, 374, 459, 2015, 315, 26703, 8294, 1109, 430, 304, 1455, 4279, 4604, 93591, 292, 7384, 11, 1093, 51692, 11, 19973, 51318, 3371, 324, 579, 11, 323, 19754, 2411, 87364, 579, 13, 18185, 1521, 10728, 17910, 11, 4869, 11, 279, 7340, 2410, 14747, 15374, 315, 220, 17, 9607, 9469, 6204, 82, 13238, 7917, 706, 14958, 3770, 220, 20, 4, 4245, 311, 18151, 520, 279, 9501, 80390, 13, 578, 358, 7497, 2128, 304, 20632, 449, 12074, 520, 279, 3907, 315, 38841, 20034, 311, 23075, 420, 88620, 555, 24919, 279, 18582, 1920, 304, 1521, 7384, 13, 18582, 374, 264, 1633, 11297, 1648, 311, 5625, 3177, 1139, 18200, 13, 362, 3254, 69010, 6118, 3521, 3695, 264, 3254, 17130, 11, 9564, 4920, 459, 364, 3274, 3634, 6, 320, 31520, 570, 4452, 11, 433, 374, 3284, 311, 7068, 1403, 477, 810, 17130, 87693, 13840, 304, 4040, 5347, 1965, 1076, 1105, 422, 279, 4907, 315, 279, 10672, 3177, 374, 40044, 3544, 11, 810, 11951, 11, 422, 279, 69010, 4907, 374, 11157, 279, 3769, 596, 7200, 42510, 4907, 13, 6104, 279, 18582, 25885, 374, 4856, 64481, 304, 20155, 5347, 1965, 1076, 1105, 11, 433, 574, 3685, 311, 387, 1633, 11297, 304, 220, 17, 9607, 7384, 11, 719, 574, 539, 19168, 9526, 750, 4245, 311, 1063, 11156, 9669, 11, 1093, 6300, 220, 17, 9607, 350, 6204, 39975, 323, 24955, 9533, 29393, 19179, 13, 763, 420, 4007, 11, 279, 2128, 13468, 18582, 304, 220, 17, 9607, 350, 6204, 82, 11, 32125, 220, 17, 39, 5364, 78, 6777, 17, 323, 220, 17, 39, 13299, 1542, 17, 12631, 11, 369, 279, 1176, 892, 26, 264, 9455, 430, 374, 3685, 311, 7417, 279, 1510, 15374, 315, 220, 17, 9607, 350, 6204, 13238, 7917, 11, 1524, 2133, 7953, 279, 48083, 3258, 12, 26860, 74333, 4017, 315, 220, 1644, 13, 22, 14697, 330, 8140, 502, 3135, 17210, 311, 279, 16188, 8830, 315, 279, 18582, 25885, 304, 220, 17, 9607, 9469, 6204, 13, 1442, 832, 927, 6716, 279, 3729, 18151, 323, 51181, 304, 11469, 4604, 93591, 1233, 449, 18582, 11, 872, 7340, 2410, 14747, 15374, 1436, 387, 7319, 709, 311, 220, 2790, 4, 1359, 2795, 13566, 1283, 68, 12336, 11, 356, 691, 2599, 7690, 13, 330, 2028, 502, 20622, 316, 2229, 15009, 6209, 279, 13336, 369, 264, 502, 9659, 315, 11297, 11, 27220, 11, 323, 19303, 13238, 7917, 1210, 220, 128257, 198 ]

2,114

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Particle transfer across the placenta has been suggested but to date, no direct evidence in real-life, human context exists. Here we report the presence of black carbon (BC) particles as part of combustion-derived particulate matter in human placentae using white-light generation under femtosecond pulsed illumination. BC is identified in all screened placentae, with an average (SD) particle count of 0.95 × 10 4 (0.66 × 10 4 ) and 2.09 × 10 4 (0.9 × 10 4 ) particles per mm 3 for low and high exposed mothers, respectively. Furthermore, the placental BC load is positively associated with mothers’ residential BC exposure during pregnancy (0.63–2.42 µg per m 3 ). Our finding that BC particles accumulate on the fetal side of the placenta suggests that ambient particulates could be transported towards the fetus and represents a potential mechanism explaining the detrimental health effects of pollution from early life onwards. Introduction Fetal development is a critical window of exposure-related susceptibility because the etiology of diseases in adulthood may have a fetal origin and may be attributed to adverse effects of in utero environmental exposures. This causality concept is known as the Developmental Origins of Health and Disease or Barker hypothesis 1 . Ambient outdoor air pollution exposure is such a detrimental environmental factor that has been identified in this context 2 , 3 . Various studies have already described associations between prenatal ambient air pollution exposure and impaired birth outcomes 4 . For instance, combustion-related PM, including BC, is associated with lower birth weight 5 , 6 , preterm birth 7 , 8 , and intrauterine growth restriction 9 , 10 . Up to now, it remains unclear how exactly adverse effects are provoked in the fetus but various potential mechanisms have been proposed including both indirect (e.g., intrauterine inflammation) and/or direct (e.g., particle translocation) manners 11 , 12 , 13 . Numerous studies have indisputably demonstrated that particulate inhalation results in health problems far beyond the lungs 14 . For example, research in different areas of the world with high 15 , moderate 16 , and low 17 ambient PM showed that long-term exposure to particulate air pollution impedes cognitive performance. Accordingly, Maher et al. 18 could detect the presence of combustion-derived nanoparticles from air pollution in the frontal cortex of autopsy brain samples. More importantly, the latter was one of the first studies that provided evidence of particle translocation in humans. Recently, we found BC particles from ambient air pollution in the urine of healthy children 19 , showing the ubiquity of this environmental contaminant having the potential to reach various organ systems. Appropriately, the question arises in which distant organs, such as the placenta, the particles originating from the systemic circulation might deposit. The placenta is a temporary organ that presents a natural barrier between mother and fetus during the entire pregnancy. While it was first considered to be an impenetrable barrier for xenobiotics, it has been shown that several environmental pollutants like alcohol and therapeutics can cross the placenta 20 , 21 . In recent years, studies were conducted to investigate whether (nano)particles can pass the placental barrier. However, these investigations are limited to in vitro cell cultures, ex vivo models and animal studies 22 , 23 . Hence, particle translocation to the human placenta following inhalation under real-life conditions is insufficiently studied while being essential in understanding the effects on fetal health 24 . Here, we postulate that BC particles are able to translocate from the mothers’ lungs to the placenta. Within this framework, we employ our recently established method for detecting carbonaceous particles based on the non-incandescence related white-light (WL) generation under femtosecond pulsed illumination 25 . The study is performed on a subset of term placentae from mothers enrolled within the ENVIR ON AGE birth cohort study and on preterm placentae from spontaneous terminated pregnancies. We report the presence of BC particles at both the fetal and maternal side of all screened term and preterm placentae. The carbonaceous nature of those particulates and their placental embedment to preclude external contamination are confirmed. In addition, the BC load from the term placentae is positively associated with the residential BC exposure of the mothers during gestation. These results suggest that ambient particulates can be transported through the placental barrier towards the fetus, even during early and vulnerable stages of pregnancy. Hence, it strengthens the hypothesis that direct effects induced by the presence of ambient combustion-related particulates are at least partially responsible for observed detrimental health effects from early life onwards. Results Experimental protocol for BC detection in placentae We used our previously established technique based on the WL generation of carbonaceous particles under femtosecond pulsed laser illumination 25 to study the presence and location of BC particles in human placenta (Fig. 1 ). Under femtosecond pulsed illumination, placental tissue generates various label-free signals including second harmonic generation (SHG) and two-photon excited autofluorescence (TPAF). The SHG signal is originating from collagen type I while the TPAF emanates from various structures, e.g., placental cells, elastin and red blood cells. Both the SHG and TPAF signals were generated simultaneously but spectrally separated and detected. The present BC particles were analyzed based on two of the characteristic WL features: (i) the emission signals saturate compared to the TPAF and SHG, which allows thresholding of the particles in each of the two detection channels, i.e., TPAF and SHG, and (ii) the emitted WL ranges over the whole visible spectrum, so the thresholded particles should be present in both channels. A flowchart of the employed protocol is depicted in Fig. 1 . Every step was designed and monitored to preclude any possible contamination. Fig. 1 Flowchart of the experimental protocol for BC detection in the placenta. a Five biopsies are taken in total, of which four on the fetal side of the placenta at distinct positions oriented according to the main blood vessel (black arrow), and one (biopsy 5) at the maternal side of biopsy 1. After sample collection, the biopsies", "role": "user" }, { "content": "A new study suggests when a pregnant woman breathes in air pollution, it can travel beyond her lungs to the placenta that guards her fetus. Pollution composed of tiny particles from car exhaust, factory smokestacks and other sources is dangerous to everyone's health, and during pregnancy it's been linked to premature births and low birth weight. But scientists don't understand why, something that could affect care for women in highly polluted areas. One theory is that the particles lodge in mom's lungs and trigger potentially harmful inflammation. Tuesday, Belgian researchers reported another possibility, that any risk might be more direct. A novel scanning technique spotted a type of particle pollution—sootlike black carbon—on placentas donated by 28 new mothers, they reported in Nature Communications. The placenta nourishes a developing fetus and tries to block damaging substances in the mother's bloodstream. The Hasselt University team found the particles accumulated on the side of the placenta closest to the fetus, near where the umbilical cord emerges. That's not proof the soot actually crossed the placenta to reach the fetus—or that it's responsible for any ill effects, cautioned Dr. Yoel Sadovsky of the University of Pittsburgh Medical Center, a leading placenta expert who wasn't involved with the new research. And it's a small study. Still, \"just finding it at the placenta is important,\" Sadovsky said. \"The next question would be how much of these black carbon particles need to be there to cause damage.\" Scientists already had some clues from animal studies that particles could reach the placenta, but Tuesday's study is a first with human placentas. The Belgian researchers developed a way to scan placenta samples using ultra-short pulses from a laser that made the black carbon particles flash a bright white light, so they could be measured. The researchers included placentas from 10 mothers who lived in areas with high pollution and 10 others from low areas. The higher the exposure to pollution, the more particles the researchers counted in the placentas. \"As the fetal organs are under full development, this might have some health risks,\" said Hasselt environment and public health specialist Tim Nawrot, the study's senior author. He is doing additional research to try to tell. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Particle transfer across the placenta has been suggested but to date, no direct evidence in real-life, human context exists. Here we report the presence of black carbon (BC) particles as part of combustion-derived particulate matter in human placentae using white-light generation under femtosecond pulsed illumination. BC is identified in all screened placentae, with an average (SD) particle count of 0.95 × 10 4 (0.66 × 10 4 ) and 2.09 × 10 4 (0.9 × 10 4 ) particles per mm 3 for low and high exposed mothers, respectively. Furthermore, the placental BC load is positively associated with mothers’ residential BC exposure during pregnancy (0.63–2.42 µg per m 3 ). Our finding that BC particles accumulate on the fetal side of the placenta suggests that ambient particulates could be transported towards the fetus and represents a potential mechanism explaining the detrimental health effects of pollution from early life onwards. Introduction Fetal development is a critical window of exposure-related susceptibility because the etiology of diseases in adulthood may have a fetal origin and may be attributed to adverse effects of in utero environmental exposures. This causality concept is known as the Developmental Origins of Health and Disease or Barker hypothesis 1 . Ambient outdoor air pollution exposure is such a detrimental environmental factor that has been identified in this context 2 , 3 . Various studies have already described associations between prenatal ambient air pollution exposure and impaired birth outcomes 4 . For instance, combustion-related PM, including BC, is associated with lower birth weight 5 , 6 , preterm birth 7 , 8 , and intrauterine growth restriction 9 , 10 . Up to now, it remains unclear how exactly adverse effects are provoked in the fetus but various potential mechanisms have been proposed including both indirect (e.g., intrauterine inflammation) and/or direct (e.g., particle translocation) manners 11 , 12 , 13 . Numerous studies have indisputably demonstrated that particulate inhalation results in health problems far beyond the lungs 14 . For example, research in different areas of the world with high 15 , moderate 16 , and low 17 ambient PM showed that long-term exposure to particulate air pollution impedes cognitive performance. Accordingly, Maher et al. 18 could detect the presence of combustion-derived nanoparticles from air pollution in the frontal cortex of autopsy brain samples. More importantly, the latter was one of the first studies that provided evidence of particle translocation in humans. Recently, we found BC particles from ambient air pollution in the urine of healthy children 19 , showing the ubiquity of this environmental contaminant having the potential to reach various organ systems. Appropriately, the question arises in which distant organs, such as the placenta, the particles originating from the systemic circulation might deposit. The placenta is a temporary organ that presents a natural barrier between mother and fetus during the entire pregnancy. While it was first considered to be an impenetrable barrier for xenobiotics, it has been shown that several environmental pollutants like alcohol and therapeutics can cross the placenta 20 , 21 . In recent years, studies were conducted to investigate whether (nano)particles can pass the placental barrier. However, these investigations are limited to in vitro cell cultures, ex vivo models and animal studies 22 , 23 . Hence, particle translocation to the human placenta following inhalation under real-life conditions is insufficiently studied while being essential in understanding the effects on fetal health 24 . Here, we postulate that BC particles are able to translocate from the mothers’ lungs to the placenta. Within this framework, we employ our recently established method for detecting carbonaceous particles based on the non-incandescence related white-light (WL) generation under femtosecond pulsed illumination 25 . The study is performed on a subset of term placentae from mothers enrolled within the ENVIR ON AGE birth cohort study and on preterm placentae from spontaneous terminated pregnancies. We report the presence of BC particles at both the fetal and maternal side of all screened term and preterm placentae. The carbonaceous nature of those particulates and their placental embedment to preclude external contamination are confirmed. In addition, the BC load from the term placentae is positively associated with the residential BC exposure of the mothers during gestation. These results suggest that ambient particulates can be transported through the placental barrier towards the fetus, even during early and vulnerable stages of pregnancy. Hence, it strengthens the hypothesis that direct effects induced by the presence of ambient combustion-related particulates are at least partially responsible for observed detrimental health effects from early life onwards. Results Experimental protocol for BC detection in placentae We used our previously established technique based on the WL generation of carbonaceous particles under femtosecond pulsed laser illumination 25 to study the presence and location of BC particles in human placenta (Fig. 1 ). Under femtosecond pulsed illumination, placental tissue generates various label-free signals including second harmonic generation (SHG) and two-photon excited autofluorescence (TPAF). The SHG signal is originating from collagen type I while the TPAF emanates from various structures, e.g., placental cells, elastin and red blood cells. Both the SHG and TPAF signals were generated simultaneously but spectrally separated and detected. The present BC particles were analyzed based on two of the characteristic WL features: (i) the emission signals saturate compared to the TPAF and SHG, which allows thresholding of the particles in each of the two detection channels, i.e., TPAF and SHG, and (ii) the emitted WL ranges over the whole visible spectrum, so the thresholded particles should be present in both channels. A flowchart of the employed protocol is depicted in Fig. 1 . Every step was designed and monitored to preclude any possible contamination. Fig. 1 Flowchart of the experimental protocol for BC detection in the placenta. a Five biopsies are taken in total, of which four on the fetal side of the placenta at distinct positions oriented according to the main blood vessel (black arrow), and one (biopsy 5) at the maternal side of biopsy 1. After sample collection, the biopsies<|im_end|> <|im_start|>assistant A new study suggests when a pregnant woman breathes in air pollution, it can travel beyond her lungs to the placenta that guards her fetus. Pollution composed of tiny particles from car exhaust, factory smokestacks and other sources is dangerous to everyone's health, and during pregnancy it's been linked to premature births and low birth weight. But scientists don't understand why, something that could affect care for women in highly polluted areas. One theory is that the particles lodge in mom's lungs and trigger potentially harmful inflammation. Tuesday, Belgian researchers reported another possibility, that any risk might be more direct. A novel scanning technique spotted a type of particle pollution—sootlike black carbon—on placentas donated by 28 new mothers, they reported in Nature Communications. The placenta nourishes a developing fetus and tries to block damaging substances in the mother's bloodstream. The Hasselt University team found the particles accumulated on the side of the placenta closest to the fetus, near where the umbilical cord emerges. That's not proof the soot actually crossed the placenta to reach the fetus—or that it's responsible for any ill effects, cautioned Dr. Yoel Sadovsky of the University of Pittsburgh Medical Center, a leading placenta expert who wasn't involved with the new research. And it's a small study. Still, "just finding it at the placenta is important," Sadovsky said. "The next question would be how much of these black carbon particles need to be there to cause damage." Scientists already had some clues from animal studies that particles could reach the placenta, but Tuesday's study is a first with human placentas. The Belgian researchers developed a way to scan placenta samples using ultra-short pulses from a laser that made the black carbon particles flash a bright white light, so they could be measured. The researchers included placentas from 10 mothers who lived in areas with high pollution and 10 others from low areas. The higher the exposure to pollution, the more particles the researchers counted in the placentas. "As the fetal organs are under full development, this might have some health risks," said Hasselt environment and public health specialist Tim Nawrot, the study's senior author. He is doing additional research to try to tell. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 36954, 8481, 4028, 279, 29960, 16985, 706, 1027, 12090, 719, 311, 2457, 11, 912, 2167, 6029, 304, 1972, 26928, 11, 3823, 2317, 6866, 13, 5810, 584, 1934, 279, 9546, 315, 3776, 12782, 320, 5002, 8, 19252, 439, 961, 315, 59333, 72286, 2598, 6468, 5030, 304, 3823, 628, 18680, 6043, 1701, 4251, 18179, 9659, 1234, 5103, 83, 974, 1321, 7893, 32424, 77052, 13, 18531, 374, 11054, 304, 682, 58677, 628, 18680, 6043, 11, 449, 459, 5578, 320, 5608, 8, 19320, 1797, 315, 220, 15, 13, 2721, 25800, 220, 605, 220, 19, 320, 15, 13, 2287, 25800, 220, 605, 220, 19, 883, 323, 220, 17, 13, 2545, 25800, 220, 605, 220, 19, 320, 15, 13, 24, 25800, 220, 605, 220, 19, 883, 19252, 824, 9653, 220, 18, 369, 3428, 323, 1579, 15246, 27698, 11, 15947, 13, 24296, 11, 279, 29960, 6430, 18531, 2865, 374, 40646, 5938, 449, 27698, 529, 20658, 18531, 14675, 2391, 20209, 320, 15, 13, 5495, 4235, 17, 13, 2983, 64012, 70, 824, 296, 220, 18, 7609, 5751, 9455, 430, 18531, 19252, 47376, 389, 279, 63746, 3185, 315, 279, 29960, 16985, 13533, 430, 35288, 2598, 24031, 1436, 387, 40460, 7119, 279, 76688, 323, 11105, 264, 4754, 17383, 26073, 279, 65069, 2890, 6372, 315, 25793, 505, 4216, 2324, 60525, 13, 29438, 435, 22029, 4500, 374, 264, 9200, 3321, 315, 14675, 14228, 88636, 1606, 279, 1880, 31226, 315, 19338, 304, 64033, 1253, 617, 264, 63746, 6371, 323, 1253, 387, 30706, 311, 31959, 6372, 315, 304, 8791, 2382, 12434, 70530, 13, 1115, 25540, 2786, 7434, 374, 3967, 439, 279, 11050, 278, 70591, 315, 6401, 323, 31974, 477, 81504, 31178, 220, 16, 662, 93279, 16166, 3805, 25793, 14675, 374, 1778, 264, 65069, 12434, 8331, 430, 706, 1027, 11054, 304, 420, 2317, 220, 17, 1174, 220, 18, 662, 40741, 7978, 617, 2736, 7633, 30257, 1990, 97128, 35288, 3805, 25793, 14675, 323, 50160, 7342, 20124, 220, 19, 662, 1789, 2937, 11, 59333, 14228, 5975, 11, 2737, 18531, 11, 374, 5938, 449, 4827, 7342, 4785, 220, 20, 1174, 220, 21, 1174, 864, 5098, 7342, 220, 22, 1174, 220, 23, 1174, 323, 50938, 29051, 483, 6650, 20020, 220, 24, 1174, 220, 605, 662, 3216, 311, 1457, 11, 433, 8625, 25420, 1268, 7041, 31959, 6372, 527, 76566, 304, 279, 76688, 719, 5370, 4754, 24717, 617, 1027, 11223, 2737, 2225, 25636, 320, 68, 1326, 2637, 50938, 29051, 483, 37140, 8, 323, 5255, 2167, 320, 68, 1326, 2637, 19320, 1380, 2588, 8, 70570, 220, 806, 1174, 220, 717, 1174, 220, 1032, 662, 86915, 7978, 617, 83975, 631, 2915, 21091, 430, 2598, 6468, 77773, 367, 3135, 304, 2890, 5435, 3117, 7953, 279, 45274, 220, 975, 662, 1789, 3187, 11, 3495, 304, 2204, 5789, 315, 279, 1917, 449, 1579, 220, 868, 1174, 24070, 220, 845, 1174, 323, 3428, 220, 1114, 35288, 5975, 8710, 430, 1317, 9860, 14675, 311, 2598, 6468, 3805, 25793, 50502, 288, 25702, 5178, 13, 63909, 11, 97268, 1880, 453, 13, 220, 972, 1436, 11388, 279, 9546, 315, 59333, 72286, 94753, 505, 3805, 25793, 304, 279, 66746, 49370, 315, 76901, 8271, 10688, 13, 4497, 23659, 11, 279, 15629, 574, 832, 315, 279, 1176, 7978, 430, 3984, 6029, 315, 19320, 1380, 2588, 304, 12966, 13, 42096, 11, 584, 1766, 18531, 19252, 505, 35288, 3805, 25793, 304, 279, 40335, 315, 9498, 2911, 220, 777, 1174, 9204, 279, 53336, 488, 315, 420, 12434, 35522, 519, 3515, 279, 4754, 311, 5662, 5370, 2942, 6067, 13, 86822, 2718, 11, 279, 3488, 48282, 304, 902, 29827, 36853, 11, 1778, 439, 279, 29960, 16985, 11, 279, 19252, 71373, 505, 279, 46417, 35855, 2643, 16946, 13, 578, 29960, 16985, 374, 264, 13643, 2942, 430, 18911, 264, 5933, 22881, 1990, 6691, 323, 76688, 2391, 279, 4553, 20209, 13, 6104, 433, 574, 1176, 6646, 311, 387, 459, 737, 2821, 17820, 481, 22881, 369, 53265, 677, 83300, 11, 433, 706, 1027, 6982, 430, 3892, 12434, 83661, 1093, 13200, 323, 9139, 88886, 649, 5425, 279, 29960, 16985, 220, 508, 1174, 220, 1691, 662, 763, 3293, 1667, 11, 7978, 1051, 13375, 311, 19874, 3508, 320, 94725, 8, 69598, 649, 1522, 279, 29960, 6430, 22881, 13, 4452, 11, 1521, 26969, 527, 7347, 311, 304, 55004, 2849, 27833, 11, 506, 41294, 4211, 323, 10065, 7978, 220, 1313, 1174, 220, 1419, 662, 32140, 11, 19320, 1380, 2588, 311, 279, 3823, 29960, 16985, 2768, 77773, 367, 1234, 1972, 26928, 4787, 374, 39413, 398, 20041, 1418, 1694, 7718, 304, 8830, 279, 6372, 389, 63746, 2890, 220, 1187, 662, 5810, 11, 584, 1772, 6468, 430, 18531, 19252, 527, 3025, 311, 1380, 23207, 505, 279, 27698, 529, 45274, 311, 279, 29960, 16985, 13, 25218, 420, 12914, 11, 584, 3539, 1057, 6051, 9749, 1749, 369, 54626, 12782, 77140, 19252, 3196, 389, 279, 2536, 86719, 438, 3380, 768, 5552, 4251, 18179, 320, 62239, 8, 9659, 1234, 5103, 83, 974, 1321, 7893, 32424, 77052, 220, 914, 662, 578, 4007, 374, 10887, 389, 264, 27084, 315, 4751, 628, 18680, 6043, 505, 27698, 37191, 2949, 279, 33891, 2871, 6328, 91688, 7342, 41944, 4007, 323, 389, 864, 5098, 628, 18680, 6043, 505, 54557, 32372, 82308, 13, 1226, 1934, 279, 9546, 315, 18531, 19252, 520, 2225, 279, 63746, 323, 50150, 3185, 315, 682, 58677, 4751, 323, 864, 5098, 628, 18680, 6043, 13, 578, 12782, 77140, 7138, 315, 1884, 2598, 24031, 323, 872, 29960, 6430, 11840, 479, 311, 864, 866, 9434, 47810, 527, 11007, 13, 763, 5369, 11, 279, 18531, 2865, 505, 279, 4751, 628, 18680, 6043, 374, 40646, 5938, 449, 279, 20658, 18531, 14675, 315, 279, 27698, 2391, 13033, 367, 13, 4314, 3135, 4284, 430, 35288, 2598, 24031, 649, 387, 40460, 1555, 279, 29960, 6430, 22881, 7119, 279, 76688, 11, 1524, 2391, 4216, 323, 20134, 18094, 315, 20209, 13, 32140, 11, 433, 96931, 279, 31178, 430, 2167, 6372, 36572, 555, 279, 9546, 315, 35288, 59333, 14228, 2598, 24031, 527, 520, 3325, 26310, 8647, 369, 13468, 65069, 2890, 6372, 505, 4216, 2324, 60525, 13, 18591, 57708, 11766, 369, 18531, 18468, 304, 628, 18680, 6043, 1226, 1511, 1057, 8767, 9749, 15105, 3196, 389, 279, 60614, 9659, 315, 12782, 77140, 19252, 1234, 5103, 83, 974, 1321, 7893, 32424, 21120, 77052, 220, 914, 311, 4007, 279, 9546, 323, 3813, 315, 18531, 19252, 304, 3823, 29960, 16985, 320, 30035, 13, 220, 16, 7609, 9636, 5103, 83, 974, 1321, 7893, 32424, 77052, 11, 29960, 6430, 20438, 27983, 5370, 2440, 12862, 17738, 2737, 2132, 82341, 9659, 320, 8758, 38, 8, 323, 1403, 63837, 26934, 12304, 45545, 10036, 4692, 36634, 320, 4334, 8440, 570, 578, 6570, 38, 8450, 374, 71373, 505, 71313, 955, 358, 1418, 279, 350, 8201, 37, 69239, 988, 505, 5370, 14726, 11, 384, 1326, 2637, 29960, 6430, 7917, 11, 92185, 258, 323, 2579, 6680, 7917, 13, 11995, 279, 6570, 38, 323, 350, 8201, 37, 17738, 1051, 8066, 25291, 719, 9618, 81, 750, 19180, 323, 16914, 13, 578, 3118, 18531, 19252, 1051, 30239, 3196, 389, 1403, 315, 279, 29683, 60614, 4519, 25, 320, 72, 8, 279, 41353, 17738, 94577, 349, 7863, 311, 279, 350, 8201, 37, 323, 6570, 38, 11, 902, 6276, 12447, 287, 315, 279, 19252, 304, 1855, 315, 279, 1403, 18468, 12006, 11, 602, 1770, 2637, 350, 8201, 37, 323, 6570, 38, 11, 323, 320, 3893, 8, 279, 48042, 60614, 21986, 927, 279, 4459, 9621, 20326, 11, 779, 279, 12447, 291, 19252, 1288, 387, 3118, 304, 2225, 12006, 13, 362, 6530, 16320, 315, 279, 20011, 11766, 374, 44894, 304, 23966, 13, 220, 16, 662, 7357, 3094, 574, 6319, 323, 41223, 311, 864, 866, 904, 3284, 47810, 13, 23966, 13, 220, 16, 23260, 16320, 315, 279, 22772, 11766, 369, 18531, 18468, 304, 279, 29960, 16985, 13, 264, 21594, 6160, 3806, 552, 527, 4529, 304, 2860, 11, 315, 902, 3116, 389, 279, 63746, 3185, 315, 279, 29960, 16985, 520, 12742, 10093, 42208, 4184, 311, 279, 1925, 6680, 27274, 320, 11708, 18404, 705, 323, 832, 320, 8385, 49292, 220, 20, 8, 520, 279, 50150, 3185, 315, 99647, 220, 16, 13, 4740, 6205, 4526, 11, 279, 6160, 3806, 552, 128257, 198, 128256, 78191, 198, 32, 502, 4007, 13533, 994, 264, 20895, 5333, 11745, 288, 304, 3805, 25793, 11, 433, 649, 5944, 7953, 1077, 45274, 311, 279, 29960, 16985, 430, 27270, 1077, 76688, 13, 96201, 24306, 315, 13987, 19252, 505, 1841, 17960, 11, 8803, 16603, 7848, 82, 323, 1023, 8336, 374, 11660, 311, 5127, 596, 2890, 11, 323, 2391, 20209, 433, 596, 1027, 10815, 311, 42227, 66332, 323, 3428, 7342, 4785, 13, 2030, 14248, 1541, 956, 3619, 3249, 11, 2555, 430, 1436, 7958, 2512, 369, 3278, 304, 7701, 95869, 5789, 13, 3861, 10334, 374, 430, 279, 19252, 60891, 304, 3450, 596, 45274, 323, 8346, 13893, 28856, 37140, 13, 7742, 11, 49162, 12074, 5068, 2500, 13336, 11, 430, 904, 5326, 2643, 387, 810, 2167, 13, 362, 11775, 36201, 15105, 30652, 264, 955, 315, 19320, 25793, 2345, 708, 354, 4908, 3776, 12782, 2345, 263, 628, 18680, 300, 34468, 555, 220, 1591, 502, 27698, 11, 814, 5068, 304, 22037, 26545, 13, 578, 29960, 16985, 46798, 21168, 264, 11469, 76688, 323, 16696, 311, 2565, 34446, 33155, 304, 279, 6691, 596, 100216, 13, 578, 43122, 3903, 3907, 2128, 1766, 279, 19252, 41165, 389, 279, 3185, 315, 279, 29960, 16985, 18585, 311, 279, 76688, 11, 3221, 1405, 279, 37781, 321, 950, 23125, 59696, 13, 3011, 596, 539, 11311, 279, 779, 354, 3604, 28129, 279, 29960, 16985, 311, 5662, 279, 76688, 51749, 430, 433, 596, 8647, 369, 904, 5986, 6372, 11, 85432, 2999, 13, 44188, 301, 31781, 79678, 315, 279, 3907, 315, 28627, 13235, 5955, 11, 264, 6522, 29960, 16985, 6335, 889, 5828, 956, 6532, 449, 279, 502, 3495, 13, 1628, 433, 596, 264, 2678, 4007, 13, 16782, 11, 330, 4345, 9455, 433, 520, 279, 29960, 16985, 374, 3062, 1359, 31781, 79678, 1071, 13, 330, 791, 1828, 3488, 1053, 387, 1268, 1790, 315, 1521, 3776, 12782, 19252, 1205, 311, 387, 1070, 311, 5353, 5674, 1210, 57116, 2736, 1047, 1063, 43775, 505, 10065, 7978, 430, 19252, 1436, 5662, 279, 29960, 16985, 11, 719, 7742, 596, 4007, 374, 264, 1176, 449, 3823, 628, 18680, 300, 13, 578, 49162, 12074, 8040, 264, 1648, 311, 8737, 29960, 16985, 10688, 1701, 24955, 69751, 66557, 505, 264, 21120, 430, 1903, 279, 3776, 12782, 19252, 8381, 264, 10107, 4251, 3177, 11, 779, 814, 1436, 387, 17303, 13, 578, 12074, 5343, 628, 18680, 300, 505, 220, 605, 27698, 889, 12439, 304, 5789, 449, 1579, 25793, 323, 220, 605, 3885, 505, 3428, 5789, 13, 578, 5190, 279, 14675, 311, 25793, 11, 279, 810, 19252, 279, 12074, 31094, 304, 279, 628, 18680, 300, 13, 330, 2170, 279, 63746, 36853, 527, 1234, 2539, 4500, 11, 420, 2643, 617, 1063, 2890, 15635, 1359, 1071, 43122, 3903, 4676, 323, 586, 2890, 24687, 9538, 90810, 4744, 11, 279, 4007, 596, 10195, 3229, 13, 1283, 374, 3815, 5217, 3495, 311, 1456, 311, 3371, 13, 220, 128257, 198 ]

1,802

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Earthquake ruptures cause mass redistribution, which is expected to induce transient gravity perturbations simultaneously at all distances from the source before the arrival of P-waves. A recent research paper reported the detection of such prompt gravity signals from the 2011 Tohoku-Oki earthquake by comparing observed acceleration waveforms and model simulations. The 11 observed waveforms presented in that paper recorded in East Asia shared a similar trend above the background seismic noise and were in good agreement with the simulations. However, the signal detection was less quantitative because the significance of the observed signals was not discussed and the waveforms at other stations in the region were not shown. In this study, similar trends were not observed in most of the data recorded near the stations used in the aforementioned study, suggesting that the reported signals were only local noises. We thus took a different approach to identify the prompt signals. We optimized the multi-channel data recorded by superconducting gravimeters, broadband seismometers, and tiltmeters. Though no signal was identified in the single-trace records, the stacked trace of the broadband seismometer array data in Japan showed a clear signal above the reduced noise level. The signal amplitude was 0.25 nm/s 2 for an average distance of 987 km from the event hypocenter. This detection was confirmed with a statistical significance of 7\\sigma 7\\sigma , where \\sigma \\sigma is the standard deviation of the amplitude of the background noise. This result provided the first constraint on the amplitude of the observed prompt signals and may serve as a reference in the detection of prompt signals in future earthquakes. Introduction Compressional seismic waves radiating from an earthquake accompany density perturbations, which give rise to widespread transient gravity perturbations \\delta \\varvec{g} \\delta \\varvec{g} , even ahead of the wave front. The interest in earthquake-induced prompt gravity perturbations has increased in terms of both theoretical prediction and data signal detection with their potential for earthquake early warning (Harms et al. 2015 ; Harms 2016 ; Montagner et al. 2016 ; Heaton 2017 ; Vallée et al. 2017 ; Kimura 2018 ; Kimura and Kame 2019 ). In this paper, “prompt” denotes the time period between the event origin time and the P-wave arrival time. Study by Montagner et al. ( 2016 ) was the first to discuss prompt gravity signals in observed data. They searched for the signal from the 2011 Mw 9.0 Tohoku-Oki earthquake in the records of a superconducting gravimeter (SG) at Kamioka (approximately 510 km from the epicenter) and five nearby broadband seismometers of the Full Range Seismograph Network of Japan (F-net). Though they failed to identify a prompt signal with an amplitude that was obviously above the background noise level, they found that the 30-s average value immediately before the P-wave arrival was more prominent than the noise level with a statistical significance greater than 99% (corresponding to approximately 3\\sigma 3\\sigma if the background noise has a normal distribution, where \\sigma \\sigma is the standard deviation of the noise). Based on this finding, they claimed the presence of a prompt gravity signal from the event. However, 99% significance seems considerably low for definite signal detection because it means that one in hundred samples exceeds a reference level; this is too frequent to claim an anomaly in time series analysis. Heaton ( 2017 ) replied to Montagner et al. ( 2016 ) with an objection that their data analysis did not include the appropriate response of the Earth. He pointed out that in the measurement of prompt gravity perturbations, the acceleration motion of the observational site \\ddot{\\varvec{u}} \\ddot{\\varvec{u}} has to be considered because the gravimeter output \\left( \\varvec{a} \\right)_{z} \\left( \\varvec{a} \\right)_{z} is affected by \\ddot{\\varvec{u}} \\ddot{\\varvec{u}} , i.e., \\left( \\varvec{a} \\right)_{z} = \\left( {\\delta \\varvec{g}} \\right)_{z} - \\left( {\\ddot{\\varvec{u}}} \\right)_{z} \\left( \\varvec{a} \\right)_{z} = \\left( {\\delta \\varvec{g}} \\right)_{z} - \\left( {\\ddot{\\varvec{u}}} \\right)_{z} , where \\left( \\varvec{x} \\right)_{z} \\left( \\varvec{x} \\right)_{z} indicates the vertical component of vector \\varvec{x} \\varvec{x} with upward being positive. He exemplified in a simple spherical Earth model that the Earth’s motion due to prompt gravity perturbations mostly decreases the gravimeter’s sensitivity. Vallée et al. ( 2017 ) reported the detection of prompt gravity signals from the 2011 event based on both data analysis and theoretical modeling. From the records of regional broadband seismic stations in the Japanese islands and the Asian continent, they selected 11 waveforms based on the study’s criteria. Nine waveforms among them showed a consistent visible downward trend starting from the origin time up to the respective P-wave arrival times (Figure 1 of Vallée et al. 2017 ). They then numerically simulated the prompt signals for the 11 stations considering the acceleration motion of the observational sites, i.e., a direct scenario based on Heaton ( 2017 ). To synthesize the sensor output \\left( \\varvec{a} \\right)_{z} \\left( \\varvec{a} \\right)_{z} , they evaluated both the gravity perturbation \\delta \\varvec{g} \\delta \\varvec{g} and the ground acceleration \\ddot{\\varvec{u}} \\ddot{\\varvec{u}} directly generated by \\delta \\varvec{g} \\delta \\varvec{g} in a semi-infinite flat Earth model. The 11 pairs of observed and synthetic waveforms showed similarities to one another (Figure 3 in Vallée et al. 2017 ). However, their signal detection was relatively less quantitative. In contrast to Montagner et al. ( 2016 ), they did not discuss the significance of the observed signals with respect to background noise. In addition, the 11 observational stations they used were only a small subset of the available approximately 200 stations. Fig. 1 a Model prediction of the prompt gravity perturbation \\left( {\\delta \\varvec{g}^{\\text{H}} } \\right)_{z} \\left( {\\delta \\varvec{g}^{\\text{H}} } \\right)_{z} (vertical component with upward positive) of the 2011 Tohoku-Oki earthquake for Kamioka Observatory. We used the infinite homogeneous Earth model of Harms et al. ( 2015 ), and no filter was applied. Time 0 was set to the event origin time t_{\\text{eq}} t_{\\text{eq}} . The P-wave arrival time on the gravimetric record is 05:47:32.4 UTC (68.1 s after t_{\\text{eq}} t_{\\text{eq}} ). b Distribution of the prompt gravity perturbation \\left( {\\delta \\varvec{g}^{\\text{H}} } \\right)_{z} \\left( {\\delta", "role": "user" }, { "content": "Every year, earthquakes worldwide claim hundreds or even thousands of lives. Forewarning allows people to head for safety and a matter of seconds could spell the difference between life and death. UTokyo researchers have demonstrated a new earthquake detection method—their technique exploits subtle telltale gravitational signals traveling ahead of the tremors. Future research could boost early warning systems. The shock of the 2011 Tohoku earthquake in eastern Japan still resonates for many. It caused unimaginable devastation, but also generated vast amounts of seismic and other kinds of data. Years later, researchers still mine this data to improve models and find novel ways to use it, which could help people in the future. A team of researchers from the University of Tokyo's Earthquake Research Institute (ERI) found something in this data that could advance earthquake prediction research and might someday even save lives. It all started when ERI Associate Professor Shingo Watada read an interesting physics paper on an unrelated topic by J. Harms from Istituto Nazionale di Fisica Nucleare in Italy. The paper suggests gravimeters—sensors that measure the strength of local gravity—could theoretically detect earthquakes. \"This got me thinking,\" said Watada. \"If we have enough seismic and gravitational data from the time and place that a big earthquake hits, we could learn to detect earthquakes with gravimeters as well as seismometers. This could be an important tool for future research of seismic phenomena.\" Contour maps depict changes in gravity gradient immediately before the earthquake hits.The epicenter of the 2011 Tohoku earthquake is marked by (✩) Credit: ©2019 Kimura Masaya The idea works like this: Earthquakes occur when a point along the edge of a tectonic plate comprising the Earth's surface makes a sudden movement. This generates seismic waves that radiate from that point at six to eight kilometers per second. These waves transmit energy through the Earth and rapidly alter the density of the subsurface material they pass through. Dense material imparts a slightly greater gravitational attraction than less dense material. As gravity propagates at light speed, sensitive gravimeters can pick up these changes in density ahead of the seismic waves' arrival. \"This is the first time anyone has shown definitive earthquake signals with such a method. Others have investigated the idea, yet not found reliable signals,\" said ERI postgraduate Masaya Kimura. \"Our approach is unique, as we examined a broader range of sensors active during the 2011 earthquake. And we used special processing methods to isolate quiet gravitational signals from the noisy data.\" Japan is very seismically active, so it's no surprise there are extensive networks of seismic instruments on land and at sea in the region. The researchers used a range of seismic data from these, as well as superconducting gravimeters (SGs) in Kamioka, Gifu Prefecture, and Matsushiro, Nagano Prefecture, in central Japan. A TOBA with door open to reveal cryogenically cooled sensor platform inside. Credit: ©2019 Ando Masaki The signal analysis they performed was extremely reliable scoring what scientists term a 7-sigma accuracy, meaning there is only a one-in-a-trillion chance a result is incorrect. The researchers say this proves the concept and will be useful in the calibration of future instruments built specifically to detect earthquakes. Associate Professor Masaki Ando from the Department of Physics invented a novel kind of gravimeter, the torsion bar antenna (TOBA), which aims to be the first such instrument. \"SGs and seismometers are not ideal, as the sensors within them move together with the instrument, which almost cancels subtle signals from earthquakes,\" explained ERI Associate Professor Nobuki Kame. \"This is known as an Einstein's elevator, or the equivalence principle. However, the TOBA will overcome this problem. It senses changes in gravity gradient despite motion. It was originally designed to detect gravitational waves from the Big Bang, like 'earthquakes' in space, but our purpose is more down to Earth.\" The team dreams of a network of TOBA distributed around seismically active regions, an early warning system that could alert people 10 seconds before the first ground shaking waves arrive from an epicenter 100 kilometers away. Many earthquake deaths occur as people are caught off-guard inside buildings that collapse on them. Imagine the difference 10 seconds could make. This will take time, but the researchers continually refine models to improve accuracy of the method for eventual use in the field. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Earthquake ruptures cause mass redistribution, which is expected to induce transient gravity perturbations simultaneously at all distances from the source before the arrival of P-waves. A recent research paper reported the detection of such prompt gravity signals from the 2011 Tohoku-Oki earthquake by comparing observed acceleration waveforms and model simulations. The 11 observed waveforms presented in that paper recorded in East Asia shared a similar trend above the background seismic noise and were in good agreement with the simulations. However, the signal detection was less quantitative because the significance of the observed signals was not discussed and the waveforms at other stations in the region were not shown. In this study, similar trends were not observed in most of the data recorded near the stations used in the aforementioned study, suggesting that the reported signals were only local noises. We thus took a different approach to identify the prompt signals. We optimized the multi-channel data recorded by superconducting gravimeters, broadband seismometers, and tiltmeters. Though no signal was identified in the single-trace records, the stacked trace of the broadband seismometer array data in Japan showed a clear signal above the reduced noise level. The signal amplitude was 0.25 nm/s 2 for an average distance of 987 km from the event hypocenter. This detection was confirmed with a statistical significance of 7\sigma 7\sigma , where \sigma \sigma is the standard deviation of the amplitude of the background noise. This result provided the first constraint on the amplitude of the observed prompt signals and may serve as a reference in the detection of prompt signals in future earthquakes. Introduction Compressional seismic waves radiating from an earthquake accompany density perturbations, which give rise to widespread transient gravity perturbations \delta \varvec{g} \delta \varvec{g} , even ahead of the wave front. The interest in earthquake-induced prompt gravity perturbations has increased in terms of both theoretical prediction and data signal detection with their potential for earthquake early warning (Harms et al. 2015 ; Harms 2016 ; Montagner et al. 2016 ; Heaton 2017 ; Vallée et al. 2017 ; Kimura 2018 ; Kimura and Kame 2019 ). In this paper, “prompt” denotes the time period between the event origin time and the P-wave arrival time. Study by Montagner et al. ( 2016 ) was the first to discuss prompt gravity signals in observed data. They searched for the signal from the 2011 Mw 9.0 Tohoku-Oki earthquake in the records of a superconducting gravimeter (SG) at Kamioka (approximately 510 km from the epicenter) and five nearby broadband seismometers of the Full Range Seismograph Network of Japan (F-net). Though they failed to identify a prompt signal with an amplitude that was obviously above the background noise level, they found that the 30-s average value immediately before the P-wave arrival was more prominent than the noise level with a statistical significance greater than 99% (corresponding to approximately 3\sigma 3\sigma if the background noise has a normal distribution, where \sigma \sigma is the standard deviation of the noise). Based on this finding, they claimed the presence of a prompt gravity signal from the event. However, 99% significance seems considerably low for definite signal detection because it means that one in hundred samples exceeds a reference level; this is too frequent to claim an anomaly in time series analysis. Heaton ( 2017 ) replied to Montagner et al. ( 2016 ) with an objection that their data analysis did not include the appropriate response of the Earth. He pointed out that in the measurement of prompt gravity perturbations, the acceleration motion of the observational site \ddot{\varvec{u}} \ddot{\varvec{u}} has to be considered because the gravimeter output \left( \varvec{a} \right)_{z} \left( \varvec{a} \right)_{z} is affected by \ddot{\varvec{u}} \ddot{\varvec{u}} , i.e., \left( \varvec{a} \right)_{z} = \left( {\delta \varvec{g}} \right)_{z} - \left( {\ddot{\varvec{u}}} \right)_{z} \left( \varvec{a} \right)_{z} = \left( {\delta \varvec{g}} \right)_{z} - \left( {\ddot{\varvec{u}}} \right)_{z} , where \left( \varvec{x} \right)_{z} \left( \varvec{x} \right)_{z} indicates the vertical component of vector \varvec{x} \varvec{x} with upward being positive. He exemplified in a simple spherical Earth model that the Earth’s motion due to prompt gravity perturbations mostly decreases the gravimeter’s sensitivity. Vallée et al. ( 2017 ) reported the detection of prompt gravity signals from the 2011 event based on both data analysis and theoretical modeling. From the records of regional broadband seismic stations in the Japanese islands and the Asian continent, they selected 11 waveforms based on the study’s criteria. Nine waveforms among them showed a consistent visible downward trend starting from the origin time up to the respective P-wave arrival times (Figure 1 of Vallée et al. 2017 ). They then numerically simulated the prompt signals for the 11 stations considering the acceleration motion of the observational sites, i.e., a direct scenario based on Heaton ( 2017 ). To synthesize the sensor output \left( \varvec{a} \right)_{z} \left( \varvec{a} \right)_{z} , they evaluated both the gravity perturbation \delta \varvec{g} \delta \varvec{g} and the ground acceleration \ddot{\varvec{u}} \ddot{\varvec{u}} directly generated by \delta \varvec{g} \delta \varvec{g} in a semi-infinite flat Earth model. The 11 pairs of observed and synthetic waveforms showed similarities to one another (Figure 3 in Vallée et al. 2017 ). However, their signal detection was relatively less quantitative. In contrast to Montagner et al. ( 2016 ), they did not discuss the significance of the observed signals with respect to background noise. In addition, the 11 observational stations they used were only a small subset of the available approximately 200 stations. Fig. 1 a Model prediction of the prompt gravity perturbation \left( {\delta \varvec{g}^{\text{H}} } \right)_{z} \left( {\delta \varvec{g}^{\text{H}} } \right)_{z} (vertical component with upward positive) of the 2011 Tohoku-Oki earthquake for Kamioka Observatory. We used the infinite homogeneous Earth model of Harms et al. ( 2015 ), and no filter was applied. Time 0 was set to the event origin time t_{\text{eq}} t_{\text{eq}} . The P-wave arrival time on the gravimetric record is 05:47:32.4 UTC (68.1 s after t_{\text{eq}} t_{\text{eq}} ). b Distribution of the prompt gravity perturbation \left( {\delta \varvec{g}^{\text{H}} } \right)_{z} \left( {\delta<|im_end|> <|im_start|>assistant Every year, earthquakes worldwide claim hundreds or even thousands of lives. Forewarning allows people to head for safety and a matter of seconds could spell the difference between life and death. UTokyo researchers have demonstrated a new earthquake detection method—their technique exploits subtle telltale gravitational signals traveling ahead of the tremors. Future research could boost early warning systems. The shock of the 2011 Tohoku earthquake in eastern Japan still resonates for many. It caused unimaginable devastation, but also generated vast amounts of seismic and other kinds of data. Years later, researchers still mine this data to improve models and find novel ways to use it, which could help people in the future. A team of researchers from the University of Tokyo's Earthquake Research Institute (ERI) found something in this data that could advance earthquake prediction research and might someday even save lives. It all started when ERI Associate Professor Shingo Watada read an interesting physics paper on an unrelated topic by J. Harms from Istituto Nazionale di Fisica Nucleare in Italy. The paper suggests gravimeters—sensors that measure the strength of local gravity—could theoretically detect earthquakes. "This got me thinking," said Watada. "If we have enough seismic and gravitational data from the time and place that a big earthquake hits, we could learn to detect earthquakes with gravimeters as well as seismometers. This could be an important tool for future research of seismic phenomena." Contour maps depict changes in gravity gradient immediately before the earthquake hits.The epicenter of the 2011 Tohoku earthquake is marked by (✩) Credit: ©2019 Kimura Masaya The idea works like this: Earthquakes occur when a point along the edge of a tectonic plate comprising the Earth's surface makes a sudden movement. This generates seismic waves that radiate from that point at six to eight kilometers per second. These waves transmit energy through the Earth and rapidly alter the density of the subsurface material they pass through. Dense material imparts a slightly greater gravitational attraction than less dense material. As gravity propagates at light speed, sensitive gravimeters can pick up these changes in density ahead of the seismic waves' arrival. "This is the first time anyone has shown definitive earthquake signals with such a method. Others have investigated the idea, yet not found reliable signals," said ERI postgraduate Masaya Kimura. "Our approach is unique, as we examined a broader range of sensors active during the 2011 earthquake. And we used special processing methods to isolate quiet gravitational signals from the noisy data." Japan is very seismically active, so it's no surprise there are extensive networks of seismic instruments on land and at sea in the region. The researchers used a range of seismic data from these, as well as superconducting gravimeters (SGs) in Kamioka, Gifu Prefecture, and Matsushiro, Nagano Prefecture, in central Japan. A TOBA with door open to reveal cryogenically cooled sensor platform inside. Credit: ©2019 Ando Masaki The signal analysis they performed was extremely reliable scoring what scientists term a 7-sigma accuracy, meaning there is only a one-in-a-trillion chance a result is incorrect. The researchers say this proves the concept and will be useful in the calibration of future instruments built specifically to detect earthquakes. Associate Professor Masaki Ando from the Department of Physics invented a novel kind of gravimeter, the torsion bar antenna (TOBA), which aims to be the first such instrument. "SGs and seismometers are not ideal, as the sensors within them move together with the instrument, which almost cancels subtle signals from earthquakes," explained ERI Associate Professor Nobuki Kame. "This is known as an Einstein's elevator, or the equivalence principle. However, the TOBA will overcome this problem. It senses changes in gravity gradient despite motion. It was originally designed to detect gravitational waves from the Big Bang, like 'earthquakes' in space, but our purpose is more down to Earth." The team dreams of a network of TOBA distributed around seismically active regions, an early warning system that could alert people 10 seconds before the first ground shaking waves arrive from an epicenter 100 kilometers away. Many earthquake deaths occur as people are caught off-guard inside buildings that collapse on them. Imagine the difference 10 seconds could make. This will take time, but the researchers continually refine models to improve accuracy of the method for eventual use in the field. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 9420, 67818, 61053, 1439, 5353, 3148, 72160, 11, 902, 374, 3685, 311, 49853, 41658, 24128, 18713, 9225, 811, 25291, 520, 682, 27650, 505, 279, 2592, 1603, 279, 19163, 315, 393, 2695, 4798, 13, 362, 3293, 3495, 5684, 5068, 279, 18468, 315, 1778, 10137, 24128, 17738, 505, 279, 220, 679, 16, 2057, 71, 16900, 24540, 6780, 38413, 555, 27393, 13468, 31903, 12330, 10008, 323, 1646, 47590, 13, 578, 220, 806, 13468, 12330, 10008, 10666, 304, 430, 5684, 12715, 304, 6460, 13936, 6222, 264, 4528, 9327, 3485, 279, 4092, 72579, 12248, 323, 1051, 304, 1695, 9306, 449, 279, 47590, 13, 4452, 11, 279, 8450, 18468, 574, 2753, 47616, 1606, 279, 26431, 315, 279, 13468, 17738, 574, 539, 14407, 323, 279, 12330, 10008, 520, 1023, 17789, 304, 279, 5654, 1051, 539, 6982, 13, 763, 420, 4007, 11, 4528, 18845, 1051, 539, 13468, 304, 1455, 315, 279, 828, 12715, 3221, 279, 17789, 1511, 304, 279, 46752, 4007, 11, 23377, 430, 279, 5068, 17738, 1051, 1193, 2254, 58448, 13, 1226, 8617, 3952, 264, 2204, 5603, 311, 10765, 279, 10137, 17738, 13, 1226, 34440, 279, 7447, 54968, 828, 12715, 555, 2307, 77752, 287, 29059, 55336, 11, 41925, 513, 2191, 33504, 11, 323, 37300, 76, 2481, 13, 18056, 912, 8450, 574, 11054, 304, 279, 3254, 10398, 580, 7576, 11, 279, 42415, 11917, 315, 279, 41925, 513, 2191, 21037, 1358, 828, 304, 6457, 8710, 264, 2867, 8450, 3485, 279, 11293, 12248, 2237, 13, 578, 8450, 45209, 574, 220, 15, 13, 914, 26807, 2754, 220, 17, 369, 459, 5578, 6138, 315, 220, 22207, 13437, 505, 279, 1567, 67586, 1992, 13, 1115, 18468, 574, 11007, 449, 264, 29564, 26431, 315, 220, 22, 59, 25956, 220, 22, 59, 25956, 1174, 1405, 1144, 25956, 1144, 25956, 374, 279, 5410, 38664, 315, 279, 45209, 315, 279, 4092, 12248, 13, 1115, 1121, 3984, 279, 1176, 22295, 389, 279, 45209, 315, 279, 13468, 10137, 17738, 323, 1253, 8854, 439, 264, 5905, 304, 279, 18468, 315, 10137, 17738, 304, 3938, 66579, 13, 29438, 1219, 1911, 4001, 72579, 17301, 12164, 1113, 505, 459, 38413, 19780, 17915, 18713, 9225, 811, 11, 902, 3041, 10205, 311, 24716, 41658, 24128, 18713, 9225, 811, 1144, 20869, 1144, 959, 4175, 90, 70, 92, 1144, 20869, 1144, 959, 4175, 90, 70, 92, 1174, 1524, 8469, 315, 279, 12330, 4156, 13, 578, 2802, 304, 38413, 38973, 10137, 24128, 18713, 9225, 811, 706, 7319, 304, 3878, 315, 2225, 32887, 20212, 323, 828, 8450, 18468, 449, 872, 4754, 369, 38413, 4216, 10163, 320, 39, 16293, 1880, 453, 13, 220, 679, 20, 2652, 5340, 1026, 220, 679, 21, 2652, 9995, 40538, 1880, 453, 13, 220, 679, 21, 2652, 1283, 24444, 220, 679, 22, 2652, 79763, 8047, 1880, 453, 13, 220, 679, 22, 2652, 13818, 5808, 220, 679, 23, 2652, 13818, 5808, 323, 735, 373, 220, 679, 24, 7609, 763, 420, 5684, 11, 1054, 41681, 863, 72214, 279, 892, 4261, 1990, 279, 1567, 6371, 892, 323, 279, 393, 89354, 19163, 892, 13, 19723, 555, 9995, 40538, 1880, 453, 13, 320, 220, 679, 21, 883, 574, 279, 1176, 311, 4358, 10137, 24128, 17738, 304, 13468, 828, 13, 2435, 27600, 369, 279, 8450, 505, 279, 220, 679, 16, 386, 86, 220, 24, 13, 15, 2057, 71, 16900, 24540, 6780, 38413, 304, 279, 7576, 315, 264, 2307, 77752, 287, 29059, 26402, 320, 7939, 8, 520, 99966, 31866, 320, 97836, 220, 15633, 13437, 505, 279, 25706, 1992, 8, 323, 4330, 14373, 41925, 513, 2191, 33504, 315, 279, 8797, 16842, 1369, 2191, 3257, 8304, 315, 6457, 320, 37, 67596, 570, 18056, 814, 4745, 311, 10765, 264, 10137, 8450, 449, 459, 45209, 430, 574, 14224, 3485, 279, 4092, 12248, 2237, 11, 814, 1766, 430, 279, 220, 966, 1355, 5578, 907, 7214, 1603, 279, 393, 89354, 19163, 574, 810, 21102, 1109, 279, 12248, 2237, 449, 264, 29564, 26431, 7191, 1109, 220, 1484, 4, 320, 6133, 6961, 287, 311, 13489, 220, 18, 59, 25956, 220, 18, 59, 25956, 422, 279, 4092, 12248, 706, 264, 4725, 8141, 11, 1405, 1144, 25956, 1144, 25956, 374, 279, 5410, 38664, 315, 279, 12248, 570, 20817, 389, 420, 9455, 11, 814, 11922, 279, 9546, 315, 264, 10137, 24128, 8450, 505, 279, 1567, 13, 4452, 11, 220, 1484, 4, 26431, 5084, 33452, 3428, 369, 44870, 8450, 18468, 1606, 433, 3445, 430, 832, 304, 7895, 10688, 36375, 264, 5905, 2237, 26, 420, 374, 2288, 21420, 311, 3802, 459, 64048, 304, 892, 4101, 6492, 13, 1283, 24444, 320, 220, 679, 22, 883, 20592, 311, 9995, 40538, 1880, 453, 13, 320, 220, 679, 21, 883, 449, 459, 46655, 430, 872, 828, 6492, 1550, 539, 2997, 279, 8475, 2077, 315, 279, 9420, 13, 1283, 14618, 704, 430, 304, 279, 19179, 315, 10137, 24128, 18713, 9225, 811, 11, 279, 31903, 11633, 315, 279, 90380, 2816, 1144, 634, 354, 36802, 959, 4175, 90, 84, 3500, 1144, 634, 354, 36802, 959, 4175, 90, 84, 3500, 706, 311, 387, 6646, 1606, 279, 29059, 26402, 2612, 1144, 2414, 7, 1144, 959, 4175, 90, 64, 92, 1144, 1315, 8, 15511, 89, 92, 1144, 2414, 7, 1144, 959, 4175, 90, 64, 92, 1144, 1315, 8, 15511, 89, 92, 374, 11754, 555, 1144, 634, 354, 36802, 959, 4175, 90, 84, 3500, 1144, 634, 354, 36802, 959, 4175, 90, 84, 3500, 1174, 602, 1770, 2637, 1144, 2414, 7, 1144, 959, 4175, 90, 64, 92, 1144, 1315, 8, 15511, 89, 92, 284, 1144, 2414, 7, 29252, 20869, 1144, 959, 4175, 90, 70, 3500, 1144, 1315, 8, 15511, 89, 92, 482, 1144, 2414, 7, 29252, 634, 354, 36802, 959, 4175, 90, 84, 76642, 1144, 1315, 8, 15511, 89, 92, 1144, 2414, 7, 1144, 959, 4175, 90, 64, 92, 1144, 1315, 8, 15511, 89, 92, 284, 1144, 2414, 7, 29252, 20869, 1144, 959, 4175, 90, 70, 3500, 1144, 1315, 8, 15511, 89, 92, 482, 1144, 2414, 7, 29252, 634, 354, 36802, 959, 4175, 90, 84, 76642, 1144, 1315, 8, 15511, 89, 92, 1174, 1405, 1144, 2414, 7, 1144, 959, 4175, 46440, 92, 1144, 1315, 8, 15511, 89, 92, 1144, 2414, 7, 1144, 959, 4175, 46440, 92, 1144, 1315, 8, 15511, 89, 92, 15151, 279, 12414, 3777, 315, 4724, 1144, 959, 4175, 46440, 92, 1144, 959, 4175, 46440, 92, 449, 40872, 1694, 6928, 13, 1283, 39039, 1908, 304, 264, 4382, 65251, 9420, 1646, 430, 279, 9420, 753, 11633, 4245, 311, 10137, 24128, 18713, 9225, 811, 10213, 43154, 279, 29059, 26402, 753, 27541, 13, 79763, 8047, 1880, 453, 13, 320, 220, 679, 22, 883, 5068, 279, 18468, 315, 10137, 24128, 17738, 505, 279, 220, 679, 16, 1567, 3196, 389, 2225, 828, 6492, 323, 32887, 34579, 13, 5659, 279, 7576, 315, 15481, 41925, 72579, 17789, 304, 279, 11002, 30100, 323, 279, 14875, 32843, 11, 814, 4183, 220, 806, 12330, 10008, 3196, 389, 279, 4007, 753, 13186, 13, 38166, 12330, 10008, 4315, 1124, 8710, 264, 13263, 9621, 45578, 9327, 6041, 505, 279, 6371, 892, 709, 311, 279, 20081, 393, 89354, 19163, 3115, 320, 22804, 220, 16, 315, 79763, 8047, 1880, 453, 13, 220, 679, 22, 7609, 2435, 1243, 8015, 2740, 46836, 279, 10137, 17738, 369, 279, 220, 806, 17789, 13126, 279, 31903, 11633, 315, 279, 90380, 6732, 11, 602, 1770, 2637, 264, 2167, 15398, 3196, 389, 1283, 24444, 320, 220, 679, 22, 7609, 2057, 6925, 27985, 279, 12271, 2612, 1144, 2414, 7, 1144, 959, 4175, 90, 64, 92, 1144, 1315, 8, 15511, 89, 92, 1144, 2414, 7, 1144, 959, 4175, 90, 64, 92, 1144, 1315, 8, 15511, 89, 92, 1174, 814, 26126, 2225, 279, 24128, 18713, 65916, 1144, 20869, 1144, 959, 4175, 90, 70, 92, 1144, 20869, 1144, 959, 4175, 90, 70, 92, 323, 279, 5015, 31903, 1144, 634, 354, 36802, 959, 4175, 90, 84, 3500, 1144, 634, 354, 36802, 959, 4175, 90, 84, 3500, 6089, 8066, 555, 1144, 20869, 1144, 959, 4175, 90, 70, 92, 1144, 20869, 1144, 959, 4175, 90, 70, 92, 304, 264, 18768, 3502, 26806, 10269, 9420, 1646, 13, 578, 220, 806, 13840, 315, 13468, 323, 28367, 12330, 10008, 8710, 43874, 311, 832, 2500, 320, 22804, 220, 18, 304, 79763, 8047, 1880, 453, 13, 220, 679, 22, 7609, 4452, 11, 872, 8450, 18468, 574, 12309, 2753, 47616, 13, 763, 13168, 311, 9995, 40538, 1880, 453, 13, 320, 220, 679, 21, 7026, 814, 1550, 539, 4358, 279, 26431, 315, 279, 13468, 17738, 449, 5201, 311, 4092, 12248, 13, 763, 5369, 11, 279, 220, 806, 90380, 17789, 814, 1511, 1051, 1193, 264, 2678, 27084, 315, 279, 2561, 13489, 220, 1049, 17789, 13, 23966, 13, 220, 16, 264, 5008, 20212, 315, 279, 10137, 24128, 18713, 65916, 1144, 2414, 7, 29252, 20869, 1144, 959, 4175, 90, 70, 92, 61, 36802, 1342, 90, 39, 3500, 335, 1144, 1315, 8, 15511, 89, 92, 1144, 2414, 7, 29252, 20869, 1144, 959, 4175, 90, 70, 92, 61, 36802, 1342, 90, 39, 3500, 335, 1144, 1315, 8, 15511, 89, 92, 320, 15651, 3777, 449, 40872, 6928, 8, 315, 279, 220, 679, 16, 2057, 71, 16900, 24540, 6780, 38413, 369, 99966, 31866, 58974, 13, 1226, 1511, 279, 24746, 87282, 9420, 1646, 315, 5340, 1026, 1880, 453, 13, 320, 220, 679, 20, 7026, 323, 912, 4141, 574, 9435, 13, 4212, 220, 15, 574, 743, 311, 279, 1567, 6371, 892, 259, 15511, 59, 1342, 90, 11251, 3500, 259, 15511, 59, 1342, 90, 11251, 3500, 662, 578, 393, 89354, 19163, 892, 389, 279, 29059, 318, 16743, 3335, 374, 220, 2304, 25, 2618, 25, 843, 13, 19, 28503, 320, 2614, 13, 16, 274, 1306, 259, 15511, 59, 1342, 90, 11251, 3500, 259, 15511, 59, 1342, 90, 11251, 3500, 7609, 293, 35009, 315, 279, 10137, 24128, 18713, 65916, 1144, 2414, 7, 29252, 20869, 1144, 959, 4175, 90, 70, 92, 61, 36802, 1342, 90, 39, 3500, 335, 1144, 1315, 8, 15511, 89, 92, 1144, 2414, 7, 29252, 20869, 128257, 198, 128256, 78191, 198, 11769, 1060, 11, 66579, 15603, 3802, 11758, 477, 1524, 9214, 315, 6439, 13, 8371, 19464, 6276, 1274, 311, 2010, 369, 7296, 323, 264, 5030, 315, 6622, 1436, 13141, 279, 6811, 1990, 2324, 323, 4648, 13, 26639, 564, 16417, 12074, 617, 21091, 264, 502, 38413, 18468, 1749, 22416, 404, 15105, 63488, 27545, 3371, 83, 1604, 71019, 17738, 21646, 8469, 315, 279, 18659, 1105, 13, 12781, 3495, 1436, 7916, 4216, 10163, 6067, 13, 578, 10988, 315, 279, 220, 679, 16, 2057, 71, 16900, 38413, 304, 24024, 6457, 2103, 29280, 988, 369, 1690, 13, 1102, 9057, 87212, 481, 83015, 11, 719, 1101, 8066, 13057, 15055, 315, 72579, 323, 1023, 13124, 315, 828, 13, 23116, 3010, 11, 12074, 2103, 10705, 420, 828, 311, 7417, 4211, 323, 1505, 11775, 5627, 311, 1005, 433, 11, 902, 1436, 1520, 1274, 304, 279, 3938, 13, 362, 2128, 315, 12074, 505, 279, 3907, 315, 27286, 596, 9420, 67818, 8483, 10181, 320, 643, 40, 8, 1766, 2555, 304, 420, 828, 430, 1436, 12178, 38413, 20212, 3495, 323, 2643, 54108, 1524, 3665, 6439, 13, 1102, 682, 3940, 994, 469, 4403, 33468, 17054, 1443, 29008, 21350, 2649, 1373, 459, 7185, 22027, 5684, 389, 459, 46305, 8712, 555, 622, 13, 5340, 1026, 505, 358, 3781, 1564, 29874, 56797, 1891, 435, 285, 3074, 452, 22935, 548, 304, 15704, 13, 578, 5684, 13533, 29059, 55336, 2345, 82, 27627, 430, 6767, 279, 8333, 315, 2254, 24128, 2345, 29177, 63234, 11388, 66579, 13, 330, 2028, 2751, 757, 7422, 1359, 1071, 21350, 2649, 13, 330, 2746, 584, 617, 3403, 72579, 323, 71019, 828, 505, 279, 892, 323, 2035, 430, 264, 2466, 38413, 13280, 11, 584, 1436, 4048, 311, 11388, 66579, 449, 29059, 55336, 439, 1664, 439, 513, 2191, 33504, 13, 1115, 1436, 387, 459, 3062, 5507, 369, 3938, 3495, 315, 72579, 44247, 1210, 2140, 414, 14370, 43504, 4442, 304, 24128, 20779, 7214, 1603, 279, 38413, 13280, 11829, 25706, 1992, 315, 279, 220, 679, 16, 2057, 71, 16900, 38413, 374, 13160, 555, 320, 38798, 102, 8, 16666, 25, 7388, 679, 24, 13818, 5808, 20459, 12874, 578, 4623, 4375, 1093, 420, 25, 9420, 447, 2094, 12446, 994, 264, 1486, 3235, 279, 6964, 315, 264, 259, 440, 14338, 12235, 46338, 279, 9420, 596, 7479, 3727, 264, 11210, 7351, 13, 1115, 27983, 72579, 17301, 430, 12164, 349, 505, 430, 1486, 520, 4848, 311, 8223, 41668, 824, 2132, 13, 4314, 17301, 30382, 4907, 1555, 279, 9420, 323, 19019, 11857, 279, 17915, 315, 279, 5258, 10730, 3769, 814, 1522, 1555, 13, 43622, 3769, 3242, 7183, 264, 10284, 7191, 71019, 33464, 1109, 2753, 29050, 3769, 13, 1666, 24128, 17425, 988, 520, 3177, 4732, 11, 16614, 29059, 55336, 649, 3820, 709, 1521, 4442, 304, 17915, 8469, 315, 279, 72579, 17301, 6, 19163, 13, 330, 2028, 374, 279, 1176, 892, 5606, 706, 6982, 45813, 38413, 17738, 449, 1778, 264, 1749, 13, 26080, 617, 27313, 279, 4623, 11, 3686, 539, 1766, 15062, 17738, 1359, 1071, 469, 4403, 1772, 28770, 20459, 12874, 13818, 5808, 13, 330, 8140, 5603, 374, 5016, 11, 439, 584, 25078, 264, 27927, 2134, 315, 26148, 4642, 2391, 279, 220, 679, 16, 38413, 13, 1628, 584, 1511, 3361, 8863, 5528, 311, 43223, 11594, 71019, 17738, 505, 279, 50380, 828, 1210, 6457, 374, 1633, 513, 2191, 2740, 4642, 11, 779, 433, 596, 912, 13051, 1070, 527, 16781, 14488, 315, 72579, 24198, 389, 4363, 323, 520, 9581, 304, 279, 5654, 13, 578, 12074, 1511, 264, 2134, 315, 72579, 828, 505, 1521, 11, 439, 1664, 439, 2307, 77752, 287, 29059, 55336, 320, 7939, 82, 8, 304, 99966, 31866, 11, 480, 21519, 43688, 63293, 11, 323, 68279, 1136, 8869, 11, 30162, 5770, 43688, 63293, 11, 304, 8792, 6457, 13, 362, 5257, 7209, 449, 6134, 1825, 311, 16805, 16106, 11968, 2740, 65410, 12271, 5452, 4871, 13, 16666, 25, 7388, 679, 24, 1628, 78, 20459, 14966, 578, 8450, 6492, 814, 10887, 574, 9193, 15062, 20413, 1148, 14248, 4751, 264, 220, 22, 1355, 11750, 13708, 11, 7438, 1070, 374, 1193, 264, 832, 3502, 7561, 10398, 15068, 6140, 264, 1121, 374, 15465, 13, 578, 12074, 2019, 420, 36862, 279, 7434, 323, 690, 387, 5505, 304, 279, 38711, 315, 3938, 24198, 5918, 11951, 311, 11388, 66579, 13, 33468, 17054, 20459, 14966, 1628, 78, 505, 279, 6011, 315, 28415, 36592, 264, 11775, 3169, 315, 29059, 26402, 11, 279, 95560, 290, 3703, 41032, 320, 5319, 7209, 705, 902, 22262, 311, 387, 279, 1176, 1778, 14473, 13, 330, 7939, 82, 323, 513, 2191, 33504, 527, 539, 10728, 11, 439, 279, 26148, 2949, 1124, 3351, 3871, 449, 279, 14473, 11, 902, 4661, 63409, 2053, 27545, 17738, 505, 66579, 1359, 11497, 469, 4403, 33468, 17054, 19554, 22227, 735, 373, 13, 330, 2028, 374, 3967, 439, 459, 55152, 596, 39736, 11, 477, 279, 85262, 17966, 13, 4452, 11, 279, 5257, 7209, 690, 23075, 420, 3575, 13, 1102, 38207, 4442, 304, 24128, 20779, 8994, 11633, 13, 1102, 574, 13517, 6319, 311, 11388, 71019, 17301, 505, 279, 6295, 17343, 11, 1093, 364, 28641, 447, 2094, 6, 304, 3634, 11, 719, 1057, 7580, 374, 810, 1523, 311, 9420, 1210, 578, 2128, 19226, 315, 264, 4009, 315, 5257, 7209, 4332, 2212, 513, 2191, 2740, 4642, 13918, 11, 459, 4216, 10163, 1887, 430, 1436, 5225, 1274, 220, 605, 6622, 1603, 279, 1176, 5015, 38839, 17301, 17782, 505, 459, 25706, 1992, 220, 1041, 41668, 3201, 13, 9176, 38413, 16779, 12446, 439, 1274, 527, 10791, 1022, 94081, 4871, 14016, 430, 18678, 389, 1124, 13, 38891, 279, 6811, 220, 605, 6622, 1436, 1304, 13, 1115, 690, 1935, 892, 11, 719, 279, 12074, 35611, 46464, 4211, 311, 7417, 13708, 315, 279, 1749, 369, 42835, 1005, 304, 279, 2115, 13, 220, 128257, 198 ]

2,555

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Determining the levels of protein–protein interactions is essential for the analysis of signaling within the cell, characterization of mutation effects, protein function and activation in health and disease, among others. Herein, we describe MolBoolean – a method to detect interactions between endogenous proteins in various subcellular compartments, utilizing antibody-DNA conjugates for identification and signal amplification. In contrast to proximity ligation assays, MolBoolean simultaneously indicates the relative abundances of protein A and B not interacting with each other, as well as the pool of A and B proteins that are proximal enough to be considered an AB complex. MolBoolean is applicable both in fixed cells and tissue sections. The specific and quantifiable data that the method generates provide opportunities for both diagnostic use and medical research. Introduction Proteomics-based approaches have proven essential in various research settings for purposes such as detection of markers in cancer diagnostics, understanding fundamental research questions like signal transduction mechanisms, regulation of gene expression and mutation effects, identification of vaccine targets, elucidation of the mechanisms of drug action, etc. Over the years, a plethora of such methods to suit the complexity and diversity of research questions has been developed. Several of them are based on genetic constructs, where candidate proteins are fused with reporter molecules that upon interaction reconstitute a functional reporter (e.g., yeast two-hybrid 1 , mammalian membrane two-hybrid 2 , and bimolecular fluorescence complementation 3 ). Alternatively, Förster resonance energy transfer (FRET) can be used to determine proximal binding of fluorophores, with a concomitant change in emission spectra/lifetime 4 . More specifically, FRET is based on the transfer of energy between light-sensitive molecules—a donor and an acceptor, which has an absorption spectrum overlapping with the emission spectrum of the donor. The efficiency of the resonance energy transfer is strongly dependent on the distance between the fluorophores 5 . While FRET is a sensitive technique suitable for determining intermolecular proximity in the range of 1–10 nm 6 , among its limitations are the low signal-to-noise ratio 7 and the necessity to fuse the target proteins to the acceptor/donor, which makes the method unfit for clinical use. An additional consideration to keep in mind is that the distance between fluorophores is not necessarily identical to that of the target proteins. To determine interactions between native proteins, most methods rely on antibodies conjugated to functional groups, for example, antibody-based FRET 8 , in situ proximity ligation assay (in situ PLA) 9 , 10 , or proximity-dependent initiation of hybridization chain reaction (proxHCR) 11 . Both in situ PLA and proxHCR rely on dual-target recognition with secondary antibodies conjugated to oligonucleotides (so-called proximity probes), and utilize DNA as a reporter of proximity events, which allows for powerful signal amplification and improved signal-to-noise ratio over traditional FRET. It is important to emphasize that what all of the above-mentioned methods detect is proximity between proteins. For in situ PLA, the proximity threshold is determined by the antibody size and the oligonucleotide length of the probes. The hybridization of a pair of circularization oligos to the probes, resulting in the creation of a circular ligation product, is only possible when the attachment points of the oligonucleotide components of the probes are located within FRET range (below 10 nm) 6 . When primary antibodies are conjugated to the oligonucleotides (i.e., in the case of primary probes) the maximal theoretical distance between targeted epitopes is 30 nm 9 , while for secondary proximity probes it is estimated to be 40 nm. However, highly expressed proteins may be localized very close to each other—less than 40 nm apart—even if they do not interact. In order to confidently interpret data generated with such methods, it is crucial to obtain information not only on the number of proximity events, but also on the amounts of free proteins involved that can be used to normalize data. To be able to detect both the proteins in complex and the pool of non-interacting proteins, we developed a method—MolBoolean—which is based on the Boolean operators NOT and AND on a molecular level. It reports the amounts of protein A and protein B that do not participate in an interaction with each other (NOT), while at the same time also visualizes the pool of A and B proteins that are proximal enough to be considered an AB complex (AND). In this work, we first demonstrate the utilization of MolBoolean for specific dual detection of single proteins, using a pair of antibodies targeting one protein. To establish the applicability of MolBoolean for simultaneous detection and quantification of free proteins and proteins in complex, we then investigate multiple established protein–protein interactions described in literature. In order to highlight our method’s versatility, we perform stainings against proteins localized in various cell compartments, as well as observe changes in free and complex-bound states upon ligand stimulation, siRNA silencing, and other conditions vs no-treatment conditions. Further, we validate the use of MolBoolean not only in fixed cells, but also in different types of formalin-fixed paraffin-embedded (FFPE) tissue sections. In parallel to the MolBoolean analyses, we perform well-established classic techniques not only to validate our findings, but also to provide grounds to compare and contrast the merits of MolBoolean with those of in situ PLA (visualizing protein interactions) and immunofluorescence (IF, suitable also for visualization of free proteins and compartmentalization). We herein demonstrate that MolBoolean provides information on protein interaction in a manner similar to in situ PLA (i.e., by detecting discrete rolling circle amplification products (RCPs)), but also on the relative quantities of individual proteins, which allows for quantification of the RCPs in each category on a single cell level. Results Principle of the MolBoolean method Similar to in situ PLA, MolBoolean, too, relies on the use of proximity probes and rolling circle amplification (RCA) as means for generating and amplifying signal. However, MolBoolean uses a preformed DNA circle as information receiver that would later indicate whether one or two proteins have been detected. At the basis of MolBoolean, like other immunoassays, is the specific binding", "role": "user" }, { "content": "Proteins constitute principal building blocks in all living organisms. They are often described as the workers of the cell, where they⁠—together or individually⁠—perform numerous essential tasks. If something goes wrong, the consequences are often serious. Both research and health care have expressed the need for effective tools to analyze the functions and activities of proteins, and in a new article in scientific journal Nature Communications, Professor Ola Söderberg's team introduces MolBoolean, a technology that is expected to open important doors in cell and cancer research. \"MolBoolean is a method to determine levels of a pair of proteins in individual cells, while in parallel identifying the percentage of these proteins that bind each other. We have continued to develop a tool that we created in 2006, which today is used all over the world, and the functions that we are now adding generate information about the relative amounts of different proteins as well as relative amounts of protein complexes, thus making the cells' activity status and communication more visible,\" says Ola Söderberg, Professor of Pharmaceutical Cell Biology at Uppsala University. \"This can be compared to assessing a restaurant; 10 positive reviews give some information, but it is important to know whether they are based on ten or 1,000 opinions,\" The group's results are piquing great interest in both academia and industry, and currently the Stockholm-based company Atlas Antibodies—which recently overtook the patent for MolBoolean—is preparing the method for the market. The tool is expected to be of great value in research, and in the long term, also in health care to improve diagnosis and choice of treatment for cancer. Schematic representation of the MolBoolean principle for detection of interacting and free proteins A and B. a After binding their respective target proteins A and B, proximity probes A (black and magenta) and B (black and green) hybridize to the circle. Arrows signify oligonucleotide polarity. b The circle gets enzymatically nicked (cyan arrowhead indicates nicking position). c The circle gets invaded by reporter tags (tag A in magenta, tag B in green). d Enzymatic ligation of the reporter tags to the circle follows. e Rolling circle amplification (RCA) creates long concatemeric products (RCPs). f RCPs are detected via fluorescently labeled tag-specific detection oligonucleotides. Credit: Nature Communications (2022). DOI: 10.1038/s41467-022-32395-w \"Our research aims to develop tools to visualize processes within cells and to increase, for example, the knowledge of what happens in cancer cells. Knowing the balance between free and interacting proteins is important when studying cell signaling, and we believe that MolBoolean will be appreciated in many research laboratories,\" states Doroteya Raykova, researcher at the Department of Pharmaceutical Biosciences and first author of the article. MolBoolean is developed by Ola Söderberg's group at Uppsala University's Faculty of Pharmacy. The work has been carried out in collaboration with researchers at the universities of Porto and Uppsala, SciLifeLab and Atlas Antibodies. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Determining the levels of protein–protein interactions is essential for the analysis of signaling within the cell, characterization of mutation effects, protein function and activation in health and disease, among others. Herein, we describe MolBoolean – a method to detect interactions between endogenous proteins in various subcellular compartments, utilizing antibody-DNA conjugates for identification and signal amplification. In contrast to proximity ligation assays, MolBoolean simultaneously indicates the relative abundances of protein A and B not interacting with each other, as well as the pool of A and B proteins that are proximal enough to be considered an AB complex. MolBoolean is applicable both in fixed cells and tissue sections. The specific and quantifiable data that the method generates provide opportunities for both diagnostic use and medical research. Introduction Proteomics-based approaches have proven essential in various research settings for purposes such as detection of markers in cancer diagnostics, understanding fundamental research questions like signal transduction mechanisms, regulation of gene expression and mutation effects, identification of vaccine targets, elucidation of the mechanisms of drug action, etc. Over the years, a plethora of such methods to suit the complexity and diversity of research questions has been developed. Several of them are based on genetic constructs, where candidate proteins are fused with reporter molecules that upon interaction reconstitute a functional reporter (e.g., yeast two-hybrid 1 , mammalian membrane two-hybrid 2 , and bimolecular fluorescence complementation 3 ). Alternatively, Förster resonance energy transfer (FRET) can be used to determine proximal binding of fluorophores, with a concomitant change in emission spectra/lifetime 4 . More specifically, FRET is based on the transfer of energy between light-sensitive molecules—a donor and an acceptor, which has an absorption spectrum overlapping with the emission spectrum of the donor. The efficiency of the resonance energy transfer is strongly dependent on the distance between the fluorophores 5 . While FRET is a sensitive technique suitable for determining intermolecular proximity in the range of 1–10 nm 6 , among its limitations are the low signal-to-noise ratio 7 and the necessity to fuse the target proteins to the acceptor/donor, which makes the method unfit for clinical use. An additional consideration to keep in mind is that the distance between fluorophores is not necessarily identical to that of the target proteins. To determine interactions between native proteins, most methods rely on antibodies conjugated to functional groups, for example, antibody-based FRET 8 , in situ proximity ligation assay (in situ PLA) 9 , 10 , or proximity-dependent initiation of hybridization chain reaction (proxHCR) 11 . Both in situ PLA and proxHCR rely on dual-target recognition with secondary antibodies conjugated to oligonucleotides (so-called proximity probes), and utilize DNA as a reporter of proximity events, which allows for powerful signal amplification and improved signal-to-noise ratio over traditional FRET. It is important to emphasize that what all of the above-mentioned methods detect is proximity between proteins. For in situ PLA, the proximity threshold is determined by the antibody size and the oligonucleotide length of the probes. The hybridization of a pair of circularization oligos to the probes, resulting in the creation of a circular ligation product, is only possible when the attachment points of the oligonucleotide components of the probes are located within FRET range (below 10 nm) 6 . When primary antibodies are conjugated to the oligonucleotides (i.e., in the case of primary probes) the maximal theoretical distance between targeted epitopes is 30 nm 9 , while for secondary proximity probes it is estimated to be 40 nm. However, highly expressed proteins may be localized very close to each other—less than 40 nm apart—even if they do not interact. In order to confidently interpret data generated with such methods, it is crucial to obtain information not only on the number of proximity events, but also on the amounts of free proteins involved that can be used to normalize data. To be able to detect both the proteins in complex and the pool of non-interacting proteins, we developed a method—MolBoolean—which is based on the Boolean operators NOT and AND on a molecular level. It reports the amounts of protein A and protein B that do not participate in an interaction with each other (NOT), while at the same time also visualizes the pool of A and B proteins that are proximal enough to be considered an AB complex (AND). In this work, we first demonstrate the utilization of MolBoolean for specific dual detection of single proteins, using a pair of antibodies targeting one protein. To establish the applicability of MolBoolean for simultaneous detection and quantification of free proteins and proteins in complex, we then investigate multiple established protein–protein interactions described in literature. In order to highlight our method’s versatility, we perform stainings against proteins localized in various cell compartments, as well as observe changes in free and complex-bound states upon ligand stimulation, siRNA silencing, and other conditions vs no-treatment conditions. Further, we validate the use of MolBoolean not only in fixed cells, but also in different types of formalin-fixed paraffin-embedded (FFPE) tissue sections. In parallel to the MolBoolean analyses, we perform well-established classic techniques not only to validate our findings, but also to provide grounds to compare and contrast the merits of MolBoolean with those of in situ PLA (visualizing protein interactions) and immunofluorescence (IF, suitable also for visualization of free proteins and compartmentalization). We herein demonstrate that MolBoolean provides information on protein interaction in a manner similar to in situ PLA (i.e., by detecting discrete rolling circle amplification products (RCPs)), but also on the relative quantities of individual proteins, which allows for quantification of the RCPs in each category on a single cell level. Results Principle of the MolBoolean method Similar to in situ PLA, MolBoolean, too, relies on the use of proximity probes and rolling circle amplification (RCA) as means for generating and amplifying signal. However, MolBoolean uses a preformed DNA circle as information receiver that would later indicate whether one or two proteins have been detected. At the basis of MolBoolean, like other immunoassays, is the specific binding<|im_end|> <|im_start|>assistant Proteins constitute principal building blocks in all living organisms. They are often described as the workers of the cell, where they⁠—together or individually⁠—perform numerous essential tasks. If something goes wrong, the consequences are often serious. Both research and health care have expressed the need for effective tools to analyze the functions and activities of proteins, and in a new article in scientific journal Nature Communications, Professor Ola Söderberg's team introduces MolBoolean, a technology that is expected to open important doors in cell and cancer research. "MolBoolean is a method to determine levels of a pair of proteins in individual cells, while in parallel identifying the percentage of these proteins that bind each other. We have continued to develop a tool that we created in 2006, which today is used all over the world, and the functions that we are now adding generate information about the relative amounts of different proteins as well as relative amounts of protein complexes, thus making the cells' activity status and communication more visible," says Ola Söderberg, Professor of Pharmaceutical Cell Biology at Uppsala University. "This can be compared to assessing a restaurant; 10 positive reviews give some information, but it is important to know whether they are based on ten or 1,000 opinions," The group's results are piquing great interest in both academia and industry, and currently the Stockholm-based company Atlas Antibodies—which recently overtook the patent for MolBoolean—is preparing the method for the market. The tool is expected to be of great value in research, and in the long term, also in health care to improve diagnosis and choice of treatment for cancer. Schematic representation of the MolBoolean principle for detection of interacting and free proteins A and B. a After binding their respective target proteins A and B, proximity probes A (black and magenta) and B (black and green) hybridize to the circle. Arrows signify oligonucleotide polarity. b The circle gets enzymatically nicked (cyan arrowhead indicates nicking position). c The circle gets invaded by reporter tags (tag A in magenta, tag B in green). d Enzymatic ligation of the reporter tags to the circle follows. e Rolling circle amplification (RCA) creates long concatemeric products (RCPs). f RCPs are detected via fluorescently labeled tag-specific detection oligonucleotides. Credit: Nature Communications (2022). DOI: 10.1038/s41467-022-32395-w "Our research aims to develop tools to visualize processes within cells and to increase, for example, the knowledge of what happens in cancer cells. Knowing the balance between free and interacting proteins is important when studying cell signaling, and we believe that MolBoolean will be appreciated in many research laboratories," states Doroteya Raykova, researcher at the Department of Pharmaceutical Biosciences and first author of the article. MolBoolean is developed by Ola Söderberg's group at Uppsala University's Faculty of Pharmacy. The work has been carried out in collaboration with researchers at the universities of Porto and Uppsala, SciLifeLab and Atlas Antibodies. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 36007, 287, 279, 5990, 315, 13128, 4235, 79565, 22639, 374, 7718, 369, 279, 6492, 315, 43080, 2949, 279, 2849, 11, 60993, 315, 27472, 6372, 11, 13128, 734, 323, 15449, 304, 2890, 323, 8624, 11, 4315, 3885, 13, 5810, 258, 11, 584, 7664, 33518, 7035, 1389, 264, 1749, 311, 11388, 22639, 1990, 842, 53595, 28896, 304, 5370, 1207, 5997, 1299, 87352, 11, 35988, 63052, 9607, 7476, 64380, 988, 369, 22654, 323, 8450, 23201, 2461, 13, 763, 13168, 311, 37843, 326, 18413, 99592, 11, 33518, 7035, 25291, 15151, 279, 8844, 23325, 3095, 315, 13128, 362, 323, 426, 539, 45830, 449, 1855, 1023, 11, 439, 1664, 439, 279, 7463, 315, 362, 323, 426, 28896, 430, 527, 22267, 2931, 3403, 311, 387, 6646, 459, 14469, 6485, 13, 33518, 7035, 374, 8581, 2225, 304, 8521, 7917, 323, 20438, 14491, 13, 578, 3230, 323, 10484, 23444, 828, 430, 279, 1749, 27983, 3493, 10708, 369, 2225, 15439, 1005, 323, 6593, 3495, 13, 29438, 15542, 24203, 6108, 20414, 617, 17033, 7718, 304, 5370, 3495, 5110, 369, 10096, 1778, 439, 18468, 315, 24915, 304, 9572, 50518, 11, 8830, 16188, 3495, 4860, 1093, 8450, 1380, 23985, 24717, 11, 19812, 315, 15207, 7645, 323, 27472, 6372, 11, 22654, 315, 25474, 11811, 11, 97298, 367, 315, 279, 24717, 315, 5623, 1957, 11, 5099, 13, 6193, 279, 1667, 11, 264, 68706, 315, 1778, 5528, 311, 7937, 279, 23965, 323, 20057, 315, 3495, 4860, 706, 1027, 8040, 13, 26778, 315, 1124, 527, 3196, 389, 19465, 57327, 11, 1405, 9322, 28896, 527, 75754, 449, 19496, 35715, 430, 5304, 16628, 312, 1040, 275, 1088, 264, 16003, 19496, 320, 68, 1326, 2637, 41580, 1403, 2902, 94490, 220, 16, 1174, 36041, 10700, 39654, 1403, 2902, 94490, 220, 17, 1174, 323, 293, 318, 43943, 97332, 23606, 367, 220, 18, 7609, 39578, 11, 87567, 3751, 58081, 4907, 8481, 320, 37, 39164, 8, 649, 387, 1511, 311, 8417, 22267, 2931, 11212, 315, 54736, 5237, 4692, 11, 449, 264, 390, 884, 52044, 2349, 304, 41353, 63697, 13631, 29615, 220, 19, 662, 4497, 11951, 11, 435, 39164, 374, 3196, 389, 279, 8481, 315, 4907, 1990, 3177, 57767, 35715, 29096, 35558, 323, 459, 4287, 269, 11, 902, 706, 459, 44225, 20326, 50917, 449, 279, 41353, 20326, 315, 279, 35558, 13, 578, 15374, 315, 279, 58081, 4907, 8481, 374, 16917, 18222, 389, 279, 6138, 1990, 279, 54736, 5237, 4692, 220, 20, 662, 6104, 435, 39164, 374, 264, 16614, 15105, 14791, 369, 26679, 958, 76, 43943, 37843, 304, 279, 2134, 315, 220, 16, 4235, 605, 26807, 220, 21, 1174, 4315, 1202, 9669, 527, 279, 3428, 8450, 4791, 29466, 1082, 11595, 220, 22, 323, 279, 32961, 311, 32802, 279, 2218, 28896, 311, 279, 4287, 269, 3529, 55137, 11, 902, 3727, 279, 1749, 94567, 369, 14830, 1005, 13, 1556, 5217, 18361, 311, 2567, 304, 4059, 374, 430, 279, 6138, 1990, 54736, 5237, 4692, 374, 539, 14647, 20086, 311, 430, 315, 279, 2218, 28896, 13, 2057, 8417, 22639, 1990, 10068, 28896, 11, 1455, 5528, 17631, 389, 59854, 64380, 660, 311, 16003, 5315, 11, 369, 3187, 11, 63052, 6108, 435, 39164, 220, 23, 1174, 304, 10109, 37843, 326, 18413, 65033, 320, 258, 10109, 98066, 8, 220, 24, 1174, 220, 605, 1174, 477, 37843, 43918, 61568, 315, 26038, 2065, 8957, 13010, 320, 42598, 39, 9150, 8, 220, 806, 662, 11995, 304, 10109, 98066, 323, 22267, 39, 9150, 17631, 389, 19091, 18996, 18324, 449, 14580, 59854, 64380, 660, 311, 55984, 263, 22935, 354, 3422, 320, 708, 19434, 37843, 63610, 705, 323, 29166, 15922, 439, 264, 19496, 315, 37843, 4455, 11, 902, 6276, 369, 8147, 8450, 23201, 2461, 323, 13241, 8450, 4791, 29466, 1082, 11595, 927, 8776, 435, 39164, 13, 1102, 374, 3062, 311, 47032, 430, 1148, 682, 315, 279, 3485, 12, 37691, 5528, 11388, 374, 37843, 1990, 28896, 13, 1789, 304, 10109, 98066, 11, 279, 37843, 12447, 374, 11075, 555, 279, 63052, 1404, 323, 279, 55984, 263, 22935, 69044, 3160, 315, 279, 63610, 13, 578, 26038, 2065, 315, 264, 6857, 315, 28029, 2065, 55984, 437, 311, 279, 63610, 11, 13239, 304, 279, 9886, 315, 264, 28029, 326, 18413, 2027, 11, 374, 1193, 3284, 994, 279, 20581, 3585, 315, 279, 55984, 263, 22935, 69044, 6956, 315, 279, 63610, 527, 7559, 2949, 435, 39164, 2134, 320, 54277, 220, 605, 26807, 8, 220, 21, 662, 3277, 6156, 59854, 527, 64380, 660, 311, 279, 55984, 263, 22935, 354, 3422, 320, 72, 1770, 2637, 304, 279, 1162, 315, 6156, 63610, 8, 279, 54229, 32887, 6138, 1990, 17550, 67422, 19031, 374, 220, 966, 26807, 220, 24, 1174, 1418, 369, 14580, 37843, 63610, 433, 374, 13240, 311, 387, 220, 1272, 26807, 13, 4452, 11, 7701, 13605, 28896, 1253, 387, 44589, 1633, 3345, 311, 1855, 1023, 2345, 1752, 1109, 220, 1272, 26807, 10980, 80078, 422, 814, 656, 539, 16681, 13, 763, 2015, 311, 78076, 14532, 828, 8066, 449, 1778, 5528, 11, 433, 374, 16996, 311, 6994, 2038, 539, 1193, 389, 279, 1396, 315, 37843, 4455, 11, 719, 1101, 389, 279, 15055, 315, 1949, 28896, 6532, 430, 649, 387, 1511, 311, 22436, 828, 13, 2057, 387, 3025, 311, 11388, 2225, 279, 28896, 304, 6485, 323, 279, 7463, 315, 2536, 45994, 36022, 28896, 11, 584, 8040, 264, 1749, 2345, 44, 337, 7035, 50004, 374, 3196, 389, 279, 7137, 20197, 4276, 323, 3651, 389, 264, 31206, 2237, 13, 1102, 6821, 279, 15055, 315, 13128, 362, 323, 13128, 426, 430, 656, 539, 16136, 304, 459, 16628, 449, 1855, 1023, 320, 14394, 705, 1418, 520, 279, 1890, 892, 1101, 9302, 4861, 279, 7463, 315, 362, 323, 426, 28896, 430, 527, 22267, 2931, 3403, 311, 387, 6646, 459, 14469, 6485, 320, 4064, 570, 763, 420, 990, 11, 584, 1176, 20461, 279, 50549, 315, 33518, 7035, 369, 3230, 19091, 18468, 315, 3254, 28896, 11, 1701, 264, 6857, 315, 59854, 25103, 832, 13128, 13, 2057, 5813, 279, 4666, 2968, 315, 33518, 7035, 369, 58632, 18468, 323, 10484, 2461, 315, 1949, 28896, 323, 28896, 304, 6485, 11, 584, 1243, 19874, 5361, 9749, 13128, 4235, 79565, 22639, 7633, 304, 17649, 13, 763, 2015, 311, 11415, 1057, 1749, 753, 60112, 11, 584, 2804, 53064, 826, 2403, 28896, 44589, 304, 5370, 2849, 87352, 11, 439, 1664, 439, 23846, 4442, 304, 1949, 323, 6485, 50962, 5415, 5304, 29413, 438, 41959, 11, 4502, 31820, 5554, 11627, 11, 323, 1023, 4787, 6296, 912, 2442, 35320, 4787, 13, 15903, 11, 584, 9788, 279, 1005, 315, 33518, 7035, 539, 1193, 304, 8521, 7917, 11, 719, 1101, 304, 2204, 4595, 315, 16287, 258, 54864, 1370, 2715, 258, 12, 70964, 320, 1785, 1777, 8, 20438, 14491, 13, 763, 15638, 311, 279, 33518, 7035, 29060, 11, 584, 2804, 1664, 64868, 11670, 12823, 539, 1193, 311, 9788, 1057, 14955, 11, 719, 1101, 311, 3493, 21319, 311, 9616, 323, 13168, 279, 50932, 315, 33518, 7035, 449, 1884, 315, 304, 10109, 98066, 320, 30318, 4954, 13128, 22639, 8, 323, 33119, 1073, 10036, 4692, 36634, 320, 2843, 11, 14791, 1101, 369, 42148, 315, 1949, 28896, 323, 44598, 278, 2065, 570, 1226, 36881, 20461, 430, 33518, 7035, 5825, 2038, 389, 13128, 16628, 304, 264, 11827, 4528, 311, 304, 10109, 98066, 320, 72, 1770, 2637, 555, 54626, 44279, 20700, 12960, 23201, 2461, 3956, 320, 49, 7269, 82, 5850, 719, 1101, 389, 279, 8844, 33776, 315, 3927, 28896, 11, 902, 6276, 369, 10484, 2461, 315, 279, 432, 7269, 82, 304, 1855, 5699, 389, 264, 3254, 2849, 2237, 13, 18591, 82086, 315, 279, 33518, 7035, 1749, 22196, 311, 304, 10109, 98066, 11, 33518, 7035, 11, 2288, 11, 34744, 389, 279, 1005, 315, 37843, 63610, 323, 20700, 12960, 23201, 2461, 320, 49, 5158, 8, 439, 3445, 369, 24038, 323, 23201, 7922, 8450, 13, 4452, 11, 33518, 7035, 5829, 264, 864, 10365, 15922, 12960, 439, 2038, 14291, 430, 1053, 3010, 13519, 3508, 832, 477, 1403, 28896, 617, 1027, 16914, 13, 2468, 279, 8197, 315, 33518, 7035, 11, 1093, 1023, 4998, 16711, 395, 954, 11, 374, 279, 3230, 11212, 128257, 198, 128256, 78191, 198, 1360, 668, 1354, 35256, 12717, 4857, 10215, 304, 682, 5496, 44304, 13, 2435, 527, 3629, 7633, 439, 279, 7487, 315, 279, 2849, 11, 1405, 814, 53233, 254, 2345, 998, 3522, 477, 32399, 53233, 254, 2345, 29588, 12387, 7718, 9256, 13, 1442, 2555, 5900, 5076, 11, 279, 16296, 527, 3629, 6129, 13, 11995, 3495, 323, 2890, 2512, 617, 13605, 279, 1205, 369, 7524, 7526, 311, 24564, 279, 5865, 323, 7640, 315, 28896, 11, 323, 304, 264, 502, 4652, 304, 12624, 8486, 22037, 26545, 11, 17054, 507, 4355, 328, 3029, 1126, 7881, 596, 2128, 40019, 33518, 7035, 11, 264, 5557, 430, 374, 3685, 311, 1825, 3062, 14365, 304, 2849, 323, 9572, 3495, 13, 330, 44, 337, 7035, 374, 264, 1749, 311, 8417, 5990, 315, 264, 6857, 315, 28896, 304, 3927, 7917, 11, 1418, 304, 15638, 25607, 279, 11668, 315, 1521, 28896, 430, 10950, 1855, 1023, 13, 1226, 617, 8738, 311, 2274, 264, 5507, 430, 584, 3549, 304, 220, 1049, 21, 11, 902, 3432, 374, 1511, 682, 927, 279, 1917, 11, 323, 279, 5865, 430, 584, 527, 1457, 7999, 7068, 2038, 922, 279, 8844, 15055, 315, 2204, 28896, 439, 1664, 439, 8844, 15055, 315, 13128, 69125, 11, 8617, 3339, 279, 7917, 6, 5820, 2704, 323, 10758, 810, 9621, 1359, 2795, 507, 4355, 328, 3029, 1126, 7881, 11, 17054, 315, 59373, 14299, 40023, 520, 549, 60643, 6181, 3907, 13, 330, 2028, 649, 387, 7863, 311, 47614, 264, 10960, 26, 220, 605, 6928, 8544, 3041, 1063, 2038, 11, 719, 433, 374, 3062, 311, 1440, 3508, 814, 527, 3196, 389, 5899, 477, 220, 16, 11, 931, 18463, 1359, 578, 1912, 596, 3135, 527, 281, 5118, 287, 2294, 2802, 304, 2225, 67671, 323, 5064, 11, 323, 5131, 279, 53182, 6108, 2883, 43443, 95951, 10233, 50004, 6051, 927, 91453, 279, 25589, 369, 33518, 7035, 55434, 20646, 279, 1749, 369, 279, 3157, 13, 578, 5507, 374, 3685, 311, 387, 315, 2294, 907, 304, 3495, 11, 323, 304, 279, 1317, 4751, 11, 1101, 304, 2890, 2512, 311, 7417, 23842, 323, 5873, 315, 6514, 369, 9572, 13, 328, 82149, 13340, 315, 279, 33518, 7035, 17966, 369, 18468, 315, 45830, 323, 1949, 28896, 362, 323, 426, 13, 264, 4740, 11212, 872, 20081, 2218, 28896, 362, 323, 426, 11, 37843, 63610, 362, 320, 11708, 323, 4983, 16985, 8, 323, 426, 320, 11708, 323, 6307, 8, 26038, 553, 311, 279, 12960, 13, 1676, 1849, 89522, 55984, 263, 22935, 69044, 76790, 13, 293, 578, 12960, 5334, 32011, 7167, 16370, 291, 320, 70846, 18404, 2025, 15151, 16370, 287, 2361, 570, 272, 578, 12960, 5334, 64765, 555, 19496, 9681, 320, 4681, 362, 304, 4983, 16985, 11, 4877, 426, 304, 6307, 570, 294, 2998, 21436, 780, 326, 18413, 315, 279, 19496, 9681, 311, 279, 12960, 11263, 13, 384, 46048, 12960, 23201, 2461, 320, 49, 5158, 8, 11705, 1317, 34820, 336, 11893, 3956, 320, 49, 7269, 82, 570, 282, 432, 7269, 82, 527, 16914, 4669, 74864, 398, 30929, 4877, 19440, 18468, 55984, 263, 22935, 354, 3422, 13, 16666, 25, 22037, 26545, 320, 2366, 17, 570, 59670, 25, 220, 605, 13, 6889, 23, 2754, 17448, 3080, 12, 18642, 12, 15726, 2721, 2695, 330, 8140, 3495, 22262, 311, 2274, 7526, 311, 51187, 11618, 2949, 7917, 323, 311, 5376, 11, 369, 3187, 11, 279, 6677, 315, 1148, 8741, 304, 9572, 7917, 13, 58733, 279, 8335, 1990, 1949, 323, 45830, 28896, 374, 3062, 994, 21630, 2849, 43080, 11, 323, 584, 4510, 430, 33518, 7035, 690, 387, 26893, 304, 1690, 3495, 70760, 1359, 5415, 25225, 354, 78989, 13558, 116278, 11, 32185, 520, 279, 6011, 315, 59373, 77948, 5979, 2436, 323, 1176, 3229, 315, 279, 4652, 13, 33518, 7035, 374, 8040, 555, 507, 4355, 328, 3029, 1126, 7881, 596, 1912, 520, 549, 60643, 6181, 3907, 596, 42904, 315, 48175, 13, 578, 990, 706, 1027, 11953, 704, 304, 20632, 449, 12074, 520, 279, 23978, 315, 70798, 323, 549, 60643, 6181, 11, 41472, 26833, 30146, 323, 43443, 95951, 10233, 13, 220, 128257, 198 ]

1,973

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Background and purpose Currently, there is neither a standard protocol for vessel wall MR imaging of intracranial atherosclerotic disease (ICAD) nor a gold standard phantom to compare MR sequences. In this study, a plaque phantom is developed and characterized that provides a platform for establishing a uniform imaging approach for ICAD. Materials and methods A patient specific injection mold was 3D printed to construct a geometrically accurate ICAD phantom. Polyvinyl alcohol hydrogel was infused into the core shell mold to form the stenotic artery. The ICAD phantom incorporated materials mimicking a stenotic vessel and plaque components, including fibrous cap and lipid core. Two phantoms were scanned using high resolution cone beam CT and compared with four different 3 T MRI systems across eight different sites over a period of 18 months. Inter-phantom variability was assessed by lumen dimensions and contrast to noise ratio (CNR). Results Quantitative evaluation of the minimum lumen radius in the stenosis showed that the radius was on average 0.80 mm (95% CI 0.77 to 0.82 mm) in model 1 and 0.77 mm (95% CI 0.74 to 0.81 mm) in model 2. The highest CNRs were observed for comparisons between lipid and vessel wall. To evaluate manufacturing reproducibility, the CNR variability between the two models had an average absolute difference of 4.31 (95% CI 3.82 to 5.78). Variation in CNR between the images from the same scanner separated by 7 months was 2.5–6.2, showing reproducible phantom durability. Conclusions A plaque phantom composed of a stenotic vessel wall and plaque components was successfully constructed for multicenter high resolution MRI standardization. Atherosclerosis MRI Stenosis Vessel Wall googletag.cmd.push(function() { googletag.display(\"dfp-ad-mpu\"); }); Statistics from Altmetric.com See more details Picked up by 6 news outlets Tweeted by 4 Mentioned by 1 peer review sites On 1 Facebook pages 44 readers on Mendeley Request Permissions If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways. ?xml version=\"1.0\" encoding=\"UTF-8\" ? Request permissions Atherosclerosis MRI Stenosis Vessel Wall Introduction Recent randomized trials showed that despite treatment of intracranial atherosclerosis (ICAD) with aggressive medical management, some patients still have a high risk of stroke. 1 , 2 More rigorous patient selection based on characteristics of intracranial plaques may make it possible to identify patients who would benefit from new therapies, such as refined endovascular procedures 3–5 or novel medical therapies. High resolution MRI (HRMRI) is also a promising technique to differentiate various pathologies that may be the cause of intracranial artery stenosis (eg, atherosclerosis vs vasculitis vs other vasculopathy) and allow characterization of ICAD plaque composition. 6–10 While HRMRI research has been growing throughout the past decade with great success in carotid artery plaque analysis, 11 , 12 its clinical application to ICAD has been limited by a lack of standardization. The approach to developing HRMRI imaging in ICAD has been fragmented, with most investigators focused on designing and validating their own sequences in small, underpowered, single center studies. There is currently no universal standard protocol for HRMRI imaging that would facilitate multicenter studies. Furthermore, data generated by HRMRI are dependent on MR instrumentation, sequence parameters used, the MR environment, and well as patient factors, which can make comparisons of results from multiple centers difficult. In order to advance the field of HRMRI ICAD research, establishment of a multicenter network to provide a research infrastructure for promoting collaboration, sharing of protocols and data, and providing a quick and efficient mechanism for studying HRMRI in ICAD is needed. A critical factor for the development of such a multicenter HRMRI ICAD network is the need for a static model, or phantom, to standardize image quality across sequences and centers. We have developed a patient specific basilar artery stenosis imaging phantom to provide the image quality assessment and standardization that is required for the development of a multicenter international HRMRI ICAD network. Our MRI phantom has been specially designed to evaluate, analyze, and optimize the performance of MRI scanners or sequences suitable for imaging small structures. Since the intracranial arteries are very small (average diameter 2–5 mm), with even smaller plaque components, the ability of an individual MRI scanner to generate high quality images of such small structures must be established. Our phantom is based on details from a patient's HRMRI ICAD images, and will enable practical assessment of the image quality obtained from HRMRI sequences using various MR instruments at various sites, without subjecting multiple human subjects to long time periods in the MRI scanner and controlling for patient motion artifacts, during sequence assessment and optimization. Herein, we describe the design and construction of the phantom and the methods used to assess MR image quality at multiple sites. Methods Phantom construction With permission from our institutional review board and informed consent, HRMRI imaging data from a patient with ICAD was used to acquire a detailed structure of plaque components ( figure 1 A). The images were segmented for the lumen, fibrous cap, and lipid core (Mimics and Magics; Materialise, Leuven, Belgium) ( figure 1 B). The computer model ( figure 2 A) was used to create the infusion mold by 3D printing ( figure 2 B), as previously described. 13 Polyvinyl alcohol (PVA Mowiol 56-98; Höchst AG, Frankfurt/Main, Germany) with an average molecular weight of 195 000 g/mol and a hydrolysis degree of 98% was mixed with dimethyl sulfoxide (DMSO, D4540; Sigma-Aldrich, St Louis, Missouri, USA) and water. The mixture was allowed to cool to room temperature and was then infused into the acrylonitrile butadiene styrene core shell mold by liquid injection molding, followed by three freeze–thaw cycles for curing. The core shell mold was immersed in xylene for acrylonitrile butadiene styrene dissolution, yielding a PVA stenotic vessel wall ( figure 2 C). Download figure Open in new tab Download powerpoint Figure 1 Frontal maximum intensity projection image from time", "role": "user" }, { "content": "A collaboration between stroke neurologists at the Medical University of South Carolina (MUSC) and bioengineers at the University of Massachusetts has led to the creation of a realistic, 3D-printed phantom of a stenotic intracranial artery that is being used to standardize protocols for high-resolution MRI, also known as vessel-wall MRI, at a network of U.S. and Chinese institutions, according to an article published online March 9, 2017 by the Journal of NeuroInterventional Surgery. High-resolution or vessel-wall MRI has been used to study the plaque components in vessels in the brain for more than ten years and has the potential to elucidate the underlying pathology of intracranial atherosclerotic disease (ICAD), the leading cause of stroke worldwide, as well as to gauge patient risk and inform clinical trials of new therapies. However, progress has been stymied by the lack of standardization in high-resolution MRI protocols, which poses an obstacle to multicenter trials. \"There is a lot of exciting research that is possible with high-resolution MRI techniques, but it has much less opportunity to affect patient care if it can't be systematically distributed to multiple sites and multiple populations,\" says Tanya N. Turan, M.D., director of the MUSC Stroke Division and senior author of the article. To overcome this obstacle, Turan worked with bioengineers at the University of Massachusetts to produce a phantom of a stenotic intracranial vessel using imaging sequences obtained from a single patient with ICAD at MUSC. The 3-D printed ICAD phantom mimics both the stenotic vessel and its plaque components, including the fibrous cap and the lipid core. The phantom is being shared with collaborating institutions so that it can be used to standardize high-resolution MRI protocols. The imaging data presented in the Journal of NeuroInterventional Surgery article demonstrate the feasibility of using the phantom for standardization and were obtained from six U.S. and two Chinese sites. Frontal maximum intensity projection image from time of flight MR showing a focal stenosis of the basilar artery (A, top panel, arrow). Single axial slice of high resolution vessel wall MRI showing intracranial atherosclerosis of the basilar artery (A, bottom panel, arrow). The resulting patient specific virtual phantom of atherosclerotic plaque (B) with fibrous cap (C, top panel) and lipid core (C, bottom panel). Credit: Reproduced from Development of a high resolution MRI intracranial atherosclerosis imaging phantom, Chueh et al, published online on March 9, 2017 by the Journal of NeuroInterventional Surgery with permission from BMJ Publishing Group Ltd. Producing the phantom was a major step in the right direction for standardizing high-resolution MRI ICAD protocols. However, several more years may be necessary to complete the process. The next major challenge for these investigators will be establishing parameters for MRI machines from a variety of manufacturers. So far, MRI parameters have been established for Siemens and GE systems but work is still under way on Philips systems. The phantom is also being shared with sites in China, where the burden of intracranial stenosis is especially high. Turan is collaborating with Weihai Xu, M.D., of Peking Union Medical College, the lead Chinese site, to collect additional data to assess interrater reliability among the participating institutions. Once high-resolution MRI protocols have been standardized and good interrater reliability demonstrated, the international team plans to conduct a prospective observational trial to examine risk prediction at participating centers, which would more quickly meet the required patient enrollment than would a trial conducted in the U.S. alone. \"We're only going to be able to advance the field more quickly if we work together,\" says Turan. \"The phantom gives us the tool to be able to work together.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Background and purpose Currently, there is neither a standard protocol for vessel wall MR imaging of intracranial atherosclerotic disease (ICAD) nor a gold standard phantom to compare MR sequences. In this study, a plaque phantom is developed and characterized that provides a platform for establishing a uniform imaging approach for ICAD. Materials and methods A patient specific injection mold was 3D printed to construct a geometrically accurate ICAD phantom. Polyvinyl alcohol hydrogel was infused into the core shell mold to form the stenotic artery. The ICAD phantom incorporated materials mimicking a stenotic vessel and plaque components, including fibrous cap and lipid core. Two phantoms were scanned using high resolution cone beam CT and compared with four different 3 T MRI systems across eight different sites over a period of 18 months. Inter-phantom variability was assessed by lumen dimensions and contrast to noise ratio (CNR). Results Quantitative evaluation of the minimum lumen radius in the stenosis showed that the radius was on average 0.80 mm (95% CI 0.77 to 0.82 mm) in model 1 and 0.77 mm (95% CI 0.74 to 0.81 mm) in model 2. The highest CNRs were observed for comparisons between lipid and vessel wall. To evaluate manufacturing reproducibility, the CNR variability between the two models had an average absolute difference of 4.31 (95% CI 3.82 to 5.78). Variation in CNR between the images from the same scanner separated by 7 months was 2.5–6.2, showing reproducible phantom durability. Conclusions A plaque phantom composed of a stenotic vessel wall and plaque components was successfully constructed for multicenter high resolution MRI standardization. Atherosclerosis MRI Stenosis Vessel Wall googletag.cmd.push(function() { googletag.display("dfp-ad-mpu"); }); Statistics from Altmetric.com See more details Picked up by 6 news outlets Tweeted by 4 Mentioned by 1 peer review sites On 1 Facebook pages 44 readers on Mendeley Request Permissions If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways. ?xml version="1.0" encoding="UTF-8" ? Request permissions Atherosclerosis MRI Stenosis Vessel Wall Introduction Recent randomized trials showed that despite treatment of intracranial atherosclerosis (ICAD) with aggressive medical management, some patients still have a high risk of stroke. 1 , 2 More rigorous patient selection based on characteristics of intracranial plaques may make it possible to identify patients who would benefit from new therapies, such as refined endovascular procedures 3–5 or novel medical therapies. High resolution MRI (HRMRI) is also a promising technique to differentiate various pathologies that may be the cause of intracranial artery stenosis (eg, atherosclerosis vs vasculitis vs other vasculopathy) and allow characterization of ICAD plaque composition. 6–10 While HRMRI research has been growing throughout the past decade with great success in carotid artery plaque analysis, 11 , 12 its clinical application to ICAD has been limited by a lack of standardization. The approach to developing HRMRI imaging in ICAD has been fragmented, with most investigators focused on designing and validating their own sequences in small, underpowered, single center studies. There is currently no universal standard protocol for HRMRI imaging that would facilitate multicenter studies. Furthermore, data generated by HRMRI are dependent on MR instrumentation, sequence parameters used, the MR environment, and well as patient factors, which can make comparisons of results from multiple centers difficult. In order to advance the field of HRMRI ICAD research, establishment of a multicenter network to provide a research infrastructure for promoting collaboration, sharing of protocols and data, and providing a quick and efficient mechanism for studying HRMRI in ICAD is needed. A critical factor for the development of such a multicenter HRMRI ICAD network is the need for a static model, or phantom, to standardize image quality across sequences and centers. We have developed a patient specific basilar artery stenosis imaging phantom to provide the image quality assessment and standardization that is required for the development of a multicenter international HRMRI ICAD network. Our MRI phantom has been specially designed to evaluate, analyze, and optimize the performance of MRI scanners or sequences suitable for imaging small structures. Since the intracranial arteries are very small (average diameter 2–5 mm), with even smaller plaque components, the ability of an individual MRI scanner to generate high quality images of such small structures must be established. Our phantom is based on details from a patient's HRMRI ICAD images, and will enable practical assessment of the image quality obtained from HRMRI sequences using various MR instruments at various sites, without subjecting multiple human subjects to long time periods in the MRI scanner and controlling for patient motion artifacts, during sequence assessment and optimization. Herein, we describe the design and construction of the phantom and the methods used to assess MR image quality at multiple sites. Methods Phantom construction With permission from our institutional review board and informed consent, HRMRI imaging data from a patient with ICAD was used to acquire a detailed structure of plaque components ( figure 1 A). The images were segmented for the lumen, fibrous cap, and lipid core (Mimics and Magics; Materialise, Leuven, Belgium) ( figure 1 B). The computer model ( figure 2 A) was used to create the infusion mold by 3D printing ( figure 2 B), as previously described. 13 Polyvinyl alcohol (PVA Mowiol 56-98; Höchst AG, Frankfurt/Main, Germany) with an average molecular weight of 195 000 g/mol and a hydrolysis degree of 98% was mixed with dimethyl sulfoxide (DMSO, D4540; Sigma-Aldrich, St Louis, Missouri, USA) and water. The mixture was allowed to cool to room temperature and was then infused into the acrylonitrile butadiene styrene core shell mold by liquid injection molding, followed by three freeze–thaw cycles for curing. The core shell mold was immersed in xylene for acrylonitrile butadiene styrene dissolution, yielding a PVA stenotic vessel wall ( figure 2 C). Download figure Open in new tab Download powerpoint Figure 1 Frontal maximum intensity projection image from time<|im_end|> <|im_start|>assistant A collaboration between stroke neurologists at the Medical University of South Carolina (MUSC) and bioengineers at the University of Massachusetts has led to the creation of a realistic, 3D-printed phantom of a stenotic intracranial artery that is being used to standardize protocols for high-resolution MRI, also known as vessel-wall MRI, at a network of U.S. and Chinese institutions, according to an article published online March 9, 2017 by the Journal of NeuroInterventional Surgery. High-resolution or vessel-wall MRI has been used to study the plaque components in vessels in the brain for more than ten years and has the potential to elucidate the underlying pathology of intracranial atherosclerotic disease (ICAD), the leading cause of stroke worldwide, as well as to gauge patient risk and inform clinical trials of new therapies. However, progress has been stymied by the lack of standardization in high-resolution MRI protocols, which poses an obstacle to multicenter trials. "There is a lot of exciting research that is possible with high-resolution MRI techniques, but it has much less opportunity to affect patient care if it can't be systematically distributed to multiple sites and multiple populations," says Tanya N. Turan, M.D., director of the MUSC Stroke Division and senior author of the article. To overcome this obstacle, Turan worked with bioengineers at the University of Massachusetts to produce a phantom of a stenotic intracranial vessel using imaging sequences obtained from a single patient with ICAD at MUSC. The 3-D printed ICAD phantom mimics both the stenotic vessel and its plaque components, including the fibrous cap and the lipid core. The phantom is being shared with collaborating institutions so that it can be used to standardize high-resolution MRI protocols. The imaging data presented in the Journal of NeuroInterventional Surgery article demonstrate the feasibility of using the phantom for standardization and were obtained from six U.S. and two Chinese sites. Frontal maximum intensity projection image from time of flight MR showing a focal stenosis of the basilar artery (A, top panel, arrow). Single axial slice of high resolution vessel wall MRI showing intracranial atherosclerosis of the basilar artery (A, bottom panel, arrow). The resulting patient specific virtual phantom of atherosclerotic plaque (B) with fibrous cap (C, top panel) and lipid core (C, bottom panel). Credit: Reproduced from Development of a high resolution MRI intracranial atherosclerosis imaging phantom, Chueh et al, published online on March 9, 2017 by the Journal of NeuroInterventional Surgery with permission from BMJ Publishing Group Ltd. Producing the phantom was a major step in the right direction for standardizing high-resolution MRI ICAD protocols. However, several more years may be necessary to complete the process. The next major challenge for these investigators will be establishing parameters for MRI machines from a variety of manufacturers. So far, MRI parameters have been established for Siemens and GE systems but work is still under way on Philips systems. The phantom is also being shared with sites in China, where the burden of intracranial stenosis is especially high. Turan is collaborating with Weihai Xu, M.D., of Peking Union Medical College, the lead Chinese site, to collect additional data to assess interrater reliability among the participating institutions. Once high-resolution MRI protocols have been standardized and good interrater reliability demonstrated, the international team plans to conduct a prospective observational trial to examine risk prediction at participating centers, which would more quickly meet the required patient enrollment than would a trial conducted in the U.S. alone. "We're only going to be able to advance the field more quickly if we work together," says Turan. "The phantom gives us the tool to be able to work together." <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 25837, 323, 7580, 25122, 11, 1070, 374, 14188, 264, 5410, 11766, 369, 27274, 7147, 29433, 32758, 315, 10805, 582, 6713, 532, 264, 91882, 566, 261, 14546, 8624, 320, 1341, 1846, 8, 6463, 264, 6761, 5410, 70808, 311, 9616, 29433, 24630, 13, 763, 420, 4007, 11, 264, 61464, 70808, 374, 8040, 323, 32971, 430, 5825, 264, 5452, 369, 31692, 264, 14113, 32758, 5603, 369, 19845, 1846, 13, 32009, 323, 5528, 362, 8893, 3230, 26127, 29561, 574, 220, 18, 35, 17124, 311, 9429, 264, 53584, 750, 13687, 19845, 1846, 70808, 13, 19294, 9799, 4010, 13200, 17055, 29952, 574, 72903, 1139, 279, 6332, 12811, 29561, 311, 1376, 279, 357, 268, 14546, 65415, 13, 578, 19845, 1846, 70808, 32762, 7384, 28003, 16671, 264, 357, 268, 14546, 27274, 323, 61464, 6956, 11, 2737, 16178, 27620, 2107, 323, 68700, 6332, 13, 9220, 1343, 519, 7085, 1051, 48548, 1701, 1579, 11175, 22949, 24310, 19084, 323, 7863, 449, 3116, 2204, 220, 18, 350, 52460, 6067, 4028, 8223, 2204, 6732, 927, 264, 4261, 315, 220, 972, 4038, 13, 5783, 12, 28022, 316, 54709, 574, 32448, 555, 326, 28999, 15696, 323, 13168, 311, 12248, 11595, 320, 34, 27416, 570, 18591, 32541, 22018, 16865, 315, 279, 8187, 326, 28999, 10801, 304, 279, 357, 268, 10934, 8710, 430, 279, 10801, 574, 389, 5578, 220, 15, 13, 1490, 9653, 320, 2721, 4, 21351, 220, 15, 13, 2813, 311, 220, 15, 13, 6086, 9653, 8, 304, 1646, 220, 16, 323, 220, 15, 13, 2813, 9653, 320, 2721, 4, 21351, 220, 15, 13, 5728, 311, 220, 15, 13, 5932, 9653, 8, 304, 1646, 220, 17, 13, 578, 8592, 25914, 43427, 1051, 13468, 369, 36595, 1990, 68700, 323, 27274, 7147, 13, 2057, 15806, 15266, 53823, 7697, 3225, 11, 279, 25914, 49, 54709, 1990, 279, 1403, 4211, 1047, 459, 5578, 10973, 6811, 315, 220, 19, 13, 2148, 320, 2721, 4, 21351, 220, 18, 13, 6086, 311, 220, 20, 13, 2495, 570, 89585, 304, 25914, 49, 1990, 279, 5448, 505, 279, 1890, 21438, 19180, 555, 220, 22, 4038, 574, 220, 17, 13, 20, 4235, 21, 13, 17, 11, 9204, 53823, 79385, 70808, 39665, 13, 1221, 24436, 362, 61464, 70808, 24306, 315, 264, 357, 268, 14546, 27274, 7147, 323, 61464, 6956, 574, 7946, 20968, 369, 92520, 1992, 1579, 11175, 52460, 5410, 2065, 13, 362, 91882, 91711, 52460, 800, 268, 10934, 650, 36648, 9935, 48569, 1169, 351, 26808, 2615, 2993, 368, 314, 48569, 1169, 351, 8344, 446, 3013, 79, 26831, 12, 1331, 84, 5146, 18605, 25647, 505, 24610, 16282, 916, 3580, 810, 3649, 393, 19011, 709, 555, 220, 21, 3754, 28183, 26213, 291, 555, 220, 19, 86248, 291, 555, 220, 16, 14734, 3477, 6732, 1952, 220, 16, 5690, 6959, 220, 2096, 13016, 389, 386, 11178, 3258, 6274, 54457, 1442, 499, 6562, 311, 27068, 904, 477, 682, 315, 420, 4652, 4587, 1005, 279, 2723, 3770, 902, 690, 1935, 499, 311, 279, 3028, 93230, 5955, 753, 10734, 4026, 2532, 13, 1472, 690, 387, 3025, 311, 636, 264, 4062, 3430, 323, 9888, 8041, 311, 27068, 279, 2262, 304, 1690, 2204, 5627, 13, 949, 6591, 2373, 429, 16, 13, 15, 1, 11418, 429, 8729, 12, 23, 1, 949, 6274, 8709, 362, 91882, 91711, 52460, 800, 268, 10934, 650, 36648, 9935, 29438, 35390, 47341, 19622, 8710, 430, 8994, 6514, 315, 10805, 582, 6713, 532, 264, 91882, 91711, 320, 1341, 1846, 8, 449, 19738, 6593, 6373, 11, 1063, 6978, 2103, 617, 264, 1579, 5326, 315, 12943, 13, 220, 16, 1174, 220, 17, 4497, 47999, 8893, 6727, 3196, 389, 17910, 315, 10805, 582, 6713, 532, 40852, 14295, 1253, 1304, 433, 3284, 311, 10765, 6978, 889, 1053, 8935, 505, 502, 52312, 11, 1778, 439, 38291, 842, 869, 50804, 16346, 220, 18, 4235, 20, 477, 11775, 6593, 52312, 13, 5234, 11175, 52460, 320, 17526, 79770, 8, 374, 1101, 264, 26455, 15105, 311, 54263, 5370, 1853, 9268, 430, 1253, 387, 279, 5353, 315, 10805, 582, 6713, 532, 65415, 357, 268, 10934, 320, 797, 11, 264, 91882, 91711, 6296, 44496, 3395, 20000, 6296, 1023, 44496, 3395, 54042, 8, 323, 2187, 60993, 315, 19845, 1846, 61464, 18528, 13, 220, 21, 4235, 605, 6104, 23096, 79770, 3495, 706, 1027, 7982, 6957, 279, 3347, 13515, 449, 2294, 2450, 304, 1841, 354, 307, 65415, 61464, 6492, 11, 220, 806, 1174, 220, 717, 1202, 14830, 3851, 311, 19845, 1846, 706, 1027, 7347, 555, 264, 6996, 315, 5410, 2065, 13, 578, 5603, 311, 11469, 23096, 79770, 32758, 304, 19845, 1846, 706, 1027, 87195, 11, 449, 1455, 26453, 10968, 389, 30829, 323, 69772, 872, 1866, 24630, 304, 2678, 11, 1234, 52616, 11, 3254, 4219, 7978, 13, 2684, 374, 5131, 912, 20789, 5410, 11766, 369, 23096, 79770, 32758, 430, 1053, 28696, 92520, 1992, 7978, 13, 24296, 11, 828, 8066, 555, 23096, 79770, 527, 18222, 389, 29433, 78133, 11, 8668, 5137, 1511, 11, 279, 29433, 4676, 11, 323, 1664, 439, 8893, 9547, 11, 902, 649, 1304, 36595, 315, 3135, 505, 5361, 19169, 5107, 13, 763, 2015, 311, 12178, 279, 2115, 315, 23096, 79770, 19845, 1846, 3495, 11, 21967, 315, 264, 92520, 1992, 4009, 311, 3493, 264, 3495, 14054, 369, 22923, 20632, 11, 11821, 315, 32885, 323, 828, 11, 323, 8405, 264, 4062, 323, 11297, 17383, 369, 21630, 23096, 79770, 304, 19845, 1846, 374, 4460, 13, 362, 9200, 8331, 369, 279, 4500, 315, 1778, 264, 92520, 1992, 23096, 79770, 19845, 1846, 4009, 374, 279, 1205, 369, 264, 1118, 1646, 11, 477, 70808, 11, 311, 5410, 553, 2217, 4367, 4028, 24630, 323, 19169, 13, 1226, 617, 8040, 264, 8893, 3230, 3122, 3653, 65415, 357, 268, 10934, 32758, 70808, 311, 3493, 279, 2217, 4367, 15813, 323, 5410, 2065, 430, 374, 2631, 369, 279, 4500, 315, 264, 92520, 1992, 6625, 23096, 79770, 19845, 1846, 4009, 13, 5751, 52460, 70808, 706, 1027, 35426, 6319, 311, 15806, 11, 24564, 11, 323, 30536, 279, 5178, 315, 52460, 95146, 477, 24630, 14791, 369, 32758, 2678, 14726, 13, 8876, 279, 10805, 582, 6713, 532, 85648, 527, 1633, 2678, 320, 17645, 23899, 220, 17, 4235, 20, 9653, 705, 449, 1524, 9333, 61464, 6956, 11, 279, 5845, 315, 459, 3927, 52460, 21438, 311, 7068, 1579, 4367, 5448, 315, 1778, 2678, 14726, 2011, 387, 9749, 13, 5751, 70808, 374, 3196, 389, 3649, 505, 264, 8893, 596, 23096, 79770, 19845, 1846, 5448, 11, 323, 690, 7431, 15325, 15813, 315, 279, 2217, 4367, 12457, 505, 23096, 79770, 24630, 1701, 5370, 29433, 24198, 520, 5370, 6732, 11, 2085, 3917, 287, 5361, 3823, 15223, 311, 1317, 892, 18852, 304, 279, 52460, 21438, 323, 26991, 369, 8893, 11633, 36136, 11, 2391, 8668, 15813, 323, 26329, 13, 5810, 258, 11, 584, 7664, 279, 2955, 323, 8246, 315, 279, 70808, 323, 279, 5528, 1511, 311, 8720, 29433, 2217, 4367, 520, 5361, 6732, 13, 19331, 47297, 8246, 3161, 8041, 505, 1057, 33232, 3477, 4580, 323, 16369, 14771, 11, 23096, 79770, 32758, 828, 505, 264, 8893, 449, 19845, 1846, 574, 1511, 311, 21953, 264, 11944, 6070, 315, 61464, 6956, 320, 7216, 220, 16, 362, 570, 578, 5448, 1051, 86045, 369, 279, 326, 28999, 11, 16178, 27620, 2107, 11, 323, 68700, 6332, 320, 44, 318, 1233, 323, 7023, 1233, 26, 10441, 1082, 11, 2009, 84, 1055, 11, 34061, 8, 320, 7216, 220, 16, 426, 570, 578, 6500, 1646, 320, 7216, 220, 17, 362, 8, 574, 1511, 311, 1893, 279, 71308, 29561, 555, 220, 18, 35, 18991, 320, 7216, 220, 17, 426, 705, 439, 8767, 7633, 13, 220, 1032, 19294, 9799, 4010, 13200, 320, 47, 13114, 386, 363, 25947, 220, 3487, 12, 3264, 26, 71364, 331, 267, 15432, 11, 56284, 66341, 11, 10057, 8, 449, 459, 5578, 31206, 4785, 315, 220, 6280, 220, 931, 342, 39971, 323, 264, 17055, 398, 14744, 8547, 315, 220, 3264, 4, 574, 9709, 449, 5213, 42972, 26858, 15361, 579, 320, 35, 4931, 46, 11, 423, 20555, 15, 26, 50637, 6830, 509, 14172, 11, 800, 12140, 11, 25378, 11, 7427, 8, 323, 3090, 13, 578, 21655, 574, 5535, 311, 7155, 311, 3130, 9499, 323, 574, 1243, 72903, 1139, 279, 1645, 894, 12490, 22288, 458, 719, 2836, 1994, 18078, 48009, 6332, 12811, 29561, 555, 14812, 26127, 66157, 11, 8272, 555, 2380, 31030, 4235, 339, 675, 25492, 369, 97330, 13, 578, 6332, 12811, 29561, 574, 78308, 304, 865, 64651, 369, 1645, 894, 12490, 22288, 458, 719, 2836, 1994, 18078, 48009, 81359, 11, 78504, 264, 393, 13114, 357, 268, 14546, 27274, 7147, 320, 7216, 220, 17, 356, 570, 8745, 7216, 5377, 304, 502, 5769, 8745, 2410, 2837, 19575, 220, 16, 15248, 278, 7340, 21261, 22343, 2217, 505, 892, 128257, 198, 128256, 78191, 198, 32, 20632, 1990, 12943, 18247, 848, 1705, 520, 279, 13235, 3907, 315, 4987, 13030, 320, 44, 2078, 34, 8, 323, 17332, 8680, 388, 520, 279, 3907, 315, 22108, 706, 6197, 311, 279, 9886, 315, 264, 26569, 11, 220, 18, 35, 43245, 291, 70808, 315, 264, 357, 268, 14546, 10805, 582, 6713, 532, 65415, 430, 374, 1694, 1511, 311, 5410, 553, 32885, 369, 1579, 64036, 52460, 11, 1101, 3967, 439, 27274, 86111, 52460, 11, 520, 264, 4009, 315, 549, 815, 13, 323, 8620, 14673, 11, 4184, 311, 459, 4652, 4756, 2930, 5587, 220, 24, 11, 220, 679, 22, 555, 279, 10139, 315, 32359, 1090, 47698, 278, 48190, 13, 5234, 64036, 477, 27274, 86111, 52460, 706, 1027, 1511, 311, 4007, 279, 61464, 6956, 304, 31080, 304, 279, 8271, 369, 810, 1109, 5899, 1667, 323, 706, 279, 4754, 311, 97298, 349, 279, 16940, 77041, 315, 10805, 582, 6713, 532, 264, 91882, 566, 261, 14546, 8624, 320, 1341, 1846, 705, 279, 6522, 5353, 315, 12943, 15603, 11, 439, 1664, 439, 311, 31990, 8893, 5326, 323, 6179, 14830, 19622, 315, 502, 52312, 13, 4452, 11, 5208, 706, 1027, 357, 1631, 1142, 555, 279, 6996, 315, 5410, 2065, 304, 1579, 64036, 52460, 32885, 11, 902, 34103, 459, 33287, 311, 92520, 1992, 19622, 13, 330, 3947, 374, 264, 2763, 315, 13548, 3495, 430, 374, 3284, 449, 1579, 64036, 52460, 12823, 11, 719, 433, 706, 1790, 2753, 6776, 311, 7958, 8893, 2512, 422, 433, 649, 956, 387, 60826, 4332, 311, 5361, 6732, 323, 5361, 22673, 1359, 2795, 350, 25041, 452, 13, 8877, 276, 11, 386, 920, 2637, 7690, 315, 279, 386, 2078, 34, 70034, 14829, 323, 10195, 3229, 315, 279, 4652, 13, 2057, 23075, 420, 33287, 11, 8877, 276, 6575, 449, 17332, 8680, 388, 520, 279, 3907, 315, 22108, 311, 8356, 264, 70808, 315, 264, 357, 268, 14546, 10805, 582, 6713, 532, 27274, 1701, 32758, 24630, 12457, 505, 264, 3254, 8893, 449, 19845, 1846, 520, 386, 2078, 34, 13, 578, 220, 18, 9607, 17124, 19845, 1846, 70808, 28003, 1233, 2225, 279, 357, 268, 14546, 27274, 323, 1202, 61464, 6956, 11, 2737, 279, 16178, 27620, 2107, 323, 279, 68700, 6332, 13, 578, 70808, 374, 1694, 6222, 449, 73301, 14673, 779, 430, 433, 649, 387, 1511, 311, 5410, 553, 1579, 64036, 52460, 32885, 13, 578, 32758, 828, 10666, 304, 279, 10139, 315, 32359, 1090, 47698, 278, 48190, 4652, 20461, 279, 69543, 315, 1701, 279, 70808, 369, 5410, 2065, 323, 1051, 12457, 505, 4848, 549, 815, 13, 323, 1403, 8620, 6732, 13, 15248, 278, 7340, 21261, 22343, 2217, 505, 892, 315, 11213, 29433, 9204, 264, 42199, 357, 268, 10934, 315, 279, 3122, 3653, 65415, 320, 32, 11, 1948, 7090, 11, 18404, 570, 11579, 98280, 16363, 315, 1579, 11175, 27274, 7147, 52460, 9204, 10805, 582, 6713, 532, 264, 91882, 91711, 315, 279, 3122, 3653, 65415, 320, 32, 11, 5740, 7090, 11, 18404, 570, 578, 13239, 8893, 3230, 4200, 70808, 315, 264, 91882, 566, 261, 14546, 61464, 320, 33, 8, 449, 16178, 27620, 2107, 320, 34, 11, 1948, 7090, 8, 323, 68700, 6332, 320, 34, 11, 5740, 7090, 570, 16666, 25, 3402, 30317, 505, 11050, 315, 264, 1579, 11175, 52460, 10805, 582, 6713, 532, 264, 91882, 91711, 32758, 70808, 11, 921, 361, 71, 1880, 453, 11, 4756, 2930, 389, 5587, 220, 24, 11, 220, 679, 22, 555, 279, 10139, 315, 32359, 1090, 47698, 278, 48190, 449, 8041, 505, 20387, 41, 37933, 5856, 12604, 13, 12311, 6253, 279, 70808, 574, 264, 3682, 3094, 304, 279, 1314, 5216, 369, 5410, 4954, 1579, 64036, 52460, 19845, 1846, 32885, 13, 4452, 11, 3892, 810, 1667, 1253, 387, 5995, 311, 4686, 279, 1920, 13, 578, 1828, 3682, 8815, 369, 1521, 26453, 690, 387, 31692, 5137, 369, 52460, 12933, 505, 264, 8205, 315, 17032, 13, 2100, 3117, 11, 52460, 5137, 617, 1027, 9749, 369, 91324, 323, 30957, 6067, 719, 990, 374, 2103, 1234, 1648, 389, 74603, 6067, 13, 578, 70808, 374, 1101, 1694, 6222, 449, 6732, 304, 5734, 11, 1405, 279, 23104, 315, 10805, 582, 6713, 532, 357, 268, 10934, 374, 5423, 1579, 13, 8877, 276, 374, 73301, 449, 1226, 7141, 2192, 57514, 11, 386, 920, 2637, 315, 393, 59952, 9323, 13235, 9304, 11, 279, 3063, 8620, 2816, 11, 311, 6667, 5217, 828, 311, 8720, 958, 81, 977, 31638, 4315, 279, 24435, 14673, 13, 9843, 1579, 64036, 52460, 32885, 617, 1027, 51114, 323, 1695, 958, 81, 977, 31638, 21091, 11, 279, 6625, 2128, 6787, 311, 6929, 264, 33547, 90380, 9269, 311, 21635, 5326, 20212, 520, 24435, 19169, 11, 902, 1053, 810, 6288, 3449, 279, 2631, 8893, 39148, 1109, 1053, 264, 9269, 13375, 304, 279, 549, 815, 13, 7636, 13, 330, 1687, 2351, 1193, 2133, 311, 387, 3025, 311, 12178, 279, 2115, 810, 6288, 422, 584, 990, 3871, 1359, 2795, 8877, 276, 13, 330, 791, 70808, 6835, 603, 279, 5507, 311, 387, 3025, 311, 990, 3871, 1210, 220, 128257, 198 ]

2,225

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Metals cannot be extracted by electrolysis of transition-metal sulfides because as liquids they are semiconductors, which exhibit high levels of electronic conduction and metal dissolution. Herein by introduction of a distinct secondary electrolyte, we reveal a high-throughput electro-desulfurization process that directly converts semiconducting molten stibnite (Sb 2 S 3 ) into pure (99.9%) liquid antimony and sulfur vapour. At the bottom of the cell liquid antimony pools beneath cathodically polarized molten stibnite. At the top of the cell sulfur issues from a carbon anode immersed in an immiscible secondary molten salt electrolyte disposed above molten stibnite, thereby blocking electronic shorting across the cell. As opposed to conventional extraction practices, direct sulfide electrolysis completely avoids generation of problematic fugitive emissions (CO 2 , CO and SO 2 ), significantly reduces energy consumption, increases productivity in a single-step process (lower capital and operating costs) and is broadly applicable to a host of electronically conductive transition-metal chalcogenides. Introduction Direct electrochemical reduction of ores can improve metal recovery by simplifying the process, reducing energy consumption, as well as capital and operating costs, and offering cleaner, sustainable extraction pathways. The earliest example is aluminium production, thanks to the invention in 1886 of the Hall–Héroult process, which displaced the once conventional pyrometallurgical route and turned aluminium from a precious metal costing more than silver into a common structural material 1 . More recently, as an alternative to the established pyrometallurgical processes for titanium metal production (Hunter and Kroll), Fray, Farthing and Chen presented the idea of direct electrolytic reduction of solid titanium dioxide, the so-called FFC process 2 . On the horizon is molten oxide electrolysis, which has been shown by Sadoway et al. to produce liquid iron and by-product oxygen 3 , 4 . Analogous progress with electrolytic reduction of molten sulfides has been obstructed by their high melting temperature, which results in high vapour pressure, the lack of a practical inert anode, and the high degree of electronic conductivity and metal solubility in these melts 5 , 6 , 7 , 8 , 9 , 10 , which results in unacceptably high levels of cell shorting with attendant high energy consumption and low Faradaic efficiency 11 , 12 . Attempts to suppress electronic shorting across the cell typically resort to diluting the semiconducting compound in an ionic melt 13 , 14 with the intention of decreasing the electronic conductivity of the feedstock by lowering the concentration of solvated electrons or by creating trapping centres that lower electronic mobility 8 . Yet dilution unfavourably decreases mass transport with resultant loss in cell productivity. In some instances candidate additives can compete for electro-extraction with the element of interest and at high current density co-deposit, which renders the product unmarketable without further purification. In a radical departure from ionic dilution, here we instead adopt a different strategy, one that does not attempt to reduce electronic conduction of the feedstock but rather inhibits electron access to one of the cell’s electrodes by deployment of a discrete electron-blocking secondary molten electrolyte so as to enable direct metal recovery from ores that were previously deemed electrochemically irreducible. By way of example we demonstrate the production of high-purity liquid antimony via direct electrolysis of the molten semiconductor, antimony sulfide (Sb 2 S 3 ), derived from its predominant ore (mineral stibnite), in stark contrast to the more complicated traditional pyrometallurgical and hydrometallurgical extraction pathways ( Supplementary Note 1 ). Furthermore, since all reactants and products are fluid, we have the scalable conditions for a simple, continuous and high-throughput industrial process. Easy metal recovery is further enabled by the density ranking of Sb, Sb 2 S 3 and the secondary molten halide electrolyte, which self-segregate into three immiscible layers. Results Layout of electrolysis cell As seen in Fig. 1 , at the bottom of the cell higher density liquid antimony pools beneath cathodically polarized molten stibnite. At the top of the cell, sulfur issues from a carbon anode immersed in the electron-blocking secondary halide electrolyte, a separate layer distinct from the underlying molten stibnite feedstock. We observe high metal production rates and total conversion of the feedstock. Complete fluidity enables ready collection of products. Figure 1: Schematic of three-layered electrolysis cell. Schematic illustrating the use of an electron-blocking secondary electrolyte for direct electrolytic conversion of molten semiconducting Sb 2 S 3 into liquid Sb and sulfur vapour. Full size image Selection of electrolyte According to the phase diagrams 15 , 16 , Na 2 S and K 2 S are highly soluble in molten NaCl–KCl. This was confirmed experimentally in a transparent fused quartz cell charged with molten NaCl 50.6mol% –KCl 49.1% and 2 wt% Na 2 S. As shown in Supplementary Fig. 1 , molten NaCl–KCl–Na 2 S was observed to be uniform, red in colour and devoid of any precipitates, indicative of a single-phase liquid. In contrast, Sb 2 S 3 has only limited solubility in molten NaCl–KCl–Na 2 S at 700 °C (ref. 17 ). On this basis, we chose Na 2 S dissolved in molten NaCl–KCl to serve as a secondary electrolyte that conducts sulfide ion while obstructing the flow of electrons. Halides have previously been used in the FFC process for the reduction of solid-state feedstocks, including sulfides 18 , 19 . For example, solid MoS 2 was electrolysed in molten CaCl 2 to produce Mo (ref. 20 ). However, it was found that slow S 2– transport throttled productivity and caused CaS contamination. In another instance, tungsten powder was prepared by electrochemical reduction of solid WS 2 in molten NaCl–KCl (ref. 21 ). While these results demonstrate electrolytic reduction of a sulfide compound at moderate temperatures, conversion of solid feedstock into solid metal product is necessarily confined to three-phase conductor/insulator/electrolyte reaction sites, which impedes throughput rendering the process challenging at industrial scale for its low space-time yield 22 , 23 . Herein we overcome these limitations by resorting to an all-fluid system: molten semiconducting feedstock converting to liquid metal product and sulfur vapour by-product, the", "role": "user" }, { "content": "The MIT researchers were trying to develop a new battery, but it didn't work out that way. Instead, thanks to an unexpected finding in their lab tests, what they discovered was a whole new way of producing the metal antimony—and potentially a new way of smelting other metals, as well. The discovery could lead to metal-production systems that are much less expensive and that virtually eliminate the greenhouse gas emissions associated with most traditional metal smelting. Although antimony itself is not a widely used metal, the same principles may also be applied to producing much more abundant and economically important metals such as copper and nickel, the researchers say. The surprising finding is reported this week in the journal Nature Communications, in a paper by Donald Sadoway, the John F. Elliott Professor of Materials Chemistry; postdoc Huayi Yin; and visiting scholar Brice Chung. \"We were trying to develop a different electrochemistry for a battery,\" Sadoway explains, as an extension of the variety of chemical formulations for the all-liquid, high temperature storage batteries that his lab has been developing for several years. The different parts of these batteries are composed of molten metals or salts that have different densities and thus inherently form separate layers, much as oil floats on top of water. \"We wanted to investigate the utility of putting a second electrolyte between the positive and negative electrodes\" of the liquid battery, Sadoway says. Unexpected results But the experiment didn't go quite as planned. \"We found that when we went to charge this putative battery, we were in fact producing liquid antimony instead of charging the battery,\" Sadoway says. Then, the quest was on to figure out what had just happened. The material they were using, antimony sulfide, is a molten semiconductor, which normally would not allow for the kind of electrolytic process that is used to produce aluminum and some other metals through the application of an electric current. \"Antimony sulfide is a very good conductor of electrons,\" Sadoway says. \"But if you want to do electrolysis, you only want an ionic conductor\"—that is, a material that is good at conducting molecules that have a net electric charge. But by adding another layer on top of the molten semiconductor, one that is a very good ionic conductor, it turned out the electrolysis process worked very well in this \"battery,\" separating the metal out of the sulfide compound to form a pool of 99.9 percent pure antimony at the bottom of their cell, while pure sulfur gas accumulated at the top, where it could be collected for use as a chemical feedstock. In typical smelting processes, the sulfur would immediately bond with oxygen in the air to form sulfur dioxide, a significant air pollutant and the major cause of acid rain. But instead this contained process provides highly purified metal without the need to worry about scrubbing out the polluting gas. Simple, efficient process Electrolysis is much more efficient than traditional heat-based smelting methods, because it is a single-step continuous process, Sadoway explains. The discovery of that process is what transformed aluminum, more than a century ago, from a precious metal more valuable than silver into a widely used inexpensive commodity. If the process could be applied to other common industrial metals such as copper, it would have the potential to significantly lower prices as well as reduce the air pollution and greenhouse gas emissions associated with traditional production. \"The thing that made this such an exciting finding,\" Sadoway says, \"is that we could imagine doing the same for copper and nickel, metals that are used in large quantities.\" It made sense to start with antimony because it has a much lower melting point—just 631 degrees Celsius—compared to copper's 1,085 C. Though the higher melting temperatures of other metals add complication to designing an overall production system, the underlying physical principles are the same, and so such systems should eventually be feasible, he says. \"Antimony was a good test vehicle for the idea, but we could imagine doing something similar for much more common metals,\" Sadoway says. And while this demonstration used an ore that is a sulfide (metal combined with sulfur), \"we see no reason why this approach couldn't be generalized to oxide feedstocks,\" which represent the other major category of metal ores. Such a process would produce pure oxygen as the secondary product, instead of sulfur. Ultimately, if steel could be produced by such a process, it could have a major impact, because \"steel-making is the number one source of anthropogenic carbon dioxide,\" the main greenhouse gas, Sadoway says. But that will be a more difficult process to develop because of iron's high melting point of about 1,540 C. \"This paper demonstrates a novel approach to produce transition metals by direct electrolysis of their sulfides,\" says John Hryn, an Institute Senior Fellow at Northwestern University and a senior advisor at Argonne National Laboratory, who was not involved in this work. He praised the MIT team's use of a second electrolyte in the cell to counter the effects of electron conduction, \"which has previously stymied efficient high-volume production of transition metals by electrolysis. This seminal paper should usher in a new environmentally sound methodology for extraction of metals from sulfide ores.\" Hryn adds that although this demonstration used one specific metal, \"The primary value of using antimony is that it can be a demonstration metal for other transition-metal recovery by electrolysis.\" In addition, he says, \"The potential goes beyond the production of transition metals by electrolysis. The value is the approach used to control electronic conduction in an electrolytic cell, which has value beyond metal production.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Metals cannot be extracted by electrolysis of transition-metal sulfides because as liquids they are semiconductors, which exhibit high levels of electronic conduction and metal dissolution. Herein by introduction of a distinct secondary electrolyte, we reveal a high-throughput electro-desulfurization process that directly converts semiconducting molten stibnite (Sb 2 S 3 ) into pure (99.9%) liquid antimony and sulfur vapour. At the bottom of the cell liquid antimony pools beneath cathodically polarized molten stibnite. At the top of the cell sulfur issues from a carbon anode immersed in an immiscible secondary molten salt electrolyte disposed above molten stibnite, thereby blocking electronic shorting across the cell. As opposed to conventional extraction practices, direct sulfide electrolysis completely avoids generation of problematic fugitive emissions (CO 2 , CO and SO 2 ), significantly reduces energy consumption, increases productivity in a single-step process (lower capital and operating costs) and is broadly applicable to a host of electronically conductive transition-metal chalcogenides. Introduction Direct electrochemical reduction of ores can improve metal recovery by simplifying the process, reducing energy consumption, as well as capital and operating costs, and offering cleaner, sustainable extraction pathways. The earliest example is aluminium production, thanks to the invention in 1886 of the Hall–Héroult process, which displaced the once conventional pyrometallurgical route and turned aluminium from a precious metal costing more than silver into a common structural material 1 . More recently, as an alternative to the established pyrometallurgical processes for titanium metal production (Hunter and Kroll), Fray, Farthing and Chen presented the idea of direct electrolytic reduction of solid titanium dioxide, the so-called FFC process 2 . On the horizon is molten oxide electrolysis, which has been shown by Sadoway et al. to produce liquid iron and by-product oxygen 3 , 4 . Analogous progress with electrolytic reduction of molten sulfides has been obstructed by their high melting temperature, which results in high vapour pressure, the lack of a practical inert anode, and the high degree of electronic conductivity and metal solubility in these melts 5 , 6 , 7 , 8 , 9 , 10 , which results in unacceptably high levels of cell shorting with attendant high energy consumption and low Faradaic efficiency 11 , 12 . Attempts to suppress electronic shorting across the cell typically resort to diluting the semiconducting compound in an ionic melt 13 , 14 with the intention of decreasing the electronic conductivity of the feedstock by lowering the concentration of solvated electrons or by creating trapping centres that lower electronic mobility 8 . Yet dilution unfavourably decreases mass transport with resultant loss in cell productivity. In some instances candidate additives can compete for electro-extraction with the element of interest and at high current density co-deposit, which renders the product unmarketable without further purification. In a radical departure from ionic dilution, here we instead adopt a different strategy, one that does not attempt to reduce electronic conduction of the feedstock but rather inhibits electron access to one of the cell’s electrodes by deployment of a discrete electron-blocking secondary molten electrolyte so as to enable direct metal recovery from ores that were previously deemed electrochemically irreducible. By way of example we demonstrate the production of high-purity liquid antimony via direct electrolysis of the molten semiconductor, antimony sulfide (Sb 2 S 3 ), derived from its predominant ore (mineral stibnite), in stark contrast to the more complicated traditional pyrometallurgical and hydrometallurgical extraction pathways ( Supplementary Note 1 ). Furthermore, since all reactants and products are fluid, we have the scalable conditions for a simple, continuous and high-throughput industrial process. Easy metal recovery is further enabled by the density ranking of Sb, Sb 2 S 3 and the secondary molten halide electrolyte, which self-segregate into three immiscible layers. Results Layout of electrolysis cell As seen in Fig. 1 , at the bottom of the cell higher density liquid antimony pools beneath cathodically polarized molten stibnite. At the top of the cell, sulfur issues from a carbon anode immersed in the electron-blocking secondary halide electrolyte, a separate layer distinct from the underlying molten stibnite feedstock. We observe high metal production rates and total conversion of the feedstock. Complete fluidity enables ready collection of products. Figure 1: Schematic of three-layered electrolysis cell. Schematic illustrating the use of an electron-blocking secondary electrolyte for direct electrolytic conversion of molten semiconducting Sb 2 S 3 into liquid Sb and sulfur vapour. Full size image Selection of electrolyte According to the phase diagrams 15 , 16 , Na 2 S and K 2 S are highly soluble in molten NaCl–KCl. This was confirmed experimentally in a transparent fused quartz cell charged with molten NaCl 50.6mol% –KCl 49.1% and 2 wt% Na 2 S. As shown in Supplementary Fig. 1 , molten NaCl–KCl–Na 2 S was observed to be uniform, red in colour and devoid of any precipitates, indicative of a single-phase liquid. In contrast, Sb 2 S 3 has only limited solubility in molten NaCl–KCl–Na 2 S at 700 °C (ref. 17 ). On this basis, we chose Na 2 S dissolved in molten NaCl–KCl to serve as a secondary electrolyte that conducts sulfide ion while obstructing the flow of electrons. Halides have previously been used in the FFC process for the reduction of solid-state feedstocks, including sulfides 18 , 19 . For example, solid MoS 2 was electrolysed in molten CaCl 2 to produce Mo (ref. 20 ). However, it was found that slow S 2– transport throttled productivity and caused CaS contamination. In another instance, tungsten powder was prepared by electrochemical reduction of solid WS 2 in molten NaCl–KCl (ref. 21 ). While these results demonstrate electrolytic reduction of a sulfide compound at moderate temperatures, conversion of solid feedstock into solid metal product is necessarily confined to three-phase conductor/insulator/electrolyte reaction sites, which impedes throughput rendering the process challenging at industrial scale for its low space-time yield 22 , 23 . Herein we overcome these limitations by resorting to an all-fluid system: molten semiconducting feedstock converting to liquid metal product and sulfur vapour by-product, the<|im_end|> <|im_start|>assistant The MIT researchers were trying to develop a new battery, but it didn't work out that way. Instead, thanks to an unexpected finding in their lab tests, what they discovered was a whole new way of producing the metal antimony—and potentially a new way of smelting other metals, as well. The discovery could lead to metal-production systems that are much less expensive and that virtually eliminate the greenhouse gas emissions associated with most traditional metal smelting. Although antimony itself is not a widely used metal, the same principles may also be applied to producing much more abundant and economically important metals such as copper and nickel, the researchers say. The surprising finding is reported this week in the journal Nature Communications, in a paper by Donald Sadoway, the John F. Elliott Professor of Materials Chemistry; postdoc Huayi Yin; and visiting scholar Brice Chung. "We were trying to develop a different electrochemistry for a battery," Sadoway explains, as an extension of the variety of chemical formulations for the all-liquid, high temperature storage batteries that his lab has been developing for several years. The different parts of these batteries are composed of molten metals or salts that have different densities and thus inherently form separate layers, much as oil floats on top of water. "We wanted to investigate the utility of putting a second electrolyte between the positive and negative electrodes" of the liquid battery, Sadoway says. Unexpected results But the experiment didn't go quite as planned. "We found that when we went to charge this putative battery, we were in fact producing liquid antimony instead of charging the battery," Sadoway says. Then, the quest was on to figure out what had just happened. The material they were using, antimony sulfide, is a molten semiconductor, which normally would not allow for the kind of electrolytic process that is used to produce aluminum and some other metals through the application of an electric current. "Antimony sulfide is a very good conductor of electrons," Sadoway says. "But if you want to do electrolysis, you only want an ionic conductor"—that is, a material that is good at conducting molecules that have a net electric charge. But by adding another layer on top of the molten semiconductor, one that is a very good ionic conductor, it turned out the electrolysis process worked very well in this "battery," separating the metal out of the sulfide compound to form a pool of 99.9 percent pure antimony at the bottom of their cell, while pure sulfur gas accumulated at the top, where it could be collected for use as a chemical feedstock. In typical smelting processes, the sulfur would immediately bond with oxygen in the air to form sulfur dioxide, a significant air pollutant and the major cause of acid rain. But instead this contained process provides highly purified metal without the need to worry about scrubbing out the polluting gas. Simple, efficient process Electrolysis is much more efficient than traditional heat-based smelting methods, because it is a single-step continuous process, Sadoway explains. The discovery of that process is what transformed aluminum, more than a century ago, from a precious metal more valuable than silver into a widely used inexpensive commodity. If the process could be applied to other common industrial metals such as copper, it would have the potential to significantly lower prices as well as reduce the air pollution and greenhouse gas emissions associated with traditional production. "The thing that made this such an exciting finding," Sadoway says, "is that we could imagine doing the same for copper and nickel, metals that are used in large quantities." It made sense to start with antimony because it has a much lower melting point—just 631 degrees Celsius—compared to copper's 1,085 C. Though the higher melting temperatures of other metals add complication to designing an overall production system, the underlying physical principles are the same, and so such systems should eventually be feasible, he says. "Antimony was a good test vehicle for the idea, but we could imagine doing something similar for much more common metals," Sadoway says. And while this demonstration used an ore that is a sulfide (metal combined with sulfur), "we see no reason why this approach couldn't be generalized to oxide feedstocks," which represent the other major category of metal ores. Such a process would produce pure oxygen as the secondary product, instead of sulfur. Ultimately, if steel could be produced by such a process, it could have a major impact, because "steel-making is the number one source of anthropogenic carbon dioxide," the main greenhouse gas, Sadoway says. But that will be a more difficult process to develop because of iron's high melting point of about 1,540 C. "This paper demonstrates a novel approach to produce transition metals by direct electrolysis of their sulfides," says John Hryn, an Institute Senior Fellow at Northwestern University and a senior advisor at Argonne National Laboratory, who was not involved in this work. He praised the MIT team's use of a second electrolyte in the cell to counter the effects of electron conduction, "which has previously stymied efficient high-volume production of transition metals by electrolysis. This seminal paper should usher in a new environmentally sound methodology for extraction of metals from sulfide ores." Hryn adds that although this demonstration used one specific metal, "The primary value of using antimony is that it can be a demonstration metal for other transition-metal recovery by electrolysis." In addition, he says, "The potential goes beyond the production of transition metals by electrolysis. The value is the approach used to control electronic conduction in an electrolytic cell, which has value beyond metal production." <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 93815, 4250, 387, 28532, 555, 73396, 14744, 315, 9320, 89932, 40769, 3422, 1606, 439, 67849, 814, 527, 5347, 1965, 1076, 1105, 11, 902, 31324, 1579, 5990, 315, 14683, 390, 23985, 323, 9501, 81359, 13, 5810, 258, 555, 17219, 315, 264, 12742, 14580, 73396, 668, 11, 584, 16805, 264, 1579, 43847, 631, 25396, 25520, 14643, 324, 2065, 1920, 430, 6089, 33822, 5347, 1965, 1076, 287, 22337, 2002, 357, 581, 62664, 320, 50, 65, 220, 17, 328, 220, 18, 883, 1139, 10748, 320, 1484, 13, 24, 11587, 14812, 3276, 65556, 323, 72591, 68857, 414, 13, 2468, 279, 5740, 315, 279, 2849, 14812, 3276, 65556, 34239, 24923, 31747, 347, 2740, 25685, 1534, 22337, 2002, 357, 581, 62664, 13, 2468, 279, 1948, 315, 279, 2849, 72591, 4819, 505, 264, 12782, 459, 536, 78308, 304, 459, 4998, 3510, 1260, 14580, 22337, 2002, 12290, 73396, 668, 26655, 3485, 22337, 2002, 357, 581, 62664, 11, 28592, 22978, 14683, 2875, 287, 4028, 279, 2849, 13, 1666, 16475, 311, 21349, 33289, 12659, 11, 2167, 40769, 579, 73396, 14744, 6724, 55952, 9659, 315, 36033, 49184, 3486, 20748, 320, 8445, 220, 17, 1174, 7432, 323, 5745, 220, 17, 7026, 12207, 26338, 4907, 15652, 11, 12992, 26206, 304, 264, 3254, 30308, 1920, 320, 15115, 6864, 323, 10565, 7194, 8, 323, 374, 44029, 8581, 311, 264, 3552, 315, 71870, 6929, 535, 9320, 89932, 523, 17356, 11968, 3422, 13, 29438, 7286, 25396, 32056, 14278, 315, 76158, 649, 7417, 9501, 13654, 555, 15858, 7922, 279, 1920, 11, 18189, 4907, 15652, 11, 439, 1664, 439, 6864, 323, 10565, 7194, 11, 323, 10209, 32981, 11, 22556, 33289, 44014, 13, 578, 30758, 3187, 374, 55993, 5788, 11, 9523, 311, 279, 28229, 304, 220, 9367, 21, 315, 279, 11166, 4235, 39, 978, 583, 4937, 1920, 11, 902, 49246, 279, 3131, 21349, 4611, 442, 295, 543, 57673, 6149, 323, 6656, 55993, 505, 264, 27498, 9501, 54824, 810, 1109, 15310, 1139, 264, 4279, 24693, 3769, 220, 16, 662, 4497, 6051, 11, 439, 459, 10778, 311, 279, 9749, 4611, 442, 295, 543, 57673, 11618, 369, 71404, 9501, 5788, 320, 86791, 323, 735, 1119, 705, 2939, 352, 11, 13759, 1626, 323, 25507, 10666, 279, 4623, 315, 2167, 73396, 29150, 14278, 315, 6573, 71404, 40589, 11, 279, 779, 19434, 435, 6897, 1920, 220, 17, 662, 1952, 279, 35174, 374, 22337, 2002, 51180, 73396, 14744, 11, 902, 706, 1027, 6982, 555, 328, 5967, 352, 1880, 453, 13, 311, 8356, 14812, 11245, 323, 555, 29745, 24463, 220, 18, 1174, 220, 19, 662, 64546, 788, 5208, 449, 73396, 29150, 14278, 315, 22337, 2002, 40769, 3422, 706, 1027, 54292, 291, 555, 872, 1579, 50684, 9499, 11, 902, 3135, 304, 1579, 68857, 414, 7410, 11, 279, 6996, 315, 264, 15325, 81073, 459, 536, 11, 323, 279, 1579, 8547, 315, 14683, 98971, 323, 9501, 2092, 392, 1429, 304, 1521, 99191, 220, 20, 1174, 220, 21, 1174, 220, 22, 1174, 220, 23, 1174, 220, 24, 1174, 220, 605, 1174, 902, 3135, 304, 653, 10543, 2915, 1579, 5990, 315, 2849, 2875, 287, 449, 65022, 1579, 4907, 15652, 323, 3428, 13759, 2649, 292, 15374, 220, 806, 1174, 220, 717, 662, 84400, 311, 28321, 14683, 2875, 287, 4028, 279, 2849, 11383, 22541, 311, 19371, 10831, 279, 5347, 1965, 1076, 287, 24549, 304, 459, 220, 21427, 30099, 220, 1032, 1174, 220, 975, 449, 279, 14944, 315, 44649, 279, 14683, 98971, 315, 279, 5510, 13787, 555, 46301, 279, 20545, 315, 2092, 85, 660, 57678, 477, 555, 6968, 93669, 36282, 430, 4827, 14683, 31139, 220, 23, 662, 14968, 19371, 1516, 9662, 27089, 2915, 43154, 3148, 7710, 449, 84913, 4814, 304, 2849, 26206, 13, 763, 1063, 13422, 9322, 85286, 649, 20874, 369, 25396, 10397, 27523, 449, 279, 2449, 315, 2802, 323, 520, 1579, 1510, 17915, 1080, 6953, 2792, 11, 902, 45382, 279, 2027, 653, 19859, 481, 2085, 4726, 94536, 13, 763, 264, 18336, 25959, 505, 220, 21427, 19371, 1516, 11, 1618, 584, 4619, 11142, 264, 2204, 8446, 11, 832, 430, 1587, 539, 4879, 311, 8108, 14683, 390, 23985, 315, 279, 5510, 13787, 719, 4856, 20747, 1220, 17130, 2680, 311, 832, 315, 279, 2849, 753, 80390, 555, 24047, 315, 264, 44279, 17130, 79861, 14580, 22337, 2002, 73396, 668, 779, 439, 311, 7431, 2167, 9501, 13654, 505, 76158, 430, 1051, 8767, 25660, 25396, 2464, 2740, 25912, 79385, 13, 3296, 1648, 315, 3187, 584, 20461, 279, 5788, 315, 1579, 2320, 5631, 14812, 3276, 65556, 4669, 2167, 73396, 14744, 315, 279, 22337, 2002, 87836, 11, 3276, 65556, 40769, 579, 320, 50, 65, 220, 17, 328, 220, 18, 7026, 14592, 505, 1202, 96531, 16536, 320, 1083, 3333, 357, 581, 62664, 705, 304, 38246, 13168, 311, 279, 810, 17395, 8776, 4611, 442, 295, 543, 57673, 323, 6409, 67, 442, 295, 543, 57673, 33289, 44014, 320, 99371, 7181, 220, 16, 7609, 24296, 11, 2533, 682, 14085, 1821, 323, 3956, 527, 15962, 11, 584, 617, 279, 69311, 4787, 369, 264, 4382, 11, 19815, 323, 1579, 43847, 631, 13076, 1920, 13, 19122, 9501, 13654, 374, 4726, 9147, 555, 279, 17915, 23862, 315, 109116, 11, 109116, 220, 17, 328, 220, 18, 323, 279, 14580, 22337, 2002, 15104, 579, 73396, 668, 11, 902, 659, 7962, 14574, 1139, 2380, 4998, 3510, 1260, 13931, 13, 18591, 14141, 315, 73396, 14744, 2849, 1666, 3970, 304, 23966, 13, 220, 16, 1174, 520, 279, 5740, 315, 279, 2849, 5190, 17915, 14812, 3276, 65556, 34239, 24923, 31747, 347, 2740, 25685, 1534, 22337, 2002, 357, 581, 62664, 13, 2468, 279, 1948, 315, 279, 2849, 11, 72591, 4819, 505, 264, 12782, 459, 536, 78308, 304, 279, 17130, 79861, 14580, 15104, 579, 73396, 668, 11, 264, 8821, 6324, 12742, 505, 279, 16940, 22337, 2002, 357, 581, 62664, 5510, 13787, 13, 1226, 23846, 1579, 9501, 5788, 7969, 323, 2860, 14747, 315, 279, 5510, 13787, 13, 19121, 15962, 488, 20682, 5644, 4526, 315, 3956, 13, 19575, 220, 16, 25, 328, 82149, 315, 2380, 48435, 291, 73396, 14744, 2849, 13, 328, 82149, 94012, 279, 1005, 315, 459, 17130, 79861, 14580, 73396, 668, 369, 2167, 73396, 29150, 14747, 315, 22337, 2002, 5347, 1965, 1076, 287, 109116, 220, 17, 328, 220, 18, 1139, 14812, 109116, 323, 72591, 68857, 414, 13, 8797, 1404, 2217, 25117, 315, 73396, 668, 10771, 311, 279, 10474, 47287, 220, 868, 1174, 220, 845, 1174, 13106, 220, 17, 328, 323, 735, 220, 17, 328, 527, 7701, 88045, 304, 22337, 2002, 13106, 5176, 4235, 42, 5176, 13, 1115, 574, 11007, 9526, 750, 304, 264, 18300, 75754, 52255, 2849, 11684, 449, 22337, 2002, 13106, 5176, 220, 1135, 13, 21, 45444, 4, 1389, 42, 5176, 220, 2491, 13, 16, 4, 323, 220, 17, 41573, 4, 13106, 220, 17, 328, 13, 1666, 6982, 304, 99371, 23966, 13, 220, 16, 1174, 22337, 2002, 13106, 5176, 4235, 42, 5176, 4235, 16589, 220, 17, 328, 574, 13468, 311, 387, 14113, 11, 2579, 304, 12745, 323, 76939, 315, 904, 36841, 82829, 11, 64005, 315, 264, 3254, 82710, 14812, 13, 763, 13168, 11, 109116, 220, 17, 328, 220, 18, 706, 1193, 7347, 2092, 392, 1429, 304, 22337, 2002, 13106, 5176, 4235, 42, 5176, 4235, 16589, 220, 17, 328, 520, 220, 7007, 37386, 34, 320, 1116, 13, 220, 1114, 7609, 1952, 420, 8197, 11, 584, 14896, 13106, 220, 17, 328, 56767, 304, 22337, 2002, 13106, 5176, 4235, 42, 5176, 311, 8854, 439, 264, 14580, 73396, 668, 430, 74198, 40769, 579, 28772, 1418, 54292, 287, 279, 6530, 315, 57678, 13, 20442, 3422, 617, 8767, 1027, 1511, 304, 279, 435, 6897, 1920, 369, 279, 14278, 315, 6573, 21395, 5510, 69127, 11, 2737, 40769, 3422, 220, 972, 1174, 220, 777, 662, 1789, 3187, 11, 6573, 6178, 50, 220, 17, 574, 73396, 32424, 304, 22337, 2002, 14751, 5176, 220, 17, 311, 8356, 6178, 320, 1116, 13, 220, 508, 7609, 4452, 11, 433, 574, 1766, 430, 6435, 328, 220, 17, 4235, 7710, 81072, 839, 26206, 323, 9057, 14751, 50, 47810, 13, 763, 2500, 2937, 11, 85307, 16172, 17138, 574, 10235, 555, 25396, 32056, 14278, 315, 6573, 25950, 220, 17, 304, 22337, 2002, 13106, 5176, 4235, 42, 5176, 320, 1116, 13, 220, 1691, 7609, 6104, 1521, 3135, 20461, 73396, 29150, 14278, 315, 264, 40769, 579, 24549, 520, 24070, 20472, 11, 14747, 315, 6573, 5510, 13787, 1139, 6573, 9501, 2027, 374, 14647, 45408, 311, 2380, 82710, 61856, 14, 1354, 10733, 16954, 772, 299, 398, 668, 13010, 6732, 11, 902, 50502, 288, 64862, 21568, 279, 1920, 17436, 520, 13076, 5569, 369, 1202, 3428, 3634, 7394, 7692, 220, 1313, 1174, 220, 1419, 662, 5810, 258, 584, 23075, 1521, 9669, 555, 22541, 287, 311, 459, 682, 17878, 1887, 25, 22337, 2002, 5347, 1965, 1076, 287, 5510, 13787, 34537, 311, 14812, 9501, 2027, 323, 72591, 68857, 414, 555, 29745, 11, 279, 128257, 198, 128256, 78191, 198, 791, 15210, 12074, 1051, 4560, 311, 2274, 264, 502, 11863, 11, 719, 433, 3287, 956, 990, 704, 430, 1648, 13, 12361, 11, 9523, 311, 459, 16907, 9455, 304, 872, 10278, 7177, 11, 1148, 814, 11352, 574, 264, 4459, 502, 1648, 315, 17843, 279, 9501, 3276, 65556, 17223, 13893, 264, 502, 1648, 315, 1554, 301, 1303, 1023, 37182, 11, 439, 1664, 13, 578, 18841, 1436, 3063, 311, 9501, 70666, 6067, 430, 527, 1790, 2753, 11646, 323, 430, 21907, 22472, 279, 37647, 6962, 20748, 5938, 449, 1455, 8776, 9501, 1554, 301, 1303, 13, 10541, 3276, 65556, 5196, 374, 539, 264, 13882, 1511, 9501, 11, 279, 1890, 16565, 1253, 1101, 387, 9435, 311, 17843, 1790, 810, 44611, 323, 47379, 3062, 37182, 1778, 439, 24166, 323, 52349, 11, 279, 12074, 2019, 13, 578, 15206, 9455, 374, 5068, 420, 2046, 304, 279, 8486, 22037, 26545, 11, 304, 264, 5684, 555, 9641, 328, 5967, 352, 11, 279, 3842, 435, 13, 48644, 17054, 315, 32009, 42846, 26, 1772, 5349, 22546, 112717, 83958, 26, 323, 17136, 18640, 3320, 560, 88425, 13, 330, 1687, 1051, 4560, 311, 2274, 264, 2204, 25396, 52755, 369, 264, 11863, 1359, 328, 5967, 352, 15100, 11, 439, 459, 9070, 315, 279, 8205, 315, 11742, 98077, 369, 279, 682, 12, 54737, 11, 1579, 9499, 5942, 27360, 430, 813, 10278, 706, 1027, 11469, 369, 3892, 1667, 13, 578, 2204, 5596, 315, 1521, 27360, 527, 24306, 315, 22337, 2002, 37182, 477, 78235, 430, 617, 2204, 90816, 323, 8617, 49188, 1376, 8821, 13931, 11, 1790, 439, 5707, 49002, 389, 1948, 315, 3090, 13, 330, 1687, 4934, 311, 19874, 279, 15919, 315, 10917, 264, 2132, 73396, 668, 1990, 279, 6928, 323, 8389, 80390, 1, 315, 279, 14812, 11863, 11, 328, 5967, 352, 2795, 13, 71500, 3135, 2030, 279, 9526, 3287, 956, 733, 5115, 439, 13205, 13, 330, 1687, 1766, 430, 994, 584, 4024, 311, 6900, 420, 2231, 1413, 11863, 11, 584, 1051, 304, 2144, 17843, 14812, 3276, 65556, 4619, 315, 23468, 279, 11863, 1359, 328, 5967, 352, 2795, 13, 5112, 11, 279, 2271, 574, 389, 311, 7216, 704, 1148, 1047, 1120, 7077, 13, 578, 3769, 814, 1051, 1701, 11, 3276, 65556, 40769, 579, 11, 374, 264, 22337, 2002, 87836, 11, 902, 14614, 1053, 539, 2187, 369, 279, 3169, 315, 73396, 29150, 1920, 430, 374, 1511, 311, 8356, 25674, 323, 1063, 1023, 37182, 1555, 279, 3851, 315, 459, 9249, 1510, 13, 330, 17555, 65556, 40769, 579, 374, 264, 1633, 1695, 61856, 315, 57678, 1359, 328, 5967, 352, 2795, 13, 330, 4071, 422, 499, 1390, 311, 656, 73396, 14744, 11, 499, 1193, 1390, 459, 220, 21427, 61856, 66101, 9210, 374, 11, 264, 3769, 430, 374, 1695, 520, 31474, 35715, 430, 617, 264, 4272, 9249, 6900, 13, 2030, 555, 7999, 2500, 6324, 389, 1948, 315, 279, 22337, 2002, 87836, 11, 832, 430, 374, 264, 1633, 1695, 220, 21427, 61856, 11, 433, 6656, 704, 279, 73396, 14744, 1920, 6575, 1633, 1664, 304, 420, 330, 75459, 1359, 50545, 279, 9501, 704, 315, 279, 40769, 579, 24549, 311, 1376, 264, 7463, 315, 220, 1484, 13, 24, 3346, 10748, 3276, 65556, 520, 279, 5740, 315, 872, 2849, 11, 1418, 10748, 72591, 6962, 41165, 520, 279, 1948, 11, 1405, 433, 1436, 387, 14890, 369, 1005, 439, 264, 11742, 5510, 13787, 13, 763, 14595, 1554, 301, 1303, 11618, 11, 279, 72591, 1053, 7214, 11049, 449, 24463, 304, 279, 3805, 311, 1376, 72591, 40589, 11, 264, 5199, 3805, 71134, 519, 323, 279, 3682, 5353, 315, 13935, 11422, 13, 2030, 4619, 420, 13282, 1920, 5825, 7701, 92600, 9501, 2085, 279, 1205, 311, 11196, 922, 46001, 7278, 704, 279, 7230, 10831, 6962, 13, 9170, 11, 11297, 1920, 69390, 398, 14744, 374, 1790, 810, 11297, 1109, 8776, 8798, 6108, 1554, 301, 1303, 5528, 11, 1606, 433, 374, 264, 3254, 30308, 19815, 1920, 11, 328, 5967, 352, 15100, 13, 578, 18841, 315, 430, 1920, 374, 1148, 24411, 25674, 11, 810, 1109, 264, 9478, 4227, 11, 505, 264, 27498, 9501, 810, 15525, 1109, 15310, 1139, 264, 13882, 1511, 44252, 38983, 13, 1442, 279, 1920, 1436, 387, 9435, 311, 1023, 4279, 13076, 37182, 1778, 439, 24166, 11, 433, 1053, 617, 279, 4754, 311, 12207, 4827, 7729, 439, 1664, 439, 8108, 279, 3805, 25793, 323, 37647, 6962, 20748, 5938, 449, 8776, 5788, 13, 330, 791, 3245, 430, 1903, 420, 1778, 459, 13548, 9455, 1359, 328, 5967, 352, 2795, 11, 330, 285, 430, 584, 1436, 13085, 3815, 279, 1890, 369, 24166, 323, 52349, 11, 37182, 430, 527, 1511, 304, 3544, 33776, 1210, 1102, 1903, 5647, 311, 1212, 449, 3276, 65556, 1606, 433, 706, 264, 1790, 4827, 50684, 1486, 2345, 4345, 220, 21729, 12628, 62447, 2345, 5807, 1636, 311, 24166, 596, 220, 16, 11, 24646, 356, 13, 18056, 279, 5190, 50684, 20472, 315, 1023, 37182, 923, 86919, 311, 30829, 459, 8244, 5788, 1887, 11, 279, 16940, 7106, 16565, 527, 279, 1890, 11, 323, 779, 1778, 6067, 1288, 9778, 387, 43303, 11, 568, 2795, 13, 330, 17555, 65556, 574, 264, 1695, 1296, 7458, 369, 279, 4623, 11, 719, 584, 1436, 13085, 3815, 2555, 4528, 369, 1790, 810, 4279, 37182, 1359, 328, 5967, 352, 2795, 13, 1628, 1418, 420, 30816, 1511, 459, 16536, 430, 374, 264, 40769, 579, 320, 55108, 11093, 449, 72591, 705, 330, 906, 1518, 912, 2944, 3249, 420, 5603, 7846, 956, 387, 67217, 311, 51180, 5510, 69127, 1359, 902, 4097, 279, 1023, 3682, 5699, 315, 9501, 76158, 13, 15483, 264, 1920, 1053, 8356, 10748, 24463, 439, 279, 14580, 2027, 11, 4619, 315, 72591, 13, 55106, 11, 422, 9699, 1436, 387, 9124, 555, 1778, 264, 1920, 11, 433, 1436, 617, 264, 3682, 5536, 11, 1606, 330, 62654, 28846, 374, 279, 1396, 832, 2592, 315, 41416, 29569, 12782, 40589, 1359, 279, 1925, 37647, 6962, 11, 328, 5967, 352, 2795, 13, 2030, 430, 690, 387, 264, 810, 5107, 1920, 311, 2274, 1606, 315, 11245, 596, 1579, 50684, 1486, 315, 922, 220, 16, 11, 17048, 356, 13, 330, 2028, 5684, 32216, 264, 11775, 5603, 311, 8356, 9320, 37182, 555, 2167, 73396, 14744, 315, 872, 40769, 3422, 1359, 2795, 3842, 473, 61343, 11, 459, 10181, 19903, 37946, 520, 67363, 3907, 323, 264, 10195, 37713, 520, 7793, 30052, 5165, 32184, 11, 889, 574, 539, 6532, 304, 420, 990, 13, 1283, 37475, 279, 15210, 2128, 596, 1005, 315, 264, 2132, 73396, 668, 304, 279, 2849, 311, 5663, 279, 6372, 315, 17130, 390, 23985, 11, 330, 8370, 706, 8767, 357, 1631, 1142, 11297, 1579, 67868, 5788, 315, 9320, 37182, 555, 73396, 14744, 13, 1115, 90773, 5684, 1288, 64260, 304, 264, 502, 57340, 5222, 38152, 369, 33289, 315, 37182, 505, 40769, 579, 76158, 1210, 473, 61343, 11621, 430, 8051, 420, 30816, 1511, 832, 3230, 9501, 11, 330, 791, 6156, 907, 315, 1701, 3276, 65556, 374, 430, 433, 649, 387, 264, 30816, 9501, 369, 1023, 9320, 89932, 13654, 555, 73396, 14744, 1210, 763, 5369, 11, 568, 2795, 11, 330, 791, 4754, 5900, 7953, 279, 5788, 315, 9320, 37182, 555, 73396, 14744, 13, 578, 907, 374, 279, 5603, 1511, 311, 2585, 14683, 390, 23985, 304, 459, 73396, 29150, 2849, 11, 902, 706, 907, 7953, 9501, 5788, 1210, 220, 128257, 198 ]

2,611

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Virtual reality (VR) provides a valuable research tool for studying what occurs when sensorimotor feedback loops are manipulated. Here we measured whether exposure to a novel temporal relationship between action and sensory reaction in VR causes recalibration of time perception. We asked 31 participants to perform time perception tasks where the interval of a moving probe was reproduced using continuous or discrete motor methods. These time perception tasks were completed pre- and post-exposure to dynamic VR content in a block-counterbalanced order. One group of participants experienced a standard VR task (“normal-time”), while another group had their real-world movements coupled to the flow of time in the virtual space (“movement contingent time-flow; MCTF”). We expected this novel action-perception relationship to affect continuous motor time perception performance, but not discrete motor time perception. The results indicated duration-dependent recalibration specific to a motor task involving continuous movement such that the probe intervals were under-estimated by approximately 15% following exposure to VR with the MCTF manipulation. Control tasks in VR and non-VR settings produced similar results to those of the normal-time VR group, confirming the specificity of the MCTF manipulation. The findings provide valuable insights into the potential impact of VR on sensorimotor recalibration. Understanding this process will be valuable for the development and implementation of rehabilitation practices. Introduction The ability to estimate the passage of time with precision is fundamental to our ability to perceive and interact with the world. One key characteristic of time perception is that it is highly plastic, supporting the ability to adapt to changing environmental conditions 1 , 2 , 3 , 4 . Although the plasticity of time perception has been well established, several open questions remain regarding the strength, persistence, and specificity of temporal recalibration effects. For instance, do these recalibration effects generalize across different modes of duration estimation (e.g., continuous and discrete motor reproduction)? Answering such questions will improve the understanding of the computational and neural basis for time perception, which has gained significant interest of late partially due to the appeal of preventing or reversing maladaptive changes to time perception with age 5 , 6 , 7 , 8 . Computational Perspectives of Time Perception Time perception is a multifaceted construct, and several theoretical perspectives have been proposed in the temporal processing literature (for review, see 9 ). The dominant model of temporal processing involves a central internal clock 10 , 11 , 12 , 13 . In this model, time perception is represented by the subjective count of pulses that accumulate within a given interval. There is evidence 14 that these mechanisms, theorised to underlie the conscious perception of time, also drive the timing of motor performance (also see 15 ). Research suggests that the neural pacing signal of the internal clock system, rather than being static, can be modulated by sensory inputs from external stimuli. A supra-modal system contrasts with the idea of dedicated mechanisms for each sense, although it is possible that a central mechanism subserves supra-second intervals, while sub-second intervals are processed by modality-specific systems 12 , 16 . Others have proposed models that do not require pulse intervals for timekeeping, suggesting instead that time is encoded in spatial 17 , 18 or temporal 19 patterns of neuronal firing. These state-dependent network models have gained recognition on the basis of support from psychophysical studies of temporal processing and learning mechanisms 20 , 21 , 22 . While each model has proven useful, there is a lack of compelling in vivo physiological evidence for the existence of a pacing signal or state-dependent representations of timing 23 . Neurophysiology of Time Perception Describing the processes underlying time perception at the neural level has been a major challenge in the field. Although still a matter of debate, the brain structures thought to be involved in time perception include the cerebellum, prefrontal cortex, basal ganglia, and supplementary motor area 16 , 24 , 25 . Recent transcranial magnetic stimulation (TMS) evidence has supported the role of the cerebellum and prefrontal cortex in time perception. TMS used to disrupt cerebellar activity impairs timing of sub-second durations 26 , 27 , 28 , whereas inhibitory TMS over prefrontal cortex impairs timing of supra-second durations 27 , 29 . It has been proposed that the prefrontal cortex operates in a feedback role by using the sensory information following an action to update temporal expectations 30 , whereas the cerebellum plays a feed-forward role in making temporal predictions prior to an action 16 . Basal ganglia activity is associated with the encoding of temporal processing and representation of stimulus duration, which is demonstrated by both the behavioural data of Parkinson’s patients with basal ganglia dysfunction 31 and by functional magnetic resonance imaging (fMRI) studies 24 , 32 , 33 , 34 . These neuroanatomical studies in conjunction with non-human pharmacological studies have supported the idea that timekeeping is modulated by dopamine neurotransmission, specifically at the D2 receptor 16 , 35 , 36 . Dopamine antagonists (e.g., neuroleptics) decrease subjective estimations of event duration 37 , whereas dopamine agonists (e.g., methamphetamine) lead to an increase in duration estimations 38 , 39 . Recent evidence also suggests a prominent role for GABA in time perception; magnetic resonance imaging of the rat cortex shows that elevated GABA levels correspond to underestimation in the perceived duration of sub-second intervals, possibly due to diminished awareness of visual stimuli 37 , 40 . Evidence of Temporal Recalibration Neurophysiology studies not only provide insight into the neural mechanism of the internal clock, but they also support the idea that time perception can be manipulated. The speed of this internal clock can be increased or decreased depending on the drug administered, which can lead to behavioural changes 38 , 41 . Another phenomenon that has been shown to speed up the internal clock is the click train effect, whereby listening to a train of clicks (e.g., 5 sec of clicks at 5 clicks/sec) induces a 10% decrease in the perceived duration of subsequent intervals 2", "role": "user" }, { "content": "Playing games in virtual reality (VR) could be a key tool in treating people with neurological disorders such as autism, schizophrenia and Parkinson's disease. The technology, according to a recent study from the University of Waterloo, could help individuals with these neurological conditions shift their perceptions of time, which their conditions lead them to perceive differently. \"The ability to estimate the passage of time with precision is fundamental to our ability to interact with the world,\" says co-author Séamas Weech, post-doctoral fellow in Kinesiology. \"For some individuals, however, the internal clock is maladjusted, causing timing deficiencies that affect perception and action. \"Studies like ours help us to understand how these deficiencies might be acquired, and how to recalibrate time perception in the brain.\" The UWaterloo study involved 18 females and 13 males with normal vision and no sensory, musculoskeletal or neurological disorders. The researchers used a virtual reality game, Robo Recall, to create a natural setting in which to encourage re-calibration of time perception. The key manipulation of the study was that the researchers coupled the speed and duration of visual events to the participant's body movements. The researchers measured participants' time perception abilities before and after they were exposed to the dynamic VR task. Some participants also completed non-VR time-perception tasks, such as throwing a ball, to use as a control comparison. The researchers measured the actual and perceived durations of a moving probe in the time perception tasks. They discovered that the virtual reality manipulation was associated with significant reductions in the participants' estimates of time, by around 15 percent. \"This study adds valuable proof that the perception of time is flexible, and that VR offers a potentially valuable tool for recalibrating time in the brain,\" says Weech. \"It offers a compelling application for rehabilitation initiatives that focus on how time perception breaks down in certain populations.\" Weech adds, however, that while the effects were strong during the current study, more research is needed to find out how long the effects last, and whether these signals are observable in the brain. \"For developing clinical applications, we need to know whether these effects are stable for minutes, days, or weeks afterward. A longitudinal study would provide the answer to this question.\" \"Virtual reality technology has matured dramatically,\" says Michael Barnett-Cowan, neuroscience professor in the Department of Kinesiology and senior author of the paper. \"VR now convincingly changes our experience of space and time, enabling basic research in perception to inform our understanding of how the brains of normal, injured, aged and diseased populations work and how they can be treated to perform optimally.\" The article, \"Movement-Contingent Time Flow in Virtual Reality Causes Temporal Recalibration\" was written by Ambika Bansal, Séamas Weech and Michael Barnett-Cowan, and published in Scientific Reports. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Virtual reality (VR) provides a valuable research tool for studying what occurs when sensorimotor feedback loops are manipulated. Here we measured whether exposure to a novel temporal relationship between action and sensory reaction in VR causes recalibration of time perception. We asked 31 participants to perform time perception tasks where the interval of a moving probe was reproduced using continuous or discrete motor methods. These time perception tasks were completed pre- and post-exposure to dynamic VR content in a block-counterbalanced order. One group of participants experienced a standard VR task (“normal-time”), while another group had their real-world movements coupled to the flow of time in the virtual space (“movement contingent time-flow; MCTF”). We expected this novel action-perception relationship to affect continuous motor time perception performance, but not discrete motor time perception. The results indicated duration-dependent recalibration specific to a motor task involving continuous movement such that the probe intervals were under-estimated by approximately 15% following exposure to VR with the MCTF manipulation. Control tasks in VR and non-VR settings produced similar results to those of the normal-time VR group, confirming the specificity of the MCTF manipulation. The findings provide valuable insights into the potential impact of VR on sensorimotor recalibration. Understanding this process will be valuable for the development and implementation of rehabilitation practices. Introduction The ability to estimate the passage of time with precision is fundamental to our ability to perceive and interact with the world. One key characteristic of time perception is that it is highly plastic, supporting the ability to adapt to changing environmental conditions 1 , 2 , 3 , 4 . Although the plasticity of time perception has been well established, several open questions remain regarding the strength, persistence, and specificity of temporal recalibration effects. For instance, do these recalibration effects generalize across different modes of duration estimation (e.g., continuous and discrete motor reproduction)? Answering such questions will improve the understanding of the computational and neural basis for time perception, which has gained significant interest of late partially due to the appeal of preventing or reversing maladaptive changes to time perception with age 5 , 6 , 7 , 8 . Computational Perspectives of Time Perception Time perception is a multifaceted construct, and several theoretical perspectives have been proposed in the temporal processing literature (for review, see 9 ). The dominant model of temporal processing involves a central internal clock 10 , 11 , 12 , 13 . In this model, time perception is represented by the subjective count of pulses that accumulate within a given interval. There is evidence 14 that these mechanisms, theorised to underlie the conscious perception of time, also drive the timing of motor performance (also see 15 ). Research suggests that the neural pacing signal of the internal clock system, rather than being static, can be modulated by sensory inputs from external stimuli. A supra-modal system contrasts with the idea of dedicated mechanisms for each sense, although it is possible that a central mechanism subserves supra-second intervals, while sub-second intervals are processed by modality-specific systems 12 , 16 . Others have proposed models that do not require pulse intervals for timekeeping, suggesting instead that time is encoded in spatial 17 , 18 or temporal 19 patterns of neuronal firing. These state-dependent network models have gained recognition on the basis of support from psychophysical studies of temporal processing and learning mechanisms 20 , 21 , 22 . While each model has proven useful, there is a lack of compelling in vivo physiological evidence for the existence of a pacing signal or state-dependent representations of timing 23 . Neurophysiology of Time Perception Describing the processes underlying time perception at the neural level has been a major challenge in the field. Although still a matter of debate, the brain structures thought to be involved in time perception include the cerebellum, prefrontal cortex, basal ganglia, and supplementary motor area 16 , 24 , 25 . Recent transcranial magnetic stimulation (TMS) evidence has supported the role of the cerebellum and prefrontal cortex in time perception. TMS used to disrupt cerebellar activity impairs timing of sub-second durations 26 , 27 , 28 , whereas inhibitory TMS over prefrontal cortex impairs timing of supra-second durations 27 , 29 . It has been proposed that the prefrontal cortex operates in a feedback role by using the sensory information following an action to update temporal expectations 30 , whereas the cerebellum plays a feed-forward role in making temporal predictions prior to an action 16 . Basal ganglia activity is associated with the encoding of temporal processing and representation of stimulus duration, which is demonstrated by both the behavioural data of Parkinson’s patients with basal ganglia dysfunction 31 and by functional magnetic resonance imaging (fMRI) studies 24 , 32 , 33 , 34 . These neuroanatomical studies in conjunction with non-human pharmacological studies have supported the idea that timekeeping is modulated by dopamine neurotransmission, specifically at the D2 receptor 16 , 35 , 36 . Dopamine antagonists (e.g., neuroleptics) decrease subjective estimations of event duration 37 , whereas dopamine agonists (e.g., methamphetamine) lead to an increase in duration estimations 38 , 39 . Recent evidence also suggests a prominent role for GABA in time perception; magnetic resonance imaging of the rat cortex shows that elevated GABA levels correspond to underestimation in the perceived duration of sub-second intervals, possibly due to diminished awareness of visual stimuli 37 , 40 . Evidence of Temporal Recalibration Neurophysiology studies not only provide insight into the neural mechanism of the internal clock, but they also support the idea that time perception can be manipulated. The speed of this internal clock can be increased or decreased depending on the drug administered, which can lead to behavioural changes 38 , 41 . Another phenomenon that has been shown to speed up the internal clock is the click train effect, whereby listening to a train of clicks (e.g., 5 sec of clicks at 5 clicks/sec) induces a 10% decrease in the perceived duration of subsequent intervals 2<|im_end|> <|im_start|>assistant Playing games in virtual reality (VR) could be a key tool in treating people with neurological disorders such as autism, schizophrenia and Parkinson's disease. The technology, according to a recent study from the University of Waterloo, could help individuals with these neurological conditions shift their perceptions of time, which their conditions lead them to perceive differently. "The ability to estimate the passage of time with precision is fundamental to our ability to interact with the world," says co-author Séamas Weech, post-doctoral fellow in Kinesiology. "For some individuals, however, the internal clock is maladjusted, causing timing deficiencies that affect perception and action. "Studies like ours help us to understand how these deficiencies might be acquired, and how to recalibrate time perception in the brain." The UWaterloo study involved 18 females and 13 males with normal vision and no sensory, musculoskeletal or neurological disorders. The researchers used a virtual reality game, Robo Recall, to create a natural setting in which to encourage re-calibration of time perception. The key manipulation of the study was that the researchers coupled the speed and duration of visual events to the participant's body movements. The researchers measured participants' time perception abilities before and after they were exposed to the dynamic VR task. Some participants also completed non-VR time-perception tasks, such as throwing a ball, to use as a control comparison. The researchers measured the actual and perceived durations of a moving probe in the time perception tasks. They discovered that the virtual reality manipulation was associated with significant reductions in the participants' estimates of time, by around 15 percent. "This study adds valuable proof that the perception of time is flexible, and that VR offers a potentially valuable tool for recalibrating time in the brain," says Weech. "It offers a compelling application for rehabilitation initiatives that focus on how time perception breaks down in certain populations." Weech adds, however, that while the effects were strong during the current study, more research is needed to find out how long the effects last, and whether these signals are observable in the brain. "For developing clinical applications, we need to know whether these effects are stable for minutes, days, or weeks afterward. A longitudinal study would provide the answer to this question." "Virtual reality technology has matured dramatically," says Michael Barnett-Cowan, neuroscience professor in the Department of Kinesiology and senior author of the paper. "VR now convincingly changes our experience of space and time, enabling basic research in perception to inform our understanding of how the brains of normal, injured, aged and diseased populations work and how they can be treated to perform optimally." The article, "Movement-Contingent Time Flow in Virtual Reality Causes Temporal Recalibration" was written by Ambika Bansal, Séamas Weech and Michael Barnett-Cowan, and published in Scientific Reports. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 21382, 8903, 320, 19330, 8, 5825, 264, 15525, 3495, 5507, 369, 21630, 1148, 13980, 994, 12271, 318, 10088, 11302, 30853, 527, 55315, 13, 5810, 584, 17303, 3508, 14675, 311, 264, 11775, 37015, 5133, 1990, 1957, 323, 49069, 13010, 304, 19718, 11384, 99783, 18856, 315, 892, 21063, 13, 1226, 4691, 220, 2148, 13324, 311, 2804, 892, 21063, 9256, 1405, 279, 10074, 315, 264, 7366, 22477, 574, 55717, 1701, 19815, 477, 44279, 9048, 5528, 13, 4314, 892, 21063, 9256, 1051, 8308, 864, 12, 323, 1772, 10397, 12313, 311, 8915, 19718, 2262, 304, 264, 2565, 64289, 59502, 2015, 13, 3861, 1912, 315, 13324, 10534, 264, 5410, 19718, 3465, 27179, 8416, 7394, 56955, 1418, 2500, 1912, 1047, 872, 1972, 31184, 19567, 34356, 311, 279, 6530, 315, 892, 304, 279, 4200, 3634, 27179, 62274, 59575, 892, 62413, 26, 386, 1182, 37, 65312, 1226, 3685, 420, 11775, 1957, 17453, 1010, 5133, 311, 7958, 19815, 9048, 892, 21063, 5178, 11, 719, 539, 44279, 9048, 892, 21063, 13, 578, 3135, 16717, 8250, 43918, 99783, 18856, 3230, 311, 264, 9048, 3465, 16239, 19815, 7351, 1778, 430, 279, 22477, 28090, 1051, 1234, 12, 45329, 555, 13489, 220, 868, 4, 2768, 14675, 311, 19718, 449, 279, 386, 1182, 37, 34786, 13, 7935, 9256, 304, 19718, 323, 2536, 12, 19330, 5110, 9124, 4528, 3135, 311, 1884, 315, 279, 4725, 7394, 19718, 1912, 11, 50096, 279, 76041, 315, 279, 386, 1182, 37, 34786, 13, 578, 14955, 3493, 15525, 26793, 1139, 279, 4754, 5536, 315, 19718, 389, 12271, 318, 10088, 99783, 18856, 13, 46551, 420, 1920, 690, 387, 15525, 369, 279, 4500, 323, 8292, 315, 44438, 12659, 13, 29438, 578, 5845, 311, 16430, 279, 21765, 315, 892, 449, 16437, 374, 16188, 311, 1057, 5845, 311, 45493, 323, 16681, 449, 279, 1917, 13, 3861, 1401, 29683, 315, 892, 21063, 374, 430, 433, 374, 7701, 12466, 11, 12899, 279, 5845, 311, 10737, 311, 10223, 12434, 4787, 220, 16, 1174, 220, 17, 1174, 220, 18, 1174, 220, 19, 662, 10541, 279, 12466, 488, 315, 892, 21063, 706, 1027, 1664, 9749, 11, 3892, 1825, 4860, 7293, 9002, 279, 8333, 11, 42056, 11, 323, 76041, 315, 37015, 99783, 18856, 6372, 13, 1789, 2937, 11, 656, 1521, 99783, 18856, 6372, 93640, 4028, 2204, 20362, 315, 8250, 42304, 320, 68, 1326, 2637, 19815, 323, 44279, 9048, 39656, 12106, 22559, 287, 1778, 4860, 690, 7417, 279, 8830, 315, 279, 55580, 323, 30828, 8197, 369, 892, 21063, 11, 902, 706, 18661, 5199, 2802, 315, 3389, 26310, 4245, 311, 279, 14638, 315, 27252, 477, 76283, 8811, 42662, 4442, 311, 892, 21063, 449, 4325, 220, 20, 1174, 220, 21, 1174, 220, 22, 1174, 220, 23, 662, 93028, 94985, 315, 4212, 86950, 4212, 21063, 374, 264, 62387, 582, 25489, 9429, 11, 323, 3892, 32887, 39555, 617, 1027, 11223, 304, 279, 37015, 8863, 17649, 320, 2000, 3477, 11, 1518, 220, 24, 7609, 578, 25462, 1646, 315, 37015, 8863, 18065, 264, 8792, 5419, 9042, 220, 605, 1174, 220, 806, 1174, 220, 717, 1174, 220, 1032, 662, 763, 420, 1646, 11, 892, 21063, 374, 15609, 555, 279, 44122, 1797, 315, 66557, 430, 47376, 2949, 264, 2728, 10074, 13, 2684, 374, 6029, 220, 975, 430, 1521, 24717, 11, 46820, 4147, 311, 1234, 11828, 279, 17371, 21063, 315, 892, 11, 1101, 6678, 279, 18912, 315, 9048, 5178, 320, 19171, 1518, 220, 868, 7609, 8483, 13533, 430, 279, 30828, 83240, 8450, 315, 279, 5419, 9042, 1887, 11, 4856, 1109, 1694, 1118, 11, 649, 387, 1491, 7913, 555, 49069, 11374, 505, 9434, 56688, 13, 362, 67655, 26177, 1887, 83379, 449, 279, 4623, 315, 12514, 24717, 369, 1855, 5647, 11, 8051, 433, 374, 3284, 430, 264, 8792, 17383, 5258, 13583, 67655, 44963, 28090, 11, 1418, 1207, 44963, 28090, 527, 15590, 555, 1491, 2786, 19440, 6067, 220, 717, 1174, 220, 845, 662, 26080, 617, 11223, 4211, 430, 656, 539, 1397, 28334, 28090, 369, 892, 33494, 11, 23377, 4619, 430, 892, 374, 21136, 304, 29079, 220, 1114, 1174, 220, 972, 477, 37015, 220, 777, 12912, 315, 79402, 23677, 13, 4314, 1614, 43918, 4009, 4211, 617, 18661, 18324, 389, 279, 8197, 315, 1862, 505, 8841, 91004, 7978, 315, 37015, 8863, 323, 6975, 24717, 220, 508, 1174, 220, 1691, 1174, 220, 1313, 662, 6104, 1855, 1646, 706, 17033, 5505, 11, 1070, 374, 264, 6996, 315, 29722, 304, 41294, 53194, 6029, 369, 279, 14209, 315, 264, 83240, 8450, 477, 1614, 43918, 44713, 315, 18912, 220, 1419, 662, 32359, 42305, 31226, 315, 4212, 86950, 3959, 44631, 279, 11618, 16940, 892, 21063, 520, 279, 30828, 2237, 706, 1027, 264, 3682, 8815, 304, 279, 2115, 13, 10541, 2103, 264, 5030, 315, 11249, 11, 279, 8271, 14726, 3463, 311, 387, 6532, 304, 892, 21063, 2997, 279, 28091, 17696, 372, 11, 864, 7096, 278, 49370, 11, 80710, 13481, 24235, 11, 323, 80506, 9048, 3158, 220, 845, 1174, 220, 1187, 1174, 220, 914, 662, 35390, 1380, 73085, 532, 24924, 41959, 320, 51, 4931, 8, 6029, 706, 7396, 279, 3560, 315, 279, 28091, 17696, 372, 323, 864, 7096, 278, 49370, 304, 892, 21063, 13, 350, 4931, 1511, 311, 24927, 28091, 17696, 277, 5820, 3242, 4825, 18912, 315, 1207, 44963, 90204, 220, 1627, 1174, 220, 1544, 1174, 220, 1591, 1174, 20444, 20747, 10843, 350, 4931, 927, 864, 7096, 278, 49370, 3242, 4825, 18912, 315, 67655, 44963, 90204, 220, 1544, 1174, 220, 1682, 662, 1102, 706, 1027, 11223, 430, 279, 864, 7096, 278, 49370, 27149, 304, 264, 11302, 3560, 555, 1701, 279, 49069, 2038, 2768, 459, 1957, 311, 2713, 37015, 17078, 220, 966, 1174, 20444, 279, 28091, 17696, 372, 11335, 264, 5510, 45904, 3560, 304, 3339, 37015, 20492, 4972, 311, 459, 1957, 220, 845, 662, 15004, 278, 13481, 24235, 5820, 374, 5938, 449, 279, 11418, 315, 37015, 8863, 323, 13340, 315, 39535, 8250, 11, 902, 374, 21091, 555, 2225, 279, 88979, 828, 315, 62145, 753, 6978, 449, 80710, 13481, 24235, 32403, 220, 2148, 323, 555, 16003, 24924, 58081, 32758, 320, 69, 79770, 8, 7978, 220, 1187, 1174, 220, 843, 1174, 220, 1644, 1174, 220, 1958, 662, 4314, 18247, 276, 22612, 950, 7978, 304, 32546, 449, 2536, 70095, 36449, 5848, 7978, 617, 7396, 279, 4623, 430, 892, 33494, 374, 1491, 7913, 555, 66128, 90351, 2796, 11, 11951, 520, 279, 423, 17, 35268, 220, 845, 1174, 220, 1758, 1174, 220, 1927, 662, 97674, 20588, 43215, 1705, 320, 68, 1326, 2637, 18247, 273, 418, 1233, 8, 18979, 44122, 15279, 811, 315, 1567, 8250, 220, 1806, 1174, 20444, 66128, 57770, 1705, 320, 68, 1326, 2637, 21747, 85890, 8, 3063, 311, 459, 5376, 304, 8250, 15279, 811, 220, 1987, 1174, 220, 2137, 662, 35390, 6029, 1101, 13533, 264, 21102, 3560, 369, 480, 57650, 304, 892, 21063, 26, 24924, 58081, 32758, 315, 279, 11494, 49370, 5039, 430, 32389, 480, 57650, 5990, 8024, 311, 1234, 478, 5582, 304, 279, 26617, 8250, 315, 1207, 44963, 28090, 11, 11000, 4245, 311, 54182, 17985, 315, 9302, 56688, 220, 1806, 1174, 220, 1272, 662, 44796, 315, 20539, 10020, 4158, 278, 18856, 32359, 42305, 31226, 7978, 539, 1193, 3493, 20616, 1139, 279, 30828, 17383, 315, 279, 5419, 9042, 11, 719, 814, 1101, 1862, 279, 4623, 430, 892, 21063, 649, 387, 55315, 13, 578, 4732, 315, 420, 5419, 9042, 649, 387, 7319, 477, 25983, 11911, 389, 279, 5623, 38018, 11, 902, 649, 3063, 311, 88979, 4442, 220, 1987, 1174, 220, 3174, 662, 13596, 25885, 430, 706, 1027, 6982, 311, 4732, 709, 279, 5419, 9042, 374, 279, 4299, 5542, 2515, 11, 49001, 14624, 311, 264, 5542, 315, 28849, 320, 68, 1326, 2637, 220, 20, 5819, 315, 28849, 520, 220, 20, 28849, 61171, 8, 90974, 264, 220, 605, 4, 18979, 304, 279, 26617, 8250, 315, 17876, 28090, 220, 17, 128257, 198, 128256, 78191, 198, 28571, 3953, 304, 4200, 8903, 320, 19330, 8, 1436, 387, 264, 1401, 5507, 304, 27723, 1274, 449, 64908, 24673, 1778, 439, 38281, 11, 58533, 323, 62145, 596, 8624, 13, 578, 5557, 11, 4184, 311, 264, 3293, 4007, 505, 279, 3907, 315, 77475, 11, 1436, 1520, 7931, 449, 1521, 64908, 4787, 6541, 872, 51866, 315, 892, 11, 902, 872, 4787, 3063, 1124, 311, 45493, 22009, 13, 330, 791, 5845, 311, 16430, 279, 21765, 315, 892, 449, 16437, 374, 16188, 311, 1057, 5845, 311, 16681, 449, 279, 1917, 1359, 2795, 1080, 43802, 73487, 29189, 1226, 4842, 11, 1772, 30659, 5009, 278, 12637, 304, 735, 1572, 31226, 13, 330, 2520, 1063, 7931, 11, 4869, 11, 279, 5419, 9042, 374, 8811, 88897, 11, 14718, 18912, 72946, 430, 7958, 21063, 323, 1957, 13, 330, 94607, 1093, 11604, 1520, 603, 311, 3619, 1268, 1521, 72946, 2643, 387, 19426, 11, 323, 1268, 311, 99783, 44192, 892, 21063, 304, 279, 8271, 1210, 578, 549, 29353, 48233, 4007, 6532, 220, 972, 28585, 323, 220, 1032, 25000, 449, 4725, 11376, 323, 912, 49069, 11, 3167, 79134, 86255, 477, 64908, 24673, 13, 578, 12074, 1511, 264, 4200, 8903, 1847, 11, 4997, 78, 80640, 11, 311, 1893, 264, 5933, 6376, 304, 902, 311, 15253, 312, 49236, 18856, 315, 892, 21063, 13, 578, 1401, 34786, 315, 279, 4007, 574, 430, 279, 12074, 34356, 279, 4732, 323, 8250, 315, 9302, 4455, 311, 279, 25923, 596, 2547, 19567, 13, 578, 12074, 17303, 13324, 6, 892, 21063, 18000, 1603, 323, 1306, 814, 1051, 15246, 311, 279, 8915, 19718, 3465, 13, 4427, 13324, 1101, 8308, 2536, 12, 19330, 892, 17453, 1010, 9256, 11, 1778, 439, 21939, 264, 5041, 11, 311, 1005, 439, 264, 2585, 12593, 13, 578, 12074, 17303, 279, 5150, 323, 26617, 90204, 315, 264, 7366, 22477, 304, 279, 892, 21063, 9256, 13, 2435, 11352, 430, 279, 4200, 8903, 34786, 574, 5938, 449, 5199, 47311, 304, 279, 13324, 6, 17989, 315, 892, 11, 555, 2212, 220, 868, 3346, 13, 330, 2028, 4007, 11621, 15525, 11311, 430, 279, 21063, 315, 892, 374, 19303, 11, 323, 430, 19718, 6209, 264, 13893, 15525, 5507, 369, 99783, 10892, 1113, 892, 304, 279, 8271, 1359, 2795, 1226, 4842, 13, 330, 2181, 6209, 264, 29722, 3851, 369, 44438, 28271, 430, 5357, 389, 1268, 892, 21063, 18808, 1523, 304, 3738, 22673, 1210, 1226, 4842, 11621, 11, 4869, 11, 430, 1418, 279, 6372, 1051, 3831, 2391, 279, 1510, 4007, 11, 810, 3495, 374, 4460, 311, 1505, 704, 1268, 1317, 279, 6372, 1566, 11, 323, 3508, 1521, 17738, 527, 40635, 304, 279, 8271, 13, 330, 2520, 11469, 14830, 8522, 11, 584, 1205, 311, 1440, 3508, 1521, 6372, 527, 15528, 369, 4520, 11, 2919, 11, 477, 5672, 49043, 13, 362, 68102, 4007, 1053, 3493, 279, 4320, 311, 420, 3488, 1210, 330, 34126, 8903, 5557, 706, 15196, 67, 29057, 1359, 2795, 8096, 86420, 7813, 81331, 11, 93048, 14561, 304, 279, 6011, 315, 735, 1572, 31226, 323, 10195, 3229, 315, 279, 5684, 13, 330, 19330, 1457, 36961, 11559, 4442, 1057, 3217, 315, 3634, 323, 892, 11, 28462, 6913, 3495, 304, 21063, 311, 6179, 1057, 8830, 315, 1268, 279, 35202, 315, 4725, 11, 15902, 11, 20330, 323, 6759, 1503, 22673, 990, 323, 1268, 814, 649, 387, 12020, 311, 2804, 7706, 750, 1210, 578, 4652, 11, 330, 39150, 12, 825, 287, 306, 4212, 23260, 304, 21382, 44874, 74105, 20539, 10020, 4158, 278, 18856, 1, 574, 5439, 555, 20423, 11755, 95061, 278, 11, 73487, 29189, 1226, 4842, 323, 8096, 86420, 7813, 81331, 11, 323, 4756, 304, 38130, 29140, 13, 220, 128257, 198 ]

1,866

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract High-energy particle accelerators have been crucial in providing a deeper understanding of fundamental particles and the forces that govern their interactions. To increase the energy of the particles or to reduce the size of the accelerator, new acceleration schemes need to be developed. Plasma wakefield acceleration 1 , 2 , 3 , 4 , 5 , in which the electrons in a plasma are excited, leading to strong electric fields (so called ‘wakefields’), is one such promising acceleration technique. Experiments have shown that an intense laser pulse 6 , 7 , 8 , 9 or electron bunch 10 , 11 traversing a plasma can drive electric fields of tens of gigavolts per metre and above—well beyond those achieved in conventional radio-frequency accelerators (about 0.1 gigavolt per metre). However, the low stored energy of laser pulses and electron bunches means that multiple acceleration stages are needed to reach very high particle energies 5 , 12 . The use of proton bunches is compelling because they have the potential to drive wakefields and to accelerate electrons to high energy in a single acceleration stage 13 . Long, thin proton bunches can be used because they undergo a process called self-modulation 14 , 15 , 16 , a particle–plasma interaction that splits the bunch longitudinally into a series of high-density microbunches, which then act resonantly to create large wakefields. The Advanced Wakefield (AWAKE) experiment at CERN 17 , 18 , 19 uses high-intensity proton bunches—in which each proton has an energy of 400 gigaelectronvolts, resulting in a total bunch energy of 19 kilojoules—to drive a wakefield in a ten-metre-long plasma. Electron bunches are then injected into this wakefield. Here we present measurements of electrons accelerated up to two gigaelectronvolts at the AWAKE experiment, in a demonstration of proton-driven plasma wakefield acceleration. Measurements were conducted under various plasma conditions and the acceleration was found to be consistent and reliable. The potential for this scheme to produce very high-energy electron bunches in a single accelerating stage 20 means that our results are an important step towards the development of future high-energy particle accelerators 21 , 22 . Main The layout of the AWAKE experiment is shown in Fig. 1 . A proton bunch from CERN’s Super Proton Synchrotron (SPS) accelerator co-propagates with a laser pulse (green), which creates a plasma (yellow) in a column of rubidium vapour (pink) and seeds the modulation of the proton bunch into microbunches (Fig. 1 ; red, bottom images). The protons have an energy of 400 GeV and the root-mean-square (r.m.s.) bunch length is 6–8 cm 18 . The bunch is focused to a transverse size of approximately 200 μm (r.m.s.) at the entrance of the vapour source, with the bunch population varying shot-to-shot in the range N p ≈ (2.5–3.1) × 10 11 protons per bunch. Proton extraction occurs every 15–30 s. The laser pulse used to singly ionize the rubidium in the vapour source 23 , 24 is 120 fs long with a central wavelength of 780 nm and a maximum energy of 450 mJ 25 . The pulse is focused to a waist of approximately 1 mm (full-width at half-maximum, FWHM) inside the rubidium vapour source, five times the transverse size of the proton bunch. The rubidium vapour source (Fig. 1 ; centre) has a length of 10 m and diameter of 4 cm, with rubidium flasks at each end. The rubidium vapour density and hence the plasma density n pe can be varied in the range 10 14 –10 15 cm −3 by heating the rubidium flasks to temperatures of 160–210 °C. This density range corresponds to a plasma wavelength of 1.1–3.3 mm, as detailed in Methods. A gradient in the plasma density can be introduced by heating the rubidium flasks to different temperatures. Heating the downstream (Fig. 1 ; right side) flask to a higher temperature than the upstream (left side) flask creates a positive density gradient, and vice versa. Gradients in plasma density have been shown in simulation to produce large increases in the maximum energy attainable by the injected electrons 26 . The effect of density gradients here is different from that for short drivers 27 . In addition to keeping the wake travelling at the speed of light at the witness position, the gradient prevents destruction of the bunches at the final stage of self-modulation 28 , thus increasing the wakefield amplitude at the downstream part of the plasma cell. The rubidium vapour density is monitored constantly by an interferometer-based diagnostic 29 . Fig. 1: Layout of the AWAKE experiment. The proton bunch and laser pulse propagate from left to right across the image, through a 10-m column of rubidium (Rb) vapour. This laser pulse (green, bottom images) singly ionizes the rubidium to form a plasma (yellow), which then interacts with the proton bunch (red, bottom left image). This interaction modulates the long proton bunch into a series of microbunches (bottom right image), which drive a strong wakefield in the plasma. These microbunches are millimetre-scale in the longitudinal direction ( ξ ) and submillimetre-scale in the transverse ( x ) direction. The self-modulation of the proton bunch is measured in imaging stations 1 and 2 and the optical and coherent transition radiation (OTR, CTR) diagnostics. The rubidium (pink) is supplied by two flasks at each end of the vapour source. The density is controlled by changing the temperature in these flasks and a gradient may be introduced by changing their relative temperature. Electrons (blue), generated using a radio-frequency source, propagate a short distance behind the laser pulse and are injected into the wakefield by crossing at an angle. Some of these electrons are captured in the wakefield and accelerated to high energies. The accelerated electron bunches are focused and separated from the protons by the quadrupoles and dipole magnet of the spectrometer (grey, right). These electrons interact with a scintillating screen, creating a bright intensity spot (top right image), allowing them to be imaged and their energy inferred from their position.", "role": "user" }, { "content": "Early in the morning on Saturday, 26 May 2018, the AWAKE collaboration at CERN successfully accelerated electrons for the first time using a wakefield generated by protons zipping through a plasma. A paper describing this important result was published in the journal Nature today. The electrons were accelerated by a factor of around 100 over a length of 10 metres: they were externally injected into AWAKE at an energy of around 19 MeV (million electronvolts) and attained an energy of almost 2 GeV (billion electronvolts). Although still at a very early stage of development, the use of plasma wakefields could drastically reduce the sizes, and therefore the costs, of the accelerators needed to achieve the high-energy collisions that physicists use to probe the fundamental laws of nature. The first demonstration of electron acceleration in AWAKE comes only five years after CERN approved the project in 2013 and is an important first step towards realising this vision. AWAKE, which stands for \"Advanced WAKEfield Experiment\", is a proof-of-principle R&D project investigating the use of protons to drive plasma wakefields for accelerating electrons to higher energies than can be achieved using conventional technologies. Traditional accelerators use what are known as radio-frequency (RF) cavities to kick the particle beams to higher energies. This involves alternating the electrical polarity of positively and negatively charged zones within the RF cavity, with the combination of attraction and repulsion accelerating the particles within the cavity. By contrast, in wakefield accelerators, the particles get accelerated by \"surfing\" on top of the plasma wave (or wakefield) that contains similar zones of positive and negative charges. Plasma wakefields themselves are not new ideas; they were first proposed in the late 1970s. \"Wakefield accelerators have two different beams: the beam of particles that is the target for the acceleration is known as a 'witness beam', while the beam that generates the wakefield itself is known as the 'drive beam',\" explains Allen Caldwell, spokesperson of the AWAKE collaboration. Previous examples of wakefield acceleration have relied on using electrons or lasers for the drive beam. AWAKE is the first experiment to use protons for the drive beam, and CERN provides the perfect opportunity to try the concept. Drive beams of protons penetrate deeper into the plasma than drive beams of electrons and lasers. \"Therefore,\" Caldwell adds, \"wakefield accelerators relying on protons for their drive beams can accelerate their witness beams for a greater distance, consequently allowing them to attain higher energies.\" CERN project leader for AWAKE, Edda Gschwendtner, explains how the experiment accelerated electrons for the first time. Credit: CERN AWAKE gets its drive-protons from the Super Proton Synchrotron (SPS), which is the last accelerator in the chain that delivers protons to the Large Hadron Collider (LHC). Protons from the SPS, travelling with an energy of 400 GeV, are injected into a so-called \"plasma cell\" of AWAKE, which contains Rubidium gas uniformly heated to around 200 ºC. These protons are accompanied by a laser pulse that transforms the Rubidium gas into a plasma – a special state of ionised gas – by ejecting electrons from the gas atoms. As this drive beam of positively charged protons travels through the plasma, it causes the otherwise-randomly-distributed negatively charged electrons within the plasma to oscillate in a wavelike pattern, much like a ship moving through the water generates oscillations in its wake. Witness-electrons are then injected at an angle into this oscillating plasma at relatively low energies and \"ride\" the plasma wave to get accelerated. At the other end of the plasma, a dipole magnet bends the incoming electrons onto a detector. \"The magnetic field of the dipole can be adjusted so that only electrons with a specific energy go through to the detector and give a signal at a particular location inside it,\" says Matthew Wing, deputy spokesperson of AWAKE, who is also responsible for this apparatus, known as the electron spectrometer. \"This is how we were able to determine that the accelerated electrons reached an energy of up to 2 GeV.\" The strength at which an accelerator can accelerate a particle beam per unit of length is known as its acceleration gradient and is measured in volts-per-metre (V/m). The greater the acceleration gradient, the more effective the acceleration. The Large Electron-Positron collider (LEP), which operated at CERN between 1989 and 2000, used conventional RF cavities and had a nominal acceleration gradient of 6 MV/m. \"By accelerating electrons to 2 GeV in just 10 metres, AWAKE has demonstrated that it can achieve an average gradient of around 200 MV/m,\" says Edda Gschwendtner, technical coordinator and CERN project leader for AWAKE. Gschwendtner and colleagues are aiming to attain an eventual acceleration gradient of around 1000 MV/m (or 1 GV/m). AWAKE has made rapid progress since its inception. Civil-engineering works for the project began in 2014, and the plasma cell was installed in early 2016 in the tunnel formerly used by part of the CNGS facility at CERN. A few months later, the first drive beams of protons were injected into the plasma cell to commission the experimental apparatus, and a proton-driven wakefield was observed for the first time in late 2016. In late 2017, the electron source, electron beam line and electron spectrometer were installed in the AWAKE facility to complete the preparatory phase. Now that they have demonstrated the ability to accelerate electrons using a proton-driven plasma wakefield, the AWAKE team is looking to the future. \"Our next steps include plans for delivering accelerated electrons to a physics experiment and extending the project with a full-fledged physics programme of its own,\" notes Patric Muggli, physics coordinator for AWAKE. AWAKE will continue testing the wakefield-acceleration of electrons for the rest of 2018, after which the entire accelerator complex at CERN will undergo a two-year shutdown for upgrades and maintenance. Gschwendtner is optimistic: \"We are looking forward to obtaining more results from our experiment to demonstrate the scope of plasma wakefields as the basis for future particle accelerators.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract High-energy particle accelerators have been crucial in providing a deeper understanding of fundamental particles and the forces that govern their interactions. To increase the energy of the particles or to reduce the size of the accelerator, new acceleration schemes need to be developed. Plasma wakefield acceleration 1 , 2 , 3 , 4 , 5 , in which the electrons in a plasma are excited, leading to strong electric fields (so called ‘wakefields’), is one such promising acceleration technique. Experiments have shown that an intense laser pulse 6 , 7 , 8 , 9 or electron bunch 10 , 11 traversing a plasma can drive electric fields of tens of gigavolts per metre and above—well beyond those achieved in conventional radio-frequency accelerators (about 0.1 gigavolt per metre). However, the low stored energy of laser pulses and electron bunches means that multiple acceleration stages are needed to reach very high particle energies 5 , 12 . The use of proton bunches is compelling because they have the potential to drive wakefields and to accelerate electrons to high energy in a single acceleration stage 13 . Long, thin proton bunches can be used because they undergo a process called self-modulation 14 , 15 , 16 , a particle–plasma interaction that splits the bunch longitudinally into a series of high-density microbunches, which then act resonantly to create large wakefields. The Advanced Wakefield (AWAKE) experiment at CERN 17 , 18 , 19 uses high-intensity proton bunches—in which each proton has an energy of 400 gigaelectronvolts, resulting in a total bunch energy of 19 kilojoules—to drive a wakefield in a ten-metre-long plasma. Electron bunches are then injected into this wakefield. Here we present measurements of electrons accelerated up to two gigaelectronvolts at the AWAKE experiment, in a demonstration of proton-driven plasma wakefield acceleration. Measurements were conducted under various plasma conditions and the acceleration was found to be consistent and reliable. The potential for this scheme to produce very high-energy electron bunches in a single accelerating stage 20 means that our results are an important step towards the development of future high-energy particle accelerators 21 , 22 . Main The layout of the AWAKE experiment is shown in Fig. 1 . A proton bunch from CERN’s Super Proton Synchrotron (SPS) accelerator co-propagates with a laser pulse (green), which creates a plasma (yellow) in a column of rubidium vapour (pink) and seeds the modulation of the proton bunch into microbunches (Fig. 1 ; red, bottom images). The protons have an energy of 400 GeV and the root-mean-square (r.m.s.) bunch length is 6–8 cm 18 . The bunch is focused to a transverse size of approximately 200 μm (r.m.s.) at the entrance of the vapour source, with the bunch population varying shot-to-shot in the range N p ≈ (2.5–3.1) × 10 11 protons per bunch. Proton extraction occurs every 15–30 s. The laser pulse used to singly ionize the rubidium in the vapour source 23 , 24 is 120 fs long with a central wavelength of 780 nm and a maximum energy of 450 mJ 25 . The pulse is focused to a waist of approximately 1 mm (full-width at half-maximum, FWHM) inside the rubidium vapour source, five times the transverse size of the proton bunch. The rubidium vapour source (Fig. 1 ; centre) has a length of 10 m and diameter of 4 cm, with rubidium flasks at each end. The rubidium vapour density and hence the plasma density n pe can be varied in the range 10 14 –10 15 cm −3 by heating the rubidium flasks to temperatures of 160–210 °C. This density range corresponds to a plasma wavelength of 1.1–3.3 mm, as detailed in Methods. A gradient in the plasma density can be introduced by heating the rubidium flasks to different temperatures. Heating the downstream (Fig. 1 ; right side) flask to a higher temperature than the upstream (left side) flask creates a positive density gradient, and vice versa. Gradients in plasma density have been shown in simulation to produce large increases in the maximum energy attainable by the injected electrons 26 . The effect of density gradients here is different from that for short drivers 27 . In addition to keeping the wake travelling at the speed of light at the witness position, the gradient prevents destruction of the bunches at the final stage of self-modulation 28 , thus increasing the wakefield amplitude at the downstream part of the plasma cell. The rubidium vapour density is monitored constantly by an interferometer-based diagnostic 29 . Fig. 1: Layout of the AWAKE experiment. The proton bunch and laser pulse propagate from left to right across the image, through a 10-m column of rubidium (Rb) vapour. This laser pulse (green, bottom images) singly ionizes the rubidium to form a plasma (yellow), which then interacts with the proton bunch (red, bottom left image). This interaction modulates the long proton bunch into a series of microbunches (bottom right image), which drive a strong wakefield in the plasma. These microbunches are millimetre-scale in the longitudinal direction ( ξ ) and submillimetre-scale in the transverse ( x ) direction. The self-modulation of the proton bunch is measured in imaging stations 1 and 2 and the optical and coherent transition radiation (OTR, CTR) diagnostics. The rubidium (pink) is supplied by two flasks at each end of the vapour source. The density is controlled by changing the temperature in these flasks and a gradient may be introduced by changing their relative temperature. Electrons (blue), generated using a radio-frequency source, propagate a short distance behind the laser pulse and are injected into the wakefield by crossing at an angle. Some of these electrons are captured in the wakefield and accelerated to high energies. The accelerated electron bunches are focused and separated from the protons by the quadrupoles and dipole magnet of the spectrometer (grey, right). These electrons interact with a scintillating screen, creating a bright intensity spot (top right image), allowing them to be imaged and their energy inferred from their position.<|im_end|> <|im_start|>assistant Early in the morning on Saturday, 26 May 2018, the AWAKE collaboration at CERN successfully accelerated electrons for the first time using a wakefield generated by protons zipping through a plasma. A paper describing this important result was published in the journal Nature today. The electrons were accelerated by a factor of around 100 over a length of 10 metres: they were externally injected into AWAKE at an energy of around 19 MeV (million electronvolts) and attained an energy of almost 2 GeV (billion electronvolts). Although still at a very early stage of development, the use of plasma wakefields could drastically reduce the sizes, and therefore the costs, of the accelerators needed to achieve the high-energy collisions that physicists use to probe the fundamental laws of nature. The first demonstration of electron acceleration in AWAKE comes only five years after CERN approved the project in 2013 and is an important first step towards realising this vision. AWAKE, which stands for "Advanced WAKEfield Experiment", is a proof-of-principle R&D project investigating the use of protons to drive plasma wakefields for accelerating electrons to higher energies than can be achieved using conventional technologies. Traditional accelerators use what are known as radio-frequency (RF) cavities to kick the particle beams to higher energies. This involves alternating the electrical polarity of positively and negatively charged zones within the RF cavity, with the combination of attraction and repulsion accelerating the particles within the cavity. By contrast, in wakefield accelerators, the particles get accelerated by "surfing" on top of the plasma wave (or wakefield) that contains similar zones of positive and negative charges. Plasma wakefields themselves are not new ideas; they were first proposed in the late 1970s. "Wakefield accelerators have two different beams: the beam of particles that is the target for the acceleration is known as a 'witness beam', while the beam that generates the wakefield itself is known as the 'drive beam'," explains Allen Caldwell, spokesperson of the AWAKE collaboration. Previous examples of wakefield acceleration have relied on using electrons or lasers for the drive beam. AWAKE is the first experiment to use protons for the drive beam, and CERN provides the perfect opportunity to try the concept. Drive beams of protons penetrate deeper into the plasma than drive beams of electrons and lasers. "Therefore," Caldwell adds, "wakefield accelerators relying on protons for their drive beams can accelerate their witness beams for a greater distance, consequently allowing them to attain higher energies." CERN project leader for AWAKE, Edda Gschwendtner, explains how the experiment accelerated electrons for the first time. Credit: CERN AWAKE gets its drive-protons from the Super Proton Synchrotron (SPS), which is the last accelerator in the chain that delivers protons to the Large Hadron Collider (LHC). Protons from the SPS, travelling with an energy of 400 GeV, are injected into a so-called "plasma cell" of AWAKE, which contains Rubidium gas uniformly heated to around 200 ºC. These protons are accompanied by a laser pulse that transforms the Rubidium gas into a plasma – a special state of ionised gas – by ejecting electrons from the gas atoms. As this drive beam of positively charged protons travels through the plasma, it causes the otherwise-randomly-distributed negatively charged electrons within the plasma to oscillate in a wavelike pattern, much like a ship moving through the water generates oscillations in its wake. Witness-electrons are then injected at an angle into this oscillating plasma at relatively low energies and "ride" the plasma wave to get accelerated. At the other end of the plasma, a dipole magnet bends the incoming electrons onto a detector. "The magnetic field of the dipole can be adjusted so that only electrons with a specific energy go through to the detector and give a signal at a particular location inside it," says Matthew Wing, deputy spokesperson of AWAKE, who is also responsible for this apparatus, known as the electron spectrometer. "This is how we were able to determine that the accelerated electrons reached an energy of up to 2 GeV." The strength at which an accelerator can accelerate a particle beam per unit of length is known as its acceleration gradient and is measured in volts-per-metre (V/m). The greater the acceleration gradient, the more effective the acceleration. The Large Electron-Positron collider (LEP), which operated at CERN between 1989 and 2000, used conventional RF cavities and had a nominal acceleration gradient of 6 MV/m. "By accelerating electrons to 2 GeV in just 10 metres, AWAKE has demonstrated that it can achieve an average gradient of around 200 MV/m," says Edda Gschwendtner, technical coordinator and CERN project leader for AWAKE. Gschwendtner and colleagues are aiming to attain an eventual acceleration gradient of around 1000 MV/m (or 1 GV/m). AWAKE has made rapid progress since its inception. Civil-engineering works for the project began in 2014, and the plasma cell was installed in early 2016 in the tunnel formerly used by part of the CNGS facility at CERN. A few months later, the first drive beams of protons were injected into the plasma cell to commission the experimental apparatus, and a proton-driven wakefield was observed for the first time in late 2016. In late 2017, the electron source, electron beam line and electron spectrometer were installed in the AWAKE facility to complete the preparatory phase. Now that they have demonstrated the ability to accelerate electrons using a proton-driven plasma wakefield, the AWAKE team is looking to the future. "Our next steps include plans for delivering accelerated electrons to a physics experiment and extending the project with a full-fledged physics programme of its own," notes Patric Muggli, physics coordinator for AWAKE. AWAKE will continue testing the wakefield-acceleration of electrons for the rest of 2018, after which the entire accelerator complex at CERN will undergo a two-year shutdown for upgrades and maintenance. Gschwendtner is optimistic: "We are looking forward to obtaining more results from our experiment to demonstrate the scope of plasma wakefields as the basis for future particle accelerators." <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 5234, 65487, 19320, 14511, 3046, 617, 1027, 16996, 304, 8405, 264, 19662, 8830, 315, 16188, 19252, 323, 279, 8603, 430, 2633, 872, 22639, 13, 2057, 5376, 279, 4907, 315, 279, 19252, 477, 311, 8108, 279, 1404, 315, 279, 65456, 11, 502, 31903, 31956, 1205, 311, 387, 8040, 13, 65632, 15508, 2630, 31903, 220, 16, 1174, 220, 17, 1174, 220, 18, 1174, 220, 19, 1174, 220, 20, 1174, 304, 902, 279, 57678, 304, 264, 32426, 527, 12304, 11, 6522, 311, 3831, 9249, 5151, 320, 708, 2663, 3451, 91019, 9184, 529, 705, 374, 832, 1778, 26455, 31903, 15105, 13, 1398, 50732, 617, 6982, 430, 459, 19428, 21120, 28334, 220, 21, 1174, 220, 22, 1174, 220, 23, 1174, 220, 24, 477, 17130, 15860, 220, 605, 1174, 220, 806, 30517, 287, 264, 32426, 649, 6678, 9249, 5151, 315, 22781, 315, 23401, 402, 337, 2641, 824, 82673, 323, 3485, 2345, 9336, 7953, 1884, 17427, 304, 21349, 9063, 79412, 14511, 3046, 320, 9274, 220, 15, 13, 16, 23401, 402, 6312, 824, 82673, 570, 4452, 11, 279, 3428, 9967, 4907, 315, 21120, 66557, 323, 17130, 15860, 288, 3445, 430, 5361, 31903, 18094, 527, 4460, 311, 5662, 1633, 1579, 19320, 49969, 220, 20, 1174, 220, 717, 662, 578, 1005, 315, 82586, 15860, 288, 374, 29722, 1606, 814, 617, 279, 4754, 311, 6678, 15508, 9184, 323, 311, 43880, 57678, 311, 1579, 4907, 304, 264, 3254, 31903, 6566, 220, 1032, 662, 5843, 11, 15792, 82586, 15860, 288, 649, 387, 1511, 1606, 814, 37771, 264, 1920, 2663, 659, 17515, 2987, 220, 975, 1174, 220, 868, 1174, 220, 845, 1174, 264, 19320, 4235, 501, 23390, 16628, 430, 41567, 279, 15860, 49704, 38745, 1139, 264, 4101, 315, 1579, 89131, 8162, 65, 3265, 288, 11, 902, 1243, 1180, 29280, 18007, 311, 1893, 3544, 15508, 9184, 13, 578, 21844, 41674, 2630, 320, 14757, 26553, 8, 9526, 520, 356, 13974, 220, 1114, 1174, 220, 972, 1174, 220, 777, 5829, 1579, 20653, 8127, 82586, 15860, 288, 49525, 902, 1855, 82586, 706, 459, 4907, 315, 220, 3443, 23401, 6043, 70329, 12821, 2641, 11, 13239, 304, 264, 2860, 15860, 4907, 315, 220, 777, 15395, 21963, 283, 645, 50617, 6678, 264, 15508, 2630, 304, 264, 5899, 1474, 47987, 24725, 32426, 13, 77976, 15860, 288, 527, 1243, 41772, 1139, 420, 15508, 2630, 13, 5810, 584, 3118, 22323, 315, 57678, 49858, 709, 311, 1403, 23401, 6043, 70329, 12821, 2641, 520, 279, 34438, 26553, 9526, 11, 304, 264, 30816, 315, 82586, 32505, 32426, 15508, 2630, 31903, 13, 77917, 1051, 13375, 1234, 5370, 32426, 4787, 323, 279, 31903, 574, 1766, 311, 387, 13263, 323, 15062, 13, 578, 4754, 369, 420, 13155, 311, 8356, 1633, 1579, 65487, 17130, 15860, 288, 304, 264, 3254, 69741, 6566, 220, 508, 3445, 430, 1057, 3135, 527, 459, 3062, 3094, 7119, 279, 4500, 315, 3938, 1579, 65487, 19320, 14511, 3046, 220, 1691, 1174, 220, 1313, 662, 4802, 578, 6932, 315, 279, 34438, 26553, 9526, 374, 6982, 304, 23966, 13, 220, 16, 662, 362, 82586, 15860, 505, 356, 13974, 753, 7445, 1322, 783, 24028, 331, 299, 35785, 320, 4695, 50, 8, 65456, 1080, 77671, 351, 988, 449, 264, 21120, 28334, 320, 13553, 705, 902, 11705, 264, 32426, 320, 28969, 8, 304, 264, 3330, 315, 10485, 307, 2411, 68857, 414, 320, 64349, 8, 323, 19595, 279, 67547, 315, 279, 82586, 15860, 1139, 8162, 65, 3265, 288, 320, 30035, 13, 220, 16, 2652, 2579, 11, 5740, 5448, 570, 578, 463, 35511, 617, 459, 4907, 315, 220, 3443, 4323, 53, 323, 279, 3789, 84096, 34047, 320, 81, 749, 516, 6266, 15860, 3160, 374, 220, 21, 4235, 23, 10166, 220, 972, 662, 578, 15860, 374, 10968, 311, 264, 1380, 4550, 1404, 315, 13489, 220, 1049, 33983, 76, 320, 81, 749, 516, 6266, 520, 279, 20396, 315, 279, 68857, 414, 2592, 11, 449, 279, 15860, 7187, 29865, 6689, 4791, 64630, 304, 279, 2134, 452, 281, 118792, 320, 17, 13, 20, 4235, 18, 13, 16, 8, 25800, 220, 605, 220, 806, 463, 35511, 824, 15860, 13, 1322, 783, 33289, 13980, 1475, 220, 868, 4235, 966, 274, 13, 578, 21120, 28334, 1511, 311, 86599, 28772, 553, 279, 10485, 307, 2411, 304, 279, 68857, 414, 2592, 220, 1419, 1174, 220, 1187, 374, 220, 4364, 8789, 1317, 449, 264, 8792, 46406, 315, 220, 19423, 26807, 323, 264, 7340, 4907, 315, 220, 10617, 296, 41, 220, 914, 662, 578, 28334, 374, 10968, 311, 264, 29142, 315, 13489, 220, 16, 9653, 320, 9054, 9531, 520, 4376, 45173, 3375, 11, 435, 20484, 44, 8, 4871, 279, 10485, 307, 2411, 68857, 414, 2592, 11, 4330, 3115, 279, 1380, 4550, 1404, 315, 279, 82586, 15860, 13, 578, 10485, 307, 2411, 68857, 414, 2592, 320, 30035, 13, 220, 16, 2652, 12541, 8, 706, 264, 3160, 315, 220, 605, 296, 323, 23899, 315, 220, 19, 10166, 11, 449, 10485, 307, 2411, 1344, 4707, 520, 1855, 842, 13, 578, 10485, 307, 2411, 68857, 414, 17915, 323, 16472, 279, 32426, 17915, 308, 1069, 649, 387, 28830, 304, 279, 2134, 220, 605, 220, 975, 1389, 605, 220, 868, 10166, 25173, 18, 555, 24494, 279, 10485, 307, 2411, 1344, 4707, 311, 20472, 315, 220, 6330, 4235, 8848, 37386, 34, 13, 1115, 17915, 2134, 34310, 311, 264, 32426, 46406, 315, 220, 16, 13, 16, 4235, 18, 13, 18, 9653, 11, 439, 11944, 304, 19331, 13, 362, 20779, 304, 279, 32426, 17915, 649, 387, 11784, 555, 24494, 279, 10485, 307, 2411, 1344, 4707, 311, 2204, 20472, 13, 68954, 279, 52452, 320, 30035, 13, 220, 16, 2652, 1314, 3185, 8, 20104, 311, 264, 5190, 9499, 1109, 279, 42830, 320, 2414, 3185, 8, 20104, 11705, 264, 6928, 17915, 20779, 11, 323, 17192, 46391, 13, 2895, 37418, 304, 32426, 17915, 617, 1027, 6982, 304, 19576, 311, 8356, 3544, 12992, 304, 279, 7340, 4907, 36861, 481, 555, 279, 41772, 57678, 220, 1627, 662, 578, 2515, 315, 17915, 53249, 1618, 374, 2204, 505, 430, 369, 2875, 12050, 220, 1544, 662, 763, 5369, 311, 10494, 279, 15508, 31829, 520, 279, 4732, 315, 3177, 520, 279, 11550, 2361, 11, 279, 20779, 29034, 19814, 315, 279, 15860, 288, 520, 279, 1620, 6566, 315, 659, 17515, 2987, 220, 1591, 1174, 8617, 7859, 279, 15508, 2630, 45209, 520, 279, 52452, 961, 315, 279, 32426, 2849, 13, 578, 10485, 307, 2411, 68857, 414, 17915, 374, 41223, 15320, 555, 459, 41305, 21037, 6108, 15439, 220, 1682, 662, 23966, 13, 220, 16, 25, 14141, 315, 279, 34438, 26553, 9526, 13, 578, 82586, 15860, 323, 21120, 28334, 58514, 505, 2163, 311, 1314, 4028, 279, 2217, 11, 1555, 264, 220, 605, 1474, 3330, 315, 10485, 307, 2411, 320, 49, 65, 8, 68857, 414, 13, 1115, 21120, 28334, 320, 13553, 11, 5740, 5448, 8, 86599, 28772, 4861, 279, 10485, 307, 2411, 311, 1376, 264, 32426, 320, 28969, 705, 902, 1243, 84261, 449, 279, 82586, 15860, 320, 1171, 11, 5740, 2163, 2217, 570, 1115, 16628, 1491, 24031, 279, 1317, 82586, 15860, 1139, 264, 4101, 315, 8162, 65, 3265, 288, 320, 15205, 1314, 2217, 705, 902, 6678, 264, 3831, 15508, 2630, 304, 279, 32426, 13, 4314, 8162, 65, 3265, 288, 527, 2606, 318, 47987, 13230, 304, 279, 68102, 5216, 320, 104679, 883, 323, 1207, 26064, 318, 47987, 13230, 304, 279, 1380, 4550, 320, 865, 883, 5216, 13, 578, 659, 17515, 2987, 315, 279, 82586, 15860, 374, 17303, 304, 32758, 17789, 220, 16, 323, 220, 17, 323, 279, 29393, 323, 56887, 9320, 25407, 320, 1831, 49, 11, 356, 2434, 8, 50518, 13, 578, 10485, 307, 2411, 320, 64349, 8, 374, 17665, 555, 1403, 1344, 4707, 520, 1855, 842, 315, 279, 68857, 414, 2592, 13, 578, 17915, 374, 14400, 555, 10223, 279, 9499, 304, 1521, 1344, 4707, 323, 264, 20779, 1253, 387, 11784, 555, 10223, 872, 8844, 9499, 13, 10085, 26692, 320, 12481, 705, 8066, 1701, 264, 9063, 79412, 2592, 11, 58514, 264, 2875, 6138, 4920, 279, 21120, 28334, 323, 527, 41772, 1139, 279, 15508, 2630, 555, 27736, 520, 459, 9392, 13, 4427, 315, 1521, 57678, 527, 17439, 304, 279, 15508, 2630, 323, 49858, 311, 1579, 49969, 13, 578, 49858, 17130, 15860, 288, 527, 10968, 323, 19180, 505, 279, 463, 35511, 555, 279, 30236, 455, 7298, 323, 24522, 1286, 33297, 315, 279, 9618, 88371, 320, 35671, 11, 1314, 570, 4314, 57678, 16681, 449, 264, 1156, 396, 484, 1113, 4264, 11, 6968, 264, 10107, 21261, 7858, 320, 3565, 1314, 2217, 705, 10923, 1124, 311, 387, 737, 3359, 323, 872, 4907, 68695, 505, 872, 2361, 13, 128257, 198, 128256, 78191, 198, 42298, 304, 279, 6693, 389, 7884, 11, 220, 1627, 3297, 220, 679, 23, 11, 279, 34438, 26553, 20632, 520, 356, 13974, 7946, 49858, 57678, 369, 279, 1176, 892, 1701, 264, 15508, 2630, 8066, 555, 463, 35511, 1167, 5772, 1555, 264, 32426, 13, 362, 5684, 23524, 420, 3062, 1121, 574, 4756, 304, 279, 8486, 22037, 3432, 13, 578, 57678, 1051, 49858, 555, 264, 8331, 315, 2212, 220, 1041, 927, 264, 3160, 315, 220, 605, 37356, 25, 814, 1051, 69442, 41772, 1139, 34438, 26553, 520, 459, 4907, 315, 2212, 220, 777, 2206, 53, 320, 59413, 17130, 12821, 2641, 8, 323, 63260, 459, 4907, 315, 4661, 220, 17, 4323, 53, 320, 65, 15068, 17130, 12821, 2641, 570, 10541, 2103, 520, 264, 1633, 4216, 6566, 315, 4500, 11, 279, 1005, 315, 32426, 15508, 9184, 1436, 48863, 8108, 279, 12562, 11, 323, 9093, 279, 7194, 11, 315, 279, 14511, 3046, 4460, 311, 11322, 279, 1579, 65487, 48453, 430, 98417, 1005, 311, 22477, 279, 16188, 7016, 315, 7138, 13, 578, 1176, 30816, 315, 17130, 31903, 304, 34438, 26553, 4131, 1193, 4330, 1667, 1306, 356, 13974, 12054, 279, 2447, 304, 220, 679, 18, 323, 374, 459, 3062, 1176, 3094, 7119, 1972, 3876, 420, 11376, 13, 34438, 26553, 11, 902, 13656, 369, 330, 36557, 468, 26553, 2630, 47893, 498, 374, 264, 11311, 8838, 27748, 16379, 432, 33465, 2447, 24834, 279, 1005, 315, 463, 35511, 311, 6678, 32426, 15508, 9184, 369, 69741, 57678, 311, 5190, 49969, 1109, 649, 387, 17427, 1701, 21349, 14645, 13, 46560, 14511, 3046, 1005, 1148, 527, 3967, 439, 9063, 79412, 320, 18077, 8, 57709, 1385, 311, 10536, 279, 19320, 51045, 311, 5190, 49969, 13, 1115, 18065, 73462, 279, 20314, 76790, 315, 40646, 323, 48291, 11684, 26467, 2949, 279, 22835, 56429, 11, 449, 279, 10824, 315, 33464, 323, 2109, 34003, 69741, 279, 19252, 2949, 279, 56429, 13, 3296, 13168, 11, 304, 15508, 2630, 14511, 3046, 11, 279, 19252, 636, 49858, 555, 330, 78960, 287, 1, 389, 1948, 315, 279, 32426, 12330, 320, 269, 15508, 2630, 8, 430, 5727, 4528, 26467, 315, 6928, 323, 8389, 10405, 13, 65632, 15508, 9184, 5694, 527, 539, 502, 6848, 26, 814, 1051, 1176, 11223, 304, 279, 3389, 220, 4468, 15, 82, 13, 330, 91848, 2630, 14511, 3046, 617, 1403, 2204, 51045, 25, 279, 24310, 315, 19252, 430, 374, 279, 2218, 369, 279, 31903, 374, 3967, 439, 264, 364, 86, 8251, 24310, 518, 1418, 279, 24310, 430, 27983, 279, 15508, 2630, 5196, 374, 3967, 439, 279, 364, 33067, 24310, 38687, 15100, 20661, 82324, 11, 29003, 315, 279, 34438, 26553, 20632, 13, 30013, 10507, 315, 15508, 2630, 31903, 617, 41013, 389, 1701, 57678, 477, 72475, 369, 279, 6678, 24310, 13, 34438, 26553, 374, 279, 1176, 9526, 311, 1005, 463, 35511, 369, 279, 6678, 24310, 11, 323, 356, 13974, 5825, 279, 4832, 6776, 311, 1456, 279, 7434, 13, 16542, 51045, 315, 463, 35511, 64855, 19662, 1139, 279, 32426, 1109, 6678, 51045, 315, 57678, 323, 72475, 13, 330, 55915, 1359, 82324, 11621, 11, 330, 91019, 2630, 14511, 3046, 39661, 389, 463, 35511, 369, 872, 6678, 51045, 649, 43880, 872, 11550, 51045, 369, 264, 7191, 6138, 11, 52394, 10923, 1124, 311, 36861, 5190, 49969, 1210, 356, 13974, 2447, 7808, 369, 34438, 26553, 11, 469, 72587, 480, 21740, 41331, 83, 1215, 11, 15100, 1268, 279, 9526, 49858, 57678, 369, 279, 1176, 892, 13, 16666, 25, 356, 13974, 34438, 26553, 5334, 1202, 6678, 10039, 35511, 505, 279, 7445, 1322, 783, 24028, 331, 299, 35785, 320, 4695, 50, 705, 902, 374, 279, 1566, 65456, 304, 279, 8957, 430, 28421, 463, 35511, 311, 279, 20902, 24805, 2298, 74921, 320, 43, 23263, 570, 1322, 35511, 505, 279, 328, 5119, 11, 31829, 449, 459, 4907, 315, 220, 3443, 4323, 53, 11, 527, 41772, 1139, 264, 779, 19434, 330, 501, 23390, 2849, 1, 315, 34438, 26553, 11, 902, 5727, 13134, 307, 2411, 6962, 78909, 32813, 311, 2212, 220, 1049, 2188, 118, 34, 13, 4314, 463, 35511, 527, 24895, 555, 264, 21120, 28334, 430, 29575, 279, 13134, 307, 2411, 6962, 1139, 264, 32426, 1389, 264, 3361, 1614, 315, 28772, 4147, 6962, 1389, 555, 90574, 287, 57678, 505, 279, 6962, 33299, 13, 1666, 420, 6678, 24310, 315, 40646, 11684, 463, 35511, 35292, 1555, 279, 32426, 11, 433, 11384, 279, 6062, 92775, 398, 1773, 26204, 48291, 11684, 57678, 2949, 279, 32426, 311, 43524, 349, 304, 264, 289, 3963, 3043, 5497, 11, 1790, 1093, 264, 8448, 7366, 1555, 279, 3090, 27983, 43524, 811, 304, 1202, 15508, 13, 49999, 37081, 26692, 527, 1243, 41772, 520, 459, 9392, 1139, 420, 43524, 1113, 32426, 520, 12309, 3428, 49969, 323, 330, 1425, 1, 279, 32426, 12330, 311, 636, 49858, 13, 2468, 279, 1023, 842, 315, 279, 32426, 11, 264, 24522, 1286, 33297, 93897, 279, 19957, 57678, 8800, 264, 32314, 13, 330, 791, 24924, 2115, 315, 279, 24522, 1286, 649, 387, 24257, 779, 430, 1193, 57678, 449, 264, 3230, 4907, 733, 1555, 311, 279, 32314, 323, 3041, 264, 8450, 520, 264, 4040, 3813, 4871, 433, 1359, 2795, 19475, 35622, 11, 27158, 29003, 315, 34438, 26553, 11, 889, 374, 1101, 8647, 369, 420, 41705, 11, 3967, 439, 279, 17130, 9618, 88371, 13, 330, 2028, 374, 1268, 584, 1051, 3025, 311, 8417, 430, 279, 49858, 57678, 8813, 459, 4907, 315, 709, 311, 220, 17, 4323, 53, 1210, 578, 8333, 520, 902, 459, 65456, 649, 43880, 264, 19320, 24310, 824, 5089, 315, 3160, 374, 3967, 439, 1202, 31903, 20779, 323, 374, 17303, 304, 87167, 17453, 1474, 47987, 320, 53, 3262, 570, 578, 7191, 279, 31903, 20779, 11, 279, 810, 7524, 279, 31903, 13, 578, 20902, 77976, 12, 4964, 275, 2298, 66644, 320, 877, 47, 705, 902, 24026, 520, 356, 13974, 1990, 220, 3753, 24, 323, 220, 1049, 15, 11, 1511, 21349, 22835, 57709, 1385, 323, 1047, 264, 47855, 31903, 20779, 315, 220, 21, 43371, 3262, 13, 330, 1383, 69741, 57678, 311, 220, 17, 4323, 53, 304, 1120, 220, 605, 37356, 11, 34438, 26553, 706, 21091, 430, 433, 649, 11322, 459, 5578, 20779, 315, 2212, 220, 1049, 43371, 3262, 1359, 2795, 469, 72587, 480, 21740, 41331, 83, 1215, 11, 11156, 31384, 323, 356, 13974, 2447, 7808, 369, 34438, 26553, 13, 480, 21740, 41331, 83, 1215, 323, 18105, 527, 38178, 311, 36861, 459, 42835, 31903, 20779, 315, 2212, 220, 1041, 15, 43371, 3262, 320, 269, 220, 16, 81900, 3262, 570, 34438, 26553, 706, 1903, 11295, 5208, 2533, 1202, 54529, 13, 16803, 50725, 4776, 4375, 369, 279, 2447, 6137, 304, 220, 679, 19, 11, 323, 279, 32426, 2849, 574, 10487, 304, 4216, 220, 679, 21, 304, 279, 26711, 34833, 1511, 555, 961, 315, 279, 356, 6269, 50, 12764, 520, 356, 13974, 13, 362, 2478, 4038, 3010, 11, 279, 1176, 6678, 51045, 315, 463, 35511, 1051, 41772, 1139, 279, 32426, 2849, 311, 12396, 279, 22772, 41705, 11, 323, 264, 82586, 32505, 15508, 2630, 574, 13468, 369, 279, 1176, 892, 304, 3389, 220, 679, 21, 13, 763, 3389, 220, 679, 22, 11, 279, 17130, 2592, 11, 17130, 24310, 1584, 323, 17130, 9618, 88371, 1051, 10487, 304, 279, 34438, 26553, 12764, 311, 4686, 279, 10073, 5382, 10474, 13, 4800, 430, 814, 617, 21091, 279, 5845, 311, 43880, 57678, 1701, 264, 82586, 32505, 32426, 15508, 2630, 11, 279, 34438, 26553, 2128, 374, 3411, 311, 279, 3938, 13, 330, 8140, 1828, 7504, 2997, 6787, 369, 24944, 49858, 57678, 311, 264, 22027, 9526, 323, 33459, 279, 2447, 449, 264, 2539, 2269, 93724, 22027, 18629, 315, 1202, 1866, 1359, 8554, 7281, 2265, 386, 2661, 747, 11, 22027, 31384, 369, 34438, 26553, 13, 34438, 26553, 690, 3136, 7649, 279, 15508, 2630, 38698, 3757, 21597, 315, 57678, 369, 279, 2800, 315, 220, 679, 23, 11, 1306, 902, 279, 4553, 65456, 6485, 520, 356, 13974, 690, 37771, 264, 1403, 4771, 24700, 369, 32714, 323, 13709, 13, 480, 21740, 41331, 83, 1215, 374, 37036, 25, 330, 1687, 527, 3411, 4741, 311, 19546, 810, 3135, 505, 1057, 9526, 311, 20461, 279, 7036, 315, 32426, 15508, 9184, 439, 279, 8197, 369, 3938, 19320, 14511, 3046, 1210, 220, 128257, 198 ]

2,718

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Mesoscopic superpositions of distinguishable coherent states provide an analogue of the ‘Schrödinger’s cat’ thought experiment 1 , 2 . For mechanical oscillators these have primarily been realized using coherent wavepackets, for which the distinguishability arises as a result of the spatial separation of the superposed states 3 , 4 , 5 . Here we demonstrate superpositions composed of squeezed wavepackets, which we generate by applying an internal-state-dependent force to a single trapped ion initialized in a squeezed vacuum state with nine decibel reduction in the quadrature variance. This allows us to characterize the initial squeezed wavepacket by monitoring the onset of spin–motion entanglement, and to verify the evolution of the number states of the oscillator as a function of the duration of the force. In both cases we observe clear differences between displacements aligned with the squeezed and anti-squeezed axes. We observe coherent revivals when inverting the state-dependent force after separating the wavepackets by more than 19 times the ground-state root mean squared extent, which corresponds to 56 times the root mean squared extent of the squeezed wavepacket along the displacement direction. Aside from their fundamental nature, these states may be useful for quantum metrology 6 or quantum information processing with continuous variables 7 , 8 , 9 . Main The creation and study of non-classical states of spin systems coupled to a harmonic oscillator have provided fundamental insights into the nature of decoherence and the quantum–classical transition. These states and their control form the basis of experimental developments in quantum information processing and quantum metrology 1 , 2 , 10 . Two of the most commonly considered states of the oscillator are squeezed states and superpositions of coherent states of opposite phase, which are commonly referred to as ‘Schrödinger’s cat’ (SC) states. Squeezed states involve a reduction of the fluctuations in one quadrature of the oscillator below the ground-state uncertainty, which has been used to increase sensitivity in interferometers 11 , 12 . SC states provide a complementary sensitivity to environmental influences by separating the two parts of the state by a large distance in phase space. These states have been created in microwave and optical cavities 2 , 13 , where they are typically not entangled with another system, and also with trapped ions 1 , 3 , 4 , 5 , where all experiments performed have involved entanglement between the oscillator state and the internal electronic states of the ion. SC states have recently been used as sensitive detectors for photon scattering recoil events at the single-photon level 14 . Here we use state-dependent forces (SDFs) to create superpositions of distinct squeezed oscillator wavepackets that are entangled with a pseudo-spin encoded in the electronic states of a single trapped ion. We will refer to these states as squeezed wavepacket entangled states (SWESs) in the rest of the paper. By monitoring the spin evolution as the entanglement with the oscillator increases 15 , 16 , 17 , we are able to observe the squeezed nature of the initial state directly. We obtain a complementary measurement of the initial state by extracting the number-state probability distribution of the displaced-squeezed states that make up the superposition. In both measurements we observe clear differences depending on the force direction. We show that the SWESs are coherent by reversing the effect of the SDF, resulting in recombination of the squeezed wavepackets, which we measure through the revival of the spin coherence. The squeezed vacuum state is defined by the action of the squeezing operator on the motional ground state , where , with r and ϕ s real parameters that define the magnitude and the direction of the squeezing in phase space. To prepare squeezed states of motion in which the variance of the squeezed quadrature is reduced by about 9 dB relative to the ground-state wavepacket we use reservoir engineering, in which a bichromatic light field is used to couple the ion’s motion to the spin states of the ion, which undergo continuous optical pumping. This dissipatively pumps the motional state of the ion into the desired squeezed state, which is the dark state of the dynamics. More details about the reservoir engineering can be found in ref. 18 . This approach provides a robust basis for all experiments described below, typically requiring no recalibration over several hours of taking data. In the ideal case, the optical pumping used in the reservoir engineering results in the ion being pumped to . To create a SWES, we apply a SDF to this squeezed vacuum state by simultaneously driving the red and blue motional sidebands of the spin-flip transition 3 . The resulting interaction Hamiltonian can be written in the Lamb–Dicke approximation (LDA) as where Ω is the strength of the SDF, ϕ D is the relative phase of the two light fields, and with . For an ion prepared in , this Hamiltonian results in displacement of the motional state in phase space by an amount , which is given in units of the root mean squared (r.m.s.) extent of the harmonic oscillator ground state. An ion prepared in will be displaced by the same amount in the opposite direction. In the following equations we use α in place of α(τ) for simplicity. Starting from the state , application of the SDF ideally results in the SWES where we use the notation with the displacement operator . A projective measurement of the spin performed in the basis gives the probability of being as , where gives the overlap between the two displaced motional states, which can be written as where . When Δ ϕ = 0, the SDF is aligned with the squeezed quadrature of the state, whereas for Δ ϕ = π/2, the SDF is aligned with the anti-squeezed quadrature. At displacements for which X gives a measurable signal, monitoring the spin population as a function of the force duration τ for different choices of Δ ϕ allows us to characterize the spatial variation of the initial squeezed wavepacket 15", "role": "user" }, { "content": "ETH professor Jonathan Home and his colleagues reach deep into their bag of tricks to create so-called 'squeezed Schrödinger cats.' These quantum systems could be extremely useful for future technologies. Quantum physics is full of fascinating phenomena. Take, for instance, the cat from the famous thought experiment by the physicist Erwin Schrodinger. The cat can be dead and alive at once, since its life depends on the quantum mechanically determined state of a radioactively decaying atom which, in turn, releases toxic gas into the cat's cage. As long as one hasn't measured the state of the atom, one knows nothing about the poor cat's health either - atom and kitty are intimately \"entangled\" with each other. Equally striking, if less well known, are the so-called squeezed quantum states: Normally, Heisenberg's uncertainty principle means that one cannot measure the values of certain pairs of physical quantities, such as the position and velocity of a quantum particle, with arbitrary precision. Nevertheless, nature allows a barter trade: If the particle has been appropriately prepared, then one of the quantities can be measured a little more exactly if one is willing to accept a less precise knowledge of the other quantity. In this case the preparation of the particle is known as \"squeezing\" because the uncertainty in one variable is reduced (squeezed). Schrödinger's cat and squeezed quantum states are both important physical phenomena that lie at the heart of promising technologies of the future. Researchers at the ETH were now able successfully to combine both in a single experiment. Squeezing and shifting In their laboratory, Jonathan Home, professor of experimental quantum optics and photonics, and his colleagues catch a single electrically charged calcium ion in a tiny cage made of electric fields. Using laser beams they cool the ion down until it hardly moves inside the cage. Now the researchers reach into their bag of tricks: they \"squeeze\" the state of motion of the ion by shining laser light on it and by skilfully using the spontaneous decay of its energy states. Eventually the ion's wave function (which corresponds to the probability of finding it at a certain point in space) is literally squashed: now the physicists have a better idea of where the ion is located in space, but the uncertainty in its velocity has increased proportionately. \"This state squeezing is an important tool for us\", Jonathan Home explains. \"Together with a second tool - the so-called state-dependent forces - we are now able to produce a \"squeezed Schrödinger cat\" \". To that end the ion is once more exposed to laser beams that move it to the left or to the right. The direction of the forces induced by the laser depends on the internal energy state of the ion. This energy state can be represented by an arrow pointing up or down, also called a spin. If the ion is in an energy superposition state composed of \"spin up\" and \"spin down\", the force acts both to the left and to the right. In this way, a peculiar situation is created that is similar to Schrödinger's cat: the ion now finds itself in a hybrid state of being on the right (cat is alive) and on the left (cat is dead) at the same time. Only when one measures the spin does the ion decide whether to be on the right or on the left. Stable cats for quantum computers The Schrödinger cat prepared by professor Home and his collaborators is special in that the initial squeezing makes the ion states \"left\" and \"right\" particularly easy to distinguish. At the same time, it is also pretty large as the two ion states are far apart. \"Even without the squeezing our \"cat\" is the largest one produced to date\", Home points out. \"With the squeezing, the states \"left\" and \"right\" are even more distinguishable - they are as much as sixty times narrower than the separation between them\". All this isn't just about scientific records, however, but also about practical applications. Squeezed Schrödinger cats are particularly stable against certain types of disturbances that would normally cause the cats to lose their quantum properties and become ordinary felines. That stability could, for instance, be exploited in order to realize quantum computers, which use quantum superposition states to do their calculations. Furthermore, ultra-precise measurements could be made less sensitive to unwanted external influences. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Mesoscopic superpositions of distinguishable coherent states provide an analogue of the ‘Schrödinger’s cat’ thought experiment 1 , 2 . For mechanical oscillators these have primarily been realized using coherent wavepackets, for which the distinguishability arises as a result of the spatial separation of the superposed states 3 , 4 , 5 . Here we demonstrate superpositions composed of squeezed wavepackets, which we generate by applying an internal-state-dependent force to a single trapped ion initialized in a squeezed vacuum state with nine decibel reduction in the quadrature variance. This allows us to characterize the initial squeezed wavepacket by monitoring the onset of spin–motion entanglement, and to verify the evolution of the number states of the oscillator as a function of the duration of the force. In both cases we observe clear differences between displacements aligned with the squeezed and anti-squeezed axes. We observe coherent revivals when inverting the state-dependent force after separating the wavepackets by more than 19 times the ground-state root mean squared extent, which corresponds to 56 times the root mean squared extent of the squeezed wavepacket along the displacement direction. Aside from their fundamental nature, these states may be useful for quantum metrology 6 or quantum information processing with continuous variables 7 , 8 , 9 . Main The creation and study of non-classical states of spin systems coupled to a harmonic oscillator have provided fundamental insights into the nature of decoherence and the quantum–classical transition. These states and their control form the basis of experimental developments in quantum information processing and quantum metrology 1 , 2 , 10 . Two of the most commonly considered states of the oscillator are squeezed states and superpositions of coherent states of opposite phase, which are commonly referred to as ‘Schrödinger’s cat’ (SC) states. Squeezed states involve a reduction of the fluctuations in one quadrature of the oscillator below the ground-state uncertainty, which has been used to increase sensitivity in interferometers 11 , 12 . SC states provide a complementary sensitivity to environmental influences by separating the two parts of the state by a large distance in phase space. These states have been created in microwave and optical cavities 2 , 13 , where they are typically not entangled with another system, and also with trapped ions 1 , 3 , 4 , 5 , where all experiments performed have involved entanglement between the oscillator state and the internal electronic states of the ion. SC states have recently been used as sensitive detectors for photon scattering recoil events at the single-photon level 14 . Here we use state-dependent forces (SDFs) to create superpositions of distinct squeezed oscillator wavepackets that are entangled with a pseudo-spin encoded in the electronic states of a single trapped ion. We will refer to these states as squeezed wavepacket entangled states (SWESs) in the rest of the paper. By monitoring the spin evolution as the entanglement with the oscillator increases 15 , 16 , 17 , we are able to observe the squeezed nature of the initial state directly. We obtain a complementary measurement of the initial state by extracting the number-state probability distribution of the displaced-squeezed states that make up the superposition. In both measurements we observe clear differences depending on the force direction. We show that the SWESs are coherent by reversing the effect of the SDF, resulting in recombination of the squeezed wavepackets, which we measure through the revival of the spin coherence. The squeezed vacuum state is defined by the action of the squeezing operator on the motional ground state , where , with r and ϕ s real parameters that define the magnitude and the direction of the squeezing in phase space. To prepare squeezed states of motion in which the variance of the squeezed quadrature is reduced by about 9 dB relative to the ground-state wavepacket we use reservoir engineering, in which a bichromatic light field is used to couple the ion’s motion to the spin states of the ion, which undergo continuous optical pumping. This dissipatively pumps the motional state of the ion into the desired squeezed state, which is the dark state of the dynamics. More details about the reservoir engineering can be found in ref. 18 . This approach provides a robust basis for all experiments described below, typically requiring no recalibration over several hours of taking data. In the ideal case, the optical pumping used in the reservoir engineering results in the ion being pumped to . To create a SWES, we apply a SDF to this squeezed vacuum state by simultaneously driving the red and blue motional sidebands of the spin-flip transition 3 . The resulting interaction Hamiltonian can be written in the Lamb–Dicke approximation (LDA) as where Ω is the strength of the SDF, ϕ D is the relative phase of the two light fields, and with . For an ion prepared in , this Hamiltonian results in displacement of the motional state in phase space by an amount , which is given in units of the root mean squared (r.m.s.) extent of the harmonic oscillator ground state. An ion prepared in will be displaced by the same amount in the opposite direction. In the following equations we use α in place of α(τ) for simplicity. Starting from the state , application of the SDF ideally results in the SWES where we use the notation with the displacement operator . A projective measurement of the spin performed in the basis gives the probability of being as , where gives the overlap between the two displaced motional states, which can be written as where . When Δ ϕ = 0, the SDF is aligned with the squeezed quadrature of the state, whereas for Δ ϕ = π/2, the SDF is aligned with the anti-squeezed quadrature. At displacements for which X gives a measurable signal, monitoring the spin population as a function of the force duration τ for different choices of Δ ϕ allows us to characterize the spatial variation of the initial squeezed wavepacket 15<|im_end|> <|im_start|>assistant ETH professor Jonathan Home and his colleagues reach deep into their bag of tricks to create so-called 'squeezed Schrödinger cats.' These quantum systems could be extremely useful for future technologies. Quantum physics is full of fascinating phenomena. Take, for instance, the cat from the famous thought experiment by the physicist Erwin Schrodinger. The cat can be dead and alive at once, since its life depends on the quantum mechanically determined state of a radioactively decaying atom which, in turn, releases toxic gas into the cat's cage. As long as one hasn't measured the state of the atom, one knows nothing about the poor cat's health either - atom and kitty are intimately "entangled" with each other. Equally striking, if less well known, are the so-called squeezed quantum states: Normally, Heisenberg's uncertainty principle means that one cannot measure the values of certain pairs of physical quantities, such as the position and velocity of a quantum particle, with arbitrary precision. Nevertheless, nature allows a barter trade: If the particle has been appropriately prepared, then one of the quantities can be measured a little more exactly if one is willing to accept a less precise knowledge of the other quantity. In this case the preparation of the particle is known as "squeezing" because the uncertainty in one variable is reduced (squeezed). Schrödinger's cat and squeezed quantum states are both important physical phenomena that lie at the heart of promising technologies of the future. Researchers at the ETH were now able successfully to combine both in a single experiment. Squeezing and shifting In their laboratory, Jonathan Home, professor of experimental quantum optics and photonics, and his colleagues catch a single electrically charged calcium ion in a tiny cage made of electric fields. Using laser beams they cool the ion down until it hardly moves inside the cage. Now the researchers reach into their bag of tricks: they "squeeze" the state of motion of the ion by shining laser light on it and by skilfully using the spontaneous decay of its energy states. Eventually the ion's wave function (which corresponds to the probability of finding it at a certain point in space) is literally squashed: now the physicists have a better idea of where the ion is located in space, but the uncertainty in its velocity has increased proportionately. "This state squeezing is an important tool for us", Jonathan Home explains. "Together with a second tool - the so-called state-dependent forces - we are now able to produce a "squeezed Schrödinger cat" ". To that end the ion is once more exposed to laser beams that move it to the left or to the right. The direction of the forces induced by the laser depends on the internal energy state of the ion. This energy state can be represented by an arrow pointing up or down, also called a spin. If the ion is in an energy superposition state composed of "spin up" and "spin down", the force acts both to the left and to the right. In this way, a peculiar situation is created that is similar to Schrödinger's cat: the ion now finds itself in a hybrid state of being on the right (cat is alive) and on the left (cat is dead) at the same time. Only when one measures the spin does the ion decide whether to be on the right or on the left. Stable cats for quantum computers The Schrödinger cat prepared by professor Home and his collaborators is special in that the initial squeezing makes the ion states "left" and "right" particularly easy to distinguish. At the same time, it is also pretty large as the two ion states are far apart. "Even without the squeezing our "cat" is the largest one produced to date", Home points out. "With the squeezing, the states "left" and "right" are even more distinguishable - they are as much as sixty times narrower than the separation between them". All this isn't just about scientific records, however, but also about practical applications. Squeezed Schrödinger cats are particularly stable against certain types of disturbances that would normally cause the cats to lose their quantum properties and become ordinary felines. That stability could, for instance, be exploited in order to realize quantum computers, which use quantum superposition states to do their calculations. Furthermore, ultra-precise measurements could be made less sensitive to unwanted external influences. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 36684, 84667, 2307, 28536, 315, 33137, 481, 56887, 5415, 3493, 459, 91343, 315, 279, 3451, 50, 17207, 3029, 67, 5248, 753, 8415, 529, 3463, 9526, 220, 16, 1174, 220, 17, 662, 1789, 22936, 43524, 3046, 1521, 617, 15871, 1027, 15393, 1701, 56887, 12330, 4853, 1441, 11, 369, 902, 279, 33137, 2968, 48282, 439, 264, 1121, 315, 279, 29079, 25768, 315, 279, 2307, 3950, 5415, 220, 18, 1174, 220, 19, 1174, 220, 20, 662, 5810, 584, 20461, 2307, 28536, 24306, 315, 65262, 12330, 4853, 1441, 11, 902, 584, 7068, 555, 19486, 459, 5419, 21395, 43918, 5457, 311, 264, 3254, 31691, 28772, 17719, 304, 264, 65262, 29302, 1614, 449, 11888, 1654, 69695, 14278, 304, 279, 30236, 1598, 33373, 13, 1115, 6276, 603, 311, 70755, 279, 2926, 65262, 12330, 25868, 555, 16967, 279, 42080, 315, 12903, 4235, 49975, 1218, 526, 1001, 11, 323, 311, 10356, 279, 15740, 315, 279, 1396, 5415, 315, 279, 84741, 439, 264, 734, 315, 279, 8250, 315, 279, 5457, 13, 763, 2225, 5157, 584, 23846, 2867, 12062, 1990, 13770, 34178, 27210, 449, 279, 65262, 323, 7294, 1355, 593, 10333, 291, 25776, 13, 1226, 23846, 56887, 5891, 18734, 994, 304, 50517, 279, 1614, 43918, 5457, 1306, 50545, 279, 12330, 4853, 1441, 555, 810, 1109, 220, 777, 3115, 279, 5015, 21395, 3789, 3152, 53363, 13112, 11, 902, 34310, 311, 220, 3487, 3115, 279, 3789, 3152, 53363, 13112, 315, 279, 65262, 12330, 25868, 3235, 279, 44153, 5216, 13, 57194, 505, 872, 16188, 7138, 11, 1521, 5415, 1253, 387, 5505, 369, 31228, 34582, 36781, 220, 21, 477, 31228, 2038, 8863, 449, 19815, 7482, 220, 22, 1174, 220, 23, 1174, 220, 24, 662, 4802, 578, 9886, 323, 4007, 315, 2536, 15144, 950, 5415, 315, 12903, 6067, 34356, 311, 264, 82341, 84741, 617, 3984, 16188, 26793, 1139, 279, 7138, 315, 68652, 52461, 323, 279, 31228, 4235, 1058, 950, 9320, 13, 4314, 5415, 323, 872, 2585, 1376, 279, 8197, 315, 22772, 26006, 304, 31228, 2038, 8863, 323, 31228, 34582, 36781, 220, 16, 1174, 220, 17, 1174, 220, 605, 662, 9220, 315, 279, 1455, 17037, 6646, 5415, 315, 279, 84741, 527, 65262, 5415, 323, 2307, 28536, 315, 56887, 5415, 315, 14329, 10474, 11, 902, 527, 17037, 14183, 311, 439, 3451, 50, 17207, 3029, 67, 5248, 753, 8415, 529, 320, 3624, 8, 5415, 13, 328, 593, 10333, 291, 5415, 21736, 264, 14278, 315, 279, 65649, 304, 832, 30236, 1598, 315, 279, 84741, 3770, 279, 5015, 21395, 27924, 11, 902, 706, 1027, 1511, 311, 5376, 27541, 304, 41305, 33504, 220, 806, 1174, 220, 717, 662, 7683, 5415, 3493, 264, 58535, 27541, 311, 12434, 34453, 555, 50545, 279, 1403, 5596, 315, 279, 1614, 555, 264, 3544, 6138, 304, 10474, 3634, 13, 4314, 5415, 617, 1027, 3549, 304, 42374, 323, 29393, 57709, 1385, 220, 17, 1174, 220, 1032, 1174, 1405, 814, 527, 11383, 539, 1218, 40040, 449, 2500, 1887, 11, 323, 1101, 449, 31691, 65125, 220, 16, 1174, 220, 18, 1174, 220, 19, 1174, 220, 20, 1174, 1405, 682, 21896, 10887, 617, 6532, 1218, 526, 1001, 1990, 279, 84741, 1614, 323, 279, 5419, 14683, 5415, 315, 279, 28772, 13, 7683, 5415, 617, 6051, 1027, 1511, 439, 16614, 69087, 369, 69010, 72916, 74422, 4455, 520, 279, 3254, 63837, 26934, 2237, 220, 975, 662, 5810, 584, 1005, 1614, 43918, 8603, 320, 50, 5375, 82, 8, 311, 1893, 2307, 28536, 315, 12742, 65262, 84741, 12330, 4853, 1441, 430, 527, 1218, 40040, 449, 264, 35850, 82006, 21136, 304, 279, 14683, 5415, 315, 264, 3254, 31691, 28772, 13, 1226, 690, 8464, 311, 1521, 5415, 439, 65262, 12330, 25868, 1218, 40040, 5415, 320, 17268, 1600, 82, 8, 304, 279, 2800, 315, 279, 5684, 13, 3296, 16967, 279, 12903, 15740, 439, 279, 1218, 526, 1001, 449, 279, 84741, 12992, 220, 868, 1174, 220, 845, 1174, 220, 1114, 1174, 584, 527, 3025, 311, 23846, 279, 65262, 7138, 315, 279, 2926, 1614, 6089, 13, 1226, 6994, 264, 58535, 19179, 315, 279, 2926, 1614, 555, 60508, 279, 1396, 21395, 19463, 8141, 315, 279, 49246, 1355, 593, 10333, 291, 5415, 430, 1304, 709, 279, 2307, 3571, 13, 763, 2225, 22323, 584, 23846, 2867, 12062, 11911, 389, 279, 5457, 5216, 13, 1226, 1501, 430, 279, 13692, 1600, 82, 527, 56887, 555, 76283, 279, 2515, 315, 279, 328, 5375, 11, 13239, 304, 312, 76128, 315, 279, 65262, 12330, 4853, 1441, 11, 902, 584, 6767, 1555, 279, 57105, 315, 279, 12903, 78925, 13, 578, 65262, 29302, 1614, 374, 4613, 555, 279, 1957, 315, 279, 88807, 5793, 389, 279, 3937, 4001, 5015, 1614, 1174, 1405, 1174, 449, 436, 323, 17839, 243, 274, 1972, 5137, 430, 7124, 279, 26703, 323, 279, 5216, 315, 279, 88807, 304, 10474, 3634, 13, 2057, 10772, 65262, 5415, 315, 11633, 304, 902, 279, 33373, 315, 279, 65262, 30236, 1598, 374, 11293, 555, 922, 220, 24, 44868, 8844, 311, 279, 5015, 21395, 12330, 25868, 584, 1005, 45512, 15009, 11, 304, 902, 264, 293, 718, 99866, 3177, 2115, 374, 1511, 311, 5743, 279, 28772, 753, 11633, 311, 279, 12903, 5415, 315, 279, 28772, 11, 902, 37771, 19815, 29393, 53226, 13, 1115, 93522, 8046, 43875, 279, 3937, 4001, 1614, 315, 279, 28772, 1139, 279, 12974, 65262, 1614, 11, 902, 374, 279, 6453, 1614, 315, 279, 30295, 13, 4497, 3649, 922, 279, 45512, 15009, 649, 387, 1766, 304, 2098, 13, 220, 972, 662, 1115, 5603, 5825, 264, 22514, 8197, 369, 682, 21896, 7633, 3770, 11, 11383, 23537, 912, 99783, 18856, 927, 3892, 4207, 315, 4737, 828, 13, 763, 279, 10728, 1162, 11, 279, 29393, 53226, 1511, 304, 279, 45512, 15009, 3135, 304, 279, 28772, 1694, 62454, 311, 662, 2057, 1893, 264, 13692, 1600, 11, 584, 3881, 264, 328, 5375, 311, 420, 65262, 29302, 1614, 555, 25291, 10043, 279, 2579, 323, 6437, 3937, 4001, 3185, 43006, 315, 279, 12903, 12556, 575, 9320, 220, 18, 662, 578, 13239, 16628, 24051, 1122, 649, 387, 5439, 304, 279, 32402, 4235, 45645, 441, 57304, 320, 43, 6486, 8, 439, 1405, 117336, 374, 279, 8333, 315, 279, 328, 5375, 11, 17839, 243, 423, 374, 279, 8844, 10474, 315, 279, 1403, 3177, 5151, 11, 323, 449, 662, 1789, 459, 28772, 10235, 304, 1174, 420, 24051, 1122, 3135, 304, 44153, 315, 279, 3937, 4001, 1614, 304, 10474, 3634, 555, 459, 3392, 1174, 902, 374, 2728, 304, 8316, 315, 279, 3789, 3152, 53363, 320, 81, 749, 516, 6266, 13112, 315, 279, 82341, 84741, 5015, 1614, 13, 1556, 28772, 10235, 304, 690, 387, 49246, 555, 279, 1890, 3392, 304, 279, 14329, 5216, 13, 763, 279, 2768, 39006, 584, 1005, 19581, 304, 2035, 315, 19581, 7, 36924, 8, 369, 40075, 13, 28757, 505, 279, 1614, 1174, 3851, 315, 279, 328, 5375, 50663, 3135, 304, 279, 13692, 1600, 1405, 584, 1005, 279, 45297, 449, 279, 44153, 5793, 662, 362, 2447, 535, 19179, 315, 279, 12903, 10887, 304, 279, 8197, 6835, 279, 19463, 315, 1694, 439, 1174, 1405, 6835, 279, 28347, 1990, 279, 1403, 49246, 3937, 4001, 5415, 11, 902, 649, 387, 5439, 439, 1405, 662, 3277, 82263, 17839, 243, 284, 220, 15, 11, 279, 328, 5375, 374, 27210, 449, 279, 65262, 30236, 1598, 315, 279, 1614, 11, 20444, 369, 82263, 17839, 243, 284, 52845, 14, 17, 11, 279, 328, 5375, 374, 27210, 449, 279, 7294, 1355, 593, 10333, 291, 30236, 1598, 13, 2468, 13770, 34178, 369, 902, 1630, 6835, 264, 66303, 8450, 11, 16967, 279, 12903, 7187, 439, 264, 734, 315, 279, 5457, 8250, 39570, 369, 2204, 11709, 315, 82263, 17839, 243, 6276, 603, 311, 70755, 279, 29079, 23851, 315, 279, 2926, 65262, 12330, 25868, 220, 868, 128257, 198, 128256, 78191, 198, 7780, 14561, 24150, 5492, 323, 813, 18105, 5662, 5655, 1139, 872, 9145, 315, 29862, 311, 1893, 779, 19434, 364, 82, 593, 10333, 291, 5124, 81, 3029, 67, 5248, 19987, 3238, 4314, 31228, 6067, 1436, 387, 9193, 5505, 369, 3938, 14645, 13, 56413, 22027, 374, 2539, 315, 27387, 44247, 13, 12040, 11, 369, 2937, 11, 279, 8415, 505, 279, 11495, 3463, 9526, 555, 279, 83323, 9939, 7678, 5124, 24409, 5248, 13, 578, 8415, 649, 387, 5710, 323, 13989, 520, 3131, 11, 2533, 1202, 2324, 14117, 389, 279, 31228, 99097, 11075, 1614, 315, 264, 9063, 64119, 1654, 17718, 19670, 902, 11, 304, 2543, 11, 19786, 21503, 6962, 1139, 279, 8415, 596, 36460, 13, 1666, 1317, 439, 832, 12775, 956, 17303, 279, 1614, 315, 279, 19670, 11, 832, 8964, 4400, 922, 279, 8009, 8415, 596, 2890, 3060, 482, 19670, 323, 80921, 527, 96752, 330, 306, 40040, 1, 449, 1855, 1023, 13, 11964, 750, 21933, 11, 422, 2753, 1664, 3967, 11, 527, 279, 779, 19434, 65262, 31228, 5415, 25, 52783, 11, 1283, 24004, 7881, 596, 27924, 17966, 3445, 430, 832, 4250, 6767, 279, 2819, 315, 3738, 13840, 315, 7106, 33776, 11, 1778, 439, 279, 2361, 323, 15798, 315, 264, 31228, 19320, 11, 449, 25142, 16437, 13, 35053, 11, 7138, 6276, 264, 3703, 466, 6696, 25, 1442, 279, 19320, 706, 1027, 36001, 10235, 11, 1243, 832, 315, 279, 33776, 649, 387, 17303, 264, 2697, 810, 7041, 422, 832, 374, 10032, 311, 4287, 264, 2753, 24473, 6677, 315, 279, 1023, 12472, 13, 763, 420, 1162, 279, 18459, 315, 279, 19320, 374, 3967, 439, 330, 82, 593, 10333, 287, 1, 1606, 279, 27924, 304, 832, 3977, 374, 11293, 320, 82, 593, 10333, 291, 570, 5124, 81, 3029, 67, 5248, 596, 8415, 323, 65262, 31228, 5415, 527, 2225, 3062, 7106, 44247, 430, 10457, 520, 279, 4851, 315, 26455, 14645, 315, 279, 3938, 13, 59250, 520, 279, 38842, 1051, 1457, 3025, 7946, 311, 16343, 2225, 304, 264, 3254, 9526, 13, 328, 593, 10333, 287, 323, 32931, 763, 872, 27692, 11, 24150, 5492, 11, 14561, 315, 22772, 31228, 70985, 323, 69010, 1233, 11, 323, 813, 18105, 2339, 264, 3254, 9249, 750, 11684, 35719, 28772, 304, 264, 13987, 36460, 1903, 315, 9249, 5151, 13, 12362, 21120, 51045, 814, 7155, 279, 28772, 1523, 3156, 433, 20781, 11031, 4871, 279, 36460, 13, 4800, 279, 12074, 5662, 1139, 872, 9145, 315, 29862, 25, 814, 330, 53013, 1, 279, 1614, 315, 11633, 315, 279, 28772, 555, 49025, 21120, 3177, 389, 433, 323, 555, 1940, 321, 3725, 1701, 279, 54557, 31815, 315, 1202, 4907, 5415, 13, 38274, 279, 28772, 596, 12330, 734, 320, 8370, 34310, 311, 279, 19463, 315, 9455, 433, 520, 264, 3738, 1486, 304, 3634, 8, 374, 16280, 8330, 13883, 25, 1457, 279, 98417, 617, 264, 2731, 4623, 315, 1405, 279, 28772, 374, 7559, 304, 3634, 11, 719, 279, 27924, 304, 1202, 15798, 706, 7319, 21801, 2718, 13, 330, 2028, 1614, 88807, 374, 459, 3062, 5507, 369, 603, 498, 24150, 5492, 15100, 13, 330, 82087, 449, 264, 2132, 5507, 482, 279, 779, 19434, 1614, 43918, 8603, 482, 584, 527, 1457, 3025, 311, 8356, 264, 330, 82, 593, 10333, 291, 5124, 81, 3029, 67, 5248, 8415, 1, 6058, 2057, 430, 842, 279, 28772, 374, 3131, 810, 15246, 311, 21120, 51045, 430, 3351, 433, 311, 279, 2163, 477, 311, 279, 1314, 13, 578, 5216, 315, 279, 8603, 36572, 555, 279, 21120, 14117, 389, 279, 5419, 4907, 1614, 315, 279, 28772, 13, 1115, 4907, 1614, 649, 387, 15609, 555, 459, 18404, 22364, 709, 477, 1523, 11, 1101, 2663, 264, 12903, 13, 1442, 279, 28772, 374, 304, 459, 4907, 2307, 3571, 1614, 24306, 315, 330, 42682, 709, 1, 323, 330, 42682, 1523, 498, 279, 5457, 14385, 2225, 311, 279, 2163, 323, 311, 279, 1314, 13, 763, 420, 1648, 11, 264, 44797, 6671, 374, 3549, 430, 374, 4528, 311, 5124, 81, 3029, 67, 5248, 596, 8415, 25, 279, 28772, 1457, 14035, 5196, 304, 264, 26038, 1614, 315, 1694, 389, 279, 1314, 320, 4719, 374, 13989, 8, 323, 389, 279, 2163, 320, 4719, 374, 5710, 8, 520, 279, 1890, 892, 13, 8442, 994, 832, 11193, 279, 12903, 1587, 279, 28772, 10491, 3508, 311, 387, 389, 279, 1314, 477, 389, 279, 2163, 13, 84441, 19987, 369, 31228, 19002, 578, 5124, 81, 3029, 67, 5248, 8415, 10235, 555, 14561, 5492, 323, 813, 79119, 374, 3361, 304, 430, 279, 2926, 88807, 3727, 279, 28772, 5415, 330, 2414, 1, 323, 330, 1315, 1, 8104, 4228, 311, 33137, 13, 2468, 279, 1890, 892, 11, 433, 374, 1101, 5128, 3544, 439, 279, 1403, 28772, 5415, 527, 3117, 10980, 13, 330, 13461, 2085, 279, 88807, 1057, 330, 4719, 1, 374, 279, 7928, 832, 9124, 311, 2457, 498, 5492, 3585, 704, 13, 330, 2409, 279, 88807, 11, 279, 5415, 330, 2414, 1, 323, 330, 1315, 1, 527, 1524, 810, 33137, 481, 482, 814, 527, 439, 1790, 439, 53474, 3115, 91529, 1109, 279, 25768, 1990, 1124, 3343, 2052, 420, 4536, 956, 1120, 922, 12624, 7576, 11, 4869, 11, 719, 1101, 922, 15325, 8522, 13, 328, 593, 10333, 291, 5124, 81, 3029, 67, 5248, 19987, 527, 8104, 15528, 2403, 3738, 4595, 315, 85160, 430, 1053, 14614, 5353, 279, 19987, 311, 9229, 872, 31228, 6012, 323, 3719, 19664, 282, 11243, 13, 3011, 20334, 1436, 11, 369, 2937, 11, 387, 51763, 304, 2015, 311, 13383, 31228, 19002, 11, 902, 1005, 31228, 2307, 3571, 5415, 311, 656, 872, 29217, 13, 24296, 11, 24955, 12, 10872, 1082, 22323, 1436, 387, 1903, 2753, 16614, 311, 36021, 9434, 34453, 13, 220, 128257, 198 ]

2,175

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract The KNM-ER 2598 occipital is among the oldest fossils attributed to Homo erectus but questions have been raised about whether it may derive from a younger horizon. Here we report on efforts to relocate the KNM-ER 2598 locality and investigate its paleontological and geological context. Although located in a different East Turkana collection area (Area 13) than initially reported, the locality is stratigraphically positioned below the KBS Tuff and the outcrops show no evidence of deflation of a younger unit, supporting an age of >1.855 Ma. Newly recovered faunal material consists primarily of C 4 grazers, further confirmed by enamel isotope data. A hominin proximal 3rd metatarsal and partial ilium were discovered <50 m from the reconstructed location where KNM-ER 2598 was originally found but these cannot be associated directly with the occipital. The postcrania are consistent with fossil Homo and may represent the earliest postcrania attributable to Homo erectus . Introduction The KNM-ER 2598 specimen from East Turkana, Kenya is widely recognized as significant because it is one of the oldest fossils attributed to Homo erectus 1 , 2 , 3 , 4 , 5 . KNM-ER 2598 is a thick hominin cranial fragment preserving much of the central occipital bone, including portions of the lambdoidal suture and a distinctive Homo erectus -like occipital torus (Fig. 1 ) 6 . This fossil was collected from the outcrop surface in 1974 and was initially reported as originating from approximately the level of the KBS Tuff in East Turkana collection Area 15 6 . Later work would refine the stratigraphic placement of KNM-ER 2598 to about 4 m below the KBS Tuff and interpret the age as 1.88–1.9 million years (Ma) ago 1 , 7 . Fig. 1: KNM-ER 2598 partial occipital. a Inset image indicates the approximate anatomical location of the KNM-ER 2598 occipital. b Posterior view and right lateral view are shown. Full size image If KNM-ER 2598 is dated to nearly 1.9 Ma, it is the second chronologically oldest specimen with morphological affinities to H. erectus . The DNH 134 neurocranium from Drimolen is the oldest known Homo erectus specimen 8 . DNH 134 is a juvenile individual, which makes a categorical species attribution difficult to establish, but it has features (e.g., a teardrop-shaped superior profile, flat squamosal suture) which strongly favor a H. erectus attribution 8 . DNH 134 was recovered from a deposit with reversed paleomagnetic polarity with an associated uranium-series electron spin resonance (ESR) date of 2.04 Ma 8 , indicating that this specimen was deposited sometime within the C2r.1r reversed subchron. The most recent Geomagnetic Polarity Time Scale (GPTS 2020) associate the C2r.1r chron to the 1.934–2.120 Ma time interval 9 , 10 . Both DNH 134 and KNM-ER 2598 are critically important fossils because they are slightly older than those recovered from Dmanisi in the Republic of Georgia. The Dmanisi hominin fossils may be as old as 1.78 Ma 11 , and occupation of the site appears to extend to 1.85 Ma 11 . The Dmanisi dates, which approach the dates for the African H. erectus specimens, raise the possibility that Homo erectus origins could have occurred in Eurasia rather than on the African continent 4 . Accordingly, KNM-ER 2598 is key to anchoring the earliest evolution and dispersals of Homo erectus , but some authors have raised doubts about the age of KNM-ER 2598 12 , 13 . It has been suggested that the altimetric position of KNM-ER 2598 below the KBS Tuff may have resulted from deflation of a stratigraphically younger horizon (e.g., KBS Member) that is no longer visible on the exposed upper Burgi Member outcrop surface 12 , 13 . Regrettably, few details regarding the provenience of the fossil were offered in the initial publications 6 , 14 . Given the importance of KNM-ER 2598 for placing the early evolution and dispersal of H. erectus within Africa, it has become essential to provide a geochronological context for the KNM-ER 2598 locality. Here we report on new investigations into the KNM-ER 2598 site location, geology, and paleoecology. The geological data presented here support the interpretation that the KNM-ER 2598 occipital derives from the upper Burgi Member of the Koobi Fora Formation, conservatively dating the fossil to >1.855 Ma. Our findings also correct the location of the KNM-ER 2598 locality, demonstrating that it is situated within the boundaries of collection Area 13 rather than Area 15 in East Turkana. We report on a new hominin ilium and metatarsal recovered within close proximity of where KNM-ER 2598 originated. These hominin fossils are consistent with Homo erectus , potentially making these the oldest postcranial fossils attributable to the taxon. Finally, we contextualize the paleohabitat in East Turkana Area 13 through faunal abundance data, isotopic analyses of mammalian dental enamel, and petrographic data. Results Identification of the locality We used field-based reconnaissance combined with historical imagery to identify the KNM-ER 2598 locality (Supplementary Figs. 1 – 3 ). We used Google Earth imagery to approximate the geospatial location of KNM-ER 2598 in geographic coordinates from historical aerial photographic records housed at the National Museums of Kenya (Supplementary Fig. 1 ). The aerial imagery from the 1970s document that KNM-ER 2598 was actually discovered within the boundaries of collection Area 13. Photographs from the 1974–1975 field seasons confirm that collections were taking place in collection Area 13, based on landscape features that are still identifiable (Supplementary Fig. 2 ). Upon physical inspection of the reconstructed location, a large collapsed sandstone cairn was identified at approximately the same coordinates (N 4.26984, E 36.33848, WGS84; altitude 413.5 m above sea level) reconstructed from the aerial imagery. The sandstone cairn (Supplementary Fig. 3 ) is consistent with the markers used in the 1970s, prior to the positioning of cement plinths as hominin markers. Geological context and age Survey of the rediscovered KNM-ER 2598 locality and nearby areas within Area 13 allowed us to identify two distinct aggregates (Burgi and KBS Members) and a tuff horizon (the KBS", "role": "user" }, { "content": "A new study verifies the age and origin of one of the oldest specimens of Homo erectus—a very successful early human who roamed the world for nearly 2 million years. In doing so, the researchers also found two new specimens at the site—likely the earliest pieces of the Homo erectus skeleton yet discovered. Details are published today in the journal Nature Communications. \"Homo erectus is the first hominin that we know about that has a body plan more like our own and seemed to be on its way to being more human-like,\" said Ashley Hammond, an assistant curator in the American Museum of Natural History's Division of Anthropology and the lead author of the new study. \"It had longer lower limbs than upper limbs, a torso shaped more like ours, a larger cranial capacity than earlier hominins, and is associated with a tool industry—it's a faster, smarter hominin than Australopithecus and earliest Homo.\" In 1974, scientists at the East Turkana site in Kenya found one of the oldest pieces of evidence for H. erectus: a small skull fragment that dates to 1.9 million years. The East Turkana specimen is only surpassed in age by a 2-million-year-old skull specimen in South Africa. But there was pushback within the field, with some researchers arguing that the East Turkana specimen could have come from a younger fossil deposit and was possibly moved by water or wind to the spot where it was found. To pinpoint the locality, the researchers relied on archival materials and geological surveys. University of Witwatersrand geologist Silindokuhle Mavuso (left) and study lead author Ashley Hammond at the East Turkana site in Kenya Credit: A. Hammond/AMNH \"It was 100 percent detective work,\" said Dan Palcu, a geoscientist at the University of São Paulo and Utrecht University who coordinated the geological work. \"Imagine the reinvestigation of a 'cold case' in a detective movie. We had to go through hundreds of pages from old reports and published research, reassessing the initial evidence and searching for new clues. We also had to use satellite data and aerial imagery to find out where the fossils were discovered, recreate the 'scene,' and place it in a larger context to find the right clues for determining the age of the fossils.\" Although located in a different East Turkana collection area than initially reported, the skull specimen was found in a location that had no evidence of a younger fossil outcrop that may have washed there. This supports the original age given to the fossil. Within 50 meters of this reconstructed location, the researchers found two new hominin specimens: a partial pelvis and a foot bone. Although the researchers say they could be from the same individual, there's no way to prove that after the fossils have been separated for so long. But they might be the earliest postcrania—\"below the head\"—specimens yet discovered for H. erectus. Students from the Koobi Fora Field School surveying the East Turkana site in Kenya. Credit: A. Hammond/AMNH The scientists also collected fossilized teeth from other kinds of vertebrates, mostly mammals, from the area. From the enamel, they collected and analyzed isotope data to paint a better picture of the environment in which the H. erectus individual lived. \"Our new carbon isotope data from fossil enamel tell us that the mammals found in association with the Homo fossils in the area were all grazing on grasses,\" said Kevin Uno, a paleoecologist at Columbia University's Lamont-Doherty Earth Observatory. \"The enamel oxygen isotope data suggest it was a relatively arid habitat based on comparisons to other enamel data from this area.\" The work suggests that this early H. erectus was found in a paleoenvironment that included primarily grazers that prefer open environments to forest areas and was near a stable body of water, as documented by freshwater sponges preserved in the rocks. Key to the field work driving this study were the students and staff from the Koobi Fora Field School, which provides undergraduate and graduate students with on-the-ground experience in paleoanthropology. The school is run through a collaboration between The George Washington University and the National Museums of Kenya, and with instructors from institutions from around North America, Europe, and Africa. \"This kind of renewed collaboration not only sheds new light on verifing the age and origin of Homo erectus but also promotes the National Museums of Kenya's heritage stewardship in research and training,\" said Emmanuel Ndiema, the head of archaeology at the National Museums of Kenya. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract The KNM-ER 2598 occipital is among the oldest fossils attributed to Homo erectus but questions have been raised about whether it may derive from a younger horizon. Here we report on efforts to relocate the KNM-ER 2598 locality and investigate its paleontological and geological context. Although located in a different East Turkana collection area (Area 13) than initially reported, the locality is stratigraphically positioned below the KBS Tuff and the outcrops show no evidence of deflation of a younger unit, supporting an age of >1.855 Ma. Newly recovered faunal material consists primarily of C 4 grazers, further confirmed by enamel isotope data. A hominin proximal 3rd metatarsal and partial ilium were discovered <50 m from the reconstructed location where KNM-ER 2598 was originally found but these cannot be associated directly with the occipital. The postcrania are consistent with fossil Homo and may represent the earliest postcrania attributable to Homo erectus . Introduction The KNM-ER 2598 specimen from East Turkana, Kenya is widely recognized as significant because it is one of the oldest fossils attributed to Homo erectus 1 , 2 , 3 , 4 , 5 . KNM-ER 2598 is a thick hominin cranial fragment preserving much of the central occipital bone, including portions of the lambdoidal suture and a distinctive Homo erectus -like occipital torus (Fig. 1 ) 6 . This fossil was collected from the outcrop surface in 1974 and was initially reported as originating from approximately the level of the KBS Tuff in East Turkana collection Area 15 6 . Later work would refine the stratigraphic placement of KNM-ER 2598 to about 4 m below the KBS Tuff and interpret the age as 1.88–1.9 million years (Ma) ago 1 , 7 . Fig. 1: KNM-ER 2598 partial occipital. a Inset image indicates the approximate anatomical location of the KNM-ER 2598 occipital. b Posterior view and right lateral view are shown. Full size image If KNM-ER 2598 is dated to nearly 1.9 Ma, it is the second chronologically oldest specimen with morphological affinities to H. erectus . The DNH 134 neurocranium from Drimolen is the oldest known Homo erectus specimen 8 . DNH 134 is a juvenile individual, which makes a categorical species attribution difficult to establish, but it has features (e.g., a teardrop-shaped superior profile, flat squamosal suture) which strongly favor a H. erectus attribution 8 . DNH 134 was recovered from a deposit with reversed paleomagnetic polarity with an associated uranium-series electron spin resonance (ESR) date of 2.04 Ma 8 , indicating that this specimen was deposited sometime within the C2r.1r reversed subchron. The most recent Geomagnetic Polarity Time Scale (GPTS 2020) associate the C2r.1r chron to the 1.934–2.120 Ma time interval 9 , 10 . Both DNH 134 and KNM-ER 2598 are critically important fossils because they are slightly older than those recovered from Dmanisi in the Republic of Georgia. The Dmanisi hominin fossils may be as old as 1.78 Ma 11 , and occupation of the site appears to extend to 1.85 Ma 11 . The Dmanisi dates, which approach the dates for the African H. erectus specimens, raise the possibility that Homo erectus origins could have occurred in Eurasia rather than on the African continent 4 . Accordingly, KNM-ER 2598 is key to anchoring the earliest evolution and dispersals of Homo erectus , but some authors have raised doubts about the age of KNM-ER 2598 12 , 13 . It has been suggested that the altimetric position of KNM-ER 2598 below the KBS Tuff may have resulted from deflation of a stratigraphically younger horizon (e.g., KBS Member) that is no longer visible on the exposed upper Burgi Member outcrop surface 12 , 13 . Regrettably, few details regarding the provenience of the fossil were offered in the initial publications 6 , 14 . Given the importance of KNM-ER 2598 for placing the early evolution and dispersal of H. erectus within Africa, it has become essential to provide a geochronological context for the KNM-ER 2598 locality. Here we report on new investigations into the KNM-ER 2598 site location, geology, and paleoecology. The geological data presented here support the interpretation that the KNM-ER 2598 occipital derives from the upper Burgi Member of the Koobi Fora Formation, conservatively dating the fossil to >1.855 Ma. Our findings also correct the location of the KNM-ER 2598 locality, demonstrating that it is situated within the boundaries of collection Area 13 rather than Area 15 in East Turkana. We report on a new hominin ilium and metatarsal recovered within close proximity of where KNM-ER 2598 originated. These hominin fossils are consistent with Homo erectus , potentially making these the oldest postcranial fossils attributable to the taxon. Finally, we contextualize the paleohabitat in East Turkana Area 13 through faunal abundance data, isotopic analyses of mammalian dental enamel, and petrographic data. Results Identification of the locality We used field-based reconnaissance combined with historical imagery to identify the KNM-ER 2598 locality (Supplementary Figs. 1 – 3 ). We used Google Earth imagery to approximate the geospatial location of KNM-ER 2598 in geographic coordinates from historical aerial photographic records housed at the National Museums of Kenya (Supplementary Fig. 1 ). The aerial imagery from the 1970s document that KNM-ER 2598 was actually discovered within the boundaries of collection Area 13. Photographs from the 1974–1975 field seasons confirm that collections were taking place in collection Area 13, based on landscape features that are still identifiable (Supplementary Fig. 2 ). Upon physical inspection of the reconstructed location, a large collapsed sandstone cairn was identified at approximately the same coordinates (N 4.26984, E 36.33848, WGS84; altitude 413.5 m above sea level) reconstructed from the aerial imagery. The sandstone cairn (Supplementary Fig. 3 ) is consistent with the markers used in the 1970s, prior to the positioning of cement plinths as hominin markers. Geological context and age Survey of the rediscovered KNM-ER 2598 locality and nearby areas within Area 13 allowed us to identify two distinct aggregates (Burgi and KBS Members) and a tuff horizon (the KBS<|im_end|> <|im_start|>assistant A new study verifies the age and origin of one of the oldest specimens of Homo erectus—a very successful early human who roamed the world for nearly 2 million years. In doing so, the researchers also found two new specimens at the site—likely the earliest pieces of the Homo erectus skeleton yet discovered. Details are published today in the journal Nature Communications. "Homo erectus is the first hominin that we know about that has a body plan more like our own and seemed to be on its way to being more human-like," said Ashley Hammond, an assistant curator in the American Museum of Natural History's Division of Anthropology and the lead author of the new study. "It had longer lower limbs than upper limbs, a torso shaped more like ours, a larger cranial capacity than earlier hominins, and is associated with a tool industry—it's a faster, smarter hominin than Australopithecus and earliest Homo." In 1974, scientists at the East Turkana site in Kenya found one of the oldest pieces of evidence for H. erectus: a small skull fragment that dates to 1.9 million years. The East Turkana specimen is only surpassed in age by a 2-million-year-old skull specimen in South Africa. But there was pushback within the field, with some researchers arguing that the East Turkana specimen could have come from a younger fossil deposit and was possibly moved by water or wind to the spot where it was found. To pinpoint the locality, the researchers relied on archival materials and geological surveys. University of Witwatersrand geologist Silindokuhle Mavuso (left) and study lead author Ashley Hammond at the East Turkana site in Kenya Credit: A. Hammond/AMNH "It was 100 percent detective work," said Dan Palcu, a geoscientist at the University of São Paulo and Utrecht University who coordinated the geological work. "Imagine the reinvestigation of a 'cold case' in a detective movie. We had to go through hundreds of pages from old reports and published research, reassessing the initial evidence and searching for new clues. We also had to use satellite data and aerial imagery to find out where the fossils were discovered, recreate the 'scene,' and place it in a larger context to find the right clues for determining the age of the fossils." Although located in a different East Turkana collection area than initially reported, the skull specimen was found in a location that had no evidence of a younger fossil outcrop that may have washed there. This supports the original age given to the fossil. Within 50 meters of this reconstructed location, the researchers found two new hominin specimens: a partial pelvis and a foot bone. Although the researchers say they could be from the same individual, there's no way to prove that after the fossils have been separated for so long. But they might be the earliest postcrania—"below the head"—specimens yet discovered for H. erectus. Students from the Koobi Fora Field School surveying the East Turkana site in Kenya. Credit: A. Hammond/AMNH The scientists also collected fossilized teeth from other kinds of vertebrates, mostly mammals, from the area. From the enamel, they collected and analyzed isotope data to paint a better picture of the environment in which the H. erectus individual lived. "Our new carbon isotope data from fossil enamel tell us that the mammals found in association with the Homo fossils in the area were all grazing on grasses," said Kevin Uno, a paleoecologist at Columbia University's Lamont-Doherty Earth Observatory. "The enamel oxygen isotope data suggest it was a relatively arid habitat based on comparisons to other enamel data from this area." The work suggests that this early H. erectus was found in a paleoenvironment that included primarily grazers that prefer open environments to forest areas and was near a stable body of water, as documented by freshwater sponges preserved in the rocks. Key to the field work driving this study were the students and staff from the Koobi Fora Field School, which provides undergraduate and graduate students with on-the-ground experience in paleoanthropology. The school is run through a collaboration between The George Washington University and the National Museums of Kenya, and with instructors from institutions from around North America, Europe, and Africa. "This kind of renewed collaboration not only sheds new light on verifing the age and origin of Homo erectus but also promotes the National Museums of Kenya's heritage stewardship in research and training," said Emmanuel Ndiema, the head of archaeology at the National Museums of Kenya. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 578, 32392, 44, 12, 643, 220, 15537, 23, 3056, 575, 2223, 374, 4315, 279, 24417, 81473, 30706, 311, 84497, 38732, 355, 719, 4860, 617, 1027, 9408, 922, 3508, 433, 1253, 43530, 505, 264, 14992, 35174, 13, 5810, 584, 1934, 389, 9045, 311, 70672, 279, 32392, 44, 12, 643, 220, 15537, 23, 69187, 323, 19874, 1202, 28639, 546, 5848, 323, 86278, 2317, 13, 10541, 7559, 304, 264, 2204, 6460, 21187, 3444, 4526, 3158, 320, 8900, 220, 1032, 8, 1109, 15453, 5068, 11, 279, 69187, 374, 44397, 54967, 2740, 35328, 3770, 279, 125934, 350, 1386, 323, 279, 704, 66, 3787, 1501, 912, 6029, 315, 711, 2354, 315, 264, 14992, 5089, 11, 12899, 459, 4325, 315, 871, 16, 13, 22869, 11583, 13, 99935, 26403, 2267, 26663, 3769, 17610, 15871, 315, 356, 220, 19, 51933, 388, 11, 4726, 11007, 555, 92848, 374, 51782, 828, 13, 362, 5105, 65544, 22267, 2931, 220, 18, 6634, 2322, 44958, 278, 323, 7276, 3900, 2411, 1051, 11352, 366, 1135, 296, 505, 279, 83104, 3813, 1405, 32392, 44, 12, 643, 220, 15537, 23, 574, 13517, 1766, 719, 1521, 4250, 387, 5938, 6089, 449, 279, 3056, 575, 2223, 13, 578, 1772, 5192, 9345, 527, 13263, 449, 31376, 84497, 323, 1253, 4097, 279, 30758, 1772, 5192, 9345, 71526, 311, 84497, 38732, 355, 662, 29438, 578, 32392, 44, 12, 643, 220, 15537, 23, 58184, 505, 6460, 21187, 3444, 11, 37766, 374, 13882, 15324, 439, 5199, 1606, 433, 374, 832, 315, 279, 24417, 81473, 30706, 311, 84497, 38732, 355, 220, 16, 1174, 220, 17, 1174, 220, 18, 1174, 220, 19, 1174, 220, 20, 662, 32392, 44, 12, 643, 220, 15537, 23, 374, 264, 12314, 5105, 65544, 70637, 532, 12569, 47995, 1790, 315, 279, 8792, 3056, 575, 2223, 17685, 11, 2737, 19885, 315, 279, 39406, 67, 71916, 274, 3049, 323, 264, 35947, 84497, 38732, 355, 482, 4908, 3056, 575, 2223, 5801, 355, 320, 30035, 13, 220, 16, 883, 220, 21, 662, 1115, 31376, 574, 14890, 505, 279, 704, 35247, 7479, 304, 220, 4468, 19, 323, 574, 15453, 5068, 439, 71373, 505, 13489, 279, 2237, 315, 279, 125934, 350, 1386, 304, 6460, 21187, 3444, 4526, 12299, 220, 868, 220, 21, 662, 25929, 990, 1053, 46464, 279, 44397, 54967, 292, 22165, 315, 32392, 44, 12, 643, 220, 15537, 23, 311, 922, 220, 19, 296, 3770, 279, 125934, 350, 1386, 323, 14532, 279, 4325, 439, 220, 16, 13, 2421, 4235, 16, 13, 24, 3610, 1667, 320, 30635, 8, 4227, 220, 16, 1174, 220, 22, 662, 23966, 13, 220, 16, 25, 32392, 44, 12, 643, 220, 15537, 23, 7276, 3056, 575, 2223, 13, 264, 763, 751, 2217, 15151, 279, 45968, 75893, 950, 3813, 315, 279, 32392, 44, 12, 643, 220, 15537, 23, 3056, 575, 2223, 13, 293, 3962, 14917, 1684, 323, 1314, 45569, 1684, 527, 6982, 13, 8797, 1404, 2217, 1442, 32392, 44, 12, 643, 220, 15537, 23, 374, 30105, 311, 7154, 220, 16, 13, 24, 11583, 11, 433, 374, 279, 2132, 27076, 30450, 24417, 58184, 449, 27448, 5848, 3611, 258, 1385, 311, 473, 13, 38732, 355, 662, 578, 423, 52371, 220, 9565, 18247, 5192, 35822, 505, 2999, 318, 17648, 374, 279, 24417, 3967, 84497, 38732, 355, 58184, 220, 23, 662, 423, 52371, 220, 9565, 374, 264, 48770, 3927, 11, 902, 3727, 264, 70636, 9606, 63124, 5107, 311, 5813, 11, 719, 433, 706, 4519, 320, 68, 1326, 2637, 264, 1028, 569, 897, 35831, 16757, 5643, 11, 10269, 8330, 10808, 278, 274, 3049, 8, 902, 16917, 4799, 264, 473, 13, 38732, 355, 63124, 220, 23, 662, 423, 52371, 220, 9565, 574, 26403, 505, 264, 16946, 449, 28537, 28639, 316, 39100, 76790, 449, 459, 5938, 54944, 57432, 17130, 12903, 58081, 320, 1600, 49, 8, 2457, 315, 220, 17, 13, 2371, 11583, 220, 23, 1174, 19392, 430, 420, 58184, 574, 54568, 36113, 2949, 279, 356, 17, 81, 13, 16, 81, 28537, 1207, 7562, 13, 578, 1455, 3293, 4323, 316, 39100, 3735, 10981, 4212, 25635, 320, 38, 74793, 220, 2366, 15, 8, 22712, 279, 356, 17, 81, 13, 16, 81, 27076, 311, 279, 220, 16, 13, 24347, 4235, 17, 13, 4364, 11583, 892, 10074, 220, 24, 1174, 220, 605, 662, 11995, 423, 52371, 220, 9565, 323, 32392, 44, 12, 643, 220, 15537, 23, 527, 41440, 3062, 81473, 1606, 814, 527, 10284, 9191, 1109, 1884, 26403, 505, 423, 1543, 13532, 304, 279, 5545, 315, 16272, 13, 578, 423, 1543, 13532, 5105, 65544, 81473, 1253, 387, 439, 2362, 439, 220, 16, 13, 2495, 11583, 220, 806, 1174, 323, 30747, 315, 279, 2816, 8111, 311, 13334, 311, 220, 16, 13, 5313, 11583, 220, 806, 662, 578, 423, 1543, 13532, 13003, 11, 902, 5603, 279, 13003, 369, 279, 11904, 473, 13, 38732, 355, 57749, 11, 4933, 279, 13336, 430, 84497, 38732, 355, 33472, 1436, 617, 10222, 304, 88177, 689, 4856, 1109, 389, 279, 11904, 32843, 220, 19, 662, 63909, 11, 32392, 44, 12, 643, 220, 15537, 23, 374, 1401, 311, 34330, 5620, 279, 30758, 15740, 323, 79835, 1147, 315, 84497, 38732, 355, 1174, 719, 1063, 12283, 617, 9408, 40017, 922, 279, 4325, 315, 32392, 44, 12, 643, 220, 15537, 23, 220, 717, 1174, 220, 1032, 662, 1102, 706, 1027, 12090, 430, 279, 4902, 318, 16743, 2361, 315, 32392, 44, 12, 643, 220, 15537, 23, 3770, 279, 125934, 350, 1386, 1253, 617, 19543, 505, 711, 2354, 315, 264, 44397, 54967, 2740, 14992, 35174, 320, 68, 1326, 2637, 125934, 12308, 8, 430, 374, 912, 5129, 9621, 389, 279, 15246, 8582, 41109, 72, 12308, 704, 35247, 7479, 220, 717, 1174, 220, 1032, 662, 3263, 17708, 2915, 11, 2478, 3649, 9002, 279, 17033, 1873, 315, 279, 31376, 1051, 9076, 304, 279, 2926, 29085, 220, 21, 1174, 220, 975, 662, 16644, 279, 12939, 315, 32392, 44, 12, 643, 220, 15537, 23, 369, 25012, 279, 4216, 15740, 323, 79835, 278, 315, 473, 13, 38732, 355, 2949, 10384, 11, 433, 706, 3719, 7718, 311, 3493, 264, 3980, 5059, 2298, 5848, 2317, 369, 279, 32392, 44, 12, 643, 220, 15537, 23, 69187, 13, 5810, 584, 1934, 389, 502, 26969, 1139, 279, 32392, 44, 12, 643, 220, 15537, 23, 2816, 3813, 11, 3980, 2508, 11, 323, 28639, 78, 762, 2508, 13, 578, 86278, 828, 10666, 1618, 1862, 279, 23692, 430, 279, 32392, 44, 12, 643, 220, 15537, 23, 3056, 575, 2223, 75549, 505, 279, 8582, 41109, 72, 12308, 315, 279, 30417, 18843, 1789, 64, 72466, 11, 11357, 8046, 5029, 279, 31376, 311, 871, 16, 13, 22869, 11583, 13, 5751, 14955, 1101, 4495, 279, 3813, 315, 279, 32392, 44, 12, 643, 220, 15537, 23, 69187, 11, 45296, 430, 433, 374, 31183, 2949, 279, 23546, 315, 4526, 12299, 220, 1032, 4856, 1109, 12299, 220, 868, 304, 6460, 21187, 3444, 13, 1226, 1934, 389, 264, 502, 5105, 65544, 3900, 2411, 323, 2322, 44958, 278, 26403, 2949, 3345, 37843, 315, 1405, 32392, 44, 12, 643, 220, 15537, 23, 44853, 13, 4314, 5105, 65544, 81473, 527, 13263, 449, 84497, 38732, 355, 1174, 13893, 3339, 1521, 279, 24417, 1772, 73085, 532, 81473, 71526, 311, 279, 3827, 263, 13, 17830, 11, 584, 66251, 553, 279, 28639, 2319, 40027, 266, 304, 6460, 21187, 3444, 12299, 220, 1032, 1555, 2267, 26663, 37492, 828, 11, 69551, 25847, 29060, 315, 36041, 10700, 29106, 92848, 11, 323, 6896, 299, 86972, 828, 13, 18591, 59776, 315, 279, 69187, 1226, 1511, 2115, 6108, 88605, 11093, 449, 13970, 41545, 311, 10765, 279, 32392, 44, 12, 643, 220, 15537, 23, 69187, 320, 10254, 67082, 435, 14801, 13, 220, 16, 1389, 220, 18, 7609, 1226, 1511, 5195, 9420, 41545, 311, 45968, 279, 3980, 437, 33514, 3813, 315, 32392, 44, 12, 643, 220, 15537, 23, 304, 46139, 14259, 505, 13970, 41884, 70164, 7576, 52258, 520, 279, 5165, 51108, 6370, 315, 37766, 320, 10254, 67082, 23966, 13, 220, 16, 7609, 578, 41884, 41545, 505, 279, 220, 4468, 15, 82, 2246, 430, 32392, 44, 12, 643, 220, 15537, 23, 574, 3604, 11352, 2949, 279, 23546, 315, 4526, 12299, 220, 1032, 13, 33255, 82, 505, 279, 220, 4468, 19, 4235, 4468, 20, 2115, 15956, 7838, 430, 15661, 1051, 4737, 2035, 304, 4526, 12299, 220, 1032, 11, 3196, 389, 18921, 4519, 430, 527, 2103, 72450, 320, 10254, 67082, 23966, 13, 220, 17, 7609, 30538, 7106, 26767, 315, 279, 83104, 3813, 11, 264, 3544, 29368, 9462, 11046, 272, 1334, 77, 574, 11054, 520, 13489, 279, 1890, 14259, 320, 45, 220, 19, 13, 16955, 5833, 11, 469, 220, 1927, 13, 18633, 2166, 11, 468, 16929, 5833, 26, 36958, 220, 19288, 13, 20, 296, 3485, 9581, 2237, 8, 83104, 505, 279, 41884, 41545, 13, 578, 9462, 11046, 272, 1334, 77, 320, 10254, 67082, 23966, 13, 220, 18, 883, 374, 13263, 449, 279, 24915, 1511, 304, 279, 220, 4468, 15, 82, 11, 4972, 311, 279, 39825, 315, 24532, 628, 258, 17323, 439, 5105, 65544, 24915, 13, 80850, 2317, 323, 4325, 24507, 315, 279, 21540, 21468, 32392, 44, 12, 643, 220, 15537, 23, 69187, 323, 14373, 5789, 2949, 12299, 220, 1032, 5535, 603, 311, 10765, 1403, 12742, 71643, 320, 33, 5673, 72, 323, 125934, 17384, 8, 323, 264, 259, 1386, 35174, 320, 1820, 125934, 128257, 198, 128256, 78191, 198, 32, 502, 4007, 88956, 279, 4325, 323, 6371, 315, 832, 315, 279, 24417, 57749, 315, 84497, 38732, 355, 29096, 1633, 6992, 4216, 3823, 889, 938, 3690, 279, 1917, 369, 7154, 220, 17, 3610, 1667, 13, 763, 3815, 779, 11, 279, 12074, 1101, 1766, 1403, 502, 57749, 520, 279, 2816, 2345, 14617, 279, 30758, 9863, 315, 279, 84497, 38732, 355, 30535, 3686, 11352, 13, 12589, 527, 4756, 3432, 304, 279, 8486, 22037, 26545, 13, 330, 39, 16279, 38732, 355, 374, 279, 1176, 5105, 65544, 430, 584, 1440, 922, 430, 706, 264, 2547, 3197, 810, 1093, 1057, 1866, 323, 9508, 311, 387, 389, 1202, 1648, 311, 1694, 810, 3823, 12970, 1359, 1071, 38218, 65443, 11, 459, 18328, 87805, 304, 279, 3778, 16730, 315, 18955, 11346, 596, 14829, 315, 70384, 2508, 323, 279, 3063, 3229, 315, 279, 502, 4007, 13, 330, 2181, 1047, 5129, 4827, 49695, 1109, 8582, 49695, 11, 264, 64300, 27367, 810, 1093, 11604, 11, 264, 8294, 70637, 532, 8824, 1109, 6931, 5105, 258, 1354, 11, 323, 374, 5938, 449, 264, 5507, 5064, 44603, 596, 264, 10819, 11, 47578, 5105, 65544, 1109, 6126, 454, 275, 42750, 355, 323, 30758, 84497, 1210, 763, 220, 4468, 19, 11, 14248, 520, 279, 6460, 21187, 3444, 2816, 304, 37766, 1766, 832, 315, 279, 24417, 9863, 315, 6029, 369, 473, 13, 38732, 355, 25, 264, 2678, 35113, 12569, 430, 13003, 311, 220, 16, 13, 24, 3610, 1667, 13, 578, 6460, 21187, 3444, 58184, 374, 1193, 68328, 304, 4325, 555, 264, 220, 17, 46149, 4771, 6418, 35113, 58184, 304, 4987, 10384, 13, 2030, 1070, 574, 4585, 1445, 2949, 279, 2115, 11, 449, 1063, 12074, 30674, 430, 279, 6460, 21187, 3444, 58184, 1436, 617, 2586, 505, 264, 14992, 31376, 16946, 323, 574, 11000, 7882, 555, 3090, 477, 10160, 311, 279, 7858, 1405, 433, 574, 1766, 13, 2057, 67638, 279, 69187, 11, 279, 12074, 41013, 389, 95047, 7384, 323, 86278, 32313, 13, 3907, 315, 72959, 99759, 11588, 3980, 16549, 8211, 485, 564, 12825, 273, 386, 402, 47535, 320, 2414, 8, 323, 4007, 3063, 3229, 38218, 65443, 520, 279, 6460, 21187, 3444, 2816, 304, 37766, 16666, 25, 362, 13, 65443, 14, 1428, 52371, 330, 2181, 574, 220, 1041, 3346, 45259, 990, 1359, 1071, 11824, 11165, 20811, 11, 264, 3980, 437, 12575, 380, 520, 279, 3907, 315, 48790, 38026, 323, 549, 94970, 3907, 889, 47672, 279, 86278, 990, 13, 330, 52157, 279, 15601, 7164, 18413, 315, 264, 364, 88172, 1162, 6, 304, 264, 45259, 5818, 13, 1226, 1047, 311, 733, 1555, 11758, 315, 6959, 505, 2362, 6821, 323, 4756, 3495, 11, 32834, 434, 287, 279, 2926, 6029, 323, 15389, 369, 502, 43775, 13, 1226, 1101, 1047, 311, 1005, 24088, 828, 323, 41884, 41545, 311, 1505, 704, 1405, 279, 81473, 1051, 11352, 11, 53875, 279, 364, 23296, 2965, 323, 2035, 433, 304, 264, 8294, 2317, 311, 1505, 279, 1314, 43775, 369, 26679, 279, 4325, 315, 279, 81473, 1210, 10541, 7559, 304, 264, 2204, 6460, 21187, 3444, 4526, 3158, 1109, 15453, 5068, 11, 279, 35113, 58184, 574, 1766, 304, 264, 3813, 430, 1047, 912, 6029, 315, 264, 14992, 31376, 704, 35247, 430, 1253, 617, 38593, 1070, 13, 1115, 11815, 279, 4113, 4325, 2728, 311, 279, 31376, 13, 25218, 220, 1135, 20645, 315, 420, 83104, 3813, 11, 279, 12074, 1766, 1403, 502, 5105, 65544, 57749, 25, 264, 7276, 12077, 2749, 323, 264, 4579, 17685, 13, 10541, 279, 12074, 2019, 814, 1436, 387, 505, 279, 1890, 3927, 11, 1070, 596, 912, 1648, 311, 12391, 430, 1306, 279, 81473, 617, 1027, 19180, 369, 779, 1317, 13, 2030, 814, 2643, 387, 279, 30758, 1772, 5192, 9345, 93830, 54277, 279, 2010, 66101, 9727, 46697, 3686, 11352, 369, 473, 13, 38732, 355, 13, 20783, 505, 279, 30417, 18843, 1789, 64, 8771, 6150, 10795, 287, 279, 6460, 21187, 3444, 2816, 304, 37766, 13, 16666, 25, 362, 13, 65443, 14, 1428, 52371, 578, 14248, 1101, 14890, 31376, 1534, 18311, 505, 1023, 13124, 315, 67861, 99868, 11, 10213, 56669, 11, 505, 279, 3158, 13, 5659, 279, 92848, 11, 814, 14890, 323, 30239, 374, 51782, 828, 311, 6308, 264, 2731, 6945, 315, 279, 4676, 304, 902, 279, 473, 13, 38732, 355, 3927, 12439, 13, 330, 8140, 502, 12782, 374, 51782, 828, 505, 31376, 92848, 3371, 603, 430, 279, 56669, 1766, 304, 15360, 449, 279, 84497, 81473, 304, 279, 3158, 1051, 682, 84550, 389, 16763, 288, 1359, 1071, 16768, 84201, 11, 264, 28639, 78, 762, 16549, 520, 19326, 3907, 596, 33794, 546, 9607, 2319, 1368, 9420, 58974, 13, 330, 791, 92848, 24463, 374, 51782, 828, 4284, 433, 574, 264, 12309, 802, 307, 39646, 3196, 389, 36595, 311, 1023, 92848, 828, 505, 420, 3158, 1210, 578, 990, 13533, 430, 420, 4216, 473, 13, 38732, 355, 574, 1766, 304, 264, 28639, 16355, 3182, 430, 5343, 15871, 51933, 388, 430, 10932, 1825, 22484, 311, 13952, 5789, 323, 574, 3221, 264, 15528, 2547, 315, 3090, 11, 439, 27470, 555, 80744, 274, 621, 4282, 34683, 304, 279, 23902, 13, 5422, 311, 279, 2115, 990, 10043, 420, 4007, 1051, 279, 4236, 323, 5687, 505, 279, 30417, 18843, 1789, 64, 8771, 6150, 11, 902, 5825, 41534, 323, 19560, 4236, 449, 389, 10826, 79255, 3217, 304, 28639, 78, 32329, 897, 2508, 13, 578, 2978, 374, 1629, 1555, 264, 20632, 1990, 578, 10058, 6652, 3907, 323, 279, 5165, 51108, 6370, 315, 37766, 11, 323, 449, 54918, 505, 14673, 505, 2212, 4892, 5270, 11, 4606, 11, 323, 10384, 13, 330, 2028, 3169, 315, 36646, 20632, 539, 1193, 77039, 502, 3177, 389, 2807, 333, 287, 279, 4325, 323, 6371, 315, 84497, 38732, 355, 719, 1101, 39990, 279, 5165, 51108, 6370, 315, 37766, 596, 28948, 69606, 5383, 304, 3495, 323, 4967, 1359, 1071, 61544, 452, 8747, 9355, 11, 279, 2010, 315, 39211, 2508, 520, 279, 5165, 51108, 6370, 315, 37766, 13, 220, 128257, 198 ]

2,468

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Remote memories depend on coordinated activity in the hippocampus and frontal cortices, but the timeline of these interactions is debated. Astrocytes sense and modify neuronal activity, but their role in remote memory is scarcely explored. We expressed the G i -coupled designer receptor hM4Di in CA1 astrocytes and discovered that astrocytic manipulation during learning specifically impaired remote, but not recent, memory recall and decreased activity in the anterior cingulate cortex (ACC) during retrieval. We revealed massive recruitment of ACC-projecting CA1 neurons during memory acquisition, which was accompanied by the activation of ACC neurons. Astrocytic G i activation disrupted CA3 to CA1 communication in vivo and reduced the downstream response in the ACC. In behaving mice, it induced a projection-specific inhibition of CA1-to-ACC neurons during learning, which consequently prevented ACC recruitment. Finally, direct inhibition of CA1-to-ACC-projecting neurons spared recent and impaired remote memory. Our findings suggest that remote memory acquisition involves projection-specific functions of astrocytes in regulating CA1-to-ACC neuronal communication. Main Remote memories, weeks to decades long, continuously guide our behavior and are critically important to any organism, as the longevity of a memory is tightly connected to its significance. The ongoing interaction between the hippocampus and frontal cortical regions has been repeatedly shown to transform during the transition from recent (days long) to remote memory 1 , 2 , 3 . However, the exact time at which each region is recruited, the duration for which it remains relevant to memory function and the interactions between these regions are still debated. Astrocytes are no longer considered to merely provide homeostatic support to neurons and to encapsulate synapses, as pioneering research has shown that they can sense and modify synaptic activity as an integral part of the ‘tripartite synapse’ 4 . Interestingly, astrocytes exhibit extraordinary specificity in their effects on neuronal circuits 5 at several levels. First, astrocytes differentially affect neurons based on their genetic identity. For example, astrocytes in the striatum selectively respond to, and modulate, the input onto two populations of medium spiny neurons expressing either D1 or D2 dopamine receptors 6 . Similarly, astrocytes differentially modulate the effects of specific inhibitory cell types but not others in the same brain region 7 , 8 , 9 , 10 and selectively affect different inputs to the hippocampus 11 . Second, astrocytes exert neurotransmitter-specific effects on neuronal circuits. For instance, astrocytic activation in the central amygdala specifically depresses excitatory inputs and enhances inhibitory inputs 12 . Finally, astrocytes exhibit task-specific effects in vivo; that is, astrocytic stimulation selectively increases neuronal activity when coupled with memory acquisition, but not in the absence of learning 13 . An intriguing open question is whether astrocytes can also differentially affect neurons based on their distant projection target. The integration of novel chemogenetic and optogenetic tools in astrocyte research allows real-time reversible manipulation of these cells at the population level combined with electrophysiological and behavioral measurements. Such tools were used in brain slices to activate intracellular pathways in astrocytes and showed their ability to selectively modulate the activity of neighboring neurons in the amygdala and striatum 12 , 14 and to induce de novo long-term potentiation in the hippocampus 13 , 15 . Importantly, the reversibility of chemogenetic and optogenetic tools enables careful dissection of the effect of astrocytes during different memory stages in behaving animals 16 , 17 . The recruitment of intracellular signaling pathways in astrocytes using such tools is starting to shed light on their complex involvement in memory processes. For example, G q activation in the CA1 during acquisition (but not during recall) results in enhanced recent memory 13 , 15 , whereas G s activation results in recent memory impairment 18 . These findings point to the importance of astrocytes in memory processes, specifically at the time of learning. To explore the role of astrocytes in memory acquisition, we used the designer receptor hM4Di to activate the G i pathway in these cells. We show that this astrocytic modulation in the CA1 during learning results in a specific impairment in remote (but not recent) memory recall, which is accompanied by decreased activity in the ACC at the time of retrieval. In vivo, G i activation in astrocytes disrupts synaptic transmission from the CA3 to the CA1 and reduces downstream recruitment of the ACC. Finally, we reveal a dramatic recruitment of CA1 neurons projecting to the ACC during memory acquisition and a projection-specific inhibition of this population by G i pathway activation in CA1 astrocytes. Indeed, when we directly inhibited only CA1-to-ACC projecting neurons, recent retrieval remains intact, whereas remote memory is impaired. Results G i pathway activation in CA1 astrocytes specifically impairs the acquisition of remote memory To specifically modulate the activity of the G i pathway in CA1 astrocytes, we employed an adeno-associated virus vector (AAV8) encoding the designer receptor exclusively activated by designer drugs (DREADD) hM4Di fused to mCherry under the control of the astrocytic GFAP promoter. Stereotactic delivery of this AAV8-GFAP::hM4Di–mCherry vector resulted in CA1-specific expression that was restricted to astrocytic outer membranes (Fig. 1a,b ), with high penetrance (>85% of GFAP cells expressed hM4Di), and the promoter provided almost complete specificity (>95% hM4Di-positive cells were also GFAP-positive) (Extended Data Fig. 1a,b ). Co-staining with the neuronal marker NeuN showed <1% overlap with hM4Di expression (Extended Data Fig. 1c,d ). Fig. 1: Astrocytic G i pathway activation in the CA1 during learning specifically impairs remote contextual memory. a , Bilateral double injection of AAV8-GFAP::hM4Di–mCherry resulted in the selective expression of hM4Di in the CA1. Scale bar, 200 µm. b , hM4Di (red) was expressed in the astrocytic membrane around the soma and in the distal processes. Scale bar, 50 µm. c , Representative images (left) and quantification of c-Fos expression. CNO administration in vivo to mice expressing hM4Di (red) in CA1 astrocytes resulted in a significant increase in c-Fos expression (green) in these astrocytes compared with saline-injected controls (* P < 0.00005, n = 2–4 mice, 6–15 slices per groups). Scale bar, 50 μm. d , Representative", "role": "user" }, { "content": "Memories from a distant past, also known as remote memories, can guide the present and future behavior of humans and other living organisms on Earth. In psychology and neuroscience, the term \"remote memories\" refers to all memories related to events that took place from a few weeks to decades in the past. Many past studies have explored the neural underpinnings of remote memories or tried to identify brain regions that could be involved in how they are formed and maintained over time. So far, most findings have suggested that the interaction between the hippocampus and frontal cortical brain regions plays a key role in the consolidation of these memories. Past observations suggest that the interaction between these brain regions changes as time goes by and as memories go from being recent (i.e., a few years old) to remote. The exact time when these brain regions become involved in the formation of a memory and for how long they remain important to its endurance, however, is still poorly understood. Astrocytes are star-shaped cells that are known to have several functions, including the regulation of the metabolism, detoxification, tissue repair and providing nutrients to neurons. Recent studies have found that these cells can also change synaptic activity in the brain, thus impacting neuronal circuits at multiple levels. Researchers at the Hebrew University of Jerusalem have recently carried out a study aimed at exploring the role of astrocytes in memory acquisition. In their paper, published in Nature Neuroscience, they present a number of new observations that shed light on the unique contribution of these cells in enabling the formation of remote memories in mice, and potentially also humans. To investigate the role of astrocytes in memory formation, the researchers used a series of chemogenetic and optogenetic techniques. These techniques allow neuroscientists to manipulate astrocytes and other types of brain cells in reversible ways and to observe an animal's behavior when specific cell populations are active or inactive. In their study, the researchers used them to activate specific designer receptor pathways in astrocytes within the mouse brain. They then observed the effects of this activation on the animals' behavior and on their ability to form memories. \"We expressed the Gi-coupled designer receptor hM4Di in CA1 astrocytes and discovered that astrocytic manipulation during learning specifically impaired remote, but not recent, memory recall and decreased activity in the anterior cingulate cortex (ACC) during retrieval,\" the researchers wrote in their paper. The new findings represent a significant step forward in the understanding of astrocytes and their unique functions. Overall, they provide further evidence that astrocytes can shape neuronal networks in intricate ways and affect many cognitive functions, including the acquisition of remote memories. More specifically, the researchers observed that when a mouse was acquiring a new memory, ACC-projecting CA1 neurons were recruited in large numbers and neurons in the anterior cingulate cortex (ACC) were simultaneously activated. When they activated Gi pathways in astrocytes using chemogenetic techniques, however, the communication between CA3 and CA1 neurons was disturbed, which prevented activation in the ACC. As a result of their intervention on astrocytes, the projection typically observed between CA1 and ACC neurons in a mouse brain as the animal is learning something was repressed. This, in turn, appeared to impair the mice's ability to acquire remote memories. The findings suggest that astrocytes play an important role in the formation of remote memories in mice and potentially humans, via their ability to regulate the projection of neurons onto other areas of the brain. In this particular instance, they may control the communication between CA1 neurons and the ACC, which seems to be essential for remote memory formation. \"We revealed another capacity of astrocytes: They affect their neighboring neurons based on their projection target,\" the researchers concluded in their paper. \"This finding further expands the repertoire of sophisticated ways by which astrocytes shape neuronal networks and consequently high cognitive function.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Remote memories depend on coordinated activity in the hippocampus and frontal cortices, but the timeline of these interactions is debated. Astrocytes sense and modify neuronal activity, but their role in remote memory is scarcely explored. We expressed the G i -coupled designer receptor hM4Di in CA1 astrocytes and discovered that astrocytic manipulation during learning specifically impaired remote, but not recent, memory recall and decreased activity in the anterior cingulate cortex (ACC) during retrieval. We revealed massive recruitment of ACC-projecting CA1 neurons during memory acquisition, which was accompanied by the activation of ACC neurons. Astrocytic G i activation disrupted CA3 to CA1 communication in vivo and reduced the downstream response in the ACC. In behaving mice, it induced a projection-specific inhibition of CA1-to-ACC neurons during learning, which consequently prevented ACC recruitment. Finally, direct inhibition of CA1-to-ACC-projecting neurons spared recent and impaired remote memory. Our findings suggest that remote memory acquisition involves projection-specific functions of astrocytes in regulating CA1-to-ACC neuronal communication. Main Remote memories, weeks to decades long, continuously guide our behavior and are critically important to any organism, as the longevity of a memory is tightly connected to its significance. The ongoing interaction between the hippocampus and frontal cortical regions has been repeatedly shown to transform during the transition from recent (days long) to remote memory 1 , 2 , 3 . However, the exact time at which each region is recruited, the duration for which it remains relevant to memory function and the interactions between these regions are still debated. Astrocytes are no longer considered to merely provide homeostatic support to neurons and to encapsulate synapses, as pioneering research has shown that they can sense and modify synaptic activity as an integral part of the ‘tripartite synapse’ 4 . Interestingly, astrocytes exhibit extraordinary specificity in their effects on neuronal circuits 5 at several levels. First, astrocytes differentially affect neurons based on their genetic identity. For example, astrocytes in the striatum selectively respond to, and modulate, the input onto two populations of medium spiny neurons expressing either D1 or D2 dopamine receptors 6 . Similarly, astrocytes differentially modulate the effects of specific inhibitory cell types but not others in the same brain region 7 , 8 , 9 , 10 and selectively affect different inputs to the hippocampus 11 . Second, astrocytes exert neurotransmitter-specific effects on neuronal circuits. For instance, astrocytic activation in the central amygdala specifically depresses excitatory inputs and enhances inhibitory inputs 12 . Finally, astrocytes exhibit task-specific effects in vivo; that is, astrocytic stimulation selectively increases neuronal activity when coupled with memory acquisition, but not in the absence of learning 13 . An intriguing open question is whether astrocytes can also differentially affect neurons based on their distant projection target. The integration of novel chemogenetic and optogenetic tools in astrocyte research allows real-time reversible manipulation of these cells at the population level combined with electrophysiological and behavioral measurements. Such tools were used in brain slices to activate intracellular pathways in astrocytes and showed their ability to selectively modulate the activity of neighboring neurons in the amygdala and striatum 12 , 14 and to induce de novo long-term potentiation in the hippocampus 13 , 15 . Importantly, the reversibility of chemogenetic and optogenetic tools enables careful dissection of the effect of astrocytes during different memory stages in behaving animals 16 , 17 . The recruitment of intracellular signaling pathways in astrocytes using such tools is starting to shed light on their complex involvement in memory processes. For example, G q activation in the CA1 during acquisition (but not during recall) results in enhanced recent memory 13 , 15 , whereas G s activation results in recent memory impairment 18 . These findings point to the importance of astrocytes in memory processes, specifically at the time of learning. To explore the role of astrocytes in memory acquisition, we used the designer receptor hM4Di to activate the G i pathway in these cells. We show that this astrocytic modulation in the CA1 during learning results in a specific impairment in remote (but not recent) memory recall, which is accompanied by decreased activity in the ACC at the time of retrieval. In vivo, G i activation in astrocytes disrupts synaptic transmission from the CA3 to the CA1 and reduces downstream recruitment of the ACC. Finally, we reveal a dramatic recruitment of CA1 neurons projecting to the ACC during memory acquisition and a projection-specific inhibition of this population by G i pathway activation in CA1 astrocytes. Indeed, when we directly inhibited only CA1-to-ACC projecting neurons, recent retrieval remains intact, whereas remote memory is impaired. Results G i pathway activation in CA1 astrocytes specifically impairs the acquisition of remote memory To specifically modulate the activity of the G i pathway in CA1 astrocytes, we employed an adeno-associated virus vector (AAV8) encoding the designer receptor exclusively activated by designer drugs (DREADD) hM4Di fused to mCherry under the control of the astrocytic GFAP promoter. Stereotactic delivery of this AAV8-GFAP::hM4Di–mCherry vector resulted in CA1-specific expression that was restricted to astrocytic outer membranes (Fig. 1a,b ), with high penetrance (>85% of GFAP cells expressed hM4Di), and the promoter provided almost complete specificity (>95% hM4Di-positive cells were also GFAP-positive) (Extended Data Fig. 1a,b ). Co-staining with the neuronal marker NeuN showed <1% overlap with hM4Di expression (Extended Data Fig. 1c,d ). Fig. 1: Astrocytic G i pathway activation in the CA1 during learning specifically impairs remote contextual memory. a , Bilateral double injection of AAV8-GFAP::hM4Di–mCherry resulted in the selective expression of hM4Di in the CA1. Scale bar, 200 µm. b , hM4Di (red) was expressed in the astrocytic membrane around the soma and in the distal processes. Scale bar, 50 µm. c , Representative images (left) and quantification of c-Fos expression. CNO administration in vivo to mice expressing hM4Di (red) in CA1 astrocytes resulted in a significant increase in c-Fos expression (green) in these astrocytes compared with saline-injected controls (* P < 0.00005, n = 2–4 mice, 6–15 slices per groups). Scale bar, 50 μm. d , Representative<|im_end|> <|im_start|>assistant Memories from a distant past, also known as remote memories, can guide the present and future behavior of humans and other living organisms on Earth. In psychology and neuroscience, the term "remote memories" refers to all memories related to events that took place from a few weeks to decades in the past. Many past studies have explored the neural underpinnings of remote memories or tried to identify brain regions that could be involved in how they are formed and maintained over time. So far, most findings have suggested that the interaction between the hippocampus and frontal cortical brain regions plays a key role in the consolidation of these memories. Past observations suggest that the interaction between these brain regions changes as time goes by and as memories go from being recent (i.e., a few years old) to remote. The exact time when these brain regions become involved in the formation of a memory and for how long they remain important to its endurance, however, is still poorly understood. Astrocytes are star-shaped cells that are known to have several functions, including the regulation of the metabolism, detoxification, tissue repair and providing nutrients to neurons. Recent studies have found that these cells can also change synaptic activity in the brain, thus impacting neuronal circuits at multiple levels. Researchers at the Hebrew University of Jerusalem have recently carried out a study aimed at exploring the role of astrocytes in memory acquisition. In their paper, published in Nature Neuroscience, they present a number of new observations that shed light on the unique contribution of these cells in enabling the formation of remote memories in mice, and potentially also humans. To investigate the role of astrocytes in memory formation, the researchers used a series of chemogenetic and optogenetic techniques. These techniques allow neuroscientists to manipulate astrocytes and other types of brain cells in reversible ways and to observe an animal's behavior when specific cell populations are active or inactive. In their study, the researchers used them to activate specific designer receptor pathways in astrocytes within the mouse brain. They then observed the effects of this activation on the animals' behavior and on their ability to form memories. "We expressed the Gi-coupled designer receptor hM4Di in CA1 astrocytes and discovered that astrocytic manipulation during learning specifically impaired remote, but not recent, memory recall and decreased activity in the anterior cingulate cortex (ACC) during retrieval," the researchers wrote in their paper. The new findings represent a significant step forward in the understanding of astrocytes and their unique functions. Overall, they provide further evidence that astrocytes can shape neuronal networks in intricate ways and affect many cognitive functions, including the acquisition of remote memories. More specifically, the researchers observed that when a mouse was acquiring a new memory, ACC-projecting CA1 neurons were recruited in large numbers and neurons in the anterior cingulate cortex (ACC) were simultaneously activated. When they activated Gi pathways in astrocytes using chemogenetic techniques, however, the communication between CA3 and CA1 neurons was disturbed, which prevented activation in the ACC. As a result of their intervention on astrocytes, the projection typically observed between CA1 and ACC neurons in a mouse brain as the animal is learning something was repressed. This, in turn, appeared to impair the mice's ability to acquire remote memories. The findings suggest that astrocytes play an important role in the formation of remote memories in mice and potentially humans, via their ability to regulate the projection of neurons onto other areas of the brain. In this particular instance, they may control the communication between CA1 neurons and the ACC, which seems to be essential for remote memory formation. "We revealed another capacity of astrocytes: They affect their neighboring neurons based on their projection target," the researchers concluded in their paper. "This finding further expands the repertoire of sophisticated ways by which astrocytes shape neuronal networks and consequently high cognitive function." <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 21400, 19459, 6904, 389, 47672, 5820, 304, 279, 71206, 44651, 323, 66746, 23100, 1238, 11, 719, 279, 25845, 315, 1521, 22639, 374, 59674, 13, 65229, 11377, 2392, 5647, 323, 5719, 79402, 5820, 11, 719, 872, 3560, 304, 8870, 5044, 374, 80987, 36131, 13, 1226, 13605, 279, 480, 602, 482, 23045, 50185, 15034, 35268, 305, 44, 19, 22427, 304, 9362, 16, 47804, 11377, 2392, 323, 11352, 430, 47804, 11377, 29150, 34786, 2391, 6975, 11951, 50160, 8870, 11, 719, 539, 3293, 11, 5044, 19635, 323, 25983, 5820, 304, 279, 37229, 272, 287, 6468, 49370, 320, 30542, 8, 2391, 57470, 13, 1226, 10675, 11191, 34102, 315, 26925, 34796, 287, 9362, 16, 34313, 2391, 5044, 24279, 11, 902, 574, 24895, 555, 279, 15449, 315, 26925, 34313, 13, 65229, 11377, 29150, 480, 602, 15449, 69627, 9362, 18, 311, 9362, 16, 10758, 304, 41294, 323, 11293, 279, 52452, 2077, 304, 279, 26925, 13, 763, 87657, 24548, 11, 433, 36572, 264, 22343, 19440, 61478, 315, 9362, 16, 4791, 12, 30542, 34313, 2391, 6975, 11, 902, 52394, 32098, 26925, 34102, 13, 17830, 11, 2167, 61478, 315, 9362, 16, 4791, 12, 30542, 34796, 287, 34313, 74688, 3293, 323, 50160, 8870, 5044, 13, 5751, 14955, 4284, 430, 8870, 5044, 24279, 18065, 22343, 19440, 5865, 315, 47804, 11377, 2392, 304, 58499, 9362, 16, 4791, 12, 30542, 79402, 10758, 13, 4802, 21400, 19459, 11, 5672, 311, 11026, 1317, 11, 31978, 8641, 1057, 7865, 323, 527, 41440, 3062, 311, 904, 47120, 11, 439, 279, 58219, 315, 264, 5044, 374, 40069, 8599, 311, 1202, 26431, 13, 578, 14529, 16628, 1990, 279, 71206, 44651, 323, 66746, 83619, 13918, 706, 1027, 19352, 6982, 311, 5276, 2391, 279, 9320, 505, 3293, 320, 14097, 1317, 8, 311, 8870, 5044, 220, 16, 1174, 220, 17, 1174, 220, 18, 662, 4452, 11, 279, 4839, 892, 520, 902, 1855, 5654, 374, 45425, 11, 279, 8250, 369, 902, 433, 8625, 9959, 311, 5044, 734, 323, 279, 22639, 1990, 1521, 13918, 527, 2103, 59674, 13, 65229, 11377, 2392, 527, 912, 5129, 6646, 311, 16632, 3493, 2162, 537, 780, 1862, 311, 34313, 323, 311, 43669, 6468, 6925, 79390, 11, 439, 71674, 3495, 706, 6982, 430, 814, 649, 5647, 323, 5719, 99827, 5820, 439, 459, 26154, 961, 315, 279, 3451, 34081, 472, 635, 6925, 7629, 529, 220, 19, 662, 58603, 11, 47804, 11377, 2392, 31324, 24674, 76041, 304, 872, 6372, 389, 79402, 46121, 220, 20, 520, 3892, 5990, 13, 5629, 11, 47804, 11377, 2392, 2204, 34575, 7958, 34313, 3196, 389, 872, 19465, 9764, 13, 1789, 3187, 11, 47804, 11377, 2392, 304, 279, 6076, 27349, 82775, 6013, 311, 11, 323, 1491, 6468, 11, 279, 1988, 8800, 1403, 22673, 315, 11298, 993, 6577, 34313, 37810, 3060, 423, 16, 477, 423, 17, 66128, 44540, 220, 21, 662, 35339, 11, 47804, 11377, 2392, 2204, 34575, 1491, 6468, 279, 6372, 315, 3230, 20747, 10843, 2849, 4595, 719, 539, 3885, 304, 279, 1890, 8271, 5654, 220, 22, 1174, 220, 23, 1174, 220, 24, 1174, 220, 605, 323, 82775, 7958, 2204, 11374, 311, 279, 71206, 44651, 220, 806, 662, 10657, 11, 47804, 11377, 2392, 43844, 90351, 16517, 19440, 6372, 389, 79402, 46121, 13, 1789, 2937, 11, 47804, 11377, 29150, 15449, 304, 279, 8792, 64383, 29684, 6181, 11951, 39300, 288, 25435, 5382, 11374, 323, 57924, 20747, 10843, 11374, 220, 717, 662, 17830, 11, 47804, 11377, 2392, 31324, 3465, 19440, 6372, 304, 41294, 26, 430, 374, 11, 47804, 11377, 29150, 41959, 82775, 12992, 79402, 5820, 994, 34356, 449, 5044, 24279, 11, 719, 539, 304, 279, 19821, 315, 6975, 220, 1032, 662, 1556, 41765, 1825, 3488, 374, 3508, 47804, 11377, 2392, 649, 1101, 2204, 34575, 7958, 34313, 3196, 389, 872, 29827, 22343, 2218, 13, 578, 18052, 315, 11775, 8590, 11968, 5411, 323, 3469, 11968, 5411, 7526, 304, 47804, 11377, 668, 3495, 6276, 1972, 7394, 81193, 34786, 315, 1521, 7917, 520, 279, 7187, 2237, 11093, 449, 4135, 22761, 1065, 41314, 323, 36695, 22323, 13, 15483, 7526, 1051, 1511, 304, 8271, 35354, 311, 20891, 10805, 65441, 44014, 304, 47804, 11377, 2392, 323, 8710, 872, 5845, 311, 82775, 1491, 6468, 279, 5820, 315, 42617, 34313, 304, 279, 64383, 29684, 6181, 323, 6076, 27349, 220, 717, 1174, 220, 975, 323, 311, 49853, 409, 39423, 1317, 9860, 36875, 7246, 304, 279, 71206, 44651, 220, 1032, 1174, 220, 868, 662, 13516, 18007, 11, 279, 17888, 3225, 315, 8590, 11968, 5411, 323, 3469, 11968, 5411, 7526, 20682, 16994, 834, 2879, 315, 279, 2515, 315, 47804, 11377, 2392, 2391, 2204, 5044, 18094, 304, 87657, 10099, 220, 845, 1174, 220, 1114, 662, 578, 34102, 315, 10805, 65441, 43080, 44014, 304, 47804, 11377, 2392, 1701, 1778, 7526, 374, 6041, 311, 25351, 3177, 389, 872, 6485, 22315, 304, 5044, 11618, 13, 1789, 3187, 11, 480, 2874, 15449, 304, 279, 9362, 16, 2391, 24279, 320, 8248, 539, 2391, 19635, 8, 3135, 304, 24872, 3293, 5044, 220, 1032, 1174, 220, 868, 1174, 20444, 480, 274, 15449, 3135, 304, 3293, 5044, 53317, 220, 972, 662, 4314, 14955, 1486, 311, 279, 12939, 315, 47804, 11377, 2392, 304, 5044, 11618, 11, 11951, 520, 279, 892, 315, 6975, 13, 2057, 13488, 279, 3560, 315, 47804, 11377, 2392, 304, 5044, 24279, 11, 584, 1511, 279, 15034, 35268, 305, 44, 19, 22427, 311, 20891, 279, 480, 602, 38970, 304, 1521, 7917, 13, 1226, 1501, 430, 420, 47804, 11377, 29150, 67547, 304, 279, 9362, 16, 2391, 6975, 3135, 304, 264, 3230, 53317, 304, 8870, 320, 8248, 539, 3293, 8, 5044, 19635, 11, 902, 374, 24895, 555, 25983, 5820, 304, 279, 26925, 520, 279, 892, 315, 57470, 13, 763, 41294, 11, 480, 602, 15449, 304, 47804, 11377, 2392, 24927, 82, 99827, 18874, 505, 279, 9362, 18, 311, 279, 9362, 16, 323, 26338, 52452, 34102, 315, 279, 26925, 13, 17830, 11, 584, 16805, 264, 22520, 34102, 315, 9362, 16, 34313, 82382, 311, 279, 26925, 2391, 5044, 24279, 323, 264, 22343, 19440, 61478, 315, 420, 7187, 555, 480, 602, 38970, 15449, 304, 9362, 16, 47804, 11377, 2392, 13, 23150, 11, 994, 584, 6089, 99669, 1193, 9362, 16, 4791, 12, 30542, 82382, 34313, 11, 3293, 57470, 8625, 35539, 11, 20444, 8870, 5044, 374, 50160, 13, 18591, 480, 602, 38970, 15449, 304, 9362, 16, 47804, 11377, 2392, 11951, 3242, 4825, 279, 24279, 315, 8870, 5044, 2057, 11951, 1491, 6468, 279, 5820, 315, 279, 480, 602, 38970, 304, 9362, 16, 47804, 11377, 2392, 11, 584, 20011, 459, 1008, 12052, 75968, 17188, 4724, 320, 6157, 53, 23, 8, 11418, 279, 15034, 35268, 24121, 22756, 555, 15034, 11217, 320, 35, 9754, 35, 8, 305, 44, 19, 22427, 75754, 311, 296, 1163, 5515, 1234, 279, 2585, 315, 279, 47804, 11377, 29150, 41126, 2599, 66642, 13, 27155, 68, 354, 24045, 9889, 315, 420, 362, 8253, 23, 12279, 37, 2599, 487, 71, 44, 19, 22427, 4235, 76, 1163, 5515, 4724, 19543, 304, 9362, 16, 19440, 7645, 430, 574, 22486, 311, 47804, 11377, 29150, 16335, 79348, 320, 30035, 13, 220, 16, 64, 8568, 7026, 449, 1579, 44805, 685, 77952, 5313, 4, 315, 41126, 2599, 7917, 13605, 305, 44, 19, 22427, 705, 323, 279, 66642, 3984, 4661, 4686, 76041, 77952, 2721, 4, 305, 44, 19, 22427, 69788, 7917, 1051, 1101, 41126, 2599, 69788, 8, 320, 54290, 2956, 23966, 13, 220, 16, 64, 8568, 7609, 3623, 5594, 2101, 449, 279, 79402, 11381, 45950, 45, 8710, 366, 16, 4, 28347, 449, 305, 44, 19, 22427, 7645, 320, 54290, 2956, 23966, 13, 220, 16, 66, 12260, 7609, 23966, 13, 220, 16, 25, 65229, 11377, 29150, 480, 602, 38970, 15449, 304, 279, 9362, 16, 2391, 6975, 11951, 3242, 4825, 8870, 66251, 5044, 13, 264, 1174, 39158, 19715, 2033, 26127, 315, 362, 8253, 23, 12279, 37, 2599, 487, 71, 44, 19, 22427, 4235, 76, 1163, 5515, 19543, 304, 279, 44010, 7645, 315, 305, 44, 19, 22427, 304, 279, 9362, 16, 13, 25635, 3703, 11, 220, 1049, 64012, 76, 13, 293, 1174, 305, 44, 19, 22427, 320, 1171, 8, 574, 13605, 304, 279, 47804, 11377, 29150, 39654, 2212, 279, 58859, 323, 304, 279, 1612, 278, 11618, 13, 25635, 3703, 11, 220, 1135, 64012, 76, 13, 272, 1174, 38366, 5448, 320, 2414, 8, 323, 10484, 2461, 315, 272, 7424, 437, 7645, 13, 356, 9173, 8735, 304, 41294, 311, 24548, 37810, 305, 44, 19, 22427, 320, 1171, 8, 304, 9362, 16, 47804, 11377, 2392, 19543, 304, 264, 5199, 5376, 304, 272, 7424, 437, 7645, 320, 13553, 8, 304, 1521, 47804, 11377, 2392, 7863, 449, 99107, 3502, 29403, 11835, 4712, 393, 366, 220, 15, 13, 931, 2304, 11, 308, 284, 220, 17, 4235, 19, 24548, 11, 220, 21, 4235, 868, 35354, 824, 5315, 570, 25635, 3703, 11, 220, 1135, 33983, 76, 13, 294, 1174, 38366, 128257, 198, 128256, 78191, 198, 19346, 2490, 505, 264, 29827, 3347, 11, 1101, 3967, 439, 8870, 19459, 11, 649, 8641, 279, 3118, 323, 3938, 7865, 315, 12966, 323, 1023, 5496, 44304, 389, 9420, 13, 763, 31018, 323, 93048, 11, 279, 4751, 330, 18643, 19459, 1, 19813, 311, 682, 19459, 5552, 311, 4455, 430, 3952, 2035, 505, 264, 2478, 5672, 311, 11026, 304, 279, 3347, 13, 9176, 3347, 7978, 617, 36131, 279, 30828, 1234, 79, 6258, 826, 315, 8870, 19459, 477, 6818, 311, 10765, 8271, 13918, 430, 1436, 387, 6532, 304, 1268, 814, 527, 14454, 323, 18908, 927, 892, 13, 2100, 3117, 11, 1455, 14955, 617, 12090, 430, 279, 16628, 1990, 279, 71206, 44651, 323, 66746, 83619, 8271, 13918, 11335, 264, 1401, 3560, 304, 279, 60732, 315, 1521, 19459, 13, 24561, 24654, 4284, 430, 279, 16628, 1990, 1521, 8271, 13918, 4442, 439, 892, 5900, 555, 323, 439, 19459, 733, 505, 1694, 3293, 320, 72, 1770, 2637, 264, 2478, 1667, 2362, 8, 311, 8870, 13, 578, 4839, 892, 994, 1521, 8271, 13918, 3719, 6532, 304, 279, 18488, 315, 264, 5044, 323, 369, 1268, 1317, 814, 7293, 3062, 311, 1202, 49286, 11, 4869, 11, 374, 2103, 31555, 16365, 13, 65229, 11377, 2392, 527, 6917, 35831, 7917, 430, 527, 3967, 311, 617, 3892, 5865, 11, 2737, 279, 19812, 315, 279, 39097, 11, 61987, 2461, 11, 20438, 13023, 323, 8405, 37493, 311, 34313, 13, 35390, 7978, 617, 1766, 430, 1521, 7917, 649, 1101, 2349, 99827, 5820, 304, 279, 8271, 11, 8617, 74055, 79402, 46121, 520, 5361, 5990, 13, 59250, 520, 279, 37366, 3907, 315, 26523, 617, 6051, 11953, 704, 264, 4007, 20034, 520, 24919, 279, 3560, 315, 47804, 11377, 2392, 304, 5044, 24279, 13, 763, 872, 5684, 11, 4756, 304, 22037, 85879, 11, 814, 3118, 264, 1396, 315, 502, 24654, 430, 25351, 3177, 389, 279, 5016, 19035, 315, 1521, 7917, 304, 28462, 279, 18488, 315, 8870, 19459, 304, 24548, 11, 323, 13893, 1101, 12966, 13, 2057, 19874, 279, 3560, 315, 47804, 11377, 2392, 304, 5044, 18488, 11, 279, 12074, 1511, 264, 4101, 315, 8590, 11968, 5411, 323, 3469, 11968, 5411, 12823, 13, 4314, 12823, 2187, 18247, 56447, 1705, 311, 37735, 47804, 11377, 2392, 323, 1023, 4595, 315, 8271, 7917, 304, 81193, 5627, 323, 311, 23846, 459, 10065, 596, 7865, 994, 3230, 2849, 22673, 527, 4642, 477, 32899, 13, 763, 872, 4007, 11, 279, 12074, 1511, 1124, 311, 20891, 3230, 15034, 35268, 44014, 304, 47804, 11377, 2392, 2949, 279, 8814, 8271, 13, 2435, 1243, 13468, 279, 6372, 315, 420, 15449, 389, 279, 10099, 6, 7865, 323, 389, 872, 5845, 311, 1376, 19459, 13, 330, 1687, 13605, 279, 15754, 1824, 283, 50185, 15034, 35268, 305, 44, 19, 22427, 304, 9362, 16, 47804, 11377, 2392, 323, 11352, 430, 47804, 11377, 29150, 34786, 2391, 6975, 11951, 50160, 8870, 11, 719, 539, 3293, 11, 5044, 19635, 323, 25983, 5820, 304, 279, 37229, 272, 287, 6468, 49370, 320, 30542, 8, 2391, 57470, 1359, 279, 12074, 6267, 304, 872, 5684, 13, 578, 502, 14955, 4097, 264, 5199, 3094, 4741, 304, 279, 8830, 315, 47804, 11377, 2392, 323, 872, 5016, 5865, 13, 28993, 11, 814, 3493, 4726, 6029, 430, 47804, 11377, 2392, 649, 6211, 79402, 14488, 304, 57216, 5627, 323, 7958, 1690, 25702, 5865, 11, 2737, 279, 24279, 315, 8870, 19459, 13, 4497, 11951, 11, 279, 12074, 13468, 430, 994, 264, 8814, 574, 42990, 264, 502, 5044, 11, 26925, 34796, 287, 9362, 16, 34313, 1051, 45425, 304, 3544, 5219, 323, 34313, 304, 279, 37229, 272, 287, 6468, 49370, 320, 30542, 8, 1051, 25291, 22756, 13, 3277, 814, 22756, 15754, 44014, 304, 47804, 11377, 2392, 1701, 8590, 11968, 5411, 12823, 11, 4869, 11, 279, 10758, 1990, 9362, 18, 323, 9362, 16, 34313, 574, 56507, 11, 902, 32098, 15449, 304, 279, 26925, 13, 1666, 264, 1121, 315, 872, 21623, 389, 47804, 11377, 2392, 11, 279, 22343, 11383, 13468, 1990, 9362, 16, 323, 26925, 34313, 304, 264, 8814, 8271, 439, 279, 10065, 374, 6975, 2555, 574, 312, 14655, 13, 1115, 11, 304, 2543, 11, 9922, 311, 38974, 279, 24548, 596, 5845, 311, 21953, 8870, 19459, 13, 578, 14955, 4284, 430, 47804, 11377, 2392, 1514, 459, 3062, 3560, 304, 279, 18488, 315, 8870, 19459, 304, 24548, 323, 13893, 12966, 11, 4669, 872, 5845, 311, 37377, 279, 22343, 315, 34313, 8800, 1023, 5789, 315, 279, 8271, 13, 763, 420, 4040, 2937, 11, 814, 1253, 2585, 279, 10758, 1990, 9362, 16, 34313, 323, 279, 26925, 11, 902, 5084, 311, 387, 7718, 369, 8870, 5044, 18488, 13, 330, 1687, 10675, 2500, 8824, 315, 47804, 11377, 2392, 25, 2435, 7958, 872, 42617, 34313, 3196, 389, 872, 22343, 2218, 1359, 279, 12074, 20536, 304, 872, 5684, 13, 330, 2028, 9455, 4726, 52956, 279, 77768, 315, 27877, 5627, 555, 902, 47804, 11377, 2392, 6211, 79402, 14488, 323, 52394, 1579, 25702, 734, 1210, 220, 128257, 198 ]

2,234

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Chimeric antigen receptor (CAR) T cells mediate anti-tumour effects in a small subset of patients with cancer 1 , 2 , 3 , but dysfunction due to T cell exhaustion is an important barrier to progress 4 , 5 , 6 . To investigate the biology of exhaustion in human T cells expressing CAR receptors, we used a model system with a tonically signaling CAR, which induces hallmark features of exhaustion 6 . Exhaustion was associated with a profound defect in the production of IL-2, along with increased chromatin accessibility of AP-1 transcription factor motifs and overexpression of the bZIP and IRF transcription factors that have been implicated in mediating dysfunction in exhausted T cells 7 , 8 , 9 , 10 . Here we show that CAR T cells engineered to overexpress the canonical AP-1 factor c-Jun have enhanced expansion potential, increased functional capacity, diminished terminal differentiation and improved anti-tumour potency in five different mouse tumour models in vivo. We conclude that a functional deficiency in c-Jun mediates dysfunction in exhausted human T cells, and that engineering CAR T cells to overexpress c-Jun renders them resistant to exhaustion, thereby addressing a major barrier to progress for this emerging class of therapeutic agents. Main CAR-expressing T cells demonstrate impressive response rates in B cell malignancies, but fewer than 50% of patients experience long-term disease control 11 , 12 and CAR T cells have not mediated sustained responses in solid tumours 3 . Several factors limit the efficacy of CAR T cells, including a requirement for high antigen density for optimal CAR function enabling rapid selection of antigen loss or antigen low variants 12 , 13 , 14 , the suppressive tumour microenvironment 15 and intrinsic T cell dysfunction due to T cell exhaustion 6 , 11 , 16 . T cell exhaustion has been increasingly incriminated as a cause of CAR T cell dysfunction 6 , 11 , 16 , 17 , raising the prospect that engineering exhaustion-resistant CAR T cells could improve clinical outcomes. T cell exhaustion is characterized by high expression of inhibitory receptors and widespread transcriptional and epigenetic alterations 4 , 5 , 7 , 18 , 19 , but the mechanisms responsible for impaired function in exhausted T cells are unknown. Blockade of PD-1 can reinvigorate some exhausted T cells 20 but does not restore function fully, and trials using PD-1 blockade in combination with CAR T cells have not demonstrated efficacy 21 . Using a model in which healthy T cells are driven to exhaustion by the expression of a tonically signalling CAR, exhausted human T cells demonstrated widespread epigenomic dysregulation of AP-1 transcription factor-binding motifs and increased expression of the bZIP and IRF transcription factors that have been implicated in the regulation of exhaustion-related genes. Therefore, we tested the hypothesis that dysfunction in this setting resulted from an imbalance between activating and immunoregulatory AP-1–IRF complexes by inducing overexpression of c-Jun—an AP-1 family transcription factor associated with productive T cell activation. Consistent with this hypothesis, overexpression of c-Jun rendered CAR T cells resistant to exhaustion, as demonstrated by enhanced expansion potential in vitro and in vivo, increased functional capacity, diminished terminal differentiation and improved anti-tumour potency in multiple in vivo models. HA-28z CAR rapidly induces T cell exhaustion Exhaustion in human T cells was recently demonstrated after expression of a CAR incorporating the disialoganglioside (GD2)-specific 14g2a scFv, CD3ζ and CD28 signalling domains (GD2-28z), as a result of tonic signalling mediated via antigen-independent aggregation 6 . Here we show that CARs incorporating the 14g2a-E101K scFv, which demonstrate higher affinity for GD2 22 (HA-28z), display a more severe exhaustion phenotype (Extended Data Fig. 1a–c ). In contrast to CD19-28z CAR T cells (without tonic signalling), HA-28z CAR T cells develop profound features of exhaustion, including reduced expansion in culture, increased expression of inhibitory receptors, exaggerated effector differentiation, and diminished IFNγ and markedly decreased IL-2 production after stimulation (Fig. 1a–d , Extended Data Fig. 1d, e ). The functional defects are due to exhaustion-associated dysfunction rather than suboptimal interaction of the HA-28z CAR with its target GD2, because they are also observed in CD19-28z CAR T cells when HA-28z CAR is co-expressed using a bi-cistronic vector (Extended Data Fig. 1f ). Principal component analysis (PCA) of RNA-sequencing (RNA-seq) data demonstrated that the strongest driver of transcriptional variance was the presence of the exhausting HA-28z versus control CD19-28z CAR (Fig. 1e ), although some cell-type-specific differences were observed (Extended Data Fig. 1g ). Fig. 1: HA-28z CAR T cells manifest phenotypic, functional, transcriptional and epigenetic hallmarks of T cell exhaustion. a , Primary T cell expansion. Data are mean ± s.e.m. from n = 10 independent experiments. b , Surface expression of exhaustion-associated markers. c , Surface expression of CD45RA and CD62L to distinguish T memory stem cells (CD45RA + CD62L + ), central memory cells (CD45RA − CD62L + ), and effector memory cells (CD45RA − CD62L − ). d , IL-2 (left) and IFNγ (right) release after 24-h co-culture with CD19 + GD2 + Nalm6-GD2 leukaemia cells. Data are mean ± s.d. from triplicate wells. In b – d , one representative donor (of n = 10 experiments) is shown for each assay. P values determined by unpaired two-tailed t -tests. e , Principal component analysis (PCA) of global transcriptional profiles of naive- and central-memory-derived CD19-28z (CD19) or HA-28z (HA) CAR T cells at days 7, 10 and 14 in culture. PC1 (39.3% variance) separates CD19-28z from HA-28z CAR T cells. f , Gene expression of the top 200 genes driving PC1. Genes of interest in each cluster are listed. g , Differentially accessible chromatin regions (peaks) in CD8 + CD19-28z and HA-28z CAR T cells. Both naive and central memory cell subsets are incorporated for each CAR. h , PCA of ATAC-seq chromatin accessibility in CD19-28z or HA-28z CAR T cells. PC1 (76.9% variance) separates CD19-28z from HA-28z CAR samples. i , Global chromatin accessibility profile of CD4 + and CD8 + CD19-28z and HA-28z", "role": "user" }, { "content": "A new approach to programing cancer-fighting immune cells called CAR-T cells can prolong their activity and increase their effectiveness against human cancer cells grown in the laboratory and in mice, according to a study by researchers at the Stanford University School of Medicine. The ability to circumvent the exhaustion that the genetically engineered cells often experience after their initial burst of activity could lead to the development of a new generation of CAR-T cells that may be effective even against solid cancers—a goal that has until now eluded researchers. The studies were conducted in mice harboring human leukemia and bone cancer cells. The researchers hope to begin clinical trials in people with leukemia within the next 18 months and to eventually extend the trials to include solid cancers. \"We know that T cells are powerful enough to eradicate cancer,\" said Crystal Mackall, MD, professor of pediatrics and of medicine at Stanford and the associate director of the Stanford Cancer Institute. \"But these same T cells have evolved to have natural brakes that tamp down the potency of their response after a period of prolonged activity. We've developed a way to mitigate this exhaustion response and improve the activity of CAR-T cells against blood and solid cancers.\" Mackall, who is also the director of the Stanford Center for Cancer Cell Therapy and of the Stanford research center of the Parker Institute for Cancer Immunotherapy, treats children with blood cancers at the Bass Center for Childhood Cancer and Blood Diseases at Stanford Children's Health. Mackall is the senior author of the study, which will be published Dec. 4 in Nature. Former postdoctoral scholar Rachel Lynn, Ph.D., is the lead author. Genetically modified cells of patient CAR-T cells is an abbreviation for chimeric antigen receptor T cells. Genetically modified from a patient's own T cells, CAR-T cells are designed to track down and kill cancer cells by recognizing specific proteins on the cells' surface. CAR-T cell therapy made headlines around the world in 2017 when the Food and Drug Administration fast-tracked their approval for the treatment of children with relapsed or unresponsive acute lymphoblastic leukemia. Later that year, a version of CAR-T treatment was also approved for adults with some types of lymphoma. But although blood cancers often respond impressively to CAR-T treatment, fewer than half of treated patients experience long-term control of their disease, often because the CAR-T cells become exhausted, losing their ability to proliferate robustly and to actively attack cancer cells. Overcoming this exhaustion has been a key goal of cancer researchers for several years. Lynn and Mackall turned to a technique co-developed in the laboratory of Howard Chang, MD, Ph.D., the Virginia and D.K. Ludwig Professor of Cancer Genomics and professor of genetics at Stanford, to understand more about what happens when T cells become exhausted and whether it might be possible to inhibit this exhaustion. The technique, called ATAC-Seq, pinpoints areas of the genome where regulatory circuits overexpress or underexpress genes. \"When we used this technique to compare the genomes of healthy and exhausted T cells,\" Mackall said, \"we identified some significant differences in gene expression patterns.\" In particular, the researchers discovered that exhausted T cells demonstrate an imbalance in the activity of a major class of genes that regulate protein levels in the cells, leading to an increase in proteins that inhibit their activity. When the researchers modified CAR-T cells to restore the balance by overexpressing c-Jun, a gene that increases the expression of proteins associated with T cell activation, they saw that the cells remained active and proliferated in the laboratory even under conditions that would normally result in their exhaustion. Mice injected with human leukemia cells lived longer when treated with the modified CAR-T cells than with the regular CAR-T cells. In addition, the c-Jun expressing CAR-T cells were also able to reduce the tumor burden and extend the lifespan of laboratory mice with a human bone cancer called osteosarcoma. \"Those of us in the CAR-T cell field have wondered for some time if these cells could also be used to combat solid tumors,\" Mackall said. \"Now we've developed an approach that renders the cells exhaustion resistant and improves their activity against solid tumors in mice. Although more work needs to be done to test this in humans, we're hopeful that our findings will lead to the next generation of CAR-T cells and make a significant difference for people with many types of cancers.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Chimeric antigen receptor (CAR) T cells mediate anti-tumour effects in a small subset of patients with cancer 1 , 2 , 3 , but dysfunction due to T cell exhaustion is an important barrier to progress 4 , 5 , 6 . To investigate the biology of exhaustion in human T cells expressing CAR receptors, we used a model system with a tonically signaling CAR, which induces hallmark features of exhaustion 6 . Exhaustion was associated with a profound defect in the production of IL-2, along with increased chromatin accessibility of AP-1 transcription factor motifs and overexpression of the bZIP and IRF transcription factors that have been implicated in mediating dysfunction in exhausted T cells 7 , 8 , 9 , 10 . Here we show that CAR T cells engineered to overexpress the canonical AP-1 factor c-Jun have enhanced expansion potential, increased functional capacity, diminished terminal differentiation and improved anti-tumour potency in five different mouse tumour models in vivo. We conclude that a functional deficiency in c-Jun mediates dysfunction in exhausted human T cells, and that engineering CAR T cells to overexpress c-Jun renders them resistant to exhaustion, thereby addressing a major barrier to progress for this emerging class of therapeutic agents. Main CAR-expressing T cells demonstrate impressive response rates in B cell malignancies, but fewer than 50% of patients experience long-term disease control 11 , 12 and CAR T cells have not mediated sustained responses in solid tumours 3 . Several factors limit the efficacy of CAR T cells, including a requirement for high antigen density for optimal CAR function enabling rapid selection of antigen loss or antigen low variants 12 , 13 , 14 , the suppressive tumour microenvironment 15 and intrinsic T cell dysfunction due to T cell exhaustion 6 , 11 , 16 . T cell exhaustion has been increasingly incriminated as a cause of CAR T cell dysfunction 6 , 11 , 16 , 17 , raising the prospect that engineering exhaustion-resistant CAR T cells could improve clinical outcomes. T cell exhaustion is characterized by high expression of inhibitory receptors and widespread transcriptional and epigenetic alterations 4 , 5 , 7 , 18 , 19 , but the mechanisms responsible for impaired function in exhausted T cells are unknown. Blockade of PD-1 can reinvigorate some exhausted T cells 20 but does not restore function fully, and trials using PD-1 blockade in combination with CAR T cells have not demonstrated efficacy 21 . Using a model in which healthy T cells are driven to exhaustion by the expression of a tonically signalling CAR, exhausted human T cells demonstrated widespread epigenomic dysregulation of AP-1 transcription factor-binding motifs and increased expression of the bZIP and IRF transcription factors that have been implicated in the regulation of exhaustion-related genes. Therefore, we tested the hypothesis that dysfunction in this setting resulted from an imbalance between activating and immunoregulatory AP-1–IRF complexes by inducing overexpression of c-Jun—an AP-1 family transcription factor associated with productive T cell activation. Consistent with this hypothesis, overexpression of c-Jun rendered CAR T cells resistant to exhaustion, as demonstrated by enhanced expansion potential in vitro and in vivo, increased functional capacity, diminished terminal differentiation and improved anti-tumour potency in multiple in vivo models. HA-28z CAR rapidly induces T cell exhaustion Exhaustion in human T cells was recently demonstrated after expression of a CAR incorporating the disialoganglioside (GD2)-specific 14g2a scFv, CD3ζ and CD28 signalling domains (GD2-28z), as a result of tonic signalling mediated via antigen-independent aggregation 6 . Here we show that CARs incorporating the 14g2a-E101K scFv, which demonstrate higher affinity for GD2 22 (HA-28z), display a more severe exhaustion phenotype (Extended Data Fig. 1a–c ). In contrast to CD19-28z CAR T cells (without tonic signalling), HA-28z CAR T cells develop profound features of exhaustion, including reduced expansion in culture, increased expression of inhibitory receptors, exaggerated effector differentiation, and diminished IFNγ and markedly decreased IL-2 production after stimulation (Fig. 1a–d , Extended Data Fig. 1d, e ). The functional defects are due to exhaustion-associated dysfunction rather than suboptimal interaction of the HA-28z CAR with its target GD2, because they are also observed in CD19-28z CAR T cells when HA-28z CAR is co-expressed using a bi-cistronic vector (Extended Data Fig. 1f ). Principal component analysis (PCA) of RNA-sequencing (RNA-seq) data demonstrated that the strongest driver of transcriptional variance was the presence of the exhausting HA-28z versus control CD19-28z CAR (Fig. 1e ), although some cell-type-specific differences were observed (Extended Data Fig. 1g ). Fig. 1: HA-28z CAR T cells manifest phenotypic, functional, transcriptional and epigenetic hallmarks of T cell exhaustion. a , Primary T cell expansion. Data are mean ± s.e.m. from n = 10 independent experiments. b , Surface expression of exhaustion-associated markers. c , Surface expression of CD45RA and CD62L to distinguish T memory stem cells (CD45RA + CD62L + ), central memory cells (CD45RA − CD62L + ), and effector memory cells (CD45RA − CD62L − ). d , IL-2 (left) and IFNγ (right) release after 24-h co-culture with CD19 + GD2 + Nalm6-GD2 leukaemia cells. Data are mean ± s.d. from triplicate wells. In b – d , one representative donor (of n = 10 experiments) is shown for each assay. P values determined by unpaired two-tailed t -tests. e , Principal component analysis (PCA) of global transcriptional profiles of naive- and central-memory-derived CD19-28z (CD19) or HA-28z (HA) CAR T cells at days 7, 10 and 14 in culture. PC1 (39.3% variance) separates CD19-28z from HA-28z CAR T cells. f , Gene expression of the top 200 genes driving PC1. Genes of interest in each cluster are listed. g , Differentially accessible chromatin regions (peaks) in CD8 + CD19-28z and HA-28z CAR T cells. Both naive and central memory cell subsets are incorporated for each CAR. h , PCA of ATAC-seq chromatin accessibility in CD19-28z or HA-28z CAR T cells. PC1 (76.9% variance) separates CD19-28z from HA-28z CAR samples. i , Global chromatin accessibility profile of CD4 + and CD8 + CD19-28z and HA-28z<|im_end|> <|im_start|>assistant A new approach to programing cancer-fighting immune cells called CAR-T cells can prolong their activity and increase their effectiveness against human cancer cells grown in the laboratory and in mice, according to a study by researchers at the Stanford University School of Medicine. The ability to circumvent the exhaustion that the genetically engineered cells often experience after their initial burst of activity could lead to the development of a new generation of CAR-T cells that may be effective even against solid cancers—a goal that has until now eluded researchers. The studies were conducted in mice harboring human leukemia and bone cancer cells. The researchers hope to begin clinical trials in people with leukemia within the next 18 months and to eventually extend the trials to include solid cancers. "We know that T cells are powerful enough to eradicate cancer," said Crystal Mackall, MD, professor of pediatrics and of medicine at Stanford and the associate director of the Stanford Cancer Institute. "But these same T cells have evolved to have natural brakes that tamp down the potency of their response after a period of prolonged activity. We've developed a way to mitigate this exhaustion response and improve the activity of CAR-T cells against blood and solid cancers." Mackall, who is also the director of the Stanford Center for Cancer Cell Therapy and of the Stanford research center of the Parker Institute for Cancer Immunotherapy, treats children with blood cancers at the Bass Center for Childhood Cancer and Blood Diseases at Stanford Children's Health. Mackall is the senior author of the study, which will be published Dec. 4 in Nature. Former postdoctoral scholar Rachel Lynn, Ph.D., is the lead author. Genetically modified cells of patient CAR-T cells is an abbreviation for chimeric antigen receptor T cells. Genetically modified from a patient's own T cells, CAR-T cells are designed to track down and kill cancer cells by recognizing specific proteins on the cells' surface. CAR-T cell therapy made headlines around the world in 2017 when the Food and Drug Administration fast-tracked their approval for the treatment of children with relapsed or unresponsive acute lymphoblastic leukemia. Later that year, a version of CAR-T treatment was also approved for adults with some types of lymphoma. But although blood cancers often respond impressively to CAR-T treatment, fewer than half of treated patients experience long-term control of their disease, often because the CAR-T cells become exhausted, losing their ability to proliferate robustly and to actively attack cancer cells. Overcoming this exhaustion has been a key goal of cancer researchers for several years. Lynn and Mackall turned to a technique co-developed in the laboratory of Howard Chang, MD, Ph.D., the Virginia and D.K. Ludwig Professor of Cancer Genomics and professor of genetics at Stanford, to understand more about what happens when T cells become exhausted and whether it might be possible to inhibit this exhaustion. The technique, called ATAC-Seq, pinpoints areas of the genome where regulatory circuits overexpress or underexpress genes. "When we used this technique to compare the genomes of healthy and exhausted T cells," Mackall said, "we identified some significant differences in gene expression patterns." In particular, the researchers discovered that exhausted T cells demonstrate an imbalance in the activity of a major class of genes that regulate protein levels in the cells, leading to an increase in proteins that inhibit their activity. When the researchers modified CAR-T cells to restore the balance by overexpressing c-Jun, a gene that increases the expression of proteins associated with T cell activation, they saw that the cells remained active and proliferated in the laboratory even under conditions that would normally result in their exhaustion. Mice injected with human leukemia cells lived longer when treated with the modified CAR-T cells than with the regular CAR-T cells. In addition, the c-Jun expressing CAR-T cells were also able to reduce the tumor burden and extend the lifespan of laboratory mice with a human bone cancer called osteosarcoma. "Those of us in the CAR-T cell field have wondered for some time if these cells could also be used to combat solid tumors," Mackall said. "Now we've developed an approach that renders the cells exhaustion resistant and improves their activity against solid tumors in mice. Although more work needs to be done to test this in humans, we're hopeful that our findings will lead to the next generation of CAR-T cells and make a significant difference for people with many types of cancers." <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 921, 3212, 292, 83089, 35268, 320, 37490, 8, 350, 7917, 1812, 6629, 7294, 2442, 372, 414, 6372, 304, 264, 2678, 27084, 315, 6978, 449, 9572, 220, 16, 1174, 220, 17, 1174, 220, 18, 1174, 719, 32403, 4245, 311, 350, 2849, 70663, 374, 459, 3062, 22881, 311, 5208, 220, 19, 1174, 220, 20, 1174, 220, 21, 662, 2057, 19874, 279, 34458, 315, 70663, 304, 3823, 350, 7917, 37810, 28876, 44540, 11, 584, 1511, 264, 1646, 1887, 449, 264, 8941, 2740, 43080, 28876, 11, 902, 90974, 98799, 4519, 315, 70663, 220, 21, 662, 89334, 290, 574, 5938, 449, 264, 28254, 23011, 304, 279, 5788, 315, 11598, 12, 17, 11, 3235, 449, 7319, 22083, 15111, 40800, 315, 10314, 12, 16, 46940, 8331, 84989, 323, 927, 29199, 315, 279, 293, 62685, 323, 16646, 37, 46940, 9547, 430, 617, 1027, 69702, 304, 1812, 23747, 32403, 304, 39019, 350, 7917, 220, 22, 1174, 220, 23, 1174, 220, 24, 1174, 220, 605, 662, 5810, 584, 1501, 430, 28876, 350, 7917, 46036, 311, 927, 14107, 279, 43553, 10314, 12, 16, 8331, 272, 78834, 617, 24872, 14800, 4754, 11, 7319, 16003, 8824, 11, 54182, 15372, 60038, 323, 13241, 7294, 2442, 372, 414, 77229, 304, 4330, 2204, 8814, 15756, 414, 4211, 304, 41294, 13, 1226, 32194, 430, 264, 16003, 48294, 304, 272, 78834, 25098, 988, 32403, 304, 39019, 3823, 350, 7917, 11, 323, 430, 15009, 28876, 350, 7917, 311, 927, 14107, 272, 78834, 45382, 1124, 31785, 311, 70663, 11, 28592, 28118, 264, 3682, 22881, 311, 5208, 369, 420, 24084, 538, 315, 37471, 13307, 13, 4802, 28876, 10397, 1911, 287, 350, 7917, 20461, 16358, 2077, 7969, 304, 426, 2849, 60327, 32737, 11, 719, 17162, 1109, 220, 1135, 4, 315, 6978, 3217, 1317, 9860, 8624, 2585, 220, 806, 1174, 220, 717, 323, 28876, 350, 7917, 617, 539, 78926, 29759, 14847, 304, 6573, 15756, 2530, 220, 18, 662, 26778, 9547, 4017, 279, 41265, 315, 28876, 350, 7917, 11, 2737, 264, 16686, 369, 1579, 83089, 17915, 369, 23669, 28876, 734, 28462, 11295, 6727, 315, 83089, 4814, 477, 83089, 3428, 27103, 220, 717, 1174, 220, 1032, 1174, 220, 975, 1174, 279, 28321, 535, 15756, 414, 8162, 24175, 220, 868, 323, 47701, 350, 2849, 32403, 4245, 311, 350, 2849, 70663, 220, 21, 1174, 220, 806, 1174, 220, 845, 662, 350, 2849, 70663, 706, 1027, 15098, 3709, 6417, 15846, 439, 264, 5353, 315, 28876, 350, 2849, 32403, 220, 21, 1174, 220, 806, 1174, 220, 845, 1174, 220, 1114, 1174, 19054, 279, 22199, 430, 15009, 70663, 47056, 28876, 350, 7917, 1436, 7417, 14830, 20124, 13, 350, 2849, 70663, 374, 32971, 555, 1579, 7645, 315, 20747, 10843, 44540, 323, 24716, 46940, 278, 323, 4248, 6569, 5411, 61086, 220, 19, 1174, 220, 20, 1174, 220, 22, 1174, 220, 972, 1174, 220, 777, 1174, 719, 279, 24717, 8647, 369, 50160, 734, 304, 39019, 350, 7917, 527, 9987, 13, 8527, 1037, 315, 27572, 12, 16, 649, 312, 14386, 343, 38995, 1063, 39019, 350, 7917, 220, 508, 719, 1587, 539, 15301, 734, 7373, 11, 323, 19622, 1701, 27572, 12, 16, 77237, 304, 10824, 449, 28876, 350, 7917, 617, 539, 21091, 41265, 220, 1691, 662, 12362, 264, 1646, 304, 902, 9498, 350, 7917, 527, 16625, 311, 70663, 555, 279, 7645, 315, 264, 8941, 2740, 91977, 28876, 11, 39019, 3823, 350, 7917, 21091, 24716, 4248, 6569, 3151, 22709, 1610, 2987, 315, 10314, 12, 16, 46940, 8331, 65500, 84989, 323, 7319, 7645, 315, 279, 293, 62685, 323, 16646, 37, 46940, 9547, 430, 617, 1027, 69702, 304, 279, 19812, 315, 70663, 14228, 21389, 13, 15636, 11, 584, 12793, 279, 31178, 430, 32403, 304, 420, 6376, 19543, 505, 459, 68331, 1990, 72192, 323, 33119, 461, 70, 38220, 10314, 12, 16, 4235, 2871, 37, 69125, 555, 96811, 927, 29199, 315, 272, 78834, 85366, 10314, 12, 16, 3070, 46940, 8331, 5938, 449, 27331, 350, 2849, 15449, 13, 7440, 18620, 449, 420, 31178, 11, 927, 29199, 315, 272, 78834, 23188, 28876, 350, 7917, 31785, 311, 70663, 11, 439, 21091, 555, 24872, 14800, 4754, 304, 55004, 323, 304, 41294, 11, 7319, 16003, 8824, 11, 54182, 15372, 60038, 323, 13241, 7294, 2442, 372, 414, 77229, 304, 5361, 304, 41294, 4211, 13, 42416, 12, 1591, 89, 28876, 19019, 90974, 350, 2849, 70663, 89334, 290, 304, 3823, 350, 7917, 574, 6051, 21091, 1306, 7645, 315, 264, 28876, 52913, 279, 834, 2399, 526, 747, 437, 579, 320, 41949, 17, 7435, 52340, 220, 975, 70, 17, 64, 1156, 37, 85, 11, 11325, 18, 100644, 323, 11325, 1591, 91977, 31576, 320, 41949, 17, 12, 1591, 89, 705, 439, 264, 1121, 315, 99305, 91977, 78926, 4669, 83089, 98885, 52729, 220, 21, 662, 5810, 584, 1501, 430, 28876, 82, 52913, 279, 220, 975, 70, 17, 64, 13737, 4645, 42, 1156, 37, 85, 11, 902, 20461, 5190, 51552, 369, 40727, 17, 220, 1313, 320, 17455, 12, 1591, 89, 705, 3113, 264, 810, 15748, 70663, 82423, 320, 54290, 2956, 23966, 13, 220, 16, 64, 4235, 66, 7609, 763, 13168, 311, 11325, 777, 12, 1591, 89, 28876, 350, 7917, 320, 30096, 99305, 91977, 705, 42416, 12, 1591, 89, 28876, 350, 7917, 2274, 28254, 4519, 315, 70663, 11, 2737, 11293, 14800, 304, 7829, 11, 7319, 7645, 315, 20747, 10843, 44540, 11, 62258, 3369, 1279, 60038, 11, 323, 54182, 11812, 45, 60474, 323, 88101, 25983, 11598, 12, 17, 5788, 1306, 41959, 320, 30035, 13, 220, 16, 64, 4235, 67, 1174, 41665, 2956, 23966, 13, 220, 16, 67, 11, 384, 7609, 578, 16003, 42655, 527, 4245, 311, 70663, 75968, 32403, 4856, 1109, 1207, 2985, 2931, 16628, 315, 279, 42416, 12, 1591, 89, 28876, 449, 1202, 2218, 40727, 17, 11, 1606, 814, 527, 1101, 13468, 304, 11325, 777, 12, 1591, 89, 28876, 350, 7917, 994, 42416, 12, 1591, 89, 28876, 374, 1080, 10397, 14655, 1701, 264, 6160, 1824, 380, 8535, 4724, 320, 54290, 2956, 23966, 13, 220, 16, 69, 7609, 37409, 3777, 6492, 320, 82550, 8, 315, 41214, 12, 6741, 11627, 320, 31820, 7962, 80, 8, 828, 21091, 430, 279, 31005, 5696, 315, 46940, 278, 33373, 574, 279, 9546, 315, 279, 79953, 42416, 12, 1591, 89, 19579, 2585, 11325, 777, 12, 1591, 89, 28876, 320, 30035, 13, 220, 16, 68, 7026, 8051, 1063, 2849, 10827, 19440, 12062, 1051, 13468, 320, 54290, 2956, 23966, 13, 220, 16, 70, 7609, 23966, 13, 220, 16, 25, 42416, 12, 1591, 89, 28876, 350, 7917, 14794, 14345, 37941, 292, 11, 16003, 11, 46940, 278, 323, 4248, 6569, 5411, 14321, 15914, 315, 350, 2849, 70663, 13, 264, 1174, 26150, 350, 2849, 14800, 13, 2956, 527, 3152, 20903, 274, 1770, 749, 13, 505, 308, 284, 220, 605, 9678, 21896, 13, 293, 1174, 28061, 7645, 315, 70663, 75968, 24915, 13, 272, 1174, 28061, 7645, 315, 11325, 1774, 5726, 323, 11325, 5538, 43, 311, 33137, 350, 5044, 19646, 7917, 320, 6620, 1774, 5726, 489, 11325, 5538, 43, 489, 7026, 8792, 5044, 7917, 320, 6620, 1774, 5726, 25173, 11325, 5538, 43, 489, 7026, 323, 3369, 1279, 5044, 7917, 320, 6620, 1774, 5726, 25173, 11325, 5538, 43, 25173, 7609, 294, 1174, 11598, 12, 17, 320, 2414, 8, 323, 11812, 45, 60474, 320, 1315, 8, 4984, 1306, 220, 1187, 2902, 1080, 1824, 10745, 449, 11325, 777, 489, 40727, 17, 489, 452, 7828, 21, 12279, 35, 17, 514, 26261, 22689, 7917, 13, 2956, 527, 3152, 20903, 274, 962, 13, 505, 8577, 49895, 48396, 13, 763, 293, 1389, 294, 1174, 832, 18740, 35558, 320, 1073, 308, 284, 220, 605, 21896, 8, 374, 6982, 369, 1855, 65033, 13, 393, 2819, 11075, 555, 653, 77267, 1403, 2442, 5805, 259, 482, 24781, 13, 384, 1174, 37409, 3777, 6492, 320, 82550, 8, 315, 3728, 46940, 278, 21542, 315, 50765, 12, 323, 8792, 65196, 72286, 11325, 777, 12, 1591, 89, 320, 6620, 777, 8, 477, 42416, 12, 1591, 89, 320, 17455, 8, 28876, 350, 7917, 520, 2919, 220, 22, 11, 220, 605, 323, 220, 975, 304, 7829, 13, 6812, 16, 320, 2137, 13, 18, 4, 33373, 8, 62849, 11325, 777, 12, 1591, 89, 505, 42416, 12, 1591, 89, 28876, 350, 7917, 13, 282, 1174, 24983, 7645, 315, 279, 1948, 220, 1049, 21389, 10043, 6812, 16, 13, 9500, 288, 315, 2802, 304, 1855, 10879, 527, 10212, 13, 342, 1174, 423, 14657, 31668, 15987, 22083, 15111, 13918, 320, 375, 10011, 8, 304, 11325, 23, 489, 11325, 777, 12, 1591, 89, 323, 42416, 12, 1591, 89, 28876, 350, 7917, 13, 11995, 50765, 323, 8792, 5044, 2849, 75605, 527, 32762, 369, 1855, 28876, 13, 305, 1174, 62029, 315, 7520, 1741, 7962, 80, 22083, 15111, 40800, 304, 11325, 777, 12, 1591, 89, 477, 42416, 12, 1591, 89, 28876, 350, 7917, 13, 6812, 16, 320, 4767, 13, 24, 4, 33373, 8, 62849, 11325, 777, 12, 1591, 89, 505, 42416, 12, 1591, 89, 28876, 10688, 13, 602, 1174, 8121, 22083, 15111, 40800, 5643, 315, 11325, 19, 489, 323, 11325, 23, 489, 11325, 777, 12, 1591, 89, 323, 42416, 12, 1591, 89, 128257, 198, 128256, 78191, 198, 32, 502, 5603, 311, 2068, 287, 9572, 2269, 45850, 22852, 7917, 2663, 28876, 9469, 7917, 649, 33482, 872, 5820, 323, 5376, 872, 27375, 2403, 3823, 9572, 7917, 15042, 304, 279, 27692, 323, 304, 24548, 11, 4184, 311, 264, 4007, 555, 12074, 520, 279, 31788, 3907, 6150, 315, 19152, 13, 578, 5845, 311, 10408, 688, 279, 70663, 430, 279, 52033, 46036, 7917, 3629, 3217, 1306, 872, 2926, 21165, 315, 5820, 1436, 3063, 311, 279, 4500, 315, 264, 502, 9659, 315, 28876, 9469, 7917, 430, 1253, 387, 7524, 1524, 2403, 6573, 51423, 29096, 5915, 430, 706, 3156, 1457, 658, 38477, 12074, 13, 578, 7978, 1051, 13375, 304, 24548, 69566, 5620, 3823, 96306, 323, 17685, 9572, 7917, 13, 578, 12074, 3987, 311, 3240, 14830, 19622, 304, 1274, 449, 96306, 2949, 279, 1828, 220, 972, 4038, 323, 311, 9778, 13334, 279, 19622, 311, 2997, 6573, 51423, 13, 330, 1687, 1440, 430, 350, 7917, 527, 8147, 3403, 311, 89514, 9572, 1359, 1071, 29016, 33491, 543, 11, 14306, 11, 14561, 315, 10696, 71528, 323, 315, 16088, 520, 31788, 323, 279, 22712, 7690, 315, 279, 31788, 26211, 10181, 13, 330, 4071, 1521, 1890, 350, 7917, 617, 28995, 311, 617, 5933, 45664, 430, 76129, 1523, 279, 77229, 315, 872, 2077, 1306, 264, 4261, 315, 44387, 5820, 13, 1226, 3077, 8040, 264, 1648, 311, 50460, 420, 70663, 2077, 323, 7417, 279, 5820, 315, 28876, 9469, 7917, 2403, 6680, 323, 6573, 51423, 1210, 33491, 543, 11, 889, 374, 1101, 279, 7690, 315, 279, 31788, 5955, 369, 26211, 14299, 40143, 323, 315, 279, 31788, 3495, 4219, 315, 279, 29306, 10181, 369, 26211, 67335, 42811, 11, 32839, 2911, 449, 6680, 51423, 520, 279, 37053, 5955, 369, 72410, 26211, 323, 20671, 70674, 520, 31788, 15394, 596, 6401, 13, 33491, 543, 374, 279, 10195, 3229, 315, 279, 4007, 11, 902, 690, 387, 4756, 3799, 13, 220, 19, 304, 22037, 13, 33600, 1772, 38083, 278, 18640, 32532, 45638, 11, 2405, 920, 2637, 374, 279, 3063, 3229, 13, 9500, 37774, 11041, 7917, 315, 8893, 28876, 9469, 7917, 374, 459, 72578, 369, 523, 3212, 292, 83089, 35268, 350, 7917, 13, 9500, 37774, 11041, 505, 264, 8893, 596, 1866, 350, 7917, 11, 28876, 9469, 7917, 527, 6319, 311, 3839, 1523, 323, 5622, 9572, 7917, 555, 49183, 3230, 28896, 389, 279, 7917, 6, 7479, 13, 28876, 9469, 2849, 15419, 1903, 31186, 2212, 279, 1917, 304, 220, 679, 22, 994, 279, 12369, 323, 26166, 17128, 5043, 10398, 11440, 872, 14765, 369, 279, 6514, 315, 2911, 449, 1375, 9381, 477, 653, 52397, 30883, 43745, 677, 52279, 96306, 13, 25929, 430, 1060, 11, 264, 2373, 315, 28876, 9469, 6514, 574, 1101, 12054, 369, 12884, 449, 1063, 4595, 315, 43745, 7942, 13, 2030, 8051, 6680, 51423, 3629, 6013, 10098, 3210, 311, 28876, 9469, 6514, 11, 17162, 1109, 4376, 315, 12020, 6978, 3217, 1317, 9860, 2585, 315, 872, 8624, 11, 3629, 1606, 279, 28876, 9469, 7917, 3719, 39019, 11, 13490, 872, 5845, 311, 43036, 349, 22514, 398, 323, 311, 22815, 3440, 9572, 7917, 13, 6193, 5065, 420, 70663, 706, 1027, 264, 1401, 5915, 315, 9572, 12074, 369, 3892, 1667, 13, 45638, 323, 33491, 543, 6656, 311, 264, 15105, 1080, 49061, 291, 304, 279, 27692, 315, 20462, 44472, 11, 14306, 11, 2405, 920, 2637, 279, 13286, 323, 423, 11606, 13, 85550, 17054, 315, 26211, 9500, 24203, 323, 14561, 315, 56104, 520, 31788, 11, 311, 3619, 810, 922, 1148, 8741, 994, 350, 7917, 3719, 39019, 323, 3508, 433, 2643, 387, 3284, 311, 69033, 420, 70663, 13, 578, 15105, 11, 2663, 7520, 1741, 12, 20794, 11, 9160, 7862, 5789, 315, 279, 33869, 1405, 23331, 46121, 927, 14107, 477, 1234, 14107, 21389, 13, 330, 4599, 584, 1511, 420, 15105, 311, 9616, 279, 85381, 315, 9498, 323, 39019, 350, 7917, 1359, 33491, 543, 1071, 11, 330, 906, 11054, 1063, 5199, 12062, 304, 15207, 7645, 12912, 1210, 763, 4040, 11, 279, 12074, 11352, 430, 39019, 350, 7917, 20461, 459, 68331, 304, 279, 5820, 315, 264, 3682, 538, 315, 21389, 430, 37377, 13128, 5990, 304, 279, 7917, 11, 6522, 311, 459, 5376, 304, 28896, 430, 69033, 872, 5820, 13, 3277, 279, 12074, 11041, 28876, 9469, 7917, 311, 15301, 279, 8335, 555, 927, 14107, 287, 272, 78834, 11, 264, 15207, 430, 12992, 279, 7645, 315, 28896, 5938, 449, 350, 2849, 15449, 11, 814, 5602, 430, 279, 7917, 14958, 4642, 323, 43036, 660, 304, 279, 27692, 1524, 1234, 4787, 430, 1053, 14614, 1121, 304, 872, 70663, 13, 386, 560, 41772, 449, 3823, 96306, 7917, 12439, 5129, 994, 12020, 449, 279, 11041, 28876, 9469, 7917, 1109, 449, 279, 5912, 28876, 9469, 7917, 13, 763, 5369, 11, 279, 272, 78834, 37810, 28876, 9469, 7917, 1051, 1101, 3025, 311, 8108, 279, 36254, 23104, 323, 13334, 279, 61961, 315, 27692, 24548, 449, 264, 3823, 17685, 9572, 2663, 52368, 437, 277, 82945, 13, 330, 23025, 315, 603, 304, 279, 28876, 9469, 2849, 2115, 617, 31156, 369, 1063, 892, 422, 1521, 7917, 1436, 1101, 387, 1511, 311, 12896, 6573, 56071, 1359, 33491, 543, 1071, 13, 330, 7184, 584, 3077, 8040, 459, 5603, 430, 45382, 279, 7917, 70663, 31785, 323, 36050, 872, 5820, 2403, 6573, 56071, 304, 24548, 13, 10541, 810, 990, 3966, 311, 387, 2884, 311, 1296, 420, 304, 12966, 11, 584, 2351, 38650, 430, 1057, 14955, 690, 3063, 311, 279, 1828, 9659, 315, 28876, 9469, 7917, 323, 1304, 264, 5199, 6811, 369, 1274, 449, 1690, 4595, 315, 51423, 1210, 220, 128257, 198 ]

2,371

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Electromechanical resonators operating in the sub-terahertz regime could be of use in the development of future communication systems because they support extremely fast data rates. Such resonators are also of interest in studying quantum phenomena of mechanical entities, as they can maintain the quantum ground state at kelvin temperatures rather than the millikelvin temperatures demanded by gigahertz resonators. Here we report microelectromechanical resonators operating beyond 100 GHz. By incorporating a millimetre-wave dual-rail resonator into a thickness-shear-mode micromechanical system, we achieve efficient electromechanical transduction through enhanced on-chip impedance matching, which is key to revealing the infinitesimal displacements of these sub-terahertz mechanical modes. Our devices are based on commercially available z -cut lithium niobate thin films and patterned using standard semiconductor fabrication processes. Main Modern communication systems rely on high-quality electromechanical resonators as millimetre-wave front ends. The operating frequency directly determines the communication speed, and thus, it is appealing to use resonators of higher frequencies—such as those operating in the sub-terahertz (THz) regime—in communication devices. Micromechanical resonators in the sub-THz regime can also be used to study the quantum motion of micromechanical structures 1 , 2 , quantum entanglement of massive objects 3 , 4 and long-distance hybrid quantum networks 5 . Today, mechanical resonators in the microwave gigahertz (GHz) frequency regime are routinely refrigerated to their mechanical ground state in millikelvin environments 1 , 6 , 7 , 8 , 9 , 10 . According to the Bose–Einstein distribution, a higher-frequency millimetre-wave resonator in the sub-THz regime can maintain the quantum ground state with a temperature on the order of kelvins, making them appealing elements for accessing quantum mechanical motion. Advancing a mechanical resonator into the sub-THz regime is, however, a non-trivial task. One approach to address high-frequency mechanical motion is to use ultrafast laser pulses through an optical pump–probe scheme 11 , 12 , 13 . This, however, limits the scaling of systems for device applications. Electromechanical actuation and readout, on the other hand, can provide integrated device architectures. However, typical acoustic velocities within solids are on the order of thousands of metres per second, and thus, the acoustic wavelength for sub-THz phonons is only tens of nanometres, which creates challenges in effective transduction and nanofabrication. The recently developed thin-film lithium niobate (LN) platform is a favourable candidate to address the actuation challenge owing to its excellent piezoelectric properties and low phonon loss 14 . To circumvent the stringent requirements on the fabrication resolution in the fundamental-tone actuation scheme, efforts have been made to develop electromechanical overtones up to 60 GHz (ref. 15 ). Yet, the inverse-square decrease of the electromechanical coupling with respect to the mode order limits further advances of electromechanical overtones into the sub-THz regime. In this Article, we show that a millimetre-wave dual-rail resonator (DRR) directly on a suspended LN resonator can be used for the efficient actuation and detection of sub-THz thickness-shear-mode (T-mode) overtones. Serving as a tank circuit 16 , the DRR aids electromechanical transduction by providing on-chip impedance matching to the mechanical modes. The quality of electromechanical transduction can be characterized as the change in millimetre-wave reflection when the mechanical mode is on and off resonance since an optimum electromechanical transducer design would have a small signal reflection when in operation. Together with a well-calibrated reflection measurement setup (Supplementary Section II ) that mitigates perturbation to fragile sub-THz signals, we report electromechanical oscillations beyond 100 GHz. Based on the DRR enhancement shown in the experimental results and the achieved high signal fidelity, we project that such a DRR-enhanced electromechanical transduction scheme could be used to scale electromechanical frequencies further beyond the microwave W band. Dual-rail-coupled thickness-mode resonator The false-colour scanning electron microscopy image of the complete resonator suite—namely, the dual-rail-coupled thickness-mode resonator (DRCTR)—is shown in Fig. 1a . To mitigate anchor loss, we suspend the mechanical resonator by chemically removing the silicon dioxide (SiO 2 ) beneath the LN film. The DRR is formed on top of the thickness-mode resonator and comprises two coupled transmission lines GS 1 G and GS 2 G, short-circuited to the ground at the end of transmission line GS 2 G and probed at the start of transmission line GS 1 G. The DRR features a more uniformly distributed electric-field distribution between the lines than a typical quarter-wavelength resonator, making it advantageous to provide efficient piezoelectric coupling to the distributed thickness-mode resonator (Supplementary Section IIIC ). Such a distributive characteristic of the thickness-mode resonator originates from our device dimension being comparable with the sub-THz signal wavelength. Therefore, different from the lumped element model 17 where the mechanical resonator is modelled as lumped RLC components, our DRCTR model (Fig. 1b ) treats the mechanical resonator as distributed conductance between the coupled lines, defined as \$G_{\\mathrm{m}} = 1/\\left( {R_{\\mathrm{m}} + {1 \\over {\\mathrm{i}\\omega C_{\\mathrm{m}}}} + {\\mathrm{i}}\\omega L_{\\mathrm{m}}} \\right)\$ , where R m , C m and L m represent the distributed motional resistance, capacitance and inductance, respectively, and ω represents the signal angular frequency. Mechanical resonant frequency f and quality factor Q can be expressed as \$f = 1/\\left( {2\\uppi \\sqrt {L_{\\mathrm{m}}C_{\\mathrm{m}}} } \\right)\$ and Q = 1/(2π f R m C m ), respectively. We detect the embedded thickness-mode resonator by measuring the reflection ( Γ ) spectrum of the DRCTR with a frequency multiplier/directional coupler/downconversion approach that reduces the input/output interference and improves the sub-THz signal fidelity (Methods). The input impedance Z in can be derived from the measured reflection, following Γ = ( Z in − Z 0 )/( Z in + Z 0 ), where Z 0 = 50 Ω, is the impedance of a standard transmission line. By viewing the dual rails as a four-port network, we illustrate (Fig. 1b ) the boundary conditions of the DRCTR, where port 2 and port 4 are open-circuited and port 3 is short-circuited. In the theoretical derivation of the input impedance Z in seen at port 1 (Supplementary Section IIIB ), we treat the propagating signals on the dual rails as a superposition of the differential mode", "role": "user" }, { "content": "To further advance communication systems, increasing both their speed and efficiency, electronics engineers will need to create new and highly performing components, including electromechanical resonators. Electromechanical resonators are essential components of communications systems that can be used to generate powerful waves of specific frequencies or selectively broadcast communication signals at specific frequencies. To speed up communications further and pave the way for the next generation of wireless networks (6G), new resonators should ideally operate at sub-terahertz frequencies (i.e., at frequencies above 100GHz). In a recent paper published in Nature Electronics, a team of researchers led by Prof. Hong Tang at Yale University introduced new electromechanical resonators that could operate at these high frequencies. \"Our research emphasizes increasing the operating frequencies of electromechanical resonators to exceed 100 GHz,\" Jiacheng Xie, the lead author who carried out the study, told Tech Xplore. \"The foundation of modern communication systems relies on the continuous progress in resonator technologies, as higher-frequency oscillators lead to faster communication speeds. With the ongoing worldwide implementation of 5G communication technologies, there is a growing demand for higher-frequency resonators to support emerging technological advancements.\" The microelectromechanical resonators created by Xie and his colleagues are comprised of a millimeter-wave dual rail resonator placed on top of a suspended lithium niobate beam. To suspend this beam inside their device, the researchers chemically etched away the silicon dioxide underneath it, which also minimized the loss of acoustic waves into the surrounding space. \"To effectively stimulate and measure the sub-terahertz mechanical resonances, we employ a millimeter-wave dual rail resonator that aids the electromechanical transduction by providing improved on-chip impedance matching to the mechanical modes,\" Xie explained. \"An intuitive analogy can be drawn to the way a violin generates powerful sounds audible to listeners in large concert halls without the need for an amplifier. Although the strings determine the instrument's pitch, the violin's body functions as a broadband resonator that projects the sound, similar to how a dual-rail resonator broadcasts the sub-terahertz resonances for detection.\" Notably, the team's resonator was created using commercially available thin films of lithium niobate, which were patterned using technologies that are widely employed for the fabrication of semiconductors. This could greatly facilitate its large-scale fabrication and implementation in the future. Xie and his colleagues were the first to create electromechanical resonators that operate at frequencies beyond 100 GHz. Their work could thus have important implications for the development of 6G communication systems. \"This breakthrough has the potential to contribute to the evolution of future communication systems, as the Federal Communications Commission (FCC) has created experimental licenses for the use of frequencies between 95 GHz and 3 THz,\" Xie said. \"Furthermore, from a quantum science and technology perspective, it is beneficial to bring mechanical quantum systems out of million-dollar dilution refrigerators. Sub-THz resonators, with ultrahigh resonant frequencies, are significantly more resilient to thermal fluctuations than GHz resonators, and therefore can reach the quantum ground state at much more accessible Kelvin temperatures.\" The recent work by Xie and his colleagues could soon inform the development of other electromechanical resonators that operate at sub-terahertz frequencies. Meanwhile, the researchers plan to advance their devices further, while also trying to create other highly performing components for future communication systems. \"We will now continue our efforts to develop electromechanical resonators with even higher frequencies,\" Tang added. \"Additionally, our focus will be on creating applications leveraging our existing technologies.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Electromechanical resonators operating in the sub-terahertz regime could be of use in the development of future communication systems because they support extremely fast data rates. Such resonators are also of interest in studying quantum phenomena of mechanical entities, as they can maintain the quantum ground state at kelvin temperatures rather than the millikelvin temperatures demanded by gigahertz resonators. Here we report microelectromechanical resonators operating beyond 100 GHz. By incorporating a millimetre-wave dual-rail resonator into a thickness-shear-mode micromechanical system, we achieve efficient electromechanical transduction through enhanced on-chip impedance matching, which is key to revealing the infinitesimal displacements of these sub-terahertz mechanical modes. Our devices are based on commercially available z -cut lithium niobate thin films and patterned using standard semiconductor fabrication processes. Main Modern communication systems rely on high-quality electromechanical resonators as millimetre-wave front ends. The operating frequency directly determines the communication speed, and thus, it is appealing to use resonators of higher frequencies—such as those operating in the sub-terahertz (THz) regime—in communication devices. Micromechanical resonators in the sub-THz regime can also be used to study the quantum motion of micromechanical structures 1 , 2 , quantum entanglement of massive objects 3 , 4 and long-distance hybrid quantum networks 5 . Today, mechanical resonators in the microwave gigahertz (GHz) frequency regime are routinely refrigerated to their mechanical ground state in millikelvin environments 1 , 6 , 7 , 8 , 9 , 10 . According to the Bose–Einstein distribution, a higher-frequency millimetre-wave resonator in the sub-THz regime can maintain the quantum ground state with a temperature on the order of kelvins, making them appealing elements for accessing quantum mechanical motion. Advancing a mechanical resonator into the sub-THz regime is, however, a non-trivial task. One approach to address high-frequency mechanical motion is to use ultrafast laser pulses through an optical pump–probe scheme 11 , 12 , 13 . This, however, limits the scaling of systems for device applications. Electromechanical actuation and readout, on the other hand, can provide integrated device architectures. However, typical acoustic velocities within solids are on the order of thousands of metres per second, and thus, the acoustic wavelength for sub-THz phonons is only tens of nanometres, which creates challenges in effective transduction and nanofabrication. The recently developed thin-film lithium niobate (LN) platform is a favourable candidate to address the actuation challenge owing to its excellent piezoelectric properties and low phonon loss 14 . To circumvent the stringent requirements on the fabrication resolution in the fundamental-tone actuation scheme, efforts have been made to develop electromechanical overtones up to 60 GHz (ref. 15 ). Yet, the inverse-square decrease of the electromechanical coupling with respect to the mode order limits further advances of electromechanical overtones into the sub-THz regime. In this Article, we show that a millimetre-wave dual-rail resonator (DRR) directly on a suspended LN resonator can be used for the efficient actuation and detection of sub-THz thickness-shear-mode (T-mode) overtones. Serving as a tank circuit 16 , the DRR aids electromechanical transduction by providing on-chip impedance matching to the mechanical modes. The quality of electromechanical transduction can be characterized as the change in millimetre-wave reflection when the mechanical mode is on and off resonance since an optimum electromechanical transducer design would have a small signal reflection when in operation. Together with a well-calibrated reflection measurement setup (Supplementary Section II ) that mitigates perturbation to fragile sub-THz signals, we report electromechanical oscillations beyond 100 GHz. Based on the DRR enhancement shown in the experimental results and the achieved high signal fidelity, we project that such a DRR-enhanced electromechanical transduction scheme could be used to scale electromechanical frequencies further beyond the microwave W band. Dual-rail-coupled thickness-mode resonator The false-colour scanning electron microscopy image of the complete resonator suite—namely, the dual-rail-coupled thickness-mode resonator (DRCTR)—is shown in Fig. 1a . To mitigate anchor loss, we suspend the mechanical resonator by chemically removing the silicon dioxide (SiO 2 ) beneath the LN film. The DRR is formed on top of the thickness-mode resonator and comprises two coupled transmission lines GS 1 G and GS 2 G, short-circuited to the ground at the end of transmission line GS 2 G and probed at the start of transmission line GS 1 G. The DRR features a more uniformly distributed electric-field distribution between the lines than a typical quarter-wavelength resonator, making it advantageous to provide efficient piezoelectric coupling to the distributed thickness-mode resonator (Supplementary Section IIIC ). Such a distributive characteristic of the thickness-mode resonator originates from our device dimension being comparable with the sub-THz signal wavelength. Therefore, different from the lumped element model 17 where the mechanical resonator is modelled as lumped RLC components, our DRCTR model (Fig. 1b ) treats the mechanical resonator as distributed conductance between the coupled lines, defined as $G_{\mathrm{m}} = 1/\left( {R_{\mathrm{m}} + {1 \over {\mathrm{i}\omega C_{\mathrm{m}}}} + {\mathrm{i}}\omega L_{\mathrm{m}}} \right)$ , where R m , C m and L m represent the distributed motional resistance, capacitance and inductance, respectively, and ω represents the signal angular frequency. Mechanical resonant frequency f and quality factor Q can be expressed as $f = 1/\left( {2\uppi \sqrt {L_{\mathrm{m}}C_{\mathrm{m}}} } \right)$ and Q = 1/(2π f R m C m ), respectively. We detect the embedded thickness-mode resonator by measuring the reflection ( Γ ) spectrum of the DRCTR with a frequency multiplier/directional coupler/downconversion approach that reduces the input/output interference and improves the sub-THz signal fidelity (Methods). The input impedance Z in can be derived from the measured reflection, following Γ = ( Z in − Z 0 )/( Z in + Z 0 ), where Z 0 = 50 Ω, is the impedance of a standard transmission line. By viewing the dual rails as a four-port network, we illustrate (Fig. 1b ) the boundary conditions of the DRCTR, where port 2 and port 4 are open-circuited and port 3 is short-circuited. In the theoretical derivation of the input impedance Z in seen at port 1 (Supplementary Section IIIB ), we treat the propagating signals on the dual rails as a superposition of the differential mode<|im_end|> <|im_start|>assistant To further advance communication systems, increasing both their speed and efficiency, electronics engineers will need to create new and highly performing components, including electromechanical resonators. Electromechanical resonators are essential components of communications systems that can be used to generate powerful waves of specific frequencies or selectively broadcast communication signals at specific frequencies. To speed up communications further and pave the way for the next generation of wireless networks (6G), new resonators should ideally operate at sub-terahertz frequencies (i.e., at frequencies above 100GHz). In a recent paper published in Nature Electronics, a team of researchers led by Prof. Hong Tang at Yale University introduced new electromechanical resonators that could operate at these high frequencies. "Our research emphasizes increasing the operating frequencies of electromechanical resonators to exceed 100 GHz," Jiacheng Xie, the lead author who carried out the study, told Tech Xplore. "The foundation of modern communication systems relies on the continuous progress in resonator technologies, as higher-frequency oscillators lead to faster communication speeds. With the ongoing worldwide implementation of 5G communication technologies, there is a growing demand for higher-frequency resonators to support emerging technological advancements." The microelectromechanical resonators created by Xie and his colleagues are comprised of a millimeter-wave dual rail resonator placed on top of a suspended lithium niobate beam. To suspend this beam inside their device, the researchers chemically etched away the silicon dioxide underneath it, which also minimized the loss of acoustic waves into the surrounding space. "To effectively stimulate and measure the sub-terahertz mechanical resonances, we employ a millimeter-wave dual rail resonator that aids the electromechanical transduction by providing improved on-chip impedance matching to the mechanical modes," Xie explained. "An intuitive analogy can be drawn to the way a violin generates powerful sounds audible to listeners in large concert halls without the need for an amplifier. Although the strings determine the instrument's pitch, the violin's body functions as a broadband resonator that projects the sound, similar to how a dual-rail resonator broadcasts the sub-terahertz resonances for detection." Notably, the team's resonator was created using commercially available thin films of lithium niobate, which were patterned using technologies that are widely employed for the fabrication of semiconductors. This could greatly facilitate its large-scale fabrication and implementation in the future. Xie and his colleagues were the first to create electromechanical resonators that operate at frequencies beyond 100 GHz. Their work could thus have important implications for the development of 6G communication systems. "This breakthrough has the potential to contribute to the evolution of future communication systems, as the Federal Communications Commission (FCC) has created experimental licenses for the use of frequencies between 95 GHz and 3 THz," Xie said. "Furthermore, from a quantum science and technology perspective, it is beneficial to bring mechanical quantum systems out of million-dollar dilution refrigerators. Sub-THz resonators, with ultrahigh resonant frequencies, are significantly more resilient to thermal fluctuations than GHz resonators, and therefore can reach the quantum ground state at much more accessible Kelvin temperatures." The recent work by Xie and his colleagues could soon inform the development of other electromechanical resonators that operate at sub-terahertz frequencies. Meanwhile, the researchers plan to advance their devices further, while also trying to create other highly performing components for future communication systems. "We will now continue our efforts to develop electromechanical resonators with even higher frequencies," Tang added. "Additionally, our focus will be on creating applications leveraging our existing technologies." <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 10085, 442, 4842, 45983, 29280, 3046, 10565, 304, 279, 1207, 12, 466, 1494, 59037, 17942, 1436, 387, 315, 1005, 304, 279, 4500, 315, 3938, 10758, 6067, 1606, 814, 1862, 9193, 5043, 828, 7969, 13, 15483, 29280, 3046, 527, 1101, 315, 2802, 304, 21630, 31228, 44247, 315, 22936, 15086, 11, 439, 814, 649, 10519, 279, 31228, 5015, 1614, 520, 49328, 9799, 20472, 4856, 1109, 279, 2606, 29955, 9799, 20472, 30526, 555, 23401, 1494, 59037, 29280, 3046, 13, 5810, 584, 1934, 8162, 19493, 442, 4842, 45983, 29280, 3046, 10565, 7953, 220, 1041, 52405, 13, 3296, 52913, 264, 2606, 318, 47987, 89354, 19091, 3880, 607, 29280, 859, 1139, 264, 26839, 1355, 87160, 15331, 19748, 442, 4842, 45983, 1887, 11, 584, 11322, 11297, 54707, 4842, 45983, 1380, 23985, 1555, 24872, 389, 11843, 575, 91048, 12864, 11, 902, 374, 1401, 311, 31720, 279, 82226, 30572, 13770, 34178, 315, 1521, 1207, 12, 466, 1494, 59037, 22936, 20362, 13, 5751, 7766, 527, 3196, 389, 54453, 2561, 1167, 482, 10453, 57907, 13080, 677, 349, 15792, 12631, 323, 5497, 291, 1701, 5410, 87836, 59251, 11618, 13, 4802, 18766, 10758, 6067, 17631, 389, 1579, 22867, 54707, 4842, 45983, 29280, 3046, 439, 2606, 318, 47987, 89354, 4156, 10548, 13, 578, 10565, 11900, 6089, 27667, 279, 10758, 4732, 11, 323, 8617, 11, 433, 374, 33352, 311, 1005, 29280, 3046, 315, 5190, 34873, 2345, 21470, 439, 1884, 10565, 304, 279, 1207, 12, 466, 1494, 59037, 320, 3701, 89, 8, 17942, 49525, 10758, 7766, 13, 28095, 442, 4842, 45983, 29280, 3046, 304, 279, 1207, 12, 3701, 89, 17942, 649, 1101, 387, 1511, 311, 4007, 279, 31228, 11633, 315, 19748, 442, 4842, 45983, 14726, 220, 16, 1174, 220, 17, 1174, 31228, 1218, 526, 1001, 315, 11191, 6302, 220, 18, 1174, 220, 19, 323, 1317, 74908, 26038, 31228, 14488, 220, 20, 662, 11450, 11, 22936, 29280, 3046, 304, 279, 42374, 23401, 1494, 59037, 320, 48343, 8, 11900, 17942, 527, 40076, 30477, 660, 311, 872, 22936, 5015, 1614, 304, 2606, 29955, 9799, 22484, 220, 16, 1174, 220, 21, 1174, 220, 22, 1174, 220, 23, 1174, 220, 24, 1174, 220, 605, 662, 10771, 311, 279, 94558, 4235, 36, 37494, 8141, 11, 264, 5190, 79412, 2606, 318, 47987, 89354, 29280, 859, 304, 279, 1207, 12, 3701, 89, 17942, 649, 10519, 279, 31228, 5015, 1614, 449, 264, 9499, 389, 279, 2015, 315, 49328, 85, 1354, 11, 3339, 1124, 33352, 5540, 369, 32888, 31228, 22936, 11633, 13, 12605, 9151, 264, 22936, 29280, 859, 1139, 279, 1207, 12, 3701, 89, 17942, 374, 11, 4869, 11, 264, 2536, 10398, 27756, 3465, 13, 3861, 5603, 311, 2686, 1579, 79412, 22936, 11633, 374, 311, 1005, 24955, 9533, 21120, 66557, 1555, 459, 29393, 14155, 4235, 53429, 13155, 220, 806, 1174, 220, 717, 1174, 220, 1032, 662, 1115, 11, 4869, 11, 13693, 279, 28041, 315, 6067, 369, 3756, 8522, 13, 10085, 442, 4842, 45983, 1180, 4090, 323, 1373, 412, 11, 389, 279, 1023, 1450, 11, 649, 3493, 18751, 3756, 78335, 13, 4452, 11, 14595, 45166, 75157, 2949, 82486, 527, 389, 279, 2015, 315, 9214, 315, 37356, 824, 2132, 11, 323, 8617, 11, 279, 45166, 46406, 369, 1207, 12, 3701, 89, 51923, 2439, 374, 1193, 22781, 315, 20622, 4512, 417, 11, 902, 11705, 11774, 304, 7524, 1380, 23985, 323, 20622, 1073, 29997, 367, 13, 578, 6051, 8040, 15792, 2269, 9672, 57907, 13080, 677, 349, 320, 51316, 8, 5452, 374, 264, 82285, 9322, 311, 2686, 279, 1180, 4090, 8815, 56612, 311, 1202, 9250, 4447, 89, 4748, 47262, 6012, 323, 3428, 51923, 263, 4814, 220, 975, 662, 2057, 10408, 688, 279, 70099, 8670, 389, 279, 59251, 11175, 304, 279, 16188, 99036, 1180, 4090, 13155, 11, 9045, 617, 1027, 1903, 311, 2274, 54707, 4842, 45983, 927, 92745, 709, 311, 220, 1399, 52405, 320, 1116, 13, 220, 868, 7609, 14968, 11, 279, 29049, 34047, 18979, 315, 279, 54707, 4842, 45983, 59086, 449, 5201, 311, 279, 3941, 2015, 13693, 4726, 31003, 315, 54707, 4842, 45983, 927, 92745, 1139, 279, 1207, 12, 3701, 89, 17942, 13, 763, 420, 13659, 11, 584, 1501, 430, 264, 2606, 318, 47987, 89354, 19091, 3880, 607, 29280, 859, 320, 7842, 49, 8, 6089, 389, 264, 22340, 89282, 29280, 859, 649, 387, 1511, 369, 279, 11297, 1180, 4090, 323, 18468, 315, 1207, 12, 3701, 89, 26839, 1355, 87160, 15331, 320, 51, 15331, 8, 927, 92745, 13, 72743, 439, 264, 13192, 16622, 220, 845, 1174, 279, 423, 8268, 52797, 54707, 4842, 45983, 1380, 23985, 555, 8405, 389, 11843, 575, 91048, 12864, 311, 279, 22936, 20362, 13, 578, 4367, 315, 54707, 4842, 45983, 1380, 23985, 649, 387, 32971, 439, 279, 2349, 304, 2606, 318, 47987, 89354, 22599, 994, 279, 22936, 3941, 374, 389, 323, 1022, 58081, 2533, 459, 54767, 54707, 4842, 45983, 1380, 30038, 2955, 1053, 617, 264, 2678, 8450, 22599, 994, 304, 5784, 13, 32255, 449, 264, 1664, 49236, 61666, 22599, 19179, 6642, 320, 10254, 67082, 11360, 8105, 883, 430, 36090, 988, 18713, 65916, 311, 45350, 1207, 12, 3701, 89, 17738, 11, 584, 1934, 54707, 4842, 45983, 43524, 811, 7953, 220, 1041, 52405, 13, 20817, 389, 279, 423, 8268, 27886, 6982, 304, 279, 22772, 3135, 323, 279, 17427, 1579, 8450, 83604, 11, 584, 2447, 430, 1778, 264, 423, 8268, 84182, 4979, 54707, 4842, 45983, 1380, 23985, 13155, 1436, 387, 1511, 311, 5569, 54707, 4842, 45983, 34873, 4726, 7953, 279, 42374, 468, 7200, 13, 34759, 3880, 607, 1824, 283, 50185, 26839, 15331, 29280, 859, 578, 905, 20024, 414, 36201, 17130, 92914, 2217, 315, 279, 4686, 29280, 859, 16578, 2345, 12682, 989, 11, 279, 19091, 3880, 607, 1824, 283, 50185, 26839, 15331, 29280, 859, 320, 7842, 93193, 68850, 285, 6982, 304, 23966, 13, 220, 16, 64, 662, 2057, 50460, 17543, 4814, 11, 584, 27343, 279, 22936, 29280, 859, 555, 8590, 2740, 18054, 279, 51692, 40589, 320, 22771, 46, 220, 17, 883, 24923, 279, 89282, 4632, 13, 578, 423, 8268, 374, 14454, 389, 1948, 315, 279, 26839, 15331, 29280, 859, 323, 41095, 1403, 34356, 18874, 5238, 36370, 220, 16, 480, 323, 36370, 220, 17, 480, 11, 2875, 1824, 2496, 84, 1639, 311, 279, 5015, 520, 279, 842, 315, 18874, 1584, 36370, 220, 17, 480, 323, 463, 2788, 520, 279, 1212, 315, 18874, 1584, 36370, 220, 16, 480, 13, 578, 423, 8268, 4519, 264, 810, 78909, 4332, 9249, 19677, 8141, 1990, 279, 5238, 1109, 264, 14595, 8502, 2695, 35961, 29280, 859, 11, 3339, 433, 76824, 311, 3493, 11297, 4447, 89, 4748, 47262, 59086, 311, 279, 4332, 26839, 15331, 29280, 859, 320, 10254, 67082, 11360, 8105, 1341, 7609, 15483, 264, 2916, 6844, 29683, 315, 279, 26839, 15331, 29280, 859, 99970, 505, 1057, 3756, 13167, 1694, 30139, 449, 279, 1207, 12, 3701, 89, 8450, 46406, 13, 15636, 11, 2204, 505, 279, 49629, 291, 2449, 1646, 220, 1114, 1405, 279, 22936, 29280, 859, 374, 1646, 839, 439, 49629, 291, 432, 8724, 6956, 11, 1057, 14644, 93193, 1646, 320, 30035, 13, 220, 16, 65, 883, 32839, 279, 22936, 29280, 859, 439, 4332, 6929, 685, 1990, 279, 34356, 5238, 11, 4613, 439, 18240, 38, 15511, 59, 92650, 90, 76, 3500, 284, 220, 16, 35419, 2414, 7, 314, 49, 15511, 59, 92650, 90, 76, 3500, 489, 314, 16, 1144, 2017, 29252, 92650, 25182, 11281, 33796, 356, 15511, 59, 92650, 90, 76, 3500, 3500, 489, 29252, 92650, 25182, 3500, 59, 33796, 445, 15511, 59, 92650, 90, 76, 76642, 1144, 1315, 10929, 8, 1174, 1405, 432, 296, 1174, 356, 296, 323, 445, 296, 4097, 279, 4332, 3937, 4001, 13957, 11, 99758, 685, 323, 304, 1076, 685, 11, 15947, 11, 323, 117774, 11105, 279, 8450, 20932, 11900, 13, 51684, 29280, 519, 11900, 282, 323, 4367, 8331, 1229, 649, 387, 13605, 439, 18240, 69, 284, 220, 16, 35419, 2414, 7, 314, 17, 59, 455, 2554, 1144, 27986, 314, 43, 15511, 59, 92650, 90, 76, 3500, 34, 15511, 59, 92650, 90, 76, 76642, 335, 1144, 1315, 10929, 8, 323, 1229, 284, 220, 16, 12148, 17, 49345, 282, 432, 296, 356, 296, 7026, 15947, 13, 1226, 11388, 279, 23711, 26839, 15331, 29280, 859, 555, 30090, 279, 22599, 320, 85316, 883, 20326, 315, 279, 14644, 93193, 449, 264, 11900, 31659, 3529, 45770, 4020, 13206, 80167, 74825, 5603, 430, 26338, 279, 1988, 48116, 32317, 323, 36050, 279, 1207, 12, 3701, 89, 8450, 83604, 320, 18337, 570, 578, 1988, 91048, 1901, 304, 649, 387, 14592, 505, 279, 17303, 22599, 11, 2768, 85316, 284, 320, 1901, 304, 25173, 1901, 220, 15, 883, 12148, 1901, 304, 489, 1901, 220, 15, 7026, 1405, 1901, 220, 15, 284, 220, 1135, 117336, 11, 374, 279, 91048, 315, 264, 5410, 18874, 1584, 13, 3296, 20705, 279, 19091, 43700, 439, 264, 3116, 42557, 4009, 11, 584, 41468, 320, 30035, 13, 220, 16, 65, 883, 279, 19254, 4787, 315, 279, 14644, 93193, 11, 1405, 2700, 220, 17, 323, 2700, 220, 19, 527, 1825, 1824, 2496, 84, 1639, 323, 2700, 220, 18, 374, 2875, 1824, 2496, 84, 1639, 13, 763, 279, 32887, 96354, 315, 279, 1988, 91048, 1901, 304, 3970, 520, 2700, 220, 16, 320, 10254, 67082, 11360, 8105, 3336, 7026, 584, 4322, 279, 17425, 1113, 17738, 389, 279, 19091, 43700, 439, 264, 2307, 3571, 315, 279, 41264, 3941, 128257, 198, 128256, 78191, 198, 1271, 4726, 12178, 10758, 6067, 11, 7859, 2225, 872, 4732, 323, 15374, 11, 31591, 25175, 690, 1205, 311, 1893, 502, 323, 7701, 16785, 6956, 11, 2737, 54707, 4842, 45983, 29280, 3046, 13, 10085, 442, 4842, 45983, 29280, 3046, 527, 7718, 6956, 315, 17320, 6067, 430, 649, 387, 1511, 311, 7068, 8147, 17301, 315, 3230, 34873, 477, 82775, 13195, 10758, 17738, 520, 3230, 34873, 13, 2057, 4732, 709, 17320, 4726, 323, 94123, 279, 1648, 369, 279, 1828, 9659, 315, 21401, 14488, 320, 21, 38, 705, 502, 29280, 3046, 1288, 50663, 14816, 520, 1207, 12, 466, 1494, 59037, 34873, 320, 72, 1770, 2637, 520, 34873, 3485, 220, 1041, 48343, 570, 763, 264, 3293, 5684, 4756, 304, 22037, 38784, 11, 264, 2128, 315, 12074, 6197, 555, 8626, 13, 19730, 41462, 520, 44552, 3907, 11784, 502, 54707, 4842, 45983, 29280, 3046, 430, 1436, 14816, 520, 1521, 1579, 34873, 13, 330, 8140, 3495, 66159, 7859, 279, 10565, 34873, 315, 54707, 4842, 45983, 29280, 3046, 311, 12771, 220, 1041, 52405, 1359, 55551, 613, 833, 1630, 648, 11, 279, 3063, 3229, 889, 11953, 704, 279, 4007, 11, 3309, 17829, 1630, 79, 20763, 13, 330, 791, 16665, 315, 6617, 10758, 6067, 34744, 389, 279, 19815, 5208, 304, 29280, 859, 14645, 11, 439, 5190, 79412, 43524, 3046, 3063, 311, 10819, 10758, 25753, 13, 3161, 279, 14529, 15603, 8292, 315, 220, 20, 38, 10758, 14645, 11, 1070, 374, 264, 7982, 7631, 369, 5190, 79412, 29280, 3046, 311, 1862, 24084, 30116, 83787, 1210, 578, 8162, 19493, 442, 4842, 45983, 29280, 3046, 3549, 555, 1630, 648, 323, 813, 18105, 527, 40056, 315, 264, 2606, 26402, 89354, 19091, 13881, 29280, 859, 9277, 389, 1948, 315, 264, 22340, 57907, 13080, 677, 349, 24310, 13, 2057, 27343, 420, 24310, 4871, 872, 3756, 11, 279, 12074, 8590, 2740, 1880, 2454, 3201, 279, 51692, 40589, 30456, 433, 11, 902, 1101, 82178, 279, 4814, 315, 45166, 17301, 1139, 279, 14932, 3634, 13, 330, 1271, 13750, 51077, 323, 6767, 279, 1207, 12, 466, 1494, 59037, 22936, 29280, 3095, 11, 584, 3539, 264, 2606, 26402, 89354, 19091, 13881, 29280, 859, 430, 52797, 279, 54707, 4842, 45983, 1380, 23985, 555, 8405, 13241, 389, 11843, 575, 91048, 12864, 311, 279, 22936, 20362, 1359, 1630, 648, 11497, 13, 330, 2127, 42779, 56203, 649, 387, 15107, 311, 279, 1648, 264, 63137, 27983, 8147, 10578, 80415, 311, 24475, 304, 3544, 21497, 52473, 2085, 279, 1205, 369, 459, 61166, 13, 10541, 279, 9246, 8417, 279, 14473, 596, 9846, 11, 279, 63137, 596, 2547, 5865, 439, 264, 41925, 29280, 859, 430, 7224, 279, 5222, 11, 4528, 311, 1268, 264, 19091, 3880, 607, 29280, 859, 66198, 279, 1207, 12, 466, 1494, 59037, 29280, 3095, 369, 18468, 1210, 2876, 2915, 11, 279, 2128, 596, 29280, 859, 574, 3549, 1701, 54453, 2561, 15792, 12631, 315, 57907, 13080, 677, 349, 11, 902, 1051, 5497, 291, 1701, 14645, 430, 527, 13882, 20011, 369, 279, 59251, 315, 5347, 1965, 1076, 1105, 13, 1115, 1436, 19407, 28696, 1202, 3544, 13230, 59251, 323, 8292, 304, 279, 3938, 13, 1630, 648, 323, 813, 18105, 1051, 279, 1176, 311, 1893, 54707, 4842, 45983, 29280, 3046, 430, 14816, 520, 34873, 7953, 220, 1041, 52405, 13, 11205, 990, 1436, 8617, 617, 3062, 25127, 369, 279, 4500, 315, 220, 21, 38, 10758, 6067, 13, 330, 2028, 42445, 706, 279, 4754, 311, 17210, 311, 279, 15740, 315, 3938, 10758, 6067, 11, 439, 279, 12411, 26545, 9849, 320, 37, 3791, 8, 706, 3549, 22772, 21746, 369, 279, 1005, 315, 34873, 1990, 220, 2721, 52405, 323, 220, 18, 4534, 89, 1359, 1630, 648, 1071, 13, 330, 57417, 11, 505, 264, 31228, 8198, 323, 5557, 13356, 11, 433, 374, 24629, 311, 4546, 22936, 31228, 6067, 704, 315, 3610, 54135, 19371, 1516, 30477, 3046, 13, 3804, 12, 3701, 89, 29280, 3046, 11, 449, 37232, 1494, 1108, 29280, 519, 34873, 11, 527, 12207, 810, 59780, 311, 29487, 65649, 1109, 52405, 29280, 3046, 11, 323, 9093, 649, 5662, 279, 31228, 5015, 1614, 520, 1790, 810, 15987, 92073, 20472, 1210, 578, 3293, 990, 555, 1630, 648, 323, 813, 18105, 1436, 5246, 6179, 279, 4500, 315, 1023, 54707, 4842, 45983, 29280, 3046, 430, 14816, 520, 1207, 12, 466, 1494, 59037, 34873, 13, 26982, 11, 279, 12074, 3197, 311, 12178, 872, 7766, 4726, 11, 1418, 1101, 4560, 311, 1893, 1023, 7701, 16785, 6956, 369, 3938, 10758, 6067, 13, 330, 1687, 690, 1457, 3136, 1057, 9045, 311, 2274, 54707, 4842, 45983, 29280, 3046, 449, 1524, 5190, 34873, 1359, 41462, 3779, 13, 330, 50674, 11, 1057, 5357, 690, 387, 389, 6968, 8522, 77582, 1057, 6484, 14645, 1210, 220, 128257, 198 ]

2,277

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Long-distance migrations by marine vertebrates are often triggered by pronounced environmental cues. For the endangered basking shark ( Cetorhinus maximus ), seasonal changes in water temperature are frequently proposed as a cue for aggregation within (and dispersal from) coastal hotspots. The inference is that such movements reflect year-round occupancy within a given thermal ‘envelope’. However, the marked variance in timing, direction and depth of dispersal movements hint at a more nuanced explanation for basking sharks. Here, using data from pop-off archival transmitters deployed on individuals in Irish waters, we explored whether autumnal decreases in water temperature triggered departure from coastal habitats and how depth and location shaped the sharks’ realised thermal environment over time. Temperature was not an apparent driver of dispersal from coastal seas, and variance in daily temperature ranges reflected occupancy of different habitats; coastal mixed/stratified and offshore subtropical/tropical waters. Furthermore, individuals that moved offshore and into more southern latitudes off Africa, exhibited a distinct daily cycle of deep dives (00:00–12:00, 200 m–700 m; 12:00–00:00, 0–300 m), experiencing a more extreme range of temperatures (6.8–27.4 °C), including cooler minimum temperatures, than those remaining in European coastal habitat (9.2–17.6 °C). Collectively, these findings challenge the supposition that temperature serves as a universal driver of seasonal dispersal from coastal seas and prompts further studies of deep-water forays in offshore areas. Working on a manuscript? Avoid the common mistakes Introduction Animal migrations are defined by their reciprocity and predictability, differentiating them from other movement strategies such as nomadism, invasions and dispersal (e.g. Newson et al. 2009 ; Teitelbaum and Mueller 2019 ). For marine vertebrates, the most frequently documented migrations are seasonal (Luschi 2013 ), with animals moving in response to shifts in prey availability (Corkeron and Connor 1999 ) and/or physiological constraints aligned with changes in their ambient environment such as water temperature (Schlaff et al. 2014 ). In response to rapidly warming seas, effective plans for conservation and management must recognise that migration patterns may not be static because migration routes can shift and the timing of migratory movements can be dependent on fluid environmental conditions as they are experienced (Hays et al. 2019 ; Senner et al. 2020 ). Such management considerations are magnified for long-distance migrants that traverse territorial boundaries adding a layer of political complexity (e.g. Newson et al. 2009 ; Mackelworth et al. 2019 ; Mason et al. 2020 ). Seasonal shifts in environmental conditions have been proposed as dispersal cues for basking sharks ( Cetorhinus maximus ) that aggregate in coastal hotspots at temperate latitudes during summer months, moving typically into offshore areas with the onset of autumn (Sims et al. 2003 ; Gore et al. 2008 ; Skomal et al. 2009 ; Doherty et al. 2017a , 2017b , 2019 ; Braun et al. 2018 ; Dolton et al. 2019 ). Oscillations in plankton abundance provide an intuitive explanation for this pattern (Sims and Reid 2002 ), but prey densities appear adequate for year-round foraging (Sims 1999 ) and residence in coastal seas (Doherty et al. 2017a , b ). Likewise, water temperature has been proposed frequently as a cue for both seasonal aggregation and subsequent dispersal of basking sharks (NW Atlantic: Skomal et al. 2009 ; Siders et al. 2013 ; Braun et al. 2018 —NE Atlantic: Berrow and Heardman 1994 ; Cotton et al. 2005 ; Priede and Miller 2009 ; Witt et al. 2012 ; Miller et al. 2015 ; Austin et al. 2019 ; Doherty et al. 2019 ). The broad inference is that latitudinal movements, triggered by thermal cues, may allow individuals to remain within a given ‘envelope’ of temperatures (i.e. an optimal thermal range) throughout the year irrespective of season. Certainly, movements of basking sharks in the Northwest Atlantic appear to mirror seasonal changes in water temperature, with individuals ranging from Cape Cod, USA, to tropical waters (Skomal et al. 2009 ; Hoogenboom et al. 2015 ; Braun et al. 2018 ). Despite evidence of water temperature as a driver of basking shark movements, winter dispersal from coastal seas is not ubiquitous (Gore et al. 2008 ; Doherty et al. 2017a ), raising an interesting question. Quite simply, if migration from coastal areas is to maintain a thermal envelope, why do some animals stay and others disperse? Recent evidence from beyond the Atlantic may provide some insights, with Finucci et al. ( 2021 ) revealing that sea surface temperature (SST) aligned poorly with basking shark habitat suitability. Taken together, these findings hint at a more nuanced role for temperature in dispersal, or distinct regional differences in behaviour. Within this overall context, we examined the movements and behaviour of basking sharks in the Northeast Atlantic displaying markedly different ‘overwintering’ strategies, namely, residency in temperate coastal seas and long-distance dispersal offshore. Using archived temperature, location and depth data relayed via animal-borne satellite transmitters, we initially questioned whether decreases in coastal water temperatures during late boreal summer triggered dispersal from coastal seas in the NE Atlantic. Subsequently, we explored how depth and location shaped the sharks’ realised thermal environment over time. Methods Device deployment site Searches for sharks were conducted during calm (Beaufort Force < 3) sunny conditions to maximise the likelihood of encounters. Basking sharks were tagged between the 26th of July and the 8th of August 2012 at Malin Head, Ireland (55.37 ○ N, 7.40 ○ W). This deployment time frame was chosen to maximise data recording across autumn and winter months when sharks are known to disperse from coastal seas around Great Britain and Ireland (Sims et al. 2003 ; Doherty et al. 2017a ; Dolton et al. 2019 ). The waters around Malin Head are a seasonal aggregation area (hotspot) for basking sharks in the North East Atlantic (Johnston et al. 2019 ). Water temperature at the deployment site was recorded year-round, for fisheries purposes by the Irish Marine Institute, using Tidbit temperature probes (location: 7.55028° W, 55.15845° N) deployed at 1-m and 11-m depths (Marine Institute Data Catalogue, 2012). To illustrate the seasonal change", "role": "user" }, { "content": "If basking sharks were like Canadians, their migration habits might be easily explained: Head south to avoid winter's chill, and north again to enjoy summer's warmth. It turns out basking sharks are a more complex puzzle, Western biology professor Paul Mensink and his colleagues discovered while examining the seasonal movements of the enormous fish. Mensink and fellow researchers at Queen's University Belfast in Northern Ireland tracked four basking sharks—so large they can reach the size of a school bus—off the northernmost tip of Ireland to find out where they overwinter, and why. They affixed tags that would record the sharks' location, along with water temperature and depth. \"The assumption was that they swim to Ireland's coastal waters for the summer, because of its really productive feeding areas, and then take off for the south in winter where it's warmer. We initially thought that water temperature must be the trigger for them to leave,\" Mensink said. \"They blew our assumptions out of the water.\" Two of the four sharks, surprising the researchers, stayed put. The other two migrated south to tropical and subtropical waters off the African coast, as expected. But instead of lounging in warm waters there, these two spent much of their time in water that was deeper—and much colder—than if they'd stayed nearer to Ireland. Early each morning, these sharks would dive to depths of 200 to 700 meters, return near the surface near midday, then submerge to the chilly depths in the evening. \"It was like clockwork,\" said Mensink, a marine ecologist who specializes in educational technology and is a teaching fellow in Western's Faculty of Science. \"It's almost like the dive pattern of an animal that has to come up to the surface to breathe air—but, of course, they don't.\" During their dive cycle, the sharks put themselves through an extreme range of water temperatures: 27 C near the surface and a frigid 7 C in the depths. So why would any rational, cold-blooded creature do that? Pair of basking sharks in Inishtrahull Sound, Ireland. Credit: Emmett Johnston, Queen’s University Belfast \"Ultimately, what we suspect is they're going down to feed in what we call the deep scattering layer, which is chock full of gelatinous zooplankton and other things they feed on,\" Mensink said. And at midday, they rise nearer the surface to bask in the warmth, as their name would suggest. Meanwhile, the sharks that remained in shallower waters near Ireland's coast experienced neither extreme cold nor warmth as winter water temperatures ranged from 9 C to 17 C Unlike their offshore counterparts, the stay-at-home sharks showed little variation in depth during the six months the four animals were tracked. Their newly published study appears in the journal Environmental Biology of Fishes. As to why two lingered and the other two swam south, Mensink's team doesn't yet have an answer. Study co-author Jonathan Houghton of Queen's University Belfast said, \"This study tempts us to think about basking sharks as an oceanic species that aggregates in coastal hotspots for several months of the year (most likely for reproduction), rather than a coastal species that reluctantly heads out into the ocean when decreasing water temperatures force them to.\" The findings are a reminder that research into ocean habitats and sea animals' habits must include both depth and distance, Mensink said. \"We have to think about the ocean as a three-dimensional place.\" One important lesson of the study is that conservation of deep-ocean habitats is essential to the creatures' survival, said Queen's University Belfast researcher Emmett Johnston, lead author of the study. \"Likewise, further evidence of individual basking sharks occupying Irish coastal waters year-round has significant implications for national and European conservation efforts.\" Basking sharks are the second-largest fish in the ocean (behind whale sharks) and use their enormous mouths and gill-rakers to filter-feed tiny organisms such as zooplankton. They are deemed a vulnerable species globally. In Canada, they have been designated an endangered species off the Pacific coast. The team is collaborating on basking sharks as part of the major EU SeaMonitor, which with partners in Ireland, Northern Ireland, Scotland, Canada and the U.S., is developing a collective conservation strategy for wide-ranging marine species. Mensink's teaching and research into basking sharks includes a plan to bring Western undergraduate students into the fishes' ocean habitat through an augmented reality app in March, when they will, virtually, immerse themselves in the ocean ecosystem and \"swim\" beside the creatures. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Long-distance migrations by marine vertebrates are often triggered by pronounced environmental cues. For the endangered basking shark ( Cetorhinus maximus ), seasonal changes in water temperature are frequently proposed as a cue for aggregation within (and dispersal from) coastal hotspots. The inference is that such movements reflect year-round occupancy within a given thermal ‘envelope’. However, the marked variance in timing, direction and depth of dispersal movements hint at a more nuanced explanation for basking sharks. Here, using data from pop-off archival transmitters deployed on individuals in Irish waters, we explored whether autumnal decreases in water temperature triggered departure from coastal habitats and how depth and location shaped the sharks’ realised thermal environment over time. Temperature was not an apparent driver of dispersal from coastal seas, and variance in daily temperature ranges reflected occupancy of different habitats; coastal mixed/stratified and offshore subtropical/tropical waters. Furthermore, individuals that moved offshore and into more southern latitudes off Africa, exhibited a distinct daily cycle of deep dives (00:00–12:00, 200 m–700 m; 12:00–00:00, 0–300 m), experiencing a more extreme range of temperatures (6.8–27.4 °C), including cooler minimum temperatures, than those remaining in European coastal habitat (9.2–17.6 °C). Collectively, these findings challenge the supposition that temperature serves as a universal driver of seasonal dispersal from coastal seas and prompts further studies of deep-water forays in offshore areas. Working on a manuscript? Avoid the common mistakes Introduction Animal migrations are defined by their reciprocity and predictability, differentiating them from other movement strategies such as nomadism, invasions and dispersal (e.g. Newson et al. 2009 ; Teitelbaum and Mueller 2019 ). For marine vertebrates, the most frequently documented migrations are seasonal (Luschi 2013 ), with animals moving in response to shifts in prey availability (Corkeron and Connor 1999 ) and/or physiological constraints aligned with changes in their ambient environment such as water temperature (Schlaff et al. 2014 ). In response to rapidly warming seas, effective plans for conservation and management must recognise that migration patterns may not be static because migration routes can shift and the timing of migratory movements can be dependent on fluid environmental conditions as they are experienced (Hays et al. 2019 ; Senner et al. 2020 ). Such management considerations are magnified for long-distance migrants that traverse territorial boundaries adding a layer of political complexity (e.g. Newson et al. 2009 ; Mackelworth et al. 2019 ; Mason et al. 2020 ). Seasonal shifts in environmental conditions have been proposed as dispersal cues for basking sharks ( Cetorhinus maximus ) that aggregate in coastal hotspots at temperate latitudes during summer months, moving typically into offshore areas with the onset of autumn (Sims et al. 2003 ; Gore et al. 2008 ; Skomal et al. 2009 ; Doherty et al. 2017a , 2017b , 2019 ; Braun et al. 2018 ; Dolton et al. 2019 ). Oscillations in plankton abundance provide an intuitive explanation for this pattern (Sims and Reid 2002 ), but prey densities appear adequate for year-round foraging (Sims 1999 ) and residence in coastal seas (Doherty et al. 2017a , b ). Likewise, water temperature has been proposed frequently as a cue for both seasonal aggregation and subsequent dispersal of basking sharks (NW Atlantic: Skomal et al. 2009 ; Siders et al. 2013 ; Braun et al. 2018 —NE Atlantic: Berrow and Heardman 1994 ; Cotton et al. 2005 ; Priede and Miller 2009 ; Witt et al. 2012 ; Miller et al. 2015 ; Austin et al. 2019 ; Doherty et al. 2019 ). The broad inference is that latitudinal movements, triggered by thermal cues, may allow individuals to remain within a given ‘envelope’ of temperatures (i.e. an optimal thermal range) throughout the year irrespective of season. Certainly, movements of basking sharks in the Northwest Atlantic appear to mirror seasonal changes in water temperature, with individuals ranging from Cape Cod, USA, to tropical waters (Skomal et al. 2009 ; Hoogenboom et al. 2015 ; Braun et al. 2018 ). Despite evidence of water temperature as a driver of basking shark movements, winter dispersal from coastal seas is not ubiquitous (Gore et al. 2008 ; Doherty et al. 2017a ), raising an interesting question. Quite simply, if migration from coastal areas is to maintain a thermal envelope, why do some animals stay and others disperse? Recent evidence from beyond the Atlantic may provide some insights, with Finucci et al. ( 2021 ) revealing that sea surface temperature (SST) aligned poorly with basking shark habitat suitability. Taken together, these findings hint at a more nuanced role for temperature in dispersal, or distinct regional differences in behaviour. Within this overall context, we examined the movements and behaviour of basking sharks in the Northeast Atlantic displaying markedly different ‘overwintering’ strategies, namely, residency in temperate coastal seas and long-distance dispersal offshore. Using archived temperature, location and depth data relayed via animal-borne satellite transmitters, we initially questioned whether decreases in coastal water temperatures during late boreal summer triggered dispersal from coastal seas in the NE Atlantic. Subsequently, we explored how depth and location shaped the sharks’ realised thermal environment over time. Methods Device deployment site Searches for sharks were conducted during calm (Beaufort Force < 3) sunny conditions to maximise the likelihood of encounters. Basking sharks were tagged between the 26th of July and the 8th of August 2012 at Malin Head, Ireland (55.37 ○ N, 7.40 ○ W). This deployment time frame was chosen to maximise data recording across autumn and winter months when sharks are known to disperse from coastal seas around Great Britain and Ireland (Sims et al. 2003 ; Doherty et al. 2017a ; Dolton et al. 2019 ). The waters around Malin Head are a seasonal aggregation area (hotspot) for basking sharks in the North East Atlantic (Johnston et al. 2019 ). Water temperature at the deployment site was recorded year-round, for fisheries purposes by the Irish Marine Institute, using Tidbit temperature probes (location: 7.55028° W, 55.15845° N) deployed at 1-m and 11-m depths (Marine Institute Data Catalogue, 2012). To illustrate the seasonal change<|im_end|> <|im_start|>assistant If basking sharks were like Canadians, their migration habits might be easily explained: Head south to avoid winter's chill, and north again to enjoy summer's warmth. It turns out basking sharks are a more complex puzzle, Western biology professor Paul Mensink and his colleagues discovered while examining the seasonal movements of the enormous fish. Mensink and fellow researchers at Queen's University Belfast in Northern Ireland tracked four basking sharks—so large they can reach the size of a school bus—off the northernmost tip of Ireland to find out where they overwinter, and why. They affixed tags that would record the sharks' location, along with water temperature and depth. "The assumption was that they swim to Ireland's coastal waters for the summer, because of its really productive feeding areas, and then take off for the south in winter where it's warmer. We initially thought that water temperature must be the trigger for them to leave," Mensink said. "They blew our assumptions out of the water." Two of the four sharks, surprising the researchers, stayed put. The other two migrated south to tropical and subtropical waters off the African coast, as expected. But instead of lounging in warm waters there, these two spent much of their time in water that was deeper—and much colder—than if they'd stayed nearer to Ireland. Early each morning, these sharks would dive to depths of 200 to 700 meters, return near the surface near midday, then submerge to the chilly depths in the evening. "It was like clockwork," said Mensink, a marine ecologist who specializes in educational technology and is a teaching fellow in Western's Faculty of Science. "It's almost like the dive pattern of an animal that has to come up to the surface to breathe air—but, of course, they don't." During their dive cycle, the sharks put themselves through an extreme range of water temperatures: 27 C near the surface and a frigid 7 C in the depths. So why would any rational, cold-blooded creature do that? Pair of basking sharks in Inishtrahull Sound, Ireland. Credit: Emmett Johnston, Queen’s University Belfast "Ultimately, what we suspect is they're going down to feed in what we call the deep scattering layer, which is chock full of gelatinous zooplankton and other things they feed on," Mensink said. And at midday, they rise nearer the surface to bask in the warmth, as their name would suggest. Meanwhile, the sharks that remained in shallower waters near Ireland's coast experienced neither extreme cold nor warmth as winter water temperatures ranged from 9 C to 17 C Unlike their offshore counterparts, the stay-at-home sharks showed little variation in depth during the six months the four animals were tracked. Their newly published study appears in the journal Environmental Biology of Fishes. As to why two lingered and the other two swam south, Mensink's team doesn't yet have an answer. Study co-author Jonathan Houghton of Queen's University Belfast said, "This study tempts us to think about basking sharks as an oceanic species that aggregates in coastal hotspots for several months of the year (most likely for reproduction), rather than a coastal species that reluctantly heads out into the ocean when decreasing water temperatures force them to." The findings are a reminder that research into ocean habitats and sea animals' habits must include both depth and distance, Mensink said. "We have to think about the ocean as a three-dimensional place." One important lesson of the study is that conservation of deep-ocean habitats is essential to the creatures' survival, said Queen's University Belfast researcher Emmett Johnston, lead author of the study. "Likewise, further evidence of individual basking sharks occupying Irish coastal waters year-round has significant implications for national and European conservation efforts." Basking sharks are the second-largest fish in the ocean (behind whale sharks) and use their enormous mouths and gill-rakers to filter-feed tiny organisms such as zooplankton. They are deemed a vulnerable species globally. In Canada, they have been designated an endangered species off the Pacific coast. The team is collaborating on basking sharks as part of the major EU SeaMonitor, which with partners in Ireland, Northern Ireland, Scotland, Canada and the U.S., is developing a collective conservation strategy for wide-ranging marine species. Mensink's teaching and research into basking sharks includes a plan to bring Western undergraduate students into the fishes' ocean habitat through an augmented reality app in March, when they will, virtually, immerse themselves in the ocean ecosystem and "swim" beside the creatures. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 5843, 74908, 17500, 555, 29691, 67861, 99868, 527, 3629, 22900, 555, 38617, 12434, 57016, 13, 1789, 279, 52356, 293, 71805, 44892, 320, 356, 295, 269, 42657, 355, 31127, 355, 7026, 36899, 4442, 304, 3090, 9499, 527, 14134, 11223, 439, 264, 50498, 369, 52729, 2949, 320, 438, 79835, 278, 505, 8, 35335, 4106, 68110, 13, 578, 45478, 374, 430, 1778, 19567, 8881, 1060, 21691, 66419, 2949, 264, 2728, 29487, 3451, 268, 19384, 24535, 4452, 11, 279, 13160, 33373, 304, 18912, 11, 5216, 323, 8149, 315, 79835, 278, 19567, 13310, 520, 264, 810, 82891, 16540, 369, 293, 71805, 61535, 13, 5810, 11, 1701, 828, 505, 2477, 12744, 95047, 1380, 83189, 27167, 389, 7931, 304, 18088, 21160, 11, 584, 36131, 3508, 42774, 278, 43154, 304, 3090, 9499, 22900, 25959, 505, 35335, 71699, 323, 1268, 8149, 323, 3813, 27367, 279, 61535, 529, 41193, 29487, 4676, 927, 892, 13, 38122, 574, 539, 459, 10186, 5696, 315, 79835, 278, 505, 35335, 52840, 11, 323, 33373, 304, 7446, 9499, 21986, 27000, 66419, 315, 2204, 71699, 26, 35335, 9709, 14, 496, 266, 1908, 323, 39500, 42129, 51172, 5640, 51172, 21160, 13, 24296, 11, 7931, 430, 7882, 39500, 323, 1139, 810, 18561, 6987, 21237, 1022, 10384, 11, 51713, 264, 12742, 7446, 11008, 315, 5655, 94521, 320, 410, 25, 410, 4235, 717, 25, 410, 11, 220, 1049, 296, 4235, 7007, 296, 26, 220, 717, 25, 410, 4235, 410, 25, 410, 11, 220, 15, 4235, 3101, 296, 705, 25051, 264, 810, 14560, 2134, 315, 20472, 320, 21, 13, 23, 4235, 1544, 13, 19, 37386, 34, 705, 2737, 36921, 8187, 20472, 11, 1109, 1884, 9861, 304, 7665, 35335, 39646, 320, 24, 13, 17, 4235, 1114, 13, 21, 37386, 34, 570, 21153, 3210, 11, 1521, 14955, 8815, 279, 1043, 3571, 430, 9499, 17482, 439, 264, 20789, 5696, 315, 36899, 79835, 278, 505, 35335, 52840, 323, 52032, 4726, 7978, 315, 5655, 55051, 369, 954, 304, 39500, 5789, 13, 22938, 389, 264, 47913, 30, 35106, 279, 4279, 21294, 29438, 21995, 17500, 527, 4613, 555, 872, 67642, 9103, 323, 7168, 2968, 11, 2204, 23747, 1124, 505, 1023, 7351, 15174, 1778, 439, 9859, 329, 2191, 11, 1558, 88771, 323, 79835, 278, 320, 68, 1326, 13, 1561, 942, 1880, 453, 13, 220, 1049, 24, 2652, 2722, 57743, 59611, 323, 32767, 220, 679, 24, 7609, 1789, 29691, 67861, 99868, 11, 279, 1455, 14134, 27470, 17500, 527, 36899, 320, 43, 355, 14946, 220, 679, 18, 7026, 449, 10099, 7366, 304, 2077, 311, 29735, 304, 37693, 18539, 320, 34, 672, 20110, 323, 58280, 220, 2550, 24, 883, 323, 5255, 53194, 17413, 27210, 449, 4442, 304, 872, 35288, 4676, 1778, 439, 3090, 9499, 320, 31224, 75, 2715, 1880, 453, 13, 220, 679, 19, 7609, 763, 2077, 311, 19019, 24808, 52840, 11, 7524, 6787, 369, 29711, 323, 6373, 2011, 44917, 430, 12172, 12912, 1253, 539, 387, 1118, 1606, 12172, 11543, 649, 6541, 323, 279, 18912, 315, 9971, 5382, 19567, 649, 387, 18222, 389, 15962, 12434, 4787, 439, 814, 527, 10534, 320, 39, 954, 1880, 453, 13, 220, 679, 24, 2652, 5476, 1215, 1880, 453, 13, 220, 2366, 15, 7609, 15483, 6373, 38864, 527, 8622, 1908, 369, 1317, 74908, 32087, 430, 38646, 52482, 23546, 7999, 264, 6324, 315, 5054, 23965, 320, 68, 1326, 13, 1561, 942, 1880, 453, 13, 220, 1049, 24, 2652, 33491, 301, 20069, 1880, 453, 13, 220, 679, 24, 2652, 29927, 1880, 453, 13, 220, 2366, 15, 7609, 14598, 278, 29735, 304, 12434, 4787, 617, 1027, 11223, 439, 79835, 278, 57016, 369, 293, 71805, 61535, 320, 356, 295, 269, 42657, 355, 31127, 355, 883, 430, 24069, 304, 35335, 4106, 68110, 520, 6940, 349, 6987, 21237, 2391, 7474, 4038, 11, 7366, 11383, 1139, 39500, 5789, 449, 279, 42080, 315, 42774, 320, 50, 5861, 1880, 453, 13, 220, 1049, 18, 2652, 49625, 1880, 453, 13, 220, 1049, 23, 2652, 4923, 53911, 1880, 453, 13, 220, 1049, 24, 2652, 423, 2319, 1368, 1880, 453, 13, 220, 679, 22, 64, 1174, 220, 679, 22, 65, 1174, 220, 679, 24, 2652, 70703, 1880, 453, 13, 220, 679, 23, 2652, 25227, 783, 1880, 453, 13, 220, 679, 24, 7609, 56736, 484, 811, 304, 73187, 783, 37492, 3493, 459, 42779, 16540, 369, 420, 5497, 320, 50, 5861, 323, 38774, 220, 1049, 17, 7026, 719, 37693, 90816, 5101, 26613, 369, 1060, 21691, 369, 4210, 320, 50, 5861, 220, 2550, 24, 883, 323, 22423, 304, 35335, 52840, 320, 35, 2319, 1368, 1880, 453, 13, 220, 679, 22, 64, 1174, 293, 7609, 50487, 11, 3090, 9499, 706, 1027, 11223, 14134, 439, 264, 50498, 369, 2225, 36899, 52729, 323, 17876, 79835, 278, 315, 293, 71805, 61535, 320, 70314, 23179, 25, 4923, 53911, 1880, 453, 13, 220, 1049, 24, 2652, 328, 13572, 1880, 453, 13, 220, 679, 18, 2652, 70703, 1880, 453, 13, 220, 679, 23, 2001, 4031, 23179, 25, 9084, 654, 323, 95208, 1543, 220, 2550, 19, 2652, 38796, 1880, 453, 13, 220, 1049, 20, 2652, 393, 4588, 68, 323, 17472, 220, 1049, 24, 2652, 83276, 1880, 453, 13, 220, 679, 17, 2652, 17472, 1880, 453, 13, 220, 679, 20, 2652, 19816, 1880, 453, 13, 220, 679, 24, 2652, 423, 2319, 1368, 1880, 453, 13, 220, 679, 24, 7609, 578, 7353, 45478, 374, 430, 6987, 13138, 992, 19567, 11, 22900, 555, 29487, 57016, 11, 1253, 2187, 7931, 311, 7293, 2949, 264, 2728, 3451, 268, 19384, 529, 315, 20472, 320, 72, 1770, 13, 459, 23669, 29487, 2134, 8, 6957, 279, 1060, 76653, 315, 3280, 13, 53466, 11, 19567, 315, 293, 71805, 61535, 304, 279, 40505, 23179, 5101, 311, 18327, 36899, 4442, 304, 3090, 9499, 11, 449, 7931, 24950, 505, 29715, 34777, 11, 7427, 11, 311, 35148, 21160, 320, 19847, 53911, 1880, 453, 13, 220, 1049, 24, 2652, 17723, 11968, 96416, 1880, 453, 13, 220, 679, 20, 2652, 70703, 1880, 453, 13, 220, 679, 23, 7609, 18185, 6029, 315, 3090, 9499, 439, 264, 5696, 315, 293, 71805, 44892, 19567, 11, 12688, 79835, 278, 505, 35335, 52840, 374, 539, 64564, 320, 38, 461, 1880, 453, 13, 220, 1049, 23, 2652, 423, 2319, 1368, 1880, 453, 13, 220, 679, 22, 64, 7026, 19054, 459, 7185, 3488, 13, 58795, 5042, 11, 422, 12172, 505, 35335, 5789, 374, 311, 10519, 264, 29487, 35498, 11, 3249, 656, 1063, 10099, 4822, 323, 3885, 834, 82344, 30, 35390, 6029, 505, 7953, 279, 23179, 1253, 3493, 1063, 26793, 11, 449, 5767, 53469, 1880, 453, 13, 320, 220, 2366, 16, 883, 31720, 430, 9581, 7479, 9499, 320, 50, 790, 8, 27210, 31555, 449, 293, 71805, 44892, 39646, 81728, 13, 57074, 3871, 11, 1521, 14955, 13310, 520, 264, 810, 82891, 3560, 369, 9499, 304, 79835, 278, 11, 477, 12742, 15481, 12062, 304, 17432, 13, 25218, 420, 8244, 2317, 11, 584, 25078, 279, 19567, 323, 17432, 315, 293, 71805, 61535, 304, 279, 45680, 23179, 29040, 88101, 2204, 3451, 2017, 84028, 287, 529, 15174, 11, 32125, 11, 53966, 304, 6940, 349, 35335, 52840, 323, 1317, 74908, 79835, 278, 39500, 13, 12362, 53093, 9499, 11, 3813, 323, 8149, 828, 32951, 291, 4669, 10065, 1481, 17334, 24088, 1380, 83189, 11, 584, 15453, 29440, 3508, 43154, 304, 35335, 3090, 20472, 2391, 3389, 39786, 278, 7474, 22900, 79835, 278, 505, 35335, 52840, 304, 279, 8014, 23179, 13, 3804, 39742, 11, 584, 36131, 1268, 8149, 323, 3813, 27367, 279, 61535, 529, 41193, 29487, 4676, 927, 892, 13, 19331, 14227, 24047, 2816, 82269, 369, 61535, 1051, 13375, 2391, 19858, 320, 3513, 51628, 371, 11994, 366, 220, 18, 8, 40798, 4787, 311, 31127, 1082, 279, 29736, 315, 35006, 13, 426, 71805, 61535, 1051, 38213, 1990, 279, 220, 1627, 339, 315, 5887, 323, 279, 220, 23, 339, 315, 6287, 220, 679, 17, 520, 8560, 258, 11452, 11, 14990, 320, 2131, 13, 1806, 108437, 452, 11, 220, 22, 13, 1272, 108437, 468, 570, 1115, 24047, 892, 4124, 574, 12146, 311, 31127, 1082, 828, 14975, 4028, 42774, 323, 12688, 4038, 994, 61535, 527, 3967, 311, 834, 82344, 505, 35335, 52840, 2212, 8681, 13527, 323, 14990, 320, 50, 5861, 1880, 453, 13, 220, 1049, 18, 2652, 423, 2319, 1368, 1880, 453, 13, 220, 679, 22, 64, 2652, 25227, 783, 1880, 453, 13, 220, 679, 24, 7609, 578, 21160, 2212, 8560, 258, 11452, 527, 264, 36899, 52729, 3158, 320, 10847, 19164, 8, 369, 293, 71805, 61535, 304, 279, 4892, 6460, 23179, 320, 13379, 7876, 1880, 453, 13, 220, 679, 24, 7609, 10164, 9499, 520, 279, 24047, 2816, 574, 12715, 1060, 21691, 11, 369, 82596, 10096, 555, 279, 18088, 23820, 10181, 11, 1701, 350, 307, 4590, 9499, 63610, 320, 2588, 25, 220, 22, 13, 13506, 1591, 11877, 468, 11, 220, 2131, 13, 11286, 1774, 11877, 452, 8, 27167, 520, 220, 16, 1474, 323, 220, 806, 1474, 43957, 320, 12331, 483, 10181, 2956, 32321, 361, 11, 220, 679, 17, 570, 2057, 41468, 279, 36899, 2349, 128257, 198, 128256, 78191, 198, 2746, 293, 71805, 61535, 1051, 1093, 36262, 11, 872, 12172, 26870, 2643, 387, 6847, 11497, 25, 11452, 10007, 311, 5766, 12688, 596, 37401, 11, 323, 10411, 1578, 311, 4774, 7474, 596, 41463, 13, 1102, 10800, 704, 293, 71805, 61535, 527, 264, 810, 6485, 25649, 11, 11104, 34458, 14561, 7043, 24157, 771, 323, 813, 18105, 11352, 1418, 38936, 279, 36899, 19567, 315, 279, 23205, 7795, 13, 24157, 771, 323, 12637, 12074, 520, 16657, 596, 3907, 55339, 304, 17355, 14990, 34156, 3116, 293, 71805, 61535, 2345, 708, 3544, 814, 649, 5662, 279, 1404, 315, 264, 2978, 5951, 2345, 1885, 279, 18671, 3646, 11813, 315, 14990, 311, 1505, 704, 1405, 814, 927, 84028, 11, 323, 3249, 13, 2435, 3611, 3366, 9681, 430, 1053, 3335, 279, 61535, 6, 3813, 11, 3235, 449, 3090, 9499, 323, 8149, 13, 330, 791, 25329, 574, 430, 814, 16587, 311, 14990, 596, 35335, 21160, 369, 279, 7474, 11, 1606, 315, 1202, 2216, 27331, 26040, 5789, 11, 323, 1243, 1935, 1022, 369, 279, 10007, 304, 12688, 1405, 433, 596, 46039, 13, 1226, 15453, 3463, 430, 3090, 9499, 2011, 387, 279, 8346, 369, 1124, 311, 5387, 1359, 24157, 771, 1071, 13, 330, 7009, 42423, 1057, 32946, 704, 315, 279, 3090, 1210, 9220, 315, 279, 3116, 61535, 11, 15206, 279, 12074, 11, 20186, 2231, 13, 578, 1023, 1403, 73691, 10007, 311, 35148, 323, 42129, 51172, 21160, 1022, 279, 11904, 13962, 11, 439, 3685, 13, 2030, 4619, 315, 84244, 287, 304, 8369, 21160, 1070, 11, 1521, 1403, 7543, 1790, 315, 872, 892, 304, 3090, 430, 574, 19662, 17223, 1790, 76214, 2345, 54895, 422, 814, 4265, 20186, 87920, 311, 14990, 13, 23591, 1855, 6693, 11, 1521, 61535, 1053, 30963, 311, 43957, 315, 220, 1049, 311, 220, 7007, 20645, 11, 471, 3221, 279, 7479, 3221, 5209, 1316, 11, 1243, 1207, 19590, 311, 279, 81975, 43957, 304, 279, 11714, 13, 330, 2181, 574, 1093, 9042, 1816, 1359, 1071, 24157, 771, 11, 264, 29691, 12208, 16549, 889, 46672, 304, 16627, 5557, 323, 374, 264, 12917, 12637, 304, 11104, 596, 42904, 315, 10170, 13, 330, 2181, 596, 4661, 1093, 279, 30963, 5497, 315, 459, 10065, 430, 706, 311, 2586, 709, 311, 279, 7479, 311, 37397, 3805, 38542, 11, 315, 3388, 11, 814, 1541, 956, 1210, 12220, 872, 30963, 11008, 11, 279, 61535, 2231, 5694, 1555, 459, 14560, 2134, 315, 3090, 20472, 25, 220, 1544, 356, 3221, 279, 7479, 323, 264, 1448, 21596, 220, 22, 356, 304, 279, 43957, 13, 2100, 3249, 1053, 904, 25442, 11, 9439, 94003, 291, 17661, 656, 430, 30, 27086, 315, 293, 71805, 61535, 304, 763, 819, 376, 1494, 620, 14936, 11, 14990, 13, 16666, 25, 66555, 7211, 61582, 11, 16657, 753, 3907, 55339, 330, 67343, 11, 1148, 584, 15562, 374, 814, 2351, 2133, 1523, 311, 5510, 304, 1148, 584, 1650, 279, 5655, 72916, 6324, 11, 902, 374, 523, 1197, 2539, 315, 18316, 15111, 788, 19263, 56178, 1201, 783, 323, 1023, 2574, 814, 5510, 389, 1359, 24157, 771, 1071, 13, 1628, 520, 5209, 1316, 11, 814, 10205, 87920, 279, 7479, 311, 293, 1091, 304, 279, 41463, 11, 439, 872, 836, 1053, 4284, 13, 26982, 11, 279, 61535, 430, 14958, 304, 4985, 1223, 21160, 3221, 14990, 596, 13962, 10534, 14188, 14560, 9439, 6463, 41463, 439, 12688, 3090, 20472, 41829, 505, 220, 24, 356, 311, 220, 1114, 356, 27140, 872, 39500, 38495, 11, 279, 4822, 29883, 25389, 61535, 8710, 2697, 23851, 304, 8149, 2391, 279, 4848, 4038, 279, 3116, 10099, 1051, 34156, 13, 11205, 13945, 4756, 4007, 8111, 304, 279, 8486, 25027, 40023, 315, 17019, 288, 13, 1666, 311, 3249, 1403, 40609, 291, 323, 279, 1023, 1403, 2064, 309, 10007, 11, 24157, 771, 596, 2128, 3250, 956, 3686, 617, 459, 4320, 13, 19723, 1080, 43802, 24150, 473, 2509, 263, 315, 16657, 596, 3907, 55339, 1071, 11, 330, 2028, 4007, 1592, 13044, 603, 311, 1781, 922, 293, 71805, 61535, 439, 459, 18435, 292, 9606, 430, 71643, 304, 35335, 4106, 68110, 369, 3892, 4038, 315, 279, 1060, 320, 3646, 4461, 369, 39656, 705, 4856, 1109, 264, 35335, 9606, 430, 84185, 14971, 704, 1139, 279, 18435, 994, 44649, 3090, 20472, 5457, 1124, 311, 1210, 578, 14955, 527, 264, 27626, 430, 3495, 1139, 18435, 71699, 323, 9581, 10099, 6, 26870, 2011, 2997, 2225, 8149, 323, 6138, 11, 24157, 771, 1071, 13, 330, 1687, 617, 311, 1781, 922, 279, 18435, 439, 264, 2380, 33520, 2035, 1210, 3861, 3062, 18228, 315, 279, 4007, 374, 430, 29711, 315, 5655, 16405, 11455, 71699, 374, 7718, 311, 279, 20566, 6, 20237, 11, 1071, 16657, 596, 3907, 55339, 32185, 66555, 7211, 61582, 11, 3063, 3229, 315, 279, 4007, 13, 330, 73097, 25346, 11, 4726, 6029, 315, 3927, 293, 71805, 61535, 72280, 18088, 35335, 21160, 1060, 21691, 706, 5199, 25127, 369, 5426, 323, 7665, 29711, 9045, 1210, 426, 71805, 61535, 527, 279, 2132, 68067, 7795, 304, 279, 18435, 320, 30998, 485, 51119, 61535, 8, 323, 1005, 872, 23205, 65609, 323, 342, 484, 3880, 8476, 311, 4141, 87260, 13987, 44304, 1778, 439, 19263, 56178, 1201, 783, 13, 2435, 527, 25660, 264, 20134, 9606, 31550, 13, 763, 7008, 11, 814, 617, 1027, 24073, 459, 52356, 9606, 1022, 279, 16867, 13962, 13, 578, 2128, 374, 73301, 389, 293, 71805, 61535, 439, 961, 315, 279, 3682, 10013, 15379, 31198, 11, 902, 449, 8717, 304, 14990, 11, 17355, 14990, 11, 19627, 11, 7008, 323, 279, 549, 815, 2637, 374, 11469, 264, 22498, 29711, 8446, 369, 7029, 82105, 29691, 9606, 13, 24157, 771, 596, 12917, 323, 3495, 1139, 293, 71805, 61535, 5764, 264, 3197, 311, 4546, 11104, 41534, 4236, 1139, 279, 95461, 6, 18435, 39646, 1555, 459, 57088, 8903, 917, 304, 5587, 11, 994, 814, 690, 11, 21907, 11, 26612, 325, 5694, 304, 279, 18435, 26031, 323, 330, 2332, 318, 1, 30488, 279, 20566, 13, 220, 128257, 198 ]

2,418

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Guidelines Hypothesis Interesting Images Letter New Book Received Obituary Opinion Perspective Proceeding Paper Project Report Protocol Registered Report Reply Retraction Short Note Study Protocol Systematic Review Technical Note Tutorial Viewpoint All Article Types Advanced Search Section All Sections Air, Climate Change and Sustainability Bioeconomy of Sustainability Development Goals towards Sustainability Economic and Business Aspects of Sustainability Energy Sustainability Environmental Sustainability and Applications Green Building Hazards and Sustainability Health, Well-Being and Sustainability Pollution Prevention, Mitigation and Sustainability Psychology of Sustainability and Sustainable Development Resources and Sustainable Utilization Social Ecology and Sustainability Soil Conservation and Sustainability Sustainability in Geographic Science Sustainability, Biodiversity and Conservation Sustainable Agriculture Sustainable Chemical Engineering and Technology Sustainable Education and Approaches Sustainable Engineering and Science Sustainable Food Sustainable Forestry Sustainable Management Sustainable Materials Sustainable Oceans Sustainable Products and Services Sustainable Transportation Sustainable Urban and Rural Development Sustainable Water Management Tourism, Culture, and Heritage Waste and Recycling All Sections Special Issue All Special Issues (In)Corporate Sustainability: A Systemic Shift towards Sustainability 10th Anniversary of Sustainability—Recent Advances in Sustainability Studies 14th CIRIAF National Congress - Energy, Environment and Sustainable Development 15th CIRIAF National Congress – Environmental Footprint and Sustainable Development 16th CIRIAF National Congress – Sustainable Development, Environment and Human Health Protection 17th CIRIAF National Congress—Energy–Environmental Sustainability and Seismic Retrofit of Built Heritage 3D Printed Object or Molds for Educational Use: Design and Validation 3D Printing Applications and Sustainable Construction 3D Printing Influence in Engineering 3D Technology for Sustainable Education, Culture and Divulgation 40th Anniversary of 'The Limits to Growth' 4th Industrial Revolution and New Trends in Service Industry 5G, Energy Efficiency and Sustainability 5G: Smart Technology for Environment and Sustainable Development 5th World Sustainability Forum - Selected Papers 6th World Sustainability Forum - Selected Papers 7th World Sustainability Forum—Selected Papers 8th World Sustainability Forum—Selected Papers A Contextual and Dynamic Understanding of Sustainable Urbanisation A Decision-Making Model on the Impact of Vehicle Use on Urban Safety A Multidisciplinary Approach to Sustainability A Promising Approach: Nanotechnology A Research Agenda for Ecological Economics A Sustainable Revolution: Let's Go Sustainable to Get our Globe Cleaner A Systemic Perspective on Urban Food Supply: Assessing Different Types of Urban Agriculture Academic Contributions to the UNESCO 2019 Forum on Education for Sustainable Development and Global Citizenship Accounting, Financing and Governing Global Sustainability for Businesses and Societies Achieving a Just Transition in the Pursuit of Global Sustainability Achieving Sustainable Development Goals (SDGs) among Walking and Talking Achieving Sustainable Development Goals in COVID-19 Pandemic Times Achieving Sustainable Development of Enterprises through Digital Transformation Achieving Sustainable Public Transportation System: Travel Behaviors, New Technologies and Their Equity, Accessibility and Planning Implications Achieving Sustainable Village Development though Traditional and Innovative Approaches Achieving Zero Carbon Strategy: Towards What Direction Should Supply Chain Focus On? Adaptation or Extinction Adapting to Climate Change: The Interplay between International and Domestic Institutions in the Context of Climate Finance Adaptive Components for Building Performance Control Adaptive Reuse Processes: Bridging the Gap between Memory and New Values Additive Manufacturing and Sustainability in the Digital Age: People, Factories and Businesses of the Future Addressing Sustainability at a Community Scale Addressing Sustainable Development in the Digital Construction Age Advanced Analysis of Energy Economics and Sustainable Development in China in the Context of Carbon Neutrality Advanced Application of Green and Sustainable Computing Advanced Cutting-Edge Research on Applied Research on Human-Computer Interaction Advanced Forum for Sustainable Development Advanced IT based Future Sustainable Computing Advanced IT based Future Sustainable Computing Advanced Methodologies for Sustainability Assessment: Theory and Practice Advanced Science and Technology of Sustainable Development for Cities, Infrastructures, Living Spaces and Natural Environment: Including Collections from the Latest Papers of KRIS 2023 Advanced Technologies Applied to Renewable Energy Advanced Technology for Sustainable Development in Arid and Semi-Arid Regions Advanced Theory and Practice in Sustainable Sport Management Advances and Challenges of Green Chemistry and Engineering Advances and Challenges of Sustainability in/by Software Engineering Advances in Architectures, Big Data, and Machine Learning Techniques for Complex Internet of Things Systems Advances in Artificial Intelligence in Sustainable Business Management Advances in Corporate Governance Mechanisms and Corporate Social Responsibility Advances in Decision Making and Data Analysis for Sustainable Operations and Supply Chain Management in the Industry 4.0 Era Advances in Food and Non-Food Biomass Production, Processing and Use in Sub-Saharan Africa: Towards a Basis for a Regional Bioeconomy Advances in Gas Separation Technologies for Green Process Engineering Advances in Green Infrastructure Planning Advances in Hydrological Modelling, Quantitative Analysis and Prediction for a Changing Environment Advances in Industrial Risk Analysis and Management Advances in Machine Learning Technology in Information and Cyber Security Advances in Multiple Criteria Decision Making for Sustainability: Modeling and Applications Advances in Post Occupancy Evaluation Advances in Research and Sustainable Applications of Energy—Related Occupant Behavior in Buildings Advances in Rural and Aquatic Sustainability Advances in Sports Science and Physical Activity: New Methodological Perspectives Advances in Sustainability Oriented Innovations Advances in Sustainability Research at the University of Malta Advances in Sustainability Research from Poznan University of Technology Advances in Sustainability Research from the University of Oradea Advances in Sustainability: Selected Papers from 1st World Sustainability Forum Advances in Sustainability: Selected Papers from the Second World Sustainability Forum (2012) Advances in Sustainable Development: Selected Papers from 2016 Energy and Environment Knowledge Week Advances in Sustainable Drainage Systems and Stormwater Control Measures Advances in Sustainable Energy Systems and Environmental Remediation Technologies Advances in Sustainable Nanocomposites Advances in Sustainable Technology: The Lean 6S Methodology Advances in Sustainable Tourism and Responsible Travel Advances in the Sustainability and Resilience Interface at the Urban and Regional Levels: Sciences, Plans, Policies, and Actions for the Next Challenging Decades Advances of Digital Transformation in the Education Domain Advances of Sustainability Research: A Canadian Perspective Advances on Building Performance and Sustainability Advancing a Sustainable Future: Automation, Data Analysis, Modelling, and Simulations Advancing Sustainability through Well-Being Advancing Urban Sustainability through a Diverse Social-Ecological System Research Agenda Aerosol Pollution and Severe Weather Affordable Housing Planning for Sustainability After the Anthropocene: Time and Mobility Agricultural and Food Systems Sustainability: The Complex Challenge of Losses and Waste Agricultural Development", "role": "user" }, { "content": "The construction industry's green pivot faces a number of challenges, even as more city governments and home buyers are increasingly pushing for more sustainable new homes and buildings. Among the obstacles standing in the way of greener construction are the industry's natural cautious approach to innovation as well as its dominant profit models, which favor previously profitable habits and techniques. In a new paper published in the journal Sustainability, three Concordia researchers from the Next-Generation Cities Institute (NGCI) outline those obstacles and offer practical incentives local governments can offer to encourage private green real estate development. The study also looks at the key stakeholders and building life-cycle process to identify ways to reduce the industry's overall carbon footprint. Change is urgently needed, they write: according to the Global Alliance for Buildings and Construction and the United Nations Environment Program, construction and the built environment account for 38 percent of global greenhouse gas emissions. The study stands apart from other academic papers examining the construction industry. Its lead author, Ph.D. student Natalie Voland, is president of Montreal-based real estate developer Gestion Immobiliere Quo Vadis and co-director of Concordia's recently announced zero-carbon buildings accelerator. The paper relies largely on Voland's own experiences operating a certified B-Corp, part of an international movement that emphasizes sustainability through business. \"As a board member of the Montreal Climate Partnership, I realized very quickly that developers have no clue how to become climate neutral,\" she says. \"They didn't have the expertise or the knowledge, and the current business models do not work.\" Voland believes that this study, co-authored by Concordia Public Scholar Mostafa Saad and NGCI co-director Ursula Eicker, can be used as evidence that a massive shift towards greener buildings will eventually earn developers who create new business models standard profits for their investors and finance requirements. Sustainable precedents The authors write that the realities facing developers—the need for quick term returns on investment, stable financing and satisfying multiple stakeholders, among many others—can be addressed most easily by municipal policies and incentives that merge private goals with the public good. Fast-track zoning, density bonuses, tax breaks and expertise and supplier sharing are all tools cities can use to promote green projects. \"In my experience, these incentive-based types of zoning/regulatory processes were often blocked by city officials, who said that they would set a precedent of favorable treatment for green building projects,\" says Voland. That precedent would be the point. \"This way, the city would be telling a developer that if they build something that benefits the environment and the community, they would get an incentive that would benefit their financial models.\" Building on experience Eicker adds that Voland's experience contributes much needed depth to the subject area, which she says is lacking large datasets and academic literature. \"There is a real challenge in translating an individual like Natalie's experience into scientific facts,\" Eicker says. \"But we can substantiate parts of the existing literature by bringing her empirical knowledge into a systemic form, and that is what makes this paper so interesting. It is about real dynamics, and how we can make sustainable projects happen.\" \"This paper is like a map of what is out there now. We are mapping Natalie's experience in the industry and the real obstacles and barriers that exist,\" adds Saad. \"These may not be very evident to academics, who have to observe a subject from a very high level. We need this kind of practical experience to be able to get these insights in an academic way.\" The authors feel the paper's real-world applications can be used to explain the value of green buildings to developers, bankers and policymakers through their accelerator going forward. \"We are not trying to say, 'What is a better building?'\" explains Voland. \"We know what a better building is. It's about how we implement it.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Guidelines Hypothesis Interesting Images Letter New Book Received Obituary Opinion Perspective Proceeding Paper Project Report Protocol Registered Report Reply Retraction Short Note Study Protocol Systematic Review Technical Note Tutorial Viewpoint All Article Types Advanced Search Section All Sections Air, Climate Change and Sustainability Bioeconomy of Sustainability Development Goals towards Sustainability Economic and Business Aspects of Sustainability Energy Sustainability Environmental Sustainability and Applications Green Building Hazards and Sustainability Health, Well-Being and Sustainability Pollution Prevention, Mitigation and Sustainability Psychology of Sustainability and Sustainable Development Resources and Sustainable Utilization Social Ecology and Sustainability Soil Conservation and Sustainability Sustainability in Geographic Science Sustainability, Biodiversity and Conservation Sustainable Agriculture Sustainable Chemical Engineering and Technology Sustainable Education and Approaches Sustainable Engineering and Science Sustainable Food Sustainable Forestry Sustainable Management Sustainable Materials Sustainable Oceans Sustainable Products and Services Sustainable Transportation Sustainable Urban and Rural Development Sustainable Water Management Tourism, Culture, and Heritage Waste and Recycling All Sections Special Issue All Special Issues (In)Corporate Sustainability: A Systemic Shift towards Sustainability 10th Anniversary of Sustainability—Recent Advances in Sustainability Studies 14th CIRIAF National Congress - Energy, Environment and Sustainable Development 15th CIRIAF National Congress – Environmental Footprint and Sustainable Development 16th CIRIAF National Congress – Sustainable Development, Environment and Human Health Protection 17th CIRIAF National Congress—Energy–Environmental Sustainability and Seismic Retrofit of Built Heritage 3D Printed Object or Molds for Educational Use: Design and Validation 3D Printing Applications and Sustainable Construction 3D Printing Influence in Engineering 3D Technology for Sustainable Education, Culture and Divulgation 40th Anniversary of 'The Limits to Growth' 4th Industrial Revolution and New Trends in Service Industry 5G, Energy Efficiency and Sustainability 5G: Smart Technology for Environment and Sustainable Development 5th World Sustainability Forum - Selected Papers 6th World Sustainability Forum - Selected Papers 7th World Sustainability Forum—Selected Papers 8th World Sustainability Forum—Selected Papers A Contextual and Dynamic Understanding of Sustainable Urbanisation A Decision-Making Model on the Impact of Vehicle Use on Urban Safety A Multidisciplinary Approach to Sustainability A Promising Approach: Nanotechnology A Research Agenda for Ecological Economics A Sustainable Revolution: Let's Go Sustainable to Get our Globe Cleaner A Systemic Perspective on Urban Food Supply: Assessing Different Types of Urban Agriculture Academic Contributions to the UNESCO 2019 Forum on Education for Sustainable Development and Global Citizenship Accounting, Financing and Governing Global Sustainability for Businesses and Societies Achieving a Just Transition in the Pursuit of Global Sustainability Achieving Sustainable Development Goals (SDGs) among Walking and Talking Achieving Sustainable Development Goals in COVID-19 Pandemic Times Achieving Sustainable Development of Enterprises through Digital Transformation Achieving Sustainable Public Transportation System: Travel Behaviors, New Technologies and Their Equity, Accessibility and Planning Implications Achieving Sustainable Village Development though Traditional and Innovative Approaches Achieving Zero Carbon Strategy: Towards What Direction Should Supply Chain Focus On? Adaptation or Extinction Adapting to Climate Change: The Interplay between International and Domestic Institutions in the Context of Climate Finance Adaptive Components for Building Performance Control Adaptive Reuse Processes: Bridging the Gap between Memory and New Values Additive Manufacturing and Sustainability in the Digital Age: People, Factories and Businesses of the Future Addressing Sustainability at a Community Scale Addressing Sustainable Development in the Digital Construction Age Advanced Analysis of Energy Economics and Sustainable Development in China in the Context of Carbon Neutrality Advanced Application of Green and Sustainable Computing Advanced Cutting-Edge Research on Applied Research on Human-Computer Interaction Advanced Forum for Sustainable Development Advanced IT based Future Sustainable Computing Advanced IT based Future Sustainable Computing Advanced Methodologies for Sustainability Assessment: Theory and Practice Advanced Science and Technology of Sustainable Development for Cities, Infrastructures, Living Spaces and Natural Environment: Including Collections from the Latest Papers of KRIS 2023 Advanced Technologies Applied to Renewable Energy Advanced Technology for Sustainable Development in Arid and Semi-Arid Regions Advanced Theory and Practice in Sustainable Sport Management Advances and Challenges of Green Chemistry and Engineering Advances and Challenges of Sustainability in/by Software Engineering Advances in Architectures, Big Data, and Machine Learning Techniques for Complex Internet of Things Systems Advances in Artificial Intelligence in Sustainable Business Management Advances in Corporate Governance Mechanisms and Corporate Social Responsibility Advances in Decision Making and Data Analysis for Sustainable Operations and Supply Chain Management in the Industry 4.0 Era Advances in Food and Non-Food Biomass Production, Processing and Use in Sub-Saharan Africa: Towards a Basis for a Regional Bioeconomy Advances in Gas Separation Technologies for Green Process Engineering Advances in Green Infrastructure Planning Advances in Hydrological Modelling, Quantitative Analysis and Prediction for a Changing Environment Advances in Industrial Risk Analysis and Management Advances in Machine Learning Technology in Information and Cyber Security Advances in Multiple Criteria Decision Making for Sustainability: Modeling and Applications Advances in Post Occupancy Evaluation Advances in Research and Sustainable Applications of Energy—Related Occupant Behavior in Buildings Advances in Rural and Aquatic Sustainability Advances in Sports Science and Physical Activity: New Methodological Perspectives Advances in Sustainability Oriented Innovations Advances in Sustainability Research at the University of Malta Advances in Sustainability Research from Poznan University of Technology Advances in Sustainability Research from the University of Oradea Advances in Sustainability: Selected Papers from 1st World Sustainability Forum Advances in Sustainability: Selected Papers from the Second World Sustainability Forum (2012) Advances in Sustainable Development: Selected Papers from 2016 Energy and Environment Knowledge Week Advances in Sustainable Drainage Systems and Stormwater Control Measures Advances in Sustainable Energy Systems and Environmental Remediation Technologies Advances in Sustainable Nanocomposites Advances in Sustainable Technology: The Lean 6S Methodology Advances in Sustainable Tourism and Responsible Travel Advances in the Sustainability and Resilience Interface at the Urban and Regional Levels: Sciences, Plans, Policies, and Actions for the Next Challenging Decades Advances of Digital Transformation in the Education Domain Advances of Sustainability Research: A Canadian Perspective Advances on Building Performance and Sustainability Advancing a Sustainable Future: Automation, Data Analysis, Modelling, and Simulations Advancing Sustainability through Well-Being Advancing Urban Sustainability through a Diverse Social-Ecological System Research Agenda Aerosol Pollution and Severe Weather Affordable Housing Planning for Sustainability After the Anthropocene: Time and Mobility Agricultural and Food Systems Sustainability: The Complex Challenge of Losses and Waste Agricultural Development<|im_end|> <|im_start|>assistant The construction industry's green pivot faces a number of challenges, even as more city governments and home buyers are increasingly pushing for more sustainable new homes and buildings. Among the obstacles standing in the way of greener construction are the industry's natural cautious approach to innovation as well as its dominant profit models, which favor previously profitable habits and techniques. In a new paper published in the journal Sustainability, three Concordia researchers from the Next-Generation Cities Institute (NGCI) outline those obstacles and offer practical incentives local governments can offer to encourage private green real estate development. The study also looks at the key stakeholders and building life-cycle process to identify ways to reduce the industry's overall carbon footprint. Change is urgently needed, they write: according to the Global Alliance for Buildings and Construction and the United Nations Environment Program, construction and the built environment account for 38 percent of global greenhouse gas emissions. The study stands apart from other academic papers examining the construction industry. Its lead author, Ph.D. student Natalie Voland, is president of Montreal-based real estate developer Gestion Immobiliere Quo Vadis and co-director of Concordia's recently announced zero-carbon buildings accelerator. The paper relies largely on Voland's own experiences operating a certified B-Corp, part of an international movement that emphasizes sustainability through business. "As a board member of the Montreal Climate Partnership, I realized very quickly that developers have no clue how to become climate neutral," she says. "They didn't have the expertise or the knowledge, and the current business models do not work." Voland believes that this study, co-authored by Concordia Public Scholar Mostafa Saad and NGCI co-director Ursula Eicker, can be used as evidence that a massive shift towards greener buildings will eventually earn developers who create new business models standard profits for their investors and finance requirements. Sustainable precedents The authors write that the realities facing developers—the need for quick term returns on investment, stable financing and satisfying multiple stakeholders, among many others—can be addressed most easily by municipal policies and incentives that merge private goals with the public good. Fast-track zoning, density bonuses, tax breaks and expertise and supplier sharing are all tools cities can use to promote green projects. "In my experience, these incentive-based types of zoning/regulatory processes were often blocked by city officials, who said that they would set a precedent of favorable treatment for green building projects," says Voland. That precedent would be the point. "This way, the city would be telling a developer that if they build something that benefits the environment and the community, they would get an incentive that would benefit their financial models." Building on experience Eicker adds that Voland's experience contributes much needed depth to the subject area, which she says is lacking large datasets and academic literature. "There is a real challenge in translating an individual like Natalie's experience into scientific facts," Eicker says. "But we can substantiate parts of the existing literature by bringing her empirical knowledge into a systemic form, and that is what makes this paper so interesting. It is about real dynamics, and how we can make sustainable projects happen." "This paper is like a map of what is out there now. We are mapping Natalie's experience in the industry and the real obstacles and barriers that exist," adds Saad. "These may not be very evident to academics, who have to observe a subject from a very high level. We need this kind of practical experience to be able to get these insights in an academic way." The authors feel the paper's real-world applications can be used to explain the value of green buildings to developers, bankers and policymakers through their accelerator going forward. "We are not trying to say, 'What is a better building?'" explains Voland. "We know what a better building is. It's about how we implement it." <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 48528, 39515, 78, 13491, 71770, 12041, 27757, 1561, 6017, 39517, 507, 4590, 3620, 60767, 70288, 41870, 287, 18343, 5907, 8423, 25590, 36639, 8423, 18321, 10608, 16597, 10928, 7181, 19723, 25590, 744, 780, 10506, 27766, 7181, 49107, 2806, 2837, 2052, 13659, 21431, 21844, 7694, 11360, 2052, 60137, 6690, 11, 31636, 10604, 323, 89812, 24432, 68, 71171, 315, 89812, 11050, 55293, 7119, 89812, 23362, 323, 8184, 1666, 8132, 315, 89812, 12634, 89812, 25027, 89812, 323, 32625, 7997, 17283, 32595, 2402, 323, 89812, 6401, 11, 8489, 12, 34242, 323, 89812, 96201, 36947, 11, 22515, 18413, 323, 89812, 36673, 315, 89812, 323, 61593, 11050, 16607, 323, 61593, 10377, 2065, 9983, 78375, 323, 89812, 76619, 45435, 323, 89812, 89812, 304, 66542, 10170, 89812, 11, 426, 3205, 3050, 323, 45435, 61593, 37963, 61593, 36424, 17005, 323, 12053, 61593, 11930, 323, 19157, 14576, 61593, 17005, 323, 10170, 61593, 12369, 61593, 8371, 4720, 61593, 9744, 61593, 32009, 61593, 507, 43320, 61593, 15899, 323, 8471, 61593, 30978, 61593, 29422, 323, 58320, 11050, 61593, 10164, 9744, 52652, 11, 21023, 11, 323, 34243, 49522, 323, 81685, 2052, 60137, 9984, 26292, 2052, 9984, 37543, 320, 644, 8, 87628, 89812, 25, 362, 744, 292, 27608, 7119, 89812, 220, 605, 339, 47898, 315, 89812, 2345, 26198, 91958, 304, 89812, 19241, 220, 975, 339, 356, 2871, 5987, 37, 5165, 8151, 482, 12634, 11, 11847, 323, 61593, 11050, 220, 868, 339, 356, 2871, 5987, 37, 5165, 8151, 1389, 25027, 15819, 1374, 323, 61593, 11050, 220, 845, 339, 356, 2871, 5987, 37, 5165, 8151, 1389, 61593, 11050, 11, 11847, 323, 11344, 6401, 19721, 220, 1114, 339, 356, 2871, 5987, 37, 5165, 8151, 2345, 33775, 4235, 83166, 89812, 323, 1369, 55194, 58498, 315, 34154, 34243, 220, 18, 35, 71065, 3075, 477, 386, 18938, 369, 46945, 5560, 25, 7127, 323, 19490, 220, 18, 35, 51869, 32625, 323, 61593, 24987, 220, 18, 35, 51869, 76040, 304, 17005, 220, 18, 35, 12053, 369, 61593, 11930, 11, 21023, 323, 8940, 56099, 367, 220, 1272, 339, 47898, 315, 364, 791, 72955, 311, 34871, 6, 220, 19, 339, 25563, 22910, 323, 1561, 50730, 304, 5475, 24780, 220, 20, 38, 11, 12634, 67667, 323, 89812, 220, 20, 38, 25, 16147, 12053, 369, 11847, 323, 61593, 11050, 220, 20, 339, 4435, 89812, 17997, 482, 30402, 45231, 220, 21, 339, 4435, 89812, 17997, 482, 30402, 45231, 220, 22, 339, 4435, 89812, 17997, 2345, 6450, 45231, 220, 23, 339, 4435, 89812, 17997, 2345, 6450, 45231, 362, 9805, 940, 323, 22648, 46551, 315, 61593, 29422, 8082, 362, 41525, 5364, 1802, 5008, 389, 279, 29680, 315, 25736, 5560, 389, 29422, 19220, 362, 22950, 307, 3510, 44550, 54184, 311, 89812, 362, 18042, 3876, 54184, 25, 33242, 52536, 362, 8483, 58662, 369, 37211, 5848, 35300, 362, 61593, 22910, 25, 6914, 596, 6122, 61593, 311, 2175, 1057, 41910, 76319, 362, 744, 292, 70288, 389, 29422, 12369, 30909, 25, 82935, 287, 34496, 21431, 315, 29422, 37963, 42170, 97104, 311, 279, 81876, 220, 679, 24, 17997, 389, 11930, 369, 61593, 11050, 323, 8121, 94836, 45344, 11, 93648, 323, 94984, 1251, 8121, 89812, 369, 71190, 323, 42509, 26640, 42224, 4504, 264, 4702, 38821, 304, 279, 71760, 3159, 315, 8121, 89812, 42224, 4504, 61593, 11050, 55293, 320, 5608, 82252, 8, 4315, 40155, 323, 62022, 42224, 4504, 61593, 11050, 55293, 304, 20562, 12, 777, 34606, 8274, 8691, 42224, 4504, 61593, 11050, 315, 67056, 1555, 14434, 54752, 42224, 4504, 61593, 3142, 30978, 744, 25, 18589, 14954, 22965, 11, 1561, 25579, 323, 11205, 58588, 11, 81372, 323, 28780, 14727, 10939, 42224, 4504, 61593, 25036, 11050, 3582, 46560, 323, 98669, 19157, 14576, 42224, 4504, 18811, 22208, 28845, 25, 94965, 3639, 19438, 12540, 30909, 29625, 26891, 1952, 30, 59531, 367, 477, 9634, 22073, 2467, 391, 1303, 311, 31636, 10604, 25, 578, 5783, 1387, 1990, 7327, 323, 52849, 88880, 304, 279, 9805, 315, 31636, 23261, 87508, 35185, 369, 17283, 21304, 7935, 87508, 1050, 817, 63403, 25, 32437, 3252, 279, 59015, 1990, 14171, 323, 1561, 26028, 2758, 3486, 42177, 323, 89812, 304, 279, 14434, 13381, 25, 9029, 11, 37812, 2490, 323, 71190, 315, 279, 12781, 9356, 287, 89812, 520, 264, 12332, 25635, 9356, 287, 61593, 11050, 304, 279, 14434, 24987, 13381, 21844, 18825, 315, 12634, 35300, 323, 61593, 11050, 304, 5734, 304, 279, 9805, 315, 22208, 4275, 80381, 2786, 21844, 7473, 315, 7997, 323, 61593, 46879, 21844, 63525, 12, 11918, 8483, 389, 43608, 8483, 389, 11344, 12, 38432, 43807, 21844, 17997, 369, 61593, 11050, 21844, 8871, 3196, 12781, 61593, 46879, 21844, 8871, 3196, 12781, 61593, 46879, 21844, 6872, 9268, 369, 89812, 37357, 25, 31535, 323, 28082, 21844, 10170, 323, 12053, 315, 61593, 11050, 369, 38373, 11, 15268, 969, 47194, 11, 19048, 69156, 323, 18955, 11847, 25, 56221, 26394, 505, 279, 29257, 45231, 315, 66269, 1669, 220, 2366, 18, 21844, 25579, 43608, 311, 93438, 12634, 21844, 12053, 369, 61593, 11050, 304, 1676, 307, 323, 55738, 6830, 1907, 78447, 21844, 31535, 323, 28082, 304, 61593, 18707, 9744, 91958, 323, 69778, 315, 7997, 42846, 323, 17005, 91958, 323, 69778, 315, 89812, 304, 68833, 4476, 17005, 91958, 304, 24979, 1439, 11, 6295, 2956, 11, 323, 13257, 21579, 66044, 369, 22872, 8191, 315, 20695, 15264, 91958, 304, 59294, 22107, 304, 61593, 8184, 9744, 91958, 304, 36565, 81689, 28901, 13978, 323, 36565, 9983, 78712, 91958, 304, 41525, 25274, 323, 2956, 18825, 369, 61593, 25927, 323, 30909, 29625, 9744, 304, 279, 24780, 220, 19, 13, 15, 48688, 91958, 304, 12369, 323, 11842, 7424, 1411, 91608, 395, 25003, 11, 29225, 323, 5560, 304, 3804, 97519, 10384, 25, 94965, 264, 70128, 369, 264, 26361, 24432, 68, 71171, 91958, 304, 21523, 34199, 367, 25579, 369, 7997, 8773, 17005, 91958, 304, 7997, 45587, 28780, 91958, 304, 40602, 31356, 5768, 6427, 11, 32541, 22018, 18825, 323, 62965, 369, 264, 51269, 11847, 91958, 304, 25563, 32388, 18825, 323, 9744, 91958, 304, 13257, 21579, 12053, 304, 8245, 323, 34711, 8398, 91958, 304, 29911, 14577, 41525, 25274, 369, 89812, 25, 77349, 323, 32625, 91958, 304, 3962, 33512, 6709, 40388, 91958, 304, 8483, 323, 61593, 32625, 315, 12634, 2345, 11948, 33512, 519, 27773, 304, 74248, 91958, 304, 58320, 323, 23815, 780, 89812, 91958, 304, 13482, 10170, 323, 28479, 15330, 25, 1561, 6872, 5848, 94985, 91958, 304, 89812, 62574, 291, 55947, 811, 91958, 304, 89812, 8483, 520, 279, 3907, 315, 61750, 91958, 304, 89812, 8483, 505, 80085, 19285, 3907, 315, 12053, 91958, 304, 89812, 8483, 505, 279, 3907, 315, 2582, 1037, 64, 91958, 304, 89812, 25, 30402, 45231, 505, 220, 16, 267, 4435, 89812, 17997, 91958, 304, 89812, 25, 30402, 45231, 505, 279, 10657, 4435, 89812, 17997, 320, 679, 17, 8, 91958, 304, 61593, 11050, 25, 30402, 45231, 505, 220, 679, 21, 12634, 323, 11847, 33025, 10563, 91958, 304, 61593, 62368, 425, 15264, 323, 22620, 13284, 7935, 73656, 91958, 304, 61593, 12634, 15264, 323, 25027, 97970, 7246, 25579, 91958, 304, 61593, 33242, 12255, 81239, 91958, 304, 61593, 12053, 25, 578, 63206, 220, 21, 50, 6872, 2508, 91958, 304, 61593, 52652, 323, 68728, 18589, 91958, 304, 279, 89812, 323, 1838, 321, 1873, 20620, 520, 279, 29422, 323, 26361, 53793, 25, 23199, 11, 35695, 11, 63348, 11, 323, 27820, 369, 279, 9479, 921, 34869, 287, 3799, 3536, 91958, 315, 14434, 54752, 304, 279, 11930, 21749, 91958, 315, 89812, 8483, 25, 362, 12152, 70288, 91958, 389, 17283, 21304, 323, 89812, 12605, 9151, 264, 61593, 12781, 25, 54878, 11, 2956, 18825, 11, 5768, 6427, 11, 323, 4567, 7607, 12605, 9151, 89812, 1555, 8489, 12, 34242, 12605, 9151, 29422, 89812, 1555, 264, 423, 8194, 9983, 13737, 66, 5848, 744, 8483, 58662, 64250, 337, 96201, 323, 1369, 19846, 23454, 43606, 31433, 28780, 369, 89812, 4740, 279, 1556, 5879, 93210, 5879, 5481, 5879, 60451, 25, 4212, 323, 6178, 5879, 49938, 5879, 488, 60134, 323, 12369, 15264, 89812, 25, 578, 22872, 26323, 315, 25733, 288, 323, 49522, 60134, 11050, 128257, 198, 128256, 78191, 198, 791, 8246, 5064, 596, 6307, 27137, 12580, 264, 1396, 315, 11774, 11, 1524, 439, 810, 3363, 17047, 323, 2162, 23455, 527, 15098, 17919, 369, 810, 22556, 502, 10632, 323, 14016, 13, 22395, 279, 32116, 11509, 304, 279, 1648, 315, 2886, 804, 8246, 527, 279, 5064, 596, 5933, 46878, 5603, 311, 19297, 439, 1664, 439, 1202, 25462, 11626, 4211, 11, 902, 4799, 8767, 34235, 26870, 323, 12823, 13, 763, 264, 502, 5684, 4756, 304, 279, 8486, 89812, 11, 2380, 64193, 689, 12074, 505, 279, 9479, 12, 38238, 38373, 10181, 320, 6269, 11487, 8, 21782, 1884, 32116, 323, 3085, 15325, 36580, 2254, 17047, 649, 3085, 311, 15253, 879, 6307, 1972, 12675, 4500, 13, 578, 4007, 1101, 5992, 520, 279, 1401, 39210, 323, 4857, 2324, 78790, 1920, 311, 10765, 5627, 311, 8108, 279, 5064, 596, 8244, 12782, 43972, 13, 10604, 374, 77720, 4460, 11, 814, 3350, 25, 4184, 311, 279, 8121, 23590, 369, 74248, 323, 24987, 323, 279, 3723, 19687, 11847, 6826, 11, 8246, 323, 279, 5918, 4676, 2759, 369, 220, 1987, 3346, 315, 3728, 37647, 6962, 20748, 13, 578, 4007, 13656, 10980, 505, 1023, 14584, 16064, 38936, 279, 8246, 5064, 13, 11699, 3063, 3229, 11, 2405, 920, 13, 5575, 64120, 11119, 438, 11, 374, 4872, 315, 30613, 6108, 1972, 12675, 16131, 480, 43598, 15695, 95923, 486, 3489, 78, 93212, 285, 323, 1080, 44624, 269, 315, 64193, 689, 596, 6051, 7376, 7315, 24948, 6098, 14016, 65456, 13, 578, 5684, 34744, 14090, 389, 11119, 438, 596, 1866, 11704, 10565, 264, 23759, 426, 7813, 31215, 11, 961, 315, 459, 6625, 7351, 430, 66159, 41329, 1555, 2626, 13, 330, 2170, 264, 4580, 4562, 315, 279, 30613, 31636, 47362, 11, 358, 15393, 1633, 6288, 430, 13707, 617, 912, 31089, 1268, 311, 3719, 10182, 21277, 1359, 1364, 2795, 13, 330, 7009, 3287, 956, 617, 279, 19248, 477, 279, 6677, 11, 323, 279, 1510, 2626, 4211, 656, 539, 990, 1210, 11119, 438, 13919, 430, 420, 4007, 11, 1080, 96471, 555, 64193, 689, 3142, 25542, 7648, 36934, 16233, 329, 323, 20619, 11487, 1080, 44624, 269, 71138, 5724, 469, 5327, 11, 649, 387, 1511, 439, 6029, 430, 264, 11191, 6541, 7119, 2886, 804, 14016, 690, 9778, 7380, 13707, 889, 1893, 502, 2626, 4211, 5410, 22613, 369, 872, 15167, 323, 17452, 8670, 13, 61593, 16599, 812, 578, 12283, 3350, 430, 279, 50446, 13176, 13707, 22416, 1205, 369, 4062, 4751, 4780, 389, 9341, 11, 15528, 29642, 323, 37154, 5361, 39210, 11, 4315, 1690, 3885, 2345, 4919, 387, 20669, 1455, 6847, 555, 27512, 10396, 323, 36580, 430, 11117, 879, 9021, 449, 279, 586, 1695, 13, 17737, 54566, 66078, 11, 17915, 33321, 11, 3827, 18808, 323, 19248, 323, 19353, 11821, 527, 682, 7526, 9919, 649, 1005, 311, 12192, 6307, 7224, 13, 330, 644, 856, 3217, 11, 1521, 36210, 6108, 4595, 315, 66078, 87958, 38220, 11618, 1051, 3629, 19857, 555, 3363, 7510, 11, 889, 1071, 430, 814, 1053, 743, 264, 47891, 315, 37849, 6514, 369, 6307, 4857, 7224, 1359, 2795, 11119, 438, 13, 3011, 47891, 1053, 387, 279, 1486, 13, 330, 2028, 1648, 11, 279, 3363, 1053, 387, 11890, 264, 16131, 430, 422, 814, 1977, 2555, 430, 7720, 279, 4676, 323, 279, 4029, 11, 814, 1053, 636, 459, 36210, 430, 1053, 8935, 872, 6020, 4211, 1210, 17283, 389, 3217, 469, 5327, 11621, 430, 11119, 438, 596, 3217, 44072, 1790, 4460, 8149, 311, 279, 3917, 3158, 11, 902, 1364, 2795, 374, 32161, 3544, 30525, 323, 14584, 17649, 13, 330, 3947, 374, 264, 1972, 8815, 304, 67371, 459, 3927, 1093, 64120, 596, 3217, 1139, 12624, 13363, 1359, 469, 5327, 2795, 13, 330, 4071, 584, 649, 11153, 6629, 5596, 315, 279, 6484, 17649, 555, 12967, 1077, 46763, 6677, 1139, 264, 46417, 1376, 11, 323, 430, 374, 1148, 3727, 420, 5684, 779, 7185, 13, 1102, 374, 922, 1972, 30295, 11, 323, 1268, 584, 649, 1304, 22556, 7224, 3621, 1210, 330, 2028, 5684, 374, 1093, 264, 2472, 315, 1148, 374, 704, 1070, 1457, 13, 1226, 527, 13021, 64120, 596, 3217, 304, 279, 5064, 323, 279, 1972, 32116, 323, 30740, 430, 3073, 1359, 11621, 16233, 329, 13, 330, 9673, 1253, 539, 387, 1633, 30576, 311, 48709, 11, 889, 617, 311, 23846, 264, 3917, 505, 264, 1633, 1579, 2237, 13, 1226, 1205, 420, 3169, 315, 15325, 3217, 311, 387, 3025, 311, 636, 1521, 26793, 304, 459, 14584, 1648, 1210, 578, 12283, 2733, 279, 5684, 596, 1972, 31184, 8522, 649, 387, 1511, 311, 10552, 279, 907, 315, 6307, 14016, 311, 13707, 11, 64243, 323, 70978, 1555, 872, 65456, 2133, 4741, 13, 330, 1687, 527, 539, 4560, 311, 2019, 11, 364, 3923, 374, 264, 2731, 4857, 30, 15260, 15100, 11119, 438, 13, 330, 1687, 1440, 1148, 264, 2731, 4857, 374, 13, 1102, 596, 922, 1268, 584, 4305, 433, 1210, 220, 128257, 198 ]

2,086

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Organismal appearances are shaped by selection from both biotic and abiotic drivers. For example, Gloger’s rule describes the pervasive pattern that more pigmented populations are found in more humid areas. However, species may also converge on nearly identical colours and patterns in sympatry, often to avoid predation by mimicking noxious species. Here we leverage a massive global citizen-science database to determine how biotic and abiotic factors act in concert to shape plumage in the world’s 230 species of woodpeckers. We find that habitat and climate profoundly influence woodpecker plumage, and we recover support for the generality of Gloger’s rule. However, many species exhibit remarkable convergence explained neither by these factors nor by shared ancestry. Instead, this convergence is associated with geographic overlap between species, suggesting occasional strong selection for interspecific mimicry. Introduction The coloration and patterning of organisms is shaped over evolutionary timescales by a variety of factors, both biotic and abiotic, including temperature and humidity 1 , 2 , 3 , 4 , 5 . Gloger’s rule, for example, describes the prominent ecological pattern wherein more pigmented populations are found in more humid areas 1 , 6 , 7 , 8 . Sexual selection can push organisms to become conspicuous, whilst the risk of predation can select for inconspicuous visual signals 9 , 10 , 11 . The external appearances of animals are subject to frequent study because such work has the power to shape our understanding of phenotypic evolution. Yet, our understanding of how factors such as climate and biotic interactions with predators, competitors, and mates combine to influence evolutionary outcomes across large radiations remains rudimentary. This is true even for birds, regular subjects of research on phenotypic evolution 12 , 13 . Here, we employ a phylogenetic comparative framework, coupled with remote-sensing data and a large citizen science dataset, to examine the combined effects of climate, habitat, evolutionary history, and community composition on plumage pattern and colour evolution in woodpeckers (Picidae). This diverse avian clade of 230 bird species is an excellent group in which to examine the evolution of external appearances because they occupy a broad range of climates across many habitats. Woodpeckers also display a wide range of plumages, from species with boldly pied patterns to others with large bright red patches, to still others that are entirely dull olive (Fig. 1 ). Furthermore, woodpeckers exhibit several cases of ostensible plumage mimicry 14 , 15 , highlighted by a recent time-calibrated phylogeny 16 . Although qualitatively compelling, it is unclear if these events can be explained simply as consequences of shared climate, habitat, and evolutionary history. Regardless of the answer to this question, these purported mimicry events and the impressive variation in plumage among woodpecker species provide the raw variation that we examine here to disentangle the contribution of the various abiotic and biotic factors that drive plumage evolution. Fig. 1 Evolutionary relationships and plumage similarity among exemplar species. Climate partially determines variation in woodpecker plumage. Lines lead from tips of phylogeny (left) to centroid of each species’ geographic distribution and are coloured according to mean climate regime of each species. These species shared a common ancestor ~ 6.5 mya. The colour scale depicts a gradient from warm (yellow) to seasonally cold regions (blue). eBird records for these species are plotted in the same colours as large points on the map. All other eBird woodpecker records are overlaid as smaller points and coloured similarly. Plumage dendrogram (right) shows the plumage dissimilarity relationships among the same set of species. Veniliornis mixtus , long classified as a member of Picoides , is inferred to have invaded seasonal climates in the southern hemisphere, and accordingly evolved bold black and white plumage. Picoides fumigatus , long classified as a member of Veniliornis , is inferred to have invaded warm climates near the equator, and accordingly evolved dark, subtly marked plumage. Picoides pubescens and P. villosus are rather distantly related but largely sympatric; they are inferred to have converged on one another in plumage above and beyond what would be expected based on shared climate, habitat, and evolutionary history. Traditional scientific names are used in this figure to aid explanation, but the illustrated species are currently all members of an expanded clade, Dryobates . Illustrations © HBW Alive/Lynx Edicions, map by authors Full size image We find that climate and habitat exert strong influences on woodpecker plumage. Species from humid areas, for example, tend to be darker and less boldly patterned than those from drier regions, and thus offer compelling support of Gloger’s rule. These factors and shared evolutionary history explain some of the variation in woodpecker plumage, but they are insufficient to explain some of the dramatic convergence seen between various sympatric woodpecker species. Instead, sympatry in and of itself appears to drive certain species pairs to converge in plumage, lending credence to the notion that these species are true avian plumage mimics. Results Multidimensional, distance-based approaches To investigate how climate, habitat, social interactions, and evolutionary history determine woodpecker plumage outcomes, we used multidimensional-colour and pattern-quantification tools to measure species’ colouration and patterns, quantifying species’ plumages from a standardized source (Figs. 2 and 3 ) 12 , 17 , 18 . Evidence suggests that pattern and colour are likely processed separately in vertebrate brains, with achromatic (i.e., luminance) channels used to process pattern information 19 , and differential stimulation of cones used to encode chromatic information 20 . While both plumage colour and pattern are inherently multivariate, we reduced this complexity into a composite matrix of pairwise species differences to address whether purported convergences were a mere by-product of shared evolutionary history or, if not, whether shared climate, habitat, or geographic overlap could explain these events. We incorporated the potential for interactions between pairs of species into the analysis by quantifying pairwise geographic range overlap using millions of globally crowd-sourced citizen science observations from eBird; 21 species in complete allopatry have no chance of interacting, while increasing degrees of sympatry should correlate with the probability of evolutionarily meaningful", "role": "user" }, { "content": "In the first global test of the idea, scientists have found evidence that some woodpeckers can evolve to look like another species of woodpecker in the same neighborhood. The researchers say that this \"plumage mimicry\" isn't a fluke—it happens among pairs of distantly related woodpeckers all over the world. The study, published in the journal Nature Communications, was conducted by researchers at the Cornell Lab of Ornithology, SUNY Buffalo State, the University of British Columbia, and Manchester University. \"Habitat, climate, and genetics play a huge role in the way feather color and pattern develop,\" explains lead author Eliot Miller at the Cornell Lab. \"Species in similar environments can look similar to one another. But in some cases, there's another factor influencing the remarkable resemblance between two woodpecker species and that's mimicry. It's the same phenomenon found in some butterflies which have evolved markings that make them look like a different bad-tasting or toxic species in order to ward off predators.\" Study authors combined data on feather color, DNA sequences, eBird reports, and NASA satellite measures of vegetation for all 230 of the world's woodpecker species. It became clear, Miller says, that there have been repeated cases of distantly-related woodpeckers coming to closely resemble each other when they live in the same region of the globe. \"In North America, the classic lookalike pairing is Downy Woodpecker and the larger Hairy Woodpecker,\" Miller says. \"Our study suggests that these two species have evolved to look nearly identical above and beyond what would be expected based on their environment. Yet, these two species evolved millions of years apart Other North American lookalikes are Black-backed and Three-toed Woodpeckers. In Europe, Greater and Lesser Spotted Woodpeckers bear a striking resemblance, as do the Lineated, Robust, and Helmeted Woodpeckers of South America. Though not part of the study, Miller's take on the reason for woodpecker dopplegangers is that downies that look like the larger, more aggressive Hairy Woodpeckers might make other birds, such as nuthatches and titmice, think twice about competing with the downy for food. Some evidence supporting this idea has been found in observational studies but field experiments would be needed to more conclusively test this hypothesis. The data turned up some other interesting connections between woodpecker appearance and habitat. Many of the woodpeckers the scientists looked at in tropical regions have darker feathers. This adds to a growing body of evidence in support of \"Gloger's Rule,\" which states that organisms tend to be darker colored in more humid areas. They also found that: red-headed woodpecker species tend to live in forested habitatsblack, white, and gray colored species tend to live in open habitatswoodpeckers with red on their bellies are most often found in forestswoodpeckers with large patches of color on their bellies were most often found in open habitats Additional studies would be needed to try to ferret out why some plumage patterns seem to be linked to habitat types. \"It's really fascinating,\" says Miller. \"And it's pretty likely this is happening in other bird families, too. I first got interested in this question a decade ago from looking through bird books. I wondered how the heck some distantly related species could look so much alike—what are the odds that it could happen just by chance?\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Organismal appearances are shaped by selection from both biotic and abiotic drivers. For example, Gloger’s rule describes the pervasive pattern that more pigmented populations are found in more humid areas. However, species may also converge on nearly identical colours and patterns in sympatry, often to avoid predation by mimicking noxious species. Here we leverage a massive global citizen-science database to determine how biotic and abiotic factors act in concert to shape plumage in the world’s 230 species of woodpeckers. We find that habitat and climate profoundly influence woodpecker plumage, and we recover support for the generality of Gloger’s rule. However, many species exhibit remarkable convergence explained neither by these factors nor by shared ancestry. Instead, this convergence is associated with geographic overlap between species, suggesting occasional strong selection for interspecific mimicry. Introduction The coloration and patterning of organisms is shaped over evolutionary timescales by a variety of factors, both biotic and abiotic, including temperature and humidity 1 , 2 , 3 , 4 , 5 . Gloger’s rule, for example, describes the prominent ecological pattern wherein more pigmented populations are found in more humid areas 1 , 6 , 7 , 8 . Sexual selection can push organisms to become conspicuous, whilst the risk of predation can select for inconspicuous visual signals 9 , 10 , 11 . The external appearances of animals are subject to frequent study because such work has the power to shape our understanding of phenotypic evolution. Yet, our understanding of how factors such as climate and biotic interactions with predators, competitors, and mates combine to influence evolutionary outcomes across large radiations remains rudimentary. This is true even for birds, regular subjects of research on phenotypic evolution 12 , 13 . Here, we employ a phylogenetic comparative framework, coupled with remote-sensing data and a large citizen science dataset, to examine the combined effects of climate, habitat, evolutionary history, and community composition on plumage pattern and colour evolution in woodpeckers (Picidae). This diverse avian clade of 230 bird species is an excellent group in which to examine the evolution of external appearances because they occupy a broad range of climates across many habitats. Woodpeckers also display a wide range of plumages, from species with boldly pied patterns to others with large bright red patches, to still others that are entirely dull olive (Fig. 1 ). Furthermore, woodpeckers exhibit several cases of ostensible plumage mimicry 14 , 15 , highlighted by a recent time-calibrated phylogeny 16 . Although qualitatively compelling, it is unclear if these events can be explained simply as consequences of shared climate, habitat, and evolutionary history. Regardless of the answer to this question, these purported mimicry events and the impressive variation in plumage among woodpecker species provide the raw variation that we examine here to disentangle the contribution of the various abiotic and biotic factors that drive plumage evolution. Fig. 1 Evolutionary relationships and plumage similarity among exemplar species. Climate partially determines variation in woodpecker plumage. Lines lead from tips of phylogeny (left) to centroid of each species’ geographic distribution and are coloured according to mean climate regime of each species. These species shared a common ancestor ~ 6.5 mya. The colour scale depicts a gradient from warm (yellow) to seasonally cold regions (blue). eBird records for these species are plotted in the same colours as large points on the map. All other eBird woodpecker records are overlaid as smaller points and coloured similarly. Plumage dendrogram (right) shows the plumage dissimilarity relationships among the same set of species. Veniliornis mixtus , long classified as a member of Picoides , is inferred to have invaded seasonal climates in the southern hemisphere, and accordingly evolved bold black and white plumage. Picoides fumigatus , long classified as a member of Veniliornis , is inferred to have invaded warm climates near the equator, and accordingly evolved dark, subtly marked plumage. Picoides pubescens and P. villosus are rather distantly related but largely sympatric; they are inferred to have converged on one another in plumage above and beyond what would be expected based on shared climate, habitat, and evolutionary history. Traditional scientific names are used in this figure to aid explanation, but the illustrated species are currently all members of an expanded clade, Dryobates . Illustrations © HBW Alive/Lynx Edicions, map by authors Full size image We find that climate and habitat exert strong influences on woodpecker plumage. Species from humid areas, for example, tend to be darker and less boldly patterned than those from drier regions, and thus offer compelling support of Gloger’s rule. These factors and shared evolutionary history explain some of the variation in woodpecker plumage, but they are insufficient to explain some of the dramatic convergence seen between various sympatric woodpecker species. Instead, sympatry in and of itself appears to drive certain species pairs to converge in plumage, lending credence to the notion that these species are true avian plumage mimics. Results Multidimensional, distance-based approaches To investigate how climate, habitat, social interactions, and evolutionary history determine woodpecker plumage outcomes, we used multidimensional-colour and pattern-quantification tools to measure species’ colouration and patterns, quantifying species’ plumages from a standardized source (Figs. 2 and 3 ) 12 , 17 , 18 . Evidence suggests that pattern and colour are likely processed separately in vertebrate brains, with achromatic (i.e., luminance) channels used to process pattern information 19 , and differential stimulation of cones used to encode chromatic information 20 . While both plumage colour and pattern are inherently multivariate, we reduced this complexity into a composite matrix of pairwise species differences to address whether purported convergences were a mere by-product of shared evolutionary history or, if not, whether shared climate, habitat, or geographic overlap could explain these events. We incorporated the potential for interactions between pairs of species into the analysis by quantifying pairwise geographic range overlap using millions of globally crowd-sourced citizen science observations from eBird; 21 species in complete allopatry have no chance of interacting, while increasing degrees of sympatry should correlate with the probability of evolutionarily meaningful<|im_end|> <|im_start|>assistant In the first global test of the idea, scientists have found evidence that some woodpeckers can evolve to look like another species of woodpecker in the same neighborhood. The researchers say that this "plumage mimicry" isn't a fluke—it happens among pairs of distantly related woodpeckers all over the world. The study, published in the journal Nature Communications, was conducted by researchers at the Cornell Lab of Ornithology, SUNY Buffalo State, the University of British Columbia, and Manchester University. "Habitat, climate, and genetics play a huge role in the way feather color and pattern develop," explains lead author Eliot Miller at the Cornell Lab. "Species in similar environments can look similar to one another. But in some cases, there's another factor influencing the remarkable resemblance between two woodpecker species and that's mimicry. It's the same phenomenon found in some butterflies which have evolved markings that make them look like a different bad-tasting or toxic species in order to ward off predators." Study authors combined data on feather color, DNA sequences, eBird reports, and NASA satellite measures of vegetation for all 230 of the world's woodpecker species. It became clear, Miller says, that there have been repeated cases of distantly-related woodpeckers coming to closely resemble each other when they live in the same region of the globe. "In North America, the classic lookalike pairing is Downy Woodpecker and the larger Hairy Woodpecker," Miller says. "Our study suggests that these two species have evolved to look nearly identical above and beyond what would be expected based on their environment. Yet, these two species evolved millions of years apart Other North American lookalikes are Black-backed and Three-toed Woodpeckers. In Europe, Greater and Lesser Spotted Woodpeckers bear a striking resemblance, as do the Lineated, Robust, and Helmeted Woodpeckers of South America. Though not part of the study, Miller's take on the reason for woodpecker dopplegangers is that downies that look like the larger, more aggressive Hairy Woodpeckers might make other birds, such as nuthatches and titmice, think twice about competing with the downy for food. Some evidence supporting this idea has been found in observational studies but field experiments would be needed to more conclusively test this hypothesis. The data turned up some other interesting connections between woodpecker appearance and habitat. Many of the woodpeckers the scientists looked at in tropical regions have darker feathers. This adds to a growing body of evidence in support of "Gloger's Rule," which states that organisms tend to be darker colored in more humid areas. They also found that: red-headed woodpecker species tend to live in forested habitatsblack, white, and gray colored species tend to live in open habitatswoodpeckers with red on their bellies are most often found in forestswoodpeckers with large patches of color on their bellies were most often found in open habitats Additional studies would be needed to try to ferret out why some plumage patterns seem to be linked to habitat types. "It's really fascinating," says Miller. "And it's pretty likely this is happening in other bird families, too. I first got interested in this question a decade ago from looking through bird books. I wondered how the heck some distantly related species could look so much alike—what are the odds that it could happen just by chance?" <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 10995, 2191, 278, 27351, 527, 27367, 555, 6727, 505, 2225, 6160, 14546, 323, 671, 62114, 12050, 13, 1789, 3187, 11, 480, 848, 261, 753, 6037, 16964, 279, 71867, 5497, 430, 810, 24623, 28078, 22673, 527, 1766, 304, 810, 67038, 5789, 13, 4452, 11, 9606, 1253, 1101, 80867, 389, 7154, 20086, 27230, 323, 12912, 304, 22176, 266, 894, 11, 3629, 311, 5766, 4255, 367, 555, 28003, 16671, 912, 30351, 9606, 13, 5810, 584, 33164, 264, 11191, 3728, 22618, 31419, 1873, 4729, 311, 8417, 1268, 6160, 14546, 323, 671, 62114, 9547, 1180, 304, 21497, 311, 6211, 42272, 425, 304, 279, 1917, 753, 220, 9870, 9606, 315, 7732, 375, 377, 388, 13, 1226, 1505, 430, 39646, 323, 10182, 66278, 10383, 7732, 375, 15512, 42272, 425, 11, 323, 584, 11993, 1862, 369, 279, 1803, 2786, 315, 480, 848, 261, 753, 6037, 13, 4452, 11, 1690, 9606, 31324, 23649, 56541, 11497, 14188, 555, 1521, 9547, 6463, 555, 6222, 66004, 13, 12361, 11, 420, 56541, 374, 5938, 449, 46139, 28347, 1990, 9606, 11, 23377, 28961, 3831, 6727, 369, 82019, 15934, 56459, 894, 13, 29438, 578, 1933, 367, 323, 93093, 1251, 315, 44304, 374, 27367, 927, 41993, 3115, 31296, 555, 264, 8205, 315, 9547, 11, 2225, 6160, 14546, 323, 671, 62114, 11, 2737, 9499, 323, 38193, 220, 16, 1174, 220, 17, 1174, 220, 18, 1174, 220, 19, 1174, 220, 20, 662, 480, 848, 261, 753, 6037, 11, 369, 3187, 11, 16964, 279, 21102, 50953, 5497, 42418, 810, 24623, 28078, 22673, 527, 1766, 304, 810, 67038, 5789, 220, 16, 1174, 220, 21, 1174, 220, 22, 1174, 220, 23, 662, 39767, 6727, 649, 4585, 44304, 311, 3719, 97985, 11, 24797, 279, 5326, 315, 4255, 367, 649, 3373, 369, 28093, 2203, 292, 9373, 9302, 17738, 220, 24, 1174, 220, 605, 1174, 220, 806, 662, 578, 9434, 27351, 315, 10099, 527, 3917, 311, 21420, 4007, 1606, 1778, 990, 706, 279, 2410, 311, 6211, 1057, 8830, 315, 14345, 37941, 292, 15740, 13, 14968, 11, 1057, 8830, 315, 1268, 9547, 1778, 439, 10182, 323, 6160, 14546, 22639, 449, 56217, 11, 28650, 11, 323, 55616, 16343, 311, 10383, 41993, 20124, 4028, 3544, 12164, 811, 8625, 68330, 75643, 13, 1115, 374, 837, 1524, 369, 20229, 11, 5912, 15223, 315, 3495, 389, 14345, 37941, 292, 15740, 220, 717, 1174, 220, 1032, 662, 5810, 11, 584, 3539, 264, 37555, 86945, 5411, 55394, 12914, 11, 34356, 449, 8870, 1355, 49205, 828, 323, 264, 3544, 22618, 8198, 10550, 11, 311, 21635, 279, 11093, 6372, 315, 10182, 11, 39646, 11, 41993, 3925, 11, 323, 4029, 18528, 389, 42272, 425, 5497, 323, 12745, 15740, 304, 7732, 375, 377, 388, 320, 34905, 114405, 570, 1115, 17226, 1860, 1122, 1206, 1037, 315, 220, 9870, 12224, 9606, 374, 459, 9250, 1912, 304, 902, 311, 21635, 279, 15740, 315, 9434, 27351, 1606, 814, 48678, 264, 7353, 2134, 315, 92399, 4028, 1690, 71699, 13, 12404, 375, 377, 388, 1101, 3113, 264, 7029, 2134, 315, 42272, 1154, 11, 505, 9606, 449, 96029, 44630, 12912, 311, 3885, 449, 3544, 10107, 2579, 29760, 11, 311, 2103, 3885, 430, 527, 11622, 41630, 33213, 320, 30035, 13, 220, 16, 7609, 24296, 11, 7732, 375, 377, 388, 31324, 3892, 5157, 315, 37996, 37864, 42272, 425, 56459, 894, 220, 975, 1174, 220, 868, 1174, 27463, 555, 264, 3293, 892, 49236, 61666, 37555, 848, 33495, 220, 845, 662, 10541, 5965, 275, 8046, 29722, 11, 433, 374, 25420, 422, 1521, 4455, 649, 387, 11497, 5042, 439, 16296, 315, 6222, 10182, 11, 39646, 11, 323, 41993, 3925, 13, 44840, 315, 279, 4320, 311, 420, 3488, 11, 1521, 59860, 56459, 894, 4455, 323, 279, 16358, 23851, 304, 42272, 425, 4315, 7732, 375, 15512, 9606, 3493, 279, 7257, 23851, 430, 584, 21635, 1618, 311, 834, 306, 4134, 279, 19035, 315, 279, 5370, 671, 62114, 323, 6160, 14546, 9547, 430, 6678, 42272, 425, 15740, 13, 23966, 13, 220, 16, 38321, 661, 12135, 323, 42272, 425, 38723, 4315, 39039, 277, 9606, 13, 31636, 26310, 27667, 23851, 304, 7732, 375, 15512, 42272, 425, 13, 39333, 3063, 505, 10631, 315, 37555, 848, 33495, 320, 2414, 8, 311, 59219, 315, 1855, 9606, 529, 46139, 8141, 323, 527, 58919, 4184, 311, 3152, 10182, 17942, 315, 1855, 9606, 13, 4314, 9606, 6222, 264, 4279, 46831, 4056, 220, 21, 13, 20, 856, 64, 13, 578, 12745, 5569, 62991, 264, 20779, 505, 8369, 320, 28969, 8, 311, 3280, 750, 9439, 13918, 320, 12481, 570, 384, 66370, 7576, 369, 1521, 9606, 527, 68683, 304, 279, 1890, 27230, 439, 3544, 3585, 389, 279, 2472, 13, 2052, 1023, 384, 66370, 7732, 375, 15512, 7576, 527, 29204, 3864, 439, 9333, 3585, 323, 58919, 30293, 13, 84409, 425, 90052, 87220, 320, 1315, 8, 5039, 279, 42272, 425, 14091, 318, 49325, 12135, 4315, 279, 1890, 743, 315, 9606, 13, 18732, 4008, 1540, 285, 6651, 83, 355, 1174, 1317, 21771, 439, 264, 4562, 315, 26987, 590, 288, 1174, 374, 68695, 311, 617, 64765, 36899, 92399, 304, 279, 18561, 69766, 11, 323, 28178, 28995, 14265, 3776, 323, 4251, 42272, 425, 13, 26987, 590, 288, 282, 372, 343, 1015, 1174, 1317, 21771, 439, 264, 4562, 315, 18732, 4008, 1540, 285, 1174, 374, 68695, 311, 617, 64765, 8369, 92399, 3221, 279, 3312, 859, 11, 323, 28178, 28995, 6453, 11, 87417, 13160, 42272, 425, 13, 26987, 590, 288, 6814, 3380, 729, 323, 393, 13, 26886, 2353, 355, 527, 4856, 1612, 18007, 5552, 719, 14090, 22176, 266, 2265, 26, 814, 527, 68695, 311, 617, 97875, 389, 832, 2500, 304, 42272, 425, 3485, 323, 7953, 1148, 1053, 387, 3685, 3196, 389, 6222, 10182, 11, 39646, 11, 323, 41993, 3925, 13, 46560, 12624, 5144, 527, 1511, 304, 420, 7216, 311, 12576, 16540, 11, 719, 279, 36762, 9606, 527, 5131, 682, 3697, 315, 459, 17626, 1206, 1037, 11, 31941, 677, 988, 662, 39154, 811, 7388, 40801, 54, 66526, 7586, 1910, 87, 3279, 78210, 11, 2472, 555, 12283, 8797, 1404, 2217, 1226, 1505, 430, 10182, 323, 39646, 43844, 3831, 34453, 389, 7732, 375, 15512, 42272, 425, 13, 51567, 505, 67038, 5789, 11, 369, 3187, 11, 8541, 311, 387, 40130, 323, 2753, 96029, 5497, 291, 1109, 1884, 505, 294, 7401, 13918, 11, 323, 8617, 3085, 29722, 1862, 315, 480, 848, 261, 753, 6037, 13, 4314, 9547, 323, 6222, 41993, 3925, 10552, 1063, 315, 279, 23851, 304, 7732, 375, 15512, 42272, 425, 11, 719, 814, 527, 39413, 311, 10552, 1063, 315, 279, 22520, 56541, 3970, 1990, 5370, 22176, 266, 2265, 7732, 375, 15512, 9606, 13, 12361, 11, 22176, 266, 894, 304, 323, 315, 5196, 8111, 311, 6678, 3738, 9606, 13840, 311, 80867, 304, 42272, 425, 11, 40651, 4281, 768, 311, 279, 23035, 430, 1521, 9606, 527, 837, 1860, 1122, 42272, 425, 28003, 1233, 13, 18591, 22950, 307, 29321, 11, 6138, 6108, 20414, 2057, 19874, 1268, 10182, 11, 39646, 11, 3674, 22639, 11, 323, 41993, 3925, 8417, 7732, 375, 15512, 42272, 425, 20124, 11, 584, 1511, 64486, 29321, 20024, 414, 323, 5497, 12, 31548, 2461, 7526, 311, 6767, 9606, 529, 12745, 367, 323, 12912, 11, 10484, 7922, 9606, 529, 42272, 1154, 505, 264, 51114, 2592, 320, 37, 14801, 13, 220, 17, 323, 220, 18, 883, 220, 717, 1174, 220, 1114, 1174, 220, 972, 662, 44796, 13533, 430, 5497, 323, 12745, 527, 4461, 15590, 26214, 304, 67861, 65216, 35202, 11, 449, 34361, 99866, 320, 72, 1770, 2637, 46058, 685, 8, 12006, 1511, 311, 1920, 5497, 2038, 220, 777, 1174, 323, 41264, 41959, 315, 87992, 1511, 311, 16559, 22083, 780, 2038, 220, 508, 662, 6104, 2225, 42272, 425, 12745, 323, 5497, 527, 49188, 2814, 56522, 11, 584, 11293, 420, 23965, 1139, 264, 28814, 6303, 315, 93859, 9606, 12062, 311, 2686, 3508, 59860, 19873, 70, 2436, 1051, 264, 17983, 555, 29745, 315, 6222, 41993, 3925, 477, 11, 422, 539, 11, 3508, 6222, 10182, 11, 39646, 11, 477, 46139, 28347, 1436, 10552, 1521, 4455, 13, 1226, 32762, 279, 4754, 369, 22639, 1990, 13840, 315, 9606, 1139, 279, 6492, 555, 10484, 7922, 93859, 46139, 2134, 28347, 1701, 11990, 315, 31550, 13734, 1355, 54492, 22618, 8198, 24654, 505, 384, 66370, 26, 220, 1691, 9606, 304, 4686, 63747, 4781, 894, 617, 912, 6140, 315, 45830, 11, 1418, 7859, 12628, 315, 22176, 266, 894, 1288, 81584, 449, 279, 19463, 315, 15740, 6751, 23222, 128257, 198, 128256, 78191, 198, 644, 279, 1176, 3728, 1296, 315, 279, 4623, 11, 14248, 617, 1766, 6029, 430, 1063, 7732, 375, 377, 388, 649, 38680, 311, 1427, 1093, 2500, 9606, 315, 7732, 375, 15512, 304, 279, 1890, 12818, 13, 578, 12074, 2019, 430, 420, 330, 501, 372, 425, 56459, 894, 1, 4536, 956, 264, 1344, 10647, 44603, 8741, 4315, 13840, 315, 1612, 18007, 5552, 7732, 375, 377, 388, 682, 927, 279, 1917, 13, 578, 4007, 11, 4756, 304, 279, 8486, 22037, 26545, 11, 574, 13375, 555, 12074, 520, 279, 56819, 11868, 315, 88939, 411, 2508, 11, 57328, 56, 32489, 3314, 11, 279, 3907, 315, 8013, 19326, 11, 323, 19922, 3907, 13, 330, 39, 40027, 266, 11, 10182, 11, 323, 56104, 1514, 264, 6908, 3560, 304, 279, 1648, 50876, 1933, 323, 5497, 2274, 1359, 15100, 3063, 3229, 34362, 354, 17472, 520, 279, 56819, 11868, 13, 330, 71846, 304, 4528, 22484, 649, 1427, 4528, 311, 832, 2500, 13, 2030, 304, 1063, 5157, 11, 1070, 596, 2500, 8331, 66700, 279, 23649, 70000, 1990, 1403, 7732, 375, 15512, 9606, 323, 430, 596, 56459, 894, 13, 1102, 596, 279, 1890, 25885, 1766, 304, 1063, 81776, 902, 617, 28995, 65172, 430, 1304, 1124, 1427, 1093, 264, 2204, 3958, 2442, 15067, 477, 21503, 9606, 304, 2015, 311, 26741, 1022, 56217, 1210, 19723, 12283, 11093, 828, 389, 50876, 1933, 11, 15922, 24630, 11, 384, 66370, 6821, 11, 323, 22146, 24088, 11193, 315, 54832, 369, 682, 220, 9870, 315, 279, 1917, 596, 7732, 375, 15512, 9606, 13, 1102, 6244, 2867, 11, 17472, 2795, 11, 430, 1070, 617, 1027, 11763, 5157, 315, 1612, 18007, 14228, 7732, 375, 377, 388, 5108, 311, 15499, 52280, 1855, 1023, 994, 814, 3974, 304, 279, 1890, 5654, 315, 279, 24867, 13, 330, 644, 4892, 5270, 11, 279, 11670, 1427, 278, 3043, 48813, 374, 6419, 88, 12404, 375, 15512, 323, 279, 8294, 473, 22704, 12404, 375, 15512, 1359, 17472, 2795, 13, 330, 8140, 4007, 13533, 430, 1521, 1403, 9606, 617, 28995, 311, 1427, 7154, 20086, 3485, 323, 7953, 1148, 1053, 387, 3685, 3196, 389, 872, 4676, 13, 14968, 11, 1521, 1403, 9606, 28995, 11990, 315, 1667, 10980, 7089, 4892, 3778, 1427, 278, 12732, 527, 5348, 46128, 323, 14853, 4791, 291, 12404, 375, 377, 388, 13, 763, 4606, 11, 33381, 323, 14231, 3165, 15889, 12404, 375, 377, 388, 11984, 264, 21933, 70000, 11, 439, 656, 279, 7228, 660, 11, 4997, 592, 11, 323, 67629, 291, 12404, 375, 377, 388, 315, 4987, 5270, 13, 18056, 539, 961, 315, 279, 4007, 11, 17472, 596, 1935, 389, 279, 2944, 369, 7732, 375, 15512, 27420, 698, 70, 14381, 374, 430, 1523, 552, 430, 1427, 1093, 279, 8294, 11, 810, 19738, 473, 22704, 12404, 375, 377, 388, 2643, 1304, 1023, 20229, 11, 1778, 439, 308, 952, 9296, 323, 8305, 76, 560, 11, 1781, 11157, 922, 27260, 449, 279, 1523, 88, 369, 3691, 13, 4427, 6029, 12899, 420, 4623, 706, 1027, 1766, 304, 90380, 7978, 719, 2115, 21896, 1053, 387, 4460, 311, 810, 84082, 3210, 1296, 420, 31178, 13, 578, 828, 6656, 709, 1063, 1023, 7185, 13537, 1990, 7732, 375, 15512, 11341, 323, 39646, 13, 9176, 315, 279, 7732, 375, 377, 388, 279, 14248, 7111, 520, 304, 35148, 13918, 617, 40130, 56994, 13, 1115, 11621, 311, 264, 7982, 2547, 315, 6029, 304, 1862, 315, 330, 38, 848, 261, 596, 18592, 1359, 902, 5415, 430, 44304, 8541, 311, 387, 40130, 28296, 304, 810, 67038, 5789, 13, 2435, 1101, 1766, 430, 25, 2579, 62166, 7732, 375, 15512, 9606, 8541, 311, 3974, 304, 13952, 291, 71699, 11708, 11, 4251, 11, 323, 18004, 28296, 9606, 8541, 311, 3974, 304, 1825, 71699, 6798, 375, 377, 388, 449, 2579, 389, 872, 29519, 552, 527, 1455, 3629, 1766, 304, 36658, 6798, 375, 377, 388, 449, 3544, 29760, 315, 1933, 389, 872, 29519, 552, 1051, 1455, 3629, 1766, 304, 1825, 71699, 24086, 7978, 1053, 387, 4460, 311, 1456, 311, 18728, 2171, 704, 3249, 1063, 42272, 425, 12912, 2873, 311, 387, 10815, 311, 39646, 4595, 13, 330, 2181, 596, 2216, 27387, 1359, 2795, 17472, 13, 330, 3112, 433, 596, 5128, 4461, 420, 374, 12765, 304, 1023, 12224, 8689, 11, 2288, 13, 358, 1176, 2751, 8173, 304, 420, 3488, 264, 13515, 4227, 505, 3411, 1555, 12224, 6603, 13, 358, 31156, 1268, 279, 47781, 1063, 1612, 18007, 5552, 9606, 1436, 1427, 779, 1790, 27083, 2345, 12840, 527, 279, 21448, 430, 433, 1436, 3621, 1120, 555, 6140, 7673, 220, 128257, 198 ]

2,100

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract MLKL is the essential effector of necroptosis, a form of programmed lytic cell death. We have isolated a mouse strain with a single missense mutation, Mlkl D139V , that alters the two-helix ‘brace’ that connects the killer four-helix bundle and regulatory pseudokinase domains. This confers constitutive, RIPK3 independent killing activity to MLKL. Homozygous mutant mice develop lethal postnatal inflammation of the salivary glands and mediastinum. The normal embryonic development of Mlkl D139V homozygotes until birth, and the absence of any overt phenotype in heterozygotes provides important in vivo precedent for the capacity of cells to clear activated MLKL. These observations offer an important insight into the potential disease-modulating roles of three common human MLKL polymorphisms that encode amino acid substitutions within or adjacent to the brace region. Compound heterozygosity of these variants is found at up to 12-fold the expected frequency in patients that suffer from a pediatric autoinflammatory disease, chronic recurrent multifocal osteomyelitis (CRMO). Introduction Necroptosis is a lytic form of programmed cell death associated with the production of pro-inflammatory cytokines, the destruction of biological membranes and the release of intracellular damage associated molecular patterns (DAMPs) 1 . Necroptosis depends on the activation of the mixed lineage kinase domain-like (MLKL) pseudokinase by receptor interacting protein kinase 3 (RIPK3) 2 , 3 , 4 . RIPK3-mediated phosphorylation of MLKL triggers a conformational change 4 , 5 that facilitates the translocation to, and eventual irreversible disruption of, cellular membranes. While the precise biophysical mechanism of membrane disruption is still a matter of debate, common features of contemporary models are the formation of an MLKL oligomer and the direct association of the executioner four-helix bundle domain (4HB) of MLKL with biological membranes 6 , 7 , 8 , 9 , 10 . In mouse cells, the expression of the murine MLKL 4HB domain alone (residues 1–125), 4HB plus brace helices (1–180), or the expression of phosphomimetic or other single site pseudokinase domain (PsKD) mutants is sufficient to induce membrane translocation, oligomerization and membrane destruction 4 , 9 . While capable of disrupting synthetic liposomes when produced recombinantly, similarly truncated and equivalent single site (PsKD) mutant forms of human MLKL do not robustly induce membrane-associated oligomerization and cell death without forced dimerization 11 , 12 , 13 . Furthermore, both mouse and human MLKL mutants have been reported that have the capacity to form membrane-associated oligomers, but fail to cause irreversible membrane disruption and cell death 9 , 13 . Recent studies have revealed that necroptosis downstream of MLKL phosphorylation and membrane association can be modulated by processes that engage the endosomal sorting complex required for transport (ESCRT) family of proteins. One model proposes a role for ESCRT in limiting necroptosis via plasma membrane excision and repair 14 while other models limit plasma membrane disruption by ESCRT-mediated release of phosphorylated MLKL in extracellular vesicles 15 , 17 , 17 and/or the internalization of phosphorylated MLKL for lysosomal degradation 17 . In mice, the absence of MLKL does not appear to have obvious deleterious developmental or homeostatic effects 4 , 18 . However, genetic deletion of Fadd , Casp8 or Ripk1 , leads to inappropriate activation of MLKL and ensuing necroptosis during embryogenesis that is incompatible with life beyond embryonic day (E)10.5, E10.5 and 1–3 days post-natally, respectively 19 , 20 , 21 , 22 , 23 , 24 , 25 . Exploring the precise physiological consequences of inappropriate MLKL activation in these scenarios is complicated by the fact that FADD, Caspase-8 and RIPK1 also play important roles in cellular processes other than modulation of MLKL-induced necroptotic cell death 23 , 26 , 27 , 28 , 29 , 30 . Aberrant levels of MLKL-dependent cell death contribute to disease in several genetic and experimental mouse models 23 , 31 , 32 , 33 , 34 , 35 . In humans, MLKL mRNA and protein levels are positively correlated with survival of patients with pancreatic adenocarcinoma, cervical-, gastric-, ovarian- and colon- cancers (reviewed by ref. 36 ). Interestingly, high levels of phosphorylated MLKL are associated with reduced survival in esophageal and colon cancer patients 37 . Two missense MLKL somatic mutations identified in human cancer tissue have been found to confer a reduction in necroptotic function in cell-based assays 4 , 13 . Very recently, siblings suffering from a novel neurodegenerative disorder were reported as homozygous for a rare haplotype involving a frameshift variant in MLKL , as well as an in-frame deletion of one amino acid in the adjacent fatty acid 2-hydroxylase ( FA2H ) gene 38 . The significant enrichment of an ultra-rare MLKL stop-gain gene variant p.Q48X has been reported in Hong Kong Chinese patients suffering from a form of Alzheimer’s disease 39 , however more common germline MLKL gene variants are only weakly associated with human disease in GWAS databases. We have identified a single base pair germline mutation of mouse Mlkl that encodes a missense substitution within the MLKL brace region and confers constitutive activation independent of upstream necroptotic stimuli. Given this mutant Mlkl allele is subject to the same developmental and environmental controls on gene expression as wild-type Mlkl , the postnatal lethality in these mice provides insight into the physiological and pathological consequences of dysregulated necroptosis. In parallel, these findings inform the potential functional significance of three common human MLKL polymorphisms that encode non-conservative amino acid substitutions within, or in close proximity to, the brace helix that is mutated in the Mlkl D139V mouse. Results Generation of a constitutively active form of MLKL Mpl −/− mice, owing to genetic deletion of the major receptor for thrombopoietin, have only 10% the wild-type number of peripheral platelets. An ENU mutagenesis screen was performed to identify mutations that ameliorate thrombocytopenia in Mpl −/− mice via thrombopoietin independent platelet production 40 . A G 1 founder, designated Plt15 , had a modestly elevated platelet count of 189 × 10 6 per mL compared with the mean for Mpl −/− animals (113 ± 57 × 10 6 per mL) and yielded", "role": "user" }, { "content": "Walter and Eliza Hall Institute researchers have made significant advances in understanding the inflammatory cell death regulatory protein MLKL and its role in disease. In a trio of studies published today in the journal Nature Communications, the team used advanced imaging to visualize key steps in the activation of MLKL, revealing previously unseen details about how this protein drives an inflammatory form of cell death called necroptosis. They also showed for the first time that inherited variants of MLKL are connected to a human inflammatory disease. By examining sequence variations in human MLKL and comparing the structure of different animals' MLKL proteins, the team also provided evidence for MLKL having been subject to evolutionary pressures, potentially through its role in protecting against infections. The multidisciplinary research was led by Dr. Andre Samson, Dr. Joanne Hildebrand, Dr. Maria Kauppi, Ms Katherine Davies, Associate Professor Edwin Hawkins, Associate Professor Peter Czabotar, Professor Warren Alexander, Professor John Silke and Associate Professor James Murphy. Understanding inflammatory cell death Cell death is a way that the body protects itself from diseases, by removing unwanted or dangerous cells. In some situations—such as viral or bacterial infections—dying cells trigger inflammation to protect neighboring cells from the infection. This form of cell death is called 'necroptosis', and is tightly controlled by specific proteins within cells. Associate Professor James Murphy said the protein MLKL was an important regulator of necroptosis. \"While MLKL and necroptosis protect our bodies from infections, excessive necroptosis has been linked with inflammatory conditions such as inflammatory bowel diseases,\" he said. \"Our research team has taken several complementary approaches to better understand how MLKL functions—which could improve the understanding and treatment of diseases involving excessive necroptosis.\" One study, led by Dr. Andre Samson, used advanced imaging technologies to watch the MLKL protein in cells as they underwent necroptosis. Dr. Samson said this identified two important 'checkpoints' in necroptosis. \"We could see how MLKL changed its location as necroptosis occurred, clumping and migrating to different parts of the cell as the cell progressed towards death,\" he said. \"Intriguingly, we could see activated MLKL gather at the junctions between neighboring cells—potentially suggesting a way for one dying cell to trigger necroptosis in surrounding cells, which could be a form of protection against infections.\" Walter and Eliza Hall Institute researchers have used lattice light sheet microscopy to visualise cells dying by necroptosis, a form of inflammatory cell death. Credit: Walter and Eliza Hall Institute (adapted from video published in Samson et al, Nature Communications) Role of MLKL in inflammatory diseases Dr. Joanne Hildebrand and Dr. Maria Kauppi examined links between alterations in the MLKL protein and inflammatory conditions. Dr. Hildebrand said Institute researchers isolated a variant of MLKL that caused a lethal inflammatory condition in laboratory models. \"We discovered this form of MLKL contained a single mutation in a particular region of the protein that made MLKL hyperactive, triggering necroptosis and inflammation,\" she said. \"By searching genome databases, we discovered similar variants in the human MLKL gene are surprisingly common—around ten per cent of human genomes from around the world carry altered forms of the MLKL gene that result in a more-easily activated, more inflammatory version of the protein. The team speculated that the pro-inflammatory variant of MLKL might be associated with inflammatory diseases. \"We looked more closely at databases of genomes of people with inflammatory diseases to understand the prevalence of MLKL variants. Indeed, people with an autoinflammatory condition chronic recurrent multifocal osteomyelitis (CRMO) were much more likely to carry two copies of a pro-inflammatory variant of the MLKL gene than people without an inflammatory disease. This is the first time changes in MLKL have been associated with a human inflammatory disease,\" Dr. Hildebrand said. Evolutionary pressure on MLKL Dr. Hildebrand said the high frequency of MLKL variants in humans around the world suggested that the more inflammatory variants of the protein might have offered an evolutionary benefit at some point of human history. \"Perhaps having a more inflammatory form of MLKL meant some people could survive infectious diseases better than those people who only had the less-easily activated form of the protein,\" she said. In a separate paper, Ms Katherine Davies led research investigating the three-dimensional structure of MLKL in different vertebrate species, using the Australian Synchrotron and CSIRO Collaborative Crystallisation Centre. Dr. Davies said usually when one protein is found in different vertebrate species, the proteins in the different species have a similar structure that has been conserved during evolution. \"To our surprise, the structures of MLKL were quite different between different vertebrate species—even between closely related species such as rats and mice. In fact, rat MLKL is so different from mouse MLKL that the rat protein cannot function in mouse cells—which is surprising as many proteins are interchangeable between these two species,\" Dr. Davies said. \"We think that evolutionary pressures such as infections may have driven substantial changes in MLKL as vertebrates evolved. Animals with variant forms of MLKL may have been able to survive some pressures better than other animals, driving changes in MLKL to accumulate, much faster than for many other proteins. \"Together with the data for human variations in MLKL, this suggests MLKL is critical for cells to balance beneficial inflammation, which protects against infections, with harmful inflammation that causes inflammatory diseases,\" Dr. Davies said. Long-term research yields rewards Associate Professor James Murphy said the team's research started through studying the inflammatory variant of MLKL more than 13 years ago—at a time when MLKL's role in necroptosis was not known. \"Our most recent discoveries, made by a multidisciplinary research team, have provided a massive advance to the field of necroptosis, adding substantial detail to our understanding of MLKL. This will provide an enormous boost to a range of research into inflammatory diseases. Our team and others are already working to develop new medicines that could temper MLKL-driven inflammation, which we hope could be a new approach to treating a range of inflammatory diseases,\" Associate Professor Murphy said. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract MLKL is the essential effector of necroptosis, a form of programmed lytic cell death. We have isolated a mouse strain with a single missense mutation, Mlkl D139V , that alters the two-helix ‘brace’ that connects the killer four-helix bundle and regulatory pseudokinase domains. This confers constitutive, RIPK3 independent killing activity to MLKL. Homozygous mutant mice develop lethal postnatal inflammation of the salivary glands and mediastinum. The normal embryonic development of Mlkl D139V homozygotes until birth, and the absence of any overt phenotype in heterozygotes provides important in vivo precedent for the capacity of cells to clear activated MLKL. These observations offer an important insight into the potential disease-modulating roles of three common human MLKL polymorphisms that encode amino acid substitutions within or adjacent to the brace region. Compound heterozygosity of these variants is found at up to 12-fold the expected frequency in patients that suffer from a pediatric autoinflammatory disease, chronic recurrent multifocal osteomyelitis (CRMO). Introduction Necroptosis is a lytic form of programmed cell death associated with the production of pro-inflammatory cytokines, the destruction of biological membranes and the release of intracellular damage associated molecular patterns (DAMPs) 1 . Necroptosis depends on the activation of the mixed lineage kinase domain-like (MLKL) pseudokinase by receptor interacting protein kinase 3 (RIPK3) 2 , 3 , 4 . RIPK3-mediated phosphorylation of MLKL triggers a conformational change 4 , 5 that facilitates the translocation to, and eventual irreversible disruption of, cellular membranes. While the precise biophysical mechanism of membrane disruption is still a matter of debate, common features of contemporary models are the formation of an MLKL oligomer and the direct association of the executioner four-helix bundle domain (4HB) of MLKL with biological membranes 6 , 7 , 8 , 9 , 10 . In mouse cells, the expression of the murine MLKL 4HB domain alone (residues 1–125), 4HB plus brace helices (1–180), or the expression of phosphomimetic or other single site pseudokinase domain (PsKD) mutants is sufficient to induce membrane translocation, oligomerization and membrane destruction 4 , 9 . While capable of disrupting synthetic liposomes when produced recombinantly, similarly truncated and equivalent single site (PsKD) mutant forms of human MLKL do not robustly induce membrane-associated oligomerization and cell death without forced dimerization 11 , 12 , 13 . Furthermore, both mouse and human MLKL mutants have been reported that have the capacity to form membrane-associated oligomers, but fail to cause irreversible membrane disruption and cell death 9 , 13 . Recent studies have revealed that necroptosis downstream of MLKL phosphorylation and membrane association can be modulated by processes that engage the endosomal sorting complex required for transport (ESCRT) family of proteins. One model proposes a role for ESCRT in limiting necroptosis via plasma membrane excision and repair 14 while other models limit plasma membrane disruption by ESCRT-mediated release of phosphorylated MLKL in extracellular vesicles 15 , 17 , 17 and/or the internalization of phosphorylated MLKL for lysosomal degradation 17 . In mice, the absence of MLKL does not appear to have obvious deleterious developmental or homeostatic effects 4 , 18 . However, genetic deletion of Fadd , Casp8 or Ripk1 , leads to inappropriate activation of MLKL and ensuing necroptosis during embryogenesis that is incompatible with life beyond embryonic day (E)10.5, E10.5 and 1–3 days post-natally, respectively 19 , 20 , 21 , 22 , 23 , 24 , 25 . Exploring the precise physiological consequences of inappropriate MLKL activation in these scenarios is complicated by the fact that FADD, Caspase-8 and RIPK1 also play important roles in cellular processes other than modulation of MLKL-induced necroptotic cell death 23 , 26 , 27 , 28 , 29 , 30 . Aberrant levels of MLKL-dependent cell death contribute to disease in several genetic and experimental mouse models 23 , 31 , 32 , 33 , 34 , 35 . In humans, MLKL mRNA and protein levels are positively correlated with survival of patients with pancreatic adenocarcinoma, cervical-, gastric-, ovarian- and colon- cancers (reviewed by ref. 36 ). Interestingly, high levels of phosphorylated MLKL are associated with reduced survival in esophageal and colon cancer patients 37 . Two missense MLKL somatic mutations identified in human cancer tissue have been found to confer a reduction in necroptotic function in cell-based assays 4 , 13 . Very recently, siblings suffering from a novel neurodegenerative disorder were reported as homozygous for a rare haplotype involving a frameshift variant in MLKL , as well as an in-frame deletion of one amino acid in the adjacent fatty acid 2-hydroxylase ( FA2H ) gene 38 . The significant enrichment of an ultra-rare MLKL stop-gain gene variant p.Q48X has been reported in Hong Kong Chinese patients suffering from a form of Alzheimer’s disease 39 , however more common germline MLKL gene variants are only weakly associated with human disease in GWAS databases. We have identified a single base pair germline mutation of mouse Mlkl that encodes a missense substitution within the MLKL brace region and confers constitutive activation independent of upstream necroptotic stimuli. Given this mutant Mlkl allele is subject to the same developmental and environmental controls on gene expression as wild-type Mlkl , the postnatal lethality in these mice provides insight into the physiological and pathological consequences of dysregulated necroptosis. In parallel, these findings inform the potential functional significance of three common human MLKL polymorphisms that encode non-conservative amino acid substitutions within, or in close proximity to, the brace helix that is mutated in the Mlkl D139V mouse. Results Generation of a constitutively active form of MLKL Mpl −/− mice, owing to genetic deletion of the major receptor for thrombopoietin, have only 10% the wild-type number of peripheral platelets. An ENU mutagenesis screen was performed to identify mutations that ameliorate thrombocytopenia in Mpl −/− mice via thrombopoietin independent platelet production 40 . A G 1 founder, designated Plt15 , had a modestly elevated platelet count of 189 × 10 6 per mL compared with the mean for Mpl −/− animals (113 ± 57 × 10 6 per mL) and yielded<|im_end|> <|im_start|>assistant Walter and Eliza Hall Institute researchers have made significant advances in understanding the inflammatory cell death regulatory protein MLKL and its role in disease. In a trio of studies published today in the journal Nature Communications, the team used advanced imaging to visualize key steps in the activation of MLKL, revealing previously unseen details about how this protein drives an inflammatory form of cell death called necroptosis. They also showed for the first time that inherited variants of MLKL are connected to a human inflammatory disease. By examining sequence variations in human MLKL and comparing the structure of different animals' MLKL proteins, the team also provided evidence for MLKL having been subject to evolutionary pressures, potentially through its role in protecting against infections. The multidisciplinary research was led by Dr. Andre Samson, Dr. Joanne Hildebrand, Dr. Maria Kauppi, Ms Katherine Davies, Associate Professor Edwin Hawkins, Associate Professor Peter Czabotar, Professor Warren Alexander, Professor John Silke and Associate Professor James Murphy. Understanding inflammatory cell death Cell death is a way that the body protects itself from diseases, by removing unwanted or dangerous cells. In some situations—such as viral or bacterial infections—dying cells trigger inflammation to protect neighboring cells from the infection. This form of cell death is called 'necroptosis', and is tightly controlled by specific proteins within cells. Associate Professor James Murphy said the protein MLKL was an important regulator of necroptosis. "While MLKL and necroptosis protect our bodies from infections, excessive necroptosis has been linked with inflammatory conditions such as inflammatory bowel diseases," he said. "Our research team has taken several complementary approaches to better understand how MLKL functions—which could improve the understanding and treatment of diseases involving excessive necroptosis." One study, led by Dr. Andre Samson, used advanced imaging technologies to watch the MLKL protein in cells as they underwent necroptosis. Dr. Samson said this identified two important 'checkpoints' in necroptosis. "We could see how MLKL changed its location as necroptosis occurred, clumping and migrating to different parts of the cell as the cell progressed towards death," he said. "Intriguingly, we could see activated MLKL gather at the junctions between neighboring cells—potentially suggesting a way for one dying cell to trigger necroptosis in surrounding cells, which could be a form of protection against infections." Walter and Eliza Hall Institute researchers have used lattice light sheet microscopy to visualise cells dying by necroptosis, a form of inflammatory cell death. Credit: Walter and Eliza Hall Institute (adapted from video published in Samson et al, Nature Communications) Role of MLKL in inflammatory diseases Dr. Joanne Hildebrand and Dr. Maria Kauppi examined links between alterations in the MLKL protein and inflammatory conditions. Dr. Hildebrand said Institute researchers isolated a variant of MLKL that caused a lethal inflammatory condition in laboratory models. "We discovered this form of MLKL contained a single mutation in a particular region of the protein that made MLKL hyperactive, triggering necroptosis and inflammation," she said. "By searching genome databases, we discovered similar variants in the human MLKL gene are surprisingly common—around ten per cent of human genomes from around the world carry altered forms of the MLKL gene that result in a more-easily activated, more inflammatory version of the protein. The team speculated that the pro-inflammatory variant of MLKL might be associated with inflammatory diseases. "We looked more closely at databases of genomes of people with inflammatory diseases to understand the prevalence of MLKL variants. Indeed, people with an autoinflammatory condition chronic recurrent multifocal osteomyelitis (CRMO) were much more likely to carry two copies of a pro-inflammatory variant of the MLKL gene than people without an inflammatory disease. This is the first time changes in MLKL have been associated with a human inflammatory disease," Dr. Hildebrand said. Evolutionary pressure on MLKL Dr. Hildebrand said the high frequency of MLKL variants in humans around the world suggested that the more inflammatory variants of the protein might have offered an evolutionary benefit at some point of human history. "Perhaps having a more inflammatory form of MLKL meant some people could survive infectious diseases better than those people who only had the less-easily activated form of the protein," she said. In a separate paper, Ms Katherine Davies led research investigating the three-dimensional structure of MLKL in different vertebrate species, using the Australian Synchrotron and CSIRO Collaborative Crystallisation Centre. Dr. Davies said usually when one protein is found in different vertebrate species, the proteins in the different species have a similar structure that has been conserved during evolution. "To our surprise, the structures of MLKL were quite different between different vertebrate species—even between closely related species such as rats and mice. In fact, rat MLKL is so different from mouse MLKL that the rat protein cannot function in mouse cells—which is surprising as many proteins are interchangeable between these two species," Dr. Davies said. "We think that evolutionary pressures such as infections may have driven substantial changes in MLKL as vertebrates evolved. Animals with variant forms of MLKL may have been able to survive some pressures better than other animals, driving changes in MLKL to accumulate, much faster than for many other proteins. "Together with the data for human variations in MLKL, this suggests MLKL is critical for cells to balance beneficial inflammation, which protects against infections, with harmful inflammation that causes inflammatory diseases," Dr. Davies said. Long-term research yields rewards Associate Professor James Murphy said the team's research started through studying the inflammatory variant of MLKL more than 13 years ago—at a time when MLKL's role in necroptosis was not known. "Our most recent discoveries, made by a multidisciplinary research team, have provided a massive advance to the field of necroptosis, adding substantial detail to our understanding of MLKL. This will provide an enormous boost to a range of research into inflammatory diseases. Our team and others are already working to develop new medicines that could temper MLKL-driven inflammation, which we hope could be a new approach to treating a range of inflammatory diseases," Associate Professor Murphy said. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 20187, 54083, 374, 279, 7718, 3369, 1279, 315, 19591, 299, 418, 10934, 11, 264, 1376, 315, 56168, 14869, 29150, 2849, 4648, 13, 1226, 617, 25181, 264, 8814, 26800, 449, 264, 3254, 3194, 1137, 27472, 11, 386, 75, 10784, 423, 10125, 53, 1174, 430, 88687, 279, 1403, 2902, 68818, 3451, 32337, 529, 430, 34161, 279, 25534, 3116, 2902, 68818, 13190, 323, 23331, 51743, 79117, 521, 31576, 13, 1115, 2389, 388, 9129, 6844, 11, 91964, 42, 18, 9678, 13419, 5820, 311, 20187, 54083, 13, 13525, 76523, 70, 788, 61618, 24548, 2274, 45089, 1772, 74439, 37140, 315, 279, 4371, 344, 661, 82375, 323, 25098, 561, 258, 372, 13, 578, 4725, 44481, 14338, 4500, 315, 386, 75, 10784, 423, 10125, 53, 55513, 4341, 70, 6429, 3156, 7342, 11, 323, 279, 19821, 315, 904, 43661, 82423, 304, 30548, 76523, 70, 6429, 5825, 3062, 304, 41294, 47891, 369, 279, 8824, 315, 7917, 311, 2867, 22756, 20187, 54083, 13, 4314, 24654, 3085, 459, 3062, 20616, 1139, 279, 4754, 8624, 17515, 15853, 13073, 315, 2380, 4279, 3823, 20187, 54083, 46033, 16751, 13978, 430, 16559, 42500, 13935, 94750, 2949, 477, 24894, 311, 279, 33964, 5654, 13, 62672, 30548, 76523, 70, 22828, 315, 1521, 27103, 374, 1766, 520, 709, 311, 220, 717, 24325, 279, 3685, 11900, 304, 6978, 430, 7831, 505, 264, 53166, 3313, 258, 55097, 8624, 11, 21249, 65174, 62387, 3768, 52368, 5650, 301, 20000, 320, 9150, 10754, 570, 29438, 64224, 299, 418, 10934, 374, 264, 14869, 29150, 1376, 315, 56168, 2849, 4648, 5938, 449, 279, 5788, 315, 463, 67595, 83185, 1572, 11, 279, 19814, 315, 24156, 79348, 323, 279, 4984, 315, 10805, 65441, 5674, 5938, 31206, 12912, 320, 35, 16407, 82, 8, 220, 16, 662, 64224, 299, 418, 10934, 14117, 389, 279, 15449, 315, 279, 9709, 65009, 82160, 8106, 12970, 320, 2735, 54083, 8, 51743, 79117, 521, 555, 35268, 45830, 13128, 82160, 220, 18, 320, 49, 3378, 42, 18, 8, 220, 17, 1174, 220, 18, 1174, 220, 19, 662, 91964, 42, 18, 82076, 95089, 2354, 315, 20187, 54083, 31854, 264, 390, 1659, 278, 2349, 220, 19, 1174, 220, 20, 430, 73633, 279, 1380, 2588, 311, 11, 323, 42835, 93294, 44219, 315, 11, 35693, 79348, 13, 6104, 279, 24473, 6160, 91004, 17383, 315, 39654, 44219, 374, 2103, 264, 5030, 315, 11249, 11, 4279, 4519, 315, 19225, 4211, 527, 279, 18488, 315, 459, 20187, 54083, 55984, 26429, 323, 279, 2167, 15360, 315, 279, 11572, 261, 3116, 2902, 68818, 13190, 8106, 320, 19, 31825, 8, 315, 20187, 54083, 449, 24156, 79348, 220, 21, 1174, 220, 22, 1174, 220, 23, 1174, 220, 24, 1174, 220, 605, 662, 763, 8814, 7917, 11, 279, 7645, 315, 279, 8309, 483, 20187, 54083, 220, 19, 31825, 8106, 7636, 320, 417, 307, 1157, 220, 16, 4235, 6549, 705, 220, 19, 31825, 5636, 33964, 11591, 1238, 320, 16, 4235, 5245, 705, 477, 279, 7645, 315, 33088, 316, 318, 5411, 477, 1023, 3254, 2816, 51743, 79117, 521, 8106, 320, 21051, 90709, 8, 88754, 374, 14343, 311, 49853, 39654, 1380, 2588, 11, 55984, 26429, 2065, 323, 39654, 19814, 220, 19, 1174, 220, 24, 662, 6104, 13171, 315, 87843, 28367, 19588, 58375, 994, 9124, 38301, 7006, 18007, 11, 30293, 60856, 323, 13890, 3254, 2816, 320, 21051, 90709, 8, 61618, 7739, 315, 3823, 20187, 54083, 656, 539, 22514, 398, 49853, 39654, 75968, 55984, 26429, 2065, 323, 2849, 4648, 2085, 9770, 294, 3212, 2065, 220, 806, 1174, 220, 717, 1174, 220, 1032, 662, 24296, 11, 2225, 8814, 323, 3823, 20187, 54083, 88754, 617, 1027, 5068, 430, 617, 279, 8824, 311, 1376, 39654, 75968, 55984, 69638, 11, 719, 3775, 311, 5353, 93294, 39654, 44219, 323, 2849, 4648, 220, 24, 1174, 220, 1032, 662, 35390, 7978, 617, 10675, 430, 19591, 299, 418, 10934, 52452, 315, 20187, 54083, 95089, 2354, 323, 39654, 15360, 649, 387, 1491, 7913, 555, 11618, 430, 16988, 279, 842, 96108, 29373, 6485, 2631, 369, 7710, 320, 54814, 5463, 8, 3070, 315, 28896, 13, 3861, 1646, 55725, 264, 3560, 369, 44374, 5463, 304, 33994, 19591, 299, 418, 10934, 4669, 32426, 39654, 3521, 1854, 323, 13023, 220, 975, 1418, 1023, 4211, 4017, 32426, 39654, 44219, 555, 44374, 5463, 82076, 4984, 315, 95089, 22851, 20187, 54083, 304, 11741, 65441, 65635, 4440, 220, 868, 1174, 220, 1114, 1174, 220, 1114, 323, 5255, 279, 5419, 2065, 315, 95089, 22851, 20187, 54083, 369, 84495, 96108, 53568, 220, 1114, 662, 763, 24548, 11, 279, 19821, 315, 20187, 54083, 1587, 539, 5101, 311, 617, 8196, 60393, 466, 1245, 48006, 477, 2162, 537, 780, 6372, 220, 19, 1174, 220, 972, 662, 4452, 11, 19465, 37166, 315, 435, 723, 1174, 11301, 79, 23, 477, 36537, 74, 16, 1174, 11767, 311, 33781, 15449, 315, 20187, 54083, 323, 72758, 19591, 299, 418, 10934, 2391, 44481, 52379, 430, 374, 53924, 449, 2324, 7953, 44481, 14338, 1938, 320, 36, 8, 605, 13, 20, 11, 469, 605, 13, 20, 323, 220, 16, 4235, 18, 2919, 1772, 5392, 266, 750, 11, 15947, 220, 777, 1174, 220, 508, 1174, 220, 1691, 1174, 220, 1313, 1174, 220, 1419, 1174, 220, 1187, 1174, 220, 914, 662, 18491, 5620, 279, 24473, 53194, 16296, 315, 33781, 20187, 54083, 15449, 304, 1521, 26350, 374, 17395, 555, 279, 2144, 430, 435, 16040, 11, 11301, 79, 521, 12, 23, 323, 91964, 42, 16, 1101, 1514, 3062, 13073, 304, 35693, 11618, 1023, 1109, 67547, 315, 20187, 54083, 38973, 19591, 299, 418, 14546, 2849, 4648, 220, 1419, 1174, 220, 1627, 1174, 220, 1544, 1174, 220, 1591, 1174, 220, 1682, 1174, 220, 966, 662, 3765, 618, 519, 5990, 315, 20187, 54083, 43918, 2849, 4648, 17210, 311, 8624, 304, 3892, 19465, 323, 22772, 8814, 4211, 220, 1419, 1174, 220, 2148, 1174, 220, 843, 1174, 220, 1644, 1174, 220, 1958, 1174, 220, 1758, 662, 763, 12966, 11, 20187, 54083, 78872, 323, 13128, 5990, 527, 40646, 49393, 449, 20237, 315, 6978, 449, 98144, 100213, 511, 8362, 258, 7942, 11, 67827, 37619, 89385, 37619, 85542, 12, 323, 15235, 12, 51423, 320, 19981, 291, 555, 2098, 13, 220, 1927, 7609, 58603, 11, 1579, 5990, 315, 95089, 22851, 20187, 54083, 527, 5938, 449, 11293, 20237, 304, 1560, 99054, 278, 323, 15235, 9572, 6978, 220, 1806, 662, 9220, 3194, 1137, 20187, 54083, 1794, 780, 34684, 11054, 304, 3823, 9572, 20438, 617, 1027, 1766, 311, 49843, 264, 14278, 304, 19591, 299, 418, 14546, 734, 304, 2849, 6108, 99592, 220, 19, 1174, 220, 1032, 662, 15668, 6051, 11, 37783, 16066, 505, 264, 11775, 18247, 451, 7642, 1413, 19823, 1051, 5068, 439, 55513, 4341, 70, 788, 369, 264, 9024, 46900, 75, 4249, 16239, 264, 14418, 48933, 11678, 304, 20187, 54083, 1174, 439, 1664, 439, 459, 304, 47867, 37166, 315, 832, 42500, 13935, 304, 279, 24894, 40085, 13935, 220, 17, 2902, 68107, 87, 4010, 521, 320, 15358, 17, 39, 883, 15207, 220, 1987, 662, 578, 5199, 70272, 315, 459, 24955, 3880, 548, 20187, 54083, 3009, 2427, 467, 15207, 11678, 281, 10208, 2166, 55, 706, 1027, 5068, 304, 19730, 18711, 8620, 6978, 16066, 505, 264, 1376, 315, 44531, 753, 8624, 220, 2137, 1174, 4869, 810, 4279, 17684, 1029, 483, 20187, 54083, 15207, 27103, 527, 1193, 7621, 398, 5938, 449, 3823, 8624, 304, 42353, 1950, 32906, 13, 1226, 617, 11054, 264, 3254, 2385, 6857, 17684, 1029, 483, 27472, 315, 8814, 386, 75, 10784, 430, 3289, 2601, 264, 3194, 1137, 50068, 2949, 279, 20187, 54083, 33964, 5654, 323, 2389, 388, 9129, 6844, 15449, 9678, 315, 42830, 19591, 299, 418, 14546, 56688, 13, 16644, 420, 61618, 386, 75, 10784, 70510, 374, 3917, 311, 279, 1890, 48006, 323, 12434, 11835, 389, 15207, 7645, 439, 8545, 10827, 386, 75, 10784, 1174, 279, 1772, 74439, 98522, 2786, 304, 1521, 24548, 5825, 20616, 1139, 279, 53194, 323, 89961, 16296, 315, 22709, 81722, 19591, 299, 418, 10934, 13, 763, 15638, 11, 1521, 14955, 6179, 279, 4754, 16003, 26431, 315, 2380, 4279, 3823, 20187, 54083, 46033, 16751, 13978, 430, 16559, 2536, 69604, 54268, 42500, 13935, 94750, 2949, 11, 477, 304, 3345, 37843, 311, 11, 279, 33964, 11591, 953, 430, 374, 85922, 304, 279, 386, 75, 10784, 423, 10125, 53, 8814, 13, 18591, 24367, 315, 264, 9129, 332, 3210, 4642, 1376, 315, 20187, 54083, 386, 501, 25173, 14, 34363, 24548, 11, 56612, 311, 19465, 37166, 315, 279, 3682, 35268, 369, 84664, 65, 56809, 3978, 258, 11, 617, 1193, 220, 605, 4, 279, 8545, 10827, 1396, 315, 35688, 12235, 10145, 13, 1556, 469, 4013, 5318, 8703, 14093, 4264, 574, 10887, 311, 10765, 34684, 430, 126641, 2521, 349, 84664, 65, 511, 16820, 2569, 689, 304, 386, 501, 25173, 14, 34363, 24548, 4669, 84664, 65, 56809, 3978, 258, 9678, 12235, 1169, 5788, 220, 1272, 662, 362, 480, 220, 16, 19533, 11, 24073, 1856, 83, 868, 1174, 1047, 264, 27946, 398, 32389, 12235, 1169, 1797, 315, 220, 9378, 25800, 220, 605, 220, 21, 824, 65170, 7863, 449, 279, 3152, 369, 386, 501, 25173, 14, 34363, 10099, 320, 8190, 20903, 220, 3226, 25800, 220, 605, 220, 21, 824, 65170, 8, 323, 58487, 128257, 198, 128256, 78191, 198, 54, 38377, 323, 4072, 17528, 11166, 10181, 12074, 617, 1903, 5199, 31003, 304, 8830, 279, 47288, 2849, 4648, 23331, 13128, 20187, 54083, 323, 1202, 3560, 304, 8624, 13, 763, 264, 35062, 315, 7978, 4756, 3432, 304, 279, 8486, 22037, 26545, 11, 279, 2128, 1511, 11084, 32758, 311, 51187, 1401, 7504, 304, 279, 15449, 315, 20187, 54083, 11, 31720, 8767, 64233, 3649, 922, 1268, 420, 13128, 20722, 459, 47288, 1376, 315, 2849, 4648, 2663, 19591, 299, 418, 10934, 13, 2435, 1101, 8710, 369, 279, 1176, 892, 430, 28088, 27103, 315, 20187, 54083, 527, 8599, 311, 264, 3823, 47288, 8624, 13, 3296, 38936, 8668, 27339, 304, 3823, 20187, 54083, 323, 27393, 279, 6070, 315, 2204, 10099, 6, 20187, 54083, 28896, 11, 279, 2128, 1101, 3984, 6029, 369, 20187, 54083, 3515, 1027, 3917, 311, 41993, 40850, 11, 13893, 1555, 1202, 3560, 304, 22973, 2403, 30020, 13, 578, 64486, 3510, 44550, 3495, 574, 6197, 555, 2999, 13, 27525, 8388, 942, 11, 2999, 13, 11186, 20991, 473, 35376, 13781, 11, 2999, 13, 23880, 23109, 455, 2554, 11, 16450, 62426, 56872, 11, 33468, 17054, 76249, 70687, 11, 33468, 17054, 11291, 123203, 370, 354, 277, 11, 17054, 26713, 20643, 11, 17054, 3842, 8211, 441, 323, 33468, 17054, 7957, 31053, 13, 46551, 47288, 2849, 4648, 14299, 4648, 374, 264, 1648, 430, 279, 2547, 36236, 5196, 505, 19338, 11, 555, 18054, 36021, 477, 11660, 7917, 13, 763, 1063, 15082, 2345, 21470, 439, 29962, 477, 45964, 30020, 2345, 67, 7169, 7917, 8346, 37140, 311, 6144, 42617, 7917, 505, 279, 19405, 13, 1115, 1376, 315, 2849, 4648, 374, 2663, 364, 77, 762, 299, 418, 10934, 518, 323, 374, 40069, 14400, 555, 3230, 28896, 2949, 7917, 13, 33468, 17054, 7957, 31053, 1071, 279, 13128, 20187, 54083, 574, 459, 3062, 40704, 315, 19591, 299, 418, 10934, 13, 330, 8142, 20187, 54083, 323, 19591, 299, 418, 10934, 6144, 1057, 13162, 505, 30020, 11, 27639, 19591, 299, 418, 10934, 706, 1027, 10815, 449, 47288, 4787, 1778, 439, 47288, 66358, 19338, 1359, 568, 1071, 13, 330, 8140, 3495, 2128, 706, 4529, 3892, 58535, 20414, 311, 2731, 3619, 1268, 20187, 54083, 5865, 50004, 1436, 7417, 279, 8830, 323, 6514, 315, 19338, 16239, 27639, 19591, 299, 418, 10934, 1210, 3861, 4007, 11, 6197, 555, 2999, 13, 27525, 8388, 942, 11, 1511, 11084, 32758, 14645, 311, 3821, 279, 20187, 54083, 13128, 304, 7917, 439, 814, 55093, 19591, 299, 418, 10934, 13, 2999, 13, 8388, 942, 1071, 420, 11054, 1403, 3062, 364, 2071, 7862, 6, 304, 19591, 299, 418, 10934, 13, 330, 1687, 1436, 1518, 1268, 20187, 54083, 5614, 1202, 3813, 439, 19591, 299, 418, 10934, 10222, 11, 1206, 55432, 323, 85626, 311, 2204, 5596, 315, 279, 2849, 439, 279, 2849, 62916, 7119, 4648, 1359, 568, 1071, 13, 330, 644, 376, 343, 7623, 398, 11, 584, 1436, 1518, 22756, 20187, 54083, 9762, 520, 279, 49341, 82, 1990, 42617, 7917, 2345, 19644, 31668, 23377, 264, 1648, 369, 832, 23069, 2849, 311, 8346, 19591, 299, 418, 10934, 304, 14932, 7917, 11, 902, 1436, 387, 264, 1376, 315, 9313, 2403, 30020, 1210, 33305, 323, 4072, 17528, 11166, 10181, 12074, 617, 1511, 55372, 3177, 11071, 92914, 311, 9302, 1082, 7917, 23069, 555, 19591, 299, 418, 10934, 11, 264, 1376, 315, 47288, 2849, 4648, 13, 16666, 25, 33305, 323, 4072, 17528, 11166, 10181, 320, 89171, 291, 505, 2835, 4756, 304, 8388, 942, 1880, 453, 11, 22037, 26545, 8, 15766, 315, 20187, 54083, 304, 47288, 19338, 2999, 13, 11186, 20991, 473, 35376, 13781, 323, 2999, 13, 23880, 23109, 455, 2554, 25078, 7902, 1990, 61086, 304, 279, 20187, 54083, 13128, 323, 47288, 4787, 13, 2999, 13, 473, 35376, 13781, 1071, 10181, 12074, 25181, 264, 11678, 315, 20187, 54083, 430, 9057, 264, 45089, 47288, 3044, 304, 27692, 4211, 13, 330, 1687, 11352, 420, 1376, 315, 20187, 54083, 13282, 264, 3254, 27472, 304, 264, 4040, 5654, 315, 279, 13128, 430, 1903, 20187, 54083, 17508, 3104, 11, 52605, 19591, 299, 418, 10934, 323, 37140, 1359, 1364, 1071, 13, 330, 1383, 15389, 33869, 32906, 11, 584, 11352, 4528, 27103, 304, 279, 3823, 20187, 54083, 15207, 527, 29392, 4279, 2345, 20019, 5899, 824, 2960, 315, 3823, 85381, 505, 2212, 279, 1917, 6920, 29852, 7739, 315, 279, 20187, 54083, 15207, 430, 1121, 304, 264, 810, 5773, 38367, 22756, 11, 810, 47288, 2373, 315, 279, 13128, 13, 578, 2128, 74877, 430, 279, 463, 67595, 11678, 315, 20187, 54083, 2643, 387, 5938, 449, 47288, 19338, 13, 330, 1687, 7111, 810, 15499, 520, 32906, 315, 85381, 315, 1274, 449, 47288, 19338, 311, 3619, 279, 38009, 315, 20187, 54083, 27103, 13, 23150, 11, 1274, 449, 459, 3313, 258, 55097, 3044, 21249, 65174, 62387, 3768, 52368, 5650, 301, 20000, 320, 9150, 10754, 8, 1051, 1790, 810, 4461, 311, 6920, 1403, 11236, 315, 264, 463, 67595, 11678, 315, 279, 20187, 54083, 15207, 1109, 1274, 2085, 459, 47288, 8624, 13, 1115, 374, 279, 1176, 892, 4442, 304, 20187, 54083, 617, 1027, 5938, 449, 264, 3823, 47288, 8624, 1359, 2999, 13, 473, 35376, 13781, 1071, 13, 38321, 661, 7410, 389, 20187, 54083, 2999, 13, 473, 35376, 13781, 1071, 279, 1579, 11900, 315, 20187, 54083, 27103, 304, 12966, 2212, 279, 1917, 12090, 430, 279, 810, 47288, 27103, 315, 279, 13128, 2643, 617, 9076, 459, 41993, 8935, 520, 1063, 1486, 315, 3823, 3925, 13, 330, 32576, 3515, 264, 810, 47288, 1376, 315, 20187, 54083, 8967, 1063, 1274, 1436, 18167, 50600, 19338, 2731, 1109, 1884, 1274, 889, 1193, 1047, 279, 2753, 5773, 38367, 22756, 1376, 315, 279, 13128, 1359, 1364, 1071, 13, 763, 264, 8821, 5684, 11, 16450, 62426, 56872, 6197, 3495, 24834, 279, 2380, 33520, 6070, 315, 20187, 54083, 304, 2204, 67861, 65216, 9606, 11, 1701, 279, 13673, 24028, 331, 299, 35785, 323, 10211, 68884, 49681, 1413, 4656, 599, 543, 8082, 14821, 13, 2999, 13, 56872, 1071, 6118, 994, 832, 13128, 374, 1766, 304, 2204, 67861, 65216, 9606, 11, 279, 28896, 304, 279, 2204, 9606, 617, 264, 4528, 6070, 430, 706, 1027, 1615, 2841, 2391, 15740, 13, 330, 1271, 1057, 13051, 11, 279, 14726, 315, 20187, 54083, 1051, 5115, 2204, 1990, 2204, 67861, 65216, 9606, 80078, 1990, 15499, 5552, 9606, 1778, 439, 32510, 323, 24548, 13, 763, 2144, 11, 11494, 20187, 54083, 374, 779, 2204, 505, 8814, 20187, 54083, 430, 279, 11494, 13128, 4250, 734, 304, 8814, 7917, 50004, 374, 15206, 439, 1690, 28896, 527, 91229, 1990, 1521, 1403, 9606, 1359, 2999, 13, 56872, 1071, 13, 330, 1687, 1781, 430, 41993, 40850, 1778, 439, 30020, 1253, 617, 16625, 12190, 4442, 304, 20187, 54083, 439, 67861, 99868, 28995, 13, 47966, 449, 11678, 7739, 315, 20187, 54083, 1253, 617, 1027, 3025, 311, 18167, 1063, 40850, 2731, 1109, 1023, 10099, 11, 10043, 4442, 304, 20187, 54083, 311, 47376, 11, 1790, 10819, 1109, 369, 1690, 1023, 28896, 13, 330, 82087, 449, 279, 828, 369, 3823, 27339, 304, 20187, 54083, 11, 420, 13533, 20187, 54083, 374, 9200, 369, 7917, 311, 8335, 24629, 37140, 11, 902, 36236, 2403, 30020, 11, 449, 28856, 37140, 430, 11384, 47288, 19338, 1359, 2999, 13, 56872, 1071, 13, 5843, 9860, 3495, 36508, 21845, 33468, 17054, 7957, 31053, 1071, 279, 2128, 596, 3495, 3940, 1555, 21630, 279, 47288, 11678, 315, 20187, 54083, 810, 1109, 220, 1032, 1667, 4227, 99563, 264, 892, 994, 20187, 54083, 596, 3560, 304, 19591, 299, 418, 10934, 574, 539, 3967, 13, 330, 8140, 1455, 3293, 54098, 11, 1903, 555, 264, 64486, 3510, 44550, 3495, 2128, 11, 617, 3984, 264, 11191, 12178, 311, 279, 2115, 315, 19591, 299, 418, 10934, 11, 7999, 12190, 7872, 311, 1057, 8830, 315, 20187, 54083, 13, 1115, 690, 3493, 459, 23205, 7916, 311, 264, 2134, 315, 3495, 1139, 47288, 19338, 13, 5751, 2128, 323, 3885, 527, 2736, 3318, 311, 2274, 502, 39653, 430, 1436, 6940, 20187, 54083, 32505, 37140, 11, 902, 584, 3987, 1436, 387, 264, 502, 5603, 311, 27723, 264, 2134, 315, 47288, 19338, 1359, 33468, 17054, 31053, 1071, 13, 220, 128257, 198 ]

2,782

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract The ecosystem services afforded by coastal wetlands are threatened by climate change and other anthropogenic stressors. The Kennedy Space Center and Merritt Island National Wildlife Refuge in east central Florida offer a representative site for investigating how changes to vegetation distribution interact with management to impact coastal protection. Here, salt marshes are converting to mangroves, and mosquito impoundment structures are being modified. The resulting changes to vegetation composition and topography influence coastal protection services in wetlands. We used a model-based assessment of wave attenuation and erosion to compare vegetation (mangrove, salt marsh) and impoundment state (intact, graded). Our findings suggest that the habitat needed to attenuate 90% of wave height is significantly larger for salt marshes than mangroves. Erosion prevention was significantly higher (470%) in scenarios with mangroves than in salt marshes. Intact berms attenuated waves over shorter distances, but did not significantly reduce erosion. Differences in coastal protection were driven more by vegetation than by impoundment state. Overall, our findings reveal that mangroves provide more coastal protection services, and therefore more coastal protection value, than salt marshes in east central Florida. Other coastal regions undergoing similar habitat conversion may also benefit from increased coastal protection in the future. Access provided by Universität des es, -und Working on a manuscript? Avoid the common mistakes Introduction Many of the world’s coastal systems are threatened by climate change and anthropogenic development. Climate change impacts are prevalent in coastal systems where increasing temperatures, rising seas, and coastal storm events alter ecosystem structure, function, and resiliency (Day et al., 2008 ; Wong et al., 2014 ). In addition, climate change induces secondary impacts, for example, in the form of shifts in species’ ranges (Parmesan & Yohe, 2003 ; Walther, 2004 ). For coastal ecosystems, this phenomenon is exemplified by the poleward expansion of mangroves into predominantly salt marsh ecosystems (Saintilan et al., 2014 ). Although the mechanisms which drive or limit mangrove expansion have been well studied globally (Saintilan et al., 2014 ; Osland et al., 2016a ), less is known about the ecosystem service impacts that may arise from such dramatic habitat conversion. Climate change impacts may be amplified in coastal areas where humans both impact and depend on ecosystem services a great deal. In general, coastal wetlands are regarded as one of the most economically valuable ecosystems (de Groot et al., 2012 ). As of late, there is increasing interest in the potential of natural ecosystems, or “green infrastructure,” to provide protective services (Gómez-Baggethun & Barton, 2013 ; Lovell & Taylor, 2013 ; Saleh & Weinstein, 2016 ). Natural coastal ecosystems prevent damage and shield coastal communities from waves and storm surge associated with storm events (Costanza et al., 2008 ; Gedan et al., 2011 ; Arkema et al., 2013 ; Guannel et al., 2016 ). However, habitat conversion and coastal development is changing the structure and function of coastal ecosystems, which will alter their capacity to deliver these services. The protective services provided by coastal systems are determined by several scale-dependent factors. At the local scale (meters to 100s of meters), wetland vegetation protects coastlines by attenuating waves, reducing erosion, and promoting sediment deposition (Gedan et al., 2011 ). These benefits are provided by physical plant structures that induce wave-breaking and dampen wave energy through flow separation and friction (Koch et al., 2009 ; Gedan et al., 2011 ; Duarte et al., 2013 ). The coastal protection capabilities of salt marsh and mangrove vegetation can vary greatly due to individual plant characteristics such as morphology, biomass, stem rigidity, and structural complexity, which differentially affect wave attenuation, sediment accretion, and erosion prevention (Koch et al., 2009 ; Duarte et al., 2013 ). Vegetation characteristics at the landscape level also play a role in coastal protection. For example, greater stem densities and stand size have been shown to increase wave attenuation and shoreline stabilization in both mangroves (Alongi, 2008 ) and salt marshes (Shepard et al., 2011 ). However, the ability of vegetation to stabilize the coast can vary non-linearly with habitat size and is also dependent on physical factors like coastal geomorphology and topography (Alongi, 2008 ; Koch et al., 2009 ; Shepard et al., 2011 ; Duarte et al., 2013 ). Due to the high spatial variability in the factors influencing coastal protection services, additional site-specific investigations and comparative studies are needed to fill existing data gaps and to improve how coastal protection services are evaluated (Woodward & Wui, 2001 ; Koch et al., 2009 ). Evidence that coastal habitats provide protective services has been shown through field assessments, laboratory investigations, and modeling approaches for a number of vegetation types and geomorphic settings (Wamsley et al., 2010 ; Gedan et al., 2011 ; Shepard et al., 2011 ; Duarte et al., 2013 ; Barbier, 2016 ). However, there have not been any studies that have compared coastal protection capabilities of mangroves and salt marsh in the same location and geomorphic setting. As a result, these studies may have limited application to ecotonal regions where mangrove and salt marsh habitats converge. Here, mangrove morphologies diverge from tropical norms (Morrisey et al., 2010 ), habitat distributions are dynamic (Saintilan & Rogers, 2015 ; Osland et al., 2016b ), and anthropogenic influence is often high (Halpern et al., 2008 ; Crain et al., 2009 ). In recent decades, mangrove abundance in coastal wetlands along the eastern coast of Florida has been increasing and mangrove range limits have been shifting northward, in concert with global trends (Osland et al., 2013 ; Cavanaugh et al., 2014 , 2015 ; Williams et al., 2014 ; Rodriguez et al., 2016 ). In addition to salt marsh-to-mangrove conversion, the wetlands of this region are impacted by changing management regimes regarding mosquito control and hydrology (Rey & Kain, 1989 ). The large-scale implementation of mosquito impoundment structures in the coastal counties of eastern Florida dates back to the 1950s (Brockmeyer et al., 1996 ). A mosquito impoundment is a wetland that has been diked to allow for the management", "role": "user" }, { "content": "The threat to coastal regions posed by climate change, overdevelopment and other human caused stressors is well-established. Among the most prized and valuable land throughout the world, shorelines everywhere are imperiled by sea level rise, beach erosion and flooding. But a recently published NASA-funded research study in which Villanova University Biology Professor Samantha Chapman played a key role has discovered a new, natural phenomenon that could offer an economic and ecological solution to coastal wetland protection—the spread of mangrove trees. Mangroves are tropical trees that grow in coastal intertidal zones, notable for their dense tangles of prop roots which serve as highly effective shields for coastlines by reducing the force of breaking waves, decreasing erosion and increasing sediment deposition. These trees are rapidly moving northward in Florida due to the lack of hard freezes. Once there, they change habitats previously dominated by salt marshes into mangrove swamps. The new study, titled, \"Impacts of mangrove encroachment and mosquito impoundment on coastal protection services,\" compares the coastal protection value of salt marshes with mangroves along Florida's East central coast and the overlying area of The Merritt Island National Wildlife Refuge (MINWR) in which NASA's Kennedy Space Center (KSC) is located. The study, published in Hydrobiologia, turned up some remarkable results in comparing the protective value of salt marshes to mangroves. Mangrove expansion was the clear winner in providing superior coastal protection over salt marshes. Mangrove habitats provide a staggering 800 per cent more coastal protection than salt marshes. In all, mangrove habitats could provide $4.9 million worth of coastal protection more than manmade barriers. In the U.S. alone, the study points out, wetland coastal protection services provide an estimated $23.2 billion per year of protection against economic losses as well as deaths associated with major storm events. Although the impact of impending climate change is uncertain, the study concludes that \"Integrating ecosystem-based approaches and ecological engineering may offer a way to mitigate and adapt to the effects of rising seas and intensifying storms.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract The ecosystem services afforded by coastal wetlands are threatened by climate change and other anthropogenic stressors. The Kennedy Space Center and Merritt Island National Wildlife Refuge in east central Florida offer a representative site for investigating how changes to vegetation distribution interact with management to impact coastal protection. Here, salt marshes are converting to mangroves, and mosquito impoundment structures are being modified. The resulting changes to vegetation composition and topography influence coastal protection services in wetlands. We used a model-based assessment of wave attenuation and erosion to compare vegetation (mangrove, salt marsh) and impoundment state (intact, graded). Our findings suggest that the habitat needed to attenuate 90% of wave height is significantly larger for salt marshes than mangroves. Erosion prevention was significantly higher (470%) in scenarios with mangroves than in salt marshes. Intact berms attenuated waves over shorter distances, but did not significantly reduce erosion. Differences in coastal protection were driven more by vegetation than by impoundment state. Overall, our findings reveal that mangroves provide more coastal protection services, and therefore more coastal protection value, than salt marshes in east central Florida. Other coastal regions undergoing similar habitat conversion may also benefit from increased coastal protection in the future. Access provided by Universität des es, -und Working on a manuscript? Avoid the common mistakes Introduction Many of the world’s coastal systems are threatened by climate change and anthropogenic development. Climate change impacts are prevalent in coastal systems where increasing temperatures, rising seas, and coastal storm events alter ecosystem structure, function, and resiliency (Day et al., 2008 ; Wong et al., 2014 ). In addition, climate change induces secondary impacts, for example, in the form of shifts in species’ ranges (Parmesan & Yohe, 2003 ; Walther, 2004 ). For coastal ecosystems, this phenomenon is exemplified by the poleward expansion of mangroves into predominantly salt marsh ecosystems (Saintilan et al., 2014 ). Although the mechanisms which drive or limit mangrove expansion have been well studied globally (Saintilan et al., 2014 ; Osland et al., 2016a ), less is known about the ecosystem service impacts that may arise from such dramatic habitat conversion. Climate change impacts may be amplified in coastal areas where humans both impact and depend on ecosystem services a great deal. In general, coastal wetlands are regarded as one of the most economically valuable ecosystems (de Groot et al., 2012 ). As of late, there is increasing interest in the potential of natural ecosystems, or “green infrastructure,” to provide protective services (Gómez-Baggethun & Barton, 2013 ; Lovell & Taylor, 2013 ; Saleh & Weinstein, 2016 ). Natural coastal ecosystems prevent damage and shield coastal communities from waves and storm surge associated with storm events (Costanza et al., 2008 ; Gedan et al., 2011 ; Arkema et al., 2013 ; Guannel et al., 2016 ). However, habitat conversion and coastal development is changing the structure and function of coastal ecosystems, which will alter their capacity to deliver these services. The protective services provided by coastal systems are determined by several scale-dependent factors. At the local scale (meters to 100s of meters), wetland vegetation protects coastlines by attenuating waves, reducing erosion, and promoting sediment deposition (Gedan et al., 2011 ). These benefits are provided by physical plant structures that induce wave-breaking and dampen wave energy through flow separation and friction (Koch et al., 2009 ; Gedan et al., 2011 ; Duarte et al., 2013 ). The coastal protection capabilities of salt marsh and mangrove vegetation can vary greatly due to individual plant characteristics such as morphology, biomass, stem rigidity, and structural complexity, which differentially affect wave attenuation, sediment accretion, and erosion prevention (Koch et al., 2009 ; Duarte et al., 2013 ). Vegetation characteristics at the landscape level also play a role in coastal protection. For example, greater stem densities and stand size have been shown to increase wave attenuation and shoreline stabilization in both mangroves (Alongi, 2008 ) and salt marshes (Shepard et al., 2011 ). However, the ability of vegetation to stabilize the coast can vary non-linearly with habitat size and is also dependent on physical factors like coastal geomorphology and topography (Alongi, 2008 ; Koch et al., 2009 ; Shepard et al., 2011 ; Duarte et al., 2013 ). Due to the high spatial variability in the factors influencing coastal protection services, additional site-specific investigations and comparative studies are needed to fill existing data gaps and to improve how coastal protection services are evaluated (Woodward & Wui, 2001 ; Koch et al., 2009 ). Evidence that coastal habitats provide protective services has been shown through field assessments, laboratory investigations, and modeling approaches for a number of vegetation types and geomorphic settings (Wamsley et al., 2010 ; Gedan et al., 2011 ; Shepard et al., 2011 ; Duarte et al., 2013 ; Barbier, 2016 ). However, there have not been any studies that have compared coastal protection capabilities of mangroves and salt marsh in the same location and geomorphic setting. As a result, these studies may have limited application to ecotonal regions where mangrove and salt marsh habitats converge. Here, mangrove morphologies diverge from tropical norms (Morrisey et al., 2010 ), habitat distributions are dynamic (Saintilan & Rogers, 2015 ; Osland et al., 2016b ), and anthropogenic influence is often high (Halpern et al., 2008 ; Crain et al., 2009 ). In recent decades, mangrove abundance in coastal wetlands along the eastern coast of Florida has been increasing and mangrove range limits have been shifting northward, in concert with global trends (Osland et al., 2013 ; Cavanaugh et al., 2014 , 2015 ; Williams et al., 2014 ; Rodriguez et al., 2016 ). In addition to salt marsh-to-mangrove conversion, the wetlands of this region are impacted by changing management regimes regarding mosquito control and hydrology (Rey & Kain, 1989 ). The large-scale implementation of mosquito impoundment structures in the coastal counties of eastern Florida dates back to the 1950s (Brockmeyer et al., 1996 ). A mosquito impoundment is a wetland that has been diked to allow for the management<|im_end|> <|im_start|>assistant The threat to coastal regions posed by climate change, overdevelopment and other human caused stressors is well-established. Among the most prized and valuable land throughout the world, shorelines everywhere are imperiled by sea level rise, beach erosion and flooding. But a recently published NASA-funded research study in which Villanova University Biology Professor Samantha Chapman played a key role has discovered a new, natural phenomenon that could offer an economic and ecological solution to coastal wetland protection—the spread of mangrove trees. Mangroves are tropical trees that grow in coastal intertidal zones, notable for their dense tangles of prop roots which serve as highly effective shields for coastlines by reducing the force of breaking waves, decreasing erosion and increasing sediment deposition. These trees are rapidly moving northward in Florida due to the lack of hard freezes. Once there, they change habitats previously dominated by salt marshes into mangrove swamps. The new study, titled, "Impacts of mangrove encroachment and mosquito impoundment on coastal protection services," compares the coastal protection value of salt marshes with mangroves along Florida's East central coast and the overlying area of The Merritt Island National Wildlife Refuge (MINWR) in which NASA's Kennedy Space Center (KSC) is located. The study, published in Hydrobiologia, turned up some remarkable results in comparing the protective value of salt marshes to mangroves. Mangrove expansion was the clear winner in providing superior coastal protection over salt marshes. Mangrove habitats provide a staggering 800 per cent more coastal protection than salt marshes. In all, mangrove habitats could provide $4.9 million worth of coastal protection more than manmade barriers. In the U.S. alone, the study points out, wetland coastal protection services provide an estimated $23.2 billion per year of protection against economic losses as well as deaths associated with major storm events. Although the impact of impending climate change is uncertain, the study concludes that "Integrating ecosystem-based approaches and ecological engineering may offer a way to mitigate and adapt to the effects of rising seas and intensifying storms." <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 578, 26031, 3600, 66699, 555, 35335, 14739, 8329, 527, 21699, 555, 10182, 2349, 323, 1023, 41416, 29569, 8631, 1105, 13, 578, 24573, 11746, 5955, 323, 48961, 1468, 10951, 5165, 42649, 52219, 304, 11226, 8792, 9784, 3085, 264, 18740, 2816, 369, 24834, 1268, 4442, 311, 54832, 8141, 16681, 449, 6373, 311, 5536, 35335, 9313, 13, 5810, 11, 12290, 33096, 288, 527, 34537, 311, 51296, 299, 2396, 11, 323, 50646, 3242, 801, 479, 14726, 527, 1694, 11041, 13, 578, 13239, 4442, 311, 54832, 18528, 323, 1948, 5814, 10383, 35335, 9313, 3600, 304, 14739, 8329, 13, 1226, 1511, 264, 1646, 6108, 15813, 315, 12330, 95218, 323, 58097, 311, 9616, 54832, 320, 76, 526, 51515, 11, 12290, 33096, 8, 323, 3242, 801, 479, 1614, 320, 396, 533, 11, 80273, 570, 5751, 14955, 4284, 430, 279, 39646, 4460, 311, 57732, 349, 220, 1954, 4, 315, 12330, 2673, 374, 12207, 8294, 369, 12290, 33096, 288, 1109, 51296, 299, 2396, 13, 469, 3714, 290, 27344, 574, 12207, 5190, 320, 17711, 11587, 304, 26350, 449, 51296, 299, 2396, 1109, 304, 12290, 33096, 288, 13, 1357, 533, 10418, 1026, 57732, 660, 17301, 927, 24210, 27650, 11, 719, 1550, 539, 12207, 8108, 58097, 13, 86897, 304, 35335, 9313, 1051, 16625, 810, 555, 54832, 1109, 555, 3242, 801, 479, 1614, 13, 28993, 11, 1057, 14955, 16805, 430, 51296, 299, 2396, 3493, 810, 35335, 9313, 3600, 11, 323, 9093, 810, 35335, 9313, 907, 11, 1109, 12290, 33096, 288, 304, 11226, 8792, 9784, 13, 7089, 35335, 13918, 47397, 4528, 39646, 14747, 1253, 1101, 8935, 505, 7319, 35335, 9313, 304, 279, 3938, 13, 9742, 3984, 555, 15915, 37714, 951, 1560, 11, 482, 1263, 22938, 389, 264, 47913, 30, 35106, 279, 4279, 21294, 29438, 9176, 315, 279, 1917, 753, 35335, 6067, 527, 21699, 555, 10182, 2349, 323, 41416, 29569, 4500, 13, 31636, 2349, 25949, 527, 46941, 304, 35335, 6067, 1405, 7859, 20472, 11, 16448, 52840, 11, 323, 35335, 13766, 4455, 11857, 26031, 6070, 11, 734, 11, 323, 594, 4008, 2301, 320, 10369, 1880, 453, 2637, 220, 1049, 23, 2652, 56728, 1880, 453, 2637, 220, 679, 19, 7609, 763, 5369, 11, 10182, 2349, 90974, 14580, 25949, 11, 369, 3187, 11, 304, 279, 1376, 315, 29735, 304, 9606, 529, 21986, 320, 41211, 63524, 612, 44188, 383, 11, 220, 1049, 18, 2652, 14916, 700, 11, 220, 1049, 19, 7609, 1789, 35335, 61951, 11, 420, 25885, 374, 39039, 1908, 555, 279, 26078, 1637, 14800, 315, 51296, 299, 2396, 1139, 47904, 12290, 33096, 61951, 320, 57475, 90459, 1880, 453, 2637, 220, 679, 19, 7609, 10541, 279, 24717, 902, 6678, 477, 4017, 51296, 51515, 14800, 617, 1027, 1664, 20041, 31550, 320, 57475, 90459, 1880, 453, 2637, 220, 679, 19, 2652, 15796, 1974, 1880, 453, 2637, 220, 679, 21, 64, 7026, 2753, 374, 3967, 922, 279, 26031, 2532, 25949, 430, 1253, 31889, 505, 1778, 22520, 39646, 14747, 13, 31636, 2349, 25949, 1253, 387, 83598, 304, 35335, 5789, 1405, 12966, 2225, 5536, 323, 6904, 389, 26031, 3600, 264, 2294, 3568, 13, 763, 4689, 11, 35335, 14739, 8329, 527, 27458, 439, 832, 315, 279, 1455, 47379, 15525, 61951, 320, 451, 480, 2959, 1880, 453, 2637, 220, 679, 17, 7609, 1666, 315, 3389, 11, 1070, 374, 7859, 2802, 304, 279, 4754, 315, 5933, 61951, 11, 477, 1054, 13553, 14054, 2476, 311, 3493, 29219, 3600, 320, 38, 1832, 83256, 7826, 351, 456, 71, 359, 612, 70317, 11, 220, 679, 18, 2652, 35393, 616, 612, 16844, 11, 220, 679, 18, 2652, 13618, 71, 612, 56682, 11, 220, 679, 21, 7609, 18955, 35335, 61951, 5471, 5674, 323, 20858, 35335, 10977, 505, 17301, 323, 13766, 22531, 5938, 449, 13766, 4455, 320, 15289, 27564, 1880, 453, 2637, 220, 1049, 23, 2652, 65577, 276, 1880, 453, 2637, 220, 679, 16, 2652, 22791, 9355, 1880, 453, 2637, 220, 679, 18, 2652, 4673, 2659, 1880, 453, 2637, 220, 679, 21, 7609, 4452, 11, 39646, 14747, 323, 35335, 4500, 374, 10223, 279, 6070, 323, 734, 315, 35335, 61951, 11, 902, 690, 11857, 872, 8824, 311, 6493, 1521, 3600, 13, 578, 29219, 3600, 3984, 555, 35335, 6067, 527, 11075, 555, 3892, 5569, 43918, 9547, 13, 2468, 279, 2254, 5569, 320, 76, 2481, 311, 220, 1041, 82, 315, 20645, 705, 14739, 1974, 54832, 36236, 13962, 8128, 555, 57732, 1113, 17301, 11, 18189, 58097, 11, 323, 22923, 59132, 65374, 320, 38, 291, 276, 1880, 453, 2637, 220, 679, 16, 7609, 4314, 7720, 527, 3984, 555, 7106, 6136, 14726, 430, 49853, 12330, 55407, 323, 41369, 268, 12330, 4907, 1555, 6530, 25768, 323, 39676, 320, 42, 5059, 1880, 453, 2637, 220, 1049, 24, 2652, 65577, 276, 1880, 453, 2637, 220, 679, 16, 2652, 16062, 20430, 1880, 453, 2637, 220, 679, 18, 7609, 578, 35335, 9313, 17357, 315, 12290, 33096, 323, 51296, 51515, 54832, 649, 13592, 19407, 4245, 311, 3927, 6136, 17910, 1778, 439, 79612, 11, 58758, 11, 19646, 13552, 19025, 11, 323, 24693, 23965, 11, 902, 2204, 34575, 7958, 12330, 95218, 11, 59132, 1046, 2171, 290, 11, 323, 58097, 27344, 320, 42, 5059, 1880, 453, 2637, 220, 1049, 24, 2652, 16062, 20430, 1880, 453, 2637, 220, 679, 18, 7609, 43800, 367, 17910, 520, 279, 18921, 2237, 1101, 1514, 264, 3560, 304, 35335, 9313, 13, 1789, 3187, 11, 7191, 19646, 90816, 323, 2559, 1404, 617, 1027, 6982, 311, 5376, 12330, 95218, 323, 99164, 83938, 304, 2225, 51296, 299, 2396, 320, 50909, 72, 11, 220, 1049, 23, 883, 323, 12290, 33096, 288, 320, 8100, 62743, 1880, 453, 2637, 220, 679, 16, 7609, 4452, 11, 279, 5845, 315, 54832, 311, 70236, 279, 13962, 649, 13592, 2536, 62399, 398, 449, 39646, 1404, 323, 374, 1101, 18222, 389, 7106, 9547, 1093, 35335, 28355, 16751, 2508, 323, 1948, 5814, 320, 50909, 72, 11, 220, 1049, 23, 2652, 40593, 1880, 453, 2637, 220, 1049, 24, 2652, 72919, 1880, 453, 2637, 220, 679, 16, 2652, 16062, 20430, 1880, 453, 2637, 220, 679, 18, 7609, 24586, 311, 279, 1579, 29079, 54709, 304, 279, 9547, 66700, 35335, 9313, 3600, 11, 5217, 2816, 19440, 26969, 323, 55394, 7978, 527, 4460, 311, 5266, 6484, 828, 33251, 323, 311, 7417, 1268, 35335, 9313, 3600, 527, 26126, 320, 49492, 1637, 612, 468, 2005, 11, 220, 1049, 16, 2652, 40593, 1880, 453, 2637, 220, 1049, 24, 7609, 44796, 430, 35335, 71699, 3493, 29219, 3600, 706, 1027, 6982, 1555, 2115, 41300, 11, 27692, 26969, 11, 323, 34579, 20414, 369, 264, 1396, 315, 54832, 4595, 323, 28355, 41969, 5110, 320, 54, 4214, 3258, 1880, 453, 2637, 220, 679, 15, 2652, 65577, 276, 1880, 453, 2637, 220, 679, 16, 2652, 72919, 1880, 453, 2637, 220, 679, 16, 2652, 16062, 20430, 1880, 453, 2637, 220, 679, 18, 2652, 47142, 1291, 11, 220, 679, 21, 7609, 4452, 11, 1070, 617, 539, 1027, 904, 7978, 430, 617, 7863, 35335, 9313, 17357, 315, 51296, 299, 2396, 323, 12290, 33096, 304, 279, 1890, 3813, 323, 28355, 41969, 6376, 13, 1666, 264, 1121, 11, 1521, 7978, 1253, 617, 7347, 3851, 311, 12208, 354, 25180, 13918, 1405, 51296, 51515, 323, 12290, 33096, 71699, 80867, 13, 5810, 11, 51296, 51515, 27448, 9268, 37441, 713, 505, 35148, 40851, 320, 44, 17847, 1082, 88, 1880, 453, 2637, 220, 679, 15, 7026, 39646, 43785, 527, 8915, 320, 57475, 90459, 612, 34467, 11, 220, 679, 20, 2652, 15796, 1974, 1880, 453, 2637, 220, 679, 21, 65, 7026, 323, 41416, 29569, 10383, 374, 3629, 1579, 320, 57041, 716, 77, 1880, 453, 2637, 220, 1049, 23, 2652, 4656, 467, 1880, 453, 2637, 220, 1049, 24, 7609, 763, 3293, 11026, 11, 51296, 51515, 37492, 304, 35335, 14739, 8329, 3235, 279, 24024, 13962, 315, 9784, 706, 1027, 7859, 323, 51296, 51515, 2134, 13693, 617, 1027, 32931, 10411, 1637, 11, 304, 21497, 449, 3728, 18845, 320, 29967, 1974, 1880, 453, 2637, 220, 679, 18, 2652, 356, 35814, 1880, 453, 2637, 220, 679, 19, 1174, 220, 679, 20, 2652, 13926, 1880, 453, 2637, 220, 679, 19, 2652, 41732, 1880, 453, 2637, 220, 679, 21, 7609, 763, 5369, 311, 12290, 33096, 4791, 1474, 526, 51515, 14747, 11, 279, 14739, 8329, 315, 420, 5654, 527, 40028, 555, 10223, 6373, 61911, 9002, 50646, 2585, 323, 17055, 36781, 320, 697, 88, 612, 735, 467, 11, 220, 3753, 24, 7609, 578, 3544, 13230, 8292, 315, 50646, 3242, 801, 479, 14726, 304, 279, 35335, 31276, 315, 24024, 9784, 13003, 1203, 311, 279, 220, 6280, 15, 82, 320, 33, 21161, 76, 35472, 1880, 453, 2637, 220, 2550, 21, 7609, 362, 50646, 3242, 801, 479, 374, 264, 14739, 1974, 430, 706, 1027, 294, 43708, 311, 2187, 369, 279, 6373, 128257, 198, 128256, 78191, 198, 791, 6023, 311, 35335, 13918, 37260, 555, 10182, 2349, 11, 927, 30671, 323, 1023, 3823, 9057, 8631, 1105, 374, 1664, 64868, 13, 22395, 279, 1455, 87630, 323, 15525, 4363, 6957, 279, 1917, 11, 31284, 8128, 17277, 527, 17190, 2230, 555, 9581, 2237, 10205, 11, 11573, 58097, 323, 39262, 13, 2030, 264, 6051, 4756, 22146, 50701, 3495, 4007, 304, 902, 16959, 86563, 3907, 40023, 17054, 63908, 60914, 6476, 264, 1401, 3560, 706, 11352, 264, 502, 11, 5933, 25885, 430, 1436, 3085, 459, 7100, 323, 50953, 6425, 311, 35335, 14739, 1974, 9313, 22416, 9041, 315, 51296, 51515, 12690, 13, 60148, 299, 2396, 527, 35148, 12690, 430, 3139, 304, 35335, 958, 25453, 278, 26467, 11, 28289, 369, 872, 29050, 259, 17694, 315, 2047, 20282, 902, 8854, 439, 7701, 7524, 53765, 369, 13962, 8128, 555, 18189, 279, 5457, 315, 15061, 17301, 11, 44649, 58097, 323, 7859, 59132, 65374, 13, 4314, 12690, 527, 19019, 7366, 10411, 1637, 304, 9784, 4245, 311, 279, 6996, 315, 2653, 94477, 13, 9843, 1070, 11, 814, 2349, 71699, 8767, 30801, 555, 12290, 33096, 288, 1139, 51296, 51515, 2064, 14989, 13, 578, 502, 4007, 11, 25891, 11, 330, 26282, 11613, 315, 51296, 51515, 3289, 299, 9064, 323, 50646, 3242, 801, 479, 389, 35335, 9313, 3600, 1359, 43565, 279, 35335, 9313, 907, 315, 12290, 33096, 288, 449, 51296, 299, 2396, 3235, 9784, 596, 6460, 8792, 13962, 323, 279, 927, 6852, 3158, 315, 578, 48961, 1468, 10951, 5165, 42649, 52219, 320, 16818, 18408, 8, 304, 902, 22146, 596, 24573, 11746, 5955, 320, 42, 3624, 8, 374, 7559, 13, 578, 4007, 11, 4756, 304, 40602, 8385, 39073, 11, 6656, 709, 1063, 23649, 3135, 304, 27393, 279, 29219, 907, 315, 12290, 33096, 288, 311, 51296, 299, 2396, 13, 60148, 51515, 14800, 574, 279, 2867, 13946, 304, 8405, 16757, 35335, 9313, 927, 12290, 33096, 288, 13, 60148, 51515, 71699, 3493, 264, 55944, 220, 4728, 824, 2960, 810, 35335, 9313, 1109, 12290, 33096, 288, 13, 763, 682, 11, 51296, 51515, 71699, 1436, 3493, 400, 19, 13, 24, 3610, 5922, 315, 35335, 9313, 810, 1109, 893, 28010, 30740, 13, 763, 279, 549, 815, 13, 7636, 11, 279, 4007, 3585, 704, 11, 14739, 1974, 35335, 9313, 3600, 3493, 459, 13240, 400, 1419, 13, 17, 7239, 824, 1060, 315, 9313, 2403, 7100, 18151, 439, 1664, 439, 16779, 5938, 449, 3682, 13766, 4455, 13, 10541, 279, 5536, 315, 63561, 10182, 2349, 374, 36218, 11, 279, 4007, 45537, 430, 330, 1090, 14750, 1113, 26031, 6108, 20414, 323, 50953, 15009, 1253, 3085, 264, 1648, 311, 50460, 323, 10737, 311, 279, 6372, 315, 16448, 52840, 323, 25228, 7922, 44583, 1210, 220, 128257, 198 ]

1,854

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Our immediate observations must be supplemented with contextual information to resolve ambiguities. However, the context is often ambiguous too, and thus it should be inferred itself to guide behavior. Here, we introduce a novel hierarchical task (airplane task) in which participants should infer a higher-level, contextual variable to inform probabilistic inference about a hidden dependent variable at a lower level. By controlling the reliability of past sensory evidence through varying the sample size of the observations, we find that humans estimate the reliability of the context and combine it with current sensory uncertainty to inform their confidence reports. Behavior closely follows inference by probabilistic message passing between latent variables across hierarchical state representations. Commonly reported inferential fallacies, such as sample size insensitivity, are not present, and neither did participants appear to rely on simple heuristics. Our results reveal uncertainty-sensitive integration of information at different hierarchical levels and temporal scales. Introduction As sensory evidence is inherently ambiguous, it needs to be integrated with contextual information to minimize the uncertainty of our perception of the world and thus allow for successful behavior. Suppose that we observe just a few passengers exiting an airplane at an airport whose city hosts a soccer final. If we find that four of them are supporters of the red team and two support the blue team, we might conclude that there were more supporters of the red team in the airplane. This inference, based on incomplete sensory evidence, can be improved by contextual information. For instance, there might be many more blue than red supporters in the world. Then, despite our initial observation, we might want to revise our inference and rather conclude, based on the context, that the airplane carried more blue than red supporters. While in the previous example context was certain and by itself able to resolve observational ambiguity, contextual information is very often ambiguous. For instance, we might just know that there is an event in the city that attracts more of a certain type of people, but we do not know which type. Extending our example, we would first need to infer the context (whether the event attracts more people of the red or blue type) by observing samples of passengers leaving several airplanes. By using the inferred context, we can better estimate whether the next plane carries more of one type of people given only on a small sample of its passengers. Thus, in real-life, both observations and context commonly provide incomplete information about a behaviorally relevant latent variable. In these cases, inference should be based on probabilistic representations of both observational and contextual information 1 , 2 , 3 , 4 , 5 , 6 . Indeed, recent work has shown that humans can track a contextual binary variable embedded in noise that partially informs about what specific actions need to be performed to obtain reward 7 . Additionally, humans can infer the transition probability between two stimuli where the transition probability itself undergoes unexpected changes, defining a partially observable context 8 . These results and other studies suggest that a refined form of uncertainty representation is held at several hierarchical levels by the brain 9 , 10 , 11 , 12 , 13 , 14 . However, in this previous research, the reliability of the context has rarely been manipulated directly and independently 15 from the reliability of the current observation 1 , 7 , 8 . Therefore, it is unclear up to what degree contextual inference reflects its uncertainty and interacts with the inferred reliability of the current observation as it would be expected from representing it with a joint probability distribution over both observations and context. While some effects predicted by hierarchical probabilistic inference have been previously reported in isolation, no study has—to our knowledge—thoroughly assessed a body of behavioral predictions of hierarchical probabilistic inference and tested them against alternative heuristics model. To address the above question, we developed a reliability-based hierarchical integration task that allows us to directly control reliability in order to evidence characteristic patterns of probabilistic inference. Our task was intuitively framed to our participants using the analogy of flight arrivals to an airport whose city hosts an event, rather than relying on an abstract or mathematical description of the dependencies between the latent variables. The goal was to decide whether the flight just landed carried more passengers of the red or blue type based on the observation of only a small sample of passengers leaving the airplane, and to report the confidence in that decision. However, as the event is known to tend to attract more of either of the two types of passengers, knowledge of this context, if inferred correctly, would be useful to solve the task. The crucial ingredient of our task is that inference of the context is based on the observation of small samples of passengers exiting previously arrived planes, making the context partially, but not fully, observable. By manipulating both the tendency and the sample size, we can control the reliability of previous observations upon which inference about the context should be based. Overall, this task structure creates hierarchical dependencies among latent variables that should be resolved by bottom-up (inferring the context from previous observations) and top-down message passing (inferring the current state by combining current observations with the inferred context) 6 . We find that participants can track and use the inferred reliability of previous observations suggesting that they build a probabilistic representation of the context. The inferred context is integrated with the current observations to guide decisions and confidence judgments about the value of a latent variable at a lower hierarchical level. Decision confidence is found to closely correspond to the actual accuracy of making correct decisions. As a clear signature of probabilistic inference over the context, we find that the sample size of previous observations is used by our participants to infer the reliability of the context. This in turn has a strong effect on decision confidence of a lower-level variable that depends on", "role": "user" }, { "content": "How do human beings perceive their environment and make their decisions? To successfully interact with the immediate environment, for human beings it is not enough to have basic evidence of the world around them. This information by itself is insufficient because it is inherently ambiguous and requires integrating into a particular context to minimize the uncertainty of sensory perception. But, at the same time, the context is ambiguous. For example, am I in a safe or a dangerous place? A study published on 28 November in Nature Communications by Philipp Schustek, Alexandre Hyafil and Rubén Moreno-Bote, researchers at the Center for Brain and Cognition (CBC) of the Department of Information and Communication Technologies (DTIC) at UPF, suggests that the brain has a refined form of representation of uncertainty at several hierarchical levels, including context. Hence, the brain has a very detailed, almost mathematical probabilistic representation of all that surrounds us we consider important. \"The notions of probability, though intuitive, are very difficult to quantify and use rigorously. For example, my statistics students often fail to solve some of the problems I pose in class. In our study, we find that a complicated mathematical problem involving the use of the most sophisticated rules of probability can be solved intuitively if it is presented simply and in a natural context,\" asserts Rubén Moreno-Bote, coordinator of the Research Group on Theoretical and Cognitive Neuroscience at the CBC. Cognitive tasks of hierarchical integration Let us suppose that a city airport is hosting a football final and we look at a few passengers who are leaving a plane. If we note that four of them are fans of the red team and two of the blue team, we could conclude that more fans of the red team are attending the final than of the blue team. This inference, based on incomplete sensory evidence, could be improved with contextual information. For example, if worldwide there are more fans of the blue team than of the red team, despite our initial observation, we would review our inference counting how many supporters of each group are travelling on the plane to more accurately confirm whether more fans of the red team have really come to the city than of the blue team. Or, we could also do the opposite, basing ourselves on the context inferring whether the sample observed follows the more general context or not. The researchers designed their experiments presenting hierarchical integration tasks using the plane task. \"For the study, we told our participants that they are at an airport where planes can arrive carrying more of one type of person than of another, for example, more supporters of Barça than of Madrid. On seeing a handful of passengers leaving several aircraft, the participants can predict with mathematical precision the likelihood that the next plane will be carrying more passengers of a certain type,\" Moreno-Bote explains. \"In general, this structure of tasks creates hierarchical dependencies among the hidden variables to be solved bottom up (deducing the context of previous observations) and then passing the message top down (deducing the current status combining current observations with the inferred context),\" the authors explain. The results showed that the participants, based on their preliminary observations, built a probabilistic representation of the context. These results help to understand how people form mental representations of what surrounds us and how we assign and perceive the uncertainty of this context. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Our immediate observations must be supplemented with contextual information to resolve ambiguities. However, the context is often ambiguous too, and thus it should be inferred itself to guide behavior. Here, we introduce a novel hierarchical task (airplane task) in which participants should infer a higher-level, contextual variable to inform probabilistic inference about a hidden dependent variable at a lower level. By controlling the reliability of past sensory evidence through varying the sample size of the observations, we find that humans estimate the reliability of the context and combine it with current sensory uncertainty to inform their confidence reports. Behavior closely follows inference by probabilistic message passing between latent variables across hierarchical state representations. Commonly reported inferential fallacies, such as sample size insensitivity, are not present, and neither did participants appear to rely on simple heuristics. Our results reveal uncertainty-sensitive integration of information at different hierarchical levels and temporal scales. Introduction As sensory evidence is inherently ambiguous, it needs to be integrated with contextual information to minimize the uncertainty of our perception of the world and thus allow for successful behavior. Suppose that we observe just a few passengers exiting an airplane at an airport whose city hosts a soccer final. If we find that four of them are supporters of the red team and two support the blue team, we might conclude that there were more supporters of the red team in the airplane. This inference, based on incomplete sensory evidence, can be improved by contextual information. For instance, there might be many more blue than red supporters in the world. Then, despite our initial observation, we might want to revise our inference and rather conclude, based on the context, that the airplane carried more blue than red supporters. While in the previous example context was certain and by itself able to resolve observational ambiguity, contextual information is very often ambiguous. For instance, we might just know that there is an event in the city that attracts more of a certain type of people, but we do not know which type. Extending our example, we would first need to infer the context (whether the event attracts more people of the red or blue type) by observing samples of passengers leaving several airplanes. By using the inferred context, we can better estimate whether the next plane carries more of one type of people given only on a small sample of its passengers. Thus, in real-life, both observations and context commonly provide incomplete information about a behaviorally relevant latent variable. In these cases, inference should be based on probabilistic representations of both observational and contextual information 1 , 2 , 3 , 4 , 5 , 6 . Indeed, recent work has shown that humans can track a contextual binary variable embedded in noise that partially informs about what specific actions need to be performed to obtain reward 7 . Additionally, humans can infer the transition probability between two stimuli where the transition probability itself undergoes unexpected changes, defining a partially observable context 8 . These results and other studies suggest that a refined form of uncertainty representation is held at several hierarchical levels by the brain 9 , 10 , 11 , 12 , 13 , 14 . However, in this previous research, the reliability of the context has rarely been manipulated directly and independently 15 from the reliability of the current observation 1 , 7 , 8 . Therefore, it is unclear up to what degree contextual inference reflects its uncertainty and interacts with the inferred reliability of the current observation as it would be expected from representing it with a joint probability distribution over both observations and context. While some effects predicted by hierarchical probabilistic inference have been previously reported in isolation, no study has—to our knowledge—thoroughly assessed a body of behavioral predictions of hierarchical probabilistic inference and tested them against alternative heuristics model. To address the above question, we developed a reliability-based hierarchical integration task that allows us to directly control reliability in order to evidence characteristic patterns of probabilistic inference. Our task was intuitively framed to our participants using the analogy of flight arrivals to an airport whose city hosts an event, rather than relying on an abstract or mathematical description of the dependencies between the latent variables. The goal was to decide whether the flight just landed carried more passengers of the red or blue type based on the observation of only a small sample of passengers leaving the airplane, and to report the confidence in that decision. However, as the event is known to tend to attract more of either of the two types of passengers, knowledge of this context, if inferred correctly, would be useful to solve the task. The crucial ingredient of our task is that inference of the context is based on the observation of small samples of passengers exiting previously arrived planes, making the context partially, but not fully, observable. By manipulating both the tendency and the sample size, we can control the reliability of previous observations upon which inference about the context should be based. Overall, this task structure creates hierarchical dependencies among latent variables that should be resolved by bottom-up (inferring the context from previous observations) and top-down message passing (inferring the current state by combining current observations with the inferred context) 6 . We find that participants can track and use the inferred reliability of previous observations suggesting that they build a probabilistic representation of the context. The inferred context is integrated with the current observations to guide decisions and confidence judgments about the value of a latent variable at a lower hierarchical level. Decision confidence is found to closely correspond to the actual accuracy of making correct decisions. As a clear signature of probabilistic inference over the context, we find that the sample size of previous observations is used by our participants to infer the reliability of the context. This in turn has a strong effect on decision confidence of a lower-level variable that depends on<|im_end|> <|im_start|>assistant How do human beings perceive their environment and make their decisions? To successfully interact with the immediate environment, for human beings it is not enough to have basic evidence of the world around them. This information by itself is insufficient because it is inherently ambiguous and requires integrating into a particular context to minimize the uncertainty of sensory perception. But, at the same time, the context is ambiguous. For example, am I in a safe or a dangerous place? A study published on 28 November in Nature Communications by Philipp Schustek, Alexandre Hyafil and Rubén Moreno-Bote, researchers at the Center for Brain and Cognition (CBC) of the Department of Information and Communication Technologies (DTIC) at UPF, suggests that the brain has a refined form of representation of uncertainty at several hierarchical levels, including context. Hence, the brain has a very detailed, almost mathematical probabilistic representation of all that surrounds us we consider important. "The notions of probability, though intuitive, are very difficult to quantify and use rigorously. For example, my statistics students often fail to solve some of the problems I pose in class. In our study, we find that a complicated mathematical problem involving the use of the most sophisticated rules of probability can be solved intuitively if it is presented simply and in a natural context," asserts Rubén Moreno-Bote, coordinator of the Research Group on Theoretical and Cognitive Neuroscience at the CBC. Cognitive tasks of hierarchical integration Let us suppose that a city airport is hosting a football final and we look at a few passengers who are leaving a plane. If we note that four of them are fans of the red team and two of the blue team, we could conclude that more fans of the red team are attending the final than of the blue team. This inference, based on incomplete sensory evidence, could be improved with contextual information. For example, if worldwide there are more fans of the blue team than of the red team, despite our initial observation, we would review our inference counting how many supporters of each group are travelling on the plane to more accurately confirm whether more fans of the red team have really come to the city than of the blue team. Or, we could also do the opposite, basing ourselves on the context inferring whether the sample observed follows the more general context or not. The researchers designed their experiments presenting hierarchical integration tasks using the plane task. "For the study, we told our participants that they are at an airport where planes can arrive carrying more of one type of person than of another, for example, more supporters of Barça than of Madrid. On seeing a handful of passengers leaving several aircraft, the participants can predict with mathematical precision the likelihood that the next plane will be carrying more passengers of a certain type," Moreno-Bote explains. "In general, this structure of tasks creates hierarchical dependencies among the hidden variables to be solved bottom up (deducing the context of previous observations) and then passing the message top down (deducing the current status combining current observations with the inferred context)," the authors explain. The results showed that the participants, based on their preliminary observations, built a probabilistic representation of the context. These results help to understand how people form mental representations of what surrounds us and how we assign and perceive the uncertainty of this context. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 5751, 14247, 24654, 2011, 387, 89804, 449, 66251, 2038, 311, 9006, 62397, 1385, 13, 4452, 11, 279, 2317, 374, 3629, 55861, 2288, 11, 323, 8617, 433, 1288, 387, 68695, 5196, 311, 8641, 7865, 13, 5810, 11, 584, 19678, 264, 11775, 70994, 3465, 320, 1334, 19563, 3465, 8, 304, 902, 13324, 1288, 24499, 264, 5190, 11852, 11, 66251, 3977, 311, 6179, 85193, 4633, 45478, 922, 264, 8340, 18222, 3977, 520, 264, 4827, 2237, 13, 3296, 26991, 279, 31638, 315, 3347, 49069, 6029, 1555, 29865, 279, 6205, 1404, 315, 279, 24654, 11, 584, 1505, 430, 12966, 16430, 279, 31638, 315, 279, 2317, 323, 16343, 433, 449, 1510, 49069, 27924, 311, 6179, 872, 12410, 6821, 13, 27773, 15499, 11263, 45478, 555, 85193, 4633, 1984, 12579, 1990, 42767, 7482, 4028, 70994, 1614, 44713, 13, 7874, 398, 5068, 24499, 2335, 4498, 27121, 11, 1778, 439, 6205, 1404, 1672, 48937, 11, 527, 539, 3118, 11, 323, 14188, 1550, 13324, 5101, 311, 17631, 389, 4382, 568, 324, 5706, 13, 5751, 3135, 16805, 27924, 57767, 18052, 315, 2038, 520, 2204, 70994, 5990, 323, 37015, 29505, 13, 29438, 1666, 49069, 6029, 374, 49188, 55861, 11, 433, 3966, 311, 387, 18751, 449, 66251, 2038, 311, 30437, 279, 27924, 315, 1057, 21063, 315, 279, 1917, 323, 8617, 2187, 369, 6992, 7865, 13, 83710, 430, 584, 23846, 1120, 264, 2478, 22961, 45848, 459, 44024, 520, 459, 17149, 6832, 3363, 18939, 264, 22963, 1620, 13, 1442, 584, 1505, 430, 3116, 315, 1124, 527, 15879, 315, 279, 2579, 2128, 323, 1403, 1862, 279, 6437, 2128, 11, 584, 2643, 32194, 430, 1070, 1051, 810, 15879, 315, 279, 2579, 2128, 304, 279, 44024, 13, 1115, 45478, 11, 3196, 389, 33243, 49069, 6029, 11, 649, 387, 13241, 555, 66251, 2038, 13, 1789, 2937, 11, 1070, 2643, 387, 1690, 810, 6437, 1109, 2579, 15879, 304, 279, 1917, 13, 5112, 11, 8994, 1057, 2926, 22695, 11, 584, 2643, 1390, 311, 65836, 1057, 45478, 323, 4856, 32194, 11, 3196, 389, 279, 2317, 11, 430, 279, 44024, 11953, 810, 6437, 1109, 2579, 15879, 13, 6104, 304, 279, 3766, 3187, 2317, 574, 3738, 323, 555, 5196, 3025, 311, 9006, 90380, 72868, 11, 66251, 2038, 374, 1633, 3629, 55861, 13, 1789, 2937, 11, 584, 2643, 1120, 1440, 430, 1070, 374, 459, 1567, 304, 279, 3363, 430, 61191, 810, 315, 264, 3738, 955, 315, 1274, 11, 719, 584, 656, 539, 1440, 902, 955, 13, 9634, 2518, 1057, 3187, 11, 584, 1053, 1176, 1205, 311, 24499, 279, 2317, 320, 49864, 279, 1567, 61191, 810, 1274, 315, 279, 2579, 477, 6437, 955, 8, 555, 46071, 10688, 315, 22961, 9564, 3892, 76481, 13, 3296, 1701, 279, 68695, 2317, 11, 584, 649, 2731, 16430, 3508, 279, 1828, 11277, 24266, 810, 315, 832, 955, 315, 1274, 2728, 1193, 389, 264, 2678, 6205, 315, 1202, 22961, 13, 14636, 11, 304, 1972, 26928, 11, 2225, 24654, 323, 2317, 17037, 3493, 33243, 2038, 922, 264, 7865, 750, 9959, 42767, 3977, 13, 763, 1521, 5157, 11, 45478, 1288, 387, 3196, 389, 85193, 4633, 44713, 315, 2225, 90380, 323, 66251, 2038, 220, 16, 1174, 220, 17, 1174, 220, 18, 1174, 220, 19, 1174, 220, 20, 1174, 220, 21, 662, 23150, 11, 3293, 990, 706, 6982, 430, 12966, 649, 3839, 264, 66251, 8026, 3977, 23711, 304, 12248, 430, 26310, 64252, 922, 1148, 3230, 6299, 1205, 311, 387, 10887, 311, 6994, 11565, 220, 22, 662, 23212, 11, 12966, 649, 24499, 279, 9320, 19463, 1990, 1403, 56688, 1405, 279, 9320, 19463, 5196, 37771, 288, 16907, 4442, 11, 27409, 264, 26310, 40635, 2317, 220, 23, 662, 4314, 3135, 323, 1023, 7978, 4284, 430, 264, 38291, 1376, 315, 27924, 13340, 374, 5762, 520, 3892, 70994, 5990, 555, 279, 8271, 220, 24, 1174, 220, 605, 1174, 220, 806, 1174, 220, 717, 1174, 220, 1032, 1174, 220, 975, 662, 4452, 11, 304, 420, 3766, 3495, 11, 279, 31638, 315, 279, 2317, 706, 19029, 1027, 55315, 6089, 323, 29235, 220, 868, 505, 279, 31638, 315, 279, 1510, 22695, 220, 16, 1174, 220, 22, 1174, 220, 23, 662, 15636, 11, 433, 374, 25420, 709, 311, 1148, 8547, 66251, 45478, 27053, 1202, 27924, 323, 84261, 449, 279, 68695, 31638, 315, 279, 1510, 22695, 439, 433, 1053, 387, 3685, 505, 14393, 433, 449, 264, 10496, 19463, 8141, 927, 2225, 24654, 323, 2317, 13, 6104, 1063, 6372, 19698, 555, 70994, 85193, 4633, 45478, 617, 1027, 8767, 5068, 304, 31398, 11, 912, 4007, 706, 50617, 1057, 6677, 2345, 339, 14776, 398, 32448, 264, 2547, 315, 36695, 20492, 315, 70994, 85193, 4633, 45478, 323, 12793, 1124, 2403, 10778, 568, 324, 5706, 1646, 13, 2057, 2686, 279, 3485, 3488, 11, 584, 8040, 264, 31638, 6108, 70994, 18052, 3465, 430, 6276, 603, 311, 6089, 2585, 31638, 304, 2015, 311, 6029, 29683, 12912, 315, 85193, 4633, 45478, 13, 5751, 3465, 574, 97301, 3210, 47093, 311, 1057, 13324, 1701, 279, 56203, 315, 11213, 70147, 311, 459, 17149, 6832, 3363, 18939, 459, 1567, 11, 4856, 1109, 39661, 389, 459, 8278, 477, 37072, 4096, 315, 279, 20113, 1990, 279, 42767, 7482, 13, 578, 5915, 574, 311, 10491, 3508, 279, 11213, 1120, 27212, 11953, 810, 22961, 315, 279, 2579, 477, 6437, 955, 3196, 389, 279, 22695, 315, 1193, 264, 2678, 6205, 315, 22961, 9564, 279, 44024, 11, 323, 311, 1934, 279, 12410, 304, 430, 5597, 13, 4452, 11, 439, 279, 1567, 374, 3967, 311, 8541, 311, 9504, 810, 315, 3060, 315, 279, 1403, 4595, 315, 22961, 11, 6677, 315, 420, 2317, 11, 422, 68695, 12722, 11, 1053, 387, 5505, 311, 11886, 279, 3465, 13, 578, 16996, 25795, 315, 1057, 3465, 374, 430, 45478, 315, 279, 2317, 374, 3196, 389, 279, 22695, 315, 2678, 10688, 315, 22961, 45848, 8767, 11721, 25761, 11, 3339, 279, 2317, 26310, 11, 719, 539, 7373, 11, 40635, 13, 3296, 63614, 2225, 279, 31954, 323, 279, 6205, 1404, 11, 584, 649, 2585, 279, 31638, 315, 3766, 24654, 5304, 902, 45478, 922, 279, 2317, 1288, 387, 3196, 13, 28993, 11, 420, 3465, 6070, 11705, 70994, 20113, 4315, 42767, 7482, 430, 1288, 387, 20250, 555, 5740, 5352, 320, 13885, 14782, 279, 2317, 505, 3766, 24654, 8, 323, 1948, 15220, 1984, 12579, 320, 13885, 14782, 279, 1510, 1614, 555, 35271, 1510, 24654, 449, 279, 68695, 2317, 8, 220, 21, 662, 1226, 1505, 430, 13324, 649, 3839, 323, 1005, 279, 68695, 31638, 315, 3766, 24654, 23377, 430, 814, 1977, 264, 85193, 4633, 13340, 315, 279, 2317, 13, 578, 68695, 2317, 374, 18751, 449, 279, 1510, 24654, 311, 8641, 11429, 323, 12410, 59358, 922, 279, 907, 315, 264, 42767, 3977, 520, 264, 4827, 70994, 2237, 13, 41525, 12410, 374, 1766, 311, 15499, 8024, 311, 279, 5150, 13708, 315, 3339, 4495, 11429, 13, 1666, 264, 2867, 12223, 315, 85193, 4633, 45478, 927, 279, 2317, 11, 584, 1505, 430, 279, 6205, 1404, 315, 3766, 24654, 374, 1511, 555, 1057, 13324, 311, 24499, 279, 31638, 315, 279, 2317, 13, 1115, 304, 2543, 706, 264, 3831, 2515, 389, 5597, 12410, 315, 264, 4827, 11852, 3977, 430, 14117, 389, 128257, 198, 128256, 78191, 198, 4438, 656, 3823, 23837, 45493, 872, 4676, 323, 1304, 872, 11429, 30, 2057, 7946, 16681, 449, 279, 14247, 4676, 11, 369, 3823, 23837, 433, 374, 539, 3403, 311, 617, 6913, 6029, 315, 279, 1917, 2212, 1124, 13, 1115, 2038, 555, 5196, 374, 39413, 1606, 433, 374, 49188, 55861, 323, 7612, 54952, 1139, 264, 4040, 2317, 311, 30437, 279, 27924, 315, 49069, 21063, 13, 2030, 11, 520, 279, 1890, 892, 11, 279, 2317, 374, 55861, 13, 1789, 3187, 11, 1097, 358, 304, 264, 6220, 477, 264, 11660, 2035, 30, 362, 4007, 4756, 389, 220, 1591, 6841, 304, 22037, 26545, 555, 20540, 5124, 592, 1247, 11, 90154, 10320, 44062, 323, 13134, 10610, 79275, 7826, 1295, 11, 12074, 520, 279, 5955, 369, 31417, 323, 356, 31756, 320, 71072, 8, 315, 279, 6011, 315, 8245, 323, 31966, 25579, 320, 10822, 1341, 8, 520, 12250, 37, 11, 13533, 430, 279, 8271, 706, 264, 38291, 1376, 315, 13340, 315, 27924, 520, 3892, 70994, 5990, 11, 2737, 2317, 13, 32140, 11, 279, 8271, 706, 264, 1633, 11944, 11, 4661, 37072, 85193, 4633, 13340, 315, 682, 430, 71374, 603, 584, 2980, 3062, 13, 330, 791, 59682, 315, 19463, 11, 3582, 42779, 11, 527, 1633, 5107, 311, 76498, 323, 1005, 78477, 7162, 13, 1789, 3187, 11, 856, 13443, 4236, 3629, 3775, 311, 11886, 1063, 315, 279, 5435, 358, 17477, 304, 538, 13, 763, 1057, 4007, 11, 584, 1505, 430, 264, 17395, 37072, 3575, 16239, 279, 1005, 315, 279, 1455, 27877, 5718, 315, 19463, 649, 387, 29056, 97301, 3210, 422, 433, 374, 10666, 5042, 323, 304, 264, 5933, 2317, 1359, 57876, 13134, 10610, 79275, 7826, 1295, 11, 31384, 315, 279, 8483, 5856, 389, 578, 91867, 323, 73235, 85879, 520, 279, 46612, 13, 73235, 9256, 315, 70994, 18052, 6914, 603, 23289, 430, 264, 3363, 17149, 374, 20256, 264, 9141, 1620, 323, 584, 1427, 520, 264, 2478, 22961, 889, 527, 9564, 264, 11277, 13, 1442, 584, 5296, 430, 3116, 315, 1124, 527, 7359, 315, 279, 2579, 2128, 323, 1403, 315, 279, 6437, 2128, 11, 584, 1436, 32194, 430, 810, 7359, 315, 279, 2579, 2128, 527, 24096, 279, 1620, 1109, 315, 279, 6437, 2128, 13, 1115, 45478, 11, 3196, 389, 33243, 49069, 6029, 11, 1436, 387, 13241, 449, 66251, 2038, 13, 1789, 3187, 11, 422, 15603, 1070, 527, 810, 7359, 315, 279, 6437, 2128, 1109, 315, 279, 2579, 2128, 11, 8994, 1057, 2926, 22695, 11, 584, 1053, 3477, 1057, 45478, 26060, 1268, 1690, 15879, 315, 1855, 1912, 527, 31829, 389, 279, 11277, 311, 810, 30357, 7838, 3508, 810, 7359, 315, 279, 2579, 2128, 617, 2216, 2586, 311, 279, 3363, 1109, 315, 279, 6437, 2128, 13, 2582, 11, 584, 1436, 1101, 656, 279, 14329, 11, 3122, 287, 13520, 389, 279, 2317, 4225, 14782, 3508, 279, 6205, 13468, 11263, 279, 810, 4689, 2317, 477, 539, 13, 578, 12074, 6319, 872, 21896, 32644, 70994, 18052, 9256, 1701, 279, 11277, 3465, 13, 330, 2520, 279, 4007, 11, 584, 3309, 1057, 13324, 430, 814, 527, 520, 459, 17149, 1405, 25761, 649, 17782, 15691, 810, 315, 832, 955, 315, 1732, 1109, 315, 2500, 11, 369, 3187, 11, 810, 15879, 315, 4821, 17930, 1109, 315, 25048, 13, 1952, 9298, 264, 23810, 315, 22961, 9564, 3892, 14467, 11, 279, 13324, 649, 7168, 449, 37072, 16437, 279, 29736, 430, 279, 1828, 11277, 690, 387, 15691, 810, 22961, 315, 264, 3738, 955, 1359, 79275, 7826, 1295, 15100, 13, 330, 644, 4689, 11, 420, 6070, 315, 9256, 11705, 70994, 20113, 4315, 279, 8340, 7482, 311, 387, 29056, 5740, 709, 320, 9988, 59144, 279, 2317, 315, 3766, 24654, 8, 323, 1243, 12579, 279, 1984, 1948, 1523, 320, 9988, 59144, 279, 1510, 2704, 35271, 1510, 24654, 449, 279, 68695, 2317, 36493, 279, 12283, 10552, 13, 578, 3135, 8710, 430, 279, 13324, 11, 3196, 389, 872, 33269, 24654, 11, 5918, 264, 85193, 4633, 13340, 315, 279, 2317, 13, 4314, 3135, 1520, 311, 3619, 1268, 1274, 1376, 10723, 44713, 315, 1148, 71374, 603, 323, 1268, 584, 9993, 323, 45493, 279, 27924, 315, 420, 2317, 13, 220, 128257, 198 ]

1,836

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Background While it is known that exposure to traffic-related air pollution causes an enormous global toll on human health, neurobiological underpinnings therein remain elusive. The study addresses this gap in knowledge. Methods We performed the first controlled human exposure study using functional MRI with an efficient order-randomized double-blind crossover study of diesel exhaust (DE) and control (filtered air; FA) in 25 healthy adults (14 males, 11 females; 19–49 years old; no withdrawals). Analyses were carried out using a mixed effects model in FLAME. Z (Gaussianised T/F) statistic images were thresholded non-parametrically using clusters determined by Z > 2.3 and a (corrected) cluster significance threshold of p = 0.05. Results All 25 adults went through the exposures and functional MRI imaging were collected. Exposure to DE yielded a decrease in functional connectivity compared to exposure to FA, shown through the comparison of DE and FA in post-exposure measurement of functional connectivity. Conclusion We observed short-term pollution-attributable decrements in default mode network functional connectivity. Decrements in brain connectivity causes many detrimental effects to the human body so this finding should guide policy change in air pollution exposure regulation. Trial registration University of British Columbia Clinical Research Ethics Board (# H12-03025), Vancouver Coastal Health Ethics Board (# V12-03025), and Health Canada’s Research Ethics Board (# 2012-0040). Peer Review reports Background Exposure to traffic-related air pollution (TRAP) has long been associated with a range of adverse health effects, principally cardiovascular and respiratory [ 1 ]. This poses an enormous global burden, in terms of morbidity and lost productivity, as well as deaths estimated at approximately five million per year worldwide [ 2 ]. This profound toll is increasingly appreciated as including impacts on the central nervous system, but the data therein remains immature. Further, neurobiological underpinnings of these observations remain elusive, although some preliminary data suggest direct transmission of particles via the olfactory bulb and/or secondary transmission of inflammation likely generated more proximally [ 3 – 5 ]. Given the profound implications for public health across essentially all communities [ 6 ], data that adds overall biologic plausibility and also specific evidence of affected body systems are critically needed in order to support observational data [ 7 – 10 ]. Therefore, we performed the first controlled human exposure study to TRAP, using an established and safe paradigm of diluted diesel exhaust, that examines changes in functional MRI in an efficient crossover study (namely, diesel exhaust [DE] or filtered air [FA] exposure following light exercise), allowing observation of short-term effects on brain connectivity in this context. Methods Participants A total of 100 MRI acquisitions were obtained in the current study. Twenty-five adult participants were tested immediately pre- and post-exposure to diesel exhaust (DE) and immediately pre- and post-exposure to filtered air (FA) for comparison. All participants were recruited through posters in the community, online notices, and e-mail notifications to the Vancouver Coastal Health Staff List-Serve. Inclusion criteria for participants were as follows: between 19 and 49 years of age, able to converse in English, healthy, non-smoking, not pregnant or breast-feeding, and without any contraindications for MRI. So long as inclusion criteria were met, the only exclusion criteria was claustrophobia. Procedure The study employed a controlled, double-blinded crossover design at the Air Pollution Exposure Lab. Each participant was tested in both the control condition (exposure to FA) and the experimental condition (exposure to DE) with four data acquisitions: (1) pre-FA; (2) post-FA; (3) pre-DE and (4) post-DE. The order of exposure to FA and DE was randomized and counterbalanced across participants, with a two-week delay between conditions. Both participants and individuals involved in collecting the MRI data were blinded to the condition, a technique that has been shown not only nominal but also effective [ 11 ]. FA or DE (nominal concentration: 300 µg of particulate matter of 2.5 microns or less [PM 2.5 ]/m 3 ) exposure occurred for 120 min [ 12 ]. During exposure, participants cycled on a stationary bicycle at light effort (that which yields ventilation at 15 L/min/m 2 ) for 15 min, during the first quarter of each hour, to maintain a representative level of activity. Image acquisition The following MRI protocol was employed pre-FA, post-FA, pre-DE and post-DE for each participant. All images were acquired at BC Children’s Hospital on a 3 Tesla GE Discovery MR750 MRI scanner. A whole-brain anatomical MRI scan was acquired with a T1-weighted FSPGR 3D sequence, with the following parameters: a repetition time (TR) of 8.148 ms, an echo time of 3.172 ms, voxel size of 1 × 1 × 1 mm, and a flip angle of 8°. A functional MRI (fMRI) scan was obtained during resting state (with eyes open or closed). The resting state fMRI scan was 6 min in duration and obtained with a T2*-weighted echo-planar imaging sequence with the following parameters: a repetition time of 2000 ms, an echo time of 19 ms, 180 volumes, 39 slices, and a voxel size of 3 × 3 × 3 mm. Additional task-based scans were obtained following resting state scans, but were ancillary to the hypotheses being tested here. Functional MRI data analyses All analysis steps were performed using tools within the Functional MRI of the Brain Software Library (FSL; Analysis Group, FMRIB, Oxford, UK, ) [ 13 ]. Non-brain tissue in the raw T1 images was removed using the automated Brain Extraction Tool, followed by manual verification and optimization for each subject. A seed-based approach was used to examine functional connectivity in the default mode network (DMN) [ 14 ]. The FEAT function was used to pre-process the data including skull removal (using the Brain Extraction Tool), motion correction (using MCFLIRT) [ 15 ], and highpass temporal filtering (using Gaussian-weighted least-squares straight line fitting with σ = 50.0 s). No smoothing was applied. Registration of the functional data to the high-resolution structural image was carried out using the boundary-based registration algorithm. Registration of the high-resolution structural images to standard space was carried out using FLIRT [ 15 , 16 ] and", "role": "user" }, { "content": "A new study by researchers at the University of British Columbia and the University of Victoria has shown that common levels of traffic pollution can impair human brain function in only a matter of hours. The findings, published in the journal Environmental Health, show that just two hours of exposure to diesel exhaust causes a decrease in the brain's functional connectivity—a measure of how The study provides the first evidence in humans, from a controlled experiment, of altered brain network connectivity induced by air pollution. \"For many decades, scientists thought the brain may be protected from the harmful effects of air pollution,\" said senior study author Dr. Chris Carlsten, professor and head of respiratory medicine and the Canada Research Chair in occupational and environmental lung disease at UBC. \"This study, which is the first of its kind in the world, provides fresh evidence supporting a connection between air pollution and cognition.\" For the study, the researchers briefly exposed 25 healthy adults to diesel exhaust and filtered air at different times in a laboratory setting. Brain activity was measured before and after each exposure using functional magnetic resonance imaging (fMRI). The researchers analyzed changes in the brain's default mode network (DMN), a set of inter-connected brain regions that play an important role in memory and internal thought. The fMRI revealed that participants had decreased functional connectivity in widespread regions of the DMN after exposure to diesel exhaust, compared to filtered air. \"We know that altered functional connectivity in the DMN has been associated with reduced cognitive performance and symptoms of depression, so it's concerning to see traffic pollution interrupting these same networks,\" said Dr. Jodie Gawryluk, a psychology professor at the University of Victoria and the study's first author. \"While more research is needed to fully understand the functional impacts of these changes, it's possible that they may impair people's thinking or ability to work.\" Taking steps to protect yourself Notably, the changes in the brain were temporary and participants' connectivity returned to normal after the exposure. Dr. Carlsten speculated that the effects could be long lasting where exposure is continuous. He said that people should be mindful of the air they're breathing and take appropriate steps to minimize their exposure to potentially harmful air pollutants like car exhaust. \"People may want to think twice the next time they're stuck in traffic with the windows rolled down,\" said Dr. Carlsten. \"It's important to ensure that your car's air filter is in good working order, and if you're walking or biking down a busy street, consider diverting to a less busy route.\" While the current study only looked at the cognitive impacts of traffic-derived pollution, Dr. Carlsten said that other products of combustion are likely a concern. \"Air pollution is now recognized as the largest environmental threat to human health and we are increasingly seeing the impacts across all major organ systems,\" says Dr. Carlsten. \"I expect we would see similar impacts on the brain from exposure to other air pollutants, like forest fire smoke. With the increasing incidence of neurocognitive disorders, it's an important consideration for public health officials and policymakers.\" The study was conducted at UBC's Air Pollution Exposure Laboratory, located at Vancouver General Hospital, which is equipped with a state-of-the-art exposure booth that can mimic what it is like to breathe a variety of air pollutants. In this study, which was carefully designed and approved for safety, the researchers used freshly-generated exhaust that was diluted and aged to reflect real-world conditions. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Background While it is known that exposure to traffic-related air pollution causes an enormous global toll on human health, neurobiological underpinnings therein remain elusive. The study addresses this gap in knowledge. Methods We performed the first controlled human exposure study using functional MRI with an efficient order-randomized double-blind crossover study of diesel exhaust (DE) and control (filtered air; FA) in 25 healthy adults (14 males, 11 females; 19–49 years old; no withdrawals). Analyses were carried out using a mixed effects model in FLAME. Z (Gaussianised T/F) statistic images were thresholded non-parametrically using clusters determined by Z > 2.3 and a (corrected) cluster significance threshold of p = 0.05. Results All 25 adults went through the exposures and functional MRI imaging were collected. Exposure to DE yielded a decrease in functional connectivity compared to exposure to FA, shown through the comparison of DE and FA in post-exposure measurement of functional connectivity. Conclusion We observed short-term pollution-attributable decrements in default mode network functional connectivity. Decrements in brain connectivity causes many detrimental effects to the human body so this finding should guide policy change in air pollution exposure regulation. Trial registration University of British Columbia Clinical Research Ethics Board (# H12-03025), Vancouver Coastal Health Ethics Board (# V12-03025), and Health Canada’s Research Ethics Board (# 2012-0040). Peer Review reports Background Exposure to traffic-related air pollution (TRAP) has long been associated with a range of adverse health effects, principally cardiovascular and respiratory [ 1 ]. This poses an enormous global burden, in terms of morbidity and lost productivity, as well as deaths estimated at approximately five million per year worldwide [ 2 ]. This profound toll is increasingly appreciated as including impacts on the central nervous system, but the data therein remains immature. Further, neurobiological underpinnings of these observations remain elusive, although some preliminary data suggest direct transmission of particles via the olfactory bulb and/or secondary transmission of inflammation likely generated more proximally [ 3 – 5 ]. Given the profound implications for public health across essentially all communities [ 6 ], data that adds overall biologic plausibility and also specific evidence of affected body systems are critically needed in order to support observational data [ 7 – 10 ]. Therefore, we performed the first controlled human exposure study to TRAP, using an established and safe paradigm of diluted diesel exhaust, that examines changes in functional MRI in an efficient crossover study (namely, diesel exhaust [DE] or filtered air [FA] exposure following light exercise), allowing observation of short-term effects on brain connectivity in this context. Methods Participants A total of 100 MRI acquisitions were obtained in the current study. Twenty-five adult participants were tested immediately pre- and post-exposure to diesel exhaust (DE) and immediately pre- and post-exposure to filtered air (FA) for comparison. All participants were recruited through posters in the community, online notices, and e-mail notifications to the Vancouver Coastal Health Staff List-Serve. Inclusion criteria for participants were as follows: between 19 and 49 years of age, able to converse in English, healthy, non-smoking, not pregnant or breast-feeding, and without any contraindications for MRI. So long as inclusion criteria were met, the only exclusion criteria was claustrophobia. Procedure The study employed a controlled, double-blinded crossover design at the Air Pollution Exposure Lab. Each participant was tested in both the control condition (exposure to FA) and the experimental condition (exposure to DE) with four data acquisitions: (1) pre-FA; (2) post-FA; (3) pre-DE and (4) post-DE. The order of exposure to FA and DE was randomized and counterbalanced across participants, with a two-week delay between conditions. Both participants and individuals involved in collecting the MRI data were blinded to the condition, a technique that has been shown not only nominal but also effective [ 11 ]. FA or DE (nominal concentration: 300 µg of particulate matter of 2.5 microns or less [PM 2.5 ]/m 3 ) exposure occurred for 120 min [ 12 ]. During exposure, participants cycled on a stationary bicycle at light effort (that which yields ventilation at 15 L/min/m 2 ) for 15 min, during the first quarter of each hour, to maintain a representative level of activity. Image acquisition The following MRI protocol was employed pre-FA, post-FA, pre-DE and post-DE for each participant. All images were acquired at BC Children’s Hospital on a 3 Tesla GE Discovery MR750 MRI scanner. A whole-brain anatomical MRI scan was acquired with a T1-weighted FSPGR 3D sequence, with the following parameters: a repetition time (TR) of 8.148 ms, an echo time of 3.172 ms, voxel size of 1 × 1 × 1 mm, and a flip angle of 8°. A functional MRI (fMRI) scan was obtained during resting state (with eyes open or closed). The resting state fMRI scan was 6 min in duration and obtained with a T2*-weighted echo-planar imaging sequence with the following parameters: a repetition time of 2000 ms, an echo time of 19 ms, 180 volumes, 39 slices, and a voxel size of 3 × 3 × 3 mm. Additional task-based scans were obtained following resting state scans, but were ancillary to the hypotheses being tested here. Functional MRI data analyses All analysis steps were performed using tools within the Functional MRI of the Brain Software Library (FSL; Analysis Group, FMRIB, Oxford, UK, ) [ 13 ]. Non-brain tissue in the raw T1 images was removed using the automated Brain Extraction Tool, followed by manual verification and optimization for each subject. A seed-based approach was used to examine functional connectivity in the default mode network (DMN) [ 14 ]. The FEAT function was used to pre-process the data including skull removal (using the Brain Extraction Tool), motion correction (using MCFLIRT) [ 15 ], and highpass temporal filtering (using Gaussian-weighted least-squares straight line fitting with σ = 50.0 s). No smoothing was applied. Registration of the functional data to the high-resolution structural image was carried out using the boundary-based registration algorithm. Registration of the high-resolution structural images to standard space was carried out using FLIRT [ 15 , 16 ] and<|im_end|> <|im_start|>assistant A new study by researchers at the University of British Columbia and the University of Victoria has shown that common levels of traffic pollution can impair human brain function in only a matter of hours. The findings, published in the journal Environmental Health, show that just two hours of exposure to diesel exhaust causes a decrease in the brain's functional connectivity—a measure of how The study provides the first evidence in humans, from a controlled experiment, of altered brain network connectivity induced by air pollution. "For many decades, scientists thought the brain may be protected from the harmful effects of air pollution," said senior study author Dr. Chris Carlsten, professor and head of respiratory medicine and the Canada Research Chair in occupational and environmental lung disease at UBC. "This study, which is the first of its kind in the world, provides fresh evidence supporting a connection between air pollution and cognition." For the study, the researchers briefly exposed 25 healthy adults to diesel exhaust and filtered air at different times in a laboratory setting. Brain activity was measured before and after each exposure using functional magnetic resonance imaging (fMRI). The researchers analyzed changes in the brain's default mode network (DMN), a set of inter-connected brain regions that play an important role in memory and internal thought. The fMRI revealed that participants had decreased functional connectivity in widespread regions of the DMN after exposure to diesel exhaust, compared to filtered air. "We know that altered functional connectivity in the DMN has been associated with reduced cognitive performance and symptoms of depression, so it's concerning to see traffic pollution interrupting these same networks," said Dr. Jodie Gawryluk, a psychology professor at the University of Victoria and the study's first author. "While more research is needed to fully understand the functional impacts of these changes, it's possible that they may impair people's thinking or ability to work." Taking steps to protect yourself Notably, the changes in the brain were temporary and participants' connectivity returned to normal after the exposure. Dr. Carlsten speculated that the effects could be long lasting where exposure is continuous. He said that people should be mindful of the air they're breathing and take appropriate steps to minimize their exposure to potentially harmful air pollutants like car exhaust. "People may want to think twice the next time they're stuck in traffic with the windows rolled down," said Dr. Carlsten. "It's important to ensure that your car's air filter is in good working order, and if you're walking or biking down a busy street, consider diverting to a less busy route." While the current study only looked at the cognitive impacts of traffic-derived pollution, Dr. Carlsten said that other products of combustion are likely a concern. "Air pollution is now recognized as the largest environmental threat to human health and we are increasingly seeing the impacts across all major organ systems," says Dr. Carlsten. "I expect we would see similar impacts on the brain from exposure to other air pollutants, like forest fire smoke. With the increasing incidence of neurocognitive disorders, it's an important consideration for public health officials and policymakers." The study was conducted at UBC's Air Pollution Exposure Laboratory, located at Vancouver General Hospital, which is equipped with a state-of-the-art exposure booth that can mimic what it is like to breathe a variety of air pollutants. In this study, which was carefully designed and approved for safety, the researchers used freshly-generated exhaust that was diluted and aged to reflect real-world conditions. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 25837, 6104, 433, 374, 3967, 430, 14675, 311, 9629, 14228, 3805, 25793, 11384, 459, 23205, 3728, 26936, 389, 3823, 2890, 11, 18247, 8385, 5848, 1234, 79, 6258, 826, 58179, 7293, 66684, 13, 578, 4007, 14564, 420, 13225, 304, 6677, 13, 19331, 1226, 10887, 279, 1176, 14400, 3823, 14675, 4007, 1701, 16003, 52460, 449, 459, 11297, 2015, 92775, 1534, 2033, 95449, 49480, 4007, 315, 33880, 17960, 320, 1170, 8, 323, 2585, 320, 42231, 3805, 26, 15358, 8, 304, 220, 914, 9498, 12884, 320, 975, 25000, 11, 220, 806, 28585, 26, 220, 777, 4235, 2491, 1667, 2362, 26, 912, 86304, 570, 20017, 73279, 1051, 11953, 704, 1701, 264, 9709, 6372, 1646, 304, 13062, 2797, 13, 1901, 320, 38, 48072, 4147, 350, 12598, 8, 43589, 5448, 1051, 12447, 291, 2536, 74066, 16743, 750, 1701, 28066, 11075, 555, 1901, 871, 220, 17, 13, 18, 323, 264, 320, 20523, 291, 8, 10879, 26431, 12447, 315, 281, 284, 220, 15, 13, 2304, 13, 18591, 2052, 220, 914, 12884, 4024, 1555, 279, 70530, 323, 16003, 52460, 32758, 1051, 14890, 13, 71866, 311, 3467, 58487, 264, 18979, 304, 16003, 31357, 7863, 311, 14675, 311, 15358, 11, 6982, 1555, 279, 12593, 315, 3467, 323, 15358, 304, 1772, 10397, 12313, 19179, 315, 16003, 31357, 13, 74977, 1226, 13468, 2875, 9860, 25793, 29883, 1356, 6047, 9927, 1392, 304, 1670, 3941, 4009, 16003, 31357, 13, 65201, 1392, 304, 8271, 31357, 11384, 1690, 65069, 6372, 311, 279, 3823, 2547, 779, 420, 9455, 1288, 8641, 4947, 2349, 304, 3805, 25793, 14675, 19812, 13, 41574, 12506, 3907, 315, 8013, 19326, 33135, 8483, 50281, 8925, 30183, 473, 717, 12, 14649, 914, 705, 23393, 72658, 6401, 50281, 8925, 30183, 650, 717, 12, 14649, 914, 705, 323, 6401, 7008, 753, 8483, 50281, 8925, 30183, 220, 679, 17, 12, 8759, 15, 570, 46247, 10506, 6821, 25837, 71866, 311, 9629, 14228, 3805, 25793, 320, 2434, 2599, 8, 706, 1317, 1027, 5938, 449, 264, 2134, 315, 31959, 2890, 6372, 11, 92381, 41713, 323, 42631, 510, 220, 16, 21087, 1115, 34103, 459, 23205, 3728, 23104, 11, 304, 3878, 315, 93144, 19025, 323, 5675, 26206, 11, 439, 1664, 439, 16779, 13240, 520, 13489, 4330, 3610, 824, 1060, 15603, 510, 220, 17, 21087, 1115, 28254, 26936, 374, 15098, 26893, 439, 2737, 25949, 389, 279, 8792, 23418, 1887, 11, 719, 279, 828, 58179, 8625, 86525, 13, 15903, 11, 18247, 8385, 5848, 1234, 79, 6258, 826, 315, 1521, 24654, 7293, 66684, 11, 8051, 1063, 33269, 828, 4284, 2167, 18874, 315, 19252, 4669, 279, 8492, 22348, 46912, 323, 5255, 14580, 18874, 315, 37140, 4461, 8066, 810, 22267, 318, 750, 510, 220, 18, 1389, 220, 20, 21087, 16644, 279, 28254, 25127, 369, 586, 2890, 4028, 16168, 682, 10977, 510, 220, 21, 10881, 828, 430, 11621, 8244, 6160, 39227, 628, 12119, 3225, 323, 1101, 3230, 6029, 315, 11754, 2547, 6067, 527, 41440, 4460, 304, 2015, 311, 1862, 90380, 828, 510, 220, 22, 1389, 220, 605, 21087, 15636, 11, 584, 10887, 279, 1176, 14400, 3823, 14675, 4007, 311, 5091, 2599, 11, 1701, 459, 9749, 323, 6220, 49340, 315, 80703, 33880, 17960, 11, 430, 49095, 4442, 304, 16003, 52460, 304, 459, 11297, 49480, 4007, 320, 12682, 989, 11, 33880, 17960, 510, 1170, 60, 477, 18797, 3805, 510, 3711, 60, 14675, 2768, 3177, 10368, 705, 10923, 22695, 315, 2875, 9860, 6372, 389, 8271, 31357, 304, 420, 2317, 13, 19331, 52878, 362, 2860, 315, 220, 1041, 52460, 63948, 1051, 12457, 304, 279, 1510, 4007, 13, 44956, 36399, 6822, 13324, 1051, 12793, 7214, 864, 12, 323, 1772, 10397, 12313, 311, 33880, 17960, 320, 1170, 8, 323, 7214, 864, 12, 323, 1772, 10397, 12313, 311, 18797, 3805, 320, 3711, 8, 369, 12593, 13, 2052, 13324, 1051, 45425, 1555, 39568, 304, 279, 4029, 11, 2930, 35871, 11, 323, 384, 11724, 22736, 311, 279, 23393, 72658, 6401, 17381, 1796, 6354, 5976, 13, 763, 9134, 13186, 369, 13324, 1051, 439, 11263, 25, 1990, 220, 777, 323, 220, 2491, 1667, 315, 4325, 11, 3025, 311, 95340, 304, 6498, 11, 9498, 11, 2536, 4773, 10979, 11, 539, 20895, 477, 17659, 12, 46519, 11, 323, 2085, 904, 6155, 467, 30780, 811, 369, 52460, 13, 2100, 1317, 439, 28286, 13186, 1051, 2322, 11, 279, 1193, 42308, 13186, 574, 87804, 592, 22761, 41163, 13, 45546, 578, 4007, 20011, 264, 14400, 11, 2033, 16677, 17003, 49480, 2955, 520, 279, 6690, 96201, 71866, 11868, 13, 9062, 25923, 574, 12793, 304, 2225, 279, 2585, 3044, 320, 327, 12313, 311, 15358, 8, 323, 279, 22772, 3044, 320, 327, 12313, 311, 3467, 8, 449, 3116, 828, 63948, 25, 320, 16, 8, 864, 12, 3711, 26, 320, 17, 8, 1772, 12, 3711, 26, 320, 18, 8, 864, 12, 1170, 323, 320, 19, 8, 1772, 12, 1170, 13, 578, 2015, 315, 14675, 311, 15358, 323, 3467, 574, 47341, 323, 5663, 59502, 4028, 13324, 11, 449, 264, 1403, 30609, 7781, 1990, 4787, 13, 11995, 13324, 323, 7931, 6532, 304, 26984, 279, 52460, 828, 1051, 90216, 311, 279, 3044, 11, 264, 15105, 430, 706, 1027, 6982, 539, 1193, 47855, 719, 1101, 7524, 510, 220, 806, 21087, 15358, 477, 3467, 320, 17101, 992, 20545, 25, 220, 3101, 64012, 70, 315, 2598, 6468, 5030, 315, 220, 17, 13, 20, 19748, 26692, 477, 2753, 510, 8971, 220, 17, 13, 20, 2331, 14, 76, 220, 18, 883, 14675, 10222, 369, 220, 4364, 1332, 510, 220, 717, 21087, 12220, 14675, 11, 13324, 272, 37676, 389, 264, 53735, 36086, 520, 3177, 5149, 320, 9210, 902, 36508, 56234, 520, 220, 868, 445, 45273, 3262, 220, 17, 883, 369, 220, 868, 1332, 11, 2391, 279, 1176, 8502, 315, 1855, 6596, 11, 311, 10519, 264, 18740, 2237, 315, 5820, 13, 4758, 24279, 578, 2768, 52460, 11766, 574, 20011, 864, 12, 3711, 11, 1772, 12, 3711, 11, 864, 12, 1170, 323, 1772, 12, 1170, 369, 1855, 25923, 13, 2052, 5448, 1051, 19426, 520, 18531, 15394, 753, 15429, 389, 264, 220, 18, 28298, 30957, 39193, 29433, 11711, 52460, 21438, 13, 362, 4459, 31217, 467, 75893, 950, 52460, 8737, 574, 19426, 449, 264, 350, 16, 12923, 291, 435, 4695, 8796, 220, 18, 35, 8668, 11, 449, 279, 2768, 5137, 25, 264, 54515, 892, 320, 2434, 8, 315, 220, 23, 13, 10410, 10030, 11, 459, 1722, 892, 315, 220, 18, 13, 10861, 10030, 11, 61284, 1404, 315, 220, 16, 25800, 220, 16, 25800, 220, 16, 9653, 11, 323, 264, 18791, 9392, 315, 220, 23, 11877, 13, 362, 16003, 52460, 320, 69, 79770, 8, 8737, 574, 12457, 2391, 41219, 1614, 320, 4291, 6548, 1825, 477, 8036, 570, 578, 41219, 1614, 282, 79770, 8737, 574, 220, 21, 1332, 304, 8250, 323, 12457, 449, 264, 350, 17, 74077, 80896, 1722, 74081, 277, 32758, 8668, 449, 279, 2768, 5137, 25, 264, 54515, 892, 315, 220, 1049, 15, 10030, 11, 459, 1722, 892, 315, 220, 777, 10030, 11, 220, 5245, 27378, 11, 220, 2137, 35354, 11, 323, 264, 61284, 1404, 315, 220, 18, 25800, 220, 18, 25800, 220, 18, 9653, 13, 24086, 3465, 6108, 43739, 1051, 12457, 2768, 41219, 1614, 43739, 11, 719, 1051, 46845, 35605, 311, 279, 74513, 1694, 12793, 1618, 13, 55550, 52460, 828, 29060, 2052, 6492, 7504, 1051, 10887, 1701, 7526, 2949, 279, 55550, 52460, 315, 279, 31417, 4476, 11896, 320, 37, 8143, 26, 18825, 5856, 11, 435, 18953, 3336, 11, 26275, 11, 6560, 11, 883, 510, 220, 1032, 21087, 11842, 31217, 467, 20438, 304, 279, 7257, 350, 16, 5448, 574, 7108, 1701, 279, 28598, 31417, 95606, 13782, 11, 8272, 555, 11630, 23751, 323, 26329, 369, 1855, 3917, 13, 362, 10533, 6108, 5603, 574, 1511, 311, 21635, 16003, 31357, 304, 279, 1670, 3941, 4009, 320, 8561, 45, 8, 510, 220, 975, 21087, 578, 29031, 835, 734, 574, 1511, 311, 864, 51194, 279, 828, 2737, 35113, 17065, 320, 985, 279, 31417, 95606, 13782, 705, 11633, 27358, 320, 985, 21539, 6254, 31621, 8, 510, 220, 868, 10881, 323, 1579, 6519, 37015, 30770, 320, 985, 49668, 12923, 291, 3325, 1355, 41956, 7833, 1584, 27442, 449, 48823, 284, 220, 1135, 13, 15, 274, 570, 2360, 63061, 574, 9435, 13, 25532, 315, 279, 16003, 828, 311, 279, 1579, 64036, 24693, 2217, 574, 11953, 704, 1701, 279, 19254, 6108, 12506, 12384, 13, 25532, 315, 279, 1579, 64036, 24693, 5448, 311, 5410, 3634, 574, 11953, 704, 1701, 13062, 31621, 510, 220, 868, 1174, 220, 845, 2331, 323, 128257, 198, 128256, 78191, 198, 32, 502, 4007, 555, 12074, 520, 279, 3907, 315, 8013, 19326, 323, 279, 3907, 315, 23225, 706, 6982, 430, 4279, 5990, 315, 9629, 25793, 649, 38974, 3823, 8271, 734, 304, 1193, 264, 5030, 315, 4207, 13, 578, 14955, 11, 4756, 304, 279, 8486, 25027, 6401, 11, 1501, 430, 1120, 1403, 4207, 315, 14675, 311, 33880, 17960, 11384, 264, 18979, 304, 279, 8271, 596, 16003, 31357, 29096, 6767, 315, 1268, 578, 4007, 5825, 279, 1176, 6029, 304, 12966, 11, 505, 264, 14400, 9526, 11, 315, 29852, 8271, 4009, 31357, 36572, 555, 3805, 25793, 13, 330, 2520, 1690, 11026, 11, 14248, 3463, 279, 8271, 1253, 387, 2682, 505, 279, 28856, 6372, 315, 3805, 25793, 1359, 1071, 10195, 4007, 3229, 2999, 13, 11517, 22770, 16172, 11, 14561, 323, 2010, 315, 42631, 16088, 323, 279, 7008, 8483, 16478, 304, 65195, 323, 12434, 21271, 8624, 520, 549, 5002, 13, 330, 2028, 4007, 11, 902, 374, 279, 1176, 315, 1202, 3169, 304, 279, 1917, 11, 5825, 7878, 6029, 12899, 264, 3717, 1990, 3805, 25793, 323, 75310, 1210, 1789, 279, 4007, 11, 279, 12074, 27851, 15246, 220, 914, 9498, 12884, 311, 33880, 17960, 323, 18797, 3805, 520, 2204, 3115, 304, 264, 27692, 6376, 13, 31417, 5820, 574, 17303, 1603, 323, 1306, 1855, 14675, 1701, 16003, 24924, 58081, 32758, 320, 69, 79770, 570, 578, 12074, 30239, 4442, 304, 279, 8271, 596, 1670, 3941, 4009, 320, 8561, 45, 705, 264, 743, 315, 958, 73288, 8271, 13918, 430, 1514, 459, 3062, 3560, 304, 5044, 323, 5419, 3463, 13, 578, 282, 79770, 10675, 430, 13324, 1047, 25983, 16003, 31357, 304, 24716, 13918, 315, 279, 20804, 45, 1306, 14675, 311, 33880, 17960, 11, 7863, 311, 18797, 3805, 13, 330, 1687, 1440, 430, 29852, 16003, 31357, 304, 279, 20804, 45, 706, 1027, 5938, 449, 11293, 25702, 5178, 323, 13803, 315, 18710, 11, 779, 433, 596, 18815, 311, 1518, 9629, 25793, 12956, 287, 1521, 1890, 14488, 1359, 1071, 2999, 13, 622, 86449, 86638, 894, 102847, 11, 264, 31018, 14561, 520, 279, 3907, 315, 23225, 323, 279, 4007, 596, 1176, 3229, 13, 330, 8142, 810, 3495, 374, 4460, 311, 7373, 3619, 279, 16003, 25949, 315, 1521, 4442, 11, 433, 596, 3284, 430, 814, 1253, 38974, 1274, 596, 7422, 477, 5845, 311, 990, 1210, 36925, 7504, 311, 6144, 6261, 2876, 2915, 11, 279, 4442, 304, 279, 8271, 1051, 13643, 323, 13324, 6, 31357, 6052, 311, 4725, 1306, 279, 14675, 13, 2999, 13, 22770, 16172, 74877, 430, 279, 6372, 1436, 387, 1317, 29869, 1405, 14675, 374, 19815, 13, 1283, 1071, 430, 1274, 1288, 387, 63442, 315, 279, 3805, 814, 2351, 27027, 323, 1935, 8475, 7504, 311, 30437, 872, 14675, 311, 13893, 28856, 3805, 83661, 1093, 1841, 17960, 13, 330, 16298, 1253, 1390, 311, 1781, 11157, 279, 1828, 892, 814, 2351, 16075, 304, 9629, 449, 279, 11276, 23255, 1523, 1359, 1071, 2999, 13, 22770, 16172, 13, 330, 2181, 596, 3062, 311, 6106, 430, 701, 1841, 596, 3805, 4141, 374, 304, 1695, 3318, 2015, 11, 323, 422, 499, 2351, 11689, 477, 67180, 1523, 264, 13326, 8761, 11, 2980, 37098, 287, 311, 264, 2753, 13326, 6149, 1210, 6104, 279, 1510, 4007, 1193, 7111, 520, 279, 25702, 25949, 315, 9629, 72286, 25793, 11, 2999, 13, 22770, 16172, 1071, 430, 1023, 3956, 315, 59333, 527, 4461, 264, 4747, 13, 330, 26777, 25793, 374, 1457, 15324, 439, 279, 7928, 12434, 6023, 311, 3823, 2890, 323, 584, 527, 15098, 9298, 279, 25949, 4028, 682, 3682, 2942, 6067, 1359, 2795, 2999, 13, 22770, 16172, 13, 330, 40, 1755, 584, 1053, 1518, 4528, 25949, 389, 279, 8271, 505, 14675, 311, 1023, 3805, 83661, 11, 1093, 13952, 4027, 16603, 13, 3161, 279, 7859, 39775, 315, 18247, 66, 51549, 24673, 11, 433, 596, 459, 3062, 18361, 369, 586, 2890, 7510, 323, 70978, 1210, 578, 4007, 574, 13375, 520, 549, 5002, 596, 6690, 96201, 71866, 32184, 11, 7559, 520, 23393, 3331, 15429, 11, 902, 374, 19167, 449, 264, 1614, 8838, 10826, 38921, 14675, 36506, 430, 649, 56459, 1148, 433, 374, 1093, 311, 37397, 264, 8205, 315, 3805, 83661, 13, 763, 420, 4007, 11, 902, 574, 15884, 6319, 323, 12054, 369, 7296, 11, 279, 12074, 1511, 50999, 16581, 17960, 430, 574, 80703, 323, 20330, 311, 8881, 1972, 31184, 4787, 13, 220, 128257, 198 ]

2,085

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Caspase-8 is the initiator caspase of extrinsic apoptosis 1 , 2 and inhibits necroptosis mediated by RIPK3 and MLKL. Accordingly, caspase-8 deficiency in mice causes embryonic lethality 3 , which can be rescued by deletion of either Ripk3 or Mlkl 4 , 5 , 6 . Here we show that the expression of enzymatically inactive CASP8(C362S) causes embryonic lethality in mice by inducing necroptosis and pyroptosis. Similar to Casp8 −/− mice 3 , 7 , Casp8 C362S/C362S mouse embryos died after endothelial cell necroptosis leading to cardiovascular defects. MLKL deficiency rescued the cardiovascular phenotype but unexpectedly caused perinatal lethality in Casp8 C362S/C362S mice, indicating that CASP8(C362S) causes necroptosis-independent death at later stages of embryonic development. Specific loss of the catalytic activity of caspase-8 in intestinal epithelial cells induced intestinal inflammation similar to intestinal epithelial cell-specific Casp8 knockout mice 8 . Inhibition of necroptosis by additional deletion of Mlkl severely aggravated intestinal inflammation and caused premature lethality in Mlkl knockout mice with specific loss of caspase-8 catalytic activity in intestinal epithelial cells. Expression of CASP8(C362S) triggered the formation of ASC specks, activation of caspase-1 and secretion of IL-1β. Both embryonic lethality and premature death were completely rescued in Casp8 C362S/C362S Mlkl −/− Asc −/− or Casp8 C362S/C362S Mlkl −/− Casp1 −/− mice, indicating that the activation of the inflammasome promotes CASP8(C362S)-mediated tissue pathology when necroptosis is blocked. Therefore, caspase-8 represents the molecular switch that controls apoptosis, necroptosis and pyroptosis, and prevents tissue damage during embryonic development and adulthood. Main In addition to its role in apoptosis and necroptosis, recent in vitro studies have indicated that caspase-8 induces the production of cytokines by acting as a scaffolding protein and that this role is independent of its enzymatic activity 9 , 10 . The scaffold function of caspase-8 was also shown to be involved in the double-stranded RNA (dsRNA)-induced activation of the NLRP3 inflammasome in macrophages 11 . Additional studies indicate that the enzymatic activity of caspase-8 is required for the activation of NF-κB and secretion of cytokines in response to activated antigen receptors, Fc receptors or Toll-like receptors (TLRs), independently of cell death 12 , 13 . To investigate the physiological role of the enzymatic activity of caspase-8, we generated knock-in mice that expressed catalytically inactive caspase-8 by mutating Cys362 in the substrate binding pocket to serine (C362S) (Extended Data Fig. 1a ). Although heterozygous Casp8 C362S/WT mice were viable (Extended Data Fig. 1b ), Casp8 C362S/C362S embryos died around embryonic day 11.5 (E11.5). Hyperaemia in the abdominal areas was detected in Casp8 C362S/C362S embryos (Fig. 1a ), presumably owing to defects in vascular development, which resembles the phenotype of Casp8 −/− embryos 7 . In order to address the role of caspase-8 in vascular development, we used Tie2 cre (also known as Tek cre ) mice, in which efficient Cre-mediated recombination is induced in all endothelial cells and most haematopoietic cells 14 . Loss of the catalytic activity of caspase-8 in Casp8 C362S/fl Tie2 cre mice or specific knockout of caspase-8 in the endothelial cells of Casp8 fl/fl Tie2 cre mice caused embryonic lethality at the same developmental stage as Casp8 C362S/C362S embryos (Extended Data Fig. 1c, d ). Casp8 C362S/fl Tie2 cre and Casp8 fl/fl Tie2 cre embryos showed the same gross pathology associated with a decrease in yolk-sac vascularization (Fig. 1b and Extended Data Fig. 1d ). Fig. 1: The enzymatic activity of caspase-8 is required to inhibit necroptosis. a , b , Representative images of Casp8 WT/WT ( n = 5), Casp8 C362S/WT ( n = 8), Casp8 C362S/C362S ( n = 3), Casp8 −/− ( n = 3), Casp8 C362S/fl ( n = 5) and Casp8 C362S/fl Tie2 cre ( n = 5) mouse embryos at E11.5 ( a , b , top). CD31 staining as endothelial marker of whole-mount yolk sacs ( b , bottom). Scale bars, 100 µm. c , Representative images of 9-day-old (P9) Casp8 C362S/fl ( n = 3) and Casp8 C362S/fl K14 cre ( n = 3) mice (top left) and skin sections stained with haematoxylin and eosin (H&E) (top right, bottom. Scale bars, 100 µm (magnification, top) and 300 µm (bottom). d , Ileal sections from 10-week-old Casp8 C362S/fl ( n = 3) and Casp8 C362S/fl Villin cre ( n = 4) mice stained with H&E (left), for lysozyme (Paneth cells, middle) and periodic acid–Schiff (PAS) (right). Scale bars, 100 µm. e , f , Count of Paneth cells ( e ) and dead IECs ( f ) (per crypt per mouse, n = 3). Dots, individual mice. Data are mean ± s.e.m. One-way analysis of variance (ANOVA) followed by Dunnett’s post-analysis. Source data Full size image Specific loss of the catalytic activity of caspase-8 in epidermal keratinocytes or intestinal epithelial cells was achieved by crossing Casp8 C362S/fl mice with Krt14 cre (also known as K14 cre ) mice 15 or Vil1 cre (also known as Villin cre ) mice 16 , respectively. Loss of the catalytic activity of caspase-8 in these two cell types caused similar pathologies to caspase-8 deficiency in these tissues. Casp8 C362S/fl K14 cre and Casp8 fl/fl K14 cre mice developed inflammatory skin lesions with focal epidermal thickening and scaling that appeared 5–7 days after birth and these lesions gradually increased in size and distribution and covered large cutaneous areas (Fig. 1c and Extended Data Fig. 1e ). Histological skin analyses revealed epidermal hyperplasia and immune-cell infiltration into the dermis of Casp8 C362S/fl K14 cre and Casp8 fl/fl K14 cre mice as has previously been shown by transgenic overexpression of CASP8(C362S) in epidermal keratinocytes 17 . Mice with intestinal epithelial cell (IEC)-specific loss of caspase-8 catalytic activity ( Casp8 C362S/fl Villin cre ) developed ileitis at 8–10 weeks of age, associated with increased numbers of dying IECs, an altered distribution of goblet cells and loss of Paneth cells; a phenotype that is similar to that found in Casp8 fl/fl Villin cre mice 8 (Fig. 1d–f and Extended Data Fig. 2a, b ). Together, these results demonstrate", "role": "user" }, { "content": "The enzyme caspase-8 induces a molecular cell death programme called pyroptosis without involving its enzymatic activity, a new study by Hamid Kashkar published in Nature shows. In order to safeguard healthy and functioning tissues, cells utilize different cell death mechanisms to dispose of unwanted cells (e.g. infected or aged cells). Apoptosis is a 'cellular suicide programme' that does not cause tissue injury and is induced by caspase-8. Necroptosis is another mode of regulated cell death which causes cellular damage and is normally engaged when caspase-8 is inhibited. Pyroptosis describes an inflammatory mode of regulated cellular death process, which is normally activated in response to microbial pathogens and is central for mounting anti-microbial immunity. Hamid Kashkar and his team have now shown that caspase-8 not only controls apoptosis and necroptosis but pyroptosis as well. The study \"Caspase-8 is the molecular switch for apoptosis, necroptosis and pyroptosis\" was published in Nature. The research team studied the biological roles of caspase-8 in cell cultures and mice. Kashkar's group showed that the enzymatic activity of caspase-8 is required to inhibit pyroptosis. \"We found out that the expression of inactive caspase-8 causes embryonic lethality and inflammatory tissue destruction. This could only be restored when necroptosis and pyroptosis were simultaneously blocked,\" Hamid Kashkar explains. The lack of caspase-8 enzymatic activity primarily causes necroptotic cell death. Interestingly, when necroptosis is blocked, the inactive caspase-8 serves as a protein scaffold for the formation of a signalling protein complex called inflammasome, which ultimately induces pyroptosis. \"Microbial pathogens are heavily reliant on the fate of infected cells and have evolved a number of strategies to inhibit apoptosis and necroptosis,\" Hamid Kashkar adds. The current study hypothesises that these strategies may have driven the counter-evolution of pyroptosis to secure cellular death as a host defence mechanism. The caspase-8-mediated switch between different modes of cell death adds a critical layer to the plasticity of cell death-induced immunity, which is increasingly involved in aging-associated disorders. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Caspase-8 is the initiator caspase of extrinsic apoptosis 1 , 2 and inhibits necroptosis mediated by RIPK3 and MLKL. Accordingly, caspase-8 deficiency in mice causes embryonic lethality 3 , which can be rescued by deletion of either Ripk3 or Mlkl 4 , 5 , 6 . Here we show that the expression of enzymatically inactive CASP8(C362S) causes embryonic lethality in mice by inducing necroptosis and pyroptosis. Similar to Casp8 −/− mice 3 , 7 , Casp8 C362S/C362S mouse embryos died after endothelial cell necroptosis leading to cardiovascular defects. MLKL deficiency rescued the cardiovascular phenotype but unexpectedly caused perinatal lethality in Casp8 C362S/C362S mice, indicating that CASP8(C362S) causes necroptosis-independent death at later stages of embryonic development. Specific loss of the catalytic activity of caspase-8 in intestinal epithelial cells induced intestinal inflammation similar to intestinal epithelial cell-specific Casp8 knockout mice 8 . Inhibition of necroptosis by additional deletion of Mlkl severely aggravated intestinal inflammation and caused premature lethality in Mlkl knockout mice with specific loss of caspase-8 catalytic activity in intestinal epithelial cells. Expression of CASP8(C362S) triggered the formation of ASC specks, activation of caspase-1 and secretion of IL-1β. Both embryonic lethality and premature death were completely rescued in Casp8 C362S/C362S Mlkl −/− Asc −/− or Casp8 C362S/C362S Mlkl −/− Casp1 −/− mice, indicating that the activation of the inflammasome promotes CASP8(C362S)-mediated tissue pathology when necroptosis is blocked. Therefore, caspase-8 represents the molecular switch that controls apoptosis, necroptosis and pyroptosis, and prevents tissue damage during embryonic development and adulthood. Main In addition to its role in apoptosis and necroptosis, recent in vitro studies have indicated that caspase-8 induces the production of cytokines by acting as a scaffolding protein and that this role is independent of its enzymatic activity 9 , 10 . The scaffold function of caspase-8 was also shown to be involved in the double-stranded RNA (dsRNA)-induced activation of the NLRP3 inflammasome in macrophages 11 . Additional studies indicate that the enzymatic activity of caspase-8 is required for the activation of NF-κB and secretion of cytokines in response to activated antigen receptors, Fc receptors or Toll-like receptors (TLRs), independently of cell death 12 , 13 . To investigate the physiological role of the enzymatic activity of caspase-8, we generated knock-in mice that expressed catalytically inactive caspase-8 by mutating Cys362 in the substrate binding pocket to serine (C362S) (Extended Data Fig. 1a ). Although heterozygous Casp8 C362S/WT mice were viable (Extended Data Fig. 1b ), Casp8 C362S/C362S embryos died around embryonic day 11.5 (E11.5). Hyperaemia in the abdominal areas was detected in Casp8 C362S/C362S embryos (Fig. 1a ), presumably owing to defects in vascular development, which resembles the phenotype of Casp8 −/− embryos 7 . In order to address the role of caspase-8 in vascular development, we used Tie2 cre (also known as Tek cre ) mice, in which efficient Cre-mediated recombination is induced in all endothelial cells and most haematopoietic cells 14 . Loss of the catalytic activity of caspase-8 in Casp8 C362S/fl Tie2 cre mice or specific knockout of caspase-8 in the endothelial cells of Casp8 fl/fl Tie2 cre mice caused embryonic lethality at the same developmental stage as Casp8 C362S/C362S embryos (Extended Data Fig. 1c, d ). Casp8 C362S/fl Tie2 cre and Casp8 fl/fl Tie2 cre embryos showed the same gross pathology associated with a decrease in yolk-sac vascularization (Fig. 1b and Extended Data Fig. 1d ). Fig. 1: The enzymatic activity of caspase-8 is required to inhibit necroptosis. a , b , Representative images of Casp8 WT/WT ( n = 5), Casp8 C362S/WT ( n = 8), Casp8 C362S/C362S ( n = 3), Casp8 −/− ( n = 3), Casp8 C362S/fl ( n = 5) and Casp8 C362S/fl Tie2 cre ( n = 5) mouse embryos at E11.5 ( a , b , top). CD31 staining as endothelial marker of whole-mount yolk sacs ( b , bottom). Scale bars, 100 µm. c , Representative images of 9-day-old (P9) Casp8 C362S/fl ( n = 3) and Casp8 C362S/fl K14 cre ( n = 3) mice (top left) and skin sections stained with haematoxylin and eosin (H&E) (top right, bottom. Scale bars, 100 µm (magnification, top) and 300 µm (bottom). d , Ileal sections from 10-week-old Casp8 C362S/fl ( n = 3) and Casp8 C362S/fl Villin cre ( n = 4) mice stained with H&E (left), for lysozyme (Paneth cells, middle) and periodic acid–Schiff (PAS) (right). Scale bars, 100 µm. e , f , Count of Paneth cells ( e ) and dead IECs ( f ) (per crypt per mouse, n = 3). Dots, individual mice. Data are mean ± s.e.m. One-way analysis of variance (ANOVA) followed by Dunnett’s post-analysis. Source data Full size image Specific loss of the catalytic activity of caspase-8 in epidermal keratinocytes or intestinal epithelial cells was achieved by crossing Casp8 C362S/fl mice with Krt14 cre (also known as K14 cre ) mice 15 or Vil1 cre (also known as Villin cre ) mice 16 , respectively. Loss of the catalytic activity of caspase-8 in these two cell types caused similar pathologies to caspase-8 deficiency in these tissues. Casp8 C362S/fl K14 cre and Casp8 fl/fl K14 cre mice developed inflammatory skin lesions with focal epidermal thickening and scaling that appeared 5–7 days after birth and these lesions gradually increased in size and distribution and covered large cutaneous areas (Fig. 1c and Extended Data Fig. 1e ). Histological skin analyses revealed epidermal hyperplasia and immune-cell infiltration into the dermis of Casp8 C362S/fl K14 cre and Casp8 fl/fl K14 cre mice as has previously been shown by transgenic overexpression of CASP8(C362S) in epidermal keratinocytes 17 . Mice with intestinal epithelial cell (IEC)-specific loss of caspase-8 catalytic activity ( Casp8 C362S/fl Villin cre ) developed ileitis at 8–10 weeks of age, associated with increased numbers of dying IECs, an altered distribution of goblet cells and loss of Paneth cells; a phenotype that is similar to that found in Casp8 fl/fl Villin cre mice 8 (Fig. 1d–f and Extended Data Fig. 2a, b ). Together, these results demonstrate<|im_end|> <|im_start|>assistant The enzyme caspase-8 induces a molecular cell death programme called pyroptosis without involving its enzymatic activity, a new study by Hamid Kashkar published in Nature shows. In order to safeguard healthy and functioning tissues, cells utilize different cell death mechanisms to dispose of unwanted cells (e.g. infected or aged cells). Apoptosis is a 'cellular suicide programme' that does not cause tissue injury and is induced by caspase-8. Necroptosis is another mode of regulated cell death which causes cellular damage and is normally engaged when caspase-8 is inhibited. Pyroptosis describes an inflammatory mode of regulated cellular death process, which is normally activated in response to microbial pathogens and is central for mounting anti-microbial immunity. Hamid Kashkar and his team have now shown that caspase-8 not only controls apoptosis and necroptosis but pyroptosis as well. The study "Caspase-8 is the molecular switch for apoptosis, necroptosis and pyroptosis" was published in Nature. The research team studied the biological roles of caspase-8 in cell cultures and mice. Kashkar's group showed that the enzymatic activity of caspase-8 is required to inhibit pyroptosis. "We found out that the expression of inactive caspase-8 causes embryonic lethality and inflammatory tissue destruction. This could only be restored when necroptosis and pyroptosis were simultaneously blocked," Hamid Kashkar explains. The lack of caspase-8 enzymatic activity primarily causes necroptotic cell death. Interestingly, when necroptosis is blocked, the inactive caspase-8 serves as a protein scaffold for the formation of a signalling protein complex called inflammasome, which ultimately induces pyroptosis. "Microbial pathogens are heavily reliant on the fate of infected cells and have evolved a number of strategies to inhibit apoptosis and necroptosis," Hamid Kashkar adds. The current study hypothesises that these strategies may have driven the counter-evolution of pyroptosis to secure cellular death as a host defence mechanism. The caspase-8-mediated switch between different modes of cell death adds a critical layer to the plasticity of cell death-induced immunity, which is increasingly involved in aging-associated disorders. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 11301, 79, 521, 12, 23, 374, 279, 99140, 4865, 79, 521, 315, 11741, 28692, 95874, 220, 16, 1174, 220, 17, 323, 20747, 1220, 19591, 299, 418, 10934, 78926, 555, 91964, 42, 18, 323, 20187, 54083, 13, 63909, 11, 4865, 79, 521, 12, 23, 48294, 304, 24548, 11384, 44481, 14338, 98522, 2786, 220, 18, 1174, 902, 649, 387, 45433, 555, 37166, 315, 3060, 36537, 74, 18, 477, 386, 75, 10784, 220, 19, 1174, 220, 20, 1174, 220, 21, 662, 5810, 584, 1501, 430, 279, 7645, 315, 32011, 7167, 32899, 42890, 47, 23, 3100, 18509, 50, 8, 11384, 44481, 14338, 98522, 2786, 304, 24548, 555, 96811, 19591, 299, 418, 10934, 323, 4611, 299, 418, 10934, 13, 22196, 311, 11301, 79, 23, 25173, 14, 34363, 24548, 220, 18, 1174, 220, 22, 1174, 11301, 79, 23, 356, 18509, 50, 11547, 18509, 50, 8814, 89873, 8636, 1306, 93329, 59544, 2849, 19591, 299, 418, 10934, 6522, 311, 41713, 42655, 13, 20187, 54083, 48294, 45433, 279, 41713, 82423, 719, 51709, 9057, 824, 258, 4306, 98522, 2786, 304, 11301, 79, 23, 356, 18509, 50, 11547, 18509, 50, 24548, 11, 19392, 430, 42890, 47, 23, 3100, 18509, 50, 8, 11384, 19591, 299, 418, 10934, 98885, 4648, 520, 3010, 18094, 315, 44481, 14338, 4500, 13, 29362, 4814, 315, 279, 34454, 70504, 5820, 315, 4865, 79, 521, 12, 23, 304, 63900, 64779, 59544, 7917, 36572, 63900, 37140, 4528, 311, 63900, 64779, 59544, 2849, 19440, 11301, 79, 23, 77173, 24548, 220, 23, 662, 763, 60073, 315, 19591, 299, 418, 10934, 555, 5217, 37166, 315, 386, 75, 10784, 35906, 63368, 63900, 37140, 323, 9057, 42227, 98522, 2786, 304, 386, 75, 10784, 77173, 24548, 449, 3230, 4814, 315, 4865, 79, 521, 12, 23, 34454, 70504, 5820, 304, 63900, 64779, 59544, 7917, 13, 16783, 315, 42890, 47, 23, 3100, 18509, 50, 8, 22900, 279, 18488, 315, 20382, 2395, 14895, 11, 15449, 315, 4865, 79, 521, 12, 16, 323, 87067, 315, 11598, 12, 16, 52355, 13, 11995, 44481, 14338, 98522, 2786, 323, 42227, 4648, 1051, 6724, 45433, 304, 11301, 79, 23, 356, 18509, 50, 11547, 18509, 50, 386, 75, 10784, 25173, 14, 34363, 40660, 25173, 14, 34363, 477, 11301, 79, 23, 356, 18509, 50, 11547, 18509, 50, 386, 75, 10784, 25173, 14, 34363, 11301, 79, 16, 25173, 14, 34363, 24548, 11, 19392, 430, 279, 15449, 315, 279, 4704, 309, 7044, 638, 39990, 42890, 47, 23, 3100, 18509, 50, 7435, 4503, 660, 20438, 77041, 994, 19591, 299, 418, 10934, 374, 19857, 13, 15636, 11, 4865, 79, 521, 12, 23, 11105, 279, 31206, 3480, 430, 11835, 95874, 11, 19591, 299, 418, 10934, 323, 4611, 299, 418, 10934, 11, 323, 29034, 20438, 5674, 2391, 44481, 14338, 4500, 323, 64033, 13, 4802, 763, 5369, 311, 1202, 3560, 304, 95874, 323, 19591, 299, 418, 10934, 11, 3293, 304, 55004, 7978, 617, 16717, 430, 4865, 79, 521, 12, 23, 90974, 279, 5788, 315, 83185, 1572, 555, 15718, 439, 264, 57250, 15345, 13128, 323, 430, 420, 3560, 374, 9678, 315, 1202, 32011, 780, 5820, 220, 24, 1174, 220, 605, 662, 578, 85552, 734, 315, 4865, 79, 521, 12, 23, 574, 1101, 6982, 311, 387, 6532, 304, 279, 2033, 42728, 6601, 41214, 320, 5469, 31820, 7435, 485, 24921, 15449, 315, 279, 452, 20721, 47, 18, 4704, 309, 7044, 638, 304, 18563, 764, 1154, 220, 806, 662, 24086, 7978, 13519, 430, 279, 32011, 780, 5820, 315, 4865, 79, 521, 12, 23, 374, 2631, 369, 279, 15449, 315, 45827, 12, 68437, 33, 323, 87067, 315, 83185, 1572, 304, 2077, 311, 22756, 83089, 44540, 11, 435, 66, 44540, 477, 86394, 12970, 44540, 320, 13778, 43427, 705, 29235, 315, 2849, 4648, 220, 717, 1174, 220, 1032, 662, 2057, 19874, 279, 53194, 3560, 315, 279, 32011, 780, 5820, 315, 4865, 79, 521, 12, 23, 11, 584, 8066, 14459, 3502, 24548, 430, 13605, 34454, 16820, 2740, 32899, 4865, 79, 521, 12, 23, 555, 97618, 356, 1065, 18509, 304, 279, 54057, 11212, 18301, 311, 1446, 483, 320, 34, 18509, 50, 8, 320, 54290, 2956, 23966, 13, 220, 16, 64, 7609, 10541, 30548, 76523, 70, 788, 11301, 79, 23, 356, 18509, 50, 14, 18961, 24548, 1051, 31528, 320, 54290, 2956, 23966, 13, 220, 16, 65, 7026, 11301, 79, 23, 356, 18509, 50, 11547, 18509, 50, 89873, 8636, 2212, 44481, 14338, 1938, 220, 806, 13, 20, 320, 36, 806, 13, 20, 570, 33832, 64, 22689, 304, 279, 57056, 5789, 574, 16914, 304, 11301, 79, 23, 356, 18509, 50, 11547, 18509, 50, 89873, 320, 30035, 13, 220, 16, 64, 7026, 36548, 56612, 311, 42655, 304, 64603, 4500, 11, 902, 53291, 279, 82423, 315, 11301, 79, 23, 25173, 14, 34363, 89873, 220, 22, 662, 763, 2015, 311, 2686, 279, 3560, 315, 4865, 79, 521, 12, 23, 304, 64603, 4500, 11, 584, 1511, 59825, 17, 1922, 320, 19171, 3967, 439, 56534, 1922, 883, 24548, 11, 304, 902, 11297, 7948, 82076, 312, 76128, 374, 36572, 304, 682, 93329, 59544, 7917, 323, 1455, 6520, 43698, 56809, 3978, 292, 7917, 220, 975, 662, 25733, 315, 279, 34454, 70504, 5820, 315, 4865, 79, 521, 12, 23, 304, 11301, 79, 23, 356, 18509, 50, 59403, 59825, 17, 1922, 24548, 477, 3230, 77173, 315, 4865, 79, 521, 12, 23, 304, 279, 93329, 59544, 7917, 315, 11301, 79, 23, 1344, 59403, 59825, 17, 1922, 24548, 9057, 44481, 14338, 98522, 2786, 520, 279, 1890, 48006, 6566, 439, 11301, 79, 23, 356, 18509, 50, 11547, 18509, 50, 89873, 320, 54290, 2956, 23966, 13, 220, 16, 66, 11, 294, 7609, 11301, 79, 23, 356, 18509, 50, 59403, 59825, 17, 1922, 323, 11301, 79, 23, 1344, 59403, 59825, 17, 1922, 89873, 8710, 279, 1890, 20547, 77041, 5938, 449, 264, 18979, 304, 379, 23427, 1355, 582, 64603, 2065, 320, 30035, 13, 220, 16, 65, 323, 41665, 2956, 23966, 13, 220, 16, 67, 7609, 23966, 13, 220, 16, 25, 578, 32011, 780, 5820, 315, 4865, 79, 521, 12, 23, 374, 2631, 311, 69033, 19591, 299, 418, 10934, 13, 264, 1174, 293, 1174, 38366, 5448, 315, 11301, 79, 23, 59199, 14, 18961, 320, 308, 284, 220, 20, 705, 11301, 79, 23, 356, 18509, 50, 14, 18961, 320, 308, 284, 220, 23, 705, 11301, 79, 23, 356, 18509, 50, 11547, 18509, 50, 320, 308, 284, 220, 18, 705, 11301, 79, 23, 25173, 14, 34363, 320, 308, 284, 220, 18, 705, 11301, 79, 23, 356, 18509, 50, 59403, 320, 308, 284, 220, 20, 8, 323, 11301, 79, 23, 356, 18509, 50, 59403, 59825, 17, 1922, 320, 308, 284, 220, 20, 8, 8814, 89873, 520, 469, 806, 13, 20, 320, 264, 1174, 293, 1174, 1948, 570, 11325, 2148, 88896, 439, 93329, 59544, 11381, 315, 4459, 60688, 379, 23427, 11347, 82, 320, 293, 1174, 5740, 570, 25635, 16283, 11, 220, 1041, 64012, 76, 13, 272, 1174, 38366, 5448, 315, 220, 24, 11477, 6418, 320, 47, 24, 8, 11301, 79, 23, 356, 18509, 50, 59403, 320, 308, 284, 220, 18, 8, 323, 11301, 79, 23, 356, 18509, 50, 59403, 735, 975, 1922, 320, 308, 284, 220, 18, 8, 24548, 320, 3565, 2163, 8, 323, 6930, 14491, 61152, 449, 6520, 336, 4428, 4223, 3817, 323, 62894, 258, 320, 39, 69248, 8, 320, 3565, 1314, 11, 5740, 13, 25635, 16283, 11, 220, 1041, 64012, 76, 320, 76, 3326, 2461, 11, 1948, 8, 323, 220, 3101, 64012, 76, 320, 15205, 570, 294, 1174, 358, 273, 278, 14491, 505, 220, 605, 30609, 6418, 11301, 79, 23, 356, 18509, 50, 59403, 320, 308, 284, 220, 18, 8, 323, 11301, 79, 23, 356, 18509, 50, 59403, 16959, 258, 1922, 320, 308, 284, 220, 19, 8, 24548, 61152, 449, 473, 69248, 320, 2414, 705, 369, 14869, 708, 21436, 68, 320, 36793, 774, 7917, 11, 6278, 8, 323, 39445, 13935, 4235, 31224, 3168, 320, 47, 1950, 8, 320, 1315, 570, 25635, 16283, 11, 220, 1041, 64012, 76, 13, 384, 1174, 282, 1174, 4605, 315, 11233, 774, 7917, 320, 384, 883, 323, 5710, 358, 7650, 82, 320, 282, 883, 320, 716, 14774, 824, 8814, 11, 308, 284, 220, 18, 570, 423, 2469, 11, 3927, 24548, 13, 2956, 527, 3152, 20903, 274, 1770, 749, 13, 3861, 27896, 6492, 315, 33373, 320, 55994, 13114, 8, 8272, 555, 29838, 83824, 753, 1772, 56536, 13, 8922, 828, 8797, 1404, 2217, 29362, 4814, 315, 279, 34454, 70504, 5820, 315, 4865, 79, 521, 12, 23, 304, 4248, 1814, 14991, 34801, 15111, 57878, 477, 63900, 64779, 59544, 7917, 574, 17427, 555, 27736, 11301, 79, 23, 356, 18509, 50, 59403, 24548, 449, 735, 3423, 975, 1922, 320, 19171, 3967, 439, 735, 975, 1922, 883, 24548, 220, 868, 477, 64749, 16, 1922, 320, 19171, 3967, 439, 16959, 258, 1922, 883, 24548, 220, 845, 1174, 15947, 13, 25733, 315, 279, 34454, 70504, 5820, 315, 4865, 79, 521, 12, 23, 304, 1521, 1403, 2849, 4595, 9057, 4528, 1853, 9268, 311, 4865, 79, 521, 12, 23, 48294, 304, 1521, 39881, 13, 11301, 79, 23, 356, 18509, 50, 59403, 735, 975, 1922, 323, 11301, 79, 23, 1344, 59403, 735, 975, 1922, 24548, 8040, 47288, 6930, 63324, 449, 42199, 4248, 1814, 14991, 12314, 6147, 323, 28041, 430, 9922, 220, 20, 4235, 22, 2919, 1306, 7342, 323, 1521, 63324, 27115, 7319, 304, 1404, 323, 8141, 323, 9960, 3544, 4018, 18133, 5789, 320, 30035, 13, 220, 16, 66, 323, 41665, 2956, 23966, 13, 220, 16, 68, 7609, 67005, 5848, 6930, 29060, 10675, 4248, 1814, 14991, 17508, 501, 36259, 323, 22852, 33001, 98835, 1139, 279, 2761, 34965, 315, 11301, 79, 23, 356, 18509, 50, 59403, 735, 975, 1922, 323, 11301, 79, 23, 1344, 59403, 735, 975, 1922, 24548, 439, 706, 8767, 1027, 6982, 555, 1380, 89305, 927, 29199, 315, 42890, 47, 23, 3100, 18509, 50, 8, 304, 4248, 1814, 14991, 34801, 15111, 57878, 220, 1114, 662, 386, 560, 449, 63900, 64779, 59544, 2849, 320, 5484, 34, 7435, 52340, 4814, 315, 4865, 79, 521, 12, 23, 34454, 70504, 5820, 320, 11301, 79, 23, 356, 18509, 50, 59403, 16959, 258, 1922, 883, 8040, 31905, 20000, 520, 220, 23, 4235, 605, 5672, 315, 4325, 11, 5938, 449, 7319, 5219, 315, 23069, 358, 7650, 82, 11, 459, 29852, 8141, 315, 75517, 1169, 7917, 323, 4814, 315, 11233, 774, 7917, 26, 264, 82423, 430, 374, 4528, 311, 430, 1766, 304, 11301, 79, 23, 1344, 59403, 16959, 258, 1922, 24548, 220, 23, 320, 30035, 13, 220, 16, 67, 4235, 69, 323, 41665, 2956, 23966, 13, 220, 17, 64, 11, 293, 7609, 32255, 11, 1521, 3135, 20461, 128257, 198, 128256, 78191, 198, 791, 49242, 4865, 79, 521, 12, 23, 90974, 264, 31206, 2849, 4648, 18629, 2663, 4611, 299, 418, 10934, 2085, 16239, 1202, 32011, 780, 5820, 11, 264, 502, 4007, 555, 9777, 307, 42708, 29234, 4756, 304, 22037, 5039, 13, 763, 2015, 311, 49071, 9498, 323, 31301, 39881, 11, 7917, 29166, 2204, 2849, 4648, 24717, 311, 28490, 315, 36021, 7917, 320, 68, 1326, 13, 29374, 477, 20330, 7917, 570, 5345, 2985, 10934, 374, 264, 364, 5997, 1299, 18639, 18629, 6, 430, 1587, 539, 5353, 20438, 11134, 323, 374, 36572, 555, 4865, 79, 521, 12, 23, 13, 64224, 299, 418, 10934, 374, 2500, 3941, 315, 35319, 2849, 4648, 902, 11384, 35693, 5674, 323, 374, 14614, 17045, 994, 4865, 79, 521, 12, 23, 374, 99669, 13, 5468, 299, 418, 10934, 16964, 459, 47288, 3941, 315, 35319, 35693, 4648, 1920, 11, 902, 374, 14614, 22756, 304, 2077, 311, 75418, 78284, 323, 374, 8792, 369, 34739, 7294, 1474, 83059, 40368, 13, 9777, 307, 42708, 29234, 323, 813, 2128, 617, 1457, 6982, 430, 4865, 79, 521, 12, 23, 539, 1193, 11835, 95874, 323, 19591, 299, 418, 10934, 719, 4611, 299, 418, 10934, 439, 1664, 13, 578, 4007, 330, 34, 13671, 521, 12, 23, 374, 279, 31206, 3480, 369, 95874, 11, 19591, 299, 418, 10934, 323, 4611, 299, 418, 10934, 1, 574, 4756, 304, 22037, 13, 578, 3495, 2128, 20041, 279, 24156, 13073, 315, 4865, 79, 521, 12, 23, 304, 2849, 27833, 323, 24548, 13, 42708, 29234, 596, 1912, 8710, 430, 279, 32011, 780, 5820, 315, 4865, 79, 521, 12, 23, 374, 2631, 311, 69033, 4611, 299, 418, 10934, 13, 330, 1687, 1766, 704, 430, 279, 7645, 315, 32899, 4865, 79, 521, 12, 23, 11384, 44481, 14338, 98522, 2786, 323, 47288, 20438, 19814, 13, 1115, 1436, 1193, 387, 28101, 994, 19591, 299, 418, 10934, 323, 4611, 299, 418, 10934, 1051, 25291, 19857, 1359, 9777, 307, 42708, 29234, 15100, 13, 578, 6996, 315, 4865, 79, 521, 12, 23, 32011, 780, 5820, 15871, 11384, 19591, 299, 418, 14546, 2849, 4648, 13, 58603, 11, 994, 19591, 299, 418, 10934, 374, 19857, 11, 279, 32899, 4865, 79, 521, 12, 23, 17482, 439, 264, 13128, 85552, 369, 279, 18488, 315, 264, 91977, 13128, 6485, 2663, 4704, 309, 7044, 638, 11, 902, 13967, 90974, 4611, 299, 418, 10934, 13, 330, 35709, 48059, 78284, 527, 17345, 89227, 389, 279, 25382, 315, 29374, 7917, 323, 617, 28995, 264, 1396, 315, 15174, 311, 69033, 95874, 323, 19591, 299, 418, 10934, 1359, 9777, 307, 42708, 29234, 11621, 13, 578, 1510, 4007, 22601, 6509, 5014, 430, 1521, 15174, 1253, 617, 16625, 279, 5663, 91345, 3294, 315, 4611, 299, 418, 10934, 311, 9966, 35693, 4648, 439, 264, 3552, 23682, 17383, 13, 578, 4865, 79, 521, 12, 23, 82076, 3480, 1990, 2204, 20362, 315, 2849, 4648, 11621, 264, 9200, 6324, 311, 279, 12466, 488, 315, 2849, 4648, 38973, 40368, 11, 902, 374, 15098, 6532, 304, 30084, 75968, 24673, 13, 220, 128257, 198 ]

2,219

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Microorganisms that activate plant immune responses have attracted considerable attention as potential biocontrol agents in agriculture because they could reduce agrochemical use. However, conventional methods to screen for such microorganisms using whole plants and pathogens are generally laborious and time consuming. Here, we describe a general strategy using cultured plant cells to identify microorganisms that activate plant defense responses based on plant–microbe interactions. Microbial cells were incubated with tobacco BY-2 cells, followed by treatment with cryptogein, a proteinaceous elicitor of tobacco immune responses secreted by an oomycete. Cryptogein-induced production of reactive oxygen species (ROS) in BY-2 cells served as a marker to evaluate the potential of microorganisms to activate plant defense responses. Twenty-nine bacterial strains isolated from the interior of Brassica rapa var. perviridis plants were screened, and 8 strains that enhanced cryptogein-induced ROS production in BY-2 cells were selected. Following application of these strains to the root tip of Arabidopsis seedlings, two strains, Delftia sp. BR1R-2 and Arthrobacter sp. BR2S-6, were found to induce whole-plant resistance to bacterial pathogens ( Pseudomonas syringae pv. tomato DC3000 and Pectobacterium carotovora subsp. carotovora NBRC 14082). Pathogen-induced expression of plant defense-related genes ( PR-1 , PR-5 , and PDF1.2 ) was enhanced by the pretreatment with strain BR1R-2. This cell–cell interaction-based platform is readily applicable to large-scale screening for microorganisms that enhance plant defense responses under various environmental conditions. Introduction Plants have evolved unique immune responses to protect against a variety of pathogens 1 , 2 . Plants perceive pathogen invasion via interactions between pattern recognition receptors on the cell surface and conserved molecular signature molecules known as pathogen/microbe-associated molecular patterns (PAMPs/MAMPs). Following pathogen recognition, a series of defense responses is induced, collectively known as PAMP-triggered immunity (PTI). Over time, however, specific pathogens have acquired the ability to suppress PTI in plants. These pathogens secrete various PTI-interfering effectors in the host plants. However, if the host plants acquire the ability to recognize these effectors via R (resistance) proteins, effector-triggered immunity (ETI) is induced, which involves stronger and longer-lasting responses than PTI. Early defense responses common to PTI and ETI include an increase in cytosolic Ca 2+ concentration, production of reactive oxygen species (ROS), activation of the mitogen-activated protein kinases (MAPKs), expression of various defense-related genes, and increased biosynthesis of phytoalexins and defense hormones, such as salicylic acid (SA) and jasmonic acid (JA) 3 , 4 , 5 . In addition to these local defense responses, plants exhibit systemically induced defense responses collectively known as systemic acquired resistance (SAR) 6 . In SAR, when pathogen-stimulated plants are subsequently challenged by pathogens, they exhibit more rapid and/or stronger activation of defense responses that enable them to resist to a wide range of pathogens. For example, inoculation of Arabidopsis thaliana with the pathogenic bacterium Pseudomonas syringae pv. tomato triggers SAR, which in turn induces resistance to the pathogenic oomycete Peronospora parasitica 7 . In addition to pathogen-induced SAR, non-pathogenic microorganisms can induce systemic defense responses known as induced systemic resistance (ISR) 8 . For example, the rhizobacterium Pseudomonas fluorescens WCS417r can trigger ISR in several plant species, including Arabidopsis and carnation 9 , 10 . Pretreatment of Arabidopsis with Streptomyces sp. strain EN27, an endophytic actinobacterium isolated from wheat, enhances resistance to the bacterial pathogen Pectobacterium carotovora subsp. carotovora and fungal pathogen Fusarium oxysporum 11 . The well-known beneficial bacterium Paraburkholderia phytofirmans PsJN can induce Arabidopsis resistance to P. syringae pv. tomato through ISR 12 , 13 . Microorganisms that activate plant immune responses have a high potential for application as biocontrol agents in agriculture because they could reduce the demand for pesticides 14 , 15 . Such microorganisms have attracted considerable attention because they function like vaccines without producing undesirable effects (e.g., growth inhibition) in plants 8 , 15 . Endophytes are particularly well suited for use as biocontrol agents due to their inherent ability to stably colonize the interior of plants. However, conventional methods to screen for such microorganisms use whole plants and pathogens and thus tend to be laborious and time consuming 9 , 10 , 11 , resulting in the identification of few microorganisms that activate plant defense responses. Moreover, microorganisms that produce antimicrobial compounds or exclude pathogens via niche competition can also be selected using conventional methods based on observation of disease symptoms. Therefore, these conventional methods are not suitable for direct screening for microorganisms that activate plant defense responses. Cultured plant cells are useful as a simplified experimental system for studying plant immunity 16 . Tobacco BY-2 cells, which exhibit rapid and stable growth, are typical cultured plant cells 17 . Cryptogein, a proteinaceous elicitor of plant immune responses produced by the pathogenic oomycete Phytophthora cryptogea , is a well-studied model useful for elucidating the mechanisms of plant defense responses in BY-2 cells 18 , 19 , 20 , 21 , 22 , 23 . Upon recognizing cryptogein, BY-2 cells exhibit plasma membrane ion fluxes, an increase in cytosolic Ca 2+ concentration, and NADPH oxidase–dependent ROS production 19 . These initial responses are accompanied by activation of MAPKs and accumulation of defense-related gene transcripts 21 , 22 . Cryptogein-induced ROS production is closely correlated with the expression of defense-related genes and hypersensitive cell death; thus, it could be a suitable marker for evaluating defense responses in BY-2 cells 18 , 21 , 22 . These findings suggest that monitoring cryptogein-induced ROS production in BY-2 cells is a suitable experimental system for screening for microorganisms or chemicals that activate plant immune responses. In this study, we describe a system based on plant–microbe interactions through physical and chemical signals for exploring the potential of microorganisms to activate plant immune responses. We monitored cryptogein-induced ROS production in BY-2 cells as an efficient marker to identify microorganisms capable of activating plant defense responses. This system involves incubation of a microorganism with tobacco BY-2 cells, followed by treatment with cryptogein and quantitative detection of ROS production via chemiluminescence. Our system streamlines the process of screening for microorganisms that “prime” and potentiate plant immune responses,", "role": "user" }, { "content": "Plants have evolved unique immunity mechanisms that they can activate upon detecting the presence of a pathogen. Interestingly, the presence of some nonpathogenic microorganisms can also prompt a plant to activate its systemic immunity mechanisms, and some studies have shown that pretreating agricultural crops with such \"immunity-activating\" nonpathogenic microorganisms can leave the crops better prepared to fight off infections from pathogenic microorganisms. In effect, this means that immunity-activating nonpathogenic microorganisms can function like vaccines for plants, providing a low-risk stimulus for the plant's immune system that prepares it for dealing with genuine threats. These are exciting findings for crop scientists because they suggest the possibility of using such pretreatment as a form of biological pest control that would reduce the need for agricultural pesticides. However, before pretreatment with nonpathogenic microorganisms can become a standard agricultural technology, scientists need a way to screen microorganisms for the ability to stimulate plant immune systems without harming the plants. There is currently no simple method for evaluating the ability of microorganisms to activate plant immune systems. Conventional methods involve the use of whole plants and microorganisms, and this inevitably makes conventional screening a time-consuming and expensive affair. To address this problem, Associate Professor Toshiki Furuya and Professor Kazuyuki Kuchitsu of Tokyo University of Science and their colleagues decided to develop a screening strategy involving cultured plant cells. A description of their method appears in a paper recently published in Scientific Reports. The first step in this screening strategy involves incubating the candidate microorganism together with BY-2 cells, which are tobacco plant cells known for their rapid and stable growth rates. The next step is to treat the BY-2 cells with cryptogein, which is a protein secreted by fungus-like pathogenic microorganisms that can elicit immune responses from tobacco plants. A key part of the cryptogein-induced immune responses is the production of a class of chemicals called reactive oxygen species (ROS), and scientists can easily measure cryptogein-induced ROS production and use it as a metric for evaluating the effects of the nonpathogenic microorganisms. To put it simply, an effective pretreatment agent will increase the BY-2 cells' ROS production levels (i.e., cause the cells to exhibit stronger immune system activation) in response to cryptogein exposure. Microbe-Based Replacements for Chemical Pesticide Replacement.A team of scientists from Tokyo University of Science has developed a screening method based on cultured plant cells that makes such testing easier. This may lead to microorganism-based crop protection methods that reduce the need for chemical pesticides. Credit: Tokyo University of Science To test the practicability of their screening strategy, Dr. Furuya and his colleagues used the strategy on 29 bacterial strains isolated from the interior of the Japanese mustard spinach plant (Brassica rapa var. perviridis), and they found that 8 strains boosted cryptogein-induced ROS production. They then further tested those 8 strains by applying them to the root tips of seedlings from the Arabidopsis genus, which contains species commonly used as model organisms for studies of plant biology. Interestingly, 2 of the 8 tested strains induced whole-plant resistance to bacterial pathogens. Based on the proof-of-concept findings concerning those 2 bacterial strains, Dr. Furuya proudly notes that his team's screening method \"can streamline the acquisition of microorganisms that activate the immune system of plants.\" When asked how he envisions the screening method affecting agricultural practices, he explains that he expects his team's screening system \"to be a technology that contributes to the practical application and spread of microbial alternatives to chemical pesticides.\" In time, the novel screening method developed by Dr. Furuya and team may make it significantly easier for crop scientists create greener agricultural methods that rely on the defense mechanisms that plants themselves have evolved over millions of years. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Microorganisms that activate plant immune responses have attracted considerable attention as potential biocontrol agents in agriculture because they could reduce agrochemical use. However, conventional methods to screen for such microorganisms using whole plants and pathogens are generally laborious and time consuming. Here, we describe a general strategy using cultured plant cells to identify microorganisms that activate plant defense responses based on plant–microbe interactions. Microbial cells were incubated with tobacco BY-2 cells, followed by treatment with cryptogein, a proteinaceous elicitor of tobacco immune responses secreted by an oomycete. Cryptogein-induced production of reactive oxygen species (ROS) in BY-2 cells served as a marker to evaluate the potential of microorganisms to activate plant defense responses. Twenty-nine bacterial strains isolated from the interior of Brassica rapa var. perviridis plants were screened, and 8 strains that enhanced cryptogein-induced ROS production in BY-2 cells were selected. Following application of these strains to the root tip of Arabidopsis seedlings, two strains, Delftia sp. BR1R-2 and Arthrobacter sp. BR2S-6, were found to induce whole-plant resistance to bacterial pathogens ( Pseudomonas syringae pv. tomato DC3000 and Pectobacterium carotovora subsp. carotovora NBRC 14082). Pathogen-induced expression of plant defense-related genes ( PR-1 , PR-5 , and PDF1.2 ) was enhanced by the pretreatment with strain BR1R-2. This cell–cell interaction-based platform is readily applicable to large-scale screening for microorganisms that enhance plant defense responses under various environmental conditions. Introduction Plants have evolved unique immune responses to protect against a variety of pathogens 1 , 2 . Plants perceive pathogen invasion via interactions between pattern recognition receptors on the cell surface and conserved molecular signature molecules known as pathogen/microbe-associated molecular patterns (PAMPs/MAMPs). Following pathogen recognition, a series of defense responses is induced, collectively known as PAMP-triggered immunity (PTI). Over time, however, specific pathogens have acquired the ability to suppress PTI in plants. These pathogens secrete various PTI-interfering effectors in the host plants. However, if the host plants acquire the ability to recognize these effectors via R (resistance) proteins, effector-triggered immunity (ETI) is induced, which involves stronger and longer-lasting responses than PTI. Early defense responses common to PTI and ETI include an increase in cytosolic Ca 2+ concentration, production of reactive oxygen species (ROS), activation of the mitogen-activated protein kinases (MAPKs), expression of various defense-related genes, and increased biosynthesis of phytoalexins and defense hormones, such as salicylic acid (SA) and jasmonic acid (JA) 3 , 4 , 5 . In addition to these local defense responses, plants exhibit systemically induced defense responses collectively known as systemic acquired resistance (SAR) 6 . In SAR, when pathogen-stimulated plants are subsequently challenged by pathogens, they exhibit more rapid and/or stronger activation of defense responses that enable them to resist to a wide range of pathogens. For example, inoculation of Arabidopsis thaliana with the pathogenic bacterium Pseudomonas syringae pv. tomato triggers SAR, which in turn induces resistance to the pathogenic oomycete Peronospora parasitica 7 . In addition to pathogen-induced SAR, non-pathogenic microorganisms can induce systemic defense responses known as induced systemic resistance (ISR) 8 . For example, the rhizobacterium Pseudomonas fluorescens WCS417r can trigger ISR in several plant species, including Arabidopsis and carnation 9 , 10 . Pretreatment of Arabidopsis with Streptomyces sp. strain EN27, an endophytic actinobacterium isolated from wheat, enhances resistance to the bacterial pathogen Pectobacterium carotovora subsp. carotovora and fungal pathogen Fusarium oxysporum 11 . The well-known beneficial bacterium Paraburkholderia phytofirmans PsJN can induce Arabidopsis resistance to P. syringae pv. tomato through ISR 12 , 13 . Microorganisms that activate plant immune responses have a high potential for application as biocontrol agents in agriculture because they could reduce the demand for pesticides 14 , 15 . Such microorganisms have attracted considerable attention because they function like vaccines without producing undesirable effects (e.g., growth inhibition) in plants 8 , 15 . Endophytes are particularly well suited for use as biocontrol agents due to their inherent ability to stably colonize the interior of plants. However, conventional methods to screen for such microorganisms use whole plants and pathogens and thus tend to be laborious and time consuming 9 , 10 , 11 , resulting in the identification of few microorganisms that activate plant defense responses. Moreover, microorganisms that produce antimicrobial compounds or exclude pathogens via niche competition can also be selected using conventional methods based on observation of disease symptoms. Therefore, these conventional methods are not suitable for direct screening for microorganisms that activate plant defense responses. Cultured plant cells are useful as a simplified experimental system for studying plant immunity 16 . Tobacco BY-2 cells, which exhibit rapid and stable growth, are typical cultured plant cells 17 . Cryptogein, a proteinaceous elicitor of plant immune responses produced by the pathogenic oomycete Phytophthora cryptogea , is a well-studied model useful for elucidating the mechanisms of plant defense responses in BY-2 cells 18 , 19 , 20 , 21 , 22 , 23 . Upon recognizing cryptogein, BY-2 cells exhibit plasma membrane ion fluxes, an increase in cytosolic Ca 2+ concentration, and NADPH oxidase–dependent ROS production 19 . These initial responses are accompanied by activation of MAPKs and accumulation of defense-related gene transcripts 21 , 22 . Cryptogein-induced ROS production is closely correlated with the expression of defense-related genes and hypersensitive cell death; thus, it could be a suitable marker for evaluating defense responses in BY-2 cells 18 , 21 , 22 . These findings suggest that monitoring cryptogein-induced ROS production in BY-2 cells is a suitable experimental system for screening for microorganisms or chemicals that activate plant immune responses. In this study, we describe a system based on plant–microbe interactions through physical and chemical signals for exploring the potential of microorganisms to activate plant immune responses. We monitored cryptogein-induced ROS production in BY-2 cells as an efficient marker to identify microorganisms capable of activating plant defense responses. This system involves incubation of a microorganism with tobacco BY-2 cells, followed by treatment with cryptogein and quantitative detection of ROS production via chemiluminescence. Our system streamlines the process of screening for microorganisms that “prime” and potentiate plant immune responses,<|im_end|> <|im_start|>assistant Plants have evolved unique immunity mechanisms that they can activate upon detecting the presence of a pathogen. Interestingly, the presence of some nonpathogenic microorganisms can also prompt a plant to activate its systemic immunity mechanisms, and some studies have shown that pretreating agricultural crops with such "immunity-activating" nonpathogenic microorganisms can leave the crops better prepared to fight off infections from pathogenic microorganisms. In effect, this means that immunity-activating nonpathogenic microorganisms can function like vaccines for plants, providing a low-risk stimulus for the plant's immune system that prepares it for dealing with genuine threats. These are exciting findings for crop scientists because they suggest the possibility of using such pretreatment as a form of biological pest control that would reduce the need for agricultural pesticides. However, before pretreatment with nonpathogenic microorganisms can become a standard agricultural technology, scientists need a way to screen microorganisms for the ability to stimulate plant immune systems without harming the plants. There is currently no simple method for evaluating the ability of microorganisms to activate plant immune systems. Conventional methods involve the use of whole plants and microorganisms, and this inevitably makes conventional screening a time-consuming and expensive affair. To address this problem, Associate Professor Toshiki Furuya and Professor Kazuyuki Kuchitsu of Tokyo University of Science and their colleagues decided to develop a screening strategy involving cultured plant cells. A description of their method appears in a paper recently published in Scientific Reports. The first step in this screening strategy involves incubating the candidate microorganism together with BY-2 cells, which are tobacco plant cells known for their rapid and stable growth rates. The next step is to treat the BY-2 cells with cryptogein, which is a protein secreted by fungus-like pathogenic microorganisms that can elicit immune responses from tobacco plants. A key part of the cryptogein-induced immune responses is the production of a class of chemicals called reactive oxygen species (ROS), and scientists can easily measure cryptogein-induced ROS production and use it as a metric for evaluating the effects of the nonpathogenic microorganisms. To put it simply, an effective pretreatment agent will increase the BY-2 cells' ROS production levels (i.e., cause the cells to exhibit stronger immune system activation) in response to cryptogein exposure. Microbe-Based Replacements for Chemical Pesticide Replacement.A team of scientists from Tokyo University of Science has developed a screening method based on cultured plant cells that makes such testing easier. This may lead to microorganism-based crop protection methods that reduce the need for chemical pesticides. Credit: Tokyo University of Science To test the practicability of their screening strategy, Dr. Furuya and his colleagues used the strategy on 29 bacterial strains isolated from the interior of the Japanese mustard spinach plant (Brassica rapa var. perviridis), and they found that 8 strains boosted cryptogein-induced ROS production. They then further tested those 8 strains by applying them to the root tips of seedlings from the Arabidopsis genus, which contains species commonly used as model organisms for studies of plant biology. Interestingly, 2 of the 8 tested strains induced whole-plant resistance to bacterial pathogens. Based on the proof-of-concept findings concerning those 2 bacterial strains, Dr. Furuya proudly notes that his team's screening method "can streamline the acquisition of microorganisms that activate the immune system of plants." When asked how he envisions the screening method affecting agricultural practices, he explains that he expects his team's screening system "to be a technology that contributes to the practical application and spread of microbial alternatives to chemical pesticides." In time, the novel screening method developed by Dr. Furuya and team may make it significantly easier for crop scientists create greener agricultural methods that rely on the defense mechanisms that plants themselves have evolved over millions of years. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 18654, 76991, 430, 20891, 6136, 22852, 14847, 617, 29123, 24779, 6666, 439, 4754, 17332, 2935, 13307, 304, 30029, 1606, 814, 1436, 8108, 945, 299, 32056, 1005, 13, 4452, 11, 21349, 5528, 311, 4264, 369, 1778, 8162, 76991, 1701, 4459, 11012, 323, 78284, 527, 8965, 9511, 1245, 323, 892, 35208, 13, 5810, 11, 584, 7664, 264, 4689, 8446, 1701, 89948, 6136, 7917, 311, 10765, 8162, 76991, 430, 20891, 6136, 9232, 14847, 3196, 389, 6136, 4235, 41543, 1395, 22639, 13, 18654, 48059, 7917, 1051, 49727, 660, 449, 27531, 7866, 12, 17, 7917, 11, 8272, 555, 6514, 449, 14774, 41632, 258, 11, 264, 13128, 77140, 95360, 1960, 315, 27531, 22852, 14847, 6367, 291, 555, 459, 297, 316, 3418, 7870, 13, 38547, 41632, 258, 38973, 5788, 315, 56563, 24463, 9606, 320, 34539, 8, 304, 7866, 12, 17, 7917, 10434, 439, 264, 11381, 311, 15806, 279, 4754, 315, 8162, 76991, 311, 20891, 6136, 9232, 14847, 13, 44956, 86703, 45964, 42400, 25181, 505, 279, 15135, 315, 59129, 3074, 7477, 64, 767, 13, 47274, 404, 85342, 11012, 1051, 58677, 11, 323, 220, 23, 42400, 430, 24872, 14774, 41632, 258, 38973, 38517, 5788, 304, 7866, 12, 17, 7917, 1051, 4183, 13, 23548, 3851, 315, 1521, 42400, 311, 279, 3789, 11813, 315, 10989, 307, 33906, 10533, 19342, 11, 1403, 42400, 11, 423, 491, 83, 689, 993, 13, 19333, 16, 49, 12, 17, 323, 109588, 23576, 2540, 993, 13, 19333, 17, 50, 12, 21, 11, 1051, 1766, 311, 49853, 4459, 12, 21494, 13957, 311, 45964, 78284, 320, 393, 40512, 35685, 300, 6705, 12928, 6043, 34591, 13, 42120, 11162, 3101, 15, 323, 393, 440, 677, 2540, 2411, 1841, 354, 869, 6347, 1207, 2203, 13, 1841, 354, 869, 6347, 36079, 7532, 220, 6860, 6086, 570, 8092, 11968, 38973, 7645, 315, 6136, 9232, 14228, 21389, 320, 8743, 12, 16, 1174, 8743, 12, 20, 1174, 323, 11612, 16, 13, 17, 883, 574, 24872, 555, 279, 4509, 35320, 449, 26800, 19333, 16, 49, 12, 17, 13, 1115, 2849, 4235, 5997, 16628, 6108, 5452, 374, 31368, 8581, 311, 3544, 13230, 23061, 369, 8162, 76991, 430, 18885, 6136, 9232, 14847, 1234, 5370, 12434, 4787, 13, 29438, 50298, 617, 28995, 5016, 22852, 14847, 311, 6144, 2403, 264, 8205, 315, 78284, 220, 16, 1174, 220, 17, 662, 50298, 45493, 1853, 11968, 30215, 4669, 22639, 1990, 5497, 18324, 44540, 389, 279, 2849, 7479, 323, 1615, 2841, 31206, 12223, 35715, 3967, 439, 1853, 11968, 3262, 2823, 1395, 75968, 31206, 12912, 320, 47, 16407, 82, 10482, 16407, 82, 570, 23548, 1853, 11968, 18324, 11, 264, 4101, 315, 9232, 14847, 374, 36572, 11, 45925, 3967, 439, 393, 16407, 59087, 291, 40368, 320, 2898, 40, 570, 6193, 892, 11, 4869, 11, 3230, 78284, 617, 19426, 279, 5845, 311, 28321, 19932, 40, 304, 11012, 13, 4314, 78284, 513, 9537, 5370, 19932, 40, 45994, 809, 287, 2515, 1105, 304, 279, 3552, 11012, 13, 4452, 11, 422, 279, 3552, 11012, 21953, 279, 5845, 311, 15641, 1521, 2515, 1105, 4669, 432, 320, 417, 4011, 8, 28896, 11, 3369, 1279, 59087, 291, 40368, 320, 1372, 40, 8, 374, 36572, 11, 902, 18065, 16643, 323, 5129, 65265, 14847, 1109, 19932, 40, 13, 23591, 9232, 14847, 4279, 311, 19932, 40, 323, 18241, 40, 2997, 459, 5376, 304, 9693, 43681, 7918, 14751, 220, 17, 10, 20545, 11, 5788, 315, 56563, 24463, 9606, 320, 34539, 705, 15449, 315, 279, 5568, 11968, 12, 31262, 13128, 24890, 2315, 320, 18082, 42, 82, 705, 7645, 315, 5370, 9232, 14228, 21389, 11, 323, 7319, 49554, 74767, 315, 37555, 998, 56975, 1354, 323, 9232, 44315, 11, 1778, 439, 4371, 2912, 416, 13935, 320, 7934, 8, 323, 111806, 74689, 13935, 320, 45280, 8, 220, 18, 1174, 220, 19, 1174, 220, 20, 662, 763, 5369, 311, 1521, 2254, 9232, 14847, 11, 11012, 31324, 1887, 2740, 36572, 9232, 14847, 45925, 3967, 439, 46417, 19426, 13957, 320, 50, 946, 8, 220, 21, 662, 763, 69878, 11, 994, 1853, 11968, 5594, 318, 7913, 11012, 527, 28520, 29991, 555, 78284, 11, 814, 31324, 810, 11295, 323, 5255, 16643, 15449, 315, 9232, 14847, 430, 7431, 1124, 311, 22884, 311, 264, 7029, 2134, 315, 78284, 13, 1789, 3187, 11, 87018, 2987, 315, 10989, 307, 33906, 270, 10700, 64, 449, 279, 1853, 29569, 17854, 2411, 393, 40512, 35685, 300, 6705, 12928, 6043, 34591, 13, 42120, 31854, 69878, 11, 902, 304, 2543, 90974, 13957, 311, 279, 1853, 29569, 297, 316, 3418, 7870, 3700, 263, 437, 71764, 33403, 275, 3074, 220, 22, 662, 763, 5369, 311, 1853, 11968, 38973, 69878, 11, 2536, 34195, 29569, 8162, 76991, 649, 49853, 46417, 9232, 14847, 3967, 439, 36572, 46417, 13957, 320, 84715, 8, 220, 23, 662, 1789, 3187, 11, 279, 22408, 450, 677, 2540, 2411, 393, 40512, 35685, 300, 51881, 66, 729, 99451, 19561, 81, 649, 8346, 79013, 304, 3892, 6136, 9606, 11, 2737, 10989, 307, 33906, 323, 39438, 367, 220, 24, 1174, 220, 605, 662, 63039, 35320, 315, 10989, 307, 33906, 449, 36772, 418, 5650, 1634, 993, 13, 26800, 5301, 1544, 11, 459, 842, 5237, 70504, 1180, 258, 677, 2540, 2411, 25181, 505, 34153, 11, 57924, 13957, 311, 279, 45964, 1853, 11968, 393, 440, 677, 2540, 2411, 1841, 354, 869, 6347, 1207, 2203, 13, 1841, 354, 869, 6347, 323, 95447, 1853, 11968, 94400, 34765, 19488, 1065, 4406, 372, 220, 806, 662, 578, 1664, 22015, 24629, 17854, 2411, 4366, 370, 324, 74, 4346, 689, 37555, 998, 8978, 598, 12065, 41, 45, 649, 49853, 10989, 307, 33906, 13957, 311, 393, 13, 6705, 12928, 6043, 34591, 13, 42120, 1555, 79013, 220, 717, 1174, 220, 1032, 662, 18654, 76991, 430, 20891, 6136, 22852, 14847, 617, 264, 1579, 4754, 369, 3851, 439, 17332, 2935, 13307, 304, 30029, 1606, 814, 1436, 8108, 279, 7631, 369, 61257, 220, 975, 1174, 220, 868, 662, 15483, 8162, 76991, 617, 29123, 24779, 6666, 1606, 814, 734, 1093, 40300, 2085, 17843, 77344, 6372, 320, 68, 1326, 2637, 6650, 61478, 8, 304, 11012, 220, 23, 1174, 220, 868, 662, 4060, 118930, 2392, 527, 8104, 1664, 32599, 369, 1005, 439, 17332, 2935, 13307, 4245, 311, 872, 38088, 5845, 311, 357, 2915, 15235, 553, 279, 15135, 315, 11012, 13, 4452, 11, 21349, 5528, 311, 4264, 369, 1778, 8162, 76991, 1005, 4459, 11012, 323, 78284, 323, 8617, 8541, 311, 387, 9511, 1245, 323, 892, 35208, 220, 24, 1174, 220, 605, 1174, 220, 806, 1174, 13239, 304, 279, 22654, 315, 2478, 8162, 76991, 430, 20891, 6136, 9232, 14847, 13, 23674, 11, 8162, 76991, 430, 8356, 79312, 83059, 32246, 477, 22429, 78284, 4669, 35149, 10937, 649, 1101, 387, 4183, 1701, 21349, 5528, 3196, 389, 22695, 315, 8624, 13803, 13, 15636, 11, 1521, 21349, 5528, 527, 539, 14791, 369, 2167, 23061, 369, 8162, 76991, 430, 20891, 6136, 9232, 14847, 13, 26676, 3149, 6136, 7917, 527, 5505, 439, 264, 44899, 22772, 1887, 369, 21630, 6136, 40368, 220, 845, 662, 66210, 7866, 12, 17, 7917, 11, 902, 31324, 11295, 323, 15528, 6650, 11, 527, 14595, 89948, 6136, 7917, 220, 1114, 662, 38547, 41632, 258, 11, 264, 13128, 77140, 95360, 1960, 315, 6136, 22852, 14847, 9124, 555, 279, 1853, 29569, 297, 316, 3418, 7870, 93682, 3565, 71, 65783, 14774, 540, 12791, 1174, 374, 264, 1664, 5594, 664, 1142, 1646, 5505, 369, 97298, 1113, 279, 24717, 315, 6136, 9232, 14847, 304, 7866, 12, 17, 7917, 220, 972, 1174, 220, 777, 1174, 220, 508, 1174, 220, 1691, 1174, 220, 1313, 1174, 220, 1419, 662, 30538, 49183, 14774, 41632, 258, 11, 7866, 12, 17, 7917, 31324, 32426, 39654, 28772, 31405, 288, 11, 459, 5376, 304, 9693, 43681, 7918, 14751, 220, 17, 10, 20545, 11, 323, 452, 1846, 11079, 36172, 521, 4235, 38655, 38517, 5788, 220, 777, 662, 4314, 2926, 14847, 527, 24895, 555, 15449, 315, 28322, 42, 82, 323, 46835, 315, 9232, 14228, 15207, 61412, 220, 1691, 1174, 220, 1313, 662, 38547, 41632, 258, 38973, 38517, 5788, 374, 15499, 49393, 449, 279, 7645, 315, 9232, 14228, 21389, 323, 87752, 19245, 2849, 4648, 26, 8617, 11, 433, 1436, 387, 264, 14791, 11381, 369, 38663, 9232, 14847, 304, 7866, 12, 17, 7917, 220, 972, 1174, 220, 1691, 1174, 220, 1313, 662, 4314, 14955, 4284, 430, 16967, 14774, 41632, 258, 38973, 38517, 5788, 304, 7866, 12, 17, 7917, 374, 264, 14791, 22772, 1887, 369, 23061, 369, 8162, 76991, 477, 26333, 430, 20891, 6136, 22852, 14847, 13, 763, 420, 4007, 11, 584, 7664, 264, 1887, 3196, 389, 6136, 4235, 41543, 1395, 22639, 1555, 7106, 323, 11742, 17738, 369, 24919, 279, 4754, 315, 8162, 76991, 311, 20891, 6136, 22852, 14847, 13, 1226, 41223, 14774, 41632, 258, 38973, 38517, 5788, 304, 7866, 12, 17, 7917, 439, 459, 11297, 11381, 311, 10765, 8162, 76991, 13171, 315, 72192, 6136, 9232, 14847, 13, 1115, 1887, 18065, 49727, 367, 315, 264, 8162, 8629, 2191, 449, 27531, 7866, 12, 17, 7917, 11, 8272, 555, 6514, 449, 14774, 41632, 258, 323, 47616, 18468, 315, 38517, 5788, 4669, 8590, 321, 372, 1572, 36634, 13, 5751, 1887, 4365, 8128, 279, 1920, 315, 23061, 369, 8162, 76991, 430, 1054, 33438, 863, 323, 36875, 6629, 6136, 22852, 14847, 11, 128257, 198, 128256, 78191, 198, 2169, 1821, 617, 28995, 5016, 40368, 24717, 430, 814, 649, 20891, 5304, 54626, 279, 9546, 315, 264, 1853, 11968, 13, 58603, 11, 279, 9546, 315, 1063, 2536, 2398, 29569, 8162, 76991, 649, 1101, 10137, 264, 6136, 311, 20891, 1202, 46417, 40368, 24717, 11, 323, 1063, 7978, 617, 6982, 430, 4509, 73910, 29149, 31665, 449, 1778, 330, 12828, 2498, 12, 9035, 1113, 1, 2536, 2398, 29569, 8162, 76991, 649, 5387, 279, 31665, 2731, 10235, 311, 4465, 1022, 30020, 505, 1853, 29569, 8162, 76991, 13, 763, 2515, 11, 420, 3445, 430, 40368, 12, 9035, 1113, 2536, 2398, 29569, 8162, 76991, 649, 734, 1093, 40300, 369, 11012, 11, 8405, 264, 3428, 46570, 39535, 369, 279, 6136, 596, 22852, 1887, 430, 48542, 433, 369, 14892, 449, 22785, 18208, 13, 4314, 527, 13548, 14955, 369, 19641, 14248, 1606, 814, 4284, 279, 13336, 315, 1701, 1778, 4509, 35320, 439, 264, 1376, 315, 24156, 44885, 2585, 430, 1053, 8108, 279, 1205, 369, 29149, 61257, 13, 4452, 11, 1603, 4509, 35320, 449, 2536, 2398, 29569, 8162, 76991, 649, 3719, 264, 5410, 29149, 5557, 11, 14248, 1205, 264, 1648, 311, 4264, 8162, 76991, 369, 279, 5845, 311, 51077, 6136, 22852, 6067, 2085, 90255, 279, 11012, 13, 2684, 374, 5131, 912, 4382, 1749, 369, 38663, 279, 5845, 315, 8162, 76991, 311, 20891, 6136, 22852, 6067, 13, 1221, 44322, 5528, 21736, 279, 1005, 315, 4459, 11012, 323, 8162, 76991, 11, 323, 420, 40605, 3727, 21349, 23061, 264, 892, 70840, 323, 11646, 31017, 13, 2057, 2686, 420, 3575, 11, 33468, 17054, 350, 9451, 7723, 50940, 45644, 323, 17054, 36074, 4168, 22227, 735, 1412, 50657, 315, 27286, 3907, 315, 10170, 323, 872, 18105, 6773, 311, 2274, 264, 23061, 8446, 16239, 89948, 6136, 7917, 13, 362, 4096, 315, 872, 1749, 8111, 304, 264, 5684, 6051, 4756, 304, 38130, 29140, 13, 578, 1176, 3094, 304, 420, 23061, 8446, 18065, 49727, 1113, 279, 9322, 8162, 8629, 2191, 3871, 449, 7866, 12, 17, 7917, 11, 902, 527, 27531, 6136, 7917, 3967, 369, 872, 11295, 323, 15528, 6650, 7969, 13, 578, 1828, 3094, 374, 311, 4322, 279, 7866, 12, 17, 7917, 449, 14774, 41632, 258, 11, 902, 374, 264, 13128, 6367, 291, 555, 79902, 12970, 1853, 29569, 8162, 76991, 430, 649, 658, 19195, 22852, 14847, 505, 27531, 11012, 13, 362, 1401, 961, 315, 279, 14774, 41632, 258, 38973, 22852, 14847, 374, 279, 5788, 315, 264, 538, 315, 26333, 2663, 56563, 24463, 9606, 320, 34539, 705, 323, 14248, 649, 6847, 6767, 14774, 41632, 258, 38973, 38517, 5788, 323, 1005, 433, 439, 264, 18767, 369, 38663, 279, 6372, 315, 279, 2536, 2398, 29569, 8162, 76991, 13, 2057, 2231, 433, 5042, 11, 459, 7524, 4509, 35320, 8479, 690, 5376, 279, 7866, 12, 17, 7917, 6, 38517, 5788, 5990, 320, 72, 1770, 2637, 5353, 279, 7917, 311, 31324, 16643, 22852, 1887, 15449, 8, 304, 2077, 311, 14774, 41632, 258, 14675, 13, 18654, 1395, 61439, 1050, 64635, 369, 36424, 393, 10027, 579, 47312, 885, 2128, 315, 14248, 505, 27286, 3907, 315, 10170, 706, 8040, 264, 23061, 1749, 3196, 389, 89948, 6136, 7917, 430, 3727, 1778, 7649, 8831, 13, 1115, 1253, 3063, 311, 8162, 8629, 2191, 6108, 19641, 9313, 5528, 430, 8108, 279, 1205, 369, 11742, 61257, 13, 16666, 25, 27286, 3907, 315, 10170, 2057, 1296, 279, 3856, 292, 2968, 315, 872, 23061, 8446, 11, 2999, 13, 50940, 45644, 323, 813, 18105, 1511, 279, 8446, 389, 220, 1682, 45964, 42400, 25181, 505, 279, 15135, 315, 279, 11002, 65407, 68798, 6136, 320, 6971, 395, 3074, 7477, 64, 767, 13, 47274, 404, 85342, 705, 323, 814, 1766, 430, 220, 23, 42400, 65208, 14774, 41632, 258, 38973, 38517, 5788, 13, 2435, 1243, 4726, 12793, 1884, 220, 23, 42400, 555, 19486, 1124, 311, 279, 3789, 10631, 315, 10533, 19342, 505, 279, 10989, 307, 33906, 64677, 11, 902, 5727, 9606, 17037, 1511, 439, 1646, 44304, 369, 7978, 315, 6136, 34458, 13, 58603, 11, 220, 17, 315, 279, 220, 23, 12793, 42400, 36572, 4459, 12, 21494, 13957, 311, 45964, 78284, 13, 20817, 389, 279, 11311, 8838, 15204, 1512, 14955, 18815, 1884, 220, 17, 45964, 42400, 11, 2999, 13, 50940, 45644, 45909, 8554, 430, 813, 2128, 596, 23061, 1749, 330, 4919, 82703, 279, 24279, 315, 8162, 76991, 430, 20891, 279, 22852, 1887, 315, 11012, 1210, 3277, 4691, 1268, 568, 665, 41115, 279, 23061, 1749, 28987, 29149, 12659, 11, 568, 15100, 430, 568, 25283, 813, 2128, 596, 23061, 1887, 330, 998, 387, 264, 5557, 430, 44072, 311, 279, 15325, 3851, 323, 9041, 315, 75418, 27548, 311, 11742, 61257, 1210, 763, 892, 11, 279, 11775, 23061, 1749, 8040, 555, 2999, 13, 50940, 45644, 323, 2128, 1253, 1304, 433, 12207, 8831, 369, 19641, 14248, 1893, 2886, 804, 29149, 5528, 430, 17631, 389, 279, 9232, 24717, 430, 11012, 5694, 617, 28995, 927, 11990, 315, 1667, 13, 220, 128257, 198 ]

2,290

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Receptor tyrosine kinase (RTK)–RAS signalling through the downstream mitogen-activated protein kinase (MAPK) cascade regulates cell proliferation and survival. The SHOC2–MRAS–PP1C holophosphatase complex functions as a key regulator of RTK–RAS signalling by removing an inhibitory phosphorylation event on the RAF family of proteins to potentiate MAPK signalling 1 . SHOC2 forms a ternary complex with MRAS and PP1C, and human germline gain-of-function mutations in this complex result in congenital RASopathy syndromes 2 , 3 , 4 , 5 . However, the structure and assembly of this complex are poorly understood. Here we use cryo-electron microscopy to resolve the structure of the SHOC2–MRAS–PP1C complex. We define the biophysical principles of holoenzyme interactions, elucidate the assembly order of the complex, and systematically interrogate the functional consequence of nearly all of the possible missense variants of SHOC2 through deep mutational scanning. We show that SHOC2 binds PP1C and MRAS through the concave surface of the leucine-rich repeat region and further engages PP1C through the N-terminal disordered region that contains a cryptic RVXF motif. Complex formation is initially mediated by interactions between SHOC2 and PP1C and is stabilized by the binding of GTP-loaded MRAS. These observations explain how mutant versions of SHOC2 in RASopathies and cancer stabilize the interactions of complex members to enhance holophosphatase activity. Together, this integrative structure–function model comprehensively defines key binding interactions within the SHOC2–MRAS–PP1C holophosphatase complex and will inform therapeutic development . Main SHOC2 is a scaffold protein composed of leucine-rich repeats (LRRs) that bind directly to the catalytic subunit of PP1 (PP1C). Activation of MRAS leads to membrane localization of the SHOC2–MRAS–PP1C (SMP) complex and to the dephosphorylation of proteins of the RAF family at a key inhibitory phosphorylation site, including S259 on CRAF (RAF1), S365 on BRAF and S214 on ARAF (hereafter collectively referred to as ‘S259’); this results in the release of autoinhibition and the potentiation of RAF activation 1 , 6 . The SMP holophosphatase has a critical role in the RAS–MAPK pathway signalling that underlies normal developmental processes as well as oncogenic signalling in cancer. Activating mutations in SHOC2, PP1C, and MRAS are found in Noonan-like syndrome, a ‘RASopathy' syndrome that is characterized by congenital cardiac, skeletal, and cognitive deficits 2 , 6 , 7 , 8 . SHOC2 is essential for the proliferation and survival of several cancers including RAS-driven leukaemia; melanoma; and models of non-small cell lung cancer 9 , 10 . Moreover, depletion of SHOC2 sensitizes RAS-driven cancers to MEK inhibition through the disruption of RTK-mediated feedback signalling and through MEK-inhibitor-induced RAF dimerization 11 , 12 . However, gaps in our knowledge of the biophysical basis of complex assembly and function limit our understanding of the mechanisms of disease and opportunities for therapeutic targeting of this ternary complex. Structure of the SMP complex To understand the role of SHOC2 in RAS–MAPK pathway signalling, we solved the SHOC2 structure alone and in complex with PP1C and MRAS. Specifically, we developed an optimized expression system to produce wild-type human SHOC2 and PP1C, as well as constitutively active GTP-bound MRAS(Q71L) (Fig. 1a and Methods ). We first used X-ray crystallography to solve the structure of the wild-type SHOC2 apoprotein at 1.8-Å resolution (Fig. 1b and Extended Data Table 1 ). The apo-SHOC2 structure is a canonical LRR protein that consists of 20 tandem LRR domains. These LRR domains concatenate to form a conventional solenoid structure that has an average LRR corkscrew rotation of ~4 o (Fig. 1b ) and is stabilized by an N-terminal flanking α-helix and a C-terminal helix-turn-helix. Each LRR is composed of 22–24 amino acids containing a β-strand followed by a descending loop, an α-helix and an ascending loop. The LRR β-strands assemble in parallel to generate the concave surface of the solenoid, whereas the α-helices form most of the convex surface. Internal to the structure, the conserved leucine residues of the LRR motif, LXXLXLXN(X) 1–2 L, condense to form the hydrophobic core of the protein, whereas the conserved asparagine residue participates in a highly stabilizing 'asparagine ladder' motif that has been shown to be critical to the LRR fold 13 . The SHOC2 structure does not show the presence of the flexible hinge within the medial LRRs that was predicted in previous computational models of SHOC2 (refs. 14 , 15 ). Fig. 1: Structure of apo-SHOC2 and the SMP holophosphatase complex. a , Schematic diagram of members of the SMP complex. Truncation of constructs is indicated with dashed lines. MRAS switch 1 (SI), switch 2 (SII) and the hypervariable region (HVR) are annotated. *indicates the 2–63-deletion construct that was used for cryo-EM; ** indicates the 2–88-deletion SHOC2 construct that was used for X-ray crystallography. b , Overview of the crystal structure of apo-SHOC2 along with a cross-sectional representation of the LRR domain. c , d , Side views of the cryo-EM structure of the SHOC2 complex with SHOC2 in teal), MRAS in maroon, and PP1C in yellow. A ribbon representation and view of MRAS ( c ) and PP1C ( d ) are shown with relevant structural features annotated. d , Manganese ions (red), hydrophobic (H), C-terminal (C) and acidic (A) grooves are shown. Full size image As the conformation and binding interfaces of SHOC2 that are involved in complex formation with PP1C and MRAS cannot be inferred from the structure of the apoprotein alone, we used single-particle cryo-electron microscopy (cryo-EM) to resolve the holophosphatase complex of an N-terminally truncated SHOC2, wild-type PP1C and GTP-loaded MRAS(Q71L) (Fig. 1c,d , Extended Data Fig. 1 and Extended Data Table 2 ). The resulting structure at 2.9-Å resolution unambiguously defined a ternary complex in which SHOC2 engages both PP1C and MRAS through its concave surface (Fig. 1d ). The overall structure of SHOC2 observed in the holoenzyme complex is similar to the isolated apoprotein. Through protein–protein interactions, the SHOC2 complex buries a total of 5,934 Å 2 of solvent-accessible surface area, with SHOC2–PP1C, SHOC2–MRAS and MRAS–PP1C covering 3,019 Å 2 , 1,729 Å 2 and 1,186 Å 2 , respectively (Extended Data Fig.", "role": "user" }, { "content": "Some of the most infamous drivers of cancer are mutations in RAS genes, which lead to tumor growth in about a quarter of all cancer patients. Scientists at the Broad Institute of MIT and Harvard and the Dana-Farber Cancer Institute have determined the molecular structure of a RAS-pathway protein called SHOC2 and two other proteins it binds to. This three-protein assembly, called the SHOC2-MRAS-PP1C (\"SMP\") complex, regulates the RAS signaling pathway and helps cancer cells with RAS mutations survive. The high-resolution structure of this complex, revealed through X-ray crystallography and cryogenic electron microscopy, suggests possible ways that drugs can bind to it to inhibit the RAS pathway and block cancer growth. The study, published in Nature, highlights a potential therapeutic strategy for a signaling pathway that has been difficult to target with drugs. The work is the result of a collaboration between researchers at Dana-Farber, Deerfield Discovery and Development, a subsidiary of Deerfield Management Company, and in the Broad's Cancer Program, Genetic Perturbation Platform, and the Center for the Development of Therapeutics (CDoT). \"By solving the structure, we've learned a lot about how SHOC2 operates in this circuit, which points out ways in which you can therapeutically intervene,\" said study co-senior author and Broad institute member William Hahn of the Cancer Program. Hahn is also the William Rosenberg Professor of Medicine, executive vice president and the chief operating officer at Dana-Farber. SHOC2 protein structure. Credit: Broad Institute and Dana-Farber Cancer Institute SHOC2 story Hahn, co-senior author Andrew Aguirre, an oncologist at Dana-Farber and a Broad associate member, and Jason Kwon, a postdoctoral fellow in Hahn's lab, first identified SHOC2 as a possible drug target in 2019. They and their colleagues with Broad's Cancer Dependency Map project were studying essential genes in cancers with mutations in RAS proteins. At the time, cancer drugs called MEK inhibitors had been developed to target mutations in RAS proteins, but they were effective in only a fraction of cancer patients. The team wondered whether another protein was enabling mutated RAS proteins to bypass these inhibitors. In their 2019 study, the team used CRISPR-Cas9 to knock out genes one-by-one across the entire genome to see which ones might be causing RAS-mutated cancer cells to resist the effects of MEK inhibitors. The researchers found that when they deleted the SHOC2 gene or decreased its expression, the MEK inhibitors were highly effective at eliminating cancer cells, revealing SHOC2 as a culprit in resistance to MEK inhibitors. Protein puzzle The team decided to further study SHOC2 as a potential target, which included solving its structure. That's when researchers from CDoT and Deerfield Discovery and Development joined the team. \"We identified SHOC2 genetically and knew that it was important, but in order to therapeutically exploit it, we have to know the structure of the protein to identify critical, functional regions,\" said Kwon, project lead and co-first author of the paper. The team worked with CDoT scientists, including co-first authors Behnoush Hajian, a research scientist, Yuemin Bian, a computational scientist, and co-senior author Christopher Lemke, director of protein science and structural biology. They used X-ray crystallography and cryogenic electron microscopy to solve high-resolution structures of SHOC2 and the proteins it interacts with. They found that on its own, SHOC2 is a horseshoe-shaped scaffolding protein with a smooth surface, making it challenging for drugs to bind to it. However, further analyses revealed the structural details of how SHOC2 brings together and binds to two key proteins, PP1C and MRAS, which are also part of the RAS signaling pathway. The team solved the structure of this three-protein SMP complex, which revealed new pockets between the component proteins where researchers might be able to fit a drug. \"You look at SHOC2 by itself, and you think 'I can't do anything with that,'\" said Broad Institute scientist Alex Burgin, CDoT's senior director. \"But when I first saw the SMP complex, right away, I could see multiple pockets where you can imagine binding a drug. And it became really exciting to me as soon as I saw the structure because it created a new path forward.\" From structure to function The scientists, working with colleagues in Broad's Genetic Perturbation Platform, also analyzed the effect of mutations in each amino acid of SHOC2 on the protein's function, using a method called deep mutational scanning. The data they generated could be used to identify new links between SHOC2 mutations and other diseases. For example, previous work has shown that mutations in this protein cause Noonan-like Syndrome, a congenital condition that affects the development of bodily features. \"What's really enabling is that by already having tested every possible mutation, you can rapidly learn and rationalize the structure and be confident what the consequences of those mutations are,\" said Hahn. \"I think this paper really brings to light how powerful that information is.\" The researchers hope that their findings will clarify the clinical relevance of SHOC2 mutations and help drugmakers find compounds that bind to the SMP complex to shut down SHOC2. The aim would be to create new drugs targeting the SMP complex that could work alone or in combination with MEK inhibitors to suppress the effects of RAS mutations and effectively block cancer growth. \"Through great teamwork leveraging diverse expertise in cancer cell signaling, functional genetic screening and structural biology, we've been able to rapidly go from discovery of SHOC2 as a high-priority target to a comprehensive structure-function roadmap for drug development. We hope that this work opens up promising avenues to create much needed new therapies for RAS-mutant cancers,\" said Aguirre. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Receptor tyrosine kinase (RTK)–RAS signalling through the downstream mitogen-activated protein kinase (MAPK) cascade regulates cell proliferation and survival. The SHOC2–MRAS–PP1C holophosphatase complex functions as a key regulator of RTK–RAS signalling by removing an inhibitory phosphorylation event on the RAF family of proteins to potentiate MAPK signalling 1 . SHOC2 forms a ternary complex with MRAS and PP1C, and human germline gain-of-function mutations in this complex result in congenital RASopathy syndromes 2 , 3 , 4 , 5 . However, the structure and assembly of this complex are poorly understood. Here we use cryo-electron microscopy to resolve the structure of the SHOC2–MRAS–PP1C complex. We define the biophysical principles of holoenzyme interactions, elucidate the assembly order of the complex, and systematically interrogate the functional consequence of nearly all of the possible missense variants of SHOC2 through deep mutational scanning. We show that SHOC2 binds PP1C and MRAS through the concave surface of the leucine-rich repeat region and further engages PP1C through the N-terminal disordered region that contains a cryptic RVXF motif. Complex formation is initially mediated by interactions between SHOC2 and PP1C and is stabilized by the binding of GTP-loaded MRAS. These observations explain how mutant versions of SHOC2 in RASopathies and cancer stabilize the interactions of complex members to enhance holophosphatase activity. Together, this integrative structure–function model comprehensively defines key binding interactions within the SHOC2–MRAS–PP1C holophosphatase complex and will inform therapeutic development . Main SHOC2 is a scaffold protein composed of leucine-rich repeats (LRRs) that bind directly to the catalytic subunit of PP1 (PP1C). Activation of MRAS leads to membrane localization of the SHOC2–MRAS–PP1C (SMP) complex and to the dephosphorylation of proteins of the RAF family at a key inhibitory phosphorylation site, including S259 on CRAF (RAF1), S365 on BRAF and S214 on ARAF (hereafter collectively referred to as ‘S259’); this results in the release of autoinhibition and the potentiation of RAF activation 1 , 6 . The SMP holophosphatase has a critical role in the RAS–MAPK pathway signalling that underlies normal developmental processes as well as oncogenic signalling in cancer. Activating mutations in SHOC2, PP1C, and MRAS are found in Noonan-like syndrome, a ‘RASopathy' syndrome that is characterized by congenital cardiac, skeletal, and cognitive deficits 2 , 6 , 7 , 8 . SHOC2 is essential for the proliferation and survival of several cancers including RAS-driven leukaemia; melanoma; and models of non-small cell lung cancer 9 , 10 . Moreover, depletion of SHOC2 sensitizes RAS-driven cancers to MEK inhibition through the disruption of RTK-mediated feedback signalling and through MEK-inhibitor-induced RAF dimerization 11 , 12 . However, gaps in our knowledge of the biophysical basis of complex assembly and function limit our understanding of the mechanisms of disease and opportunities for therapeutic targeting of this ternary complex. Structure of the SMP complex To understand the role of SHOC2 in RAS–MAPK pathway signalling, we solved the SHOC2 structure alone and in complex with PP1C and MRAS. Specifically, we developed an optimized expression system to produce wild-type human SHOC2 and PP1C, as well as constitutively active GTP-bound MRAS(Q71L) (Fig. 1a and Methods ). We first used X-ray crystallography to solve the structure of the wild-type SHOC2 apoprotein at 1.8-Å resolution (Fig. 1b and Extended Data Table 1 ). The apo-SHOC2 structure is a canonical LRR protein that consists of 20 tandem LRR domains. These LRR domains concatenate to form a conventional solenoid structure that has an average LRR corkscrew rotation of ~4 o (Fig. 1b ) and is stabilized by an N-terminal flanking α-helix and a C-terminal helix-turn-helix. Each LRR is composed of 22–24 amino acids containing a β-strand followed by a descending loop, an α-helix and an ascending loop. The LRR β-strands assemble in parallel to generate the concave surface of the solenoid, whereas the α-helices form most of the convex surface. Internal to the structure, the conserved leucine residues of the LRR motif, LXXLXLXN(X) 1–2 L, condense to form the hydrophobic core of the protein, whereas the conserved asparagine residue participates in a highly stabilizing 'asparagine ladder' motif that has been shown to be critical to the LRR fold 13 . The SHOC2 structure does not show the presence of the flexible hinge within the medial LRRs that was predicted in previous computational models of SHOC2 (refs. 14 , 15 ). Fig. 1: Structure of apo-SHOC2 and the SMP holophosphatase complex. a , Schematic diagram of members of the SMP complex. Truncation of constructs is indicated with dashed lines. MRAS switch 1 (SI), switch 2 (SII) and the hypervariable region (HVR) are annotated. *indicates the 2–63-deletion construct that was used for cryo-EM; ** indicates the 2–88-deletion SHOC2 construct that was used for X-ray crystallography. b , Overview of the crystal structure of apo-SHOC2 along with a cross-sectional representation of the LRR domain. c , d , Side views of the cryo-EM structure of the SHOC2 complex with SHOC2 in teal), MRAS in maroon, and PP1C in yellow. A ribbon representation and view of MRAS ( c ) and PP1C ( d ) are shown with relevant structural features annotated. d , Manganese ions (red), hydrophobic (H), C-terminal (C) and acidic (A) grooves are shown. Full size image As the conformation and binding interfaces of SHOC2 that are involved in complex formation with PP1C and MRAS cannot be inferred from the structure of the apoprotein alone, we used single-particle cryo-electron microscopy (cryo-EM) to resolve the holophosphatase complex of an N-terminally truncated SHOC2, wild-type PP1C and GTP-loaded MRAS(Q71L) (Fig. 1c,d , Extended Data Fig. 1 and Extended Data Table 2 ). The resulting structure at 2.9-Å resolution unambiguously defined a ternary complex in which SHOC2 engages both PP1C and MRAS through its concave surface (Fig. 1d ). The overall structure of SHOC2 observed in the holoenzyme complex is similar to the isolated apoprotein. Through protein–protein interactions, the SHOC2 complex buries a total of 5,934 Å 2 of solvent-accessible surface area, with SHOC2–PP1C, SHOC2–MRAS and MRAS–PP1C covering 3,019 Å 2 , 1,729 Å 2 and 1,186 Å 2 , respectively (Extended Data Fig.<|im_end|> <|im_start|>assistant Some of the most infamous drivers of cancer are mutations in RAS genes, which lead to tumor growth in about a quarter of all cancer patients. Scientists at the Broad Institute of MIT and Harvard and the Dana-Farber Cancer Institute have determined the molecular structure of a RAS-pathway protein called SHOC2 and two other proteins it binds to. This three-protein assembly, called the SHOC2-MRAS-PP1C ("SMP") complex, regulates the RAS signaling pathway and helps cancer cells with RAS mutations survive. The high-resolution structure of this complex, revealed through X-ray crystallography and cryogenic electron microscopy, suggests possible ways that drugs can bind to it to inhibit the RAS pathway and block cancer growth. The study, published in Nature, highlights a potential therapeutic strategy for a signaling pathway that has been difficult to target with drugs. The work is the result of a collaboration between researchers at Dana-Farber, Deerfield Discovery and Development, a subsidiary of Deerfield Management Company, and in the Broad's Cancer Program, Genetic Perturbation Platform, and the Center for the Development of Therapeutics (CDoT). "By solving the structure, we've learned a lot about how SHOC2 operates in this circuit, which points out ways in which you can therapeutically intervene," said study co-senior author and Broad institute member William Hahn of the Cancer Program. Hahn is also the William Rosenberg Professor of Medicine, executive vice president and the chief operating officer at Dana-Farber. SHOC2 protein structure. Credit: Broad Institute and Dana-Farber Cancer Institute SHOC2 story Hahn, co-senior author Andrew Aguirre, an oncologist at Dana-Farber and a Broad associate member, and Jason Kwon, a postdoctoral fellow in Hahn's lab, first identified SHOC2 as a possible drug target in 2019. They and their colleagues with Broad's Cancer Dependency Map project were studying essential genes in cancers with mutations in RAS proteins. At the time, cancer drugs called MEK inhibitors had been developed to target mutations in RAS proteins, but they were effective in only a fraction of cancer patients. The team wondered whether another protein was enabling mutated RAS proteins to bypass these inhibitors. In their 2019 study, the team used CRISPR-Cas9 to knock out genes one-by-one across the entire genome to see which ones might be causing RAS-mutated cancer cells to resist the effects of MEK inhibitors. The researchers found that when they deleted the SHOC2 gene or decreased its expression, the MEK inhibitors were highly effective at eliminating cancer cells, revealing SHOC2 as a culprit in resistance to MEK inhibitors. Protein puzzle The team decided to further study SHOC2 as a potential target, which included solving its structure. That's when researchers from CDoT and Deerfield Discovery and Development joined the team. "We identified SHOC2 genetically and knew that it was important, but in order to therapeutically exploit it, we have to know the structure of the protein to identify critical, functional regions," said Kwon, project lead and co-first author of the paper. The team worked with CDoT scientists, including co-first authors Behnoush Hajian, a research scientist, Yuemin Bian, a computational scientist, and co-senior author Christopher Lemke, director of protein science and structural biology. They used X-ray crystallography and cryogenic electron microscopy to solve high-resolution structures of SHOC2 and the proteins it interacts with. They found that on its own, SHOC2 is a horseshoe-shaped scaffolding protein with a smooth surface, making it challenging for drugs to bind to it. However, further analyses revealed the structural details of how SHOC2 brings together and binds to two key proteins, PP1C and MRAS, which are also part of the RAS signaling pathway. The team solved the structure of this three-protein SMP complex, which revealed new pockets between the component proteins where researchers might be able to fit a drug. "You look at SHOC2 by itself, and you think 'I can't do anything with that,'" said Broad Institute scientist Alex Burgin, CDoT's senior director. "But when I first saw the SMP complex, right away, I could see multiple pockets where you can imagine binding a drug. And it became really exciting to me as soon as I saw the structure because it created a new path forward." From structure to function The scientists, working with colleagues in Broad's Genetic Perturbation Platform, also analyzed the effect of mutations in each amino acid of SHOC2 on the protein's function, using a method called deep mutational scanning. The data they generated could be used to identify new links between SHOC2 mutations and other diseases. For example, previous work has shown that mutations in this protein cause Noonan-like Syndrome, a congenital condition that affects the development of bodily features. "What's really enabling is that by already having tested every possible mutation, you can rapidly learn and rationalize the structure and be confident what the consequences of those mutations are," said Hahn. "I think this paper really brings to light how powerful that information is." The researchers hope that their findings will clarify the clinical relevance of SHOC2 mutations and help drugmakers find compounds that bind to the SMP complex to shut down SHOC2. The aim would be to create new drugs targeting the SMP complex that could work alone or in combination with MEK inhibitors to suppress the effects of RAS mutations and effectively block cancer growth. "Through great teamwork leveraging diverse expertise in cancer cell signaling, functional genetic screening and structural biology, we've been able to rapidly go from discovery of SHOC2 as a high-priority target to a comprehensive structure-function roadmap for drug development. We hope that this work opens up promising avenues to create much needed new therapies for RAS-mutant cancers," said Aguirre. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 1050, 15709, 13892, 3714, 483, 82160, 320, 5463, 42, 8, 4235, 49, 1950, 91977, 1555, 279, 52452, 5568, 11968, 12, 31262, 13128, 82160, 320, 18082, 42, 8, 43118, 80412, 2849, 53840, 323, 20237, 13, 578, 6570, 7767, 17, 4235, 18953, 1950, 4235, 4505, 16, 34, 24429, 5237, 24527, 266, 521, 6485, 5865, 439, 264, 1401, 40704, 315, 10860, 42, 4235, 49, 1950, 91977, 555, 18054, 459, 20747, 10843, 95089, 2354, 1567, 389, 279, 72152, 3070, 315, 28896, 311, 36875, 6629, 28322, 42, 91977, 220, 16, 662, 6570, 7767, 17, 7739, 264, 72717, 661, 6485, 449, 29433, 1950, 323, 30950, 16, 34, 11, 323, 3823, 17684, 1029, 483, 8895, 8838, 34849, 34684, 304, 420, 6485, 1121, 304, 83066, 2223, 432, 1950, 54042, 22013, 442, 288, 220, 17, 1174, 220, 18, 1174, 220, 19, 1174, 220, 20, 662, 4452, 11, 279, 6070, 323, 14956, 315, 420, 6485, 527, 31555, 16365, 13, 5810, 584, 1005, 16106, 78, 37081, 2298, 92914, 311, 9006, 279, 6070, 315, 279, 6570, 7767, 17, 4235, 18953, 1950, 4235, 4505, 16, 34, 6485, 13, 1226, 7124, 279, 6160, 91004, 16565, 315, 305, 10216, 65728, 22639, 11, 97298, 349, 279, 14956, 2015, 315, 279, 6485, 11, 323, 60826, 37539, 349, 279, 16003, 29774, 315, 7154, 682, 315, 279, 3284, 3194, 1137, 27103, 315, 6570, 7767, 17, 1555, 5655, 5318, 1697, 36201, 13, 1226, 1501, 430, 6570, 7767, 17, 58585, 30950, 16, 34, 323, 29433, 1950, 1555, 279, 3613, 525, 7479, 315, 279, 514, 1791, 483, 41947, 13454, 5654, 323, 4726, 69589, 30950, 16, 34, 1555, 279, 452, 91723, 834, 10767, 5654, 430, 5727, 264, 14774, 292, 33570, 67238, 60612, 13, 22872, 18488, 374, 15453, 78926, 555, 22639, 1990, 6570, 7767, 17, 323, 30950, 16, 34, 323, 374, 93163, 555, 279, 11212, 315, 480, 4334, 79170, 29433, 1950, 13, 4314, 24654, 10552, 1268, 61618, 11028, 315, 6570, 7767, 17, 304, 432, 1950, 36211, 552, 323, 9572, 70236, 279, 22639, 315, 6485, 3697, 311, 18885, 24429, 5237, 24527, 266, 521, 5820, 13, 32255, 11, 420, 8936, 1413, 6070, 4235, 1723, 1646, 12963, 28014, 19170, 1401, 11212, 22639, 2949, 279, 6570, 7767, 17, 4235, 18953, 1950, 4235, 4505, 16, 34, 24429, 5237, 24527, 266, 521, 6485, 323, 690, 6179, 37471, 4500, 662, 4802, 6570, 7767, 17, 374, 264, 85552, 13128, 24306, 315, 514, 1791, 483, 41947, 44694, 320, 43, 8268, 82, 8, 430, 10950, 6089, 311, 279, 34454, 70504, 1207, 3928, 315, 30950, 16, 320, 4505, 16, 34, 570, 50747, 315, 29433, 1950, 11767, 311, 39654, 53404, 315, 279, 6570, 7767, 17, 4235, 18953, 1950, 4235, 4505, 16, 34, 320, 50, 5901, 8, 6485, 323, 311, 279, 409, 764, 24527, 683, 2354, 315, 28896, 315, 279, 72152, 3070, 520, 264, 1401, 20747, 10843, 95089, 2354, 2816, 11, 2737, 328, 15537, 389, 94767, 37, 320, 5726, 37, 16, 705, 328, 12676, 389, 74863, 37, 323, 328, 11584, 389, 362, 5726, 37, 320, 6881, 10924, 45925, 14183, 311, 439, 3451, 50, 15537, 529, 1237, 420, 3135, 304, 279, 4984, 315, 3313, 258, 60073, 323, 279, 36875, 7246, 315, 72152, 15449, 220, 16, 1174, 220, 21, 662, 578, 93900, 24429, 5237, 24527, 266, 521, 706, 264, 9200, 3560, 304, 279, 432, 1950, 4235, 18082, 42, 38970, 91977, 430, 1234, 49201, 4725, 48006, 11618, 439, 1664, 439, 78970, 29569, 91977, 304, 9572, 13, 15050, 1113, 34684, 304, 6570, 7767, 17, 11, 30950, 16, 34, 11, 323, 29433, 1950, 527, 1766, 304, 83956, 276, 12970, 28439, 11, 264, 3451, 49, 1950, 54042, 6, 28439, 430, 374, 32971, 555, 83066, 2223, 47345, 11, 69397, 11, 323, 25702, 57096, 220, 17, 1174, 220, 21, 1174, 220, 22, 1174, 220, 23, 662, 6570, 7767, 17, 374, 7718, 369, 279, 53840, 323, 20237, 315, 3892, 51423, 2737, 432, 1950, 32505, 514, 26261, 22689, 26, 68012, 7942, 26, 323, 4211, 315, 2536, 34859, 2849, 21271, 9572, 220, 24, 1174, 220, 605, 662, 23674, 11, 92948, 315, 6570, 7767, 17, 74633, 4861, 432, 1950, 32505, 51423, 311, 16691, 42, 61478, 1555, 279, 44219, 315, 10860, 42, 82076, 11302, 91977, 323, 1555, 16691, 42, 3502, 5923, 1960, 38973, 72152, 294, 3212, 2065, 220, 806, 1174, 220, 717, 662, 4452, 11, 33251, 304, 1057, 6677, 315, 279, 6160, 91004, 8197, 315, 6485, 14956, 323, 734, 4017, 1057, 8830, 315, 279, 24717, 315, 8624, 323, 10708, 369, 37471, 25103, 315, 420, 72717, 661, 6485, 13, 29696, 315, 279, 93900, 6485, 2057, 3619, 279, 3560, 315, 6570, 7767, 17, 304, 432, 1950, 4235, 18082, 42, 38970, 91977, 11, 584, 29056, 279, 6570, 7767, 17, 6070, 7636, 323, 304, 6485, 449, 30950, 16, 34, 323, 29433, 1950, 13, 45863, 11, 584, 8040, 459, 34440, 7645, 1887, 311, 8356, 8545, 10827, 3823, 6570, 7767, 17, 323, 30950, 16, 34, 11, 439, 1664, 439, 9129, 332, 3210, 4642, 480, 4334, 50962, 29433, 1950, 6386, 6028, 43, 8, 320, 30035, 13, 220, 16, 64, 323, 19331, 7609, 1226, 1176, 1511, 1630, 30630, 26110, 848, 1976, 88, 311, 11886, 279, 6070, 315, 279, 8545, 10827, 6570, 7767, 17, 1469, 454, 91748, 520, 220, 16, 13, 23, 12, 106453, 11175, 320, 30035, 13, 220, 16, 65, 323, 41665, 2956, 6771, 220, 16, 7609, 578, 73990, 6354, 39, 7767, 17, 6070, 374, 264, 43553, 445, 8268, 13128, 430, 17610, 315, 220, 508, 67042, 445, 8268, 31576, 13, 4314, 445, 8268, 31576, 78884, 311, 1376, 264, 21349, 2092, 268, 590, 6070, 430, 706, 459, 5578, 445, 8268, 272, 74402, 39717, 12984, 315, 4056, 19, 297, 320, 30035, 13, 220, 16, 65, 883, 323, 374, 93163, 555, 459, 452, 91723, 1344, 33434, 19581, 2902, 68818, 323, 264, 356, 91723, 11591, 953, 65051, 2902, 68818, 13, 9062, 445, 8268, 374, 24306, 315, 220, 1313, 4235, 1187, 42500, 33969, 8649, 264, 34318, 42728, 438, 8272, 555, 264, 44184, 6471, 11, 459, 19581, 2902, 68818, 323, 459, 36488, 6471, 13, 578, 445, 8268, 34318, 42728, 2914, 42840, 304, 15638, 311, 7068, 279, 3613, 525, 7479, 315, 279, 2092, 268, 590, 11, 20444, 279, 19581, 2902, 301, 1238, 1376, 1455, 315, 279, 67030, 7479, 13, 15774, 311, 279, 6070, 11, 279, 1615, 2841, 514, 1791, 483, 71783, 315, 279, 445, 8268, 60612, 11, 445, 6277, 43, 37630, 55, 45, 7799, 8, 220, 16, 4235, 17, 445, 11, 9955, 1137, 311, 1376, 279, 17055, 764, 31906, 6332, 315, 279, 13128, 11, 20444, 279, 1615, 2841, 439, 1768, 24281, 49232, 91287, 304, 264, 7701, 27276, 4954, 364, 300, 1768, 24281, 36865, 6, 60612, 430, 706, 1027, 6982, 311, 387, 9200, 311, 279, 445, 8268, 11816, 220, 1032, 662, 578, 6570, 7767, 17, 6070, 1587, 539, 1501, 279, 9546, 315, 279, 19303, 76693, 2949, 279, 97348, 445, 8268, 82, 430, 574, 19698, 304, 3766, 55580, 4211, 315, 6570, 7767, 17, 320, 16541, 13, 220, 975, 1174, 220, 868, 7609, 23966, 13, 220, 16, 25, 29696, 315, 73990, 6354, 39, 7767, 17, 323, 279, 93900, 24429, 5237, 24527, 266, 521, 6485, 13, 264, 1174, 328, 82149, 13861, 315, 3697, 315, 279, 93900, 6485, 13, 1183, 1371, 367, 315, 57327, 374, 16717, 449, 67822, 5238, 13, 29433, 1950, 3480, 220, 16, 320, 14137, 705, 3480, 220, 17, 320, 50, 5660, 8, 323, 279, 9950, 651, 277, 2205, 5654, 320, 39, 19330, 8, 527, 63951, 13, 353, 485, 25858, 279, 220, 17, 4235, 5495, 6953, 53725, 9429, 430, 574, 1511, 369, 16106, 78, 12, 2783, 26, 3146, 15151, 279, 220, 17, 4235, 2421, 6953, 53725, 6570, 7767, 17, 9429, 430, 574, 1511, 369, 1630, 30630, 26110, 848, 1976, 88, 13, 293, 1174, 35907, 315, 279, 26110, 6070, 315, 73990, 6354, 39, 7767, 17, 3235, 449, 264, 5425, 97319, 13340, 315, 279, 445, 8268, 8106, 13, 272, 1174, 294, 1174, 17072, 6325, 315, 279, 16106, 78, 12, 2783, 6070, 315, 279, 6570, 7767, 17, 6485, 449, 6570, 7767, 17, 304, 95707, 705, 29433, 1950, 304, 3678, 9186, 11, 323, 30950, 16, 34, 304, 14071, 13, 362, 45667, 13340, 323, 1684, 315, 29433, 1950, 320, 272, 883, 323, 30950, 16, 34, 320, 294, 883, 527, 6982, 449, 9959, 24693, 4519, 63951, 13, 294, 1174, 386, 66964, 65125, 320, 1171, 705, 17055, 764, 31906, 320, 39, 705, 356, 91723, 320, 34, 8, 323, 84903, 320, 32, 8, 10707, 10296, 527, 6982, 13, 8797, 1404, 2217, 1666, 279, 390, 1659, 323, 11212, 25066, 315, 6570, 7767, 17, 430, 527, 6532, 304, 6485, 18488, 449, 30950, 16, 34, 323, 29433, 1950, 4250, 387, 68695, 505, 279, 6070, 315, 279, 1469, 454, 91748, 7636, 11, 584, 1511, 3254, 2320, 7203, 16106, 78, 37081, 2298, 92914, 320, 62238, 78, 12, 2783, 8, 311, 9006, 279, 24429, 5237, 24527, 266, 521, 6485, 315, 459, 452, 12, 23827, 750, 60856, 6570, 7767, 17, 11, 8545, 10827, 30950, 16, 34, 323, 480, 4334, 79170, 29433, 1950, 6386, 6028, 43, 8, 320, 30035, 13, 220, 16, 66, 12260, 1174, 41665, 2956, 23966, 13, 220, 16, 323, 41665, 2956, 6771, 220, 17, 7609, 578, 13239, 6070, 520, 220, 17, 13, 24, 12, 106453, 11175, 653, 3042, 27843, 7162, 4613, 264, 72717, 661, 6485, 304, 902, 6570, 7767, 17, 69589, 2225, 30950, 16, 34, 323, 29433, 1950, 1555, 1202, 3613, 525, 7479, 320, 30035, 13, 220, 16, 67, 7609, 578, 8244, 6070, 315, 6570, 7767, 17, 13468, 304, 279, 305, 10216, 65728, 6485, 374, 4528, 311, 279, 25181, 1469, 454, 91748, 13, 17331, 13128, 4235, 79565, 22639, 11, 279, 6570, 7767, 17, 6485, 7951, 552, 264, 2860, 315, 220, 20, 11, 24347, 80352, 220, 17, 315, 69996, 43256, 1260, 7479, 3158, 11, 449, 6570, 7767, 17, 4235, 4505, 16, 34, 11, 6570, 7767, 17, 4235, 18953, 1950, 323, 29433, 1950, 4235, 4505, 16, 34, 18702, 220, 18, 11, 18089, 80352, 220, 17, 1174, 220, 16, 11, 22194, 80352, 220, 17, 323, 220, 16, 11, 9714, 80352, 220, 17, 1174, 15947, 320, 54290, 2956, 23966, 13, 128257, 198, 128256, 78191, 198, 8538, 315, 279, 1455, 39633, 12050, 315, 9572, 527, 34684, 304, 432, 1950, 21389, 11, 902, 3063, 311, 36254, 6650, 304, 922, 264, 8502, 315, 682, 9572, 6978, 13, 57116, 520, 279, 16273, 10181, 315, 15210, 323, 25996, 323, 279, 47713, 7424, 277, 655, 26211, 10181, 617, 11075, 279, 31206, 6070, 315, 264, 432, 1950, 34195, 3195, 13128, 2663, 6570, 7767, 17, 323, 1403, 1023, 28896, 433, 58585, 311, 13, 1115, 2380, 10039, 39340, 14956, 11, 2663, 279, 6570, 7767, 17, 5364, 49, 1950, 12, 4505, 16, 34, 3573, 50, 5901, 909, 6485, 11, 80412, 279, 432, 1950, 43080, 38970, 323, 8779, 9572, 7917, 449, 432, 1950, 34684, 18167, 13, 578, 1579, 64036, 6070, 315, 420, 6485, 11, 10675, 1555, 1630, 30630, 26110, 848, 1976, 88, 323, 16106, 29569, 17130, 92914, 11, 13533, 3284, 5627, 430, 11217, 649, 10950, 311, 433, 311, 69033, 279, 432, 1950, 38970, 323, 2565, 9572, 6650, 13, 578, 4007, 11, 4756, 304, 22037, 11, 22020, 264, 4754, 37471, 8446, 369, 264, 43080, 38970, 430, 706, 1027, 5107, 311, 2218, 449, 11217, 13, 578, 990, 374, 279, 1121, 315, 264, 20632, 1990, 12074, 520, 47713, 7424, 277, 655, 11, 64191, 2630, 39193, 323, 11050, 11, 264, 41164, 315, 64191, 2630, 9744, 8351, 11, 323, 304, 279, 16273, 596, 26211, 6826, 11, 75226, 82884, 65916, 17916, 11, 323, 279, 5955, 369, 279, 11050, 315, 23258, 88886, 320, 34, 5519, 51, 570, 330, 1383, 22581, 279, 6070, 11, 584, 3077, 9687, 264, 2763, 922, 1268, 6570, 7767, 17, 27149, 304, 420, 16622, 11, 902, 3585, 704, 5627, 304, 902, 499, 649, 9139, 27596, 2740, 55579, 1359, 1071, 4007, 1080, 1355, 268, 2521, 3229, 323, 16273, 44798, 4562, 12656, 473, 30660, 315, 279, 26211, 6826, 13, 473, 30660, 374, 1101, 279, 12656, 97707, 17054, 315, 19152, 11, 11145, 17192, 4872, 323, 279, 10388, 10565, 9640, 520, 47713, 7424, 277, 655, 13, 6570, 7767, 17, 13128, 6070, 13, 16666, 25, 16273, 10181, 323, 47713, 7424, 277, 655, 26211, 10181, 6570, 7767, 17, 3446, 473, 30660, 11, 1080, 1355, 268, 2521, 3229, 13929, 4701, 21581, 265, 11, 459, 78970, 16549, 520, 47713, 7424, 277, 655, 323, 264, 16273, 22712, 4562, 11, 323, 18984, 735, 55767, 11, 264, 1772, 38083, 278, 12637, 304, 473, 30660, 596, 10278, 11, 1176, 11054, 6570, 7767, 17, 439, 264, 3284, 5623, 2218, 304, 220, 679, 24, 13, 2435, 323, 872, 18105, 449, 16273, 596, 26211, 34077, 5135, 2447, 1051, 21630, 7718, 21389, 304, 51423, 449, 34684, 304, 432, 1950, 28896, 13, 2468, 279, 892, 11, 9572, 11217, 2663, 16691, 42, 68642, 1047, 1027, 8040, 311, 2218, 34684, 304, 432, 1950, 28896, 11, 719, 814, 1051, 7524, 304, 1193, 264, 19983, 315, 9572, 6978, 13, 578, 2128, 31156, 3508, 2500, 13128, 574, 28462, 85922, 432, 1950, 28896, 311, 31818, 1521, 68642, 13, 763, 872, 220, 679, 24, 4007, 11, 279, 2128, 1511, 12904, 1669, 6616, 7813, 300, 24, 311, 14459, 704, 21389, 832, 14656, 19101, 4028, 279, 4553, 33869, 311, 1518, 902, 6305, 2643, 387, 14718, 432, 1950, 1474, 332, 660, 9572, 7917, 311, 22884, 279, 6372, 315, 16691, 42, 68642, 13, 578, 12074, 1766, 430, 994, 814, 11309, 279, 6570, 7767, 17, 15207, 477, 25983, 1202, 7645, 11, 279, 16691, 42, 68642, 1051, 7701, 7524, 520, 40599, 9572, 7917, 11, 31720, 6570, 7767, 17, 439, 264, 75283, 304, 13957, 311, 16691, 42, 68642, 13, 49475, 25649, 578, 2128, 6773, 311, 4726, 4007, 6570, 7767, 17, 439, 264, 4754, 2218, 11, 902, 5343, 22581, 1202, 6070, 13, 3011, 596, 994, 12074, 505, 356, 5519, 51, 323, 64191, 2630, 39193, 323, 11050, 11096, 279, 2128, 13, 330, 1687, 11054, 6570, 7767, 17, 52033, 323, 7020, 430, 433, 574, 3062, 11, 719, 304, 2015, 311, 9139, 27596, 2740, 33294, 433, 11, 584, 617, 311, 1440, 279, 6070, 315, 279, 13128, 311, 10765, 9200, 11, 16003, 13918, 1359, 1071, 735, 55767, 11, 2447, 3063, 323, 1080, 38043, 3229, 315, 279, 5684, 13, 578, 2128, 6575, 449, 356, 5519, 51, 14248, 11, 2737, 1080, 38043, 12283, 14954, 77, 788, 71, 84526, 1122, 11, 264, 3495, 28568, 11, 28372, 26768, 68045, 11, 264, 55580, 28568, 11, 323, 1080, 1355, 268, 2521, 3229, 26035, 48506, 441, 11, 7690, 315, 13128, 8198, 323, 24693, 34458, 13, 2435, 1511, 1630, 30630, 26110, 848, 1976, 88, 323, 16106, 29569, 17130, 92914, 311, 11886, 1579, 64036, 14726, 315, 6570, 7767, 17, 323, 279, 28896, 433, 84261, 449, 13, 2435, 1766, 430, 389, 1202, 1866, 11, 6570, 7767, 17, 374, 264, 60475, 4385, 4748, 35831, 57250, 15345, 13128, 449, 264, 11113, 7479, 11, 3339, 433, 17436, 369, 11217, 311, 10950, 311, 433, 13, 4452, 11, 4726, 29060, 10675, 279, 24693, 3649, 315, 1268, 6570, 7767, 17, 12716, 3871, 323, 58585, 311, 1403, 1401, 28896, 11, 30950, 16, 34, 323, 29433, 1950, 11, 902, 527, 1101, 961, 315, 279, 432, 1950, 43080, 38970, 13, 578, 2128, 29056, 279, 6070, 315, 420, 2380, 10039, 39340, 93900, 6485, 11, 902, 10675, 502, 30278, 1990, 279, 3777, 28896, 1405, 12074, 2643, 387, 3025, 311, 5052, 264, 5623, 13, 330, 2675, 1427, 520, 6570, 7767, 17, 555, 5196, 11, 323, 499, 1781, 364, 40, 649, 956, 656, 4205, 449, 430, 49982, 1071, 16273, 10181, 28568, 8683, 41109, 258, 11, 356, 5519, 51, 596, 10195, 7690, 13, 330, 4071, 994, 358, 1176, 5602, 279, 93900, 6485, 11, 1314, 3201, 11, 358, 1436, 1518, 5361, 30278, 1405, 499, 649, 13085, 11212, 264, 5623, 13, 1628, 433, 6244, 2216, 13548, 311, 757, 439, 5246, 439, 358, 5602, 279, 6070, 1606, 433, 3549, 264, 502, 1853, 4741, 1210, 5659, 6070, 311, 734, 578, 14248, 11, 3318, 449, 18105, 304, 16273, 596, 75226, 82884, 65916, 17916, 11, 1101, 30239, 279, 2515, 315, 34684, 304, 1855, 42500, 13935, 315, 6570, 7767, 17, 389, 279, 13128, 596, 734, 11, 1701, 264, 1749, 2663, 5655, 5318, 1697, 36201, 13, 578, 828, 814, 8066, 1436, 387, 1511, 311, 10765, 502, 7902, 1990, 6570, 7767, 17, 34684, 323, 1023, 19338, 13, 1789, 3187, 11, 3766, 990, 706, 6982, 430, 34684, 304, 420, 13128, 5353, 83956, 276, 12970, 57496, 11, 264, 83066, 2223, 3044, 430, 22223, 279, 4500, 315, 48131, 4519, 13, 330, 3923, 596, 2216, 28462, 374, 430, 555, 2736, 3515, 12793, 1475, 3284, 27472, 11, 499, 649, 19019, 4048, 323, 25442, 553, 279, 6070, 323, 387, 16913, 1148, 279, 16296, 315, 1884, 34684, 527, 1359, 1071, 473, 30660, 13, 330, 40, 1781, 420, 5684, 2216, 12716, 311, 3177, 1268, 8147, 430, 2038, 374, 1210, 578, 12074, 3987, 430, 872, 14955, 690, 38263, 279, 14830, 41961, 315, 6570, 7767, 17, 34684, 323, 1520, 5623, 20481, 1505, 32246, 430, 10950, 311, 279, 93900, 6485, 311, 9495, 1523, 6570, 7767, 17, 13, 578, 9395, 1053, 387, 311, 1893, 502, 11217, 25103, 279, 93900, 6485, 430, 1436, 990, 7636, 477, 304, 10824, 449, 16691, 42, 68642, 311, 28321, 279, 6372, 315, 432, 1950, 34684, 323, 13750, 2565, 9572, 6650, 13, 330, 24798, 2294, 84633, 77582, 17226, 19248, 304, 9572, 2849, 43080, 11, 16003, 19465, 23061, 323, 24693, 34458, 11, 584, 3077, 1027, 3025, 311, 19019, 733, 505, 18841, 315, 6570, 7767, 17, 439, 264, 1579, 2320, 8948, 2218, 311, 264, 16195, 6070, 34849, 69917, 369, 5623, 4500, 13, 1226, 3987, 430, 420, 990, 16264, 709, 26455, 73234, 311, 1893, 1790, 4460, 502, 52312, 369, 432, 1950, 1474, 332, 519, 51423, 1359, 1071, 4701, 21581, 265, 13, 220, 128257, 198 ]

2,877

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Food trade plays a key role in achieving global food security. With a growing consumer demand for diverse food products, transportation has emerged as a key link in food supply chains. We estimate the carbon footprint of food-miles by using a global multi-region accounting framework. We calculate food-miles based on the countries and sectors of origin and the destination countries, and distinguish the relevant international and domestic transport distances and commodity masses. When the entire upstream food supply chain is considered, global food-miles correspond to about 3.0 GtCO 2 e (3.5–7.5 times higher than previously estimated), indicating that transport accounts for about 19% of total food-system emissions (stemming from transport, production and land-use change). Global freight transport associated with vegetable and fruit consumption contributes 36% of food-miles emissions—almost twice the amount of greenhouse gases released during their production. To mitigate the environmental impact of food, a shift towards plant-based foods must be coupled with more locally produced items, mainly in affluent countries. Main Since 1995, amid rapid globalization, worldwide agricultural and food trade has more than doubled, reaching US$1.5 trillion in 2018 1 . Internationally traded food provides 19% of globally consumed calories 2 and thus plays an important role in achieving global food security 3 , 4 , 5 , 6 . Reductions in transportation cost remain one of the main driving forces leading to the rapid growth of food trade 1 . The concept of ‘food-miles’ takes into account the distance travelled by food products from points of production to consumption, and is aimed at indicating the associated environmental impact (for example, energy use, emissions) 7 . ‘Food-miles’ are generally measured as tonne-kilometres (tkm, a unit for measuring freight transport, representing the transport of 1 t of goods by a given transport mode over a distance of 1 km), that is, the distance travelled in kilometres multiplied by the mass in tonnes for each transported food item 8 . Carbon footprint assessments of food-miles have usually been limited to selected food commodities (for example, tomato ketchup in Sweden 9 , canned tomato 10 in Italy, beef 11 and wheat 12 in the United States, and finfish in Western Australia 13 ) due to the large amount of data required to model all food categories. In these existing studies, product life-cycle assessment (LCA) is extensively used to track environmental performance throughout the entire life cycle of food commodities within a predefined boundary, resulting in a wide range of environmental impact estimates, with transport representing between 0.04% and 90% of production-related emissions 9 , 10 , 11 , 12 , 13 . Although such bottom-up LCA studies include detailed information on specific food products, they have limitations: (1) LCA requires defining a system boundary, and thus suffers from truncation errors due to the omission of contributions beyond that boundary 14 and, consequently, (2) comparisons between studies are often not possible because of differences in scope, and (3) the focus of these studies on a small portion of the total food supply makes it difficult to derive more general conclusions about the overall food sector 15 . A few analyses have been carried out for food suppliers at the national (for example, the United Kingdom 16 , Canada 17 , Spain 18 and Iran 19 ), city 20 and global 21 , 22 levels. Most of these studies only contain food-miles emissions resulting from direct food suppliers without considering entire upstream supply chains 16 , 17 , 18 , 19 , 20 , 21 , 22 , attributing 0.61–3.4% (refs. 16 , 17 , 18 , 19 ) of national and 0.8–1.6% (refs. 20 , 21 , 22 ) (0.4–0.86 GtCO 2 e) of global greenhouse gas (GHG) emissions to food transport (see Supplementary Notes and Supplementary Methods for a detailed literature review). To conclude, although carbon emissions associated with food production are well documented 23 , 24 , the carbon footprint of the global trade of food, accounting for the entire food supply chain, has not been comprehensively quantified. Here we provide a comprehensive global estimate of the carbon footprint of global food-miles. We first compare food-miles emissions with the total food-system emissions (stemming from transport, production and land-use change). Food-miles emissions are derived through an multi-region input–output (MRIO) model that integrates physical transportation distance, mass, modes and emissions coefficients into global supply chains ( Supplementary Notes and Supplementary Methods ). The total food-system emissions integrate food-miles emissions, food production and land-use change emissions, where the production emissions are estimated based on a standard MRIO-based carbon footprint calculation method that is widely used in high-impact footprint studies such as on biodiversity 25 , nitrogen emissions 26 and carbon emissions from global tourism 27 ( Supplementary Notes and Supplementary Methods ). We further present: (1) food-miles flow maps covering the entire global supply-chain network, and (2) domestic and international food-miles and emissions broken down by 74 countries/regions, 37 economic sectors and four transportation modes (4 × 74 2 × 37 2 ≈ 30 million direct trade connections). We compare food-miles and emissions from both destination and origin perspectives across all international trade routes to reflect the responsibility borne by importers and exporters. We also demonstrate our methodological advances in a comparison with simplified food-miles approaches. Our conclusions for improved food systems management highlight the need for an integrated strategy to food security and environment protection. Methods are summarized at the end, with further details in Supplementary Notes and Supplementary Methods . Results and discussion On the back of global food expenditure of around US$5 trillion in 2017, we estimate that the global food system (excluding land use and land-use change activities) was associated with 15.8 GtCO 2 e (transport of 3.0 Gt, production of 7.1 Gt and land-use change activities of 5.7 Gt) 22 (Fig. 1 c), representing about 30% of the world’s GHG emissions (52.5 Gt); 28 this is in line with previous estimates of 21–37% (ref. 23 ). Global food trade is becoming increasingly diversified and complex. Our", "role": "user" }, { "content": "In 2007, 'locavore'—a person who only eats food grown or produced within a 100-mile (161km) radius—was the Oxford Word of the Year. Now, 15 years later, University of Sydney researchers urge it to trend once more. They have found that 19 percent of global food system greenhouse gas emissions are caused by transportation. This is up to seven times higher than previously estimated, and far exceeds the transport emissions of other commodities. For example, transport accounts for only seven percent of industry and utilities emissions. The researchers say that especially among affluent countries, the biggest food transport emitters per capita, eating locally grown and produced food should be a priority. Dr. Mengyu Li from the University of Sydney School of Physics is the lead author of the study, to be published in Nature Food. She said: \"Our study estimates global food systems, due to transport, production, and land use change, contribute about 30 percent of total human-produced greenhouse gas emissions. So, food transport—at around six percent—is a sizeable proportion of overall emissions. \"Food transport emissions add up to nearly half of direct emissions from road vehicles.\" Nutritional ecologist and co-author, Professor David Raubenheimer, said: \"Prior to our study, most of the attention in sustainable food research has been on the high emissions associated with animal-derived foods, compared with plants. \"Our study shows that in addition to shifting towards a plant-based diet, eating locally is ideal, especially in affluent countries\". Rich countries excessively contribute Using their own framework called FoodLab, the researchers calculated that food transport corresponds to about 3 gigatonnes of emissions annually—equivalent to 19 percent of food-related emissions. Their analysis incorporates 74 countries (origin and destination); 37 economic sectors (such as vegetables and fruit; livestock; coal; and manufacturing); international and domestic transport distances; and food masses. While China, the United States, India, and Russia are the top food transport emitters, overall, high-income countries are disproportionate contributors. Countries such as the United States, Germany, France, and Japan constitute 12.5 percent of the world's population yet generate nearly half (46 percent) of food transport emissions. Examples of supply chains terminating in red meat consumption by households in China. Circles represent food production emissions; arrows represent transport emissions. Credit: Mengyu Li/University of Sydney. Australia is the second largest exporter of food transport emissions, given the breadth and volume of its primary production. Transport emissions are also food type dependent. With fruit and vegetables, for example, transport generates nearly double the number of emissions than production. Fruit and vegetables together constitute over a third of food transport emissions. \"Since vegetables and fruit require temperature-controlled transportation, their food miles emissions are higher,\" Dr. Li said. The locavore discount The researchers calculated the reduction in emissions if the global population ate only locally: 0.38 gigatonnes, equivalent to emissions from driving one tonne to the Sun and back, 6,000 times. Though they acknowledge this scenario is not realistic, for example, because many regions cannot be self-sufficient in food supply, it could be implemented to varying degrees. \"For example, there is considerable potential for peri-urban agriculture to nourish urban residents,\" co-author Professor Manfred Lenzen said. This aside, richer countries can reduce their food transport emissions through various mechanisms. These include investing in cleaner energy sources for vehicles, and incentivising food businesses to use less emissions-intensive production and distribution methods, such as natural refrigerants. \"Both investors and governments can help by creating environments that foster sustainable food supply,\" Professor Lenzen said. Yet supply is driven by demand—meaning the consumer has the ultimate power to change this situation. \"Changing consumers' attitudes and behavior towards sustainable diets can reap environmental benefits on the grandest scale,\" added Professor Raubenheimer. \"One example is the habit of consumers in affluent countries demanding unseasonal foods year-round, which need to be transported from elsewhere. \"Eating local seasonal alternatives, as we have throughout most of the history of our species, will help provide a healthy planet for future generations.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Food trade plays a key role in achieving global food security. With a growing consumer demand for diverse food products, transportation has emerged as a key link in food supply chains. We estimate the carbon footprint of food-miles by using a global multi-region accounting framework. We calculate food-miles based on the countries and sectors of origin and the destination countries, and distinguish the relevant international and domestic transport distances and commodity masses. When the entire upstream food supply chain is considered, global food-miles correspond to about 3.0 GtCO 2 e (3.5–7.5 times higher than previously estimated), indicating that transport accounts for about 19% of total food-system emissions (stemming from transport, production and land-use change). Global freight transport associated with vegetable and fruit consumption contributes 36% of food-miles emissions—almost twice the amount of greenhouse gases released during their production. To mitigate the environmental impact of food, a shift towards plant-based foods must be coupled with more locally produced items, mainly in affluent countries. Main Since 1995, amid rapid globalization, worldwide agricultural and food trade has more than doubled, reaching US$1.5 trillion in 2018 1 . Internationally traded food provides 19% of globally consumed calories 2 and thus plays an important role in achieving global food security 3 , 4 , 5 , 6 . Reductions in transportation cost remain one of the main driving forces leading to the rapid growth of food trade 1 . The concept of ‘food-miles’ takes into account the distance travelled by food products from points of production to consumption, and is aimed at indicating the associated environmental impact (for example, energy use, emissions) 7 . ‘Food-miles’ are generally measured as tonne-kilometres (tkm, a unit for measuring freight transport, representing the transport of 1 t of goods by a given transport mode over a distance of 1 km), that is, the distance travelled in kilometres multiplied by the mass in tonnes for each transported food item 8 . Carbon footprint assessments of food-miles have usually been limited to selected food commodities (for example, tomato ketchup in Sweden 9 , canned tomato 10 in Italy, beef 11 and wheat 12 in the United States, and finfish in Western Australia 13 ) due to the large amount of data required to model all food categories. In these existing studies, product life-cycle assessment (LCA) is extensively used to track environmental performance throughout the entire life cycle of food commodities within a predefined boundary, resulting in a wide range of environmental impact estimates, with transport representing between 0.04% and 90% of production-related emissions 9 , 10 , 11 , 12 , 13 . Although such bottom-up LCA studies include detailed information on specific food products, they have limitations: (1) LCA requires defining a system boundary, and thus suffers from truncation errors due to the omission of contributions beyond that boundary 14 and, consequently, (2) comparisons between studies are often not possible because of differences in scope, and (3) the focus of these studies on a small portion of the total food supply makes it difficult to derive more general conclusions about the overall food sector 15 . A few analyses have been carried out for food suppliers at the national (for example, the United Kingdom 16 , Canada 17 , Spain 18 and Iran 19 ), city 20 and global 21 , 22 levels. Most of these studies only contain food-miles emissions resulting from direct food suppliers without considering entire upstream supply chains 16 , 17 , 18 , 19 , 20 , 21 , 22 , attributing 0.61–3.4% (refs. 16 , 17 , 18 , 19 ) of national and 0.8–1.6% (refs. 20 , 21 , 22 ) (0.4–0.86 GtCO 2 e) of global greenhouse gas (GHG) emissions to food transport (see Supplementary Notes and Supplementary Methods for a detailed literature review). To conclude, although carbon emissions associated with food production are well documented 23 , 24 , the carbon footprint of the global trade of food, accounting for the entire food supply chain, has not been comprehensively quantified. Here we provide a comprehensive global estimate of the carbon footprint of global food-miles. We first compare food-miles emissions with the total food-system emissions (stemming from transport, production and land-use change). Food-miles emissions are derived through an multi-region input–output (MRIO) model that integrates physical transportation distance, mass, modes and emissions coefficients into global supply chains ( Supplementary Notes and Supplementary Methods ). The total food-system emissions integrate food-miles emissions, food production and land-use change emissions, where the production emissions are estimated based on a standard MRIO-based carbon footprint calculation method that is widely used in high-impact footprint studies such as on biodiversity 25 , nitrogen emissions 26 and carbon emissions from global tourism 27 ( Supplementary Notes and Supplementary Methods ). We further present: (1) food-miles flow maps covering the entire global supply-chain network, and (2) domestic and international food-miles and emissions broken down by 74 countries/regions, 37 economic sectors and four transportation modes (4 × 74 2 × 37 2 ≈ 30 million direct trade connections). We compare food-miles and emissions from both destination and origin perspectives across all international trade routes to reflect the responsibility borne by importers and exporters. We also demonstrate our methodological advances in a comparison with simplified food-miles approaches. Our conclusions for improved food systems management highlight the need for an integrated strategy to food security and environment protection. Methods are summarized at the end, with further details in Supplementary Notes and Supplementary Methods . Results and discussion On the back of global food expenditure of around US$5 trillion in 2017, we estimate that the global food system (excluding land use and land-use change activities) was associated with 15.8 GtCO 2 e (transport of 3.0 Gt, production of 7.1 Gt and land-use change activities of 5.7 Gt) 22 (Fig. 1 c), representing about 30% of the world’s GHG emissions (52.5 Gt); 28 this is in line with previous estimates of 21–37% (ref. 23 ). Global food trade is becoming increasingly diversified and complex. Our<|im_end|> <|im_start|>assistant In 2007, 'locavore'—a person who only eats food grown or produced within a 100-mile (161km) radius—was the Oxford Word of the Year. Now, 15 years later, University of Sydney researchers urge it to trend once more. They have found that 19 percent of global food system greenhouse gas emissions are caused by transportation. This is up to seven times higher than previously estimated, and far exceeds the transport emissions of other commodities. For example, transport accounts for only seven percent of industry and utilities emissions. The researchers say that especially among affluent countries, the biggest food transport emitters per capita, eating locally grown and produced food should be a priority. Dr. Mengyu Li from the University of Sydney School of Physics is the lead author of the study, to be published in Nature Food. She said: "Our study estimates global food systems, due to transport, production, and land use change, contribute about 30 percent of total human-produced greenhouse gas emissions. So, food transport—at around six percent—is a sizeable proportion of overall emissions. "Food transport emissions add up to nearly half of direct emissions from road vehicles." Nutritional ecologist and co-author, Professor David Raubenheimer, said: "Prior to our study, most of the attention in sustainable food research has been on the high emissions associated with animal-derived foods, compared with plants. "Our study shows that in addition to shifting towards a plant-based diet, eating locally is ideal, especially in affluent countries". Rich countries excessively contribute Using their own framework called FoodLab, the researchers calculated that food transport corresponds to about 3 gigatonnes of emissions annually—equivalent to 19 percent of food-related emissions. Their analysis incorporates 74 countries (origin and destination); 37 economic sectors (such as vegetables and fruit; livestock; coal; and manufacturing); international and domestic transport distances; and food masses. While China, the United States, India, and Russia are the top food transport emitters, overall, high-income countries are disproportionate contributors. Countries such as the United States, Germany, France, and Japan constitute 12.5 percent of the world's population yet generate nearly half (46 percent) of food transport emissions. Examples of supply chains terminating in red meat consumption by households in China. Circles represent food production emissions; arrows represent transport emissions. Credit: Mengyu Li/University of Sydney. Australia is the second largest exporter of food transport emissions, given the breadth and volume of its primary production. Transport emissions are also food type dependent. With fruit and vegetables, for example, transport generates nearly double the number of emissions than production. Fruit and vegetables together constitute over a third of food transport emissions. "Since vegetables and fruit require temperature-controlled transportation, their food miles emissions are higher," Dr. Li said. The locavore discount The researchers calculated the reduction in emissions if the global population ate only locally: 0.38 gigatonnes, equivalent to emissions from driving one tonne to the Sun and back, 6,000 times. Though they acknowledge this scenario is not realistic, for example, because many regions cannot be self-sufficient in food supply, it could be implemented to varying degrees. "For example, there is considerable potential for peri-urban agriculture to nourish urban residents," co-author Professor Manfred Lenzen said. This aside, richer countries can reduce their food transport emissions through various mechanisms. These include investing in cleaner energy sources for vehicles, and incentivising food businesses to use less emissions-intensive production and distribution methods, such as natural refrigerants. "Both investors and governments can help by creating environments that foster sustainable food supply," Professor Lenzen said. Yet supply is driven by demand—meaning the consumer has the ultimate power to change this situation. "Changing consumers' attitudes and behavior towards sustainable diets can reap environmental benefits on the grandest scale," added Professor Raubenheimer. "One example is the habit of consumers in affluent countries demanding unseasonal foods year-round, which need to be transported from elsewhere. "Eating local seasonal alternatives, as we have throughout most of the history of our species, will help provide a healthy planet for future generations." <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 12369, 6696, 11335, 264, 1401, 3560, 304, 32145, 3728, 3691, 4868, 13, 3161, 264, 7982, 11761, 7631, 369, 17226, 3691, 3956, 11, 18386, 706, 22763, 439, 264, 1401, 2723, 304, 3691, 8312, 27271, 13, 1226, 16430, 279, 12782, 43972, 315, 3691, 1474, 3742, 555, 1701, 264, 3728, 7447, 61779, 24043, 12914, 13, 1226, 11294, 3691, 1474, 3742, 3196, 389, 279, 5961, 323, 26593, 315, 6371, 323, 279, 9284, 5961, 11, 323, 33137, 279, 9959, 6625, 323, 13018, 7710, 27650, 323, 38983, 32738, 13, 3277, 279, 4553, 42830, 3691, 8312, 8957, 374, 6646, 11, 3728, 3691, 1474, 3742, 8024, 311, 922, 220, 18, 13, 15, 480, 83, 8445, 220, 17, 384, 320, 18, 13, 20, 4235, 22, 13, 20, 3115, 5190, 1109, 8767, 13240, 705, 19392, 430, 7710, 9815, 369, 922, 220, 777, 4, 315, 2860, 3691, 37748, 20748, 320, 65188, 5424, 505, 7710, 11, 5788, 323, 4363, 25700, 2349, 570, 8121, 46217, 7710, 5938, 449, 36581, 323, 14098, 15652, 44072, 220, 1927, 4, 315, 3691, 1474, 3742, 20748, 2345, 60301, 11157, 279, 3392, 315, 37647, 45612, 6004, 2391, 872, 5788, 13, 2057, 50460, 279, 12434, 5536, 315, 3691, 11, 264, 6541, 7119, 6136, 6108, 15657, 2011, 387, 34356, 449, 810, 24392, 9124, 3673, 11, 14918, 304, 81879, 5961, 13, 4802, 8876, 220, 2550, 20, 11, 23442, 11295, 81069, 11, 15603, 29149, 323, 3691, 6696, 706, 810, 1109, 35717, 11, 19261, 2326, 3, 16, 13, 20, 32610, 304, 220, 679, 23, 220, 16, 662, 4514, 30154, 31207, 3691, 5825, 220, 777, 4, 315, 31550, 27073, 25247, 220, 17, 323, 8617, 11335, 459, 3062, 3560, 304, 32145, 3728, 3691, 4868, 220, 18, 1174, 220, 19, 1174, 220, 20, 1174, 220, 21, 662, 59200, 82, 304, 18386, 2853, 7293, 832, 315, 279, 1925, 10043, 8603, 6522, 311, 279, 11295, 6650, 315, 3691, 6696, 220, 16, 662, 578, 7434, 315, 3451, 14239, 1474, 3742, 529, 5097, 1139, 2759, 279, 6138, 46368, 555, 3691, 3956, 505, 3585, 315, 5788, 311, 15652, 11, 323, 374, 20034, 520, 19392, 279, 5938, 12434, 5536, 320, 2000, 3187, 11, 4907, 1005, 11, 20748, 8, 220, 22, 662, 3451, 27844, 1474, 3742, 529, 527, 8965, 17303, 439, 8941, 818, 12934, 321, 4512, 417, 320, 6375, 76, 11, 264, 5089, 369, 30090, 46217, 7710, 11, 14393, 279, 7710, 315, 220, 16, 259, 315, 11822, 555, 264, 2728, 7710, 3941, 927, 264, 6138, 315, 220, 16, 13437, 705, 430, 374, 11, 279, 6138, 46368, 304, 52957, 56016, 555, 279, 3148, 304, 52021, 369, 1855, 40460, 3691, 1537, 220, 23, 662, 22208, 43972, 41300, 315, 3691, 1474, 3742, 617, 6118, 1027, 7347, 311, 4183, 3691, 51967, 320, 2000, 3187, 11, 42120, 597, 91997, 304, 24067, 220, 24, 1174, 64114, 42120, 220, 605, 304, 15704, 11, 25309, 220, 806, 323, 34153, 220, 717, 304, 279, 3723, 4273, 11, 323, 1913, 18668, 304, 11104, 8494, 220, 1032, 883, 4245, 311, 279, 3544, 3392, 315, 828, 2631, 311, 1646, 682, 3691, 11306, 13, 763, 1521, 6484, 7978, 11, 2027, 2324, 78790, 15813, 320, 43, 5158, 8, 374, 42817, 1511, 311, 3839, 12434, 5178, 6957, 279, 4553, 2324, 11008, 315, 3691, 51967, 2949, 264, 64162, 19254, 11, 13239, 304, 264, 7029, 2134, 315, 12434, 5536, 17989, 11, 449, 7710, 14393, 1990, 220, 15, 13, 2371, 4, 323, 220, 1954, 4, 315, 5788, 14228, 20748, 220, 24, 1174, 220, 605, 1174, 220, 806, 1174, 220, 717, 1174, 220, 1032, 662, 10541, 1778, 5740, 5352, 445, 5158, 7978, 2997, 11944, 2038, 389, 3230, 3691, 3956, 11, 814, 617, 9669, 25, 320, 16, 8, 445, 5158, 7612, 27409, 264, 1887, 19254, 11, 323, 8617, 47521, 505, 63950, 367, 6103, 4245, 311, 279, 84218, 315, 19564, 7953, 430, 19254, 220, 975, 323, 11, 52394, 11, 320, 17, 8, 36595, 1990, 7978, 527, 3629, 539, 3284, 1606, 315, 12062, 304, 7036, 11, 323, 320, 18, 8, 279, 5357, 315, 1521, 7978, 389, 264, 2678, 13651, 315, 279, 2860, 3691, 8312, 3727, 433, 5107, 311, 43530, 810, 4689, 31342, 922, 279, 8244, 3691, 10706, 220, 868, 662, 362, 2478, 29060, 617, 1027, 11953, 704, 369, 3691, 20972, 520, 279, 5426, 320, 2000, 3187, 11, 279, 3723, 15422, 220, 845, 1174, 7008, 220, 1114, 1174, 18157, 220, 972, 323, 10471, 220, 777, 7026, 3363, 220, 508, 323, 3728, 220, 1691, 1174, 220, 1313, 5990, 13, 7648, 315, 1521, 7978, 1193, 6782, 3691, 1474, 3742, 20748, 13239, 505, 2167, 3691, 20972, 2085, 13126, 4553, 42830, 8312, 27271, 220, 845, 1174, 220, 1114, 1174, 220, 972, 1174, 220, 777, 1174, 220, 508, 1174, 220, 1691, 1174, 220, 1313, 1174, 17780, 10831, 220, 15, 13, 5547, 4235, 18, 13, 19, 4, 320, 16541, 13, 220, 845, 1174, 220, 1114, 1174, 220, 972, 1174, 220, 777, 883, 315, 5426, 323, 220, 15, 13, 23, 4235, 16, 13, 21, 4, 320, 16541, 13, 220, 508, 1174, 220, 1691, 1174, 220, 1313, 883, 320, 15, 13, 19, 4235, 15, 13, 4218, 480, 83, 8445, 220, 17, 384, 8, 315, 3728, 37647, 6962, 320, 45776, 38, 8, 20748, 311, 3691, 7710, 320, 4151, 99371, 18559, 323, 99371, 19331, 369, 264, 11944, 17649, 3477, 570, 2057, 32194, 11, 8051, 12782, 20748, 5938, 449, 3691, 5788, 527, 1664, 27470, 220, 1419, 1174, 220, 1187, 1174, 279, 12782, 43972, 315, 279, 3728, 6696, 315, 3691, 11, 24043, 369, 279, 4553, 3691, 8312, 8957, 11, 706, 539, 1027, 12963, 28014, 10484, 1908, 13, 5810, 584, 3493, 264, 16195, 3728, 16430, 315, 279, 12782, 43972, 315, 3728, 3691, 1474, 3742, 13, 1226, 1176, 9616, 3691, 1474, 3742, 20748, 449, 279, 2860, 3691, 37748, 20748, 320, 65188, 5424, 505, 7710, 11, 5788, 323, 4363, 25700, 2349, 570, 12369, 1474, 3742, 20748, 527, 14592, 1555, 459, 7447, 61779, 1988, 4235, 3081, 320, 18953, 3895, 8, 1646, 430, 75762, 7106, 18386, 6138, 11, 3148, 11, 20362, 323, 20748, 37929, 1139, 3728, 8312, 27271, 320, 99371, 18559, 323, 99371, 19331, 7609, 578, 2860, 3691, 37748, 20748, 32172, 3691, 1474, 3742, 20748, 11, 3691, 5788, 323, 4363, 25700, 2349, 20748, 11, 1405, 279, 5788, 20748, 527, 13240, 3196, 389, 264, 5410, 29433, 3895, 6108, 12782, 43972, 22702, 1749, 430, 374, 13882, 1511, 304, 1579, 12, 58400, 43972, 7978, 1778, 439, 389, 73119, 220, 914, 1174, 47503, 20748, 220, 1627, 323, 12782, 20748, 505, 3728, 32083, 220, 1544, 320, 99371, 18559, 323, 99371, 19331, 7609, 1226, 4726, 3118, 25, 320, 16, 8, 3691, 1474, 3742, 6530, 14370, 18702, 279, 4553, 3728, 8312, 66286, 4009, 11, 323, 320, 17, 8, 13018, 323, 6625, 3691, 1474, 3742, 323, 20748, 11102, 1523, 555, 220, 5728, 5961, 14, 58808, 11, 220, 1806, 7100, 26593, 323, 3116, 18386, 20362, 320, 19, 25800, 220, 5728, 220, 17, 25800, 220, 1806, 220, 17, 118792, 220, 966, 3610, 2167, 6696, 13537, 570, 1226, 9616, 3691, 1474, 3742, 323, 20748, 505, 2225, 9284, 323, 6371, 39555, 4028, 682, 6625, 6696, 11543, 311, 8881, 279, 12014, 65162, 555, 1179, 388, 323, 75948, 13, 1226, 1101, 20461, 1057, 1749, 5848, 31003, 304, 264, 12593, 449, 44899, 3691, 1474, 3742, 20414, 13, 5751, 31342, 369, 13241, 3691, 6067, 6373, 11415, 279, 1205, 369, 459, 18751, 8446, 311, 3691, 4868, 323, 4676, 9313, 13, 19331, 527, 69729, 520, 279, 842, 11, 449, 4726, 3649, 304, 99371, 18559, 323, 99371, 19331, 662, 18591, 323, 10430, 1952, 279, 1203, 315, 3728, 3691, 45426, 315, 2212, 2326, 3, 20, 32610, 304, 220, 679, 22, 11, 584, 16430, 430, 279, 3728, 3691, 1887, 320, 80095, 4363, 1005, 323, 4363, 25700, 2349, 7640, 8, 574, 5938, 449, 220, 868, 13, 23, 480, 83, 8445, 220, 17, 384, 320, 27543, 315, 220, 18, 13, 15, 480, 83, 11, 5788, 315, 220, 22, 13, 16, 480, 83, 323, 4363, 25700, 2349, 7640, 315, 220, 20, 13, 22, 480, 83, 8, 220, 1313, 320, 30035, 13, 220, 16, 272, 705, 14393, 922, 220, 966, 4, 315, 279, 1917, 753, 48584, 38, 20748, 320, 4103, 13, 20, 480, 83, 1237, 220, 1591, 420, 374, 304, 1584, 449, 3766, 17989, 315, 220, 1691, 4235, 1806, 4, 320, 1116, 13, 220, 1419, 7609, 8121, 3691, 6696, 374, 10671, 15098, 85957, 323, 6485, 13, 5751, 128257, 198, 128256, 78191, 198, 644, 220, 1049, 22, 11, 364, 1092, 402, 461, 6, 2345, 64, 1732, 889, 1193, 50777, 3691, 15042, 477, 9124, 2949, 264, 220, 1041, 43276, 320, 10718, 16400, 8, 10801, 2345, 16514, 279, 26275, 9506, 315, 279, 9941, 13, 4800, 11, 220, 868, 1667, 3010, 11, 3907, 315, 21972, 12074, 33147, 433, 311, 9327, 3131, 810, 13, 2435, 617, 1766, 430, 220, 777, 3346, 315, 3728, 3691, 1887, 37647, 6962, 20748, 527, 9057, 555, 18386, 13, 1115, 374, 709, 311, 8254, 3115, 5190, 1109, 8767, 13240, 11, 323, 3117, 36375, 279, 7710, 20748, 315, 1023, 51967, 13, 1789, 3187, 11, 7710, 9815, 369, 1193, 8254, 3346, 315, 5064, 323, 30519, 20748, 13, 578, 12074, 2019, 430, 5423, 4315, 81879, 5961, 11, 279, 8706, 3691, 7710, 991, 29163, 824, 53155, 11, 12459, 24392, 15042, 323, 9124, 3691, 1288, 387, 264, 10844, 13, 2999, 13, 61154, 41101, 14851, 505, 279, 3907, 315, 21972, 6150, 315, 28415, 374, 279, 3063, 3229, 315, 279, 4007, 11, 311, 387, 4756, 304, 22037, 12369, 13, 3005, 1071, 25, 330, 8140, 4007, 17989, 3728, 3691, 6067, 11, 4245, 311, 7710, 11, 5788, 11, 323, 4363, 1005, 2349, 11, 17210, 922, 220, 966, 3346, 315, 2860, 3823, 84561, 37647, 6962, 20748, 13, 2100, 11, 3691, 7710, 99563, 2212, 4848, 3346, 55434, 264, 1404, 481, 21801, 315, 8244, 20748, 13, 330, 27844, 7710, 20748, 923, 709, 311, 7154, 4376, 315, 2167, 20748, 505, 5754, 11731, 1210, 18878, 37842, 12208, 16549, 323, 1080, 43802, 11, 17054, 6941, 18989, 77067, 35180, 11, 1071, 25, 330, 50571, 311, 1057, 4007, 11, 1455, 315, 279, 6666, 304, 22556, 3691, 3495, 706, 1027, 389, 279, 1579, 20748, 5938, 449, 10065, 72286, 15657, 11, 7863, 449, 11012, 13, 330, 8140, 4007, 5039, 430, 304, 5369, 311, 32931, 7119, 264, 6136, 6108, 10173, 11, 12459, 24392, 374, 10728, 11, 5423, 304, 81879, 5961, 3343, 8269, 5961, 87146, 17210, 12362, 872, 1866, 12914, 2663, 12369, 30146, 11, 279, 12074, 16997, 430, 3691, 7710, 34310, 311, 922, 220, 18, 23401, 24444, 4978, 315, 20748, 30171, 2345, 26378, 12031, 311, 220, 777, 3346, 315, 3691, 14228, 20748, 13, 11205, 6492, 52924, 220, 5728, 5961, 320, 8781, 323, 9284, 1237, 220, 1806, 7100, 26593, 320, 21470, 439, 24822, 323, 14098, 26, 51876, 26, 11756, 26, 323, 15266, 1237, 6625, 323, 13018, 7710, 27650, 26, 323, 3691, 32738, 13, 6104, 5734, 11, 279, 3723, 4273, 11, 6890, 11, 323, 8524, 527, 279, 1948, 3691, 7710, 991, 29163, 11, 8244, 11, 1579, 32197, 5961, 527, 80153, 20965, 13, 54837, 1778, 439, 279, 3723, 4273, 11, 10057, 11, 9822, 11, 323, 6457, 35256, 220, 717, 13, 20, 3346, 315, 279, 1917, 596, 7187, 3686, 7068, 7154, 4376, 320, 2790, 3346, 8, 315, 3691, 7710, 20748, 13, 26379, 315, 8312, 27271, 71681, 304, 2579, 13339, 15652, 555, 29939, 304, 5734, 13, 16741, 645, 4097, 3691, 5788, 20748, 26, 38057, 4097, 7710, 20748, 13, 16666, 25, 61154, 41101, 14851, 14, 31272, 315, 21972, 13, 8494, 374, 279, 2132, 7928, 58478, 315, 3691, 7710, 20748, 11, 2728, 279, 58321, 323, 8286, 315, 1202, 6156, 5788, 13, 17159, 20748, 527, 1101, 3691, 955, 18222, 13, 3161, 14098, 323, 24822, 11, 369, 3187, 11, 7710, 27983, 7154, 2033, 279, 1396, 315, 20748, 1109, 5788, 13, 44187, 323, 24822, 3871, 35256, 927, 264, 4948, 315, 3691, 7710, 20748, 13, 330, 12834, 24822, 323, 14098, 1397, 9499, 41370, 18386, 11, 872, 3691, 8931, 20748, 527, 5190, 1359, 2999, 13, 14851, 1071, 13, 578, 1353, 402, 461, 11336, 578, 12074, 16997, 279, 14278, 304, 20748, 422, 279, 3728, 7187, 30912, 1193, 24392, 25, 220, 15, 13, 1987, 23401, 24444, 4978, 11, 13890, 311, 20748, 505, 10043, 832, 8941, 818, 311, 279, 8219, 323, 1203, 11, 220, 21, 11, 931, 3115, 13, 18056, 814, 25670, 420, 15398, 374, 539, 26569, 11, 369, 3187, 11, 1606, 1690, 13918, 4250, 387, 659, 1355, 27781, 304, 3691, 8312, 11, 433, 1436, 387, 11798, 311, 29865, 12628, 13, 330, 2520, 3187, 11, 1070, 374, 24779, 4754, 369, 62257, 12, 60159, 30029, 311, 46798, 819, 16036, 11062, 1359, 1080, 43802, 17054, 2418, 29093, 25234, 5797, 1071, 13, 1115, 16038, 11, 59774, 5961, 649, 8108, 872, 3691, 7710, 20748, 1555, 5370, 24717, 13, 4314, 2997, 26012, 304, 32981, 4907, 8336, 369, 11731, 11, 323, 84084, 3876, 3691, 9873, 311, 1005, 2753, 20748, 88092, 5788, 323, 8141, 5528, 11, 1778, 439, 5933, 30477, 1821, 13, 330, 21279, 15167, 323, 17047, 649, 1520, 555, 6968, 22484, 430, 31087, 22556, 3691, 8312, 1359, 17054, 25234, 5797, 1071, 13, 14968, 8312, 374, 16625, 555, 7631, 2345, 57865, 279, 11761, 706, 279, 17139, 2410, 311, 2349, 420, 6671, 13, 330, 60146, 13723, 6, 33726, 323, 7865, 7119, 22556, 41943, 649, 58003, 12434, 7720, 389, 279, 6800, 478, 5569, 1359, 3779, 17054, 18989, 77067, 35180, 13, 330, 4054, 3187, 374, 279, 14464, 315, 13723, 304, 81879, 5961, 26192, 653, 17217, 278, 15657, 1060, 21691, 11, 902, 1205, 311, 387, 40460, 505, 18403, 13, 330, 36, 1113, 2254, 36899, 27548, 11, 439, 584, 617, 6957, 1455, 315, 279, 3925, 315, 1057, 9606, 11, 690, 1520, 3493, 264, 9498, 11841, 369, 3938, 22540, 1210, 220, 128257, 198 ]

2,228

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract From the masses of the planets orbiting the Sun, and the abundance of elements relative to hydrogen, it is estimated that when the Solar System formed, the circumstellar disk must have had a minimum mass of around 0.01 solar masses within about 100 astronomical units of the star 1 , 2 , 3 , 4 . (One astronomical unit is the Earth–Sun distance.) The main constituent of the disk, gaseous molecular hydrogen, does not efficiently emit radiation from the disk mass reservoir 5 , and so the most common measure of the disk mass is dust thermal emission and lines of gaseous carbon monoxide 6 . Carbon monoxide emission generally indicates properties of the disk surface, and the conversion from dust emission to gas mass requires knowledge of the grain properties and the gas-to-dust mass ratio, which probably differ from their interstellar values 7 , 8 . As a result, mass estimates vary by orders of magnitude, as exemplified by the relatively old (3–10 million years) star TW Hydrae 9 , 10 , for which the range is 0.0005–0.06 solar masses 11 , 12 , 13 , 14 . Here we report the detection of the fundamental rotational transition of hydrogen deuteride from the direction of TW Hydrae. Hydrogen deuteride is a good tracer of disk gas because it follows the distribution of molecular hydrogen and its emission is sensitive to the total mass. The detection of hydrogen deuteride, combined with existing observations and detailed models, implies a disk mass of more than 0.05 solar masses, which is enough to form a planetary system like our own. Main Commonly used tracers of protoplanetary disk masses are thermal emission from dust grains and rotational lines of carbon monoxide (CO) gas. However, the methods by which these are detected rely on unconstrained assumptions. The dust detection method has to assume an opacity per gram of dust, and grain growth can change this value drastically 15 . The gas mass is then calculated by multiplying the dust mass by the gas-to-dust ratio, which is usually assumed to be ∼ 100 from measurements of the interstellar medium 16 . The gas mass thus depends on a large and uncertain correction factor. The alternative is to use rotational CO lines as gas tracers, but their emission is optically thick and therefore trace the disk surface temperature rather than the midplane mass. The use of CO as a gas tracer thus leads to large discrepancies between mass estimates for different models of TW Hya (from to , where is the solar mass), even though each matches a similar set of observations 13 , 14 . Using the Herschel Space Observatory 17 Photodetector Array Camera and Spectrometer 18 , we robustly detected (9 σ ) the lowest rotational transition, J = 1 → 0, of hydrogen deuteride (HD) in the closest ( D ≈ 55 pc) and best-studied circumstellar disk around TW Hya ( Fig. 1 ). This star is older (3–10 Myr; refs 9 , 10 , 19 ) than most stars with gas-rich circumstellar disks 8 . The abundance of deuterium atoms relative to hydrogen is well characterized, via atomic electronic transitions, to be x D = (1.5 ± 0.1) × 10 −5 in objects that reside within ∼ 100 pc of the Sun 20 . Adding a hydrogen atom to each, to form H 2 and HD, which is appropriate for much of the disk mass, provides an HD abundance relative to H 2 of x HD = 3.0 × 10 −5 . We combine the HD data with existing molecular observations to set new constraints on the disk mass within 100 au , which is the most fundamental quantity that determines whether planets can form. The disk mass also governs the primary mode of giant-planet formation, either through core accretion or gravitational instability 21 . In this context, we do not know whether the Solar System formed within a typical disk, because nearly half of the present estimates of extrasolar disk masses are less than the minimum solar nebula mass 8 . Our current census of extrasolar planetary systems furthermore suggests that even larger disk masses are necessary to form many of the exoplanetary systems seen 22 , 23 . Figure 1: Herschel detection of HD in the TW Hya protoplanetary disk. a , The fundamental J = 1 → 0 line of HD lies at ∼ 112 μm. On 20 November 2011, it was detected from the direction of the TW Hya disk at the 9 σ level. The total integrated flux is (6.3 ± 0.7) × 10 −18 W m −2 . We also report a detection of the warm disk atmosphere in CO J = 23 → 22 with a total integrated flux of (4.4 ± 0.7) × 10 −18 W m −2 . The J = 1 → 0 line of HD was previously detected by the Infrared Space Observatory in a warm gas cloud exposed to radiation from nearby stars 27 . Other transitions have also been detected in shocked regions associated with supernovae and outflows from massive stars 28 , 29 . b , Simultaneous observations of HD J = 2 → 1 are shown. For HD J = 2 → 1, we find a detection limit of <8.0 × 10 −18 W m −2 (3 σ ). We also report a detection of the OH 2 Π 1/2 9/2 → 7/2 doublet near 55.94 μm with an integrated flux of (4.93 ± 0.27) × 10 −17 W m −2 . The spectra include the observed thermal dust continuum of ∼ 3.55 Jy at both wavelengths. PowerPoint slide Full size image With smaller rotational energy spacings and a weak electric dipole moment, HD J = 1 → 0 is one million times more emissive than H 2 for a given gas mass at a gas temperature of T gas = 20 K. The HD line flux ( F l ) sets a lower limit to the", "role": "user" }, { "content": "(Phys.org)—A star thought to have passed the age at which it can form planets may, in fact, be creating new worlds. The disk of material surrounding the surprising star called TW Hydrae may be massive enough to make even more planets than we have in our own solar system. The findings were made using the European Space Agency's Herschel Space Telescope, a mission in which NASA is a participant. At roughly 10 million years old and 176 light years away, TW Hydrae is relatively close to Earth by astronomical standards. Its planet-forming disk has been well studied. TW Hydrae is relatively young but, in theory, it is past the age at which giant plants already may have formed. \"We didn't expect to see so much gas around this star,\" said Edwin Bergin of the University of Michigan in Ann Arbor. Bergin led the new study appearing in the journal Nature. \"Typically stars of this age have cleared out their surrounding material, but this star still has enough mass to make the equivalent of 50 Jupiters,\" Bergin said. In addition to revealing the peculiar state of the star, the findings also demonstrate a new, more precise method for weighing planet-forming disks. Previous techniques for assessing the mass were indirect and uncertain. The new method can directly probe the gas that typically goes into making planets. Planets are born out of material swirling around young stars, and the mass of this material is a key factor controlling their formation. Astronomers did not know before the new study whether the disk around TW Hydrae contained enough material to form new planets similar to our own. This artist's concept illustrates the planet-forming disk around TW Hydrae, located about 175 light-years away in the Hydra, or Sea Serpent, constellation. In 2011, astronomers used the Herschel space observatory to detect copious amounts of cool water vapor, illustrated in blue, emanating from the star's planet-forming disk of dust and gas. Credit: NASA/JPL-Caltech \"Before, we had to use a proxy to guess the gas quantity in the planet-forming disks,\" said Paul Goldsmith, the NASA project scientist for Herschel at NASA's Jet Propulsion Laboratory in Pasadena, Calif. \"This is another example of Herschel's versatility and sensitivity yielding important new results about star and planet formation.\" Using Herschel, scientists were able to take a fresh look at the disk with the space telescope to analyze light coming from TW Hydrae and pick out the spectral signature of a gas called hydrogen deuteride. Simple hydrogen molecules are the main gas component of planets, but they emit light at wavelengths too short to be detected by Herschel. Gas molecules containing deuterium, a heavier version of hydrogen, emit light at longer, far-infrared wavelengths that Herschel is equipped to see. This enabled astronomers to measure the levels of hydrogen deuteride and obtain the weight of the disk with the highest precision yet. \"Knowing the mass of a planet-forming disk is crucial to understanding how and when planets take shape around other stars,\" said Glenn Wahlgren, Herschel program scientist at NASA Headquarters in Washington. Whether TW Hydrae's large disk will lead to an exotic planetary system with larger and more numerous planets than ours remains to be seen, but the new information helps define the range of possible planet scenarios. \"The new results are another important step in understanding the diversity of planetary systems in our universe,\" said Bergin. \"We are now observing systems with massive Jupiters, super-Earths, and many Neptune-like worlds. By weighing systems at their birth, we gain insight into how our own solar system formed with just one of many possible planetary configurations.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract From the masses of the planets orbiting the Sun, and the abundance of elements relative to hydrogen, it is estimated that when the Solar System formed, the circumstellar disk must have had a minimum mass of around 0.01 solar masses within about 100 astronomical units of the star 1 , 2 , 3 , 4 . (One astronomical unit is the Earth–Sun distance.) The main constituent of the disk, gaseous molecular hydrogen, does not efficiently emit radiation from the disk mass reservoir 5 , and so the most common measure of the disk mass is dust thermal emission and lines of gaseous carbon monoxide 6 . Carbon monoxide emission generally indicates properties of the disk surface, and the conversion from dust emission to gas mass requires knowledge of the grain properties and the gas-to-dust mass ratio, which probably differ from their interstellar values 7 , 8 . As a result, mass estimates vary by orders of magnitude, as exemplified by the relatively old (3–10 million years) star TW Hydrae 9 , 10 , for which the range is 0.0005–0.06 solar masses 11 , 12 , 13 , 14 . Here we report the detection of the fundamental rotational transition of hydrogen deuteride from the direction of TW Hydrae. Hydrogen deuteride is a good tracer of disk gas because it follows the distribution of molecular hydrogen and its emission is sensitive to the total mass. The detection of hydrogen deuteride, combined with existing observations and detailed models, implies a disk mass of more than 0.05 solar masses, which is enough to form a planetary system like our own. Main Commonly used tracers of protoplanetary disk masses are thermal emission from dust grains and rotational lines of carbon monoxide (CO) gas. However, the methods by which these are detected rely on unconstrained assumptions. The dust detection method has to assume an opacity per gram of dust, and grain growth can change this value drastically 15 . The gas mass is then calculated by multiplying the dust mass by the gas-to-dust ratio, which is usually assumed to be ∼ 100 from measurements of the interstellar medium 16 . The gas mass thus depends on a large and uncertain correction factor. The alternative is to use rotational CO lines as gas tracers, but their emission is optically thick and therefore trace the disk surface temperature rather than the midplane mass. The use of CO as a gas tracer thus leads to large discrepancies between mass estimates for different models of TW Hya (from to , where is the solar mass), even though each matches a similar set of observations 13 , 14 . Using the Herschel Space Observatory 17 Photodetector Array Camera and Spectrometer 18 , we robustly detected (9 σ ) the lowest rotational transition, J = 1 → 0, of hydrogen deuteride (HD) in the closest ( D ≈ 55 pc) and best-studied circumstellar disk around TW Hya ( Fig. 1 ). This star is older (3–10 Myr; refs 9 , 10 , 19 ) than most stars with gas-rich circumstellar disks 8 . The abundance of deuterium atoms relative to hydrogen is well characterized, via atomic electronic transitions, to be x D = (1.5 ± 0.1) × 10 −5 in objects that reside within ∼ 100 pc of the Sun 20 . Adding a hydrogen atom to each, to form H 2 and HD, which is appropriate for much of the disk mass, provides an HD abundance relative to H 2 of x HD = 3.0 × 10 −5 . We combine the HD data with existing molecular observations to set new constraints on the disk mass within 100 au , which is the most fundamental quantity that determines whether planets can form. The disk mass also governs the primary mode of giant-planet formation, either through core accretion or gravitational instability 21 . In this context, we do not know whether the Solar System formed within a typical disk, because nearly half of the present estimates of extrasolar disk masses are less than the minimum solar nebula mass 8 . Our current census of extrasolar planetary systems furthermore suggests that even larger disk masses are necessary to form many of the exoplanetary systems seen 22 , 23 . Figure 1: Herschel detection of HD in the TW Hya protoplanetary disk. a , The fundamental J = 1 → 0 line of HD lies at ∼ 112 μm. On 20 November 2011, it was detected from the direction of the TW Hya disk at the 9 σ level. The total integrated flux is (6.3 ± 0.7) × 10 −18 W m −2 . We also report a detection of the warm disk atmosphere in CO J = 23 → 22 with a total integrated flux of (4.4 ± 0.7) × 10 −18 W m −2 . The J = 1 → 0 line of HD was previously detected by the Infrared Space Observatory in a warm gas cloud exposed to radiation from nearby stars 27 . Other transitions have also been detected in shocked regions associated with supernovae and outflows from massive stars 28 , 29 . b , Simultaneous observations of HD J = 2 → 1 are shown. For HD J = 2 → 1, we find a detection limit of <8.0 × 10 −18 W m −2 (3 σ ). We also report a detection of the OH 2 Π 1/2 9/2 → 7/2 doublet near 55.94 μm with an integrated flux of (4.93 ± 0.27) × 10 −17 W m −2 . The spectra include the observed thermal dust continuum of ∼ 3.55 Jy at both wavelengths. PowerPoint slide Full size image With smaller rotational energy spacings and a weak electric dipole moment, HD J = 1 → 0 is one million times more emissive than H 2 for a given gas mass at a gas temperature of T gas = 20 K. The HD line flux ( F l ) sets a lower limit to the<|im_end|> <|im_start|>assistant (Phys.org)—A star thought to have passed the age at which it can form planets may, in fact, be creating new worlds. The disk of material surrounding the surprising star called TW Hydrae may be massive enough to make even more planets than we have in our own solar system. The findings were made using the European Space Agency's Herschel Space Telescope, a mission in which NASA is a participant. At roughly 10 million years old and 176 light years away, TW Hydrae is relatively close to Earth by astronomical standards. Its planet-forming disk has been well studied. TW Hydrae is relatively young but, in theory, it is past the age at which giant plants already may have formed. "We didn't expect to see so much gas around this star," said Edwin Bergin of the University of Michigan in Ann Arbor. Bergin led the new study appearing in the journal Nature. "Typically stars of this age have cleared out their surrounding material, but this star still has enough mass to make the equivalent of 50 Jupiters," Bergin said. In addition to revealing the peculiar state of the star, the findings also demonstrate a new, more precise method for weighing planet-forming disks. Previous techniques for assessing the mass were indirect and uncertain. The new method can directly probe the gas that typically goes into making planets. Planets are born out of material swirling around young stars, and the mass of this material is a key factor controlling their formation. Astronomers did not know before the new study whether the disk around TW Hydrae contained enough material to form new planets similar to our own. This artist's concept illustrates the planet-forming disk around TW Hydrae, located about 175 light-years away in the Hydra, or Sea Serpent, constellation. In 2011, astronomers used the Herschel space observatory to detect copious amounts of cool water vapor, illustrated in blue, emanating from the star's planet-forming disk of dust and gas. Credit: NASA/JPL-Caltech "Before, we had to use a proxy to guess the gas quantity in the planet-forming disks," said Paul Goldsmith, the NASA project scientist for Herschel at NASA's Jet Propulsion Laboratory in Pasadena, Calif. "This is another example of Herschel's versatility and sensitivity yielding important new results about star and planet formation." Using Herschel, scientists were able to take a fresh look at the disk with the space telescope to analyze light coming from TW Hydrae and pick out the spectral signature of a gas called hydrogen deuteride. Simple hydrogen molecules are the main gas component of planets, but they emit light at wavelengths too short to be detected by Herschel. Gas molecules containing deuterium, a heavier version of hydrogen, emit light at longer, far-infrared wavelengths that Herschel is equipped to see. This enabled astronomers to measure the levels of hydrogen deuteride and obtain the weight of the disk with the highest precision yet. "Knowing the mass of a planet-forming disk is crucial to understanding how and when planets take shape around other stars," said Glenn Wahlgren, Herschel program scientist at NASA Headquarters in Washington. Whether TW Hydrae's large disk will lead to an exotic planetary system with larger and more numerous planets than ours remains to be seen, but the new information helps define the range of possible planet scenarios. "The new results are another important step in understanding the diversity of planetary systems in our universe," said Bergin. "We are now observing systems with massive Jupiters, super-Earths, and many Neptune-like worlds. By weighing systems at their birth, we gain insight into how our own solar system formed with just one of many possible planetary configurations." <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 5659, 279, 32738, 315, 279, 33975, 27605, 287, 279, 8219, 11, 323, 279, 37492, 315, 5540, 8844, 311, 35784, 11, 433, 374, 13240, 430, 994, 279, 25450, 744, 14454, 11, 279, 10408, 78393, 13668, 2011, 617, 1047, 264, 8187, 3148, 315, 2212, 220, 15, 13, 1721, 13238, 32738, 2949, 922, 220, 1041, 87283, 8316, 315, 279, 6917, 220, 16, 1174, 220, 17, 1174, 220, 18, 1174, 220, 19, 662, 320, 4054, 87283, 5089, 374, 279, 9420, 4235, 31192, 6138, 6266, 578, 1925, 75164, 315, 279, 13668, 11, 342, 521, 788, 31206, 35784, 11, 1587, 539, 30820, 17105, 25407, 505, 279, 13668, 3148, 45512, 220, 20, 1174, 323, 779, 279, 1455, 4279, 6767, 315, 279, 13668, 3148, 374, 16174, 29487, 41353, 323, 5238, 315, 342, 521, 788, 12782, 1647, 55189, 220, 21, 662, 22208, 1647, 55189, 41353, 8965, 15151, 6012, 315, 279, 13668, 7479, 11, 323, 279, 14747, 505, 16174, 41353, 311, 6962, 3148, 7612, 6677, 315, 279, 24875, 6012, 323, 279, 6962, 4791, 1773, 592, 3148, 11595, 11, 902, 4762, 1782, 505, 872, 958, 78393, 2819, 220, 22, 1174, 220, 23, 662, 1666, 264, 1121, 11, 3148, 17989, 13592, 555, 10373, 315, 26703, 11, 439, 39039, 1908, 555, 279, 12309, 2362, 320, 18, 4235, 605, 3610, 1667, 8, 6917, 36655, 87961, 68, 220, 24, 1174, 220, 605, 1174, 369, 902, 279, 2134, 374, 220, 15, 13, 931, 20, 4235, 15, 13, 2705, 13238, 32738, 220, 806, 1174, 220, 717, 1174, 220, 1032, 1174, 220, 975, 662, 5810, 584, 1934, 279, 18468, 315, 279, 16188, 92371, 9320, 315, 35784, 409, 29051, 579, 505, 279, 5216, 315, 36655, 87961, 68, 13, 40602, 4469, 409, 29051, 579, 374, 264, 1695, 65406, 315, 13668, 6962, 1606, 433, 11263, 279, 8141, 315, 31206, 35784, 323, 1202, 41353, 374, 16614, 311, 279, 2860, 3148, 13, 578, 18468, 315, 35784, 409, 29051, 579, 11, 11093, 449, 6484, 24654, 323, 11944, 4211, 11, 24897, 264, 13668, 3148, 315, 810, 1109, 220, 15, 13, 2304, 13238, 32738, 11, 902, 374, 3403, 311, 1376, 264, 62938, 1887, 1093, 1057, 1866, 13, 4802, 7874, 398, 1511, 490, 73797, 315, 1760, 94560, 16238, 13668, 32738, 527, 29487, 41353, 505, 16174, 41936, 323, 92371, 5238, 315, 12782, 1647, 55189, 320, 8445, 8, 6962, 13, 4452, 11, 279, 5528, 555, 902, 1521, 527, 16914, 17631, 389, 26118, 58827, 32946, 13, 578, 16174, 18468, 1749, 706, 311, 9855, 459, 19172, 824, 23882, 315, 16174, 11, 323, 24875, 6650, 649, 2349, 420, 907, 48863, 220, 868, 662, 578, 6962, 3148, 374, 1243, 16997, 555, 85292, 279, 16174, 3148, 555, 279, 6962, 4791, 1773, 592, 11595, 11, 902, 374, 6118, 19655, 311, 387, 12264, 120, 220, 1041, 505, 22323, 315, 279, 958, 78393, 11298, 220, 845, 662, 578, 6962, 3148, 8617, 14117, 389, 264, 3544, 323, 36218, 27358, 8331, 13, 578, 10778, 374, 311, 1005, 92371, 7432, 5238, 439, 6962, 490, 73797, 11, 719, 872, 41353, 374, 3469, 2740, 12314, 323, 9093, 11917, 279, 13668, 7479, 9499, 4856, 1109, 279, 5209, 19563, 3148, 13, 578, 1005, 315, 7432, 439, 264, 6962, 65406, 8617, 11767, 311, 3544, 91367, 1990, 3148, 17989, 369, 2204, 4211, 315, 36655, 473, 7911, 320, 1527, 311, 1174, 1405, 374, 279, 13238, 3148, 705, 1524, 3582, 1855, 9248, 264, 4528, 743, 315, 24654, 220, 1032, 1174, 220, 975, 662, 12362, 279, 65466, 331, 301, 11746, 58974, 220, 1114, 18235, 347, 295, 1279, 2982, 14669, 323, 27726, 88371, 220, 972, 1174, 584, 22514, 398, 16914, 320, 24, 48823, 883, 279, 15821, 92371, 9320, 11, 622, 284, 220, 16, 11651, 220, 15, 11, 315, 35784, 409, 29051, 579, 320, 19694, 8, 304, 279, 18585, 320, 423, 118792, 220, 2131, 13615, 8, 323, 1888, 5594, 664, 1142, 10408, 78393, 13668, 2212, 36655, 473, 7911, 320, 23966, 13, 220, 16, 7609, 1115, 6917, 374, 9191, 320, 18, 4235, 605, 3092, 81, 26, 44243, 220, 24, 1174, 220, 605, 1174, 220, 777, 883, 1109, 1455, 9958, 449, 6962, 41947, 10408, 78393, 54858, 220, 23, 662, 578, 37492, 315, 409, 29051, 2411, 33299, 8844, 311, 35784, 374, 1664, 32971, 11, 4669, 25524, 14683, 34692, 11, 311, 387, 865, 423, 284, 320, 16, 13, 20, 20903, 220, 15, 13, 16, 8, 25800, 220, 605, 25173, 20, 304, 6302, 430, 48383, 2949, 12264, 120, 220, 1041, 13615, 315, 279, 8219, 220, 508, 662, 31470, 264, 35784, 19670, 311, 1855, 11, 311, 1376, 473, 220, 17, 323, 12445, 11, 902, 374, 8475, 369, 1790, 315, 279, 13668, 3148, 11, 5825, 459, 12445, 37492, 8844, 311, 473, 220, 17, 315, 865, 12445, 284, 220, 18, 13, 15, 25800, 220, 605, 25173, 20, 662, 1226, 16343, 279, 12445, 828, 449, 6484, 31206, 24654, 311, 743, 502, 17413, 389, 279, 13668, 3148, 2949, 220, 1041, 8065, 1174, 902, 374, 279, 1455, 16188, 12472, 430, 27667, 3508, 33975, 649, 1376, 13, 578, 13668, 3148, 1101, 2633, 82, 279, 6156, 3941, 315, 14880, 12, 51174, 18488, 11, 3060, 1555, 6332, 1046, 2171, 290, 477, 71019, 56399, 220, 1691, 662, 763, 420, 2317, 11, 584, 656, 539, 1440, 3508, 279, 25450, 744, 14454, 2949, 264, 14595, 13668, 11, 1606, 7154, 4376, 315, 279, 3118, 17989, 315, 37375, 7569, 13668, 32738, 527, 2753, 1109, 279, 8187, 13238, 81967, 5724, 3148, 220, 23, 662, 5751, 1510, 44702, 315, 37375, 7569, 62938, 6067, 78637, 13533, 430, 1524, 8294, 13668, 32738, 527, 5995, 311, 1376, 1690, 315, 279, 506, 94560, 16238, 6067, 3970, 220, 1313, 1174, 220, 1419, 662, 19575, 220, 16, 25, 65466, 331, 301, 18468, 315, 12445, 304, 279, 36655, 473, 7911, 1760, 94560, 16238, 13668, 13, 264, 1174, 578, 16188, 622, 284, 220, 16, 11651, 220, 15, 1584, 315, 12445, 15812, 520, 12264, 120, 220, 7261, 33983, 76, 13, 1952, 220, 508, 6841, 220, 679, 16, 11, 433, 574, 16914, 505, 279, 5216, 315, 279, 36655, 473, 7911, 13668, 520, 279, 220, 24, 48823, 2237, 13, 578, 2860, 18751, 31405, 374, 320, 21, 13, 18, 20903, 220, 15, 13, 22, 8, 25800, 220, 605, 25173, 972, 468, 296, 25173, 17, 662, 1226, 1101, 1934, 264, 18468, 315, 279, 8369, 13668, 16975, 304, 7432, 622, 284, 220, 1419, 11651, 220, 1313, 449, 264, 2860, 18751, 31405, 315, 320, 19, 13, 19, 20903, 220, 15, 13, 22, 8, 25800, 220, 605, 25173, 972, 468, 296, 25173, 17, 662, 578, 622, 284, 220, 16, 11651, 220, 15, 1584, 315, 12445, 574, 8767, 16914, 555, 279, 763, 82482, 11746, 58974, 304, 264, 8369, 6962, 9624, 15246, 311, 25407, 505, 14373, 9958, 220, 1544, 662, 7089, 34692, 617, 1101, 1027, 16914, 304, 27718, 13918, 5938, 449, 39887, 869, 6043, 323, 704, 39240, 505, 11191, 9958, 220, 1591, 1174, 220, 1682, 662, 293, 1174, 4567, 495, 18133, 24654, 315, 12445, 622, 284, 220, 17, 11651, 220, 16, 527, 6982, 13, 1789, 12445, 622, 284, 220, 17, 11651, 220, 16, 11, 584, 1505, 264, 18468, 4017, 315, 366, 23, 13, 15, 25800, 220, 605, 25173, 972, 468, 296, 25173, 17, 320, 18, 48823, 7609, 1226, 1101, 1934, 264, 18468, 315, 279, 29822, 220, 17, 100468, 220, 16, 14, 17, 220, 24, 14, 17, 11651, 220, 22, 14, 17, 2033, 83, 3221, 220, 2131, 13, 6281, 33983, 76, 449, 459, 18751, 31405, 315, 320, 19, 13, 6365, 20903, 220, 15, 13, 1544, 8, 25800, 220, 605, 25173, 1114, 468, 296, 25173, 17, 662, 578, 63697, 2997, 279, 13468, 29487, 16174, 86901, 315, 12264, 120, 220, 18, 13, 2131, 622, 88, 520, 2225, 93959, 13, 54600, 15332, 8797, 1404, 2217, 3161, 9333, 92371, 4907, 100108, 826, 323, 264, 7621, 9249, 24522, 1286, 4545, 11, 12445, 622, 284, 220, 16, 11651, 220, 15, 374, 832, 3610, 3115, 810, 99763, 535, 1109, 473, 220, 17, 369, 264, 2728, 6962, 3148, 520, 264, 6962, 9499, 315, 350, 6962, 284, 220, 508, 735, 13, 578, 12445, 1584, 31405, 320, 435, 326, 883, 7437, 264, 4827, 4017, 311, 279, 128257, 198, 128256, 78191, 198, 7, 67171, 2726, 68850, 32, 6917, 3463, 311, 617, 5946, 279, 4325, 520, 902, 433, 649, 1376, 33975, 1253, 11, 304, 2144, 11, 387, 6968, 502, 24800, 13, 578, 13668, 315, 3769, 14932, 279, 15206, 6917, 2663, 36655, 87961, 68, 1253, 387, 11191, 3403, 311, 1304, 1524, 810, 33975, 1109, 584, 617, 304, 1057, 1866, 13238, 1887, 13, 578, 14955, 1051, 1903, 1701, 279, 7665, 11746, 16784, 596, 65466, 331, 301, 11746, 87062, 11, 264, 9131, 304, 902, 22146, 374, 264, 25923, 13, 2468, 17715, 220, 605, 3610, 1667, 2362, 323, 220, 10967, 3177, 1667, 3201, 11, 36655, 87961, 68, 374, 12309, 3345, 311, 9420, 555, 87283, 10886, 13, 11699, 11841, 8627, 287, 13668, 706, 1027, 1664, 20041, 13, 36655, 87961, 68, 374, 12309, 3995, 719, 11, 304, 10334, 11, 433, 374, 3347, 279, 4325, 520, 902, 14880, 11012, 2736, 1253, 617, 14454, 13, 330, 1687, 3287, 956, 1755, 311, 1518, 779, 1790, 6962, 2212, 420, 6917, 1359, 1071, 76249, 31782, 258, 315, 279, 3907, 315, 14972, 304, 9489, 65639, 13, 31782, 258, 6197, 279, 502, 4007, 26449, 304, 279, 8486, 22037, 13, 330, 13129, 2740, 9958, 315, 420, 4325, 617, 23803, 704, 872, 14932, 3769, 11, 719, 420, 6917, 2103, 706, 3403, 3148, 311, 1304, 279, 13890, 315, 220, 1135, 622, 455, 275, 388, 1359, 31782, 258, 1071, 13, 763, 5369, 311, 31720, 279, 44797, 1614, 315, 279, 6917, 11, 279, 14955, 1101, 20461, 264, 502, 11, 810, 24473, 1749, 369, 47826, 11841, 8627, 287, 54858, 13, 30013, 12823, 369, 47614, 279, 3148, 1051, 25636, 323, 36218, 13, 578, 502, 1749, 649, 6089, 22477, 279, 6962, 430, 11383, 5900, 1139, 3339, 33975, 13, 9878, 1441, 527, 9405, 704, 315, 3769, 93378, 2212, 3995, 9958, 11, 323, 279, 3148, 315, 420, 3769, 374, 264, 1401, 8331, 26991, 872, 18488, 13, 39616, 14609, 388, 1550, 539, 1440, 1603, 279, 502, 4007, 3508, 279, 13668, 2212, 36655, 87961, 68, 13282, 3403, 3769, 311, 1376, 502, 33975, 4528, 311, 1057, 1866, 13, 1115, 10255, 596, 7434, 46480, 279, 11841, 8627, 287, 13668, 2212, 36655, 87961, 68, 11, 7559, 922, 220, 10005, 3177, 57188, 3201, 304, 279, 87961, 11, 477, 15379, 8409, 46225, 11, 83486, 13, 763, 220, 679, 16, 11, 87887, 1511, 279, 65466, 331, 301, 3634, 9466, 5382, 311, 11388, 6293, 1245, 15055, 315, 7155, 3090, 38752, 11, 36762, 304, 6437, 11, 69239, 1113, 505, 279, 6917, 596, 11841, 8627, 287, 13668, 315, 16174, 323, 6962, 13, 16666, 25, 22146, 32801, 2989, 76450, 18261, 330, 10438, 11, 584, 1047, 311, 1005, 264, 13594, 311, 8101, 279, 6962, 12472, 304, 279, 11841, 8627, 287, 54858, 1359, 1071, 7043, 7573, 34117, 11, 279, 22146, 2447, 28568, 369, 65466, 331, 301, 520, 22146, 596, 25365, 3998, 34003, 32184, 304, 83550, 11, 41889, 13, 330, 2028, 374, 2500, 3187, 315, 65466, 331, 301, 596, 60112, 323, 27541, 78504, 3062, 502, 3135, 922, 6917, 323, 11841, 18488, 1210, 12362, 65466, 331, 301, 11, 14248, 1051, 3025, 311, 1935, 264, 7878, 1427, 520, 279, 13668, 449, 279, 3634, 56925, 311, 24564, 3177, 5108, 505, 36655, 87961, 68, 323, 3820, 704, 279, 57077, 12223, 315, 264, 6962, 2663, 35784, 409, 29051, 579, 13, 9170, 35784, 35715, 527, 279, 1925, 6962, 3777, 315, 33975, 11, 719, 814, 17105, 3177, 520, 93959, 2288, 2875, 311, 387, 16914, 555, 65466, 331, 301, 13, 21523, 35715, 8649, 409, 29051, 2411, 11, 264, 44922, 2373, 315, 35784, 11, 17105, 3177, 520, 5129, 11, 3117, 3502, 82482, 93959, 430, 65466, 331, 301, 374, 19167, 311, 1518, 13, 1115, 9147, 87887, 311, 6767, 279, 5990, 315, 35784, 409, 29051, 579, 323, 6994, 279, 4785, 315, 279, 13668, 449, 279, 8592, 16437, 3686, 13, 330, 96621, 279, 3148, 315, 264, 11841, 8627, 287, 13668, 374, 16996, 311, 8830, 1268, 323, 994, 33975, 1935, 6211, 2212, 1023, 9958, 1359, 1071, 40208, 70690, 12082, 1466, 11, 65466, 331, 301, 2068, 28568, 520, 22146, 70736, 304, 6652, 13, 13440, 36655, 87961, 68, 596, 3544, 13668, 690, 3063, 311, 459, 39418, 62938, 1887, 449, 8294, 323, 810, 12387, 33975, 1109, 11604, 8625, 311, 387, 3970, 11, 719, 279, 502, 2038, 8779, 7124, 279, 2134, 315, 3284, 11841, 26350, 13, 330, 791, 502, 3135, 527, 2500, 3062, 3094, 304, 8830, 279, 20057, 315, 62938, 6067, 304, 1057, 15861, 1359, 1071, 31782, 258, 13, 330, 1687, 527, 1457, 46071, 6067, 449, 11191, 622, 455, 275, 388, 11, 2307, 13737, 277, 17323, 11, 323, 1690, 80724, 12970, 24800, 13, 3296, 47826, 6067, 520, 872, 7342, 11, 584, 8895, 20616, 1139, 1268, 1057, 1866, 13238, 1887, 14454, 449, 1120, 832, 315, 1690, 3284, 62938, 33483, 1210, 220, 128257, 198 ]

2,098

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Lysosomal storage diseases are a class of over 70 rare genetic diseases that are amenable to enzyme replacement therapy. Towards developing a plant-based enzyme replacement therapeutic for the lysosomal storage disease mucopolysaccharidosis I, here we expressed α- L -iduronidase in the endosperm of maize seeds by a previously uncharacterized mRNA-targeting-based mechanism. Immunolocalization, cellular fractionation and in situ RT–PCR demonstrate that the α- L -iduronidase protein and mRNA are targeted to endoplasmic reticulum (ER)-derived protein bodies and to protein body–ER regions, respectively, using regulatory (5′- and 3′-UTR) and signal-peptide coding sequences from the γ-zein gene. The maize α- L -iduronidase exhibits high activity, contains high-mannose N-glycans and is amenable to in vitro phosphorylation. This mRNA-based strategy is of widespread importance as plant N-glycan maturation is controlled and the therapeutic protein is generated in a native form. For our target enzyme, the N-glycan structures are appropriate for downstream processing, a prerequisite for its potential as a therapeutic protein. Introduction Lysosomal storage diseases (LSDs) are a broad class of genetic diseases that are caused by mutations in proteins critical for lysosomal function; collectively, they represent over 70 disorders 1 , 2 , 3 , 4 , 5 . In many of these diseases, there is a deficiency of a single hydrolase enzyme within the lysosome; all are progressive in nature, as the affected individual is unable to degrade certain macromolecules, a process essential for normal growth and homeostasis of tissues. Many LSDs are amenable to enzyme replacement therapy (ERT)—a process that takes advantage of plasma membrane receptor mechanisms that mediate cellular uptake of a recombinant purified enzyme following its intravenous delivery 6 . ERT has become established for six of the LSDs. One of the mucopolysaccharidoses, MPS I, is an LSD characterized by the deficiency of α- L -iduronidase, an enzyme involved in the stepwise degradation of glycosaminoglycans; in severely affected humans, this genetic disease is characterized by profound skeletal, cardiac, and neurological pathology and death in early childhood 7 . The average annual costs of the ERT drug for MPS I disease (Laronidase or Aldurazyme) range from $300,000 USD (children) to $800,000 USD (adults). Transgenic plants, cultured plant cells and seeds are potentially cost-effective and safe systems for large-scale production of recombinant therapeutic proteins; they offer considerable advantages as production systems, but are not without challenges 8 , 9 . The majority of human lysosomal enzymes are glycoproteins and the nature of their N-glycan structures can influence their stability, transport and biological activity. Within the Golgi complex of both plant and animal cells, enzymes convert many of the original high-mannose N-glycans of proteins to complex N-glycans through sequential reactions that rely on accessibility of the glycan chain(s) to the Golgi-processing machinery 9 , 10 . In the mammalian Golgi complex, many of the N-glycan core structures (Man 3 GlcNAc 2 ) are extended further to contain penultimate galactose and terminal sialic acid residues 10 . In contrast, typically processed N-linked glycans of plant proteins are mostly of a Man 3 GlcNAc 2 structure with or without β-1,2-xylose and/or α-1,3-fucose 9 . For glycoprotein therapeutics destined for parenteral administration (as in ERT), the presence of plant-specific xylose and/or fucose residues is problematic, because the therapeutic is potentially highly immunogenic 9 . Different strategies have been used to modify the N-glycan processing of plant-made recombinant proteins; one strategy has been to manipulate subcellular protein targeting to avoid Golgi transport 8 , 9 . This has involved the addition of C-terminal HDEL/KDEL sequences or similar motifs for endoplasmic reticulum (ER) retention, or the addition of transmembrane and cytoplasmic tail sequences that potentially act as anchors for delivering recombinant proteins to vacuolar compartments independent of the Golgi complex 11 . These strategies suffer the drawbacks of requiring the addition of foreign amino acids that remain on the mature recombinant protein. The HDEL/KDEL strategy is very efficient for controlling the N-glycosylation of some recombinant proteins, especially antibodies 12 , 13 , 14 . However, the efficacy of this strategy is protein-specific 9 . For some recombinant proteins, including human α- L -iduronidase produced in Arabidopsis seeds, there is clearly an insufficient control of N-glycan maturation 15 . The use of vacuolar anchors as a means of controlling complex N-glycan formation 11 is not yet backed up by definitive evidence. The mechanisms by which proteins of eukaryotic cells are targeted intracellularly are most commonly mediated through signals on the protein itself (for example, amino acid or carbohydrate motifs). More recently, it has been recognized that signals on mRNAs can also mediate the targeting of proteins to specific intracellular regions 16 , 17 . γ-Zein storage proteins (prolamins) of maize seeds are deposited in ER-derived protein bodies and do not transit through the Golgi complex 18 . In the present study, we exploited the potential of maize seeds for hosting the production of recombinant human α- L -iduronidase by taking advantage of their capacity for ER–protein body localization of the gene product. We hypothesized that α- L -iduronidase would be targeted to ER-derived protein bodies by mRNA targeting using γ-zein cis -elements. If successful, the 'native' recombinant therapeutic protein (that is, possessing no foreign amino acid motifs) would stably accumulate in maize endosperm cells, but have avoided transit through the Golgi complex and the consequent undesired N-glycan maturation. We found that the regulatory (5′- and 3′-untranslated region (UTR)) and signal-peptide-encoding sequences of the γ-zein gene are sufficient for direct ER–protein body deposition of the majority of the α- L -iduronidase by an mRNA-targeting-based mechanism. Moreover, the α- L -iduronidase was enzymatically active and possessed kinetic characteristics that were comparable to those of the commercial MPS I ERT product (Aldurazyme). After immunoadsorbing the minor contaminant of Golgi-modified enzyme, the affinity-purified maize recombinant α- L -iduronidase contained exclusively high-mannose N-glycans and was amenable to in vitro phosphorylation using a recombinant soluble GlcNAc-1-phosphotransferase, which is the first step to creating the mannose-6-phosphate (M6P) lysosomal sorting motif. We discuss the widespread importance of the targeting of recombinant proteins to ER-derived protein bodies", "role": "user" }, { "content": "(Phys.org)—The seeds of greenhouse-grown corn could hold the key to treating a rare, life-threatening childhood genetic disease, according to researchers from Simon Fraser University. SFU biologist Allison Kermode and her team have been carrying out multidisciplinary research toward developing enzyme therapeutics for lysosomal storage diseases - rare, but devastating childhood genetic diseases – for more than a decade. In the most severe forms of these inherited diseases, untreated patients die in early childhood because of progressive damage to all organs of the body. Currently, enzyme treatments are available for only six of the more than 70 diverse types of lysosomal storage diseases. \"In part because mammalian cell cultures have been the system of choice to produce these therapeutics, the enzymes are extremely costly to make, with treatments typically ranging from $300,000 to $500,000 per year for children, with even higher costs for adults,\" says Kermode, noting the strain on healthcare budgets in Canada and other countries is becoming an issue. Greenhouse-grown maize may become a platform for making alpha-L-iduronidase, an enzyme used to treat the lysosomal storage disease known as mucopolysaccharidosis I, according to research published in this week's Nature Communications. The findings could ultimately change how these enzyme therapeutics are made, and substantially reduce the costs of treating patients. The novel technology manipulates processes inside the maize seed that \"traffick\" messenger RNAs to certain parts of the cell as a means of controlling the subsequent sugar processing of the therapeutic protein. In this way, the researchers have been able to produce the enzyme drug in maize seeds. The product could ultimately be used as a disease therapeutic, although it is still \"early days,\" says Kermode, and several research goals remain to be accomplished before this can become a reality. Kermode says the success of the work underscores the power of multidisciplinary research that included contributions from SFU chemistry professor David Vocadlo, and from UBC Medical Genetics professor Lorne Clarke. It further underscores the importance of connections between SFU and Australia's Griffith University, through collaborative researchers Mark von Itzstein and Thomas Haselhorst. \"In 2005, we had the basis of our story worked out,\" says Kermode. \"Taking it to the next level involved their precise analyses to determine the sugar residues on the therapeutic enzyme produced by the modified maize seeds. \"When we first looked at the sugar analysis data we were amazed at how well the 'mRNA-trafficking strategy' had worked, and the high fidelity of the process for controlling the sugar-processing of the therapeutic protein. This is critical as sugar processing influences the characteristics of a protein (enzyme) therapeutic, including its safety, quality, half-life in the bloodstream, and efficacy. The work could well extend to forming a platform for the production of other protein therapeutics.\" Kermode also credits SFU research associate Xu He, the first author of the Nature Communications paper. Her funding sources included NSERC Strategic grants and a Michael Smith Foundation for Health Research Senior Scholar Award, and in related research, a Canadian Society for Mucopolysaccharide and Related Diseases grant. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Lysosomal storage diseases are a class of over 70 rare genetic diseases that are amenable to enzyme replacement therapy. Towards developing a plant-based enzyme replacement therapeutic for the lysosomal storage disease mucopolysaccharidosis I, here we expressed α- L -iduronidase in the endosperm of maize seeds by a previously uncharacterized mRNA-targeting-based mechanism. Immunolocalization, cellular fractionation and in situ RT–PCR demonstrate that the α- L -iduronidase protein and mRNA are targeted to endoplasmic reticulum (ER)-derived protein bodies and to protein body–ER regions, respectively, using regulatory (5′- and 3′-UTR) and signal-peptide coding sequences from the γ-zein gene. The maize α- L -iduronidase exhibits high activity, contains high-mannose N-glycans and is amenable to in vitro phosphorylation. This mRNA-based strategy is of widespread importance as plant N-glycan maturation is controlled and the therapeutic protein is generated in a native form. For our target enzyme, the N-glycan structures are appropriate for downstream processing, a prerequisite for its potential as a therapeutic protein. Introduction Lysosomal storage diseases (LSDs) are a broad class of genetic diseases that are caused by mutations in proteins critical for lysosomal function; collectively, they represent over 70 disorders 1 , 2 , 3 , 4 , 5 . In many of these diseases, there is a deficiency of a single hydrolase enzyme within the lysosome; all are progressive in nature, as the affected individual is unable to degrade certain macromolecules, a process essential for normal growth and homeostasis of tissues. Many LSDs are amenable to enzyme replacement therapy (ERT)—a process that takes advantage of plasma membrane receptor mechanisms that mediate cellular uptake of a recombinant purified enzyme following its intravenous delivery 6 . ERT has become established for six of the LSDs. One of the mucopolysaccharidoses, MPS I, is an LSD characterized by the deficiency of α- L -iduronidase, an enzyme involved in the stepwise degradation of glycosaminoglycans; in severely affected humans, this genetic disease is characterized by profound skeletal, cardiac, and neurological pathology and death in early childhood 7 . The average annual costs of the ERT drug for MPS I disease (Laronidase or Aldurazyme) range from $300,000 USD (children) to $800,000 USD (adults). Transgenic plants, cultured plant cells and seeds are potentially cost-effective and safe systems for large-scale production of recombinant therapeutic proteins; they offer considerable advantages as production systems, but are not without challenges 8 , 9 . The majority of human lysosomal enzymes are glycoproteins and the nature of their N-glycan structures can influence their stability, transport and biological activity. Within the Golgi complex of both plant and animal cells, enzymes convert many of the original high-mannose N-glycans of proteins to complex N-glycans through sequential reactions that rely on accessibility of the glycan chain(s) to the Golgi-processing machinery 9 , 10 . In the mammalian Golgi complex, many of the N-glycan core structures (Man 3 GlcNAc 2 ) are extended further to contain penultimate galactose and terminal sialic acid residues 10 . In contrast, typically processed N-linked glycans of plant proteins are mostly of a Man 3 GlcNAc 2 structure with or without β-1,2-xylose and/or α-1,3-fucose 9 . For glycoprotein therapeutics destined for parenteral administration (as in ERT), the presence of plant-specific xylose and/or fucose residues is problematic, because the therapeutic is potentially highly immunogenic 9 . Different strategies have been used to modify the N-glycan processing of plant-made recombinant proteins; one strategy has been to manipulate subcellular protein targeting to avoid Golgi transport 8 , 9 . This has involved the addition of C-terminal HDEL/KDEL sequences or similar motifs for endoplasmic reticulum (ER) retention, or the addition of transmembrane and cytoplasmic tail sequences that potentially act as anchors for delivering recombinant proteins to vacuolar compartments independent of the Golgi complex 11 . These strategies suffer the drawbacks of requiring the addition of foreign amino acids that remain on the mature recombinant protein. The HDEL/KDEL strategy is very efficient for controlling the N-glycosylation of some recombinant proteins, especially antibodies 12 , 13 , 14 . However, the efficacy of this strategy is protein-specific 9 . For some recombinant proteins, including human α- L -iduronidase produced in Arabidopsis seeds, there is clearly an insufficient control of N-glycan maturation 15 . The use of vacuolar anchors as a means of controlling complex N-glycan formation 11 is not yet backed up by definitive evidence. The mechanisms by which proteins of eukaryotic cells are targeted intracellularly are most commonly mediated through signals on the protein itself (for example, amino acid or carbohydrate motifs). More recently, it has been recognized that signals on mRNAs can also mediate the targeting of proteins to specific intracellular regions 16 , 17 . γ-Zein storage proteins (prolamins) of maize seeds are deposited in ER-derived protein bodies and do not transit through the Golgi complex 18 . In the present study, we exploited the potential of maize seeds for hosting the production of recombinant human α- L -iduronidase by taking advantage of their capacity for ER–protein body localization of the gene product. We hypothesized that α- L -iduronidase would be targeted to ER-derived protein bodies by mRNA targeting using γ-zein cis -elements. If successful, the 'native' recombinant therapeutic protein (that is, possessing no foreign amino acid motifs) would stably accumulate in maize endosperm cells, but have avoided transit through the Golgi complex and the consequent undesired N-glycan maturation. We found that the regulatory (5′- and 3′-untranslated region (UTR)) and signal-peptide-encoding sequences of the γ-zein gene are sufficient for direct ER–protein body deposition of the majority of the α- L -iduronidase by an mRNA-targeting-based mechanism. Moreover, the α- L -iduronidase was enzymatically active and possessed kinetic characteristics that were comparable to those of the commercial MPS I ERT product (Aldurazyme). After immunoadsorbing the minor contaminant of Golgi-modified enzyme, the affinity-purified maize recombinant α- L -iduronidase contained exclusively high-mannose N-glycans and was amenable to in vitro phosphorylation using a recombinant soluble GlcNAc-1-phosphotransferase, which is the first step to creating the mannose-6-phosphate (M6P) lysosomal sorting motif. We discuss the widespread importance of the targeting of recombinant proteins to ER-derived protein bodies<|im_end|> <|im_start|>assistant (Phys.org)—The seeds of greenhouse-grown corn could hold the key to treating a rare, life-threatening childhood genetic disease, according to researchers from Simon Fraser University. SFU biologist Allison Kermode and her team have been carrying out multidisciplinary research toward developing enzyme therapeutics for lysosomal storage diseases - rare, but devastating childhood genetic diseases – for more than a decade. In the most severe forms of these inherited diseases, untreated patients die in early childhood because of progressive damage to all organs of the body. Currently, enzyme treatments are available for only six of the more than 70 diverse types of lysosomal storage diseases. "In part because mammalian cell cultures have been the system of choice to produce these therapeutics, the enzymes are extremely costly to make, with treatments typically ranging from $300,000 to $500,000 per year for children, with even higher costs for adults," says Kermode, noting the strain on healthcare budgets in Canada and other countries is becoming an issue. Greenhouse-grown maize may become a platform for making alpha-L-iduronidase, an enzyme used to treat the lysosomal storage disease known as mucopolysaccharidosis I, according to research published in this week's Nature Communications. The findings could ultimately change how these enzyme therapeutics are made, and substantially reduce the costs of treating patients. The novel technology manipulates processes inside the maize seed that "traffick" messenger RNAs to certain parts of the cell as a means of controlling the subsequent sugar processing of the therapeutic protein. In this way, the researchers have been able to produce the enzyme drug in maize seeds. The product could ultimately be used as a disease therapeutic, although it is still "early days," says Kermode, and several research goals remain to be accomplished before this can become a reality. Kermode says the success of the work underscores the power of multidisciplinary research that included contributions from SFU chemistry professor David Vocadlo, and from UBC Medical Genetics professor Lorne Clarke. It further underscores the importance of connections between SFU and Australia's Griffith University, through collaborative researchers Mark von Itzstein and Thomas Haselhorst. "In 2005, we had the basis of our story worked out," says Kermode. "Taking it to the next level involved their precise analyses to determine the sugar residues on the therapeutic enzyme produced by the modified maize seeds. "When we first looked at the sugar analysis data we were amazed at how well the 'mRNA-trafficking strategy' had worked, and the high fidelity of the process for controlling the sugar-processing of the therapeutic protein. This is critical as sugar processing influences the characteristics of a protein (enzyme) therapeutic, including its safety, quality, half-life in the bloodstream, and efficacy. The work could well extend to forming a platform for the production of other protein therapeutics." Kermode also credits SFU research associate Xu He, the first author of the Nature Communications paper. Her funding sources included NSERC Strategic grants and a Michael Smith Foundation for Health Research Senior Scholar Award, and in related research, a Canadian Society for Mucopolysaccharide and Related Diseases grant. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 445, 1065, 96108, 5942, 19338, 527, 264, 538, 315, 927, 220, 2031, 9024, 19465, 19338, 430, 527, 1097, 12837, 311, 49242, 14039, 15419, 13, 94965, 11469, 264, 6136, 6108, 49242, 14039, 37471, 369, 279, 84495, 96108, 5942, 8624, 65104, 28765, 1065, 582, 1799, 307, 10934, 358, 11, 1618, 584, 13605, 19581, 12, 445, 482, 307, 37190, 307, 521, 304, 279, 842, 437, 20508, 315, 93307, 19595, 555, 264, 8767, 653, 19740, 1534, 78872, 18996, 287, 6108, 17383, 13, 67335, 337, 3768, 2065, 11, 35693, 19983, 367, 323, 304, 10109, 10860, 4235, 74256, 20461, 430, 279, 19581, 12, 445, 482, 307, 37190, 307, 521, 13128, 323, 78872, 527, 17550, 311, 842, 56178, 10753, 292, 2160, 292, 16903, 320, 643, 7435, 51182, 13128, 13162, 323, 311, 13128, 2547, 4235, 643, 13918, 11, 15947, 11, 1701, 23331, 320, 20, 39615, 12, 323, 220, 18, 39615, 12, 1406, 49, 8, 323, 8450, 96751, 47309, 11058, 24630, 505, 279, 63127, 12, 3059, 258, 15207, 13, 578, 93307, 19581, 12, 445, 482, 307, 37190, 307, 521, 50829, 1579, 5820, 11, 5727, 1579, 1474, 1036, 974, 452, 2427, 398, 66, 598, 323, 374, 1097, 12837, 311, 304, 55004, 95089, 2354, 13, 1115, 78872, 6108, 8446, 374, 315, 24716, 12939, 439, 6136, 452, 2427, 398, 4919, 5634, 2060, 374, 14400, 323, 279, 37471, 13128, 374, 8066, 304, 264, 10068, 1376, 13, 1789, 1057, 2218, 49242, 11, 279, 452, 2427, 398, 4919, 14726, 527, 8475, 369, 52452, 8863, 11, 264, 80884, 369, 1202, 4754, 439, 264, 37471, 13128, 13, 29438, 445, 1065, 96108, 5942, 19338, 320, 43, 5608, 82, 8, 527, 264, 7353, 538, 315, 19465, 19338, 430, 527, 9057, 555, 34684, 304, 28896, 9200, 369, 84495, 96108, 734, 26, 45925, 11, 814, 4097, 927, 220, 2031, 24673, 220, 16, 1174, 220, 17, 1174, 220, 18, 1174, 220, 19, 1174, 220, 20, 662, 763, 1690, 315, 1521, 19338, 11, 1070, 374, 264, 48294, 315, 264, 3254, 6409, 67, 1098, 521, 49242, 2949, 279, 84495, 32554, 26, 682, 527, 23053, 304, 7138, 11, 439, 279, 11754, 3927, 374, 12153, 311, 96630, 3738, 9155, 442, 82206, 11, 264, 1920, 7718, 369, 4725, 6650, 323, 2162, 537, 10949, 315, 39881, 13, 9176, 72170, 82, 527, 1097, 12837, 311, 49242, 14039, 15419, 320, 3481, 68850, 64, 1920, 430, 5097, 9610, 315, 32426, 39654, 35268, 24717, 430, 1812, 6629, 35693, 69575, 315, 264, 38301, 7006, 519, 92600, 49242, 2768, 1202, 10805, 81443, 9889, 220, 21, 662, 469, 5463, 706, 3719, 9749, 369, 4848, 315, 279, 72170, 82, 13, 3861, 315, 279, 65104, 28765, 1065, 582, 1799, 13652, 288, 11, 94043, 358, 11, 374, 459, 72170, 32971, 555, 279, 48294, 315, 19581, 12, 445, 482, 307, 37190, 307, 521, 11, 459, 49242, 6532, 304, 279, 3094, 4583, 53568, 315, 37807, 9594, 8778, 540, 398, 66, 598, 26, 304, 35906, 11754, 12966, 11, 420, 19465, 8624, 374, 32971, 555, 28254, 69397, 11, 47345, 11, 323, 64908, 77041, 323, 4648, 304, 4216, 20587, 220, 22, 662, 578, 5578, 9974, 7194, 315, 279, 469, 5463, 5623, 369, 94043, 358, 8624, 320, 43, 13055, 307, 521, 477, 31447, 324, 1394, 31218, 8, 2134, 505, 400, 3101, 11, 931, 20121, 320, 5988, 8, 311, 400, 4728, 11, 931, 20121, 320, 68956, 82, 570, 4149, 89305, 11012, 11, 89948, 6136, 7917, 323, 19595, 527, 13893, 2853, 53421, 323, 6220, 6067, 369, 3544, 13230, 5788, 315, 38301, 7006, 519, 37471, 28896, 26, 814, 3085, 24779, 22934, 439, 5788, 6067, 11, 719, 527, 539, 2085, 11774, 220, 23, 1174, 220, 24, 662, 578, 8857, 315, 3823, 84495, 96108, 56067, 527, 37807, 38828, 5646, 1354, 323, 279, 7138, 315, 872, 452, 2427, 398, 4919, 14726, 649, 10383, 872, 20334, 11, 7710, 323, 24156, 5820, 13, 25218, 279, 55679, 8376, 6485, 315, 2225, 6136, 323, 10065, 7917, 11, 56067, 5625, 1690, 315, 279, 4113, 1579, 1474, 1036, 974, 452, 2427, 398, 66, 598, 315, 28896, 311, 6485, 452, 2427, 398, 66, 598, 1555, 52100, 25481, 430, 17631, 389, 40800, 315, 279, 37807, 4919, 8957, 1161, 8, 311, 279, 55679, 8376, 70293, 26953, 220, 24, 1174, 220, 605, 662, 763, 279, 36041, 10700, 55679, 8376, 6485, 11, 1690, 315, 279, 452, 2427, 398, 4919, 6332, 14726, 320, 1692, 220, 18, 8444, 66, 7476, 66, 220, 17, 883, 527, 11838, 4726, 311, 6782, 5869, 67666, 15730, 533, 974, 323, 15372, 274, 532, 292, 13935, 71783, 220, 605, 662, 763, 13168, 11, 11383, 15590, 452, 55514, 72157, 598, 315, 6136, 28896, 527, 10213, 315, 264, 2418, 220, 18, 8444, 66, 7476, 66, 220, 17, 6070, 449, 477, 2085, 34318, 12, 16, 11, 17, 12, 4223, 1497, 323, 5255, 19581, 12, 16, 11, 18, 2269, 94697, 220, 24, 662, 1789, 37807, 38828, 91748, 9139, 88886, 51687, 369, 2748, 3333, 8735, 320, 300, 304, 469, 5463, 705, 279, 9546, 315, 6136, 19440, 31884, 1497, 323, 5255, 282, 94697, 71783, 374, 36033, 11, 1606, 279, 37471, 374, 13893, 7701, 33119, 29569, 220, 24, 662, 34496, 15174, 617, 1027, 1511, 311, 5719, 279, 452, 2427, 398, 4919, 8863, 315, 6136, 27975, 38301, 7006, 519, 28896, 26, 832, 8446, 706, 1027, 311, 37735, 1207, 5997, 1299, 13128, 25103, 311, 5766, 55679, 8376, 7710, 220, 23, 1174, 220, 24, 662, 1115, 706, 6532, 279, 5369, 315, 356, 91723, 473, 39432, 33954, 39432, 24630, 477, 4528, 84989, 369, 842, 56178, 10753, 292, 2160, 292, 16903, 320, 643, 8, 38231, 11, 477, 279, 5369, 315, 1380, 10759, 88554, 323, 9693, 99705, 10753, 292, 9986, 24630, 430, 13893, 1180, 439, 56539, 369, 24944, 38301, 7006, 519, 28896, 311, 9467, 84, 7569, 87352, 9678, 315, 279, 55679, 8376, 6485, 220, 806, 662, 4314, 15174, 7831, 279, 89173, 315, 23537, 279, 5369, 315, 7362, 42500, 33969, 430, 7293, 389, 279, 15196, 38301, 7006, 519, 13128, 13, 578, 473, 39432, 33954, 39432, 8446, 374, 1633, 11297, 369, 26991, 279, 452, 2427, 398, 9594, 79933, 315, 1063, 38301, 7006, 519, 28896, 11, 5423, 59854, 220, 717, 1174, 220, 1032, 1174, 220, 975, 662, 4452, 11, 279, 41265, 315, 420, 8446, 374, 13128, 19440, 220, 24, 662, 1789, 1063, 38301, 7006, 519, 28896, 11, 2737, 3823, 19581, 12, 445, 482, 307, 37190, 307, 521, 9124, 304, 10989, 307, 33906, 19595, 11, 1070, 374, 9539, 459, 39413, 2585, 315, 452, 2427, 398, 4919, 5634, 2060, 220, 868, 662, 578, 1005, 315, 9467, 84, 7569, 56539, 439, 264, 3445, 315, 26991, 6485, 452, 2427, 398, 4919, 18488, 220, 806, 374, 539, 3686, 22126, 709, 555, 45813, 6029, 13, 578, 24717, 555, 902, 28896, 315, 384, 3178, 661, 14546, 7917, 527, 17550, 10805, 65441, 398, 527, 1455, 17037, 78926, 1555, 17738, 389, 279, 13128, 5196, 320, 2000, 3187, 11, 42500, 13935, 477, 67732, 84989, 570, 4497, 6051, 11, 433, 706, 1027, 15324, 430, 17738, 389, 296, 51295, 2170, 649, 1101, 1812, 6629, 279, 25103, 315, 28896, 311, 3230, 10805, 65441, 13918, 220, 845, 1174, 220, 1114, 662, 63127, 11419, 72720, 5942, 28896, 320, 782, 24705, 1354, 8, 315, 93307, 19595, 527, 54568, 304, 27590, 72286, 13128, 13162, 323, 656, 539, 25032, 1555, 279, 55679, 8376, 6485, 220, 972, 662, 763, 279, 3118, 4007, 11, 584, 51763, 279, 4754, 315, 93307, 19595, 369, 20256, 279, 5788, 315, 38301, 7006, 519, 3823, 19581, 12, 445, 482, 307, 37190, 307, 521, 555, 4737, 9610, 315, 872, 8824, 369, 27590, 4235, 79565, 2547, 53404, 315, 279, 15207, 2027, 13, 1226, 22601, 83979, 430, 19581, 12, 445, 482, 307, 37190, 307, 521, 1053, 387, 17550, 311, 27590, 72286, 13128, 13162, 555, 78872, 25103, 1701, 63127, 12, 3059, 258, 67504, 482, 22138, 13, 1442, 6992, 11, 279, 364, 30838, 6, 38301, 7006, 519, 37471, 13128, 320, 9210, 374, 11, 60662, 912, 7362, 42500, 13935, 84989, 8, 1053, 357, 2915, 47376, 304, 93307, 842, 437, 20508, 7917, 11, 719, 617, 31890, 25032, 1555, 279, 55679, 8376, 6485, 323, 279, 12777, 306, 56838, 2757, 452, 2427, 398, 4919, 5634, 2060, 13, 1226, 1766, 430, 279, 23331, 320, 20, 39615, 12, 323, 220, 18, 39615, 12, 359, 54342, 5654, 320, 1406, 49, 595, 323, 8450, 96751, 47309, 12, 17600, 24630, 315, 279, 63127, 12, 3059, 258, 15207, 527, 14343, 369, 2167, 27590, 4235, 79565, 2547, 65374, 315, 279, 8857, 315, 279, 19581, 12, 445, 482, 307, 37190, 307, 521, 555, 459, 78872, 18996, 287, 6108, 17383, 13, 23674, 11, 279, 19581, 12, 445, 482, 307, 37190, 307, 521, 574, 32011, 7167, 4642, 323, 43890, 71423, 17910, 430, 1051, 30139, 311, 1884, 315, 279, 8518, 94043, 358, 469, 5463, 2027, 320, 32, 509, 324, 1394, 31218, 570, 4740, 33119, 2799, 82, 269, 7278, 279, 9099, 35522, 519, 315, 55679, 8376, 17515, 1908, 49242, 11, 279, 51552, 2320, 324, 1908, 93307, 38301, 7006, 519, 19581, 12, 445, 482, 307, 37190, 307, 521, 13282, 24121, 1579, 1474, 1036, 974, 452, 2427, 398, 66, 598, 323, 574, 1097, 12837, 311, 304, 55004, 95089, 2354, 1701, 264, 38301, 7006, 519, 88045, 8444, 66, 7476, 66, 12, 16, 63837, 24527, 354, 34489, 809, 521, 11, 902, 374, 279, 1176, 3094, 311, 6968, 279, 38908, 974, 12, 21, 63837, 93473, 320, 44, 21, 47, 8, 84495, 96108, 29373, 60612, 13, 1226, 4358, 279, 24716, 12939, 315, 279, 25103, 315, 38301, 7006, 519, 28896, 311, 27590, 72286, 13128, 13162, 128257, 198, 128256, 78191, 198, 7, 67171, 2726, 68850, 791, 19595, 315, 37647, 2427, 4935, 14095, 1436, 3412, 279, 1401, 311, 27723, 264, 9024, 11, 2324, 62999, 20587, 19465, 8624, 11, 4184, 311, 12074, 505, 22021, 56230, 3907, 13, 24360, 52, 88704, 63508, 735, 4289, 536, 323, 1077, 2128, 617, 1027, 15691, 704, 64486, 3510, 44550, 3495, 9017, 11469, 49242, 9139, 88886, 369, 84495, 96108, 5942, 19338, 482, 9024, 11, 719, 33318, 20587, 19465, 19338, 1389, 369, 810, 1109, 264, 13515, 13, 763, 279, 1455, 15748, 7739, 315, 1521, 28088, 19338, 11, 83920, 6978, 2815, 304, 4216, 20587, 1606, 315, 23053, 5674, 311, 682, 36853, 315, 279, 2547, 13, 25122, 11, 49242, 22972, 527, 2561, 369, 1193, 4848, 315, 279, 810, 1109, 220, 2031, 17226, 4595, 315, 84495, 96108, 5942, 19338, 13, 330, 644, 961, 1606, 36041, 10700, 2849, 27833, 617, 1027, 279, 1887, 315, 5873, 311, 8356, 1521, 9139, 88886, 11, 279, 56067, 527, 9193, 34348, 311, 1304, 11, 449, 22972, 11383, 24950, 505, 400, 3101, 11, 931, 311, 400, 2636, 11, 931, 824, 1060, 369, 2911, 11, 449, 1524, 5190, 7194, 369, 12884, 1359, 2795, 735, 4289, 536, 11, 27401, 279, 26800, 389, 18985, 42484, 304, 7008, 323, 1023, 5961, 374, 10671, 459, 4360, 13, 7997, 7830, 2427, 4935, 93307, 1253, 3719, 264, 5452, 369, 3339, 8451, 8288, 13193, 37190, 307, 521, 11, 459, 49242, 1511, 311, 4322, 279, 84495, 96108, 5942, 8624, 3967, 439, 65104, 28765, 1065, 582, 1799, 307, 10934, 358, 11, 4184, 311, 3495, 4756, 304, 420, 2046, 596, 22037, 26545, 13, 578, 14955, 1436, 13967, 2349, 1268, 1521, 49242, 9139, 88886, 527, 1903, 11, 323, 32302, 8108, 279, 7194, 315, 27723, 6978, 13, 578, 11775, 5557, 14951, 24031, 11618, 4871, 279, 93307, 10533, 430, 330, 2221, 544, 875, 1, 50596, 46916, 2170, 311, 3738, 5596, 315, 279, 2849, 439, 264, 3445, 315, 26991, 279, 17876, 13465, 8863, 315, 279, 37471, 13128, 13, 763, 420, 1648, 11, 279, 12074, 617, 1027, 3025, 311, 8356, 279, 49242, 5623, 304, 93307, 19595, 13, 578, 2027, 1436, 13967, 387, 1511, 439, 264, 8624, 37471, 11, 8051, 433, 374, 2103, 330, 22928, 2919, 1359, 2795, 735, 4289, 536, 11, 323, 3892, 3495, 9021, 7293, 311, 387, 27332, 1603, 420, 649, 3719, 264, 8903, 13, 735, 4289, 536, 2795, 279, 2450, 315, 279, 990, 72890, 279, 2410, 315, 64486, 3510, 44550, 3495, 430, 5343, 19564, 505, 24360, 52, 30903, 14561, 6941, 87145, 114951, 11, 323, 505, 549, 5002, 13235, 84386, 14561, 445, 17334, 43655, 13, 1102, 4726, 72890, 279, 12939, 315, 13537, 1990, 24360, 52, 323, 8494, 596, 64640, 3907, 11, 1555, 40806, 12074, 4488, 6675, 1102, 89, 12711, 323, 11355, 11697, 301, 20100, 267, 13, 330, 644, 220, 1049, 20, 11, 584, 1047, 279, 8197, 315, 1057, 3446, 6575, 704, 1359, 2795, 735, 4289, 536, 13, 330, 51197, 433, 311, 279, 1828, 2237, 6532, 872, 24473, 29060, 311, 8417, 279, 13465, 71783, 389, 279, 37471, 49242, 9124, 555, 279, 11041, 93307, 19595, 13, 330, 4599, 584, 1176, 7111, 520, 279, 13465, 6492, 828, 584, 1051, 46304, 520, 1268, 1664, 279, 364, 76, 31820, 80367, 544, 16671, 8446, 6, 1047, 6575, 11, 323, 279, 1579, 83604, 315, 279, 1920, 369, 26991, 279, 13465, 70293, 315, 279, 37471, 13128, 13, 1115, 374, 9200, 439, 13465, 8863, 34453, 279, 17910, 315, 264, 13128, 320, 65728, 8, 37471, 11, 2737, 1202, 7296, 11, 4367, 11, 4376, 26928, 304, 279, 100216, 11, 323, 41265, 13, 578, 990, 1436, 1664, 13334, 311, 30164, 264, 5452, 369, 279, 5788, 315, 1023, 13128, 9139, 88886, 1210, 735, 4289, 536, 1101, 20746, 24360, 52, 3495, 22712, 57514, 1283, 11, 279, 1176, 3229, 315, 279, 22037, 26545, 5684, 13, 6385, 11006, 8336, 5343, 3119, 28534, 46661, 25076, 323, 264, 8096, 9259, 5114, 369, 6401, 8483, 19903, 25542, 17768, 11, 323, 304, 5552, 3495, 11, 264, 12152, 13581, 369, 386, 1791, 28765, 1065, 582, 1799, 579, 323, 25368, 70674, 13500, 13, 220, 128257, 198 ]

2,205

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract The tobacco cutworm, Spodoptera litura , is among the most widespread and destructive agricultural pests, feeding on over 100 crops throughout tropical and subtropical Asia. By genome sequencing, physical mapping and transcriptome analysis, we found that the gene families encoding receptors for bitter or toxic substances and detoxification enzymes, such as cytochrome P450, carboxylesterase and glutathione- S -transferase, were massively expanded in this polyphagous species, enabling its extraordinary ability to detect and detoxify many plant secondary compounds. Larval exposure to insecticidal toxins induced expression of detoxification genes, and knockdown of representative genes using short interfering RNA (siRNA) reduced larval survival, consistent with their contribution to the insect’s natural pesticide tolerance. A population genetics study indicated that this species expanded throughout southeast Asia by migrating along a South India–South China–Japan axis, adapting to wide-ranging ecological conditions with diverse host plants and insecticides, surviving and adapting with the aid of its expanded detoxification systems. The findings of this study will enable the development of new pest management strategies for the control of major agricultural pests such as S . litura . Introduction The tobacco cutworm, Spodoptera litura (Lepidoptera, Noctuidae), is an important polyphagous pest; its larvae feed on over 100 crops 1 . This pest is widely distributed throughout tropical and subtropical areas of Asia including India, China and Japan. In India particularly, S . litura causes heavy yield loss varying between 10 and 30% 1 . High fecundity and a short life cycle under tropical conditions result in a high rate of population increase and subsequent population outbreaks. In addition, it has evolved high resistance to every class of pesticide used against it 2 , 3 , including the biopesticide Bt 4 . Few complete genome sequences have been reported for noctuids, which include many serious agricultural pests. Asian researchers launched the S . litura genome project as an international collaboration in cooperation with the Fall armyworm International Public Consortium (FAW-IPC), for which a genome project is coordinately underway 5 . By comparative genomic studies with the monophagous species Bombyx mori and other Spodoptera species such as S . frugiperda (which has a different geographical distribution), S . litura genome information can provide new insights into mechanisms of evolution, host plant specialization and ecological adaptation, which can serve as a reference for noctuids and lead to selective targets for innovative pest control. Results and discussion Genome structure and linkage map of S. litura. We sequenced and assembled a genome for S . litura comprising 438.32 Mb, which contains 15,317 predicted protein-coding genes analysed by GLEAN 6 and 31.8% repetitive elements (Supplementary Tables 1 – 4 ). Among four representative lepidopteran species with complete genome sequences 7 , 8 , 9 , S . litura harbours the smallest number of species-specific gene families (Supplementary Fig. 1a and Supplementary Table 9 ). A phylogenetic tree constructed by single-copy orthologous groups showed that S . litura separated from B . mori and Danaus plexippus about 104.7 Myr ago (Ma), and diverged approximately 147 Ma from the more basal Plutella xylostella , whereas Lepidoptera as a whole separated from Diptera about 258 Ma, consistent with reported divergence time estimates 10 (Supplementary Fig. 1b ). To construct a linkage map, a heterozygous male F1 backcross (BC1) population was established between Japanese and Indian inbred strains. The resulting genetic analysis used 6088 RAD-tags as markers to anchor 639 scaffolds covering 380.89 Mb onto 31 chromosomes, which corresponded to 87% of the genome (Supplementary Section 2). Genomic syntenies from S . litura to B . mori and to Heliconius melpomene revealed two modes of chromosomal fusion (Supplementary Tables 10 and 11 and Supplementary Fig. 2 ). In one, six S . litura chromosomes (haploid chromosome number N = 31) were fused to form three B . mori chromosomes ( N = 28). In the other, six sets of S . litura chromosomes were fused, corresponding to six H . melpomene chromosomes ( N = 21) 11 , and another eight S . litura chromosomes were fused, corresponding to four other H . melpomene chromosomes. These changes were consistent with previous reports on chromosome evolution among butterflies including Melitaea cinxia 12 and the moth Manduca sexta 13 ( Supplementary Section 2 ). Massive expansion of bitter gustatory receptor and detoxification-related gene families associated with polyphagy of Noctuidae To elucidate key genome changes associated with host plant specialization and adaptation in Lepidoptera, we compared chemosensory and detoxification-related gene families between the extremely polyphagous lepidopteran pest S . litura and the almost monophagous lepidopteran model organism B . mori . We found large expansions of the gustatory receptor (GR), cytochrome P450 (P450), carboxylesterase (COE) and glutathione- S -transferase (GST) gene families in S . litura (Table 1 ). Chemosensory genes play an essential role in host plant recognition of herbivores. GRs, especially, are highly variable among species, which could be a major factor for host plant adaptation. GRs are categorized into three classes—CO 2 receptors, sugar receptors and bitter receptors—among which bitter receptors are most variable, while CO 2 and sugar receptors are conserved 14 , 15 , 16 , 17 , 18 . Manual annotation identified 237 GR genes in the S . litura genome (Table 2 , Fig. 1a and Supplementary Table 13 ), whereas in the other lepidopteran species investigated to date, most of which are mono- and oligophagous, only about 45–80 GRs are reported 8 , 11 , 14 , 16 , 19 , 20 . Since large expansions of GR genes were also reported recently in S . frugiperda 5 and in another polyphagous noctuid, Helicoverpa armigera 21 , the expansion of GRs may be a unique adaptation mechanism for polyphagous Noctuidae to feed on a wide variety of host plants (Table 2 ). Phylogenetic analysis including GR genes of B . mori , M . sexta , H . melpomene and S . frugiperda showed clearly that greatly expanded bitter GR clades were composed of SlituGR s and SfruGR s exclusively (Supplementary Fig. 3", "role": "user" }, { "content": "As part of an international consortium, INRA researchers, in partnership with the CEA and INRIA , have sequenced one of the first genomes of a moth from the superfamily Noctuoidea: Spodoptera frugiperda, or armyworm. This crop pest – until now only known on the American continent – has become invasive in Africa since 2016. Published in Scientific Reports on 25 September 2017, this study opens up perspectives for new methods of biological control and a better understanding of the mechanisms involved in the appearance of pesticide resistance. Spodoptera frugiperda is a moth belonging to the superfamily Noctuoidea. It is also called Armyworm because the caterpillars are sometimes so numerous that they form \"carpets\" on the ground, similar to an army on the march. Unlike the majority of herbivorous insects, the Armyworm is highly polyphagous: it attacks over one hundred plant species, including crops (maize, rice, sorghum, cotton and soybean). The moth moves in large swarms and is able to fly long distances. Until now limited to America and the Caribbean, Spodoptera frugiperda is estimated to cause 600 million dollars in damage in Brazil every year according to the FAO. In America, 67 cases of insect resistance to pesticides have been identified to date, illustrating the difficulty of controlling these populations. Since January 2016, it has become invasive in Africa, where it destroys maize crops in 21 countries in the south and west parts of the continent. It is currently a threat to the European continent. Sequencing of one of the first genomes of a moth belonging to the superfamily Noctuoidea In the framework of an international public consortium called Fall Armyworm, INRA researchers, in partnership with the CEA and INRIA, sequenced the genome of Spodoptera frugiperda. They described one of the first genomes of a moth belonging to the superfamily Noctuoidea and, more specifically, studied three types of gene families in this insect. Scientists first analysed a group of genes involved in the recognition of host plants which allows them to feed or lay their eggs. By comparing the genome of S. frugiperda with the available genomes of (non-polyphagous) Lepidoptera, researchers found an expansion in the number of genes (230 versus 45 to 74 in other Lepidoptera) encoding a certain type of taste receptor. The latter are located on the moth's trump (proboscis) or under their legs. They are thought to allow them to detect toxins or bitter compounds produced by plants. The only insect known to have such taste receptor expansions is an omnivorous beetle, the red flour beetle, which also attacks a wide range of foods.Researchers also looked at other families of genes necessary to cope withr the chemical defences that plants overproduce when they are attacked (detoxification). They discovered expansions in two of the four major gene families for detoxification (encoding cytochrome P450s (CYP) or glutathione-S-transferases (GST)). These are the same genes that can be involved in resistance to pesticides.Lastly, scientists described a group of genes involved in the digestion of plant tissues. For the purpose of the study, two genomes of S. frugiperda were analysed: two genomic variants based on the insect's host plant – the maize variant and rice variant, which are found throughout their range of distribution in America. The researchers found differences between the variants in terms of the number and sequence of genes necessary to detoxify the toxins emitted by the plants and in the genes necessary for digestion. This data was made available to the international scientific community to allow specialists to identify which variant of the moth is invading Africa. Moreover, this work will also make it possible to envision new biological control methods. It will also improve understanding of the mechanisms by which pesticide resistance appears. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract The tobacco cutworm, Spodoptera litura , is among the most widespread and destructive agricultural pests, feeding on over 100 crops throughout tropical and subtropical Asia. By genome sequencing, physical mapping and transcriptome analysis, we found that the gene families encoding receptors for bitter or toxic substances and detoxification enzymes, such as cytochrome P450, carboxylesterase and glutathione- S -transferase, were massively expanded in this polyphagous species, enabling its extraordinary ability to detect and detoxify many plant secondary compounds. Larval exposure to insecticidal toxins induced expression of detoxification genes, and knockdown of representative genes using short interfering RNA (siRNA) reduced larval survival, consistent with their contribution to the insect’s natural pesticide tolerance. A population genetics study indicated that this species expanded throughout southeast Asia by migrating along a South India–South China–Japan axis, adapting to wide-ranging ecological conditions with diverse host plants and insecticides, surviving and adapting with the aid of its expanded detoxification systems. The findings of this study will enable the development of new pest management strategies for the control of major agricultural pests such as S . litura . Introduction The tobacco cutworm, Spodoptera litura (Lepidoptera, Noctuidae), is an important polyphagous pest; its larvae feed on over 100 crops 1 . This pest is widely distributed throughout tropical and subtropical areas of Asia including India, China and Japan. In India particularly, S . litura causes heavy yield loss varying between 10 and 30% 1 . High fecundity and a short life cycle under tropical conditions result in a high rate of population increase and subsequent population outbreaks. In addition, it has evolved high resistance to every class of pesticide used against it 2 , 3 , including the biopesticide Bt 4 . Few complete genome sequences have been reported for noctuids, which include many serious agricultural pests. Asian researchers launched the S . litura genome project as an international collaboration in cooperation with the Fall armyworm International Public Consortium (FAW-IPC), for which a genome project is coordinately underway 5 . By comparative genomic studies with the monophagous species Bombyx mori and other Spodoptera species such as S . frugiperda (which has a different geographical distribution), S . litura genome information can provide new insights into mechanisms of evolution, host plant specialization and ecological adaptation, which can serve as a reference for noctuids and lead to selective targets for innovative pest control. Results and discussion Genome structure and linkage map of S. litura. We sequenced and assembled a genome for S . litura comprising 438.32 Mb, which contains 15,317 predicted protein-coding genes analysed by GLEAN 6 and 31.8% repetitive elements (Supplementary Tables 1 – 4 ). Among four representative lepidopteran species with complete genome sequences 7 , 8 , 9 , S . litura harbours the smallest number of species-specific gene families (Supplementary Fig. 1a and Supplementary Table 9 ). A phylogenetic tree constructed by single-copy orthologous groups showed that S . litura separated from B . mori and Danaus plexippus about 104.7 Myr ago (Ma), and diverged approximately 147 Ma from the more basal Plutella xylostella , whereas Lepidoptera as a whole separated from Diptera about 258 Ma, consistent with reported divergence time estimates 10 (Supplementary Fig. 1b ). To construct a linkage map, a heterozygous male F1 backcross (BC1) population was established between Japanese and Indian inbred strains. The resulting genetic analysis used 6088 RAD-tags as markers to anchor 639 scaffolds covering 380.89 Mb onto 31 chromosomes, which corresponded to 87% of the genome (Supplementary Section 2). Genomic syntenies from S . litura to B . mori and to Heliconius melpomene revealed two modes of chromosomal fusion (Supplementary Tables 10 and 11 and Supplementary Fig. 2 ). In one, six S . litura chromosomes (haploid chromosome number N = 31) were fused to form three B . mori chromosomes ( N = 28). In the other, six sets of S . litura chromosomes were fused, corresponding to six H . melpomene chromosomes ( N = 21) 11 , and another eight S . litura chromosomes were fused, corresponding to four other H . melpomene chromosomes. These changes were consistent with previous reports on chromosome evolution among butterflies including Melitaea cinxia 12 and the moth Manduca sexta 13 ( Supplementary Section 2 ). Massive expansion of bitter gustatory receptor and detoxification-related gene families associated with polyphagy of Noctuidae To elucidate key genome changes associated with host plant specialization and adaptation in Lepidoptera, we compared chemosensory and detoxification-related gene families between the extremely polyphagous lepidopteran pest S . litura and the almost monophagous lepidopteran model organism B . mori . We found large expansions of the gustatory receptor (GR), cytochrome P450 (P450), carboxylesterase (COE) and glutathione- S -transferase (GST) gene families in S . litura (Table 1 ). Chemosensory genes play an essential role in host plant recognition of herbivores. GRs, especially, are highly variable among species, which could be a major factor for host plant adaptation. GRs are categorized into three classes—CO 2 receptors, sugar receptors and bitter receptors—among which bitter receptors are most variable, while CO 2 and sugar receptors are conserved 14 , 15 , 16 , 17 , 18 . Manual annotation identified 237 GR genes in the S . litura genome (Table 2 , Fig. 1a and Supplementary Table 13 ), whereas in the other lepidopteran species investigated to date, most of which are mono- and oligophagous, only about 45–80 GRs are reported 8 , 11 , 14 , 16 , 19 , 20 . Since large expansions of GR genes were also reported recently in S . frugiperda 5 and in another polyphagous noctuid, Helicoverpa armigera 21 , the expansion of GRs may be a unique adaptation mechanism for polyphagous Noctuidae to feed on a wide variety of host plants (Table 2 ). Phylogenetic analysis including GR genes of B . mori , M . sexta , H . melpomene and S . frugiperda showed clearly that greatly expanded bitter GR clades were composed of SlituGR s and SfruGR s exclusively (Supplementary Fig. 3<|im_end|> <|im_start|>assistant As part of an international consortium, INRA researchers, in partnership with the CEA and INRIA , have sequenced one of the first genomes of a moth from the superfamily Noctuoidea: Spodoptera frugiperda, or armyworm. This crop pest – until now only known on the American continent – has become invasive in Africa since 2016. Published in Scientific Reports on 25 September 2017, this study opens up perspectives for new methods of biological control and a better understanding of the mechanisms involved in the appearance of pesticide resistance. Spodoptera frugiperda is a moth belonging to the superfamily Noctuoidea. It is also called Armyworm because the caterpillars are sometimes so numerous that they form "carpets" on the ground, similar to an army on the march. Unlike the majority of herbivorous insects, the Armyworm is highly polyphagous: it attacks over one hundred plant species, including crops (maize, rice, sorghum, cotton and soybean). The moth moves in large swarms and is able to fly long distances. Until now limited to America and the Caribbean, Spodoptera frugiperda is estimated to cause 600 million dollars in damage in Brazil every year according to the FAO. In America, 67 cases of insect resistance to pesticides have been identified to date, illustrating the difficulty of controlling these populations. Since January 2016, it has become invasive in Africa, where it destroys maize crops in 21 countries in the south and west parts of the continent. It is currently a threat to the European continent. Sequencing of one of the first genomes of a moth belonging to the superfamily Noctuoidea In the framework of an international public consortium called Fall Armyworm, INRA researchers, in partnership with the CEA and INRIA, sequenced the genome of Spodoptera frugiperda. They described one of the first genomes of a moth belonging to the superfamily Noctuoidea and, more specifically, studied three types of gene families in this insect. Scientists first analysed a group of genes involved in the recognition of host plants which allows them to feed or lay their eggs. By comparing the genome of S. frugiperda with the available genomes of (non-polyphagous) Lepidoptera, researchers found an expansion in the number of genes (230 versus 45 to 74 in other Lepidoptera) encoding a certain type of taste receptor. The latter are located on the moth's trump (proboscis) or under their legs. They are thought to allow them to detect toxins or bitter compounds produced by plants. The only insect known to have such taste receptor expansions is an omnivorous beetle, the red flour beetle, which also attacks a wide range of foods.Researchers also looked at other families of genes necessary to cope withr the chemical defences that plants overproduce when they are attacked (detoxification). They discovered expansions in two of the four major gene families for detoxification (encoding cytochrome P450s (CYP) or glutathione-S-transferases (GST)). These are the same genes that can be involved in resistance to pesticides.Lastly, scientists described a group of genes involved in the digestion of plant tissues. For the purpose of the study, two genomes of S. frugiperda were analysed: two genomic variants based on the insect's host plant – the maize variant and rice variant, which are found throughout their range of distribution in America. The researchers found differences between the variants in terms of the number and sequence of genes necessary to detoxify the toxins emitted by the plants and in the genes necessary for digestion. This data was made available to the international scientific community to allow specialists to identify which variant of the moth is invading Africa. Moreover, this work will also make it possible to envision new biological control methods. It will also improve understanding of the mechanisms by which pesticide resistance appears. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 578, 27531, 4018, 56741, 11, 3165, 347, 113547, 13318, 5808, 1174, 374, 4315, 279, 1455, 24716, 323, 40652, 29149, 76056, 11, 26040, 389, 927, 220, 1041, 31665, 6957, 35148, 323, 42129, 51172, 13936, 13, 3296, 33869, 62119, 11, 7106, 13021, 323, 36815, 638, 6492, 11, 584, 1766, 430, 279, 15207, 8689, 11418, 44540, 369, 26242, 477, 21503, 33155, 323, 61987, 2461, 56067, 11, 1778, 439, 9693, 998, 33002, 393, 10617, 11, 1841, 2054, 982, 3751, 521, 323, 35169, 589, 6473, 12, 328, 482, 25163, 521, 11, 1051, 64807, 17626, 304, 420, 10062, 764, 351, 788, 9606, 11, 28462, 1202, 24674, 5845, 311, 11388, 323, 61987, 1463, 1690, 6136, 14580, 32246, 13, 32404, 838, 14675, 311, 27080, 292, 26966, 62186, 36572, 7645, 315, 61987, 2461, 21389, 11, 323, 14459, 2996, 315, 18740, 21389, 1701, 2875, 75387, 41214, 320, 6455, 31820, 8, 11293, 45555, 838, 20237, 11, 13263, 449, 872, 19035, 311, 279, 27080, 753, 5933, 84673, 25065, 13, 362, 7187, 56104, 4007, 16717, 430, 420, 9606, 17626, 6957, 42552, 13936, 555, 85626, 3235, 264, 4987, 6890, 4235, 26070, 5734, 4235, 49852, 8183, 11, 70817, 311, 7029, 82105, 50953, 4787, 449, 17226, 3552, 11012, 323, 27080, 76195, 11, 40746, 323, 70817, 449, 279, 12576, 315, 1202, 17626, 61987, 2461, 6067, 13, 578, 14955, 315, 420, 4007, 690, 7431, 279, 4500, 315, 502, 44885, 6373, 15174, 369, 279, 2585, 315, 3682, 29149, 76056, 1778, 439, 328, 662, 13318, 5808, 662, 29438, 578, 27531, 4018, 56741, 11, 3165, 347, 113547, 13318, 5808, 320, 43, 752, 307, 113547, 11, 2360, 302, 2480, 6043, 705, 374, 459, 3062, 10062, 764, 351, 788, 44885, 26, 1202, 83861, 5510, 389, 927, 220, 1041, 31665, 220, 16, 662, 1115, 44885, 374, 13882, 4332, 6957, 35148, 323, 42129, 51172, 5789, 315, 13936, 2737, 6890, 11, 5734, 323, 6457, 13, 763, 6890, 8104, 11, 328, 662, 13318, 5808, 11384, 8987, 7692, 4814, 29865, 1990, 220, 605, 323, 220, 966, 4, 220, 16, 662, 5234, 55061, 1263, 488, 323, 264, 2875, 2324, 11008, 1234, 35148, 4787, 1121, 304, 264, 1579, 4478, 315, 7187, 5376, 323, 17876, 7187, 77871, 13, 763, 5369, 11, 433, 706, 28995, 1579, 13957, 311, 1475, 538, 315, 84673, 1511, 2403, 433, 220, 17, 1174, 220, 18, 1174, 2737, 279, 17332, 30223, 14842, 426, 83, 220, 19, 662, 44015, 4686, 33869, 24630, 617, 1027, 5068, 369, 93101, 92316, 11, 902, 2997, 1690, 6129, 29149, 76056, 13, 14875, 12074, 11887, 279, 328, 662, 13318, 5808, 33869, 2447, 439, 459, 6625, 20632, 304, 23915, 449, 279, 15128, 13695, 56741, 7327, 3142, 73547, 320, 3711, 54, 12, 63219, 705, 369, 902, 264, 33869, 2447, 374, 30478, 2718, 38199, 220, 20, 662, 3296, 55394, 81064, 7978, 449, 279, 1647, 5237, 351, 788, 9606, 48452, 1729, 87, 4411, 72, 323, 1023, 3165, 347, 113547, 9606, 1778, 439, 328, 662, 1448, 773, 13154, 3315, 320, 8370, 706, 264, 2204, 54001, 8141, 705, 328, 662, 13318, 5808, 33869, 2038, 649, 3493, 502, 26793, 1139, 24717, 315, 15740, 11, 3552, 6136, 66979, 323, 50953, 34185, 11, 902, 649, 8854, 439, 264, 5905, 369, 93101, 92316, 323, 3063, 311, 44010, 11811, 369, 18699, 44885, 2585, 13, 18591, 323, 10430, 82917, 6070, 323, 72541, 2472, 315, 328, 13, 13318, 5808, 13, 1226, 11506, 5886, 323, 35105, 264, 33869, 369, 328, 662, 13318, 5808, 46338, 220, 20596, 13, 843, 51365, 11, 902, 5727, 220, 868, 11, 16718, 19698, 13128, 1824, 3785, 21389, 67458, 555, 480, 46918, 220, 21, 323, 220, 2148, 13, 23, 4, 59177, 5540, 320, 10254, 67082, 43252, 220, 16, 1389, 220, 19, 7609, 22395, 3116, 18740, 514, 10629, 2985, 261, 276, 9606, 449, 4686, 33869, 24630, 220, 22, 1174, 220, 23, 1174, 220, 24, 1174, 328, 662, 13318, 5808, 69566, 2530, 279, 25655, 1396, 315, 9606, 19440, 15207, 8689, 320, 10254, 67082, 23966, 13, 220, 16, 64, 323, 99371, 6771, 220, 24, 7609, 362, 37555, 86945, 5411, 5021, 20968, 555, 3254, 67240, 30299, 1640, 788, 5315, 8710, 430, 328, 662, 13318, 5808, 19180, 505, 426, 662, 4411, 72, 323, 47713, 355, 281, 2635, 2877, 355, 922, 220, 6849, 13, 22, 3092, 81, 4227, 320, 30635, 705, 323, 37441, 3640, 13489, 220, 10288, 11583, 505, 279, 810, 80710, 1856, 332, 6985, 31884, 55437, 6985, 1174, 20444, 121688, 307, 113547, 439, 264, 4459, 19180, 505, 7923, 418, 2473, 922, 220, 15966, 11583, 11, 13263, 449, 5068, 82258, 892, 17989, 220, 605, 320, 10254, 67082, 23966, 13, 220, 16, 65, 7609, 2057, 9429, 264, 72541, 2472, 11, 264, 30548, 76523, 70, 788, 8762, 435, 16, 1203, 29942, 320, 5002, 16, 8, 7187, 574, 9749, 1990, 11002, 323, 7904, 304, 91842, 42400, 13, 578, 13239, 19465, 6492, 1511, 220, 19944, 23, 75250, 64914, 439, 24915, 311, 17543, 220, 23079, 57250, 18938, 18702, 220, 13897, 13, 4578, 51365, 8800, 220, 2148, 83181, 11, 902, 8024, 291, 311, 220, 4044, 4, 315, 279, 33869, 320, 10254, 67082, 11360, 220, 17, 570, 9500, 3151, 6705, 43569, 552, 505, 328, 662, 13318, 5808, 311, 426, 662, 4411, 72, 323, 311, 16183, 1965, 9334, 296, 1290, 316, 1994, 10675, 1403, 20362, 315, 22083, 96108, 37608, 320, 10254, 67082, 43252, 220, 605, 323, 220, 806, 323, 99371, 23966, 13, 220, 17, 7609, 763, 832, 11, 4848, 328, 662, 13318, 5808, 83181, 320, 38910, 52196, 51815, 1396, 452, 284, 220, 2148, 8, 1051, 75754, 311, 1376, 2380, 426, 662, 4411, 72, 83181, 320, 452, 284, 220, 1591, 570, 763, 279, 1023, 11, 4848, 7437, 315, 328, 662, 13318, 5808, 83181, 1051, 75754, 11, 12435, 311, 4848, 473, 662, 296, 1290, 316, 1994, 83181, 320, 452, 284, 220, 1691, 8, 220, 806, 1174, 323, 2500, 8223, 328, 662, 13318, 5808, 83181, 1051, 75754, 11, 12435, 311, 3116, 1023, 473, 662, 296, 1290, 316, 1994, 83181, 13, 4314, 4442, 1051, 13263, 449, 3766, 6821, 389, 51815, 15740, 4315, 81776, 2737, 11220, 275, 71435, 8628, 68294, 220, 717, 323, 279, 98178, 24789, 84, 936, 38103, 64, 220, 1032, 320, 99371, 11360, 220, 17, 7609, 82564, 14800, 315, 26242, 30914, 5382, 35268, 323, 61987, 2461, 14228, 15207, 8689, 5938, 449, 10062, 764, 82770, 315, 2360, 302, 2480, 6043, 2057, 97298, 349, 1401, 33869, 4442, 5938, 449, 3552, 6136, 66979, 323, 34185, 304, 121688, 307, 113547, 11, 584, 7863, 8590, 437, 729, 683, 323, 61987, 2461, 14228, 15207, 8689, 1990, 279, 9193, 10062, 764, 351, 788, 514, 10629, 2985, 261, 276, 44885, 328, 662, 13318, 5808, 323, 279, 4661, 1647, 5237, 351, 788, 514, 10629, 2985, 261, 276, 1646, 47120, 426, 662, 4411, 72, 662, 1226, 1766, 3544, 78588, 315, 279, 30914, 5382, 35268, 320, 8796, 705, 9693, 998, 33002, 393, 10617, 320, 47, 10617, 705, 1841, 2054, 982, 3751, 521, 320, 8445, 36, 8, 323, 35169, 589, 6473, 12, 328, 482, 25163, 521, 320, 76620, 8, 15207, 8689, 304, 328, 662, 13318, 5808, 320, 2620, 220, 16, 7609, 921, 15295, 729, 683, 21389, 1514, 459, 7718, 3560, 304, 3552, 6136, 18324, 315, 39999, 344, 4692, 13, 15116, 82, 11, 5423, 11, 527, 7701, 3977, 4315, 9606, 11, 902, 1436, 387, 264, 3682, 8331, 369, 3552, 6136, 34185, 13, 15116, 82, 527, 71974, 1139, 2380, 6989, 2345, 8445, 220, 17, 44540, 11, 13465, 44540, 323, 26242, 44540, 2345, 77405, 902, 26242, 44540, 527, 1455, 3977, 11, 1418, 7432, 220, 17, 323, 13465, 44540, 527, 1615, 2841, 220, 975, 1174, 220, 868, 1174, 220, 845, 1174, 220, 1114, 1174, 220, 972, 662, 14881, 21917, 11054, 220, 14590, 15116, 21389, 304, 279, 328, 662, 13318, 5808, 33869, 320, 2620, 220, 17, 1174, 23966, 13, 220, 16, 64, 323, 99371, 6771, 220, 1032, 7026, 20444, 304, 279, 1023, 514, 10629, 2985, 261, 276, 9606, 27313, 311, 2457, 11, 1455, 315, 902, 527, 40774, 12, 323, 55984, 5237, 351, 788, 11, 1193, 922, 220, 1774, 4235, 1490, 15116, 82, 527, 5068, 220, 23, 1174, 220, 806, 1174, 220, 975, 1174, 220, 845, 1174, 220, 777, 1174, 220, 508, 662, 8876, 3544, 78588, 315, 15116, 21389, 1051, 1101, 5068, 6051, 304, 328, 662, 1448, 773, 13154, 3315, 220, 20, 323, 304, 2500, 10062, 764, 351, 788, 93101, 2480, 11, 16183, 292, 2017, 6733, 6916, 343, 2473, 220, 1691, 1174, 279, 14800, 315, 15116, 82, 1253, 387, 264, 5016, 34185, 17383, 369, 10062, 764, 351, 788, 2360, 302, 2480, 6043, 311, 5510, 389, 264, 7029, 8205, 315, 3552, 11012, 320, 2620, 220, 17, 7609, 93682, 86945, 5411, 6492, 2737, 15116, 21389, 315, 426, 662, 4411, 72, 1174, 386, 662, 38103, 64, 1174, 473, 662, 296, 1290, 316, 1994, 323, 328, 662, 1448, 773, 13154, 3315, 8710, 9539, 430, 19407, 17626, 26242, 15116, 1206, 3536, 1051, 24306, 315, 6995, 33462, 8796, 274, 323, 328, 1658, 84, 8796, 274, 24121, 320, 10254, 67082, 23966, 13, 220, 18, 128257, 198, 128256, 78191, 198, 2170, 961, 315, 459, 6625, 75094, 11, 2006, 5726, 12074, 11, 304, 15664, 449, 279, 356, 19657, 323, 2006, 79363, 1174, 617, 11506, 5886, 832, 315, 279, 1176, 85381, 315, 264, 98178, 505, 279, 2307, 19521, 2360, 302, 24012, 42877, 25, 3165, 347, 113547, 1448, 773, 13154, 3315, 11, 477, 13695, 56741, 13, 1115, 19641, 44885, 1389, 3156, 1457, 1193, 3967, 389, 279, 3778, 32843, 1389, 706, 3719, 53354, 304, 10384, 2533, 220, 679, 21, 13, 30114, 304, 38130, 29140, 389, 220, 914, 6250, 220, 679, 22, 11, 420, 4007, 16264, 709, 39555, 369, 502, 5528, 315, 24156, 2585, 323, 264, 2731, 8830, 315, 279, 24717, 6532, 304, 279, 11341, 315, 84673, 13957, 13, 3165, 347, 113547, 1448, 773, 13154, 3315, 374, 264, 98178, 33152, 311, 279, 2307, 19521, 2360, 302, 24012, 42877, 13, 1102, 374, 1101, 2663, 13309, 56741, 1606, 279, 29068, 50946, 1590, 527, 7170, 779, 12387, 430, 814, 1376, 330, 7063, 65301, 1, 389, 279, 5015, 11, 4528, 311, 459, 13695, 389, 279, 15572, 13, 27140, 279, 8857, 315, 39999, 344, 20857, 41911, 11, 279, 13309, 56741, 374, 7701, 10062, 764, 351, 788, 25, 433, 8951, 927, 832, 7895, 6136, 9606, 11, 2737, 31665, 320, 1764, 553, 11, 20228, 11, 25551, 876, 372, 11, 24428, 323, 29839, 17937, 570, 578, 98178, 11031, 304, 3544, 2064, 16293, 323, 374, 3025, 311, 11722, 1317, 27650, 13, 30070, 1457, 7347, 311, 5270, 323, 279, 35374, 11, 3165, 347, 113547, 1448, 773, 13154, 3315, 374, 13240, 311, 5353, 220, 5067, 3610, 11441, 304, 5674, 304, 16327, 1475, 1060, 4184, 311, 279, 15358, 46, 13, 763, 5270, 11, 220, 3080, 5157, 315, 27080, 13957, 311, 61257, 617, 1027, 11054, 311, 2457, 11, 94012, 279, 17250, 315, 26991, 1521, 22673, 13, 8876, 6186, 220, 679, 21, 11, 433, 706, 3719, 53354, 304, 10384, 11, 1405, 433, 60832, 93307, 31665, 304, 220, 1691, 5961, 304, 279, 10007, 323, 9909, 5596, 315, 279, 32843, 13, 1102, 374, 5131, 264, 6023, 311, 279, 7665, 32843, 13, 25848, 11627, 315, 832, 315, 279, 1176, 85381, 315, 264, 98178, 33152, 311, 279, 2307, 19521, 2360, 302, 24012, 42877, 763, 279, 12914, 315, 459, 6625, 586, 75094, 2663, 15128, 13309, 56741, 11, 2006, 5726, 12074, 11, 304, 15664, 449, 279, 356, 19657, 323, 2006, 79363, 11, 11506, 5886, 279, 33869, 315, 3165, 347, 113547, 1448, 773, 13154, 3315, 13, 2435, 7633, 832, 315, 279, 1176, 85381, 315, 264, 98178, 33152, 311, 279, 2307, 19521, 2360, 302, 24012, 42877, 323, 11, 810, 11951, 11, 20041, 2380, 4595, 315, 15207, 8689, 304, 420, 27080, 13, 57116, 1176, 67458, 264, 1912, 315, 21389, 6532, 304, 279, 18324, 315, 3552, 11012, 902, 6276, 1124, 311, 5510, 477, 11203, 872, 19335, 13, 3296, 27393, 279, 33869, 315, 328, 13, 1448, 773, 13154, 3315, 449, 279, 2561, 85381, 315, 320, 6414, 2320, 5849, 764, 351, 788, 8, 121688, 307, 113547, 11, 12074, 1766, 459, 14800, 304, 279, 1396, 315, 21389, 320, 9870, 19579, 220, 1774, 311, 220, 5728, 304, 1023, 121688, 307, 113547, 8, 11418, 264, 3738, 955, 315, 12945, 35268, 13, 578, 15629, 527, 7559, 389, 279, 98178, 596, 39155, 320, 20493, 24366, 285, 8, 477, 1234, 872, 14535, 13, 2435, 527, 3463, 311, 2187, 1124, 311, 11388, 62186, 477, 26242, 32246, 9124, 555, 11012, 13, 578, 1193, 27080, 3967, 311, 617, 1778, 12945, 35268, 78588, 374, 459, 50197, 344, 20857, 98486, 11, 279, 2579, 20415, 98486, 11, 902, 1101, 8951, 264, 7029, 2134, 315, 15657, 8542, 2974, 388, 1101, 7111, 520, 1023, 8689, 315, 21389, 5995, 311, 37586, 449, 81, 279, 11742, 711, 2436, 430, 11012, 927, 98374, 994, 814, 527, 18855, 320, 19842, 5241, 2461, 570, 2435, 11352, 78588, 304, 1403, 315, 279, 3116, 3682, 15207, 8689, 369, 61987, 2461, 320, 17600, 9693, 998, 33002, 393, 10617, 82, 320, 34, 10158, 8, 477, 35169, 589, 6473, 6354, 93791, 2315, 320, 76620, 4682, 4314, 527, 279, 1890, 21389, 430, 649, 387, 6532, 304, 13957, 311, 61257, 25709, 398, 11, 14248, 7633, 264, 1912, 315, 21389, 6532, 304, 279, 74502, 315, 6136, 39881, 13, 1789, 279, 7580, 315, 279, 4007, 11, 1403, 85381, 315, 328, 13, 1448, 773, 13154, 3315, 1051, 67458, 25, 1403, 81064, 27103, 3196, 389, 279, 27080, 596, 3552, 6136, 1389, 279, 93307, 11678, 323, 20228, 11678, 11, 902, 527, 1766, 6957, 872, 2134, 315, 8141, 304, 5270, 13, 578, 12074, 1766, 12062, 1990, 279, 27103, 304, 3878, 315, 279, 1396, 323, 8668, 315, 21389, 5995, 311, 61987, 1463, 279, 62186, 48042, 555, 279, 11012, 323, 304, 279, 21389, 5995, 369, 74502, 13, 1115, 828, 574, 1903, 2561, 311, 279, 6625, 12624, 4029, 311, 2187, 35416, 311, 10765, 902, 11678, 315, 279, 98178, 374, 83631, 10384, 13, 23674, 11, 420, 990, 690, 1101, 1304, 433, 3284, 311, 48146, 502, 24156, 2585, 5528, 13, 1102, 690, 1101, 7417, 8830, 315, 279, 24717, 555, 902, 84673, 13957, 8111, 13, 220, 128257, 198 ]

2,284

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract With the current interest in cultured meat, mammalian cell-based meat has mostly been unstructured. There is thus still a high demand for artificial steak-like meat. We demonstrate in vitro construction of engineered steak-like tissue assembled of three types of bovine cell fibers (muscle, fat, and vessel). Because actual meat is an aligned assembly of the fibers connected to the tendon for the actions of contraction and relaxation, tendon-gel integrated bioprinting was developed to construct tendon-like gels. In this study, a total of 72 fibers comprising 42 muscles, 28 adipose tissues, and 2 blood capillaries were constructed by tendon-gel integrated bioprinting and manually assembled to fabricate steak-like meat with a diameter of 5 mm and a length of 10 mm inspired by a meat cut. The developed tendon-gel integrated bioprinting here could be a promising technology for the fabrication of the desired types of steak-like cultured meats. Introduction Over the past decade, cultured meat has drawn tremendous attention from the standpoints of ethics, economics, the environment, and public health, although it is still under debate 1 . More recently, meat analogs that taste like meat but are based on plant proteins have been released commercially 1 , 2 . Although challenges remain unlike with meat analogs, cultured meat is highly sought after due to the possibility of imitating real meat through the manipulation of flavor, muscle/adipose cells’ ratio, and texture 3 , 4 . Bovine cells for cultured meat can currently be secured by two approaches 5 , 6 . One is following the obtention of edible muscle tissues from cattle, their cells are separated into each type such as muscle satellite cells, adult stem cells, and multipotent stem cells, which are then cultured to increase the number of cells. The other is from transforming somatic cells into induced pluripotent stem cells (iPSCs) and differentiating them into each cell type. Primary cultured stem cells, particularly muscle satellite cells, maintain their differentiation capability within 10 passages and thus have a limited number of divisions 7 . But, they should still be safe and acceptable for consumption. Since Post and coworkers unveiled bovine cell fiber-based hamburger, various types of cultured meat have been demonstrated. However, cultured steak with a composition and a structure similar to real steak, comprising mostly adipose cells and aligned muscle cells, is still challenging 4 , 8 , 9 . Various tissue engineering techniques could be applied, such as cell sheet engineering 10 , 11 , cell fiber engineering 12 , cell culture on a 3D-printed scaffold 13 , and 3D cell printing 14 , 15 for mimicking the structural characteristics of steak. Among them, 3D cell printing is promising due to its advantages of scalability and controllability of structure and composition 16 . Especially, a supporting bath-assisted 3D printing (SBP) technique where ink is dispensed inside a gel or a suspension with thixotropy is noteworthy. Under shear forces, the viscosity of a gel or a suspension becomes of low viscosity, enabling the ink dispensing, and it returns to a high viscosity when the shear force is released, maintaining the printed form 17 . Since the SBP is able to overcome not only the restricted ink viscosity range but also the drying problem during prolonged printing in extrusion-based 3D printing in the air-interfaced environment, several studies over the past five years have shown the feasibility of complex tissue fabrication 18 , 19 , 20 , 21 , 22 , 23 , 24 . Steak meat has an aligned structure of skeletal muscle fascicles with a diameter from around 900 μm to 2.3 mm 25 , depending on age and animal parts, formed by assembled skeletal muscle fibers, connected to the tendon for its shrinkage and relaxation movements. The muscle fibers are covered with basement membrane and the muscle fascicles are surrounded by fat together with blood capillaries (Fig. 1a ). The component ratio and location of the muscle, adipose tissues, and blood capillaries are significantly different according to the meat type and its country of origin. For example, red meat in the rump of Japanese Wagyu has only 10.7% adipose tissues, whereas the sirloin of the Wagyu has 47.5% 26 . Accordingly, the development of a methodology for assembling the three types of fibers with the desired location, ratio, and amount will be a key manufacturing technology of cultured steak. Fig. 1: Overview of the work. a Structure of steak. (i, ii) H&E- and (iii) Azan-stained images of a piece of steak. Representative images from three independent experiments are shown. All scale bars denote 100 μm (iv) Schematic of a hierarchical structure in muscle. b Schematic of the construction process for cultured steak. The first step is cell purification of tissue from cattle to obtain bovine satellite cells (bSCs) and bovine adipose-derived stem cells (bADSCs). The second is supporting bath-assisted printing (SBP) of bSCs and bADSCs to fabricate the muscle, fat, and vascular tissue with a fibrous structure. The third is the assembly of cell fibers to mimic the commercial steak’s structure. *SVF stromal vascular fraction. Full size image Here, we demonstrate a three-step strategy for the construction of engineered steak-like meat: (1) collection of edible bovine satellite cells (bSCs) and bovine adipose-derived stem cells (bADSCs) from beef meats and their subsequent expansion, (2) development of the tendon-gel-integrated bioprinting (TIP) for the fabrication of cell fibers and their subsequent differentiation to skeletal muscle, adipose, and blood capillary fibers, and (3) assembly of the differentiated cell fibers to construct engineered steak-like meat by mimicking the histological structures of an actual beef steak (Fig. 1b ). Since the tendon is a key tissue for the muscle fiber alignment and maturation, we fabricated tendon gels by TIP to enable their consecutive connection with the muscle cell fibers, inducing the formation of aligned matured muscle fibers. In this study, a total of 72 fibers comprising 42 muscle, 28 adipose, and 2 blood capillaries were constructed by TIP. They were subsequently assembled to fabricate steak-like meat with a diameter of 5 mm and", "role": "user" }, { "content": "Scientists from Osaka University used stem cells isolated from Wagyu cows to 3D-print a meat alternative containing muscle, fat, and blood vessels arranged to closely resemble conventional steaks. This work may help usher in a more sustainable future with widely available cultured meat. Wagyu can be literally translated into \"Japanese cow,\" and is famous around the globe for its high content of intramuscular fat, known as marbling or sashi. This marbling provides the beef its rich flavors and distinctive texture. However, the way cattle are raised today is often considered to be unsustainable in light of its outsized contribution to climate emissions. Currently, the available \"cultured meat\" alternatives only consist primarily of poorly organized muscle fiber cells that fail to reproduce the complex structure of real beef steaks. Now, a team of scientists led by Osaka University have used 3D-Printing to create synthetic meat that looks more like the real thing. \"Using the histological structure of Wagyu beef as a blueprint, we have developed a 3D-printing method that can produce tailor-made complex structures, like muscle fibers, fat, and blood vessels,\" lead author Dong-Hee Kang says. To overcome this challenge, the team started with two types of stem cells, called bovine satellite cells and adipose-derived stem cells. Under the right laboratory conditions, these \"multipotent\" cells can be coaxed to differentiate into every type of cell needed to produce the cultured meat. Individual fibers including muscle, fat, or blood vessels were fabricated from these cells using bioprinting. The fibers were then arranged in 3D, following the histological structure, to reproduce the structure of the real Wagyu meat, which was finally sliced perpendicularly, in a similar way to the traditional Japanese candy Kintaro-ame. This process made the reconstruction of the complex meat tissue structure possible in a customizable manner. \"By improving this technology, it will be possible to not only reproduce complex meat structures, such as the beautiful sashi of Wagyu beef, but to also make subtle adjustments to the fat and muscle components,\" senior author Michiya Matsusaki says. That is, customers would be able to order cultured meat with their desired amount of fat, based on taste and health considerations. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract With the current interest in cultured meat, mammalian cell-based meat has mostly been unstructured. There is thus still a high demand for artificial steak-like meat. We demonstrate in vitro construction of engineered steak-like tissue assembled of three types of bovine cell fibers (muscle, fat, and vessel). Because actual meat is an aligned assembly of the fibers connected to the tendon for the actions of contraction and relaxation, tendon-gel integrated bioprinting was developed to construct tendon-like gels. In this study, a total of 72 fibers comprising 42 muscles, 28 adipose tissues, and 2 blood capillaries were constructed by tendon-gel integrated bioprinting and manually assembled to fabricate steak-like meat with a diameter of 5 mm and a length of 10 mm inspired by a meat cut. The developed tendon-gel integrated bioprinting here could be a promising technology for the fabrication of the desired types of steak-like cultured meats. Introduction Over the past decade, cultured meat has drawn tremendous attention from the standpoints of ethics, economics, the environment, and public health, although it is still under debate 1 . More recently, meat analogs that taste like meat but are based on plant proteins have been released commercially 1 , 2 . Although challenges remain unlike with meat analogs, cultured meat is highly sought after due to the possibility of imitating real meat through the manipulation of flavor, muscle/adipose cells’ ratio, and texture 3 , 4 . Bovine cells for cultured meat can currently be secured by two approaches 5 , 6 . One is following the obtention of edible muscle tissues from cattle, their cells are separated into each type such as muscle satellite cells, adult stem cells, and multipotent stem cells, which are then cultured to increase the number of cells. The other is from transforming somatic cells into induced pluripotent stem cells (iPSCs) and differentiating them into each cell type. Primary cultured stem cells, particularly muscle satellite cells, maintain their differentiation capability within 10 passages and thus have a limited number of divisions 7 . But, they should still be safe and acceptable for consumption. Since Post and coworkers unveiled bovine cell fiber-based hamburger, various types of cultured meat have been demonstrated. However, cultured steak with a composition and a structure similar to real steak, comprising mostly adipose cells and aligned muscle cells, is still challenging 4 , 8 , 9 . Various tissue engineering techniques could be applied, such as cell sheet engineering 10 , 11 , cell fiber engineering 12 , cell culture on a 3D-printed scaffold 13 , and 3D cell printing 14 , 15 for mimicking the structural characteristics of steak. Among them, 3D cell printing is promising due to its advantages of scalability and controllability of structure and composition 16 . Especially, a supporting bath-assisted 3D printing (SBP) technique where ink is dispensed inside a gel or a suspension with thixotropy is noteworthy. Under shear forces, the viscosity of a gel or a suspension becomes of low viscosity, enabling the ink dispensing, and it returns to a high viscosity when the shear force is released, maintaining the printed form 17 . Since the SBP is able to overcome not only the restricted ink viscosity range but also the drying problem during prolonged printing in extrusion-based 3D printing in the air-interfaced environment, several studies over the past five years have shown the feasibility of complex tissue fabrication 18 , 19 , 20 , 21 , 22 , 23 , 24 . Steak meat has an aligned structure of skeletal muscle fascicles with a diameter from around 900 μm to 2.3 mm 25 , depending on age and animal parts, formed by assembled skeletal muscle fibers, connected to the tendon for its shrinkage and relaxation movements. The muscle fibers are covered with basement membrane and the muscle fascicles are surrounded by fat together with blood capillaries (Fig. 1a ). The component ratio and location of the muscle, adipose tissues, and blood capillaries are significantly different according to the meat type and its country of origin. For example, red meat in the rump of Japanese Wagyu has only 10.7% adipose tissues, whereas the sirloin of the Wagyu has 47.5% 26 . Accordingly, the development of a methodology for assembling the three types of fibers with the desired location, ratio, and amount will be a key manufacturing technology of cultured steak. Fig. 1: Overview of the work. a Structure of steak. (i, ii) H&E- and (iii) Azan-stained images of a piece of steak. Representative images from three independent experiments are shown. All scale bars denote 100 μm (iv) Schematic of a hierarchical structure in muscle. b Schematic of the construction process for cultured steak. The first step is cell purification of tissue from cattle to obtain bovine satellite cells (bSCs) and bovine adipose-derived stem cells (bADSCs). The second is supporting bath-assisted printing (SBP) of bSCs and bADSCs to fabricate the muscle, fat, and vascular tissue with a fibrous structure. The third is the assembly of cell fibers to mimic the commercial steak’s structure. *SVF stromal vascular fraction. Full size image Here, we demonstrate a three-step strategy for the construction of engineered steak-like meat: (1) collection of edible bovine satellite cells (bSCs) and bovine adipose-derived stem cells (bADSCs) from beef meats and their subsequent expansion, (2) development of the tendon-gel-integrated bioprinting (TIP) for the fabrication of cell fibers and their subsequent differentiation to skeletal muscle, adipose, and blood capillary fibers, and (3) assembly of the differentiated cell fibers to construct engineered steak-like meat by mimicking the histological structures of an actual beef steak (Fig. 1b ). Since the tendon is a key tissue for the muscle fiber alignment and maturation, we fabricated tendon gels by TIP to enable their consecutive connection with the muscle cell fibers, inducing the formation of aligned matured muscle fibers. In this study, a total of 72 fibers comprising 42 muscle, 28 adipose, and 2 blood capillaries were constructed by TIP. They were subsequently assembled to fabricate steak-like meat with a diameter of 5 mm and<|im_end|> <|im_start|>assistant Scientists from Osaka University used stem cells isolated from Wagyu cows to 3D-print a meat alternative containing muscle, fat, and blood vessels arranged to closely resemble conventional steaks. This work may help usher in a more sustainable future with widely available cultured meat. Wagyu can be literally translated into "Japanese cow," and is famous around the globe for its high content of intramuscular fat, known as marbling or sashi. This marbling provides the beef its rich flavors and distinctive texture. However, the way cattle are raised today is often considered to be unsustainable in light of its outsized contribution to climate emissions. Currently, the available "cultured meat" alternatives only consist primarily of poorly organized muscle fiber cells that fail to reproduce the complex structure of real beef steaks. Now, a team of scientists led by Osaka University have used 3D-Printing to create synthetic meat that looks more like the real thing. "Using the histological structure of Wagyu beef as a blueprint, we have developed a 3D-printing method that can produce tailor-made complex structures, like muscle fibers, fat, and blood vessels," lead author Dong-Hee Kang says. To overcome this challenge, the team started with two types of stem cells, called bovine satellite cells and adipose-derived stem cells. Under the right laboratory conditions, these "multipotent" cells can be coaxed to differentiate into every type of cell needed to produce the cultured meat. Individual fibers including muscle, fat, or blood vessels were fabricated from these cells using bioprinting. The fibers were then arranged in 3D, following the histological structure, to reproduce the structure of the real Wagyu meat, which was finally sliced perpendicularly, in a similar way to the traditional Japanese candy Kintaro-ame. This process made the reconstruction of the complex meat tissue structure possible in a customizable manner. "By improving this technology, it will be possible to not only reproduce complex meat structures, such as the beautiful sashi of Wagyu beef, but to also make subtle adjustments to the fat and muscle components," senior author Michiya Matsusaki says. That is, customers would be able to order cultured meat with their desired amount of fat, based on taste and health considerations. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 3161, 279, 1510, 2802, 304, 89948, 13339, 11, 36041, 10700, 2849, 6108, 13339, 706, 10213, 1027, 653, 52243, 13, 2684, 374, 8617, 2103, 264, 1579, 7631, 369, 21075, 50059, 12970, 13339, 13, 1226, 20461, 304, 55004, 8246, 315, 46036, 50059, 12970, 20438, 35105, 315, 2380, 4595, 315, 712, 62301, 2849, 49774, 320, 38827, 9326, 11, 8834, 11, 323, 27274, 570, 9393, 5150, 13339, 374, 459, 27210, 14956, 315, 279, 49774, 8599, 311, 279, 88932, 369, 279, 6299, 315, 71895, 323, 43685, 11, 88932, 2427, 301, 18751, 6160, 454, 1616, 287, 574, 8040, 311, 9429, 88932, 12970, 342, 2053, 13, 763, 420, 4007, 11, 264, 2860, 315, 220, 5332, 49774, 46338, 220, 2983, 24569, 11, 220, 1591, 30366, 974, 39881, 11, 323, 220, 17, 6680, 2107, 484, 5548, 1051, 20968, 555, 88932, 2427, 301, 18751, 6160, 454, 1616, 287, 323, 20684, 35105, 311, 13354, 349, 50059, 12970, 13339, 449, 264, 23899, 315, 220, 20, 9653, 323, 264, 3160, 315, 220, 605, 9653, 14948, 555, 264, 13339, 4018, 13, 578, 8040, 88932, 2427, 301, 18751, 6160, 454, 1616, 287, 1618, 1436, 387, 264, 26455, 5557, 369, 279, 59251, 315, 279, 12974, 4595, 315, 50059, 12970, 89948, 63875, 13, 29438, 6193, 279, 3347, 13515, 11, 89948, 13339, 706, 15107, 28040, 6666, 505, 279, 2559, 7862, 315, 32008, 11, 28989, 11, 279, 4676, 11, 323, 586, 2890, 11, 8051, 433, 374, 2103, 1234, 11249, 220, 16, 662, 4497, 6051, 11, 13339, 24291, 82, 430, 12945, 1093, 13339, 719, 527, 3196, 389, 6136, 28896, 617, 1027, 6004, 54453, 220, 16, 1174, 220, 17, 662, 10541, 11774, 7293, 20426, 449, 13339, 24291, 82, 11, 89948, 13339, 374, 7701, 16495, 1306, 4245, 311, 279, 13336, 315, 737, 50644, 1972, 13339, 1555, 279, 34786, 315, 17615, 11, 16124, 45560, 575, 974, 7917, 529, 11595, 11, 323, 10651, 220, 18, 1174, 220, 19, 662, 426, 869, 483, 7917, 369, 89948, 13339, 649, 5131, 387, 27528, 555, 1403, 20414, 220, 20, 1174, 220, 21, 662, 3861, 374, 2768, 279, 4615, 3012, 315, 67740, 16124, 39881, 505, 36952, 11, 872, 7917, 527, 19180, 1139, 1855, 955, 1778, 439, 16124, 24088, 7917, 11, 6822, 19646, 7917, 11, 323, 12842, 64632, 19646, 7917, 11, 902, 527, 1243, 89948, 311, 5376, 279, 1396, 315, 7917, 13, 578, 1023, 374, 505, 46890, 1794, 780, 7917, 1139, 36572, 60217, 575, 64632, 19646, 7917, 320, 72, 47, 3624, 82, 8, 323, 2204, 23747, 1124, 1139, 1855, 2849, 955, 13, 26150, 89948, 19646, 7917, 11, 8104, 16124, 24088, 7917, 11, 10519, 872, 60038, 23099, 2949, 220, 605, 47869, 323, 8617, 617, 264, 7347, 1396, 315, 37601, 220, 22, 662, 2030, 11, 814, 1288, 2103, 387, 6220, 323, 22281, 369, 15652, 13, 8876, 3962, 323, 84055, 39297, 712, 62301, 2849, 24722, 6108, 89847, 11, 5370, 4595, 315, 89948, 13339, 617, 1027, 21091, 13, 4452, 11, 89948, 50059, 449, 264, 18528, 323, 264, 6070, 4528, 311, 1972, 50059, 11, 46338, 10213, 30366, 974, 7917, 323, 27210, 16124, 7917, 11, 374, 2103, 17436, 220, 19, 1174, 220, 23, 1174, 220, 24, 662, 40741, 20438, 15009, 12823, 1436, 387, 9435, 11, 1778, 439, 2849, 11071, 15009, 220, 605, 1174, 220, 806, 1174, 2849, 24722, 15009, 220, 717, 1174, 2849, 7829, 389, 264, 220, 18, 35, 43245, 291, 85552, 220, 1032, 1174, 323, 220, 18, 35, 2849, 18991, 220, 975, 1174, 220, 868, 369, 28003, 16671, 279, 24693, 17910, 315, 50059, 13, 22395, 1124, 11, 220, 18, 35, 2849, 18991, 374, 26455, 4245, 311, 1202, 22934, 315, 94840, 323, 687, 1119, 2968, 315, 6070, 323, 18528, 220, 845, 662, 36625, 11, 264, 12899, 9061, 35915, 13539, 220, 18, 35, 18991, 320, 17094, 47, 8, 15105, 1405, 27513, 374, 13262, 30040, 4871, 264, 18316, 477, 264, 25288, 449, 270, 953, 354, 18237, 374, 67479, 13, 9636, 65344, 8603, 11, 279, 99530, 315, 264, 18316, 477, 264, 25288, 9221, 315, 3428, 99530, 11, 28462, 279, 27513, 36693, 287, 11, 323, 433, 4780, 311, 264, 1579, 99530, 994, 279, 65344, 5457, 374, 6004, 11, 20958, 279, 17124, 1376, 220, 1114, 662, 8876, 279, 26313, 47, 374, 3025, 311, 23075, 539, 1193, 279, 22486, 27513, 99530, 2134, 719, 1101, 279, 46479, 3575, 2391, 44387, 18991, 304, 11741, 7713, 6108, 220, 18, 35, 18991, 304, 279, 3805, 45994, 69, 4535, 4676, 11, 3892, 7978, 927, 279, 3347, 4330, 1667, 617, 6982, 279, 69543, 315, 6485, 20438, 59251, 220, 972, 1174, 220, 777, 1174, 220, 508, 1174, 220, 1691, 1174, 220, 1313, 1174, 220, 1419, 1174, 220, 1187, 662, 85343, 13339, 706, 459, 27210, 6070, 315, 69397, 16124, 15550, 4440, 449, 264, 23899, 505, 2212, 220, 7467, 33983, 76, 311, 220, 17, 13, 18, 9653, 220, 914, 1174, 11911, 389, 4325, 323, 10065, 5596, 11, 14454, 555, 35105, 69397, 16124, 49774, 11, 8599, 311, 279, 88932, 369, 1202, 30000, 425, 323, 43685, 19567, 13, 578, 16124, 49774, 527, 9960, 449, 31741, 39654, 323, 279, 16124, 15550, 4440, 527, 23712, 555, 8834, 3871, 449, 6680, 2107, 484, 5548, 320, 30035, 13, 220, 16, 64, 7609, 578, 3777, 11595, 323, 3813, 315, 279, 16124, 11, 30366, 974, 39881, 11, 323, 6680, 2107, 484, 5548, 527, 12207, 2204, 4184, 311, 279, 13339, 955, 323, 1202, 3224, 315, 6371, 13, 1789, 3187, 11, 2579, 13339, 304, 279, 436, 1538, 315, 11002, 86993, 41101, 706, 1193, 220, 605, 13, 22, 4, 30366, 974, 39881, 11, 20444, 279, 28146, 385, 258, 315, 279, 86993, 41101, 706, 220, 2618, 13, 20, 4, 220, 1627, 662, 63909, 11, 279, 4500, 315, 264, 38152, 369, 81759, 279, 2380, 4595, 315, 49774, 449, 279, 12974, 3813, 11, 11595, 11, 323, 3392, 690, 387, 264, 1401, 15266, 5557, 315, 89948, 50059, 13, 23966, 13, 220, 16, 25, 35907, 315, 279, 990, 13, 264, 29696, 315, 50059, 13, 320, 72, 11, 14799, 8, 473, 69248, 12, 323, 320, 35694, 8, 15757, 276, 5594, 2692, 5448, 315, 264, 6710, 315, 50059, 13, 38366, 5448, 505, 2380, 9678, 21896, 527, 6982, 13, 2052, 5569, 16283, 79164, 220, 1041, 33983, 76, 320, 344, 8, 328, 82149, 315, 264, 70994, 6070, 304, 16124, 13, 293, 328, 82149, 315, 279, 8246, 1920, 369, 89948, 50059, 13, 578, 1176, 3094, 374, 2849, 94536, 315, 20438, 505, 36952, 311, 6994, 712, 62301, 24088, 7917, 320, 65, 3624, 82, 8, 323, 712, 62301, 30366, 974, 72286, 19646, 7917, 320, 65, 1846, 3624, 82, 570, 578, 2132, 374, 12899, 9061, 35915, 13539, 18991, 320, 17094, 47, 8, 315, 293, 3624, 82, 323, 293, 1846, 3624, 82, 311, 13354, 349, 279, 16124, 11, 8834, 11, 323, 64603, 20438, 449, 264, 16178, 27620, 6070, 13, 578, 4948, 374, 279, 14956, 315, 2849, 49774, 311, 56459, 279, 8518, 50059, 753, 6070, 13, 353, 18282, 37, 120004, 278, 64603, 19983, 13, 8797, 1404, 2217, 5810, 11, 584, 20461, 264, 2380, 30308, 8446, 369, 279, 8246, 315, 46036, 50059, 12970, 13339, 25, 320, 16, 8, 4526, 315, 67740, 712, 62301, 24088, 7917, 320, 65, 3624, 82, 8, 323, 712, 62301, 30366, 974, 72286, 19646, 7917, 320, 65, 1846, 3624, 82, 8, 505, 25309, 63875, 323, 872, 17876, 14800, 11, 320, 17, 8, 4500, 315, 279, 88932, 2427, 301, 20653, 48272, 6160, 454, 1616, 287, 320, 51, 3378, 8, 369, 279, 59251, 315, 2849, 49774, 323, 872, 17876, 60038, 311, 69397, 16124, 11, 30366, 974, 11, 323, 6680, 2107, 35605, 49774, 11, 323, 320, 18, 8, 14956, 315, 279, 89142, 2849, 49774, 311, 9429, 46036, 50059, 12970, 13339, 555, 28003, 16671, 279, 13034, 5848, 14726, 315, 459, 5150, 25309, 50059, 320, 30035, 13, 220, 16, 65, 7609, 8876, 279, 88932, 374, 264, 1401, 20438, 369, 279, 16124, 24722, 17632, 323, 5634, 2060, 11, 584, 70554, 88932, 342, 2053, 555, 350, 3378, 311, 7431, 872, 24871, 3717, 449, 279, 16124, 2849, 49774, 11, 96811, 279, 18488, 315, 27210, 15196, 67, 16124, 49774, 13, 763, 420, 4007, 11, 264, 2860, 315, 220, 5332, 49774, 46338, 220, 2983, 16124, 11, 220, 1591, 30366, 974, 11, 323, 220, 17, 6680, 2107, 484, 5548, 1051, 20968, 555, 350, 3378, 13, 2435, 1051, 28520, 35105, 311, 13354, 349, 50059, 12970, 13339, 449, 264, 23899, 315, 220, 20, 9653, 323, 128257, 198, 128256, 78191, 198, 72326, 505, 88085, 3907, 1511, 19646, 7917, 25181, 505, 86993, 41101, 46266, 311, 220, 18, 35, 43245, 264, 13339, 10778, 8649, 16124, 11, 8834, 11, 323, 6680, 31080, 28902, 311, 15499, 52280, 21349, 4179, 10011, 13, 1115, 990, 1253, 1520, 64260, 304, 264, 810, 22556, 3938, 449, 13882, 2561, 89948, 13339, 13, 86993, 41101, 649, 387, 16280, 25548, 1139, 330, 52566, 19923, 1359, 323, 374, 11495, 2212, 279, 24867, 369, 1202, 1579, 2262, 315, 10805, 56455, 22077, 8834, 11, 3967, 439, 3678, 9894, 477, 274, 31478, 13, 1115, 3678, 9894, 5825, 279, 25309, 1202, 9257, 32523, 323, 35947, 10651, 13, 4452, 11, 279, 1648, 36952, 527, 9408, 3432, 374, 3629, 6646, 311, 387, 98609, 304, 3177, 315, 1202, 23651, 1534, 19035, 311, 10182, 20748, 13, 25122, 11, 279, 2561, 330, 93113, 3149, 13339, 1, 27548, 1193, 6824, 15871, 315, 31555, 17057, 16124, 24722, 7917, 430, 3775, 311, 23645, 279, 6485, 6070, 315, 1972, 25309, 4179, 10011, 13, 4800, 11, 264, 2128, 315, 14248, 6197, 555, 88085, 3907, 617, 1511, 220, 18, 35, 12, 39628, 311, 1893, 28367, 13339, 430, 5992, 810, 1093, 279, 1972, 3245, 13, 330, 16834, 279, 13034, 5848, 6070, 315, 86993, 41101, 25309, 439, 264, 54029, 11, 584, 617, 8040, 264, 220, 18, 35, 43245, 287, 1749, 430, 649, 8356, 52056, 27975, 6485, 14726, 11, 1093, 16124, 49774, 11, 8834, 11, 323, 6680, 31080, 1359, 3063, 3229, 53483, 12, 1548, 68, 55376, 2795, 13, 2057, 23075, 420, 8815, 11, 279, 2128, 3940, 449, 1403, 4595, 315, 19646, 7917, 11, 2663, 712, 62301, 24088, 7917, 323, 30366, 974, 72286, 19646, 7917, 13, 9636, 279, 1314, 27692, 4787, 11, 1521, 330, 79076, 64632, 1, 7917, 649, 387, 1080, 52551, 311, 54263, 1139, 1475, 955, 315, 2849, 4460, 311, 8356, 279, 89948, 13339, 13, 30440, 49774, 2737, 16124, 11, 8834, 11, 477, 6680, 31080, 1051, 70554, 505, 1521, 7917, 1701, 6160, 454, 1616, 287, 13, 578, 49774, 1051, 1243, 28902, 304, 220, 18, 35, 11, 2768, 279, 13034, 5848, 6070, 11, 311, 23645, 279, 6070, 315, 279, 1972, 86993, 41101, 13339, 11, 902, 574, 5616, 48715, 824, 3825, 49257, 11, 304, 264, 4528, 1648, 311, 279, 8776, 11002, 32656, 735, 396, 17606, 12, 373, 13, 1115, 1920, 1903, 279, 43738, 315, 279, 6485, 13339, 20438, 6070, 3284, 304, 264, 63174, 11827, 13, 330, 1383, 18899, 420, 5557, 11, 433, 690, 387, 3284, 311, 539, 1193, 23645, 6485, 13339, 14726, 11, 1778, 439, 279, 6366, 274, 31478, 315, 86993, 41101, 25309, 11, 719, 311, 1101, 1304, 27545, 34074, 311, 279, 8834, 323, 16124, 6956, 1359, 10195, 3229, 5384, 80574, 68279, 355, 14966, 2795, 13, 3011, 374, 11, 6444, 1053, 387, 3025, 311, 2015, 89948, 13339, 449, 872, 12974, 3392, 315, 8834, 11, 3196, 389, 12945, 323, 2890, 38864, 13, 220, 128257, 198 ]

1,837

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract X-ray phase-contrast imaging has recently led to a revolution in resolving power and tissue contrast in biomedical imaging, microscopy and materials science. The necessary high spatial coherence is currently provided by either large-scale synchrotron facilities with limited beamtime access or by microfocus X-ray tubes with rather limited flux. X-rays radiated by relativistic electrons driven by well-controlled high-power lasers offer a promising route to a proliferation of this powerful imaging technology. A laser-driven plasma wave accelerates and wiggles electrons, giving rise to a brilliant keV X-ray emission. This so-called betatron radiation is emitted in a collimated beam with excellent spatial coherence and remarkable spectral stability. Here we present a phase-contrast microtomogram of a biological sample using betatron X-rays. Comprehensive source characterization enables the reconstruction of absolute electron densities. Our results suggest that laser-based X-ray technology offers the potential for filling the large performance gap between synchrotron- and current X-ray tube-based sources. Introduction Since the discovery of X-ray radiation and its powerful imaging capabilities by Röntgen, X-rays have become a part of our daily life in medicine, industry and research. The conventional technique of absorption imaging utilizes the large absorption variations of X-rays in matter (that is, the imaginary part β of the refractive index n= 1− δ+iβ ) of different thickness and composition, limiting its usefulness to structures with high absorption gradients. However, the real part of the refractive index δ leads to phase variations of the X-rays depending on the sample’s electron density. The latter can be explored with much higher sensitivity by phase-contrast techniques 1 , 2 , which are far superior to conventional radiography for detecting structures in soft tissue with its rather homogeneous absorption profile. It is thus ideally suited for three-dimensional (3D) investigations of (pathologic) tissue biopsies in medical research and diagnostics 3 , but also finds applications in materials science. Computed tomography using phase-contrast images taken from different perspectives can provide the full 3D structure of the object with high resolution and enhanced contrast. Phase-contrast imaging is complementary to coherent diffractive imaging 4 , which is employed for tomographic reconstruction in the far field. Phase-contrast imaging can be implemented by free-space propagation (also known as in-line holography) 5 , crystal analyser-based 2 and crystal 3 , 6 or grating 7 interferometer-based techniques. For microscopy applications with micron-scale resolution, propagation-based phase-contrast imaging is the method of choice. It relies neither on additional X-ray optics, nor on substantial temporal coherence of the source. The only requirement is that the transverse coherence length, given by l t = λ · R / σ is larger than 8 . Here λ is the wavelength, R is the source–detector distance, σ is the source size and D = d · l /( d + l ) the defocusing distance with l as source–sample and d sample–detector distances. This is met by third-generation synchrotrons, but their size and cost prevent their proliferation in hospitals and research institutions. Microfocus X-ray tubes provide the desired spatial coherence but suffer from a modest X-ray flux, implying lengthy exposure times. To spark off widespread application of this powerful technique, a compact high-brilliance source is needed. Laser-wakefield acceleration of electrons 9 (LWFA; see Methods) has already been studied as a possible future alternative. LWFA of electron beams exhibit transverse emittances comparable to the best conventional linear accelerators and bunch durations of ∼ 5 fs full-width at half-maximum (FWHM) 10 , 11 , rendering them unique among compact sources. During the acceleration process the electrons are also wiggled transversely by the strong radial fields of the plasma wave, causing them to emit a forward-directed, incoherent X-ray beam, referred to as betatron radiation 12 , 13 , 14 (see Methods). Recent proof-of-principle experiments demonstrated the potential of laser-driven betatron sources for recording single-shot X-ray phase-contrast images based on the free-space propagation technique 15 . Here we demonstrate that this type of source—even at this early stage of development—can be readily used for real-world applications. Due to advances in LWFA stability by using a turbulence-free steady-state gas flow target 16 , 17 , we are able to produce electron bunches with high charge (400 pC) and low fluctuations in absolute charge (30%) and in cut-off energy (10%) for continuous operation of several hours. We also show experimentally in this work that the spectral shape of the betatron radiation is largely insensitive to the electron spectra fluctuation. This leads to the production of a high-flux X-ray beam with remarkable spectral stability ideally suited for multiexposure imaging. Using these beams we were for the first time able to record and quantitatively reconstruct a phase tomogram of a complex object. As an illustrative example, we chose a dried insect (Chrysoperia carnea, green lacewing). We achieved this by evaluating a set of 1,487 single-shot phase-contrast images taken from various angles ( Supplementary Movie 1 ). The microradiography images features a field of view of 7.5 × 6.9 mm 2 and a resolution of 6 μm, limited by the CCD (charge-coupled device) area and pixel size, respectively. For quantitative reconstruction of the tomogram 18 from these images, we performed a careful characterization of the X-ray source in terms of its transverse dimensions and spectrum, which is essential for the reconstruction of the absolute electron densities within the object of interest 19 . Results Source characterization In the experiment, intense short laser pulses were focused at the entrance of a hydrogen-filled gas cell (see Fig. 1 and Methods). For our pulse parameters the highest electron energies with a peak at 400 MeV, lowest divergences (1.3±0.2 mrad) FWHM and moderate charge (50 pC) were produced at plasma electron densities of 5 × 10 18 cm −3 , created from laser-induced field ionization of the target gas. Figure 1: Experimental setup. The laser pulse (1.6 J, 28 fs, 60 TW) (red) is focused by a F /16 off-axis parabola to a 22-μm diameter spot size on the entrance of a 6-mm long gas cell with an plasma electron density of n p =1.1 × 10 19", "role": "user" }, { "content": "Physicists from Ludwig-Maximilians-Universität, the Max Planck Institute of Quantum Optics and the TU München have developed a method using laser-generated X-rays and phase-contrast X-ray tomography to produce three-dimensional images of soft tissue structures in organisms. With laser light, physicists in Munich have built a miniature X-ray source. In so doing, the researchers from the Laboratory of Attosecond Physics of the Max Planck Institute of Quantum Optics and the Technische Universität München (TUM) captured three-dimensional images of ultrafine structures in the body of a living organism for the first time with the help of laser-generated X-rays. Using light-generated radiation combined with phase-contrast X-ray tomography, the scientists visualized ultrafine details of a fly measuring just a few millimeters. Until now, such radiation could only be produced in expensive ring accelerators measuring several kilometers in diameter. By contrast, the laser-driven system in combination with phase-contrast X-ray tomography only requires a university laboratory to view soft tissues. The new imaging method could make future medical applications more cost-effective and space-efficient than is possible with today's technologies. When the physicists Prof. Stefan Karsch and Prof. Franz Pfeiffer illuminate a tiny fly with X-rays, the resulting image captures even the finest hairs on the wings of the insect. The experiment is a pioneering achievement. For the first time, scientists coupled their technique for generating X-rays from laser pulses with phase-contrast X-ray tomography to visualize tissues in organisms. The result is a three-dimensional view of the insect in unprecedented detail. The X-rays required were generated by electrons that were accelerated to nearly the speed of light over a distance of approximately one centimeter by laser pulses lasting around 25 femtoseconds. A femtosecond is one millionth of a billionth of a second. The laser pulses have a power of approximately 80 terawatts (80 x 1012 watts). By way of comparison: an atomic power plant generates 1,500 megawatts (1.5 x 109 Watt). First, the laser pulse ploughs through a plasma consisting of positively charged atomic cores and their electrons like a ship through water, producing a wake of oscillating electrons. This electron wave creates a trailing wave-shaped electric field structure on which the electrons surf and by which they are accelerated in the process. The particles then start to vibrate, emitting X-rays. Each light pulse generates an X-ray pulse. The X-rays generated have special properties: They have a wavelength of approximately 0.1 nanometers, which corresponds to a duration of only about five femtoseconds, and are spatially coherent, i.e. they appear to come from a point source. For the first time, the researchers combined their laser-driven X-rays with a phase-contrast imaging method developed by a team headed by Prof. Franz Pfeiffer of the TUM. Instead of the usual absorption of radiation, they used X-ray refraction to accurately image the shapes of objects, including soft tissues. For this to work, the spatial coherence mentioned above is essential. This laser-based imaging technique enables the researchers to view structures around one tenth to one hundredth the diameter of a human hair. Another advantage is the ability to create three-dimensional images of objects. After each X-ray pulse, meaning after each frame, the specimen is rotated slightly. For example, about 1,500 individual images were taken of the fly, which were then assembled to form a 3D data set. Due to the shortness of the X-ray pulses, this technique may be used in future to freeze ultrafast processes on the femtosecond time scale e.g. in molecules - as if they were illuminated by a femtosecond flashbulb. The technology is particularly interesting for medical applications, as it is able to distinguish between differences in tissue density. Cancer tissue, for example, is less dense than healthy tissue. The method therefore opens up the prospect of detecting tumors that are less than one millimeter in diameter in an early stage of growth before they spread through the body and exert their lethal effect. For this purpose, however, researchers must shorten the wavelength of the X-rays even further in order to penetrate thicker tissue layers. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract X-ray phase-contrast imaging has recently led to a revolution in resolving power and tissue contrast in biomedical imaging, microscopy and materials science. The necessary high spatial coherence is currently provided by either large-scale synchrotron facilities with limited beamtime access or by microfocus X-ray tubes with rather limited flux. X-rays radiated by relativistic electrons driven by well-controlled high-power lasers offer a promising route to a proliferation of this powerful imaging technology. A laser-driven plasma wave accelerates and wiggles electrons, giving rise to a brilliant keV X-ray emission. This so-called betatron radiation is emitted in a collimated beam with excellent spatial coherence and remarkable spectral stability. Here we present a phase-contrast microtomogram of a biological sample using betatron X-rays. Comprehensive source characterization enables the reconstruction of absolute electron densities. Our results suggest that laser-based X-ray technology offers the potential for filling the large performance gap between synchrotron- and current X-ray tube-based sources. Introduction Since the discovery of X-ray radiation and its powerful imaging capabilities by Röntgen, X-rays have become a part of our daily life in medicine, industry and research. The conventional technique of absorption imaging utilizes the large absorption variations of X-rays in matter (that is, the imaginary part β of the refractive index n= 1− δ+iβ ) of different thickness and composition, limiting its usefulness to structures with high absorption gradients. However, the real part of the refractive index δ leads to phase variations of the X-rays depending on the sample’s electron density. The latter can be explored with much higher sensitivity by phase-contrast techniques 1 , 2 , which are far superior to conventional radiography for detecting structures in soft tissue with its rather homogeneous absorption profile. It is thus ideally suited for three-dimensional (3D) investigations of (pathologic) tissue biopsies in medical research and diagnostics 3 , but also finds applications in materials science. Computed tomography using phase-contrast images taken from different perspectives can provide the full 3D structure of the object with high resolution and enhanced contrast. Phase-contrast imaging is complementary to coherent diffractive imaging 4 , which is employed for tomographic reconstruction in the far field. Phase-contrast imaging can be implemented by free-space propagation (also known as in-line holography) 5 , crystal analyser-based 2 and crystal 3 , 6 or grating 7 interferometer-based techniques. For microscopy applications with micron-scale resolution, propagation-based phase-contrast imaging is the method of choice. It relies neither on additional X-ray optics, nor on substantial temporal coherence of the source. The only requirement is that the transverse coherence length, given by l t = λ · R / σ is larger than 8 . Here λ is the wavelength, R is the source–detector distance, σ is the source size and D = d · l /( d + l ) the defocusing distance with l as source–sample and d sample–detector distances. This is met by third-generation synchrotrons, but their size and cost prevent their proliferation in hospitals and research institutions. Microfocus X-ray tubes provide the desired spatial coherence but suffer from a modest X-ray flux, implying lengthy exposure times. To spark off widespread application of this powerful technique, a compact high-brilliance source is needed. Laser-wakefield acceleration of electrons 9 (LWFA; see Methods) has already been studied as a possible future alternative. LWFA of electron beams exhibit transverse emittances comparable to the best conventional linear accelerators and bunch durations of ∼ 5 fs full-width at half-maximum (FWHM) 10 , 11 , rendering them unique among compact sources. During the acceleration process the electrons are also wiggled transversely by the strong radial fields of the plasma wave, causing them to emit a forward-directed, incoherent X-ray beam, referred to as betatron radiation 12 , 13 , 14 (see Methods). Recent proof-of-principle experiments demonstrated the potential of laser-driven betatron sources for recording single-shot X-ray phase-contrast images based on the free-space propagation technique 15 . Here we demonstrate that this type of source—even at this early stage of development—can be readily used for real-world applications. Due to advances in LWFA stability by using a turbulence-free steady-state gas flow target 16 , 17 , we are able to produce electron bunches with high charge (400 pC) and low fluctuations in absolute charge (30%) and in cut-off energy (10%) for continuous operation of several hours. We also show experimentally in this work that the spectral shape of the betatron radiation is largely insensitive to the electron spectra fluctuation. This leads to the production of a high-flux X-ray beam with remarkable spectral stability ideally suited for multiexposure imaging. Using these beams we were for the first time able to record and quantitatively reconstruct a phase tomogram of a complex object. As an illustrative example, we chose a dried insect (Chrysoperia carnea, green lacewing). We achieved this by evaluating a set of 1,487 single-shot phase-contrast images taken from various angles ( Supplementary Movie 1 ). The microradiography images features a field of view of 7.5 × 6.9 mm 2 and a resolution of 6 μm, limited by the CCD (charge-coupled device) area and pixel size, respectively. For quantitative reconstruction of the tomogram 18 from these images, we performed a careful characterization of the X-ray source in terms of its transverse dimensions and spectrum, which is essential for the reconstruction of the absolute electron densities within the object of interest 19 . Results Source characterization In the experiment, intense short laser pulses were focused at the entrance of a hydrogen-filled gas cell (see Fig. 1 and Methods). For our pulse parameters the highest electron energies with a peak at 400 MeV, lowest divergences (1.3±0.2 mrad) FWHM and moderate charge (50 pC) were produced at plasma electron densities of 5 × 10 18 cm −3 , created from laser-induced field ionization of the target gas. Figure 1: Experimental setup. The laser pulse (1.6 J, 28 fs, 60 TW) (red) is focused by a F /16 off-axis parabola to a 22-μm diameter spot size on the entrance of a 6-mm long gas cell with an plasma electron density of n p =1.1 × 10 19<|im_end|> <|im_start|>assistant Physicists from Ludwig-Maximilians-Universität, the Max Planck Institute of Quantum Optics and the TU München have developed a method using laser-generated X-rays and phase-contrast X-ray tomography to produce three-dimensional images of soft tissue structures in organisms. With laser light, physicists in Munich have built a miniature X-ray source. In so doing, the researchers from the Laboratory of Attosecond Physics of the Max Planck Institute of Quantum Optics and the Technische Universität München (TUM) captured three-dimensional images of ultrafine structures in the body of a living organism for the first time with the help of laser-generated X-rays. Using light-generated radiation combined with phase-contrast X-ray tomography, the scientists visualized ultrafine details of a fly measuring just a few millimeters. Until now, such radiation could only be produced in expensive ring accelerators measuring several kilometers in diameter. By contrast, the laser-driven system in combination with phase-contrast X-ray tomography only requires a university laboratory to view soft tissues. The new imaging method could make future medical applications more cost-effective and space-efficient than is possible with today's technologies. When the physicists Prof. Stefan Karsch and Prof. Franz Pfeiffer illuminate a tiny fly with X-rays, the resulting image captures even the finest hairs on the wings of the insect. The experiment is a pioneering achievement. For the first time, scientists coupled their technique for generating X-rays from laser pulses with phase-contrast X-ray tomography to visualize tissues in organisms. The result is a three-dimensional view of the insect in unprecedented detail. The X-rays required were generated by electrons that were accelerated to nearly the speed of light over a distance of approximately one centimeter by laser pulses lasting around 25 femtoseconds. A femtosecond is one millionth of a billionth of a second. The laser pulses have a power of approximately 80 terawatts (80 x 1012 watts). By way of comparison: an atomic power plant generates 1,500 megawatts (1.5 x 109 Watt). First, the laser pulse ploughs through a plasma consisting of positively charged atomic cores and their electrons like a ship through water, producing a wake of oscillating electrons. This electron wave creates a trailing wave-shaped electric field structure on which the electrons surf and by which they are accelerated in the process. The particles then start to vibrate, emitting X-rays. Each light pulse generates an X-ray pulse. The X-rays generated have special properties: They have a wavelength of approximately 0.1 nanometers, which corresponds to a duration of only about five femtoseconds, and are spatially coherent, i.e. they appear to come from a point source. For the first time, the researchers combined their laser-driven X-rays with a phase-contrast imaging method developed by a team headed by Prof. Franz Pfeiffer of the TUM. Instead of the usual absorption of radiation, they used X-ray refraction to accurately image the shapes of objects, including soft tissues. For this to work, the spatial coherence mentioned above is essential. This laser-based imaging technique enables the researchers to view structures around one tenth to one hundredth the diameter of a human hair. Another advantage is the ability to create three-dimensional images of objects. After each X-ray pulse, meaning after each frame, the specimen is rotated slightly. For example, about 1,500 individual images were taken of the fly, which were then assembled to form a 3D data set. Due to the shortness of the X-ray pulses, this technique may be used in future to freeze ultrafast processes on the femtosecond time scale e.g. in molecules - as if they were illuminated by a femtosecond flashbulb. The technology is particularly interesting for medical applications, as it is able to distinguish between differences in tissue density. Cancer tissue, for example, is less dense than healthy tissue. The method therefore opens up the prospect of detecting tumors that are less than one millimeter in diameter in an early stage of growth before they spread through the body and exert their lethal effect. For this purpose, however, researchers must shorten the wavelength of the X-rays even further in order to penetrate thicker tissue layers. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 1630, 30630, 10474, 12, 85324, 32758, 706, 6051, 6197, 311, 264, 14110, 304, 53583, 2410, 323, 20438, 13168, 304, 94612, 32758, 11, 92914, 323, 7384, 8198, 13, 578, 5995, 1579, 29079, 78925, 374, 5131, 3984, 555, 3060, 3544, 13230, 6925, 331, 299, 35785, 13077, 449, 7347, 24310, 1712, 2680, 477, 555, 8162, 17870, 1630, 30630, 34083, 449, 4856, 7347, 31405, 13, 1630, 82817, 12164, 660, 555, 59425, 4633, 57678, 16625, 555, 1664, 41370, 1579, 27624, 72475, 3085, 264, 26455, 6149, 311, 264, 53840, 315, 420, 8147, 32758, 5557, 13, 362, 21120, 32505, 32426, 12330, 14511, 988, 323, 289, 20831, 645, 57678, 11, 7231, 10205, 311, 264, 20333, 2004, 53, 1630, 30630, 41353, 13, 1115, 779, 19434, 1297, 81189, 25407, 374, 48042, 304, 264, 4631, 7292, 24310, 449, 9250, 29079, 78925, 323, 23649, 57077, 20334, 13, 5810, 584, 3118, 264, 10474, 12, 85324, 8162, 38501, 13255, 315, 264, 24156, 6205, 1701, 1297, 81189, 1630, 82817, 13, 67963, 2592, 60993, 20682, 279, 43738, 315, 10973, 17130, 90816, 13, 5751, 3135, 4284, 430, 21120, 6108, 1630, 30630, 5557, 6209, 279, 4754, 369, 21973, 279, 3544, 5178, 13225, 1990, 6925, 331, 299, 35785, 12, 323, 1510, 1630, 30630, 14019, 6108, 8336, 13, 29438, 8876, 279, 18841, 315, 1630, 30630, 25407, 323, 1202, 8147, 32758, 17357, 555, 432, 3029, 406, 4469, 11, 1630, 82817, 617, 3719, 264, 961, 315, 1057, 7446, 2324, 304, 16088, 11, 5064, 323, 3495, 13, 578, 21349, 15105, 315, 44225, 32758, 60880, 279, 3544, 44225, 27339, 315, 1630, 82817, 304, 5030, 320, 9210, 374, 11, 279, 51052, 961, 34318, 315, 279, 19914, 3104, 1963, 308, 28, 220, 16, 34363, 70434, 21905, 52355, 883, 315, 2204, 26839, 323, 18528, 11, 33994, 1202, 76964, 311, 14726, 449, 1579, 44225, 53249, 13, 4452, 11, 279, 1972, 961, 315, 279, 19914, 3104, 1963, 70434, 11767, 311, 10474, 27339, 315, 279, 1630, 82817, 11911, 389, 279, 6205, 753, 17130, 17915, 13, 578, 15629, 649, 387, 36131, 449, 1790, 5190, 27541, 555, 10474, 12, 85324, 12823, 220, 16, 1174, 220, 17, 1174, 902, 527, 3117, 16757, 311, 21349, 12164, 5814, 369, 54626, 14726, 304, 8579, 20438, 449, 1202, 4856, 87282, 44225, 5643, 13, 1102, 374, 8617, 50663, 32599, 369, 2380, 33520, 320, 18, 35, 8, 26969, 315, 320, 2398, 39227, 8, 20438, 6160, 3806, 552, 304, 6593, 3495, 323, 50518, 220, 18, 1174, 719, 1101, 14035, 8522, 304, 7384, 8198, 13, 1219, 19849, 10390, 5814, 1701, 10474, 12, 85324, 5448, 4529, 505, 2204, 39555, 649, 3493, 279, 2539, 220, 18, 35, 6070, 315, 279, 1665, 449, 1579, 11175, 323, 24872, 13168, 13, 28673, 12, 85324, 32758, 374, 58535, 311, 56887, 1422, 1658, 3104, 32758, 220, 19, 1174, 902, 374, 20011, 369, 10390, 12968, 43738, 304, 279, 3117, 2115, 13, 28673, 12, 85324, 32758, 649, 387, 11798, 555, 1949, 29047, 54743, 320, 19171, 3967, 439, 304, 8614, 72927, 1976, 88, 8, 220, 20, 1174, 26110, 8678, 805, 6108, 220, 17, 323, 26110, 220, 18, 1174, 220, 21, 477, 1099, 1113, 220, 22, 41305, 21037, 6108, 12823, 13, 1789, 92914, 8522, 449, 95309, 13230, 11175, 11, 54743, 6108, 10474, 12, 85324, 32758, 374, 279, 1749, 315, 5873, 13, 1102, 34744, 14188, 389, 5217, 1630, 30630, 70985, 11, 6463, 389, 12190, 37015, 78925, 315, 279, 2592, 13, 578, 1193, 16686, 374, 430, 279, 1380, 4550, 78925, 3160, 11, 2728, 555, 326, 259, 284, 49438, 9787, 432, 611, 48823, 374, 8294, 1109, 220, 23, 662, 5810, 49438, 374, 279, 46406, 11, 432, 374, 279, 2592, 4235, 92644, 6138, 11, 48823, 374, 279, 2592, 1404, 323, 423, 284, 294, 9787, 326, 71981, 294, 489, 326, 883, 279, 711, 87595, 6138, 449, 326, 439, 2592, 4235, 13925, 323, 294, 6205, 4235, 92644, 27650, 13, 1115, 374, 2322, 555, 4948, 43927, 6925, 331, 299, 376, 2439, 11, 719, 872, 1404, 323, 2853, 5471, 872, 53840, 304, 24461, 323, 3495, 14673, 13, 18654, 17870, 1630, 30630, 34083, 3493, 279, 12974, 29079, 78925, 719, 7831, 505, 264, 27946, 1630, 30630, 31405, 11, 73967, 35306, 14675, 3115, 13, 2057, 15541, 1022, 24716, 3851, 315, 420, 8147, 15105, 11, 264, 17251, 1579, 31217, 484, 5397, 2592, 374, 4460, 13, 40708, 2695, 731, 2630, 31903, 315, 57678, 220, 24, 320, 43, 54, 3711, 26, 1518, 19331, 8, 706, 2736, 1027, 20041, 439, 264, 3284, 3938, 10778, 13, 56841, 3711, 315, 17130, 51045, 31324, 1380, 4550, 991, 1468, 3095, 30139, 311, 279, 1888, 21349, 13790, 14511, 3046, 323, 15860, 90204, 315, 12264, 120, 220, 20, 8789, 2539, 9531, 520, 4376, 45173, 3375, 320, 18723, 53248, 8, 220, 605, 1174, 220, 806, 1174, 21568, 1124, 5016, 4315, 17251, 8336, 13, 12220, 279, 31903, 1920, 279, 57678, 527, 1101, 289, 20831, 839, 1380, 3078, 989, 555, 279, 3831, 57936, 5151, 315, 279, 32426, 12330, 11, 14718, 1124, 311, 17105, 264, 4741, 86855, 11, 304, 1030, 38638, 1630, 30630, 24310, 11, 14183, 311, 439, 1297, 81189, 25407, 220, 717, 1174, 220, 1032, 1174, 220, 975, 320, 4151, 19331, 570, 35390, 11311, 8838, 27748, 16379, 21896, 21091, 279, 4754, 315, 21120, 32505, 1297, 81189, 8336, 369, 14975, 3254, 64630, 1630, 30630, 10474, 12, 85324, 5448, 3196, 389, 279, 1949, 29047, 54743, 15105, 220, 868, 662, 5810, 584, 20461, 430, 420, 955, 315, 2592, 80078, 520, 420, 4216, 6566, 315, 4500, 2345, 4919, 387, 31368, 1511, 369, 1972, 31184, 8522, 13, 24586, 311, 31003, 304, 56841, 3711, 20334, 555, 1701, 264, 95167, 12862, 24981, 21395, 6962, 6530, 2218, 220, 845, 1174, 220, 1114, 1174, 584, 527, 3025, 311, 8356, 17130, 15860, 288, 449, 1579, 6900, 320, 3443, 281, 34, 8, 323, 3428, 65649, 304, 10973, 6900, 320, 966, 11587, 323, 304, 4018, 12744, 4907, 320, 605, 11587, 369, 19815, 5784, 315, 3892, 4207, 13, 1226, 1101, 1501, 9526, 750, 304, 420, 990, 430, 279, 57077, 6211, 315, 279, 1297, 81189, 25407, 374, 14090, 71580, 311, 279, 17130, 63697, 39388, 4090, 13, 1115, 11767, 311, 279, 5788, 315, 264, 1579, 12556, 2249, 1630, 30630, 24310, 449, 23649, 57077, 20334, 50663, 32599, 369, 7447, 327, 12313, 32758, 13, 12362, 1521, 51045, 584, 1051, 369, 279, 1176, 892, 3025, 311, 3335, 323, 10484, 275, 8046, 44928, 264, 10474, 10390, 13255, 315, 264, 6485, 1665, 13, 1666, 459, 12573, 1413, 3187, 11, 584, 14896, 264, 32720, 27080, 320, 1163, 42426, 3376, 689, 1841, 33252, 11, 6307, 46793, 24510, 570, 1226, 17427, 420, 555, 38663, 264, 743, 315, 220, 16, 11, 22184, 3254, 64630, 10474, 12, 85324, 5448, 4529, 505, 5370, 27030, 320, 99371, 14270, 220, 16, 7609, 578, 19748, 7787, 2836, 5814, 5448, 4519, 264, 2115, 315, 1684, 315, 220, 22, 13, 20, 25800, 220, 21, 13, 24, 9653, 220, 17, 323, 264, 11175, 315, 220, 21, 33983, 76, 11, 7347, 555, 279, 93833, 320, 14215, 1824, 283, 50185, 3756, 8, 3158, 323, 13252, 1404, 11, 15947, 13, 1789, 47616, 43738, 315, 279, 10390, 13255, 220, 972, 505, 1521, 5448, 11, 584, 10887, 264, 16994, 60993, 315, 279, 1630, 30630, 2592, 304, 3878, 315, 1202, 1380, 4550, 15696, 323, 20326, 11, 902, 374, 7718, 369, 279, 43738, 315, 279, 10973, 17130, 90816, 2949, 279, 1665, 315, 2802, 220, 777, 662, 18591, 8922, 60993, 763, 279, 9526, 11, 19428, 2875, 21120, 66557, 1051, 10968, 520, 279, 20396, 315, 264, 35784, 44518, 6962, 2849, 320, 4151, 23966, 13, 220, 16, 323, 19331, 570, 1789, 1057, 28334, 5137, 279, 8592, 17130, 49969, 449, 264, 16557, 520, 220, 3443, 2206, 53, 11, 15821, 37441, 70, 2436, 320, 16, 13, 18, 38121, 15, 13, 17, 296, 13584, 8, 435, 20484, 44, 323, 24070, 6900, 320, 1135, 281, 34, 8, 1051, 9124, 520, 32426, 17130, 90816, 315, 220, 20, 25800, 220, 605, 220, 972, 10166, 25173, 18, 1174, 3549, 505, 21120, 38973, 2115, 28772, 2065, 315, 279, 2218, 6962, 13, 19575, 220, 16, 25, 57708, 6642, 13, 578, 21120, 28334, 320, 16, 13, 21, 622, 11, 220, 1591, 8789, 11, 220, 1399, 36655, 8, 320, 1171, 8, 374, 10968, 555, 264, 435, 611, 845, 1022, 36421, 1370, 370, 8083, 311, 264, 220, 1313, 12, 44223, 76, 23899, 7858, 1404, 389, 279, 20396, 315, 264, 220, 21, 49675, 1317, 6962, 2849, 449, 459, 32426, 17130, 17915, 315, 308, 281, 284, 16, 13, 16, 25800, 220, 605, 220, 777, 128257, 198, 128256, 78191, 198, 67171, 292, 1705, 505, 85550, 5364, 710, 318, 26707, 12, 65715, 37714, 11, 279, 7639, 9878, 377, 10181, 315, 56413, 16963, 1233, 323, 279, 70514, 90366, 617, 8040, 264, 1749, 1701, 21120, 16581, 1630, 82817, 323, 10474, 12, 85324, 1630, 30630, 10390, 5814, 311, 8356, 2380, 33520, 5448, 315, 8579, 20438, 14726, 304, 44304, 13, 3161, 21120, 3177, 11, 98417, 304, 47304, 617, 5918, 264, 57863, 1630, 30630, 2592, 13, 763, 779, 3815, 11, 279, 12074, 505, 279, 32184, 315, 7867, 974, 1321, 28415, 315, 279, 7639, 9878, 377, 10181, 315, 56413, 16963, 1233, 323, 279, 7146, 10782, 15915, 37714, 90366, 320, 51, 2864, 8, 17439, 2380, 33520, 5448, 315, 24955, 63157, 14726, 304, 279, 2547, 315, 264, 5496, 47120, 369, 279, 1176, 892, 449, 279, 1520, 315, 21120, 16581, 1630, 82817, 13, 12362, 3177, 16581, 25407, 11093, 449, 10474, 12, 85324, 1630, 30630, 10390, 5814, 11, 279, 14248, 9302, 1534, 24955, 63157, 3649, 315, 264, 11722, 30090, 1120, 264, 2478, 2606, 55336, 13, 30070, 1457, 11, 1778, 25407, 1436, 1193, 387, 9124, 304, 11646, 10264, 14511, 3046, 30090, 3892, 41668, 304, 23899, 13, 3296, 13168, 11, 279, 21120, 32505, 1887, 304, 10824, 449, 10474, 12, 85324, 1630, 30630, 10390, 5814, 1193, 7612, 264, 12374, 27692, 311, 1684, 8579, 39881, 13, 578, 502, 32758, 1749, 1436, 1304, 3938, 6593, 8522, 810, 2853, 53421, 323, 3634, 73916, 1109, 374, 3284, 449, 3432, 596, 14645, 13, 3277, 279, 98417, 8626, 13, 50002, 735, 1590, 331, 323, 8626, 13, 66620, 393, 1897, 14657, 88682, 264, 13987, 11722, 449, 1630, 82817, 11, 279, 13239, 2217, 41255, 1524, 279, 28807, 66060, 389, 279, 27296, 315, 279, 27080, 13, 578, 9526, 374, 264, 71674, 26501, 13, 1789, 279, 1176, 892, 11, 14248, 34356, 872, 15105, 369, 24038, 1630, 82817, 505, 21120, 66557, 449, 10474, 12, 85324, 1630, 30630, 10390, 5814, 311, 51187, 39881, 304, 44304, 13, 578, 1121, 374, 264, 2380, 33520, 1684, 315, 279, 27080, 304, 31069, 7872, 13, 578, 1630, 82817, 2631, 1051, 8066, 555, 57678, 430, 1051, 49858, 311, 7154, 279, 4732, 315, 3177, 927, 264, 6138, 315, 13489, 832, 2960, 26402, 555, 21120, 66557, 29869, 2212, 220, 914, 5103, 83, 76989, 13, 362, 5103, 83, 974, 1321, 374, 832, 3610, 339, 315, 264, 7239, 339, 315, 264, 2132, 13, 578, 21120, 66557, 617, 264, 2410, 315, 13489, 220, 1490, 2024, 675, 21658, 320, 1490, 865, 220, 4645, 17, 72122, 570, 3296, 1648, 315, 12593, 25, 459, 25524, 2410, 6136, 27983, 220, 16, 11, 2636, 19262, 675, 21658, 320, 16, 13, 20, 865, 220, 7743, 60075, 570, 5629, 11, 279, 21120, 28334, 628, 1409, 82, 1555, 264, 32426, 31706, 315, 40646, 11684, 25524, 36804, 323, 872, 57678, 1093, 264, 8448, 1555, 3090, 11, 17843, 264, 15508, 315, 43524, 1113, 57678, 13, 1115, 17130, 12330, 11705, 264, 28848, 12330, 35831, 9249, 2115, 6070, 389, 902, 279, 57678, 20884, 323, 555, 902, 814, 527, 49858, 304, 279, 1920, 13, 578, 19252, 1243, 1212, 311, 348, 44192, 11, 90556, 1630, 82817, 13, 9062, 3177, 28334, 27983, 459, 1630, 30630, 28334, 13, 578, 1630, 82817, 8066, 617, 3361, 6012, 25, 2435, 617, 264, 46406, 315, 13489, 220, 15, 13, 16, 20622, 33504, 11, 902, 34310, 311, 264, 8250, 315, 1193, 922, 4330, 5103, 83, 76989, 11, 323, 527, 29079, 398, 56887, 11, 602, 1770, 13, 814, 5101, 311, 2586, 505, 264, 1486, 2592, 13, 1789, 279, 1176, 892, 11, 279, 12074, 11093, 872, 21120, 32505, 1630, 82817, 449, 264, 10474, 12, 85324, 32758, 1749, 8040, 555, 264, 2128, 19946, 555, 8626, 13, 66620, 393, 1897, 14657, 315, 279, 350, 2864, 13, 12361, 315, 279, 13783, 44225, 315, 25407, 11, 814, 1511, 1630, 30630, 2098, 16597, 311, 30357, 2217, 279, 21483, 315, 6302, 11, 2737, 8579, 39881, 13, 1789, 420, 311, 990, 11, 279, 29079, 78925, 9932, 3485, 374, 7718, 13, 1115, 21120, 6108, 32758, 15105, 20682, 279, 12074, 311, 1684, 14726, 2212, 832, 56766, 311, 832, 7895, 339, 279, 23899, 315, 264, 3823, 7013, 13, 13596, 9610, 374, 279, 5845, 311, 1893, 2380, 33520, 5448, 315, 6302, 13, 4740, 1855, 1630, 30630, 28334, 11, 7438, 1306, 1855, 4124, 11, 279, 58184, 374, 46720, 10284, 13, 1789, 3187, 11, 922, 220, 16, 11, 2636, 3927, 5448, 1051, 4529, 315, 279, 11722, 11, 902, 1051, 1243, 35105, 311, 1376, 264, 220, 18, 35, 828, 743, 13, 24586, 311, 279, 2875, 2136, 315, 279, 1630, 30630, 66557, 11, 420, 15105, 1253, 387, 1511, 304, 3938, 311, 31030, 24955, 9533, 11618, 389, 279, 5103, 83, 974, 1321, 892, 5569, 384, 1326, 13, 304, 35715, 482, 439, 422, 814, 1051, 75648, 555, 264, 5103, 83, 974, 1321, 8381, 16501, 65, 13, 578, 5557, 374, 8104, 7185, 369, 6593, 8522, 11, 439, 433, 374, 3025, 311, 33137, 1990, 12062, 304, 20438, 17915, 13, 26211, 20438, 11, 369, 3187, 11, 374, 2753, 29050, 1109, 9498, 20438, 13, 578, 1749, 9093, 16264, 709, 279, 22199, 315, 54626, 56071, 430, 527, 2753, 1109, 832, 2606, 26402, 304, 23899, 304, 459, 4216, 6566, 315, 6650, 1603, 814, 9041, 1555, 279, 2547, 323, 43844, 872, 45089, 2515, 13, 1789, 420, 7580, 11, 4869, 11, 12074, 2011, 74481, 279, 46406, 315, 279, 1630, 82817, 1524, 4726, 304, 2015, 311, 64855, 59884, 20438, 13931, 13, 220, 128257, 198 ]

2,259

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract In contrast to the well-recognized permafrost carbon (C) feedback to climate change, the fate of permafrost nitrogen (N) after thaw is poorly understood. According to mounting evidence, part of the N liberated from permafrost may be released to the atmosphere as the strong greenhouse gas (GHG) nitrous oxide (N 2 O). Here, we report post-thaw N 2 O release from late Pleistocene permafrost deposits called Yedoma, which store a substantial part of permafrost C and N and are highly vulnerable to thaw. While freshly thawed, unvegetated Yedoma in disturbed areas emit little N 2 O, emissions increase within few years after stabilization, drying and revegetation with grasses to high rates (548 (133–6286) μg N m −2 day −1 ; median with (range)), exceeding by 1–2 orders of magnitude the typical rates from permafrost-affected soils. Using targeted metagenomics of key N cycling genes, we link the increase in in situ N 2 O emissions with structural changes of the microbial community responsible for N cycling. Our results highlight the importance of extra N availability from thawing Yedoma permafrost, causing a positive climate feedback from the Arctic in the form of N 2 O emissions. Introduction Rapid Arctic warming 1 and associated permafrost thaw 2 , 3 are threatening the large C and N reservoirs of northern permafrost soils 4 , 5 , 6 , accumulated under cold conditions where the decomposition rate of soil organic matter (SOM) is low 7 , 8 . Permafrost thaw is now increasingly exposing these long-term inert C and N pools to microbial decomposition and transformation processes. While it is long known that mobilization of permafrost C potentially increase the release of the greenhouse gases (GHG) carbon dioxide (CO 2 ) and methane (CH 4 ) 5 , 9 , 10 , the fate of soil N liberated upon permafrost thaw is poorly studied and more complex. There is evidence that part of liberated N may be emitted to the atmosphere as nitrogenous gases, most importantly as N 2 O 6 , which is a ~300 times more powerful GHG than CO 2 over a 100-year time horizon 11 and a dominant contributor to ozone destruction in the stratosphere 12 . The current increase in atmospheric N 2 O concentration is mainly driven by the growth of human-induced emissions, which comprise 43% of the global N 2 O emissions of 17.0 Tg N year −1 and are dominated by N 2 O release from fertilized agricultural soils 13 . Nitrous oxide emissions, although generally smaller per unit area, occur also from soils under natural vegetation with a 33% contribution to the total global N 2 O emission 13 . Tropical soils with high N turnover rates generally show the largest N 2 O emissions among natural soils, while permafrost-affected soils in cold environments have been thought to be negligible N 2 O sources. This view was challenged by a recent synthesis showing that N 2 O emissions commonly occur from permafrost soils, with a global emission between 0.08 and 1.27 Tg N year −1 , meaning a 1–23% addition to the global N 2 O emission from natural soils 6 . However, this estimate is still highly uncertain due to the overall scarcity of N 2 O flux observations from permafrost-affected soils and the lack of studies from some important permafrost soil types, including the Yedoma studied here. Late-Pleistocene aged Yedoma permafrost occurs as deep deposits (a mean thickness of ~19 m) over an area of > 1 million km 2 in the Northern Hemisphere (Fig. 1 ) 14 . The Yedoma region contains >25% of the circumarctic permafrost C stock 15 , and a yet unaccounted for and likely even larger proportion of permafrost N because of the low C/N ratio of Yedoma SOM (typically < 15) 16 , 17 . The SOM in Yedoma is thought to be easily decomposable because it was incorporated into the permafrost soon after deposition without having much time to be degraded 15 . The high ice content of Yedoma 14 makes it vulnerable for abrupt thaw and ground collapse 18 , allowing rapid mobilization of soil C and N stocks after thaw 15 . Along Arctic rivers and the coastal zone of the Arctic Shelf, thawing of Yedoma permafrost creates steep, tens-of-meters-high Yedoma exposures 19 , 20 , 21 , where many of the conditions known to promote N 2 O emissions from permafrost-affected soils 6 are met, including low C/N ratios, lack of vegetation, and suitable soil moisture content for microbial processes producing N 2 O. Fig. 1: Overview of the studied Yedoma exposures. a Location of the study sites, overlain on the map showing the extent of Yedoma deposits on the Northern Hemisphere 79 and the permafrost zonation 80 . b Kurungnakh exposure. c Duvanny Yar exposure. Photos b and c by J. Kerttula. Full size image Here, we studied N 2 O fluxes on two thawing Yedoma exposures forming retrogressive thaw slumps in Northeast Siberia: In July 2016 on Kurungnakh Island situated in the Lena River Delta and in July 2017 in Duvanny Yar located by the Kolyma River (See Methods section; Fig. 1 ). At both sites, we measured N 2 O fluxes with the static chamber technique 22 and determined the mineral N pools on transects spanning from the top of the thawing Yedoma exposure across the bare and revegetated parts down to the river shore (see Methods section; Supplementary Figs. 1 & 2 ). At the intensive study site Kurungnakh we additionally studied N transformation and N 2 O production rates in the laboratory, as well as the relative abundance of N cycling genes. We revealed an increasing trend in N 2 O emissions with drying, stabilization, and revegetation of the thawed Yedoma sediments. Increased emissions were coupled with changes in the microbial community composition responsible for soil N transformation processes. Results and discussion Nitrous oxide emissions and mineral N pools across thawing Yedoma exposures Our field flux measurements revealed substantial", "role": "user" }, { "content": "A team at UC Riverside led by computer science assistant professor Ahmed Eldawy is collaborating with researchers at Stanford University and Vanderbilt University to develop a dataset that uses data science to study the spread of wildfires. The dataset can be used to simulate the spread of wildfires to help firefighters plan emergency response and conduct evacuation. It can also help simulate how fires might spread in the near future under the effects of deforestation and climate change, and aid risk assessment and planning of new infrastructure development. The open-source dataset, named WildfireDB, contains over 17 million data points that capture how fires have spread in the contiguous United States over the last decade. The dataset can be used to train machine learning models to predict the spread of wildfires. \"One of the biggest challenges is to have a detailed and curated dataset that can be used by machine learning algorithms,\" said Eldawy. \"WildfireDB is the first comprehensive and open-source dataset that relates historical fire data with relevant covariates such as weather, vegetation, and topography.\" First responders depend on understanding and predicting how a wildfire spreads to save lives and property and to stop the fire from spreading. They need to figure out the best way to allocate limited resources across large areas. Traditionally, fire spread is modeled by tools that use physics-based modeling. This method could be improved with the addition of more variables, but until now, there was no comprehensive, open-source data source that combines fire occurrences with geo-spatial features such as mountains, rivers, towns, fuel levels, vegetation, and weather. Eldawy, along with UCR doctoral student Samriddhi Singla and undergraduate researcher Vinayak Gajjewar, utilized a novel system called Raptor, which was developed at UCR to process high-resolution satellite data such as vegetation and weather. Using Raptor, they combined historical wildfires with other geospatial features, such as weather, topography, and vegetation, to build a dataset at a scale that included the most of the United States. WildfireDB has mapped historical fire data in the contiguous United States between 2012 to 2017 with spatial and temporal resolutions that allow researchers to home in on the daily behavior of fire in regions as small as 375-meter square polygons. Each fire occurrence includes type of vegetation, fuel type, and topography. The dataset does not include Alaska or Hawaii. To use the dataset, researchers or firefighters can select information relevant to their situation from WildfireDB and train machine learning models that can model the spread of wildfires. These trained models can then be used by firefighters or researchers to predict the spread of wildfires in real time. \"Predicting the spread of wildfire in real time will allow firefighters to allocate resources accordingly and minimize loss of life and property\" said Singla, the paper's first author. A visualization of the dataset is available here. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract In contrast to the well-recognized permafrost carbon (C) feedback to climate change, the fate of permafrost nitrogen (N) after thaw is poorly understood. According to mounting evidence, part of the N liberated from permafrost may be released to the atmosphere as the strong greenhouse gas (GHG) nitrous oxide (N 2 O). Here, we report post-thaw N 2 O release from late Pleistocene permafrost deposits called Yedoma, which store a substantial part of permafrost C and N and are highly vulnerable to thaw. While freshly thawed, unvegetated Yedoma in disturbed areas emit little N 2 O, emissions increase within few years after stabilization, drying and revegetation with grasses to high rates (548 (133–6286) μg N m −2 day −1 ; median with (range)), exceeding by 1–2 orders of magnitude the typical rates from permafrost-affected soils. Using targeted metagenomics of key N cycling genes, we link the increase in in situ N 2 O emissions with structural changes of the microbial community responsible for N cycling. Our results highlight the importance of extra N availability from thawing Yedoma permafrost, causing a positive climate feedback from the Arctic in the form of N 2 O emissions. Introduction Rapid Arctic warming 1 and associated permafrost thaw 2 , 3 are threatening the large C and N reservoirs of northern permafrost soils 4 , 5 , 6 , accumulated under cold conditions where the decomposition rate of soil organic matter (SOM) is low 7 , 8 . Permafrost thaw is now increasingly exposing these long-term inert C and N pools to microbial decomposition and transformation processes. While it is long known that mobilization of permafrost C potentially increase the release of the greenhouse gases (GHG) carbon dioxide (CO 2 ) and methane (CH 4 ) 5 , 9 , 10 , the fate of soil N liberated upon permafrost thaw is poorly studied and more complex. There is evidence that part of liberated N may be emitted to the atmosphere as nitrogenous gases, most importantly as N 2 O 6 , which is a ~300 times more powerful GHG than CO 2 over a 100-year time horizon 11 and a dominant contributor to ozone destruction in the stratosphere 12 . The current increase in atmospheric N 2 O concentration is mainly driven by the growth of human-induced emissions, which comprise 43% of the global N 2 O emissions of 17.0 Tg N year −1 and are dominated by N 2 O release from fertilized agricultural soils 13 . Nitrous oxide emissions, although generally smaller per unit area, occur also from soils under natural vegetation with a 33% contribution to the total global N 2 O emission 13 . Tropical soils with high N turnover rates generally show the largest N 2 O emissions among natural soils, while permafrost-affected soils in cold environments have been thought to be negligible N 2 O sources. This view was challenged by a recent synthesis showing that N 2 O emissions commonly occur from permafrost soils, with a global emission between 0.08 and 1.27 Tg N year −1 , meaning a 1–23% addition to the global N 2 O emission from natural soils 6 . However, this estimate is still highly uncertain due to the overall scarcity of N 2 O flux observations from permafrost-affected soils and the lack of studies from some important permafrost soil types, including the Yedoma studied here. Late-Pleistocene aged Yedoma permafrost occurs as deep deposits (a mean thickness of ~19 m) over an area of > 1 million km 2 in the Northern Hemisphere (Fig. 1 ) 14 . The Yedoma region contains >25% of the circumarctic permafrost C stock 15 , and a yet unaccounted for and likely even larger proportion of permafrost N because of the low C/N ratio of Yedoma SOM (typically < 15) 16 , 17 . The SOM in Yedoma is thought to be easily decomposable because it was incorporated into the permafrost soon after deposition without having much time to be degraded 15 . The high ice content of Yedoma 14 makes it vulnerable for abrupt thaw and ground collapse 18 , allowing rapid mobilization of soil C and N stocks after thaw 15 . Along Arctic rivers and the coastal zone of the Arctic Shelf, thawing of Yedoma permafrost creates steep, tens-of-meters-high Yedoma exposures 19 , 20 , 21 , where many of the conditions known to promote N 2 O emissions from permafrost-affected soils 6 are met, including low C/N ratios, lack of vegetation, and suitable soil moisture content for microbial processes producing N 2 O. Fig. 1: Overview of the studied Yedoma exposures. a Location of the study sites, overlain on the map showing the extent of Yedoma deposits on the Northern Hemisphere 79 and the permafrost zonation 80 . b Kurungnakh exposure. c Duvanny Yar exposure. Photos b and c by J. Kerttula. Full size image Here, we studied N 2 O fluxes on two thawing Yedoma exposures forming retrogressive thaw slumps in Northeast Siberia: In July 2016 on Kurungnakh Island situated in the Lena River Delta and in July 2017 in Duvanny Yar located by the Kolyma River (See Methods section; Fig. 1 ). At both sites, we measured N 2 O fluxes with the static chamber technique 22 and determined the mineral N pools on transects spanning from the top of the thawing Yedoma exposure across the bare and revegetated parts down to the river shore (see Methods section; Supplementary Figs. 1 & 2 ). At the intensive study site Kurungnakh we additionally studied N transformation and N 2 O production rates in the laboratory, as well as the relative abundance of N cycling genes. We revealed an increasing trend in N 2 O emissions with drying, stabilization, and revegetation of the thawed Yedoma sediments. Increased emissions were coupled with changes in the microbial community composition responsible for soil N transformation processes. Results and discussion Nitrous oxide emissions and mineral N pools across thawing Yedoma exposures Our field flux measurements revealed substantial<|im_end|> <|im_start|>assistant A team at UC Riverside led by computer science assistant professor Ahmed Eldawy is collaborating with researchers at Stanford University and Vanderbilt University to develop a dataset that uses data science to study the spread of wildfires. The dataset can be used to simulate the spread of wildfires to help firefighters plan emergency response and conduct evacuation. It can also help simulate how fires might spread in the near future under the effects of deforestation and climate change, and aid risk assessment and planning of new infrastructure development. The open-source dataset, named WildfireDB, contains over 17 million data points that capture how fires have spread in the contiguous United States over the last decade. The dataset can be used to train machine learning models to predict the spread of wildfires. "One of the biggest challenges is to have a detailed and curated dataset that can be used by machine learning algorithms," said Eldawy. "WildfireDB is the first comprehensive and open-source dataset that relates historical fire data with relevant covariates such as weather, vegetation, and topography." First responders depend on understanding and predicting how a wildfire spreads to save lives and property and to stop the fire from spreading. They need to figure out the best way to allocate limited resources across large areas. Traditionally, fire spread is modeled by tools that use physics-based modeling. This method could be improved with the addition of more variables, but until now, there was no comprehensive, open-source data source that combines fire occurrences with geo-spatial features such as mountains, rivers, towns, fuel levels, vegetation, and weather. Eldawy, along with UCR doctoral student Samriddhi Singla and undergraduate researcher Vinayak Gajjewar, utilized a novel system called Raptor, which was developed at UCR to process high-resolution satellite data such as vegetation and weather. Using Raptor, they combined historical wildfires with other geospatial features, such as weather, topography, and vegetation, to build a dataset at a scale that included the most of the United States. WildfireDB has mapped historical fire data in the contiguous United States between 2012 to 2017 with spatial and temporal resolutions that allow researchers to home in on the daily behavior of fire in regions as small as 375-meter square polygons. Each fire occurrence includes type of vegetation, fuel type, and topography. The dataset does not include Alaska or Hawaii. To use the dataset, researchers or firefighters can select information relevant to their situation from WildfireDB and train machine learning models that can model the spread of wildfires. These trained models can then be used by firefighters or researchers to predict the spread of wildfires in real time. "Predicting the spread of wildfire in real time will allow firefighters to allocate resources accordingly and minimize loss of life and property" said Singla, the paper's first author. A visualization of the dataset is available here. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 763, 13168, 311, 279, 1664, 12, 47167, 824, 99161, 42602, 12782, 320, 34, 8, 11302, 311, 10182, 2349, 11, 279, 25382, 315, 824, 99161, 42602, 47503, 320, 45, 8, 1306, 86478, 374, 31555, 16365, 13, 10771, 311, 34739, 6029, 11, 961, 315, 279, 452, 85855, 505, 824, 99161, 42602, 1253, 387, 6004, 311, 279, 16975, 439, 279, 3831, 37647, 6962, 320, 45776, 38, 8, 25719, 27620, 51180, 320, 45, 220, 17, 507, 570, 5810, 11, 584, 1934, 1772, 7716, 675, 452, 220, 17, 507, 4984, 505, 3389, 33540, 380, 78782, 824, 99161, 42602, 34751, 2663, 816, 291, 7942, 11, 902, 3637, 264, 12190, 961, 315, 824, 99161, 42602, 356, 323, 452, 323, 527, 7701, 20134, 311, 86478, 13, 6104, 50999, 86478, 291, 11, 28847, 456, 660, 816, 291, 7942, 304, 56507, 5789, 17105, 2697, 452, 220, 17, 507, 11, 20748, 5376, 2949, 2478, 1667, 1306, 83938, 11, 46479, 323, 6326, 456, 367, 449, 16763, 288, 311, 1579, 7969, 320, 22287, 320, 9423, 4235, 23574, 21, 8, 33983, 70, 452, 296, 25173, 17, 1938, 25173, 16, 2652, 23369, 449, 320, 9866, 5850, 49005, 555, 220, 16, 4235, 17, 10373, 315, 26703, 279, 14595, 7969, 505, 824, 99161, 42602, 12, 32157, 69561, 13, 12362, 17550, 2322, 8703, 24203, 315, 1401, 452, 33162, 21389, 11, 584, 2723, 279, 5376, 304, 304, 10109, 452, 220, 17, 507, 20748, 449, 24693, 4442, 315, 279, 75418, 4029, 8647, 369, 452, 33162, 13, 5751, 3135, 11415, 279, 12939, 315, 5066, 452, 18539, 505, 86478, 287, 816, 291, 7942, 824, 99161, 42602, 11, 14718, 264, 6928, 10182, 11302, 505, 279, 37518, 304, 279, 1376, 315, 452, 220, 17, 507, 20748, 13, 29438, 48090, 37518, 24808, 220, 16, 323, 5938, 824, 99161, 42602, 86478, 220, 17, 1174, 220, 18, 527, 27903, 279, 3544, 356, 323, 452, 45512, 82, 315, 18671, 824, 99161, 42602, 69561, 220, 19, 1174, 220, 20, 1174, 220, 21, 1174, 41165, 1234, 9439, 4787, 1405, 279, 66266, 4478, 315, 17614, 17808, 5030, 320, 50, 1937, 8, 374, 3428, 220, 22, 1174, 220, 23, 662, 3700, 99161, 42602, 86478, 374, 1457, 15098, 47066, 1521, 1317, 9860, 81073, 356, 323, 452, 34239, 311, 75418, 66266, 323, 18475, 11618, 13, 6104, 433, 374, 1317, 3967, 430, 29905, 2065, 315, 824, 99161, 42602, 356, 13893, 5376, 279, 4984, 315, 279, 37647, 45612, 320, 45776, 38, 8, 12782, 40589, 320, 8445, 220, 17, 883, 323, 61083, 320, 2198, 220, 19, 883, 220, 20, 1174, 220, 24, 1174, 220, 605, 1174, 279, 25382, 315, 17614, 452, 85855, 5304, 824, 99161, 42602, 86478, 374, 31555, 20041, 323, 810, 6485, 13, 2684, 374, 6029, 430, 961, 315, 85855, 452, 1253, 387, 48042, 311, 279, 16975, 439, 47503, 788, 45612, 11, 1455, 23659, 439, 452, 220, 17, 507, 220, 21, 1174, 902, 374, 264, 4056, 3101, 3115, 810, 8147, 48584, 38, 1109, 7432, 220, 17, 927, 264, 220, 1041, 4771, 892, 35174, 220, 806, 323, 264, 25462, 26373, 311, 77537, 19814, 304, 279, 610, 14357, 8182, 220, 717, 662, 578, 1510, 5376, 304, 45475, 452, 220, 17, 507, 20545, 374, 14918, 16625, 555, 279, 6650, 315, 3823, 38973, 20748, 11, 902, 54350, 220, 3391, 4, 315, 279, 3728, 452, 220, 17, 507, 20748, 315, 220, 1114, 13, 15, 350, 70, 452, 1060, 25173, 16, 323, 527, 30801, 555, 452, 220, 17, 507, 4984, 505, 36214, 1534, 29149, 69561, 220, 1032, 662, 50616, 27620, 51180, 20748, 11, 8051, 8965, 9333, 824, 5089, 3158, 11, 12446, 1101, 505, 69561, 1234, 5933, 54832, 449, 264, 220, 1644, 4, 19035, 311, 279, 2860, 3728, 452, 220, 17, 507, 41353, 220, 1032, 662, 71343, 69561, 449, 1579, 452, 48639, 7969, 8965, 1501, 279, 7928, 452, 220, 17, 507, 20748, 4315, 5933, 69561, 11, 1418, 824, 99161, 42602, 12, 32157, 69561, 304, 9439, 22484, 617, 1027, 3463, 311, 387, 82802, 452, 220, 17, 507, 8336, 13, 1115, 1684, 574, 29991, 555, 264, 3293, 39975, 9204, 430, 452, 220, 17, 507, 20748, 17037, 12446, 505, 824, 99161, 42602, 69561, 11, 449, 264, 3728, 41353, 1990, 220, 15, 13, 2318, 323, 220, 16, 13, 1544, 350, 70, 452, 1060, 25173, 16, 1174, 7438, 264, 220, 16, 4235, 1419, 4, 5369, 311, 279, 3728, 452, 220, 17, 507, 41353, 505, 5933, 69561, 220, 21, 662, 4452, 11, 420, 16430, 374, 2103, 7701, 36218, 4245, 311, 279, 8244, 82484, 315, 452, 220, 17, 507, 31405, 24654, 505, 824, 99161, 42602, 12, 32157, 69561, 323, 279, 6996, 315, 7978, 505, 1063, 3062, 824, 99161, 42602, 17614, 4595, 11, 2737, 279, 816, 291, 7942, 20041, 1618, 13, 36931, 9483, 273, 380, 78782, 20330, 816, 291, 7942, 824, 99161, 42602, 13980, 439, 5655, 34751, 320, 64, 3152, 26839, 315, 4056, 777, 296, 8, 927, 459, 3158, 315, 871, 220, 16, 3610, 13437, 220, 17, 304, 279, 17355, 96878, 320, 30035, 13, 220, 16, 883, 220, 975, 662, 578, 816, 291, 7942, 5654, 5727, 871, 914, 4, 315, 279, 10408, 277, 26636, 824, 99161, 42602, 356, 5708, 220, 868, 1174, 323, 264, 3686, 653, 4711, 291, 369, 323, 4461, 1524, 8294, 21801, 315, 824, 99161, 42602, 452, 1606, 315, 279, 3428, 356, 20906, 11595, 315, 816, 291, 7942, 74390, 320, 87184, 366, 220, 868, 8, 220, 845, 1174, 220, 1114, 662, 578, 74390, 304, 816, 291, 7942, 374, 3463, 311, 387, 6847, 29602, 17877, 1606, 433, 574, 32762, 1139, 279, 824, 99161, 42602, 5246, 1306, 65374, 2085, 3515, 1790, 892, 311, 387, 91978, 220, 868, 662, 578, 1579, 10054, 2262, 315, 816, 291, 7942, 220, 975, 3727, 433, 20134, 369, 44077, 86478, 323, 5015, 18678, 220, 972, 1174, 10923, 11295, 29905, 2065, 315, 17614, 356, 323, 452, 23301, 1306, 86478, 220, 868, 662, 32944, 37518, 36617, 323, 279, 35335, 10353, 315, 279, 37518, 71446, 11, 86478, 287, 315, 816, 291, 7942, 824, 99161, 42602, 11705, 32366, 11, 22781, 8838, 1474, 2481, 28661, 816, 291, 7942, 70530, 220, 777, 1174, 220, 508, 1174, 220, 1691, 1174, 1405, 1690, 315, 279, 4787, 3967, 311, 12192, 452, 220, 17, 507, 20748, 505, 824, 99161, 42602, 12, 32157, 69561, 220, 21, 527, 2322, 11, 2737, 3428, 356, 20906, 42338, 11, 6996, 315, 54832, 11, 323, 14791, 17614, 32257, 2262, 369, 75418, 11618, 17843, 452, 220, 17, 507, 13, 23966, 13, 220, 16, 25, 35907, 315, 279, 20041, 816, 291, 7942, 70530, 13, 264, 10067, 315, 279, 4007, 6732, 11, 29204, 467, 389, 279, 2472, 9204, 279, 13112, 315, 816, 291, 7942, 34751, 389, 279, 17355, 96878, 220, 4643, 323, 279, 824, 99161, 42602, 1167, 91983, 220, 1490, 662, 293, 32375, 2234, 77, 22506, 14675, 13, 272, 423, 12328, 13184, 113381, 14675, 13, 16912, 293, 323, 272, 555, 622, 13, 735, 531, 83, 5724, 13, 8797, 1404, 2217, 5810, 11, 584, 20041, 452, 220, 17, 507, 31405, 288, 389, 1403, 86478, 287, 816, 291, 7942, 70530, 30164, 17189, 47819, 86478, 1776, 12055, 304, 45680, 68600, 689, 25, 763, 5887, 220, 679, 21, 389, 32375, 2234, 77, 22506, 10951, 31183, 304, 279, 82162, 11188, 26002, 323, 304, 5887, 220, 679, 22, 304, 423, 12328, 13184, 113381, 7559, 555, 279, 46615, 1631, 64, 11188, 320, 10031, 19331, 3857, 26, 23966, 13, 220, 16, 7609, 2468, 2225, 6732, 11, 584, 17303, 452, 220, 17, 507, 31405, 288, 449, 279, 1118, 25199, 15105, 220, 1313, 323, 11075, 279, 25107, 452, 34239, 389, 24614, 55529, 56886, 505, 279, 1948, 315, 279, 86478, 287, 816, 291, 7942, 14675, 4028, 279, 12743, 323, 6326, 456, 660, 5596, 1523, 311, 279, 15140, 31284, 320, 4151, 19331, 3857, 26, 99371, 435, 14801, 13, 220, 16, 612, 220, 17, 7609, 2468, 279, 37295, 4007, 2816, 32375, 2234, 77, 22506, 584, 37938, 20041, 452, 18475, 323, 452, 220, 17, 507, 5788, 7969, 304, 279, 27692, 11, 439, 1664, 439, 279, 8844, 37492, 315, 452, 33162, 21389, 13, 1226, 10675, 459, 7859, 9327, 304, 452, 220, 17, 507, 20748, 449, 46479, 11, 83938, 11, 323, 6326, 456, 367, 315, 279, 86478, 291, 816, 291, 7942, 11163, 12843, 13, 62697, 20748, 1051, 34356, 449, 4442, 304, 279, 75418, 4029, 18528, 8647, 369, 17614, 452, 18475, 11618, 13, 18591, 323, 10430, 50616, 27620, 51180, 20748, 323, 25107, 452, 34239, 4028, 86478, 287, 816, 291, 7942, 70530, 5751, 2115, 31405, 22323, 10675, 12190, 128257, 198, 128256, 78191, 198, 32, 2128, 520, 31613, 63941, 6197, 555, 6500, 8198, 18328, 14561, 41769, 27965, 96819, 374, 73301, 449, 12074, 520, 31788, 3907, 323, 84126, 3907, 311, 2274, 264, 10550, 430, 5829, 828, 8198, 311, 4007, 279, 9041, 315, 99482, 13, 578, 10550, 649, 387, 1511, 311, 38553, 279, 9041, 315, 99482, 311, 1520, 53206, 3197, 13147, 2077, 323, 6929, 60773, 13, 1102, 649, 1101, 1520, 38553, 1268, 27176, 2643, 9041, 304, 279, 3221, 3938, 1234, 279, 6372, 315, 711, 97893, 323, 10182, 2349, 11, 323, 12576, 5326, 15813, 323, 9293, 315, 502, 14054, 4500, 13, 578, 1825, 31874, 10550, 11, 7086, 13944, 11029, 3590, 11, 5727, 927, 220, 1114, 3610, 828, 3585, 430, 12602, 1268, 27176, 617, 9041, 304, 279, 67603, 3723, 4273, 927, 279, 1566, 13515, 13, 578, 10550, 649, 387, 1511, 311, 5542, 5780, 6975, 4211, 311, 7168, 279, 9041, 315, 99482, 13, 330, 4054, 315, 279, 8706, 11774, 374, 311, 617, 264, 11944, 323, 58732, 10550, 430, 649, 387, 1511, 555, 5780, 6975, 26249, 1359, 1071, 27965, 96819, 13, 330, 41703, 11029, 3590, 374, 279, 1176, 16195, 323, 1825, 31874, 10550, 430, 36716, 13970, 4027, 828, 449, 9959, 22590, 2850, 988, 1778, 439, 9282, 11, 54832, 11, 323, 1948, 5814, 1210, 5629, 70639, 6904, 389, 8830, 323, 52997, 1268, 264, 93225, 43653, 311, 3665, 6439, 323, 3424, 323, 311, 3009, 279, 4027, 505, 31135, 13, 2435, 1205, 311, 7216, 704, 279, 1888, 1648, 311, 22864, 7347, 5070, 4028, 3544, 5789, 13, 15415, 17868, 11, 4027, 9041, 374, 62653, 555, 7526, 430, 1005, 22027, 6108, 34579, 13, 1115, 1749, 1436, 387, 13241, 449, 279, 5369, 315, 810, 7482, 11, 719, 3156, 1457, 11, 1070, 574, 912, 16195, 11, 1825, 31874, 828, 2592, 430, 33511, 4027, 57115, 449, 28681, 1355, 33514, 4519, 1778, 439, 24405, 11, 36617, 11, 25861, 11, 10633, 5990, 11, 54832, 11, 323, 9282, 13, 27965, 96819, 11, 3235, 449, 549, 9150, 74657, 5575, 8388, 81, 1810, 6151, 11070, 4355, 323, 41534, 32185, 21016, 352, 587, 480, 1662, 73, 365, 277, 11, 34716, 264, 11775, 1887, 2663, 432, 33757, 11, 902, 574, 8040, 520, 549, 9150, 311, 1920, 1579, 64036, 24088, 828, 1778, 439, 54832, 323, 9282, 13, 12362, 432, 33757, 11, 814, 11093, 13970, 99482, 449, 1023, 3980, 437, 33514, 4519, 11, 1778, 439, 9282, 11, 1948, 5814, 11, 323, 54832, 11, 311, 1977, 264, 10550, 520, 264, 5569, 430, 5343, 279, 1455, 315, 279, 3723, 4273, 13, 13944, 11029, 3590, 706, 24784, 13970, 4027, 828, 304, 279, 67603, 3723, 4273, 1990, 220, 679, 17, 311, 220, 679, 22, 449, 29079, 323, 37015, 43595, 430, 2187, 12074, 311, 2162, 304, 389, 279, 7446, 7865, 315, 4027, 304, 13918, 439, 2678, 439, 220, 12935, 73601, 9518, 69259, 13, 9062, 4027, 32659, 5764, 955, 315, 54832, 11, 10633, 955, 11, 323, 1948, 5814, 13, 578, 10550, 1587, 539, 2997, 28366, 477, 28621, 13, 2057, 1005, 279, 10550, 11, 12074, 477, 53206, 649, 3373, 2038, 9959, 311, 872, 6671, 505, 13944, 11029, 3590, 323, 5542, 5780, 6975, 4211, 430, 649, 1646, 279, 9041, 315, 99482, 13, 4314, 16572, 4211, 649, 1243, 387, 1511, 555, 53206, 477, 12074, 311, 7168, 279, 9041, 315, 99482, 304, 1972, 892, 13, 330, 54644, 287, 279, 9041, 315, 93225, 304, 1972, 892, 690, 2187, 53206, 311, 22864, 5070, 28178, 323, 30437, 4814, 315, 2324, 323, 3424, 1, 1071, 11070, 4355, 11, 279, 5684, 596, 1176, 3229, 13, 362, 42148, 315, 279, 10550, 374, 2561, 1618, 13, 220, 128257, 198 ]

1,968

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract The vomeronasal system plays an essential role in sensing various environmental chemical cues. Here we show that mice exposed to blood and, consequently, hemoglobin results in the activation of vomeronasal sensory neurons expressing a specific vomeronasal G protein-coupled receptor, Vmn2r88, which is mediated by the interaction site, Gly17, on hemoglobin. The hemoglobin signal reaches the medial amygdala (MeA) in both male and female mice. However, it activates the dorsal part of ventromedial hypothalamus (VMHd) only in lactating female mice. As a result, in lactating mothers, hemoglobin enhances digging and rearing behavior. Manipulation of steroidogenic factor 1 (SF1)-expressing neurons in the VMHd is sufficient to induce the hemoglobin-mediated behaviors. Our results suggest that the oxygen-carrier hemoglobin plays a role as a chemosensory signal, eliciting behavioral responses in mice in a state-dependent fashion. Introduction Animals use the olfactory systems to acquire information about the external environment. Mice, for example, show vigorous sniffing behavior that allows for sensing not only volatile airborne chemicals but also nonvolatile compounds, through direct contact in the nose 1 . Volatile odorants are recognized by odorant receptors in the olfactory epithelium and often elicit acute behavioral responses, such as attraction or aversion 2 , 3 , 4 , 5 . In contrast, nonvolatile cues are detected by vomeronasal receptors in the vomeronasal organ (VNO) located beneath the nasal cavity, and usually convey sociosexual information associated with stereotypical behavior or emotional changes 6 , 7 . Secretions, such as urine, tear fluid, and saliva contain both volatile and nonvolatile olfactory cues. For example, male mouse urine contains major urinary protein 3 (MUP3), which elicits intermale aggression 8 . Male mouse tears contain exocrine gland-secreting peptide 1 (ESP1), which enhances female sexual behavior called lordosis and male aggressiveness 9 , 10 , 11 , 12 . Juvenile mice secrete ESP22, which suppresses sexual behavior in adult mice to lessen the number of competitors 13 , 14 . In addition to these intraspecies signals, the VNO also receives inter-species signals, such as rat cystatin-related protein 1 (ratCRP1), which acts as a pheromone in rats but as a predator signal in mice 15 . Olfactory cues appear to help animals take appropriate reactions to environmental changes by affecting the internal physiological state of the animal. The VNO expresses two types of G protein-coupled receptors (187 V1Rs and 121 V2Rs) that recognize various environmental cues 16 , 17 . Only a few vomeronasal ligand-receptor pairs have been revealed; ESP1 and ESP22 are detected by single specific V2R receptors, V2Rp5 (Vmn2r116) 10 and V2Rp4 (Vmn2r115) 14 , respectively. The signals received by the specific V2Rs are conveyed to the accessory olfactory bulb (AOB) first, and then to the limbic brain regions such as amygdala and hypothalamus wherein specific neural circuits regulate distinct output behaviors 10 , 12 , 14 . The vast majority of V2Rs, however, remain orphan, limiting our understanding of sensory mechanisms underlying VNO-mediated behavioral output. When we discovered the ESP1 molecule in 2005, we also reported that the submaxillary gland contains a molecule, which activates vomeronasal sensory neurons (VSNs) in the mouse VNO 9 . It was since discovered that the activity was due to contamination of blood in the gland, which motivated us to identify a molecular basis and neural mechanism in both the peripheral and limbic brain regions for the vomeronasal stimulatory activity in the blood. In this study, we first identify a vomeronasal stimulatory molecule in the blood and define its receptor. We then reveal the behavior evoked by the blood factor, and a neural pathway responsible for the output. Results Mouse VSNs activated by C57BL/6 male mice blood hemoglobin We initially investigated a molecule in mice blood, which activate VSNs. When C57BL/6 male mice were exposed to 1 µl of blood, we observed induction of expression of c-Fos, an immediate early gene, or phosphorylation of ribosomal protein S6 (pS6), a sensitive neural activity indicator, in a subset of neurons in the basal layer of the vomeronasal epithelium that expresses Gα o and vomeronasal type 2 receptors (V2Rs) (Fig. 1a, b ) 18 , 19 . Blood-dependent c-Fos expression was also observed in the posterior region of the AOB, the first center of the vomeronasal sensory system where axons of V2R-type neurons project (Fig. 1c ) 20 . The response was dose-dependent wherein 3 µl of blood induced the maximal c-Fos response in the mitral/tufted cell layer (M/T) of the AOB (Fig. 1d ). These results suggest that blood contains compound(s) that activate V2R-type VSNs. Fig. 1: Mouse VSNs activated by C57BL/6 male mice blood hemoglobin. a Representative immunohistochemical image (left) and number of c-Fos-positive cells per VNO section from male mice stimulated by blood (1 µl) or control buffer (right). n = 3 for control and blood. Error bars, S.E.M. Arrowheads represent example c-Fos-positive cells. Scale bar, 100 µm. b Representative immunohistochemical images of anti-pS6 and anti-Gαo staining (left) and number of total pS6-positive cells in the Gαo and Gα i2 zone of the VNO section from blood- or control buffer- stimulated male mice (right). Arrowheads represent example pS6-positive cells (left) and double-positive VSNs (right). n = 3 for control and blood. Error bars, S.E.M. Scale bar, 100 µm. c Representative immunohistochemical image (left) and number of total c-Fos-positive cells in the glomerular layer (Gl) and mitral/tufted cell layer (M/T) of the AOB section from male mice stimulated by blood (1 µl) (right). Arrowheads represent c-Fos positive cells. n = 3 for control and blood. Error bars, S.E.M. Arrowheads represent example c-Fos-positive cells. Scale bar, 100 µm. d The number of c-Fos-expressing cells in the M/T cell layer of the AOB sections from male mice stimulated with the indicated amount of blood. n = 3 for 0, 0.01, 0.03, 0.3, and 3 µl, and n = 4 for 0.1, 1, and 10 µl. Error bars, S.E.M. e Separation of blood by centrifuge. Separated blood components: plasma, cell lysate and residue were used for SDS-PAGE analysis and a c-Fos-inducing assay in C57BL/6 male mice. n = 3.", "role": "user" }, { "content": "Biochemists in Japan were surprised to discover that the molecule hemoglobin in the blood works not only as an oxygen carrier; when blood is spilled as a result of aggression, accident or predator attack, the molecule also acts as a chemosensory signal for lactating mother mice, prompting digging or rearing behavior to check the surrounding environment and keep their offspring safe. A paper describing the researchers' findings has just been published in the journal Nature Communications. In 2005, researchers in the lab led by Kazushige Touhara at the University of Tokyo had already discovered in the tears of male mice a pheromone—a type of chemical substance secreted by animals that influences the behavior of others in the same species—named ESP1 (exocrine gland-secreting peptide 1), which is composed of protein. When investigating how sensory neurons in the vomeronasal organ (the organ responsible for detecting chemosensory signals such as pheromones) were stimulated by ESP1, they found that an unidentified molecule from the saliva glands was also mysteriously activating these neurons. In subsequent research seeking the source of this neuron activation, the researchers found that contamination of the gland by the blood was responsible. However, the specific molecule driving the activity and the neural pathways involved remains unknown. Then the researchers first exposed male mice to a small quantity of the blood, and observed blood-dependent activation of peripheral sensory neurons located in the vomeronasal organ in the nose. They further found that this vomeronasal stimulatory activity was prompted by cell lysate (the contents of broken up blood cells), but not in plasma (the part of the blood that carries water, salts and enzymes), and so they purified the cell lysate and employed protein sequence analysis and absorption spectrum analysis to find out which molecular compounds in the lysate were inducing the neuronal activity. The results demonstrated that hemoglobin was responsible. \"Everyone, even schoolchildren, knows that hemoglobin is the oxygen-carrying molecule in the blood, so this finding of its role as a chemosensory signal in the nose came as a real surprise to us,\" said Touhara, the corresponding author of the paper and professor with the University of Tokyo's Department of Applied Biological Chemistry. Mice in their natural environment encounter the blood under specific conditions, such as upon an injury due to aggression among males, damage by predator attack, and pup delivery. Nevertheless, when the researchers investigated the effects of hemoglobin on social behaviors such as aggression and sexual behavior, they observed no obvious change in male-male aggression, maternal aggression, or sexual behavior upon hemoglobin exposure. Once they searched responsible brain regions for the hemoglobin signal, it was only in lactating mothers that a specific neural activation in one of the regions in the hypothalamus that received the information from vomeronasal sensory neurons. Therefore, the researchers started to look at the behaviors of lactating female mice upon exposure to hemoglobin. \"The mothers immediately showed digging or rearing behavior once they received hemoglobin after playing with a cotton swab soaked in it,\" Touhara continued. \"And the same behavior was observed with exposure to fresh blood.\" The researchers also found that hemoglobin in the blood stimulates vomeronasal sensory neurons through one specific receptor, Vmn2r88. Meanwhile, in mice lacking Vmn2r88, the increase of digging or rearing behavior was not observed, suggesting that this behavior is controlled by the specific ligand-receptor pair comprising hemoglobin binding to Vmn2r88. Next, by using optogenetics to manipulate neural activities in the hypothalamus with light and genetic engineering technologies, the researchers were able to replicate the digging behavior, and from this proposed a responsible neural circuitry that regulates these hemoglobin-mediated behaviors. Such digging and rearing represent a kind of exploratory and/or risk-assessment behavior, suggesting that the response to hemoglobin appears to be important for mothers to protect their pups by checking their external environment. This leads to the next question of why only lactating mothers show this behavioral response. From this study, Touhara and his team found that one of the well-known molecules in the blood, hemoglobin, works as a chemosensory molecule and its receptor-circuit mechanism is responsible for a type of exploratory and/or risk-assessment behavior in lactating female mice. It shows that animals detect the signals surrounding their living environment and display appropriate response according to their life stage. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract The vomeronasal system plays an essential role in sensing various environmental chemical cues. Here we show that mice exposed to blood and, consequently, hemoglobin results in the activation of vomeronasal sensory neurons expressing a specific vomeronasal G protein-coupled receptor, Vmn2r88, which is mediated by the interaction site, Gly17, on hemoglobin. The hemoglobin signal reaches the medial amygdala (MeA) in both male and female mice. However, it activates the dorsal part of ventromedial hypothalamus (VMHd) only in lactating female mice. As a result, in lactating mothers, hemoglobin enhances digging and rearing behavior. Manipulation of steroidogenic factor 1 (SF1)-expressing neurons in the VMHd is sufficient to induce the hemoglobin-mediated behaviors. Our results suggest that the oxygen-carrier hemoglobin plays a role as a chemosensory signal, eliciting behavioral responses in mice in a state-dependent fashion. Introduction Animals use the olfactory systems to acquire information about the external environment. Mice, for example, show vigorous sniffing behavior that allows for sensing not only volatile airborne chemicals but also nonvolatile compounds, through direct contact in the nose 1 . Volatile odorants are recognized by odorant receptors in the olfactory epithelium and often elicit acute behavioral responses, such as attraction or aversion 2 , 3 , 4 , 5 . In contrast, nonvolatile cues are detected by vomeronasal receptors in the vomeronasal organ (VNO) located beneath the nasal cavity, and usually convey sociosexual information associated with stereotypical behavior or emotional changes 6 , 7 . Secretions, such as urine, tear fluid, and saliva contain both volatile and nonvolatile olfactory cues. For example, male mouse urine contains major urinary protein 3 (MUP3), which elicits intermale aggression 8 . Male mouse tears contain exocrine gland-secreting peptide 1 (ESP1), which enhances female sexual behavior called lordosis and male aggressiveness 9 , 10 , 11 , 12 . Juvenile mice secrete ESP22, which suppresses sexual behavior in adult mice to lessen the number of competitors 13 , 14 . In addition to these intraspecies signals, the VNO also receives inter-species signals, such as rat cystatin-related protein 1 (ratCRP1), which acts as a pheromone in rats but as a predator signal in mice 15 . Olfactory cues appear to help animals take appropriate reactions to environmental changes by affecting the internal physiological state of the animal. The VNO expresses two types of G protein-coupled receptors (187 V1Rs and 121 V2Rs) that recognize various environmental cues 16 , 17 . Only a few vomeronasal ligand-receptor pairs have been revealed; ESP1 and ESP22 are detected by single specific V2R receptors, V2Rp5 (Vmn2r116) 10 and V2Rp4 (Vmn2r115) 14 , respectively. The signals received by the specific V2Rs are conveyed to the accessory olfactory bulb (AOB) first, and then to the limbic brain regions such as amygdala and hypothalamus wherein specific neural circuits regulate distinct output behaviors 10 , 12 , 14 . The vast majority of V2Rs, however, remain orphan, limiting our understanding of sensory mechanisms underlying VNO-mediated behavioral output. When we discovered the ESP1 molecule in 2005, we also reported that the submaxillary gland contains a molecule, which activates vomeronasal sensory neurons (VSNs) in the mouse VNO 9 . It was since discovered that the activity was due to contamination of blood in the gland, which motivated us to identify a molecular basis and neural mechanism in both the peripheral and limbic brain regions for the vomeronasal stimulatory activity in the blood. In this study, we first identify a vomeronasal stimulatory molecule in the blood and define its receptor. We then reveal the behavior evoked by the blood factor, and a neural pathway responsible for the output. Results Mouse VSNs activated by C57BL/6 male mice blood hemoglobin We initially investigated a molecule in mice blood, which activate VSNs. When C57BL/6 male mice were exposed to 1 µl of blood, we observed induction of expression of c-Fos, an immediate early gene, or phosphorylation of ribosomal protein S6 (pS6), a sensitive neural activity indicator, in a subset of neurons in the basal layer of the vomeronasal epithelium that expresses Gα o and vomeronasal type 2 receptors (V2Rs) (Fig. 1a, b ) 18 , 19 . Blood-dependent c-Fos expression was also observed in the posterior region of the AOB, the first center of the vomeronasal sensory system where axons of V2R-type neurons project (Fig. 1c ) 20 . The response was dose-dependent wherein 3 µl of blood induced the maximal c-Fos response in the mitral/tufted cell layer (M/T) of the AOB (Fig. 1d ). These results suggest that blood contains compound(s) that activate V2R-type VSNs. Fig. 1: Mouse VSNs activated by C57BL/6 male mice blood hemoglobin. a Representative immunohistochemical image (left) and number of c-Fos-positive cells per VNO section from male mice stimulated by blood (1 µl) or control buffer (right). n = 3 for control and blood. Error bars, S.E.M. Arrowheads represent example c-Fos-positive cells. Scale bar, 100 µm. b Representative immunohistochemical images of anti-pS6 and anti-Gαo staining (left) and number of total pS6-positive cells in the Gαo and Gα i2 zone of the VNO section from blood- or control buffer- stimulated male mice (right). Arrowheads represent example pS6-positive cells (left) and double-positive VSNs (right). n = 3 for control and blood. Error bars, S.E.M. Scale bar, 100 µm. c Representative immunohistochemical image (left) and number of total c-Fos-positive cells in the glomerular layer (Gl) and mitral/tufted cell layer (M/T) of the AOB section from male mice stimulated by blood (1 µl) (right). Arrowheads represent c-Fos positive cells. n = 3 for control and blood. Error bars, S.E.M. Arrowheads represent example c-Fos-positive cells. Scale bar, 100 µm. d The number of c-Fos-expressing cells in the M/T cell layer of the AOB sections from male mice stimulated with the indicated amount of blood. n = 3 for 0, 0.01, 0.03, 0.3, and 3 µl, and n = 4 for 0.1, 1, and 10 µl. Error bars, S.E.M. e Separation of blood by centrifuge. Separated blood components: plasma, cell lysate and residue were used for SDS-PAGE analysis and a c-Fos-inducing assay in C57BL/6 male mice. n = 3.<|im_end|> <|im_start|>assistant Biochemists in Japan were surprised to discover that the molecule hemoglobin in the blood works not only as an oxygen carrier; when blood is spilled as a result of aggression, accident or predator attack, the molecule also acts as a chemosensory signal for lactating mother mice, prompting digging or rearing behavior to check the surrounding environment and keep their offspring safe. A paper describing the researchers' findings has just been published in the journal Nature Communications. In 2005, researchers in the lab led by Kazushige Touhara at the University of Tokyo had already discovered in the tears of male mice a pheromone—a type of chemical substance secreted by animals that influences the behavior of others in the same species—named ESP1 (exocrine gland-secreting peptide 1), which is composed of protein. When investigating how sensory neurons in the vomeronasal organ (the organ responsible for detecting chemosensory signals such as pheromones) were stimulated by ESP1, they found that an unidentified molecule from the saliva glands was also mysteriously activating these neurons. In subsequent research seeking the source of this neuron activation, the researchers found that contamination of the gland by the blood was responsible. However, the specific molecule driving the activity and the neural pathways involved remains unknown. Then the researchers first exposed male mice to a small quantity of the blood, and observed blood-dependent activation of peripheral sensory neurons located in the vomeronasal organ in the nose. They further found that this vomeronasal stimulatory activity was prompted by cell lysate (the contents of broken up blood cells), but not in plasma (the part of the blood that carries water, salts and enzymes), and so they purified the cell lysate and employed protein sequence analysis and absorption spectrum analysis to find out which molecular compounds in the lysate were inducing the neuronal activity. The results demonstrated that hemoglobin was responsible. "Everyone, even schoolchildren, knows that hemoglobin is the oxygen-carrying molecule in the blood, so this finding of its role as a chemosensory signal in the nose came as a real surprise to us," said Touhara, the corresponding author of the paper and professor with the University of Tokyo's Department of Applied Biological Chemistry. Mice in their natural environment encounter the blood under specific conditions, such as upon an injury due to aggression among males, damage by predator attack, and pup delivery. Nevertheless, when the researchers investigated the effects of hemoglobin on social behaviors such as aggression and sexual behavior, they observed no obvious change in male-male aggression, maternal aggression, or sexual behavior upon hemoglobin exposure. Once they searched responsible brain regions for the hemoglobin signal, it was only in lactating mothers that a specific neural activation in one of the regions in the hypothalamus that received the information from vomeronasal sensory neurons. Therefore, the researchers started to look at the behaviors of lactating female mice upon exposure to hemoglobin. "The mothers immediately showed digging or rearing behavior once they received hemoglobin after playing with a cotton swab soaked in it," Touhara continued. "And the same behavior was observed with exposure to fresh blood." The researchers also found that hemoglobin in the blood stimulates vomeronasal sensory neurons through one specific receptor, Vmn2r88. Meanwhile, in mice lacking Vmn2r88, the increase of digging or rearing behavior was not observed, suggesting that this behavior is controlled by the specific ligand-receptor pair comprising hemoglobin binding to Vmn2r88. Next, by using optogenetics to manipulate neural activities in the hypothalamus with light and genetic engineering technologies, the researchers were able to replicate the digging behavior, and from this proposed a responsible neural circuitry that regulates these hemoglobin-mediated behaviors. Such digging and rearing represent a kind of exploratory and/or risk-assessment behavior, suggesting that the response to hemoglobin appears to be important for mothers to protect their pups by checking their external environment. This leads to the next question of why only lactating mothers show this behavioral response. From this study, Touhara and his team found that one of the well-known molecules in the blood, hemoglobin, works as a chemosensory molecule and its receptor-circuit mechanism is responsible for a type of exploratory and/or risk-assessment behavior in lactating female mice. It shows that animals detect the signals surrounding their living environment and display appropriate response according to their life stage. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 578, 22752, 20110, 116607, 1887, 11335, 459, 7718, 3560, 304, 60199, 5370, 12434, 11742, 57016, 13, 5810, 584, 1501, 430, 24548, 15246, 311, 6680, 323, 11, 52394, 11, 17728, 94855, 3135, 304, 279, 15449, 315, 22752, 20110, 116607, 49069, 34313, 37810, 264, 3230, 22752, 20110, 116607, 480, 13128, 1824, 283, 50185, 35268, 11, 650, 22524, 17, 81, 2421, 11, 902, 374, 78926, 555, 279, 16628, 2816, 11, 79183, 1114, 11, 389, 17728, 94855, 13, 578, 17728, 94855, 8450, 25501, 279, 97348, 64383, 29684, 6181, 320, 7979, 32, 8, 304, 2225, 8762, 323, 8954, 24548, 13, 4452, 11, 433, 75042, 279, 96146, 961, 315, 10594, 442, 291, 532, 45455, 17243, 355, 320, 11435, 39, 67, 8, 1193, 304, 51644, 1113, 8954, 24548, 13, 1666, 264, 1121, 11, 304, 51644, 1113, 27698, 11, 17728, 94855, 57924, 42200, 323, 312, 3329, 7865, 13, 62011, 2987, 315, 77848, 29569, 8331, 220, 16, 320, 29767, 16, 7435, 14107, 287, 34313, 304, 279, 18270, 39, 67, 374, 14343, 311, 49853, 279, 17728, 94855, 82076, 28198, 13, 5751, 3135, 4284, 430, 279, 24463, 24948, 7401, 17728, 94855, 11335, 264, 3560, 439, 264, 8590, 437, 729, 683, 8450, 11, 95360, 5977, 36695, 14847, 304, 24548, 304, 264, 1614, 43918, 11401, 13, 29438, 47966, 1005, 279, 8492, 22348, 6067, 311, 21953, 2038, 922, 279, 9434, 4676, 13, 386, 560, 11, 369, 3187, 11, 1501, 71920, 58387, 287, 7865, 430, 6276, 369, 60199, 539, 1193, 17509, 70863, 26333, 719, 1101, 2536, 28407, 32246, 11, 1555, 2167, 3729, 304, 279, 19689, 220, 16, 662, 11119, 9187, 54097, 1821, 527, 15324, 555, 54097, 519, 44540, 304, 279, 8492, 22348, 64779, 301, 2411, 323, 3629, 658, 19195, 30883, 36695, 14847, 11, 1778, 439, 33464, 477, 1860, 1349, 220, 17, 1174, 220, 18, 1174, 220, 19, 1174, 220, 20, 662, 763, 13168, 11, 2536, 28407, 57016, 527, 16914, 555, 22752, 20110, 116607, 44540, 304, 279, 22752, 20110, 116607, 2942, 320, 53, 9173, 8, 7559, 24923, 279, 72188, 56429, 11, 323, 6118, 20599, 41589, 44687, 2038, 5938, 449, 23473, 88167, 7865, 477, 14604, 4442, 220, 21, 1174, 220, 22, 662, 8769, 919, 11, 1778, 439, 40335, 11, 18036, 15962, 11, 323, 85657, 6782, 2225, 17509, 323, 2536, 28407, 8492, 22348, 57016, 13, 1789, 3187, 11, 8762, 8814, 40335, 5727, 3682, 72735, 13128, 220, 18, 320, 44, 3202, 18, 705, 902, 658, 51650, 958, 37576, 40307, 220, 23, 662, 19960, 8814, 24014, 6782, 506, 78738, 67169, 7962, 846, 1303, 72249, 220, 16, 320, 57329, 16, 705, 902, 57924, 8954, 7392, 7865, 2663, 38031, 10934, 323, 8762, 13632, 13071, 220, 24, 1174, 220, 605, 1174, 220, 806, 1174, 220, 717, 662, 22410, 40204, 24548, 513, 9537, 18609, 1313, 11, 902, 28321, 288, 7392, 7865, 304, 6822, 24548, 311, 76970, 279, 1396, 315, 28650, 220, 1032, 1174, 220, 975, 662, 763, 5369, 311, 1521, 10805, 300, 89721, 17738, 11, 279, 650, 9173, 1101, 21879, 958, 58894, 552, 17738, 11, 1778, 439, 11494, 63581, 15111, 14228, 13128, 220, 16, 320, 18071, 9150, 47, 16, 705, 902, 14385, 439, 264, 1343, 261, 316, 606, 304, 32510, 719, 439, 264, 68006, 8450, 304, 24548, 220, 868, 662, 507, 11253, 2992, 57016, 5101, 311, 1520, 10099, 1935, 8475, 25481, 311, 12434, 4442, 555, 28987, 279, 5419, 53194, 1614, 315, 279, 10065, 13, 578, 650, 9173, 61120, 1403, 4595, 315, 480, 13128, 1824, 283, 50185, 44540, 320, 9674, 650, 16, 43427, 323, 220, 7994, 650, 17, 43427, 8, 430, 15641, 5370, 12434, 57016, 220, 845, 1174, 220, 1114, 662, 8442, 264, 2478, 22752, 20110, 116607, 29413, 438, 5621, 15709, 13840, 617, 1027, 10675, 26, 18609, 16, 323, 18609, 1313, 527, 16914, 555, 3254, 3230, 650, 17, 49, 44540, 11, 650, 17, 62830, 20, 320, 53, 22524, 17, 81, 8027, 8, 220, 605, 323, 650, 17, 62830, 19, 320, 53, 22524, 17, 81, 7322, 8, 220, 975, 1174, 15947, 13, 578, 17738, 4036, 555, 279, 3230, 650, 17, 43427, 527, 73897, 311, 279, 43081, 8492, 22348, 46912, 320, 19268, 33, 8, 1176, 11, 323, 1243, 311, 279, 48694, 292, 8271, 13918, 1778, 439, 64383, 29684, 6181, 323, 45455, 17243, 355, 42418, 3230, 30828, 46121, 37377, 12742, 2612, 28198, 220, 605, 1174, 220, 717, 1174, 220, 975, 662, 578, 13057, 8857, 315, 650, 17, 43427, 11, 4869, 11, 7293, 13036, 11, 33994, 1057, 8830, 315, 49069, 24717, 16940, 650, 9173, 82076, 36695, 2612, 13, 3277, 584, 11352, 279, 18609, 16, 43030, 304, 220, 1049, 20, 11, 584, 1101, 5068, 430, 279, 1207, 2880, 35605, 67169, 5727, 264, 43030, 11, 902, 75042, 22752, 20110, 116607, 49069, 34313, 320, 53, 19503, 82, 8, 304, 279, 8814, 650, 9173, 220, 24, 662, 1102, 574, 2533, 11352, 430, 279, 5820, 574, 4245, 311, 47810, 315, 6680, 304, 279, 67169, 11, 902, 27762, 603, 311, 10765, 264, 31206, 8197, 323, 30828, 17383, 304, 2225, 279, 35688, 323, 48694, 292, 8271, 13918, 369, 279, 22752, 20110, 116607, 12936, 38220, 5820, 304, 279, 6680, 13, 763, 420, 4007, 11, 584, 1176, 10765, 264, 22752, 20110, 116607, 12936, 38220, 43030, 304, 279, 6680, 323, 7124, 1202, 35268, 13, 1226, 1243, 16805, 279, 7865, 3721, 11059, 555, 279, 6680, 8331, 11, 323, 264, 30828, 38970, 8647, 369, 279, 2612, 13, 18591, 18191, 650, 19503, 82, 22756, 555, 356, 3226, 9574, 14, 21, 8762, 24548, 6680, 17728, 94855, 1226, 15453, 27313, 264, 43030, 304, 24548, 6680, 11, 902, 20891, 650, 19503, 82, 13, 3277, 356, 3226, 9574, 14, 21, 8762, 24548, 1051, 15246, 311, 220, 16, 64012, 75, 315, 6680, 11, 584, 13468, 38156, 315, 7645, 315, 272, 7424, 437, 11, 459, 14247, 4216, 15207, 11, 477, 95089, 2354, 315, 20735, 96108, 13128, 328, 21, 320, 79, 50, 21, 705, 264, 16614, 30828, 5820, 21070, 11, 304, 264, 27084, 315, 34313, 304, 279, 80710, 6324, 315, 279, 22752, 20110, 116607, 64779, 301, 2411, 430, 61120, 480, 19481, 297, 323, 22752, 20110, 116607, 955, 220, 17, 44540, 320, 53, 17, 43427, 8, 320, 30035, 13, 220, 16, 64, 11, 293, 883, 220, 972, 1174, 220, 777, 662, 20671, 43918, 272, 7424, 437, 7645, 574, 1101, 13468, 304, 279, 46000, 5654, 315, 279, 362, 21257, 11, 279, 1176, 4219, 315, 279, 22752, 20110, 116607, 49069, 1887, 1405, 3944, 2439, 315, 650, 17, 49, 10827, 34313, 2447, 320, 30035, 13, 220, 16, 66, 883, 220, 508, 662, 578, 2077, 574, 19660, 43918, 42418, 220, 18, 64012, 75, 315, 6680, 36572, 279, 54229, 272, 7424, 437, 2077, 304, 279, 5568, 3545, 5640, 90231, 291, 2849, 6324, 320, 44, 17146, 8, 315, 279, 362, 21257, 320, 30035, 13, 220, 16, 67, 7609, 4314, 3135, 4284, 430, 6680, 5727, 24549, 1161, 8, 430, 20891, 650, 17, 49, 10827, 650, 19503, 82, 13, 23966, 13, 220, 16, 25, 18191, 650, 19503, 82, 22756, 555, 356, 3226, 9574, 14, 21, 8762, 24548, 6680, 17728, 94855, 13, 264, 38366, 33119, 2319, 26407, 32056, 2217, 320, 2414, 8, 323, 1396, 315, 272, 7424, 437, 69788, 7917, 824, 650, 9173, 3857, 505, 8762, 24548, 81471, 555, 6680, 320, 16, 64012, 75, 8, 477, 2585, 4240, 320, 1315, 570, 308, 284, 220, 18, 369, 2585, 323, 6680, 13, 4703, 16283, 11, 328, 5253, 1345, 13, 34812, 36910, 4097, 3187, 272, 7424, 437, 69788, 7917, 13, 25635, 3703, 11, 220, 1041, 64012, 76, 13, 293, 38366, 33119, 2319, 26407, 32056, 5448, 315, 7294, 2320, 50, 21, 323, 7294, 12279, 19481, 78, 88896, 320, 2414, 8, 323, 1396, 315, 2860, 281, 50, 21, 69788, 7917, 304, 279, 480, 19481, 78, 323, 480, 19481, 602, 17, 10353, 315, 279, 650, 9173, 3857, 505, 6680, 12, 477, 2585, 4240, 12, 81471, 8762, 24548, 320, 1315, 570, 34812, 36910, 4097, 3187, 281, 50, 21, 69788, 7917, 320, 2414, 8, 323, 2033, 69788, 650, 19503, 82, 320, 1315, 570, 308, 284, 220, 18, 369, 2585, 323, 6680, 13, 4703, 16283, 11, 328, 5253, 1345, 13, 25635, 3703, 11, 220, 1041, 64012, 76, 13, 272, 38366, 33119, 2319, 26407, 32056, 2217, 320, 2414, 8, 323, 1396, 315, 2860, 272, 7424, 437, 69788, 7917, 304, 279, 2840, 26429, 1299, 6324, 320, 32641, 8, 323, 5568, 3545, 5640, 90231, 291, 2849, 6324, 320, 44, 17146, 8, 315, 279, 362, 21257, 3857, 505, 8762, 24548, 81471, 555, 6680, 320, 16, 64012, 75, 8, 320, 1315, 570, 34812, 36910, 4097, 272, 7424, 437, 6928, 7917, 13, 308, 284, 220, 18, 369, 2585, 323, 6680, 13, 4703, 16283, 11, 328, 5253, 1345, 13, 34812, 36910, 4097, 3187, 272, 7424, 437, 69788, 7917, 13, 25635, 3703, 11, 220, 1041, 64012, 76, 13, 294, 578, 1396, 315, 272, 7424, 437, 10397, 1911, 287, 7917, 304, 279, 386, 17146, 2849, 6324, 315, 279, 362, 21257, 14491, 505, 8762, 24548, 81471, 449, 279, 16717, 3392, 315, 6680, 13, 308, 284, 220, 18, 369, 220, 15, 11, 220, 15, 13, 1721, 11, 220, 15, 13, 2839, 11, 220, 15, 13, 18, 11, 323, 220, 18, 64012, 75, 11, 323, 308, 284, 220, 19, 369, 220, 15, 13, 16, 11, 220, 16, 11, 323, 220, 605, 64012, 75, 13, 4703, 16283, 11, 328, 5253, 1345, 13, 384, 34199, 367, 315, 6680, 555, 74182, 4838, 13, 34199, 660, 6680, 6956, 25, 32426, 11, 2849, 84495, 349, 323, 49232, 1051, 1511, 369, 96712, 9483, 3669, 6492, 323, 264, 272, 7424, 437, 18251, 59144, 65033, 304, 356, 3226, 9574, 14, 21, 8762, 24548, 13, 308, 284, 220, 18, 13, 128257, 198, 128256, 78191, 198, 60360, 2464, 1705, 304, 6457, 1051, 14792, 311, 7142, 430, 279, 43030, 17728, 94855, 304, 279, 6680, 4375, 539, 1193, 439, 459, 24463, 19115, 26, 994, 6680, 374, 74125, 439, 264, 1121, 315, 40307, 11, 11677, 477, 68006, 3440, 11, 279, 43030, 1101, 14385, 439, 264, 8590, 437, 729, 683, 8450, 369, 51644, 1113, 6691, 24548, 11, 50745, 42200, 477, 312, 3329, 7865, 311, 1817, 279, 14932, 4676, 323, 2567, 872, 46471, 6220, 13, 362, 5684, 23524, 279, 12074, 6, 14955, 706, 1120, 1027, 4756, 304, 279, 8486, 22037, 26545, 13, 763, 220, 1049, 20, 11, 12074, 304, 279, 10278, 6197, 555, 36074, 1136, 7404, 57895, 71, 5169, 520, 279, 3907, 315, 27286, 1047, 2736, 11352, 304, 279, 24014, 315, 8762, 24548, 264, 1343, 261, 316, 606, 29096, 955, 315, 11742, 20278, 6367, 291, 555, 10099, 430, 34453, 279, 7865, 315, 3885, 304, 279, 1890, 9606, 2345, 31345, 18609, 16, 320, 327, 78738, 67169, 7962, 846, 1303, 72249, 220, 16, 705, 902, 374, 24306, 315, 13128, 13, 3277, 24834, 1268, 49069, 34313, 304, 279, 22752, 20110, 116607, 2942, 320, 1820, 2942, 8647, 369, 54626, 8590, 437, 729, 683, 17738, 1778, 439, 1343, 261, 316, 3233, 8, 1051, 81471, 555, 18609, 16, 11, 814, 1766, 430, 459, 65578, 43030, 505, 279, 85657, 82375, 574, 1101, 24212, 13610, 72192, 1521, 34313, 13, 763, 17876, 3495, 11125, 279, 2592, 315, 420, 49384, 15449, 11, 279, 12074, 1766, 430, 47810, 315, 279, 67169, 555, 279, 6680, 574, 8647, 13, 4452, 11, 279, 3230, 43030, 10043, 279, 5820, 323, 279, 30828, 44014, 6532, 8625, 9987, 13, 5112, 279, 12074, 1176, 15246, 8762, 24548, 311, 264, 2678, 12472, 315, 279, 6680, 11, 323, 13468, 6680, 43918, 15449, 315, 35688, 49069, 34313, 7559, 304, 279, 22752, 20110, 116607, 2942, 304, 279, 19689, 13, 2435, 4726, 1766, 430, 420, 22752, 20110, 116607, 12936, 38220, 5820, 574, 29746, 555, 2849, 84495, 349, 320, 1820, 8970, 315, 11102, 709, 6680, 7917, 705, 719, 539, 304, 32426, 320, 1820, 961, 315, 279, 6680, 430, 24266, 3090, 11, 78235, 323, 56067, 705, 323, 779, 814, 92600, 279, 2849, 84495, 349, 323, 20011, 13128, 8668, 6492, 323, 44225, 20326, 6492, 311, 1505, 704, 902, 31206, 32246, 304, 279, 84495, 349, 1051, 96811, 279, 79402, 5820, 13, 578, 3135, 21091, 430, 17728, 94855, 574, 8647, 13, 330, 34124, 11, 1524, 2978, 5988, 11, 8964, 430, 17728, 94855, 374, 279, 24463, 1824, 11687, 287, 43030, 304, 279, 6680, 11, 779, 420, 9455, 315, 1202, 3560, 439, 264, 8590, 437, 729, 683, 8450, 304, 279, 19689, 3782, 439, 264, 1972, 13051, 311, 603, 1359, 1071, 57895, 71, 5169, 11, 279, 12435, 3229, 315, 279, 5684, 323, 14561, 449, 279, 3907, 315, 27286, 596, 6011, 315, 43608, 63711, 42846, 13, 386, 560, 304, 872, 5933, 4676, 13123, 279, 6680, 1234, 3230, 4787, 11, 1778, 439, 5304, 459, 11134, 4245, 311, 40307, 4315, 25000, 11, 5674, 555, 68006, 3440, 11, 323, 15241, 9889, 13, 35053, 11, 994, 279, 12074, 27313, 279, 6372, 315, 17728, 94855, 389, 3674, 28198, 1778, 439, 40307, 323, 7392, 7865, 11, 814, 13468, 912, 8196, 2349, 304, 8762, 1474, 1604, 40307, 11, 50150, 40307, 11, 477, 7392, 7865, 5304, 17728, 94855, 14675, 13, 9843, 814, 27600, 8647, 8271, 13918, 369, 279, 17728, 94855, 8450, 11, 433, 574, 1193, 304, 51644, 1113, 27698, 430, 264, 3230, 30828, 15449, 304, 832, 315, 279, 13918, 304, 279, 45455, 17243, 355, 430, 4036, 279, 2038, 505, 22752, 20110, 116607, 49069, 34313, 13, 15636, 11, 279, 12074, 3940, 311, 1427, 520, 279, 28198, 315, 51644, 1113, 8954, 24548, 5304, 14675, 311, 17728, 94855, 13, 330, 791, 27698, 7214, 8710, 42200, 477, 312, 3329, 7865, 3131, 814, 4036, 17728, 94855, 1306, 5737, 449, 264, 24428, 2064, 370, 69975, 304, 433, 1359, 57895, 71, 5169, 8738, 13, 330, 3112, 279, 1890, 7865, 574, 13468, 449, 14675, 311, 7878, 6680, 1210, 578, 12074, 1101, 1766, 430, 17728, 94855, 304, 279, 6680, 95455, 22752, 20110, 116607, 49069, 34313, 1555, 832, 3230, 35268, 11, 650, 22524, 17, 81, 2421, 13, 26982, 11, 304, 24548, 32161, 650, 22524, 17, 81, 2421, 11, 279, 5376, 315, 42200, 477, 312, 3329, 7865, 574, 539, 13468, 11, 23377, 430, 420, 7865, 374, 14400, 555, 279, 3230, 29413, 438, 5621, 15709, 6857, 46338, 17728, 94855, 11212, 311, 650, 22524, 17, 81, 2421, 13, 9479, 11, 555, 1701, 3469, 11968, 25265, 311, 37735, 30828, 7640, 304, 279, 45455, 17243, 355, 449, 3177, 323, 19465, 15009, 14645, 11, 279, 12074, 1051, 3025, 311, 46113, 279, 42200, 7865, 11, 323, 505, 420, 11223, 264, 8647, 30828, 16622, 894, 430, 80412, 1521, 17728, 94855, 82076, 28198, 13, 15483, 42200, 323, 312, 3329, 4097, 264, 3169, 315, 48539, 5382, 323, 5255, 5326, 35915, 24280, 7865, 11, 23377, 430, 279, 2077, 311, 17728, 94855, 8111, 311, 387, 3062, 369, 27698, 311, 6144, 872, 90821, 555, 13598, 872, 9434, 4676, 13, 1115, 11767, 311, 279, 1828, 3488, 315, 3249, 1193, 51644, 1113, 27698, 1501, 420, 36695, 2077, 13, 5659, 420, 4007, 11, 57895, 71, 5169, 323, 813, 2128, 1766, 430, 832, 315, 279, 1664, 22015, 35715, 304, 279, 6680, 11, 17728, 94855, 11, 4375, 439, 264, 8590, 437, 729, 683, 43030, 323, 1202, 35268, 1824, 38368, 17383, 374, 8647, 369, 264, 955, 315, 48539, 5382, 323, 5255, 5326, 35915, 24280, 7865, 304, 51644, 1113, 8954, 24548, 13, 1102, 5039, 430, 10099, 11388, 279, 17738, 14932, 872, 5496, 4676, 323, 3113, 8475, 2077, 4184, 311, 872, 2324, 6566, 13, 220, 128257, 198 ]

2,485

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Precise signalling between pollen tubes and synergid cells in the ovule initiates fertilization in flowering plants 1 . Contact of the pollen tube with the ovule triggers calcium spiking in the synergids 2 , 3 that induces pollen tube rupture and sperm release. This process, termed pollen tube reception, entails the action of three synergid-expressed proteins in Arabidopsis : FERONIA (FER), a receptor-like kinase; LORELEI (LRE), a glycosylphosphatidylinositol-anchored protein; and NORTIA (NTA), a transmembrane protein of unknown function 4 , 5 , 6 . Genetic analyses have placed these three proteins in the same pathway; however, it remains unknown how they work together to enable synergid–pollen tube communication. Here we identify two pollen-tube-derived small peptides 7 that belong to the rapid alkalinization factor (RALF) family 8 as ligands for the FER–LRE co-receptor, which in turn recruits NTA to the plasma membrane. NTA functions as a calmodulin-gated calcium channel required for calcium spiking in the synergid. We also reconstitute the biochemical pathway in which FER–LRE perceives pollen-tube-derived peptides to activate the NTA calcium channel and initiate calcium spiking, a second messenger for pollen tube reception. The FER–LRE–NTA trio therefore forms a previously unanticipated receptor–channel complex in the female cell to recognize male signals and trigger the fertilization process. Main As a ubiquitous second messenger, Ca 2+ regulates many aspects of physiology and development in both animals and plants 9 , 10 , 11 , including reproduction. In animals, Ca 2+ signals drive the motility of sperm 12 and forecast successful fertilization 13 . In flowering plants, sperm are immobile and require a special delivery structure called the pollen tube, which navigates the female tissue and finds the ovule before releasing sperm 1 . From pollen germination to pollen tube guidance and pollen tube reception, each step requires intricate Ca 2+ signalling 14 . However, the molecular mechanism underlying Ca 2+ signalling in plant reproduction remains largely unknown. During pollen tube reception, interactions between the pollen tube and synergids in the ovule activates Ca 2+ oscillations in both partners, which leads to the rupture of the pollen tube and synergid cell death and the initiation of fertilization 2 , 3 , 15 , 16 . On the female side, FER, LRE and NTA are three components from the same pathway required for synergid Ca 2+ spiking in response to pollen tube arrival, but little is known regarding how they work together to mediate Ca 2+ entry. We show here that pollen tube RALFs bind to FER–LRE co-receptors, which recruit NTA, a calcium channel, to form a receptor–channel assembly. This tri-molecular complex is regulated by Ca 2+ /calmodulin (CaM)-dependent feedback inhibition to drive Ca 2+ oscillations in the synergid. RALFs trigger synergid Ca 2+ oscillation FER and LRE are both required for pollen tube reception and may function as a co-receptor for unknown signals derived from pollen tubes 4 , 5 , 17 , 18 , 19 , 20 . We hypothesized that such signals may be mediated by RALF family peptides because some RALFs bind to either FER alone 21 , 22 or to both FER and LRE-like proteins (LLGs) in other processes 23 , 24 , 25 . Among the 37 Arabidopsis RALFs, at least 8 (RALF4, RALF8, RALF9, RALF15, RALF19, RALF25, RALF26 and RALF30) are expressed in pollen tubes 7 . We expressed and purified the eight pollen-tube-derived RALF peptides and examined their interaction with FER 23 . We also included an ovule-derived RALF peptide (RALF34) that is closely related to pollen tube RALFs such as RALF4 and RALF19. The extracellular domain of FER (FER ex ) pulled down RALF4, RALF19 and RALF34 (Fig. 1a and Supplementary Fig. 1a ). Consistent with this result, RALF4 and RALF19 acted antagonistically with RALF34 for pollen tube integrity through interactions with the same receptors of the FER family 7 . Fig. 1: Pollen-derived RALFs bind to FER–LRE and trigger synergid [Ca 2+ ] cyt changes in a FER–LRE–NTA-dependent manner. a , Pull-down assays showing the interaction of GST-tagged RALFs and MBP-tagged ectodomains of FER (FER ex ). Amylose resin was used to pull down MBP, followed by western blotting with antibodies against GST and MBP. n = 3 independent repeats. b , Interaction of GST-tagged LRE and MBP-tagged ectodomains of FER with or without RALFs (RALF x ; each 100 nM) as indicated. Amylose resin pull-down and western blotting was performed as in a . n = 3 independent repeats. c , Co-IP of Myc-tagged LRE and Flag-tagged FERK565R expressed in N. benthamiana leaves with or without the addition of RALFs (each 5 μM) as indicated. Anti-Flag M2 affinity beads were used in co-IP, and western blots were probed with antibodies against Myc and Flag. n = 3 independent repeats. d – g , Representative Ca 2+ spiking patterns in synergids in response to pollen tube (PT) arrival or to 0.5 µM or 2 µM RALF4 (R4) for WT ( d ), fer-4 ( e ), lre-5 ( f ) and nta-3 ( g ). W, water. h , Ca 2+ oscillation periodicity of WT synergids in response to PT arrival or 0.5 µM RALF4 and RALF19 (R19). n = 8 ovules. i , The peak values of Ca 2+ spiking as in d – g . n values are shown in Extended Data Fig. 3 . Ovules were isolated from Col-0, fer-4 , lre-5 and nta-3 flowers harbouring the synergid-specific GCaMP6, and fluorescence was recorded using an inverted microscope. Red triangles indicate time points at which the PT arrived or RALF4 was applied. Error bars depict the mean ± s.e.m. All P values were determined by two-tailed Student’s t -test. NS, not significant. Source data Full size image As ligands for FER–LLG co-receptors, RALFs enhance interactions between FER and LLGs 23 . Consistent with this model, RALF4, RALF19 and RALF34 enhanced the interaction between GST-tagged LRE and MBP-tagged FER ex , whereas several other RALFs did not (Fig. 1b , bottom, and Supplementary Fig. 1b ). This observation was confirmed by", "role": "user" }, { "content": "Researchers in the Department of Plant and Microbial Biology (PMB) have uncovered the intricate molecular processes that precede reproduction in flowering plants. Published July 6 in Nature, the findings document a previously unknown molecular process that serves as a method of communication during fertilization. According to Professor Sheng Luan, chair of the PMB department and the paper's senior author, the exact mechanism for signaling has previously eluded researchers. \"At the molecular level, this whole process is now more clear than ever before,\" he said. Sending molecular 'love notes' Flowers reproduce sexually through pollination, a process that involves the transfer of pollen from a flower's stamen (the male fertilizing organ) to the stigma on the pistil (the female reproductive organ). Once the pollen grain lodges on the stigma, a pollen tube grows from the pollen grain to an ovule to facilitate the transfer of sperm to the egg. Luan said researchers have previously recorded the presence of calcium waves preceding the fertilization process and noted that \"they knew the calcium signal is important but didn't know exactly how it is produced.\" To analyze how the calcium wave was produced by the female cell, Luan and his co-authors introduced a biosensor to report calcium levels in the specific cell to look for signals from the male parts that trigger calcium waves. They found that pollen tubes emit several small peptides—short chains of amino acids—that can be recognized by peptide receptors on the surface of the female cell. Once activated, these receptors recruit a calcium channel to produce a calcium wave that guides the pollen tube to the ovule and initiates fertilization. Green calcium waves \"pulse\" in this recording provided by the Luan Lab. \"You could compare this to a delivery service,\" Luan explained. \"We know the small peptide molecule serves as a signal to the female part of the flower, almost like a knock on the door letting it know the pollen tube is here.\" The calcium waves ultimately cause the pollen tube to rupture and release the immobile sperm once it is inside the ovule, ensuring a successful fertilization process. \"In a way, they basically commit suicide to release the sperm,\" Luan said. \"Sometimes the female reproductive cell also dies in order to expose the egg so they can meet and produce new life. It's kind of a romantic journey for plant reproduction.\" Reinventing molecular messaging According to Luan, understanding the intricate molecular processes of fertilization may help improve the commercial yields in flowering plants. Other researchers or plant geneticists might use the findings to break the interspecies barrier, potentially opening the door to the creation of new hybrid crop species through cross-pollination. But, in addition to the potential commercial application, these findings further highlight plants' miraculous ability to communicate via molecular emissions. \"From an evolutionary point of view, plants reinvented their own molecules specific to their unique communication process,\" he added. The calcium channels identified in this study are unique to plants, suggesting they invented a way to produce signals that are different than those found in animals. Luan said researchers have studied calcium channels for more than 30 years, uncovering how they confer resistance to powdery mildew (a fungal disease that affects a wide variety of plants) or enable mechanical sensing in root systems. Their biochemical role remained unknown until this study uncovered the specific channel activity. \"Reinventing new channels to communicate in their own way, consistent with different lifestyles of plants and animals, is of general importance to biology,\" Luan said. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Precise signalling between pollen tubes and synergid cells in the ovule initiates fertilization in flowering plants 1 . Contact of the pollen tube with the ovule triggers calcium spiking in the synergids 2 , 3 that induces pollen tube rupture and sperm release. This process, termed pollen tube reception, entails the action of three synergid-expressed proteins in Arabidopsis : FERONIA (FER), a receptor-like kinase; LORELEI (LRE), a glycosylphosphatidylinositol-anchored protein; and NORTIA (NTA), a transmembrane protein of unknown function 4 , 5 , 6 . Genetic analyses have placed these three proteins in the same pathway; however, it remains unknown how they work together to enable synergid–pollen tube communication. Here we identify two pollen-tube-derived small peptides 7 that belong to the rapid alkalinization factor (RALF) family 8 as ligands for the FER–LRE co-receptor, which in turn recruits NTA to the plasma membrane. NTA functions as a calmodulin-gated calcium channel required for calcium spiking in the synergid. We also reconstitute the biochemical pathway in which FER–LRE perceives pollen-tube-derived peptides to activate the NTA calcium channel and initiate calcium spiking, a second messenger for pollen tube reception. The FER–LRE–NTA trio therefore forms a previously unanticipated receptor–channel complex in the female cell to recognize male signals and trigger the fertilization process. Main As a ubiquitous second messenger, Ca 2+ regulates many aspects of physiology and development in both animals and plants 9 , 10 , 11 , including reproduction. In animals, Ca 2+ signals drive the motility of sperm 12 and forecast successful fertilization 13 . In flowering plants, sperm are immobile and require a special delivery structure called the pollen tube, which navigates the female tissue and finds the ovule before releasing sperm 1 . From pollen germination to pollen tube guidance and pollen tube reception, each step requires intricate Ca 2+ signalling 14 . However, the molecular mechanism underlying Ca 2+ signalling in plant reproduction remains largely unknown. During pollen tube reception, interactions between the pollen tube and synergids in the ovule activates Ca 2+ oscillations in both partners, which leads to the rupture of the pollen tube and synergid cell death and the initiation of fertilization 2 , 3 , 15 , 16 . On the female side, FER, LRE and NTA are three components from the same pathway required for synergid Ca 2+ spiking in response to pollen tube arrival, but little is known regarding how they work together to mediate Ca 2+ entry. We show here that pollen tube RALFs bind to FER–LRE co-receptors, which recruit NTA, a calcium channel, to form a receptor–channel assembly. This tri-molecular complex is regulated by Ca 2+ /calmodulin (CaM)-dependent feedback inhibition to drive Ca 2+ oscillations in the synergid. RALFs trigger synergid Ca 2+ oscillation FER and LRE are both required for pollen tube reception and may function as a co-receptor for unknown signals derived from pollen tubes 4 , 5 , 17 , 18 , 19 , 20 . We hypothesized that such signals may be mediated by RALF family peptides because some RALFs bind to either FER alone 21 , 22 or to both FER and LRE-like proteins (LLGs) in other processes 23 , 24 , 25 . Among the 37 Arabidopsis RALFs, at least 8 (RALF4, RALF8, RALF9, RALF15, RALF19, RALF25, RALF26 and RALF30) are expressed in pollen tubes 7 . We expressed and purified the eight pollen-tube-derived RALF peptides and examined their interaction with FER 23 . We also included an ovule-derived RALF peptide (RALF34) that is closely related to pollen tube RALFs such as RALF4 and RALF19. The extracellular domain of FER (FER ex ) pulled down RALF4, RALF19 and RALF34 (Fig. 1a and Supplementary Fig. 1a ). Consistent with this result, RALF4 and RALF19 acted antagonistically with RALF34 for pollen tube integrity through interactions with the same receptors of the FER family 7 . Fig. 1: Pollen-derived RALFs bind to FER–LRE and trigger synergid [Ca 2+ ] cyt changes in a FER–LRE–NTA-dependent manner. a , Pull-down assays showing the interaction of GST-tagged RALFs and MBP-tagged ectodomains of FER (FER ex ). Amylose resin was used to pull down MBP, followed by western blotting with antibodies against GST and MBP. n = 3 independent repeats. b , Interaction of GST-tagged LRE and MBP-tagged ectodomains of FER with or without RALFs (RALF x ; each 100 nM) as indicated. Amylose resin pull-down and western blotting was performed as in a . n = 3 independent repeats. c , Co-IP of Myc-tagged LRE and Flag-tagged FERK565R expressed in N. benthamiana leaves with or without the addition of RALFs (each 5 μM) as indicated. Anti-Flag M2 affinity beads were used in co-IP, and western blots were probed with antibodies against Myc and Flag. n = 3 independent repeats. d – g , Representative Ca 2+ spiking patterns in synergids in response to pollen tube (PT) arrival or to 0.5 µM or 2 µM RALF4 (R4) for WT ( d ), fer-4 ( e ), lre-5 ( f ) and nta-3 ( g ). W, water. h , Ca 2+ oscillation periodicity of WT synergids in response to PT arrival or 0.5 µM RALF4 and RALF19 (R19). n = 8 ovules. i , The peak values of Ca 2+ spiking as in d – g . n values are shown in Extended Data Fig. 3 . Ovules were isolated from Col-0, fer-4 , lre-5 and nta-3 flowers harbouring the synergid-specific GCaMP6, and fluorescence was recorded using an inverted microscope. Red triangles indicate time points at which the PT arrived or RALF4 was applied. Error bars depict the mean ± s.e.m. All P values were determined by two-tailed Student’s t -test. NS, not significant. Source data Full size image As ligands for FER–LLG co-receptors, RALFs enhance interactions between FER and LLGs 23 . Consistent with this model, RALF4, RALF19 and RALF34 enhanced the interaction between GST-tagged LRE and MBP-tagged FER ex , whereas several other RALFs did not (Fig. 1b , bottom, and Supplementary Fig. 1b ). This observation was confirmed by<|im_end|> <|im_start|>assistant Researchers in the Department of Plant and Microbial Biology (PMB) have uncovered the intricate molecular processes that precede reproduction in flowering plants. Published July 6 in Nature, the findings document a previously unknown molecular process that serves as a method of communication during fertilization. According to Professor Sheng Luan, chair of the PMB department and the paper's senior author, the exact mechanism for signaling has previously eluded researchers. "At the molecular level, this whole process is now more clear than ever before," he said. Sending molecular 'love notes' Flowers reproduce sexually through pollination, a process that involves the transfer of pollen from a flower's stamen (the male fertilizing organ) to the stigma on the pistil (the female reproductive organ). Once the pollen grain lodges on the stigma, a pollen tube grows from the pollen grain to an ovule to facilitate the transfer of sperm to the egg. Luan said researchers have previously recorded the presence of calcium waves preceding the fertilization process and noted that "they knew the calcium signal is important but didn't know exactly how it is produced." To analyze how the calcium wave was produced by the female cell, Luan and his co-authors introduced a biosensor to report calcium levels in the specific cell to look for signals from the male parts that trigger calcium waves. They found that pollen tubes emit several small peptides—short chains of amino acids—that can be recognized by peptide receptors on the surface of the female cell. Once activated, these receptors recruit a calcium channel to produce a calcium wave that guides the pollen tube to the ovule and initiates fertilization. Green calcium waves "pulse" in this recording provided by the Luan Lab. "You could compare this to a delivery service," Luan explained. "We know the small peptide molecule serves as a signal to the female part of the flower, almost like a knock on the door letting it know the pollen tube is here." The calcium waves ultimately cause the pollen tube to rupture and release the immobile sperm once it is inside the ovule, ensuring a successful fertilization process. "In a way, they basically commit suicide to release the sperm," Luan said. "Sometimes the female reproductive cell also dies in order to expose the egg so they can meet and produce new life. It's kind of a romantic journey for plant reproduction." Reinventing molecular messaging According to Luan, understanding the intricate molecular processes of fertilization may help improve the commercial yields in flowering plants. Other researchers or plant geneticists might use the findings to break the interspecies barrier, potentially opening the door to the creation of new hybrid crop species through cross-pollination. But, in addition to the potential commercial application, these findings further highlight plants' miraculous ability to communicate via molecular emissions. "From an evolutionary point of view, plants reinvented their own molecules specific to their unique communication process," he added. The calcium channels identified in this study are unique to plants, suggesting they invented a way to produce signals that are different than those found in animals. Luan said researchers have studied calcium channels for more than 30 years, uncovering how they confer resistance to powdery mildew (a fungal disease that affects a wide variety of plants) or enable mechanical sensing in root systems. Their biochemical role remained unknown until this study uncovered the specific channel activity. "Reinventing new channels to communicate in their own way, consistent with different lifestyles of plants and animals, is of general importance to biology," Luan said. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 42770, 1082, 91977, 1990, 79784, 34083, 323, 6705, 1215, 35949, 7917, 304, 279, 25568, 1130, 12961, 988, 36214, 2065, 304, 82339, 11012, 220, 16, 662, 9359, 315, 279, 79784, 14019, 449, 279, 25568, 1130, 31854, 35719, 993, 19787, 304, 279, 80526, 3447, 220, 17, 1174, 220, 18, 430, 90974, 79784, 14019, 89869, 323, 40699, 4984, 13, 1115, 1920, 11, 61937, 79784, 14019, 23991, 11, 71204, 279, 1957, 315, 2380, 6705, 1215, 35949, 10397, 14655, 28896, 304, 10989, 307, 33906, 551, 435, 643, 715, 5987, 320, 26165, 705, 264, 35268, 12970, 82160, 26, 5125, 793, 877, 40, 320, 43, 793, 705, 264, 37807, 9594, 4010, 764, 24527, 266, 43686, 3817, 437, 27094, 12, 3581, 3093, 13128, 26, 323, 452, 2938, 5987, 320, 6542, 32, 705, 264, 1380, 10759, 88554, 13128, 315, 9987, 734, 220, 19, 1174, 220, 20, 1174, 220, 21, 662, 75226, 29060, 617, 9277, 1521, 2380, 28896, 304, 279, 1890, 38970, 26, 4869, 11, 433, 8625, 9987, 1268, 814, 990, 3871, 311, 7431, 6705, 1215, 35949, 4235, 31241, 268, 14019, 10758, 13, 5810, 584, 10765, 1403, 79784, 2442, 3845, 72286, 2678, 96434, 220, 22, 430, 9352, 311, 279, 11295, 58998, 36207, 2065, 8331, 320, 52831, 37, 8, 3070, 220, 23, 439, 29413, 2914, 369, 279, 435, 643, 4235, 43, 793, 1080, 5621, 15709, 11, 902, 304, 2543, 56197, 452, 15559, 311, 279, 32426, 39654, 13, 452, 15559, 5865, 439, 264, 1652, 2658, 24292, 2427, 660, 35719, 5613, 2631, 369, 35719, 993, 19787, 304, 279, 6705, 1215, 35949, 13, 1226, 1101, 312, 1040, 275, 1088, 279, 93532, 38970, 304, 902, 435, 643, 4235, 43, 793, 62822, 1924, 79784, 2442, 3845, 72286, 96434, 311, 20891, 279, 452, 15559, 35719, 5613, 323, 39201, 35719, 993, 19787, 11, 264, 2132, 50596, 369, 79784, 14019, 23991, 13, 578, 435, 643, 4235, 43, 793, 4235, 6542, 32, 35062, 9093, 7739, 264, 8767, 653, 93878, 35268, 4235, 10327, 6485, 304, 279, 8954, 2849, 311, 15641, 8762, 17738, 323, 8346, 279, 36214, 2065, 1920, 13, 4802, 1666, 264, 64564, 2132, 50596, 11, 14751, 220, 17, 10, 80412, 1690, 13878, 315, 78152, 323, 4500, 304, 2225, 10099, 323, 11012, 220, 24, 1174, 220, 605, 1174, 220, 806, 1174, 2737, 39656, 13, 763, 10099, 11, 14751, 220, 17, 10, 17738, 6678, 279, 3937, 1429, 315, 40699, 220, 717, 323, 18057, 6992, 36214, 2065, 220, 1032, 662, 763, 82339, 11012, 11, 40699, 527, 4998, 3454, 323, 1397, 264, 3361, 9889, 6070, 2663, 279, 79784, 14019, 11, 902, 34512, 988, 279, 8954, 20438, 323, 14035, 279, 25568, 1130, 1603, 28965, 40699, 220, 16, 662, 5659, 79784, 17684, 33196, 311, 79784, 14019, 19351, 323, 79784, 14019, 23991, 11, 1855, 3094, 7612, 57216, 14751, 220, 17, 10, 91977, 220, 975, 662, 4452, 11, 279, 31206, 17383, 16940, 14751, 220, 17, 10, 91977, 304, 6136, 39656, 8625, 14090, 9987, 13, 12220, 79784, 14019, 23991, 11, 22639, 1990, 279, 79784, 14019, 323, 80526, 3447, 304, 279, 25568, 1130, 75042, 14751, 220, 17, 10, 43524, 811, 304, 2225, 8717, 11, 902, 11767, 311, 279, 89869, 315, 279, 79784, 14019, 323, 6705, 1215, 35949, 2849, 4648, 323, 279, 61568, 315, 36214, 2065, 220, 17, 1174, 220, 18, 1174, 220, 868, 1174, 220, 845, 662, 1952, 279, 8954, 3185, 11, 435, 643, 11, 445, 793, 323, 452, 15559, 527, 2380, 6956, 505, 279, 1890, 38970, 2631, 369, 6705, 1215, 35949, 14751, 220, 17, 10, 993, 19787, 304, 2077, 311, 79784, 14019, 19163, 11, 719, 2697, 374, 3967, 9002, 1268, 814, 990, 3871, 311, 1812, 6629, 14751, 220, 17, 10, 4441, 13, 1226, 1501, 1618, 430, 79784, 14019, 432, 984, 49400, 10950, 311, 435, 643, 4235, 43, 793, 1080, 5621, 58650, 11, 902, 20927, 452, 15559, 11, 264, 35719, 5613, 11, 311, 1376, 264, 35268, 4235, 10327, 14956, 13, 1115, 2463, 1474, 43943, 6485, 374, 35319, 555, 14751, 220, 17, 10, 611, 5531, 2658, 24292, 320, 23389, 44, 7435, 38655, 11302, 61478, 311, 6678, 14751, 220, 17, 10, 43524, 811, 304, 279, 6705, 1215, 35949, 13, 432, 984, 49400, 8346, 6705, 1215, 35949, 14751, 220, 17, 10, 43524, 367, 435, 643, 323, 445, 793, 527, 2225, 2631, 369, 79784, 14019, 23991, 323, 1253, 734, 439, 264, 1080, 5621, 15709, 369, 9987, 17738, 14592, 505, 79784, 34083, 220, 19, 1174, 220, 20, 1174, 220, 1114, 1174, 220, 972, 1174, 220, 777, 1174, 220, 508, 662, 1226, 22601, 83979, 430, 1778, 17738, 1253, 387, 78926, 555, 432, 984, 37, 3070, 96434, 1606, 1063, 432, 984, 49400, 10950, 311, 3060, 435, 643, 7636, 220, 1691, 1174, 220, 1313, 477, 311, 2225, 435, 643, 323, 445, 793, 12970, 28896, 320, 4178, 82252, 8, 304, 1023, 11618, 220, 1419, 1174, 220, 1187, 1174, 220, 914, 662, 22395, 279, 220, 1806, 10989, 307, 33906, 432, 984, 49400, 11, 520, 3325, 220, 23, 320, 52831, 37, 19, 11, 432, 984, 37, 23, 11, 432, 984, 37, 24, 11, 432, 984, 37, 868, 11, 432, 984, 37, 777, 11, 432, 984, 37, 914, 11, 432, 984, 37, 1627, 323, 432, 984, 37, 966, 8, 527, 13605, 304, 79784, 34083, 220, 22, 662, 1226, 13605, 323, 92600, 279, 8223, 79784, 2442, 3845, 72286, 432, 984, 37, 96434, 323, 25078, 872, 16628, 449, 435, 643, 220, 1419, 662, 1226, 1101, 5343, 459, 25568, 1130, 72286, 432, 984, 37, 72249, 320, 52831, 37, 1958, 8, 430, 374, 15499, 5552, 311, 79784, 14019, 432, 984, 49400, 1778, 439, 432, 984, 37, 19, 323, 432, 984, 37, 777, 13, 578, 11741, 65441, 8106, 315, 435, 643, 320, 26165, 506, 883, 13541, 1523, 432, 984, 37, 19, 11, 432, 984, 37, 777, 323, 432, 984, 37, 1958, 320, 30035, 13, 220, 16, 64, 323, 99371, 23966, 13, 220, 16, 64, 7609, 7440, 18620, 449, 420, 1121, 11, 432, 984, 37, 19, 323, 432, 984, 37, 777, 31532, 43215, 38210, 449, 432, 984, 37, 1958, 369, 79784, 14019, 17025, 1555, 22639, 449, 279, 1890, 44540, 315, 279, 435, 643, 3070, 220, 22, 662, 23966, 13, 220, 16, 25, 25385, 268, 72286, 432, 984, 49400, 10950, 311, 435, 643, 4235, 43, 793, 323, 8346, 6705, 1215, 35949, 510, 23389, 220, 17, 10, 2331, 79909, 4442, 304, 264, 435, 643, 4235, 43, 793, 4235, 6542, 32, 43918, 11827, 13, 264, 1174, 32928, 15220, 99592, 9204, 279, 16628, 315, 33934, 39304, 3640, 432, 984, 49400, 323, 13642, 47, 39304, 3640, 77594, 85867, 1771, 315, 435, 643, 320, 26165, 506, 7609, 29793, 1497, 54614, 574, 1511, 311, 6958, 1523, 13642, 47, 11, 8272, 555, 19001, 81982, 1303, 449, 59854, 2403, 33934, 323, 13642, 47, 13, 308, 284, 220, 18, 9678, 44694, 13, 293, 1174, 43807, 315, 33934, 39304, 3640, 445, 793, 323, 13642, 47, 39304, 3640, 77594, 85867, 1771, 315, 435, 643, 449, 477, 2085, 432, 984, 49400, 320, 52831, 37, 865, 2652, 1855, 220, 1041, 308, 44, 8, 439, 16717, 13, 29793, 1497, 54614, 6958, 15220, 323, 19001, 81982, 1303, 574, 10887, 439, 304, 264, 662, 308, 284, 220, 18, 9678, 44694, 13, 272, 1174, 3623, 12, 3378, 315, 3092, 66, 39304, 3640, 445, 793, 323, 23497, 39304, 3640, 435, 643, 42, 20943, 49, 13605, 304, 452, 13, 30280, 5721, 12699, 11141, 449, 477, 2085, 279, 5369, 315, 432, 984, 49400, 320, 9739, 220, 20, 33983, 44, 8, 439, 16717, 13, 23853, 12, 12409, 386, 17, 51552, 55308, 1051, 1511, 304, 1080, 12, 3378, 11, 323, 19001, 1529, 2469, 1051, 463, 2788, 449, 59854, 2403, 3092, 66, 323, 23497, 13, 308, 284, 220, 18, 9678, 44694, 13, 294, 1389, 342, 1174, 38366, 14751, 220, 17, 10, 993, 19787, 12912, 304, 80526, 3447, 304, 2077, 311, 79784, 14019, 320, 2898, 8, 19163, 477, 311, 220, 15, 13, 20, 64012, 44, 477, 220, 17, 64012, 44, 432, 984, 37, 19, 320, 49, 19, 8, 369, 59199, 320, 294, 7026, 18728, 12, 19, 320, 384, 7026, 326, 265, 12, 20, 320, 282, 883, 323, 308, 2629, 12, 18, 320, 342, 7609, 468, 11, 3090, 13, 305, 1174, 14751, 220, 17, 10, 43524, 367, 39445, 488, 315, 59199, 80526, 3447, 304, 2077, 311, 19932, 19163, 477, 220, 15, 13, 20, 64012, 44, 432, 984, 37, 19, 323, 432, 984, 37, 777, 320, 49, 777, 570, 308, 284, 220, 23, 25568, 2482, 13, 602, 1174, 578, 16557, 2819, 315, 14751, 220, 17, 10, 993, 19787, 439, 304, 294, 1389, 342, 662, 308, 2819, 527, 6982, 304, 41665, 2956, 23966, 13, 220, 18, 662, 126183, 2482, 1051, 25181, 505, 4349, 12, 15, 11, 18728, 12, 19, 1174, 326, 265, 12, 20, 323, 308, 2629, 12, 18, 19837, 75742, 287, 279, 6705, 1215, 35949, 19440, 23186, 64, 5901, 21, 11, 323, 97332, 574, 12715, 1701, 459, 47801, 73757, 13, 3816, 43546, 13519, 892, 3585, 520, 902, 279, 19932, 11721, 477, 432, 984, 37, 19, 574, 9435, 13, 4703, 16283, 43504, 279, 3152, 20903, 274, 1770, 749, 13, 2052, 393, 2819, 1051, 11075, 555, 1403, 2442, 5805, 11988, 753, 259, 482, 1985, 13, 3119, 11, 539, 5199, 13, 8922, 828, 8797, 1404, 2217, 1666, 29413, 2914, 369, 435, 643, 4235, 4178, 38, 1080, 5621, 58650, 11, 432, 984, 49400, 18885, 22639, 1990, 435, 643, 323, 20072, 82252, 220, 1419, 662, 7440, 18620, 449, 420, 1646, 11, 432, 984, 37, 19, 11, 432, 984, 37, 777, 323, 432, 984, 37, 1958, 24872, 279, 16628, 1990, 33934, 39304, 3640, 445, 793, 323, 13642, 47, 39304, 3640, 435, 643, 506, 1174, 20444, 3892, 1023, 432, 984, 49400, 1550, 539, 320, 30035, 13, 220, 16, 65, 1174, 5740, 11, 323, 99371, 23966, 13, 220, 16, 65, 7609, 1115, 22695, 574, 11007, 555, 128257, 198, 128256, 78191, 198, 60210, 304, 279, 6011, 315, 18317, 323, 18654, 48059, 40023, 320, 47, 8578, 8, 617, 43522, 279, 57216, 31206, 11618, 430, 16599, 68, 39656, 304, 82339, 11012, 13, 30114, 5887, 220, 21, 304, 22037, 11, 279, 14955, 2246, 264, 8767, 9987, 31206, 1920, 430, 17482, 439, 264, 1749, 315, 10758, 2391, 36214, 2065, 13, 10771, 311, 17054, 1443, 833, 445, 10602, 11, 10716, 315, 279, 5975, 33, 9476, 323, 279, 5684, 596, 10195, 3229, 11, 279, 4839, 17383, 369, 43080, 706, 8767, 658, 38477, 12074, 13, 330, 1688, 279, 31206, 2237, 11, 420, 4459, 1920, 374, 1457, 810, 2867, 1109, 3596, 1603, 1359, 568, 1071, 13, 58746, 31206, 364, 31153, 8554, 6, 52645, 23645, 27681, 1555, 7230, 2617, 11, 264, 1920, 430, 18065, 279, 8481, 315, 79784, 505, 264, 23153, 596, 357, 25807, 320, 1820, 8762, 36214, 4954, 2942, 8, 311, 279, 60381, 389, 279, 24817, 321, 320, 1820, 8954, 42889, 2942, 570, 9843, 279, 79784, 24875, 36132, 4282, 389, 279, 60381, 11, 264, 79784, 14019, 28815, 505, 279, 79784, 24875, 311, 459, 25568, 1130, 311, 28696, 279, 8481, 315, 40699, 311, 279, 19151, 13, 445, 10602, 1071, 12074, 617, 8767, 12715, 279, 9546, 315, 35719, 17301, 38846, 279, 36214, 2065, 1920, 323, 10555, 430, 330, 20670, 7020, 279, 35719, 8450, 374, 3062, 719, 3287, 956, 1440, 7041, 1268, 433, 374, 9124, 1210, 2057, 24564, 1268, 279, 35719, 12330, 574, 9124, 555, 279, 8954, 2849, 11, 445, 10602, 323, 813, 1080, 34603, 1105, 11784, 264, 49554, 3890, 311, 1934, 35719, 5990, 304, 279, 3230, 2849, 311, 1427, 369, 17738, 505, 279, 8762, 5596, 430, 8346, 35719, 17301, 13, 2435, 1766, 430, 79784, 34083, 17105, 3892, 2678, 96434, 2345, 8846, 27271, 315, 42500, 33969, 41128, 649, 387, 15324, 555, 72249, 44540, 389, 279, 7479, 315, 279, 8954, 2849, 13, 9843, 22756, 11, 1521, 44540, 20927, 264, 35719, 5613, 311, 8356, 264, 35719, 12330, 430, 28292, 279, 79784, 14019, 311, 279, 25568, 1130, 323, 12961, 988, 36214, 2065, 13, 7997, 35719, 17301, 330, 79307, 1, 304, 420, 14975, 3984, 555, 279, 445, 10602, 11868, 13, 330, 2675, 1436, 9616, 420, 311, 264, 9889, 2532, 1359, 445, 10602, 11497, 13, 330, 1687, 1440, 279, 2678, 72249, 43030, 17482, 439, 264, 8450, 311, 279, 8954, 961, 315, 279, 23153, 11, 4661, 1093, 264, 14459, 389, 279, 6134, 20806, 433, 1440, 279, 79784, 14019, 374, 1618, 1210, 578, 35719, 17301, 13967, 5353, 279, 79784, 14019, 311, 89869, 323, 4984, 279, 4998, 3454, 40699, 3131, 433, 374, 4871, 279, 25568, 1130, 11, 23391, 264, 6992, 36214, 2065, 1920, 13, 330, 644, 264, 1648, 11, 814, 13524, 5379, 18639, 311, 4984, 279, 40699, 1359, 445, 10602, 1071, 13, 330, 32148, 279, 8954, 42889, 2849, 1101, 8898, 304, 2015, 311, 29241, 279, 19151, 779, 814, 649, 3449, 323, 8356, 502, 2324, 13, 1102, 596, 3169, 315, 264, 24364, 11879, 369, 6136, 39656, 1210, 47169, 82920, 31206, 30622, 10771, 311, 445, 10602, 11, 8830, 279, 57216, 31206, 11618, 315, 36214, 2065, 1253, 1520, 7417, 279, 8518, 36508, 304, 82339, 11012, 13, 7089, 12074, 477, 6136, 19465, 1705, 2643, 1005, 279, 14955, 311, 1464, 279, 82019, 89721, 22881, 11, 13893, 8736, 279, 6134, 311, 279, 9886, 315, 502, 26038, 19641, 9606, 1555, 5425, 2320, 980, 2617, 13, 2030, 11, 304, 5369, 311, 279, 4754, 8518, 3851, 11, 1521, 14955, 4726, 11415, 11012, 6, 91813, 5845, 311, 19570, 4669, 31206, 20748, 13, 330, 3915, 459, 41993, 1486, 315, 1684, 11, 11012, 15601, 74228, 872, 1866, 35715, 3230, 311, 872, 5016, 10758, 1920, 1359, 568, 3779, 13, 578, 35719, 12006, 11054, 304, 420, 4007, 527, 5016, 311, 11012, 11, 23377, 814, 36592, 264, 1648, 311, 8356, 17738, 430, 527, 2204, 1109, 1884, 1766, 304, 10099, 13, 445, 10602, 1071, 12074, 617, 20041, 35719, 12006, 369, 810, 1109, 220, 966, 1667, 11, 45063, 287, 1268, 814, 49843, 13957, 311, 7019, 67, 727, 23900, 365, 320, 64, 95447, 8624, 430, 22223, 264, 7029, 8205, 315, 11012, 8, 477, 7431, 22936, 60199, 304, 3789, 6067, 13, 11205, 93532, 3560, 14958, 9987, 3156, 420, 4007, 43522, 279, 3230, 5613, 5820, 13, 330, 697, 258, 82920, 502, 12006, 311, 19570, 304, 872, 1866, 1648, 11, 13263, 449, 2204, 79731, 315, 11012, 323, 10099, 11, 374, 315, 4689, 12939, 311, 34458, 1359, 445, 10602, 1071, 13, 220, 128257, 198 ]

2,323

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Objectives Taxing sugar-sweetened beverages (SSBs) is now advocated, and implemented, in many countries as a measure to reduce the purchase and consumption of sugar to tackle obesity. To date, there has been little consideration of the potential impact that such a measure could have if extended to other sweet foods, such as confectionery, cakes and biscuits that contribute more sugar to the diet than SSBs. The objective of this study is to compare changes in the demand for sweet snacks and SSBs arising from potential price increases. Setting Secondary data on household itemised purchases of all foods and beverages from 2012 to 2013. Participants Representative sample of 32 249 households in Great Britain. Primary and secondary outcome measures Change in food and beverage purchases due to changes in their own price and the price of other foods or beverages measured as price elasticity of demand for the full sample and by income groups. Results Chocolate and confectionery, cakes and biscuits have similar price sensitivity as SSBs, across all income groups. Unlike the case of SSBs, price increases in these categories are also likely to prompt reductions in the purchase of other sweet snacks and SSBs, which magnify the overall impact. The effects of price increases are greatest in the low-income group. Conclusions Policies that lead to increases in the price of chocolate and confectionery, cakes and biscuits may lead to additional and greater health gains than similar increases in the price of SSBs through direct reductions in the purchases of these foods and possible positive multiplier effects that reduce demand for other products. Although some uncertainty remains, the associations found in this analysis are sufficiently robust to suggest that policies—and research—concerning the use of fiscal measures should consider a broader range of products than is currently the case. price elasticity sweet snacks sugar-sweetened beverages fiscal policy This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: googletag.cmd.push(function() { googletag.display(\"dfp-ad-mpu\"); }); Statistics from Altmetric.com See more details Picked up by 77 news outlets Blogged by 2 Tweeted by 92 On 3 Facebook pages 109 readers on Mendeley 1 readers on CiteULike Linked Articles Request Permissions If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways. ?xml version=\"1.0\" encoding=\"UTF-8\" ? Request permissions price elasticity sweet snacks sugar-sweetened beverages fiscal policy Strengths and limitations of this study Detailed transaction level data on all food and beverage purchases collected electronically from a representative sample of >30 000 Great Britain households over 2 years. Transaction level data allow for separating and analysing demand for ready-to-consume sweet snacks. Demand analysis accounts for zero purchases and endogeneity of total food expenditure. Data exclude purchases of foods and beverages bought and consumed outside homes. Purchase data do not necessarily amount to consumption due to possible waste. Introduction With the global prevalence of obesity and associated health risks continuing to increase, 1 2 health-related taxes have become an established policy option intended to reduce energy intake. Most of these have focused on sugar-sweetened beverages (SSBs) due to their consistent association with energy intake, weight gain, risk of type 2 diabetes, as well as dental caries. 3 In the USA, six local jurisdictions have a tax on sugary beverages implemented due to health concerns. 4 Mexico, Finland and France apply different levels of volumetric taxes on SSBs, Hungary has adopted a system of volumetric taxes from products exceeding specified levels of sugar, and Chile taxes drinks with high levels of sugar at a rate 8% higher in comparison to drinks containing less sugar. 4 More recently, Portugal and Catalonia (Spain) implemented a two-tiered tax on sugary drinks, the United Arab Emirates and Saudi Arabia introduced a 50% tax on carbonated drinks and Brunei and Thailand introduced an excise duty on sugary drinks. 4 There are similar plans across a number of other countries such as Estonia, the Philippines, Indonesia, Israel and South Africa. 5 The UK government has confirmed an industry levy starting in April 2018 to incentivise producers to reformulate their products or, if not, to increase the price of SSBs. 6 Research to date suggests that increasing the price of SSBs generates a small, but significant, reduction in their purchase (broadly, a 10% price rise reduces purchases by 6%–8%), with a more pronounced effect in poorer households and that substitution towards other soft drink categories only minimally offsets the energy reductions achieved through decreases in SSBs. 7–18 However, there has been little research on the impact such a price increase could have on other contributors to sugar and energy intake, including alcohol 18 and sweet snack foods (such as confectionery, cakes and biscuits). With the apparent success of fiscal measures to increase the price of SSBs, it would be useful to establish whether a similar, or possibly greater, effect on consumption of snack foods could be obtained from a similar price change. The research presented here is the first to provide a direct analysis of the relationship between price increases and demand for sweet snack foods, within the context of demand for soft drink and alcoholic drink purchases, across different income groups. Methods The impact, or sensitivity, of demand for a product to price changes is termed the price elasticity of demand. This shows the per cent change in the demand for product X if its own price changes (own-price elasticity) or the price of other products (Y, Z) changes (cross-price elasticity). These elasticities are estimated from demand models. We apply a partial demand model, which models household expenditure shares on prices of different products and total expenditure, adjusted for overall price level. The demand model", "role": "user" }, { "content": "Taxing sweet snacks could lead to broader reductions in the amount of sugar purchased than similar increases in the price of sugar-sweetened beverages (SSBs), according to new research published in BMJ Open. The research team from the London School of Hygiene & Tropical Medicine, the University of Cambridge and the University of Oxford, estimate that adding 10% to the price of chocolate, confectionery, cakes and biscuits may reduce purchases by around 7%. This is a similar outcome to taxing SSBs, where previous research suggests a 10% price rise can reduce purchases by 6-8%. Crucially, however, the study found that taxing sweet snacks could have knock-on effects on the sales of other food items, reducing the purchase of soft-drinks (by 0.6-0.8%), biscuits and cakes (1.2%), and savoury snacks (1.6%). This study is an observational analysis and cannot explain why consumers change their purchasing behaviour but, although some uncertainty remains, the researchers say the associations observed suggest that relevant policies and future research should consider a broader range of fiscal measures to improve diet than is currently the case. Lead author Professor Richard Smith from the London School of Hygiene & Tropical Medicine said: \"We know that increasing the price of sugar-sweetened beverages is likely to generate a small, but significant, reduction in their purchase. However, there has been little research on the impact that a similar price increase on other sweet foods such as chocolate, confectionery, cakes and biscuits could have on the purchase of sugar. This research suggests that taxing these sweet snacks could bring greater health gains and warrants detailed consideration.\" This study, funded by the National Institute for Health Research Policy Research Programme, is the first to provide a direct analysis of the relationship between price increases and consumer demand for snack foods across different income groups. Household expenditure on food and drink items were classified into 13 different groups and examined in a national representative sample of around 32,000 UK homes. Purchasing was examined overall and then compared across low-income, middle-income and high-income households. The data (from Kantar Worldpanel) covered a two-year period in 2012 and 2013, and provided complete details of each sales transaction, in addition to social and demographic information for each household. To estimate the change in purchasing, the researchers applied a specialised tool for studying consumer demand. The researchers found that increasing the price of sweet snacks led to a decrease in purchases and may have wider effects on purchasing patterns, which they suggest could potentially bring additional benefits to public health. For example, increasing the price of chocolate snacks was estimated to bring about significant reductions in purchases across most food categories, while a price increase on biscuits showed a potential reduction in the demand for cakes (2.3%) as well as chocolate and confectionary (1.7%). The potential effects of price increases were greatest in the low-income group. Increasing the price of biscuits was linked to a reduction in the purchase of chocolate and confectionery for the low-income group (3% if price increases by 10%). No such reductions for the high-income group were seen. Increasing the price of chocolate and confectionery was estimated to have a similar effect across all income groups. Co-author Professor Susan Jebb from the University of Oxford said: \"It's impossible to study the direct effects of a tax on snack food on consumer behaviour until such policies are introduced, but these estimates show the likely impact of changes in the price. These snacks are high in sugar but often high in fat too and very energy dense, so their consumption can increase the risk of obesity. This research suggests that extending fiscal policies to include sweet snacks could be an important boost to public health, by reducing purchasing and hence consumption of these foods, particularly in low-income households.\" The authors acknowledge limitations of the study including the exclusion of purchases of foods and drink bought and consumed outside of homes (e.g. in restaurants) which they say are likely to be greater among higher income earners. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Objectives Taxing sugar-sweetened beverages (SSBs) is now advocated, and implemented, in many countries as a measure to reduce the purchase and consumption of sugar to tackle obesity. To date, there has been little consideration of the potential impact that such a measure could have if extended to other sweet foods, such as confectionery, cakes and biscuits that contribute more sugar to the diet than SSBs. The objective of this study is to compare changes in the demand for sweet snacks and SSBs arising from potential price increases. Setting Secondary data on household itemised purchases of all foods and beverages from 2012 to 2013. Participants Representative sample of 32 249 households in Great Britain. Primary and secondary outcome measures Change in food and beverage purchases due to changes in their own price and the price of other foods or beverages measured as price elasticity of demand for the full sample and by income groups. Results Chocolate and confectionery, cakes and biscuits have similar price sensitivity as SSBs, across all income groups. Unlike the case of SSBs, price increases in these categories are also likely to prompt reductions in the purchase of other sweet snacks and SSBs, which magnify the overall impact. The effects of price increases are greatest in the low-income group. Conclusions Policies that lead to increases in the price of chocolate and confectionery, cakes and biscuits may lead to additional and greater health gains than similar increases in the price of SSBs through direct reductions in the purchases of these foods and possible positive multiplier effects that reduce demand for other products. Although some uncertainty remains, the associations found in this analysis are sufficiently robust to suggest that policies—and research—concerning the use of fiscal measures should consider a broader range of products than is currently the case. price elasticity sweet snacks sugar-sweetened beverages fiscal policy This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: googletag.cmd.push(function() { googletag.display("dfp-ad-mpu"); }); Statistics from Altmetric.com See more details Picked up by 77 news outlets Blogged by 2 Tweeted by 92 On 3 Facebook pages 109 readers on Mendeley 1 readers on CiteULike Linked Articles Request Permissions If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways. ?xml version="1.0" encoding="UTF-8" ? Request permissions price elasticity sweet snacks sugar-sweetened beverages fiscal policy Strengths and limitations of this study Detailed transaction level data on all food and beverage purchases collected electronically from a representative sample of >30 000 Great Britain households over 2 years. Transaction level data allow for separating and analysing demand for ready-to-consume sweet snacks. Demand analysis accounts for zero purchases and endogeneity of total food expenditure. Data exclude purchases of foods and beverages bought and consumed outside homes. Purchase data do not necessarily amount to consumption due to possible waste. Introduction With the global prevalence of obesity and associated health risks continuing to increase, 1 2 health-related taxes have become an established policy option intended to reduce energy intake. Most of these have focused on sugar-sweetened beverages (SSBs) due to their consistent association with energy intake, weight gain, risk of type 2 diabetes, as well as dental caries. 3 In the USA, six local jurisdictions have a tax on sugary beverages implemented due to health concerns. 4 Mexico, Finland and France apply different levels of volumetric taxes on SSBs, Hungary has adopted a system of volumetric taxes from products exceeding specified levels of sugar, and Chile taxes drinks with high levels of sugar at a rate 8% higher in comparison to drinks containing less sugar. 4 More recently, Portugal and Catalonia (Spain) implemented a two-tiered tax on sugary drinks, the United Arab Emirates and Saudi Arabia introduced a 50% tax on carbonated drinks and Brunei and Thailand introduced an excise duty on sugary drinks. 4 There are similar plans across a number of other countries such as Estonia, the Philippines, Indonesia, Israel and South Africa. 5 The UK government has confirmed an industry levy starting in April 2018 to incentivise producers to reformulate their products or, if not, to increase the price of SSBs. 6 Research to date suggests that increasing the price of SSBs generates a small, but significant, reduction in their purchase (broadly, a 10% price rise reduces purchases by 6%–8%), with a more pronounced effect in poorer households and that substitution towards other soft drink categories only minimally offsets the energy reductions achieved through decreases in SSBs. 7–18 However, there has been little research on the impact such a price increase could have on other contributors to sugar and energy intake, including alcohol 18 and sweet snack foods (such as confectionery, cakes and biscuits). With the apparent success of fiscal measures to increase the price of SSBs, it would be useful to establish whether a similar, or possibly greater, effect on consumption of snack foods could be obtained from a similar price change. The research presented here is the first to provide a direct analysis of the relationship between price increases and demand for sweet snack foods, within the context of demand for soft drink and alcoholic drink purchases, across different income groups. Methods The impact, or sensitivity, of demand for a product to price changes is termed the price elasticity of demand. This shows the per cent change in the demand for product X if its own price changes (own-price elasticity) or the price of other products (Y, Z) changes (cross-price elasticity). These elasticities are estimated from demand models. We apply a partial demand model, which models household expenditure shares on prices of different products and total expenditure, adjusted for overall price level. The demand model<|im_end|> <|im_start|>assistant Taxing sweet snacks could lead to broader reductions in the amount of sugar purchased than similar increases in the price of sugar-sweetened beverages (SSBs), according to new research published in BMJ Open. The research team from the London School of Hygiene & Tropical Medicine, the University of Cambridge and the University of Oxford, estimate that adding 10% to the price of chocolate, confectionery, cakes and biscuits may reduce purchases by around 7%. This is a similar outcome to taxing SSBs, where previous research suggests a 10% price rise can reduce purchases by 6-8%. Crucially, however, the study found that taxing sweet snacks could have knock-on effects on the sales of other food items, reducing the purchase of soft-drinks (by 0.6-0.8%), biscuits and cakes (1.2%), and savoury snacks (1.6%). This study is an observational analysis and cannot explain why consumers change their purchasing behaviour but, although some uncertainty remains, the researchers say the associations observed suggest that relevant policies and future research should consider a broader range of fiscal measures to improve diet than is currently the case. Lead author Professor Richard Smith from the London School of Hygiene & Tropical Medicine said: "We know that increasing the price of sugar-sweetened beverages is likely to generate a small, but significant, reduction in their purchase. However, there has been little research on the impact that a similar price increase on other sweet foods such as chocolate, confectionery, cakes and biscuits could have on the purchase of sugar. This research suggests that taxing these sweet snacks could bring greater health gains and warrants detailed consideration." This study, funded by the National Institute for Health Research Policy Research Programme, is the first to provide a direct analysis of the relationship between price increases and consumer demand for snack foods across different income groups. Household expenditure on food and drink items were classified into 13 different groups and examined in a national representative sample of around 32,000 UK homes. Purchasing was examined overall and then compared across low-income, middle-income and high-income households. The data (from Kantar Worldpanel) covered a two-year period in 2012 and 2013, and provided complete details of each sales transaction, in addition to social and demographic information for each household. To estimate the change in purchasing, the researchers applied a specialised tool for studying consumer demand. The researchers found that increasing the price of sweet snacks led to a decrease in purchases and may have wider effects on purchasing patterns, which they suggest could potentially bring additional benefits to public health. For example, increasing the price of chocolate snacks was estimated to bring about significant reductions in purchases across most food categories, while a price increase on biscuits showed a potential reduction in the demand for cakes (2.3%) as well as chocolate and confectionary (1.7%). The potential effects of price increases were greatest in the low-income group. Increasing the price of biscuits was linked to a reduction in the purchase of chocolate and confectionery for the low-income group (3% if price increases by 10%). No such reductions for the high-income group were seen. Increasing the price of chocolate and confectionery was estimated to have a similar effect across all income groups. Co-author Professor Susan Jebb from the University of Oxford said: "It's impossible to study the direct effects of a tax on snack food on consumer behaviour until such policies are introduced, but these estimates show the likely impact of changes in the price. These snacks are high in sugar but often high in fat too and very energy dense, so their consumption can increase the risk of obesity. This research suggests that extending fiscal policies to include sweet snacks could be an important boost to public health, by reducing purchasing and hence consumption of these foods, particularly in low-income households." The authors acknowledge limitations of the study including the exclusion of purchases of foods and drink bought and consumed outside of homes (e.g. in restaurants) which they say are likely to be greater among higher income earners. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 3075, 1924, 15545, 287, 13465, 1355, 4589, 6901, 47497, 320, 1242, 75307, 8, 374, 1457, 64854, 11, 323, 11798, 11, 304, 1690, 5961, 439, 264, 6767, 311, 8108, 279, 7782, 323, 15652, 315, 13465, 311, 22118, 33048, 13, 2057, 2457, 11, 1070, 706, 1027, 2697, 18361, 315, 279, 4754, 5536, 430, 1778, 264, 6767, 1436, 617, 422, 11838, 311, 1023, 10437, 15657, 11, 1778, 439, 390, 13421, 727, 11, 48669, 323, 87076, 430, 17210, 810, 13465, 311, 279, 10173, 1109, 328, 17094, 82, 13, 578, 16945, 315, 420, 4007, 374, 311, 9616, 4442, 304, 279, 7631, 369, 10437, 43402, 323, 328, 17094, 82, 40986, 505, 4754, 3430, 12992, 13, 20638, 44634, 828, 389, 14048, 1537, 4147, 24393, 315, 682, 15657, 323, 47497, 505, 220, 679, 17, 311, 220, 679, 18, 13, 52878, 38366, 6205, 315, 220, 843, 220, 14735, 29939, 304, 8681, 13527, 13, 26150, 323, 14580, 15632, 11193, 10604, 304, 3691, 323, 43450, 24393, 4245, 311, 4442, 304, 872, 1866, 3430, 323, 279, 3430, 315, 1023, 15657, 477, 47497, 17303, 439, 3430, 95916, 315, 7631, 369, 279, 2539, 6205, 323, 555, 8070, 5315, 13, 18591, 39520, 323, 390, 13421, 727, 11, 48669, 323, 87076, 617, 4528, 3430, 27541, 439, 328, 17094, 82, 11, 4028, 682, 8070, 5315, 13, 27140, 279, 1162, 315, 328, 17094, 82, 11, 3430, 12992, 304, 1521, 11306, 527, 1101, 4461, 311, 10137, 47311, 304, 279, 7782, 315, 1023, 10437, 43402, 323, 328, 17094, 82, 11, 902, 8622, 1463, 279, 8244, 5536, 13, 578, 6372, 315, 3430, 12992, 527, 12474, 304, 279, 3428, 32197, 1912, 13, 1221, 24436, 63348, 430, 3063, 311, 12992, 304, 279, 3430, 315, 18414, 323, 390, 13421, 727, 11, 48669, 323, 87076, 1253, 3063, 311, 5217, 323, 7191, 2890, 20192, 1109, 4528, 12992, 304, 279, 3430, 315, 328, 17094, 82, 1555, 2167, 47311, 304, 279, 24393, 315, 1521, 15657, 323, 3284, 6928, 31659, 6372, 430, 8108, 7631, 369, 1023, 3956, 13, 10541, 1063, 27924, 8625, 11, 279, 30257, 1766, 304, 420, 6492, 527, 40044, 22514, 311, 4284, 430, 10396, 17223, 3495, 2345, 444, 29644, 287, 279, 1005, 315, 20323, 11193, 1288, 2980, 264, 27927, 2134, 315, 3956, 1109, 374, 5131, 279, 1162, 13, 3430, 95916, 10437, 43402, 13465, 1355, 4589, 6901, 47497, 20323, 4947, 1115, 374, 459, 5377, 9742, 4652, 4332, 304, 18859, 449, 279, 3878, 315, 279, 25248, 26667, 59418, 320, 3791, 7866, 220, 19, 13, 15, 8, 5842, 11, 902, 29790, 3885, 311, 16822, 11, 57466, 11, 10737, 323, 1977, 5304, 420, 990, 11, 369, 8518, 1005, 11, 3984, 279, 4113, 990, 374, 10489, 22628, 13, 3580, 25, 48569, 1169, 351, 26808, 2615, 2993, 368, 314, 48569, 1169, 351, 8344, 446, 3013, 79, 26831, 12, 1331, 84, 5146, 18605, 25647, 505, 24610, 16282, 916, 3580, 810, 3649, 393, 19011, 709, 555, 220, 2813, 3754, 28183, 14496, 3640, 555, 220, 17, 26213, 291, 555, 220, 6083, 1952, 220, 18, 5690, 6959, 220, 7743, 13016, 389, 386, 11178, 3258, 220, 16, 13016, 389, 356, 635, 1112, 3043, 13415, 29461, 6274, 54457, 1442, 499, 6562, 311, 27068, 904, 477, 682, 315, 420, 4652, 4587, 1005, 279, 2723, 3770, 902, 690, 1935, 499, 311, 279, 3028, 93230, 5955, 753, 10734, 4026, 2532, 13, 1472, 690, 387, 3025, 311, 636, 264, 4062, 3430, 323, 9888, 8041, 311, 27068, 279, 2262, 304, 1690, 2204, 5627, 13, 949, 6591, 2373, 429, 16, 13, 15, 1, 11418, 429, 8729, 12, 23, 1, 949, 6274, 8709, 3430, 95916, 10437, 43402, 13465, 1355, 4589, 6901, 47497, 20323, 4947, 32937, 82, 323, 9669, 315, 420, 4007, 63765, 7901, 2237, 828, 389, 682, 3691, 323, 43450, 24393, 14890, 71870, 505, 264, 18740, 6205, 315, 871, 966, 220, 931, 8681, 13527, 29939, 927, 220, 17, 1667, 13, 18351, 2237, 828, 2187, 369, 50545, 323, 22209, 287, 7631, 369, 5644, 4791, 15204, 32423, 10437, 43402, 13, 55353, 6492, 9815, 369, 7315, 24393, 323, 842, 76730, 315, 2860, 3691, 45426, 13, 2956, 22429, 24393, 315, 15657, 323, 47497, 11021, 323, 27073, 4994, 10632, 13, 32088, 828, 656, 539, 14647, 3392, 311, 15652, 4245, 311, 3284, 12571, 13, 29438, 3161, 279, 3728, 38009, 315, 33048, 323, 5938, 2890, 15635, 14691, 311, 5376, 11, 220, 16, 220, 17, 2890, 14228, 13426, 617, 3719, 459, 9749, 4947, 3072, 10825, 311, 8108, 4907, 23730, 13, 7648, 315, 1521, 617, 10968, 389, 13465, 1355, 4589, 6901, 47497, 320, 1242, 75307, 8, 4245, 311, 872, 13263, 15360, 449, 4907, 23730, 11, 4785, 8895, 11, 5326, 315, 955, 220, 17, 20335, 11, 439, 1664, 439, 29106, 1841, 552, 13, 220, 18, 763, 279, 7427, 11, 4848, 2254, 56043, 617, 264, 3827, 389, 31705, 661, 47497, 11798, 4245, 311, 2890, 10742, 13, 220, 19, 12550, 11, 37355, 323, 9822, 3881, 2204, 5990, 315, 63920, 16743, 13426, 389, 328, 17094, 82, 11, 43876, 706, 18306, 264, 1887, 315, 63920, 16743, 13426, 505, 3956, 49005, 5300, 5990, 315, 13465, 11, 323, 34100, 13426, 21662, 449, 1579, 5990, 315, 13465, 520, 264, 4478, 220, 23, 4, 5190, 304, 12593, 311, 21662, 8649, 2753, 13465, 13, 220, 19, 4497, 6051, 11, 34411, 323, 96952, 320, 75420, 8, 11798, 264, 1403, 58355, 291, 3827, 389, 31705, 661, 21662, 11, 279, 3723, 10989, 49801, 323, 18387, 23931, 11784, 264, 220, 1135, 4, 3827, 389, 12782, 660, 21662, 323, 3320, 96323, 323, 30567, 11784, 459, 3521, 1082, 14523, 389, 31705, 661, 21662, 13, 220, 19, 2684, 527, 4528, 6787, 4028, 264, 1396, 315, 1023, 5961, 1778, 439, 69462, 11, 279, 26363, 11, 24922, 11, 6921, 323, 4987, 10384, 13, 220, 20, 578, 6560, 3109, 706, 11007, 459, 5064, 77162, 6041, 304, 5936, 220, 679, 23, 311, 84084, 1082, 24190, 311, 15180, 6468, 872, 3956, 477, 11, 422, 539, 11, 311, 5376, 279, 3430, 315, 328, 17094, 82, 13, 220, 21, 8483, 311, 2457, 13533, 430, 7859, 279, 3430, 315, 328, 17094, 82, 27983, 264, 2678, 11, 719, 5199, 11, 14278, 304, 872, 7782, 320, 65, 8714, 398, 11, 264, 220, 605, 4, 3430, 10205, 26338, 24393, 555, 220, 21, 4, 4235, 23, 34971, 449, 264, 810, 38617, 2515, 304, 66281, 29939, 323, 430, 50068, 7119, 1023, 8579, 7172, 11306, 1193, 21877, 750, 36146, 279, 4907, 47311, 17427, 1555, 43154, 304, 328, 17094, 82, 13, 220, 22, 4235, 972, 4452, 11, 1070, 706, 1027, 2697, 3495, 389, 279, 5536, 1778, 264, 3430, 5376, 1436, 617, 389, 1023, 20965, 311, 13465, 323, 4907, 23730, 11, 2737, 13200, 220, 972, 323, 10437, 40459, 15657, 320, 21470, 439, 390, 13421, 727, 11, 48669, 323, 87076, 570, 3161, 279, 10186, 2450, 315, 20323, 11193, 311, 5376, 279, 3430, 315, 328, 17094, 82, 11, 433, 1053, 387, 5505, 311, 5813, 3508, 264, 4528, 11, 477, 11000, 7191, 11, 2515, 389, 15652, 315, 40459, 15657, 1436, 387, 12457, 505, 264, 4528, 3430, 2349, 13, 578, 3495, 10666, 1618, 374, 279, 1176, 311, 3493, 264, 2167, 6492, 315, 279, 5133, 1990, 3430, 12992, 323, 7631, 369, 10437, 40459, 15657, 11, 2949, 279, 2317, 315, 7631, 369, 8579, 7172, 323, 56461, 7172, 24393, 11, 4028, 2204, 8070, 5315, 13, 19331, 578, 5536, 11, 477, 27541, 11, 315, 7631, 369, 264, 2027, 311, 3430, 4442, 374, 61937, 279, 3430, 95916, 315, 7631, 13, 1115, 5039, 279, 824, 2960, 2349, 304, 279, 7631, 369, 2027, 1630, 422, 1202, 1866, 3430, 4442, 320, 785, 38408, 95916, 8, 477, 279, 3430, 315, 1023, 3956, 320, 56, 11, 1901, 8, 4442, 320, 29942, 38408, 95916, 570, 4314, 36573, 1385, 527, 13240, 505, 7631, 4211, 13, 1226, 3881, 264, 7276, 7631, 1646, 11, 902, 4211, 14048, 45426, 13551, 389, 7729, 315, 2204, 3956, 323, 2860, 45426, 11, 24257, 369, 8244, 3430, 2237, 13, 578, 7631, 1646, 128257, 198, 128256, 78191, 198, 32449, 287, 10437, 43402, 1436, 3063, 311, 27927, 47311, 304, 279, 3392, 315, 13465, 15075, 1109, 4528, 12992, 304, 279, 3430, 315, 13465, 1355, 4589, 6901, 47497, 320, 1242, 75307, 705, 4184, 311, 502, 3495, 4756, 304, 20387, 41, 5377, 13, 578, 3495, 2128, 505, 279, 7295, 6150, 315, 10320, 43312, 612, 71343, 19152, 11, 279, 3907, 315, 24562, 323, 279, 3907, 315, 26275, 11, 16430, 430, 7999, 220, 605, 4, 311, 279, 3430, 315, 18414, 11, 390, 13421, 727, 11, 48669, 323, 87076, 1253, 8108, 24393, 555, 2212, 220, 22, 14697, 1115, 374, 264, 4528, 15632, 311, 88004, 328, 17094, 82, 11, 1405, 3766, 3495, 13533, 264, 220, 605, 4, 3430, 10205, 649, 8108, 24393, 555, 220, 21, 12, 23, 14697, 76104, 34575, 11, 4869, 11, 279, 4007, 1766, 430, 88004, 10437, 43402, 1436, 617, 14459, 10539, 6372, 389, 279, 6763, 315, 1023, 3691, 3673, 11, 18189, 279, 7782, 315, 8579, 19158, 15872, 320, 1729, 220, 15, 13, 21, 12, 15, 13, 23, 34971, 87076, 323, 48669, 320, 16, 13, 17, 34971, 323, 11427, 414, 88, 43402, 320, 16, 13, 21, 53172, 1115, 4007, 374, 459, 90380, 6492, 323, 4250, 10552, 3249, 13723, 2349, 872, 23395, 17432, 719, 11, 8051, 1063, 27924, 8625, 11, 279, 12074, 2019, 279, 30257, 13468, 4284, 430, 9959, 10396, 323, 3938, 3495, 1288, 2980, 264, 27927, 2134, 315, 20323, 11193, 311, 7417, 10173, 1109, 374, 5131, 279, 1162, 13, 30982, 3229, 17054, 12131, 9259, 505, 279, 7295, 6150, 315, 10320, 43312, 612, 71343, 19152, 1071, 25, 330, 1687, 1440, 430, 7859, 279, 3430, 315, 13465, 1355, 4589, 6901, 47497, 374, 4461, 311, 7068, 264, 2678, 11, 719, 5199, 11, 14278, 304, 872, 7782, 13, 4452, 11, 1070, 706, 1027, 2697, 3495, 389, 279, 5536, 430, 264, 4528, 3430, 5376, 389, 1023, 10437, 15657, 1778, 439, 18414, 11, 390, 13421, 727, 11, 48669, 323, 87076, 1436, 617, 389, 279, 7782, 315, 13465, 13, 1115, 3495, 13533, 430, 88004, 1521, 10437, 43402, 1436, 4546, 7191, 2890, 20192, 323, 55688, 11944, 18361, 1210, 1115, 4007, 11, 24853, 555, 279, 5165, 10181, 369, 6401, 8483, 11216, 8483, 47516, 11, 374, 279, 1176, 311, 3493, 264, 2167, 6492, 315, 279, 5133, 1990, 3430, 12992, 323, 11761, 7631, 369, 40459, 15657, 4028, 2204, 8070, 5315, 13, 77073, 45426, 389, 3691, 323, 7172, 3673, 1051, 21771, 1139, 220, 1032, 2204, 5315, 323, 25078, 304, 264, 5426, 18740, 6205, 315, 2212, 220, 843, 11, 931, 6560, 10632, 13, 53792, 4522, 574, 25078, 8244, 323, 1243, 7863, 4028, 3428, 32197, 11, 6278, 32197, 323, 1579, 32197, 29939, 13, 578, 828, 320, 1527, 63262, 277, 4435, 7581, 8, 9960, 264, 1403, 4771, 4261, 304, 220, 679, 17, 323, 220, 679, 18, 11, 323, 3984, 4686, 3649, 315, 1855, 6763, 7901, 11, 304, 5369, 311, 3674, 323, 38462, 2038, 369, 1855, 14048, 13, 2057, 16430, 279, 2349, 304, 23395, 11, 279, 12074, 9435, 264, 89004, 5507, 369, 21630, 11761, 7631, 13, 578, 12074, 1766, 430, 7859, 279, 3430, 315, 10437, 43402, 6197, 311, 264, 18979, 304, 24393, 323, 1253, 617, 22622, 6372, 389, 23395, 12912, 11, 902, 814, 4284, 1436, 13893, 4546, 5217, 7720, 311, 586, 2890, 13, 1789, 3187, 11, 7859, 279, 3430, 315, 18414, 43402, 574, 13240, 311, 4546, 922, 5199, 47311, 304, 24393, 4028, 1455, 3691, 11306, 11, 1418, 264, 3430, 5376, 389, 87076, 8710, 264, 4754, 14278, 304, 279, 7631, 369, 48669, 320, 17, 13, 18, 11587, 439, 1664, 439, 18414, 323, 390, 13421, 661, 320, 16, 13, 22, 53172, 578, 4754, 6372, 315, 3430, 12992, 1051, 12474, 304, 279, 3428, 32197, 1912, 13, 74540, 279, 3430, 315, 87076, 574, 10815, 311, 264, 14278, 304, 279, 7782, 315, 18414, 323, 390, 13421, 727, 369, 279, 3428, 32197, 1912, 320, 18, 4, 422, 3430, 12992, 555, 220, 605, 53172, 2360, 1778, 47311, 369, 279, 1579, 32197, 1912, 1051, 3970, 13, 74540, 279, 3430, 315, 18414, 323, 390, 13421, 727, 574, 13240, 311, 617, 264, 4528, 2515, 4028, 682, 8070, 5315, 13, 3623, 43802, 17054, 31033, 71196, 65, 505, 279, 3907, 315, 26275, 1071, 25, 330, 2181, 596, 12266, 311, 4007, 279, 2167, 6372, 315, 264, 3827, 389, 40459, 3691, 389, 11761, 17432, 3156, 1778, 10396, 527, 11784, 11, 719, 1521, 17989, 1501, 279, 4461, 5536, 315, 4442, 304, 279, 3430, 13, 4314, 43402, 527, 1579, 304, 13465, 719, 3629, 1579, 304, 8834, 2288, 323, 1633, 4907, 29050, 11, 779, 872, 15652, 649, 5376, 279, 5326, 315, 33048, 13, 1115, 3495, 13533, 430, 33459, 20323, 10396, 311, 2997, 10437, 43402, 1436, 387, 459, 3062, 7916, 311, 586, 2890, 11, 555, 18189, 23395, 323, 16472, 15652, 315, 1521, 15657, 11, 8104, 304, 3428, 32197, 29939, 1210, 578, 12283, 25670, 9669, 315, 279, 4007, 2737, 279, 42308, 315, 24393, 315, 15657, 323, 7172, 11021, 323, 27073, 4994, 315, 10632, 320, 68, 1326, 13, 304, 15926, 8, 902, 814, 2019, 527, 4461, 311, 387, 7191, 4315, 5190, 8070, 97063, 13, 220, 128257, 198 ]

2,117

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract The interplay between hydrogen and nanovoids, despite long being recognized as a central factor in hydrogen-induced damage in structural materials, remains poorly understood. Here, focusing on tungsten as a model body-centred cubic system, we explicitly demonstrate sequential adsorption of hydrogen adatoms on Wigner–Seitz squares of nanovoids with distinct energy levels. Interaction between hydrogen adatoms on nanovoid surfaces is shown to be dominated by pairwise power-law repulsion. We establish a predictive model for quantitative determination of the configurations and energetics of hydrogen adatoms in nanovoids. This model, combined with the equation of states of hydrogen gas, enables the prediction of hydrogen molecule formation in nanovoids. Multiscale simulations, performed based on our model, show good agreement with recent thermal desorption experiments. This work clarifies fundamental physics and provides a full-scale predictive model for hydrogen trapping and bubbling in nanovoids, offering long-sought mechanistic insights that are crucial for understanding hydrogen-induced damage in structural materials. Main Hydrogen is the most abundant element in the known universe and is a typical product of corrosion; it thus exists in virtually all service environments. The exposure of metallic materials to hydrogen-rich environments can result in a range of structural damage, including hydrogen-induced cracking 1 , 2 , surface blistering/flaking 3 , 4 , 5 and porosity/swelling 6 , 7 . This damage undesirably degrades the structural and mechanical integrity of materials 8 , 9 , often causing premature and even catastrophic failure 4 , 5 and thus jeopardizing the safety and efficiency of many applications. It is generally believed that such damage originates from interactions between hydrogen and various lattice defects. One key issue among those interactions is the interplay between the hydrogen and nanovoids; this promotes the formation and growth of pressurized hydrogen bubbles and consequently leads to experimentally observable failure in structural materials 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 . Researchers have long recognized H 2 pressure build-up in a bubble core following cumulative hydrogen adsorption on the bubble surface 11 . However, the accurate characterization of structures, energetics and hydrogen pressure in bubbles has remained lacking. The development of advanced micrographic techniques has enabled the direct observation of hydrogen bubble structures at scales of tens of nanometres 4 , 10 . However, atomic details of hydrogen bubble nucleation, growth and agglomeration processes are difficult or even impossible to observe in situ. An alternative method to study hydrogen bubble formation is to measure the hydrogen thermal desorption rates during isochronal annealing 12 , 13 , 14 , 15 , 16 , which provides energetic information about hydrogen detrapping from nanovoids in metals. Nevertheless, the hydrogen thermal desorption spectra usually relate to multiple types of crystal defect at different depths 17 and are thus difficult to interpret. Multiscale simulations provide a way to circumvent such limitations to reveal the missing details 18 , 19 , 20 . The reliability of multiscale results requires accurate characterization of the relevant atomistic behaviour. At the fundamental level, ab initio calculations based on density functional theory (DFT) have been widely used to study the atomistic behaviour of hydrogen in nanovoids 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 . Most previous DFT studies have focused only on the simplest case of monovacancies 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 and/or divacancies 31 , 32 , 33 , 34 , with hydrogen empirically placed at high symmetry sites, to investigate the energetic behaviour 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 . Recent DFT work 35 , 36 , 37 has tried to extend this method to hydrogen in larger nanovoids by decomposing the nanovoids’ inner surfaces into facets of free surfaces, and empirically saturating their high symmetry sites with hard-sphere-like H adatoms. However, this facet approach fails to resolve the inherent structural complexity associated with the highly curved edges and corners in nanovoids, and the hard-sphere approximation is oversimplified to describe just the H–H interaction, thus preventing accurate assessment of the energetics and structures of multiple H atoms in the nanovoids. As well as the above DFT endeavours, notable investigations have been carried out using large-scale classical molecular dynamics (MD) simulations. Vastly different predictions of hydrogen trapping behaviour were obtained depending on the empirical interatomic potentials used 38 , 39 . Furthermore, many of the available interatomic potentials were fitted as if simulating bulk conditions and cannot reproduce H 2 molecule formation in nanovoids 35 , 38 ; this inherently precludes the ability to predict experimentally observed H 2 pressure build-up in metals 3 , 4 , 5 , 40 , 41 , 42 . Consequently, it remains difficult to determine which hydrogen trapping behaviours reported, if any, are physically meaningful and/or relevant to hydrogen bubble formation in experiments. The absence of physical models and predictability prevents an accurate analysis of hydrogen behaviour in nanovoids; obtaining mechanistic and multiscale insights into hydrogen bubbling behaviour in metals thus remains a formidable challenge. The present study aims to directly address the aforementioned challenge. Based on comprehensive first-principles calculations on a model tungsten (W) system, we explicitly demonstrate a sequential adsorption of adatoms on square Wigner–Seitz surfaces of nanovoids with distinct energy levels, and propose a power law to describe the interaction among the H adatoms. A predictive model is established to determine the energetics and stable configurations of multiple H adatoms in nanovoids. Combined with the equation of state of pressurized H 2 , this model enables quantitative assessment of the competition between H adatoms and H 2 molecules, as well as the prediction of pressurized H 2 molecule formation in nanovoids. Multiscale simulations based on the model show very good agreement with recent", "role": "user" }, { "content": "A five-year collaborative study by Chinese and Canadian scientists has produced a theoretical model via computer simulation to predict properties of hydrogen nanobubbles in metal. The international team was composed of Chinese scientists from the Institute of Solid State Physics of the Hefei Institute of Physical Science along with their Canadian partners from McGill University. The results will be published in Nature Materials on July 15. The researchers believe their study may enable quantitative understanding and evaluation of hydrogen-induced damage in hydrogen-rich environments such as fusion reactor cores. Hydrogen, the most abundant element in the known universe, is a highly anticipated fuel for fusion reactions and thus an important focus of study. In certain hydrogen-enriched environments, e.g., tungsten armor in the core of a fusion reactor, metallic material may be seriously and irreparably damaged by extensive exposure to hydrogen. Being the smallest element, hydrogen can easily penetrate metal surfaces through gaps between metal atoms. These hydrogen atoms can be readily trapped inside nanoscale voids (\"nanovoids\") in metals created either during manufacturing or by neutron irradiation in the fusion reactor. These nanobubbles get bigger and bigger under internal hydrogen pressure and finally lead to metal failure. Not surprisingly, the interplay between hydrogen and nanovoids that promote the formation and growth of bubbles is considered the key to such failure. Yet, the basic properties of hydrogen nanobubbles, such as their number and the strength of the hydrogen entrapped in the bubbles, has largely been unknown. Furthermore, available experimental techniques make it practically impossible to directly observe nanoscale hydrogen bubbles. To tackle this problem, the research team proposed instead using computer simulations based on fundamental quantum mechanics. However, the structural complexity of hydrogen nanobubbles made numerical simulation extremely complicated. As a result, the researchers needed five years to produce enough computer simulations to answer their questions. In the end, however, they discovered that hydrogen trapping behavior in nanovoids—although apparently complicated—actually follows simple rules. First, individual hydrogen atoms are adsorbed, in a mutually exclusive way, by the inner surface of nanovoids with distinct energy levels. Second, after a period of surface adsorption, hydrogen is pushed—due to limited space—to the nanovoid core where molecular hydrogen gas then accumulates. Following these rules, the team created a model that accurately predicts properties of hydrogen nanobubbles and accords well with recent experimental observations. Just as hydrogen fills nanovoids in metals, this research fills a long-standing void in understanding how hydrogen nanobubbles form in metals. The model provides a powerful tool for evaluating hydrogen-induced damage in fusion reactors, thus paving the way for harvesting fusion energy in the future. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract The interplay between hydrogen and nanovoids, despite long being recognized as a central factor in hydrogen-induced damage in structural materials, remains poorly understood. Here, focusing on tungsten as a model body-centred cubic system, we explicitly demonstrate sequential adsorption of hydrogen adatoms on Wigner–Seitz squares of nanovoids with distinct energy levels. Interaction between hydrogen adatoms on nanovoid surfaces is shown to be dominated by pairwise power-law repulsion. We establish a predictive model for quantitative determination of the configurations and energetics of hydrogen adatoms in nanovoids. This model, combined with the equation of states of hydrogen gas, enables the prediction of hydrogen molecule formation in nanovoids. Multiscale simulations, performed based on our model, show good agreement with recent thermal desorption experiments. This work clarifies fundamental physics and provides a full-scale predictive model for hydrogen trapping and bubbling in nanovoids, offering long-sought mechanistic insights that are crucial for understanding hydrogen-induced damage in structural materials. Main Hydrogen is the most abundant element in the known universe and is a typical product of corrosion; it thus exists in virtually all service environments. The exposure of metallic materials to hydrogen-rich environments can result in a range of structural damage, including hydrogen-induced cracking 1 , 2 , surface blistering/flaking 3 , 4 , 5 and porosity/swelling 6 , 7 . This damage undesirably degrades the structural and mechanical integrity of materials 8 , 9 , often causing premature and even catastrophic failure 4 , 5 and thus jeopardizing the safety and efficiency of many applications. It is generally believed that such damage originates from interactions between hydrogen and various lattice defects. One key issue among those interactions is the interplay between the hydrogen and nanovoids; this promotes the formation and growth of pressurized hydrogen bubbles and consequently leads to experimentally observable failure in structural materials 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 . Researchers have long recognized H 2 pressure build-up in a bubble core following cumulative hydrogen adsorption on the bubble surface 11 . However, the accurate characterization of structures, energetics and hydrogen pressure in bubbles has remained lacking. The development of advanced micrographic techniques has enabled the direct observation of hydrogen bubble structures at scales of tens of nanometres 4 , 10 . However, atomic details of hydrogen bubble nucleation, growth and agglomeration processes are difficult or even impossible to observe in situ. An alternative method to study hydrogen bubble formation is to measure the hydrogen thermal desorption rates during isochronal annealing 12 , 13 , 14 , 15 , 16 , which provides energetic information about hydrogen detrapping from nanovoids in metals. Nevertheless, the hydrogen thermal desorption spectra usually relate to multiple types of crystal defect at different depths 17 and are thus difficult to interpret. Multiscale simulations provide a way to circumvent such limitations to reveal the missing details 18 , 19 , 20 . The reliability of multiscale results requires accurate characterization of the relevant atomistic behaviour. At the fundamental level, ab initio calculations based on density functional theory (DFT) have been widely used to study the atomistic behaviour of hydrogen in nanovoids 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 . Most previous DFT studies have focused only on the simplest case of monovacancies 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 and/or divacancies 31 , 32 , 33 , 34 , with hydrogen empirically placed at high symmetry sites, to investigate the energetic behaviour 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 . Recent DFT work 35 , 36 , 37 has tried to extend this method to hydrogen in larger nanovoids by decomposing the nanovoids’ inner surfaces into facets of free surfaces, and empirically saturating their high symmetry sites with hard-sphere-like H adatoms. However, this facet approach fails to resolve the inherent structural complexity associated with the highly curved edges and corners in nanovoids, and the hard-sphere approximation is oversimplified to describe just the H–H interaction, thus preventing accurate assessment of the energetics and structures of multiple H atoms in the nanovoids. As well as the above DFT endeavours, notable investigations have been carried out using large-scale classical molecular dynamics (MD) simulations. Vastly different predictions of hydrogen trapping behaviour were obtained depending on the empirical interatomic potentials used 38 , 39 . Furthermore, many of the available interatomic potentials were fitted as if simulating bulk conditions and cannot reproduce H 2 molecule formation in nanovoids 35 , 38 ; this inherently precludes the ability to predict experimentally observed H 2 pressure build-up in metals 3 , 4 , 5 , 40 , 41 , 42 . Consequently, it remains difficult to determine which hydrogen trapping behaviours reported, if any, are physically meaningful and/or relevant to hydrogen bubble formation in experiments. The absence of physical models and predictability prevents an accurate analysis of hydrogen behaviour in nanovoids; obtaining mechanistic and multiscale insights into hydrogen bubbling behaviour in metals thus remains a formidable challenge. The present study aims to directly address the aforementioned challenge. Based on comprehensive first-principles calculations on a model tungsten (W) system, we explicitly demonstrate a sequential adsorption of adatoms on square Wigner–Seitz surfaces of nanovoids with distinct energy levels, and propose a power law to describe the interaction among the H adatoms. A predictive model is established to determine the energetics and stable configurations of multiple H adatoms in nanovoids. Combined with the equation of state of pressurized H 2 , this model enables quantitative assessment of the competition between H adatoms and H 2 molecules, as well as the prediction of pressurized H 2 molecule formation in nanovoids. Multiscale simulations based on the model show very good agreement with recent<|im_end|> <|im_start|>assistant A five-year collaborative study by Chinese and Canadian scientists has produced a theoretical model via computer simulation to predict properties of hydrogen nanobubbles in metal. The international team was composed of Chinese scientists from the Institute of Solid State Physics of the Hefei Institute of Physical Science along with their Canadian partners from McGill University. The results will be published in Nature Materials on July 15. The researchers believe their study may enable quantitative understanding and evaluation of hydrogen-induced damage in hydrogen-rich environments such as fusion reactor cores. Hydrogen, the most abundant element in the known universe, is a highly anticipated fuel for fusion reactions and thus an important focus of study. In certain hydrogen-enriched environments, e.g., tungsten armor in the core of a fusion reactor, metallic material may be seriously and irreparably damaged by extensive exposure to hydrogen. Being the smallest element, hydrogen can easily penetrate metal surfaces through gaps between metal atoms. These hydrogen atoms can be readily trapped inside nanoscale voids ("nanovoids") in metals created either during manufacturing or by neutron irradiation in the fusion reactor. These nanobubbles get bigger and bigger under internal hydrogen pressure and finally lead to metal failure. Not surprisingly, the interplay between hydrogen and nanovoids that promote the formation and growth of bubbles is considered the key to such failure. Yet, the basic properties of hydrogen nanobubbles, such as their number and the strength of the hydrogen entrapped in the bubbles, has largely been unknown. Furthermore, available experimental techniques make it practically impossible to directly observe nanoscale hydrogen bubbles. To tackle this problem, the research team proposed instead using computer simulations based on fundamental quantum mechanics. However, the structural complexity of hydrogen nanobubbles made numerical simulation extremely complicated. As a result, the researchers needed five years to produce enough computer simulations to answer their questions. In the end, however, they discovered that hydrogen trapping behavior in nanovoids—although apparently complicated—actually follows simple rules. First, individual hydrogen atoms are adsorbed, in a mutually exclusive way, by the inner surface of nanovoids with distinct energy levels. Second, after a period of surface adsorption, hydrogen is pushed—due to limited space—to the nanovoid core where molecular hydrogen gas then accumulates. Following these rules, the team created a model that accurately predicts properties of hydrogen nanobubbles and accords well with recent experimental observations. Just as hydrogen fills nanovoids in metals, this research fills a long-standing void in understanding how hydrogen nanobubbles form in metals. The model provides a powerful tool for evaluating hydrogen-induced damage in fusion reactors, thus paving the way for harvesting fusion energy in the future. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 578, 958, 1387, 1990, 35784, 323, 20622, 869, 17390, 11, 8994, 1317, 1694, 15324, 439, 264, 8792, 8331, 304, 35784, 38973, 5674, 304, 24693, 7384, 11, 8625, 31555, 16365, 13, 5810, 11, 21760, 389, 85307, 16172, 439, 264, 1646, 2547, 21911, 1171, 41999, 1887, 11, 584, 21650, 20461, 52100, 14058, 66181, 315, 35784, 1008, 66650, 389, 468, 78756, 4235, 1542, 11289, 32440, 315, 20622, 869, 17390, 449, 12742, 4907, 5990, 13, 43807, 1990, 35784, 1008, 66650, 389, 20622, 869, 590, 27529, 374, 6982, 311, 387, 30801, 555, 93859, 2410, 31412, 2109, 34003, 13, 1226, 5813, 264, 60336, 1646, 369, 47616, 26314, 315, 279, 33483, 323, 38556, 456, 1233, 315, 35784, 1008, 66650, 304, 20622, 869, 17390, 13, 1115, 1646, 11, 11093, 449, 279, 24524, 315, 5415, 315, 35784, 6962, 11, 20682, 279, 20212, 315, 35784, 43030, 18488, 304, 20622, 869, 17390, 13, 22950, 285, 2296, 47590, 11, 10887, 3196, 389, 1057, 1646, 11, 1501, 1695, 9306, 449, 3293, 29487, 951, 66181, 21896, 13, 1115, 990, 20064, 9803, 16188, 22027, 323, 5825, 264, 2539, 13230, 60336, 1646, 369, 35784, 93669, 323, 78869, 9894, 304, 20622, 869, 17390, 11, 10209, 1317, 1355, 2509, 7852, 4633, 26793, 430, 527, 16996, 369, 8830, 35784, 38973, 5674, 304, 24693, 7384, 13, 4802, 40602, 4469, 374, 279, 1455, 44611, 2449, 304, 279, 3967, 15861, 323, 374, 264, 14595, 2027, 315, 56488, 26, 433, 8617, 6866, 304, 21907, 682, 2532, 22484, 13, 578, 14675, 315, 46258, 7384, 311, 35784, 41947, 22484, 649, 1121, 304, 264, 2134, 315, 24693, 5674, 11, 2737, 35784, 38973, 52829, 220, 16, 1174, 220, 17, 1174, 7479, 81792, 287, 59403, 1802, 220, 18, 1174, 220, 19, 1174, 220, 20, 323, 4247, 22828, 44034, 6427, 220, 21, 1174, 220, 22, 662, 1115, 5674, 56838, 404, 2915, 409, 23142, 279, 24693, 323, 22936, 17025, 315, 7384, 220, 23, 1174, 220, 24, 1174, 3629, 14718, 42227, 323, 1524, 54677, 8060, 220, 19, 1174, 220, 20, 323, 8617, 53132, 4954, 279, 7296, 323, 15374, 315, 1690, 8522, 13, 1102, 374, 8965, 11846, 430, 1778, 5674, 99970, 505, 22639, 1990, 35784, 323, 5370, 55372, 42655, 13, 3861, 1401, 4360, 4315, 1884, 22639, 374, 279, 958, 1387, 1990, 279, 35784, 323, 20622, 869, 17390, 26, 420, 39990, 279, 18488, 323, 6650, 315, 3577, 324, 1534, 35784, 44783, 323, 52394, 11767, 311, 9526, 750, 40635, 8060, 304, 24693, 7384, 220, 18, 1174, 220, 19, 1174, 220, 20, 1174, 220, 21, 1174, 220, 22, 1174, 220, 23, 1174, 220, 24, 1174, 220, 605, 662, 59250, 617, 1317, 15324, 473, 220, 17, 7410, 1977, 5352, 304, 264, 24529, 6332, 2768, 40944, 35784, 14058, 66181, 389, 279, 24529, 7479, 220, 806, 662, 4452, 11, 279, 13687, 60993, 315, 14726, 11, 38556, 456, 1233, 323, 35784, 7410, 304, 44783, 706, 14958, 32161, 13, 578, 4500, 315, 11084, 8162, 86972, 12823, 706, 9147, 279, 2167, 22695, 315, 35784, 24529, 14726, 520, 29505, 315, 22781, 315, 20622, 4512, 417, 220, 19, 1174, 220, 605, 662, 4452, 11, 25524, 3649, 315, 35784, 24529, 31484, 367, 11, 6650, 323, 945, 6200, 316, 21597, 11618, 527, 5107, 477, 1524, 12266, 311, 23846, 304, 10109, 13, 1556, 10778, 1749, 311, 4007, 35784, 24529, 18488, 374, 311, 6767, 279, 35784, 29487, 951, 66181, 7969, 2391, 374, 5059, 2298, 278, 86997, 6260, 220, 717, 1174, 220, 1032, 1174, 220, 975, 1174, 220, 868, 1174, 220, 845, 1174, 902, 5825, 45955, 2038, 922, 35784, 35453, 3713, 505, 20622, 869, 17390, 304, 37182, 13, 35053, 11, 279, 35784, 29487, 951, 66181, 63697, 6118, 29243, 311, 5361, 4595, 315, 26110, 23011, 520, 2204, 43957, 220, 1114, 323, 527, 8617, 5107, 311, 14532, 13, 22950, 285, 2296, 47590, 3493, 264, 1648, 311, 10408, 688, 1778, 9669, 311, 16805, 279, 7554, 3649, 220, 972, 1174, 220, 777, 1174, 220, 508, 662, 578, 31638, 315, 75837, 2296, 3135, 7612, 13687, 60993, 315, 279, 9959, 19670, 4633, 17432, 13, 2468, 279, 16188, 2237, 11, 671, 3003, 822, 29217, 3196, 389, 17915, 16003, 10334, 320, 35, 4082, 8, 617, 1027, 13882, 1511, 311, 4007, 279, 19670, 4633, 17432, 315, 35784, 304, 20622, 869, 17390, 220, 1691, 1174, 220, 1313, 1174, 220, 1419, 1174, 220, 1187, 1174, 220, 914, 1174, 220, 1627, 1174, 220, 1544, 1174, 220, 1591, 1174, 220, 1682, 1174, 220, 966, 1174, 220, 2148, 1174, 220, 843, 1174, 220, 1644, 1174, 220, 1958, 1174, 220, 1758, 1174, 220, 1927, 1174, 220, 1806, 662, 7648, 3766, 423, 4082, 7978, 617, 10968, 1193, 389, 279, 45648, 1162, 315, 1647, 869, 582, 32737, 220, 1691, 1174, 220, 1313, 1174, 220, 1419, 1174, 220, 1187, 1174, 220, 914, 1174, 220, 1627, 1174, 220, 1544, 1174, 220, 1591, 1174, 220, 1682, 1174, 220, 966, 323, 5255, 3512, 582, 32737, 220, 2148, 1174, 220, 843, 1174, 220, 1644, 1174, 220, 1958, 1174, 449, 35784, 38969, 2740, 9277, 520, 1579, 46220, 6732, 11, 311, 19874, 279, 45955, 17432, 220, 1691, 1174, 220, 1313, 1174, 220, 1419, 1174, 220, 1187, 1174, 220, 914, 1174, 220, 1627, 1174, 220, 1544, 1174, 220, 1591, 1174, 220, 1682, 1174, 220, 966, 1174, 220, 2148, 1174, 220, 843, 1174, 220, 1644, 1174, 220, 1958, 1174, 220, 1758, 662, 35390, 423, 4082, 990, 220, 1758, 1174, 220, 1927, 1174, 220, 1806, 706, 6818, 311, 13334, 420, 1749, 311, 35784, 304, 8294, 20622, 869, 17390, 555, 29602, 8478, 279, 20622, 869, 17390, 529, 9358, 27529, 1139, 62814, 315, 1949, 27529, 11, 323, 38969, 2740, 94577, 1113, 872, 1579, 46220, 6732, 449, 2653, 1355, 8182, 12970, 473, 1008, 66650, 13, 4452, 11, 420, 45607, 5603, 14865, 311, 9006, 279, 38088, 24693, 23965, 5938, 449, 279, 7701, 50264, 13116, 323, 24359, 304, 20622, 869, 17390, 11, 323, 279, 2653, 1355, 8182, 57304, 374, 17918, 74937, 311, 7664, 1120, 279, 473, 4235, 39, 16628, 11, 8617, 27252, 13687, 15813, 315, 279, 38556, 456, 1233, 323, 14726, 315, 5361, 473, 33299, 304, 279, 20622, 869, 17390, 13, 1666, 1664, 439, 279, 3485, 423, 4082, 29705, 402, 2530, 11, 28289, 26969, 617, 1027, 11953, 704, 1701, 3544, 13230, 29924, 31206, 30295, 320, 6204, 8, 47590, 13, 650, 561, 398, 2204, 20492, 315, 35784, 93669, 17432, 1051, 12457, 11911, 389, 279, 46763, 958, 6756, 95358, 1511, 220, 1987, 1174, 220, 2137, 662, 24296, 11, 1690, 315, 279, 2561, 958, 6756, 95358, 1051, 29441, 439, 422, 1675, 15853, 20155, 4787, 323, 4250, 23645, 473, 220, 17, 43030, 18488, 304, 20622, 869, 17390, 220, 1758, 1174, 220, 1987, 2652, 420, 49188, 864, 7548, 279, 5845, 311, 7168, 9526, 750, 13468, 473, 220, 17, 7410, 1977, 5352, 304, 37182, 220, 18, 1174, 220, 19, 1174, 220, 20, 1174, 220, 1272, 1174, 220, 3174, 1174, 220, 2983, 662, 53123, 11, 433, 8625, 5107, 311, 8417, 902, 35784, 93669, 71177, 5068, 11, 422, 904, 11, 527, 22655, 23222, 323, 5255, 9959, 311, 35784, 24529, 18488, 304, 21896, 13, 578, 19821, 315, 7106, 4211, 323, 7168, 2968, 29034, 459, 13687, 6492, 315, 35784, 17432, 304, 20622, 869, 17390, 26, 19546, 7852, 4633, 323, 75837, 2296, 26793, 1139, 35784, 78869, 9894, 17432, 304, 37182, 8617, 8625, 264, 54829, 8815, 13, 578, 3118, 4007, 22262, 311, 6089, 2686, 279, 46752, 8815, 13, 20817, 389, 16195, 1176, 27748, 5824, 645, 29217, 389, 264, 1646, 85307, 16172, 320, 54, 8, 1887, 11, 584, 21650, 20461, 264, 52100, 14058, 66181, 315, 1008, 66650, 389, 9518, 468, 78756, 4235, 1542, 11289, 27529, 315, 20622, 869, 17390, 449, 12742, 4907, 5990, 11, 323, 30714, 264, 2410, 2383, 311, 7664, 279, 16628, 4315, 279, 473, 1008, 66650, 13, 362, 60336, 1646, 374, 9749, 311, 8417, 279, 38556, 456, 1233, 323, 15528, 33483, 315, 5361, 473, 1008, 66650, 304, 20622, 869, 17390, 13, 58752, 449, 279, 24524, 315, 1614, 315, 3577, 324, 1534, 473, 220, 17, 1174, 420, 1646, 20682, 47616, 15813, 315, 279, 10937, 1990, 473, 1008, 66650, 323, 473, 220, 17, 35715, 11, 439, 1664, 439, 279, 20212, 315, 3577, 324, 1534, 473, 220, 17, 43030, 18488, 304, 20622, 869, 17390, 13, 22950, 285, 2296, 47590, 3196, 389, 279, 1646, 1501, 1633, 1695, 9306, 449, 3293, 128257, 198, 128256, 78191, 198, 32, 4330, 4771, 40806, 4007, 555, 8620, 323, 12152, 14248, 706, 9124, 264, 32887, 1646, 4669, 6500, 19576, 311, 7168, 6012, 315, 35784, 20622, 677, 35395, 304, 9501, 13, 578, 6625, 2128, 574, 24306, 315, 8620, 14248, 505, 279, 10181, 315, 22925, 3314, 28415, 315, 279, 473, 830, 20568, 10181, 315, 28479, 10170, 3235, 449, 872, 12152, 8717, 505, 94076, 3907, 13, 578, 3135, 690, 387, 4756, 304, 22037, 32009, 389, 5887, 220, 868, 13, 578, 12074, 4510, 872, 4007, 1253, 7431, 47616, 8830, 323, 16865, 315, 35784, 38973, 5674, 304, 35784, 41947, 22484, 1778, 439, 37608, 38729, 36804, 13, 40602, 4469, 11, 279, 1455, 44611, 2449, 304, 279, 3967, 15861, 11, 374, 264, 7701, 30199, 10633, 369, 37608, 25481, 323, 8617, 459, 3062, 5357, 315, 4007, 13, 763, 3738, 35784, 21430, 14172, 291, 22484, 11, 384, 1326, 2637, 85307, 16172, 20634, 304, 279, 6332, 315, 264, 37608, 38729, 11, 46258, 3769, 1253, 387, 14243, 323, 25912, 1768, 2915, 20727, 555, 16781, 14675, 311, 35784, 13, 21347, 279, 25655, 2449, 11, 35784, 649, 6847, 64855, 9501, 27529, 1555, 33251, 1990, 9501, 33299, 13, 4314, 35784, 33299, 649, 387, 31368, 31691, 4871, 20622, 437, 2296, 742, 82, 3573, 19285, 869, 17390, 909, 304, 37182, 3549, 3060, 2391, 15266, 477, 555, 73404, 76327, 367, 304, 279, 37608, 38729, 13, 4314, 20622, 677, 35395, 636, 11493, 323, 11493, 1234, 5419, 35784, 7410, 323, 5616, 3063, 311, 9501, 8060, 13, 2876, 29392, 11, 279, 958, 1387, 1990, 35784, 323, 20622, 869, 17390, 430, 12192, 279, 18488, 323, 6650, 315, 44783, 374, 6646, 279, 1401, 311, 1778, 8060, 13, 14968, 11, 279, 6913, 6012, 315, 35784, 20622, 677, 35395, 11, 1778, 439, 872, 1396, 323, 279, 8333, 315, 279, 35784, 11751, 5795, 304, 279, 44783, 11, 706, 14090, 1027, 9987, 13, 24296, 11, 2561, 22772, 12823, 1304, 433, 32367, 12266, 311, 6089, 23846, 20622, 437, 2296, 35784, 44783, 13, 2057, 22118, 420, 3575, 11, 279, 3495, 2128, 11223, 4619, 1701, 6500, 47590, 3196, 389, 16188, 31228, 30126, 13, 4452, 11, 279, 24693, 23965, 315, 35784, 20622, 677, 35395, 1903, 35876, 19576, 9193, 17395, 13, 1666, 264, 1121, 11, 279, 12074, 4460, 4330, 1667, 311, 8356, 3403, 6500, 47590, 311, 4320, 872, 4860, 13, 763, 279, 842, 11, 4869, 11, 814, 11352, 430, 35784, 93669, 7865, 304, 20622, 869, 17390, 2345, 37241, 14132, 17395, 2345, 74128, 11263, 4382, 5718, 13, 5629, 11, 3927, 35784, 33299, 527, 14058, 269, 2788, 11, 304, 264, 53579, 14079, 1648, 11, 555, 279, 9358, 7479, 315, 20622, 869, 17390, 449, 12742, 4907, 5990, 13, 10657, 11, 1306, 264, 4261, 315, 7479, 14058, 66181, 11, 35784, 374, 15753, 2345, 24567, 311, 7347, 3634, 50617, 279, 20622, 869, 590, 6332, 1405, 31206, 35784, 6962, 1243, 15783, 24031, 13, 23548, 1521, 5718, 11, 279, 2128, 3549, 264, 1646, 430, 30357, 56978, 6012, 315, 35784, 20622, 677, 35395, 323, 1046, 2311, 1664, 449, 3293, 22772, 24654, 13, 4702, 439, 35784, 41687, 20622, 869, 17390, 304, 37182, 11, 420, 3495, 41687, 264, 1317, 56703, 742, 304, 8830, 1268, 35784, 20622, 677, 35395, 1376, 304, 37182, 13, 578, 1646, 5825, 264, 8147, 5507, 369, 38663, 35784, 38973, 5674, 304, 37608, 71573, 11, 8617, 82568, 279, 1648, 369, 66747, 37608, 4907, 304, 279, 3938, 13, 220, 128257, 198 ]

1,904

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Information about the geological timeframe during which animals radiated into their major subclades is crucial to understanding early animal ecology and evolution. Unfortunately, the pre-Cambrian fossil record is sparse and its interpretation controversial. Relaxed molecular-clock methods provide an alternative means of estimating the timing of cladogenesis deep in the metazoan tree of life. So far, thorough molecular clock studies focusing specifically on Metazoa as a whole have been based on relatively small datasets or incomplete representation of the main non-bilaterian lineages (such as sponges and ctenophores), which are fundamental for understanding early metazoan evolution. Here, we use a previously published phylogenomic dataset that includes a fair sampling of all relevant groups to estimate the timing of early animal evolution with Bayesian relaxed-clock methods. According to our results, all non-bilaterian phyla, as well as total-group Bilateria, evolved in an ancient radiation during a geologically relatively short time span, before the onset of long-term global glaciations (“Snowball Earth”; ~720–635 Ma). Importantly, this result appears robust to alterations of a number of important analytical variables, such as models of among-lineage rate variation and sets of fossil calibrations used. Introduction Our understanding of the origin and evolution of animals (Metazoa) and their major subgroups would be greatly enlightened by better knowledge about the timing of diversification early in their history. Metazoa comprises five main lineages (see Dohrmann & Wörheide 1 for a review of their phylogenetic relationships): the phyla Porifera (sponges), Placozoa ( Trichoplax ), Ctenophora (comb jellies), Cnidaria (corals, jellyfish, and their kin), and Bilateria, the mega-diverse group containing all the remaining 30 or so phyla. Most animal phyla appear in the fossil record in a relatively short period during the Cambrian (541–485 million years ago [Ma]), the so-called “Cambrian explosion” 2 , 3 , 4 . However, these Cambrian fossils already exhibit complex morphologies, supporting the idea that animals must have evolved some time during the Proterozoic (2500–541 Ma). Indeed, it is now widely agreed that animals existed at least during the later stages of the preceding Ediacaran period (635–541 Ma), as evidenced by trace fossils and some body fossils with likely metazoan affinities 5 , 6 , 7 . Unfortunately, the older fossil record is relatively scarce with respect to possible animals, and most findings are being controversially discussed 8 , which prevents reliable inferences about the origination times of the five main lineages. Therefore, molecular palaeobiological approaches 9 , 10 might aid in deciphering early animal evolution by means of divergence time estimation from genomic data of extant species (molecular clock studies). Although molecular clock studies have generally supported a deep pre-Ediacaran origin of animals and many of its major subgroups 11 , 12 , 13 , 14 , estimates of the precise timing vary widely 8 , 15 . Moreover, the majority of studies have focused either on estimating the timescale of eukaryote evolution and thus including only few animals as representatives of just one lineage within the Opisthokonta supergroup 13 , 16 , or severely undersampled the full diversity of Metazoa because they were mainly interested in the evolution of Bilateria 14 , 17 . However, reliably estimating the timing of early metazoan evolution requires that all non-bilaterian lineages be adequately represented. In a highly cited molecular clock study, Erwin et al . 12 included a variety of non-bilaterians – 20 sponges, Trichoplax , and six cnidarians. However, they did not include Ctenophora and only sampled three of the four classes of Porifera (Hexactinellida was excluded). Furthermore, the dataset they used for dating their trees is comparatively small, being composed of sequence data from seven proteins only (~2000 amino acid positions). Thus, the results of Erwin et al . 12 remain to be tested with a more complete taxon sampling and phylogenomic-scale data. Philippe et al . 18 used a 128-protein phylogenomic dataset (30,257 amino acid positions) to reconstruct animal phylogeny. This dataset includes all non-bilaterian phyla and classes, a selected sample of representatives from all three bilaterian supergroups (Deuterostomia, Ecdysozoa, Lophotrochozoa), as well as a suite of non-metazoan opisthokonts as outgroups. Supporting a well-resolved phylogeny, this dataset appears well suited for investigating the timing of deep metazoan phylogeny. However, in-depth molecular clock studies utilizing this dataset have thus far been lacking. Here, we present molecular clock analyses of the Philippe et al . 18 dataset under a variety of analytical conditions. Our results confirm previous molecular-clock estimates of an early-mid Neoproterozoic (Tonian; 1000–720 Ma) origin of crown-group Metazoa, before the onset of long-lasting global glaciations, the Sturtian and Marinoan “Snowball Earths” of the Cryogenian (720–635 Ma 19 , 20 , 21 ). In contrast to previous studies, however, our results suggest that not only crown-group Metazoa, but all non-bilaterian phyla (and at least stem-lineages of all classes), as well as total-group Bilateria, originated before the Sturtian, probably within a geologically relatively short time span. Importantly, this main conclusion is robust to a number of major assumptions that can drastically influence the outcome of molecular clock studies. Methods We conducted a range of relaxed molecular-clock analyses using the Bayesian Markov Chain Monte Carlo (MCMC) implementation PhyloBayes 22 . In order to assess the robustness of our age estimates to a number of prior assumptions, we ran analyses under (1) an autocorrelated and an uncorrelated relaxed molecular-clock model – the former assuming that the rate of molecular evolution of a lineage is correlated with the rate of its mother lineage, the latter allowing completely independent rates from lineage to lineage; (2) three different sets of fossil calibrations for internal nodes – one aiming at a maximum breadth of calibrations ( Set A ), another one excluding some potentially controversial fossils ( Set B ), and a third one adopted from Erwin et al . 12 ( Set C ); (3) different prior assumptions about the age of the root of the phylogeny (=origin of crown-group Opisthokonta) – 800, 1000, and 1360 Ma; and 4) three different alternative assumptions about the phylogenetic placement of Ctenophora (sister to Cnidaria, sister", "role": "user" }, { "content": "The initial phases of animal evolution proceeded faster than hitherto supposed: New analyses suggest that the first animal phyla emerged in rapid succession – prior to the global Ice Age that set in around 700 million years ago. The fossil record reveals that almost all of the animal phyla known today had come into existence by the beginning of the Cambrian Period some 540 million years ago. The earliest known animal fossils already exhibit complex morphologies, which implies that animals must have originated long before the onset of the Cambrian. However, taxonomically assignable fossils that can be confidently dated to pre-Cambrian times are very rare. In order to determine what the root of their family tree looked like, biologists need reliable dating information for the most ancient animal subgroups – the sponges, cnidarians, comb jellies and placozoans. Dr. Martin Dohrmann and Professor Gert Wörheide of the Division of Palaeontology and Geobiology in the Department of Earth and Environmental Sciences at LMU Munich have now used a new strategy based on the so-called molecular-clock to investigate the chronology of early animal evolution and produce a new estimate for the ages of the oldest animal groups. Their findings appear in the journal Scientific Reports. The molecular clock approach is based on the principle that mutations accumulate in the genomes of all organisms over the course of time. The extent of the genetic difference between two lineages should therefore depend on the time elapsed since they diverged from their last common ancestor. \"Our study is based on a combination of genetic data from contemporary animals and information derived from well dated fossils, which we analyzed with the help of complex computer algorithms,\" Dohrmann explains. For the study, the researchers used an unusually large dataset made up of the sequences of 128 proteins from 55 species, including representatives of all the major animal groups, focusing in particular on those that diverged very early. The analysis confirms the conclusion reached in an earlier study, which dated the origin of animals to the Neoproterozoic Era, which lasted from 1000 to 540 million years ago. However, much to their surprise, the results also suggested that the earliest phyla, and the ancestors of all bilateral animal species (the so-called Bilateria), originated within the – geologically speaking – short time-span of 50 million years. \"In addition, this early phase of evolutionary divergence appears to have preceded the extreme climate changes that led to Snowball Earth, a period marked by severe long-term global glaciation that lasted from about 720 to 635 million years ago,\" Dohrmann says. In order to assess the plausibility of the new findings, the researchers plan to carry out further analyses using more extensive datasets and improved statistical methods.\" To arrive at well-founded conclusions with respect to the morphology and ecology of the earliest animals, we also need to know more about the environmental conditions that prevailed during the Neoproterozoic, and we need more fossils that can be confidently assigned to specific taxonomic groups\", Wörheide says. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Information about the geological timeframe during which animals radiated into their major subclades is crucial to understanding early animal ecology and evolution. Unfortunately, the pre-Cambrian fossil record is sparse and its interpretation controversial. Relaxed molecular-clock methods provide an alternative means of estimating the timing of cladogenesis deep in the metazoan tree of life. So far, thorough molecular clock studies focusing specifically on Metazoa as a whole have been based on relatively small datasets or incomplete representation of the main non-bilaterian lineages (such as sponges and ctenophores), which are fundamental for understanding early metazoan evolution. Here, we use a previously published phylogenomic dataset that includes a fair sampling of all relevant groups to estimate the timing of early animal evolution with Bayesian relaxed-clock methods. According to our results, all non-bilaterian phyla, as well as total-group Bilateria, evolved in an ancient radiation during a geologically relatively short time span, before the onset of long-term global glaciations (“Snowball Earth”; ~720–635 Ma). Importantly, this result appears robust to alterations of a number of important analytical variables, such as models of among-lineage rate variation and sets of fossil calibrations used. Introduction Our understanding of the origin and evolution of animals (Metazoa) and their major subgroups would be greatly enlightened by better knowledge about the timing of diversification early in their history. Metazoa comprises five main lineages (see Dohrmann & Wörheide 1 for a review of their phylogenetic relationships): the phyla Porifera (sponges), Placozoa ( Trichoplax ), Ctenophora (comb jellies), Cnidaria (corals, jellyfish, and their kin), and Bilateria, the mega-diverse group containing all the remaining 30 or so phyla. Most animal phyla appear in the fossil record in a relatively short period during the Cambrian (541–485 million years ago [Ma]), the so-called “Cambrian explosion” 2 , 3 , 4 . However, these Cambrian fossils already exhibit complex morphologies, supporting the idea that animals must have evolved some time during the Proterozoic (2500–541 Ma). Indeed, it is now widely agreed that animals existed at least during the later stages of the preceding Ediacaran period (635–541 Ma), as evidenced by trace fossils and some body fossils with likely metazoan affinities 5 , 6 , 7 . Unfortunately, the older fossil record is relatively scarce with respect to possible animals, and most findings are being controversially discussed 8 , which prevents reliable inferences about the origination times of the five main lineages. Therefore, molecular palaeobiological approaches 9 , 10 might aid in deciphering early animal evolution by means of divergence time estimation from genomic data of extant species (molecular clock studies). Although molecular clock studies have generally supported a deep pre-Ediacaran origin of animals and many of its major subgroups 11 , 12 , 13 , 14 , estimates of the precise timing vary widely 8 , 15 . Moreover, the majority of studies have focused either on estimating the timescale of eukaryote evolution and thus including only few animals as representatives of just one lineage within the Opisthokonta supergroup 13 , 16 , or severely undersampled the full diversity of Metazoa because they were mainly interested in the evolution of Bilateria 14 , 17 . However, reliably estimating the timing of early metazoan evolution requires that all non-bilaterian lineages be adequately represented. In a highly cited molecular clock study, Erwin et al . 12 included a variety of non-bilaterians – 20 sponges, Trichoplax , and six cnidarians. However, they did not include Ctenophora and only sampled three of the four classes of Porifera (Hexactinellida was excluded). Furthermore, the dataset they used for dating their trees is comparatively small, being composed of sequence data from seven proteins only (~2000 amino acid positions). Thus, the results of Erwin et al . 12 remain to be tested with a more complete taxon sampling and phylogenomic-scale data. Philippe et al . 18 used a 128-protein phylogenomic dataset (30,257 amino acid positions) to reconstruct animal phylogeny. This dataset includes all non-bilaterian phyla and classes, a selected sample of representatives from all three bilaterian supergroups (Deuterostomia, Ecdysozoa, Lophotrochozoa), as well as a suite of non-metazoan opisthokonts as outgroups. Supporting a well-resolved phylogeny, this dataset appears well suited for investigating the timing of deep metazoan phylogeny. However, in-depth molecular clock studies utilizing this dataset have thus far been lacking. Here, we present molecular clock analyses of the Philippe et al . 18 dataset under a variety of analytical conditions. Our results confirm previous molecular-clock estimates of an early-mid Neoproterozoic (Tonian; 1000–720 Ma) origin of crown-group Metazoa, before the onset of long-lasting global glaciations, the Sturtian and Marinoan “Snowball Earths” of the Cryogenian (720–635 Ma 19 , 20 , 21 ). In contrast to previous studies, however, our results suggest that not only crown-group Metazoa, but all non-bilaterian phyla (and at least stem-lineages of all classes), as well as total-group Bilateria, originated before the Sturtian, probably within a geologically relatively short time span. Importantly, this main conclusion is robust to a number of major assumptions that can drastically influence the outcome of molecular clock studies. Methods We conducted a range of relaxed molecular-clock analyses using the Bayesian Markov Chain Monte Carlo (MCMC) implementation PhyloBayes 22 . In order to assess the robustness of our age estimates to a number of prior assumptions, we ran analyses under (1) an autocorrelated and an uncorrelated relaxed molecular-clock model – the former assuming that the rate of molecular evolution of a lineage is correlated with the rate of its mother lineage, the latter allowing completely independent rates from lineage to lineage; (2) three different sets of fossil calibrations for internal nodes – one aiming at a maximum breadth of calibrations ( Set A ), another one excluding some potentially controversial fossils ( Set B ), and a third one adopted from Erwin et al . 12 ( Set C ); (3) different prior assumptions about the age of the root of the phylogeny (=origin of crown-group Opisthokonta) – 800, 1000, and 1360 Ma; and 4) three different alternative assumptions about the phylogenetic placement of Ctenophora (sister to Cnidaria, sister<|im_end|> <|im_start|>assistant The initial phases of animal evolution proceeded faster than hitherto supposed: New analyses suggest that the first animal phyla emerged in rapid succession – prior to the global Ice Age that set in around 700 million years ago. The fossil record reveals that almost all of the animal phyla known today had come into existence by the beginning of the Cambrian Period some 540 million years ago. The earliest known animal fossils already exhibit complex morphologies, which implies that animals must have originated long before the onset of the Cambrian. However, taxonomically assignable fossils that can be confidently dated to pre-Cambrian times are very rare. In order to determine what the root of their family tree looked like, biologists need reliable dating information for the most ancient animal subgroups – the sponges, cnidarians, comb jellies and placozoans. Dr. Martin Dohrmann and Professor Gert Wörheide of the Division of Palaeontology and Geobiology in the Department of Earth and Environmental Sciences at LMU Munich have now used a new strategy based on the so-called molecular-clock to investigate the chronology of early animal evolution and produce a new estimate for the ages of the oldest animal groups. Their findings appear in the journal Scientific Reports. The molecular clock approach is based on the principle that mutations accumulate in the genomes of all organisms over the course of time. The extent of the genetic difference between two lineages should therefore depend on the time elapsed since they diverged from their last common ancestor. "Our study is based on a combination of genetic data from contemporary animals and information derived from well dated fossils, which we analyzed with the help of complex computer algorithms," Dohrmann explains. For the study, the researchers used an unusually large dataset made up of the sequences of 128 proteins from 55 species, including representatives of all the major animal groups, focusing in particular on those that diverged very early. The analysis confirms the conclusion reached in an earlier study, which dated the origin of animals to the Neoproterozoic Era, which lasted from 1000 to 540 million years ago. However, much to their surprise, the results also suggested that the earliest phyla, and the ancestors of all bilateral animal species (the so-called Bilateria), originated within the – geologically speaking – short time-span of 50 million years. "In addition, this early phase of evolutionary divergence appears to have preceded the extreme climate changes that led to Snowball Earth, a period marked by severe long-term global glaciation that lasted from about 720 to 635 million years ago," Dohrmann says. In order to assess the plausibility of the new findings, the researchers plan to carry out further analyses using more extensive datasets and improved statistical methods." To arrive at well-founded conclusions with respect to the morphology and ecology of the earliest animals, we also need to know more about the environmental conditions that prevailed during the Neoproterozoic, and we need more fossils that can be confidently assigned to specific taxonomic groups", Wörheide says. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 8245, 922, 279, 86278, 71053, 2391, 902, 10099, 12164, 660, 1139, 872, 3682, 1207, 566, 3536, 374, 16996, 311, 8830, 4216, 10065, 72546, 323, 15740, 13, 19173, 11, 279, 864, 7813, 3042, 7414, 31376, 3335, 374, 34544, 323, 1202, 23692, 20733, 13, 6649, 52551, 31206, 55388, 5528, 3493, 459, 10778, 3445, 315, 77472, 279, 18912, 315, 83858, 52379, 5655, 304, 279, 2322, 41284, 276, 5021, 315, 2324, 13, 2100, 3117, 11, 17879, 31206, 9042, 7978, 21760, 11951, 389, 6344, 1394, 20103, 439, 264, 4459, 617, 1027, 3196, 389, 12309, 2678, 30525, 477, 33243, 13340, 315, 279, 1925, 2536, 1481, 91895, 1122, 1584, 1154, 320, 21470, 439, 274, 621, 4282, 323, 272, 2002, 5237, 4692, 705, 902, 527, 16188, 369, 8830, 4216, 2322, 41284, 276, 15740, 13, 5810, 11, 584, 1005, 264, 8767, 4756, 37555, 86945, 3151, 10550, 430, 5764, 264, 6762, 25936, 315, 682, 9959, 5315, 311, 16430, 279, 18912, 315, 4216, 10065, 15740, 449, 99234, 31467, 55388, 5528, 13, 10771, 311, 1057, 3135, 11, 682, 2536, 1481, 91895, 1122, 1343, 61822, 11, 439, 1664, 439, 2860, 4449, 39158, 29283, 11, 28995, 304, 459, 14154, 25407, 2391, 264, 3980, 30450, 12309, 2875, 892, 9575, 11, 1603, 279, 42080, 315, 1317, 9860, 3728, 80616, 17583, 27179, 63385, 4047, 9420, 66545, 4056, 13104, 4235, 22276, 11583, 570, 13516, 18007, 11, 420, 1121, 8111, 22514, 311, 61086, 315, 264, 1396, 315, 3062, 44064, 7482, 11, 1778, 439, 4211, 315, 4315, 8614, 425, 4478, 23851, 323, 7437, 315, 31376, 1652, 10892, 811, 1511, 13, 29438, 5751, 8830, 315, 279, 6371, 323, 15740, 315, 10099, 320, 35773, 1394, 20103, 8, 323, 872, 3682, 1207, 17171, 1053, 387, 19407, 82315, 555, 2731, 6677, 922, 279, 18912, 315, 21797, 2461, 4216, 304, 872, 3925, 13, 6344, 1394, 20103, 41095, 4330, 1925, 1584, 1154, 320, 4151, 423, 2319, 8892, 1036, 612, 468, 9603, 383, 579, 220, 16, 369, 264, 3477, 315, 872, 37555, 86945, 5411, 12135, 1680, 279, 1343, 61822, 20388, 333, 2473, 320, 82, 621, 4282, 705, 1856, 582, 9700, 20103, 320, 1183, 718, 56178, 710, 7026, 356, 2002, 5237, 6347, 320, 22631, 503, 616, 552, 705, 356, 58444, 10649, 320, 6133, 1147, 11, 52441, 18668, 11, 323, 872, 24890, 705, 323, 39158, 29283, 11, 279, 40487, 33885, 113305, 1912, 8649, 682, 279, 9861, 220, 966, 477, 779, 1343, 61822, 13, 7648, 10065, 1343, 61822, 5101, 304, 279, 31376, 3335, 304, 264, 12309, 2875, 4261, 2391, 279, 34896, 7414, 320, 22058, 4235, 19773, 3610, 1667, 4227, 510, 30635, 9918, 279, 779, 19434, 1054, 92596, 7414, 25176, 863, 220, 17, 1174, 220, 18, 1174, 220, 19, 662, 4452, 11, 1521, 34896, 7414, 81473, 2736, 31324, 6485, 27448, 9268, 11, 12899, 279, 4623, 430, 10099, 2011, 617, 28995, 1063, 892, 2391, 279, 1322, 466, 96614, 292, 320, 5154, 15, 4235, 22058, 11583, 570, 23150, 11, 433, 374, 1457, 13882, 7378, 430, 10099, 25281, 520, 3325, 2391, 279, 3010, 18094, 315, 279, 38846, 3279, 18029, 22026, 4261, 320, 22276, 4235, 22058, 11583, 705, 439, 69457, 555, 11917, 81473, 323, 1063, 2547, 81473, 449, 4461, 2322, 41284, 276, 3611, 258, 1385, 220, 20, 1174, 220, 21, 1174, 220, 22, 662, 19173, 11, 279, 9191, 31376, 3335, 374, 12309, 59290, 449, 5201, 311, 3284, 10099, 11, 323, 1455, 14955, 527, 1694, 20733, 398, 14407, 220, 23, 1174, 902, 29034, 15062, 304, 5006, 922, 279, 2780, 2617, 3115, 315, 279, 4330, 1925, 1584, 1154, 13, 15636, 11, 31206, 11091, 6043, 18843, 5848, 20414, 220, 24, 1174, 220, 605, 2643, 12576, 304, 75277, 287, 4216, 10065, 15740, 555, 3445, 315, 82258, 892, 42304, 505, 81064, 828, 315, 1327, 519, 9606, 320, 76, 43943, 9042, 7978, 570, 10541, 31206, 9042, 7978, 617, 8965, 7396, 264, 5655, 864, 12, 2782, 18029, 22026, 6371, 315, 10099, 323, 1690, 315, 1202, 3682, 1207, 17171, 220, 806, 1174, 220, 717, 1174, 220, 1032, 1174, 220, 975, 1174, 17989, 315, 279, 24473, 18912, 13592, 13882, 220, 23, 1174, 220, 868, 662, 23674, 11, 279, 8857, 315, 7978, 617, 10968, 3060, 389, 77472, 279, 3115, 2296, 315, 384, 3178, 661, 1295, 15740, 323, 8617, 2737, 1193, 2478, 10099, 439, 24005, 315, 1120, 832, 65009, 2949, 279, 10901, 380, 71, 564, 50514, 2307, 4166, 220, 1032, 1174, 220, 845, 1174, 477, 35906, 26445, 66107, 279, 2539, 20057, 315, 6344, 1394, 20103, 1606, 814, 1051, 14918, 8173, 304, 279, 15740, 315, 39158, 29283, 220, 975, 1174, 220, 1114, 662, 4452, 11, 57482, 77472, 279, 18912, 315, 4216, 2322, 41284, 276, 15740, 7612, 430, 682, 2536, 1481, 91895, 1122, 1584, 1154, 387, 49672, 15609, 13, 763, 264, 7701, 22628, 31206, 9042, 4007, 11, 9939, 7678, 1880, 453, 662, 220, 717, 5343, 264, 8205, 315, 2536, 1481, 91895, 5493, 1389, 220, 508, 274, 621, 4282, 11, 1183, 718, 56178, 710, 1174, 323, 4848, 13979, 307, 30627, 13, 4452, 11, 814, 1550, 539, 2997, 356, 2002, 5237, 6347, 323, 1193, 49976, 2380, 315, 279, 3116, 6989, 315, 20388, 333, 2473, 320, 20956, 533, 258, 616, 4849, 574, 28544, 570, 24296, 11, 279, 10550, 814, 1511, 369, 5029, 872, 12690, 374, 71561, 2678, 11, 1694, 24306, 315, 8668, 828, 505, 8254, 28896, 1193, 31857, 1049, 15, 42500, 13935, 10093, 570, 14636, 11, 279, 3135, 315, 9939, 7678, 1880, 453, 662, 220, 717, 7293, 311, 387, 12793, 449, 264, 810, 4686, 3827, 263, 25936, 323, 37555, 86945, 3151, 13230, 828, 13, 67954, 1880, 453, 662, 220, 972, 1511, 264, 220, 4386, 10039, 39340, 37555, 86945, 3151, 10550, 320, 966, 11, 15574, 42500, 13935, 10093, 8, 311, 44928, 10065, 37555, 848, 33495, 13, 1115, 10550, 5764, 682, 2536, 1481, 91895, 1122, 1343, 61822, 323, 6989, 11, 264, 4183, 6205, 315, 24005, 505, 682, 2380, 20934, 977, 1122, 2307, 17171, 320, 1951, 29051, 537, 316, 689, 11, 469, 4484, 88, 708, 13028, 64, 11, 445, 5237, 354, 299, 971, 13028, 64, 705, 439, 1664, 439, 264, 16578, 315, 2536, 1474, 295, 41284, 276, 1200, 380, 71, 564, 546, 82, 439, 704, 17171, 13, 75096, 264, 1664, 11849, 8905, 37555, 848, 33495, 11, 420, 10550, 8111, 1664, 32599, 369, 24834, 279, 18912, 315, 5655, 2322, 41284, 276, 37555, 848, 33495, 13, 4452, 11, 304, 31410, 31206, 9042, 7978, 35988, 420, 10550, 617, 8617, 3117, 1027, 32161, 13, 5810, 11, 584, 3118, 31206, 9042, 29060, 315, 279, 67954, 1880, 453, 662, 220, 972, 10550, 1234, 264, 8205, 315, 44064, 4787, 13, 5751, 3135, 7838, 3766, 31206, 55388, 17989, 315, 459, 4216, 1474, 307, 4275, 47026, 466, 96614, 292, 320, 70551, 1122, 26, 220, 1041, 15, 4235, 13104, 11583, 8, 6371, 315, 27631, 4449, 6344, 1394, 20103, 11, 1603, 279, 42080, 315, 1317, 65265, 3728, 80616, 17583, 11, 279, 800, 5757, 1122, 323, 89366, 276, 1054, 63385, 4047, 9420, 82, 863, 315, 279, 43805, 11968, 1122, 320, 13104, 4235, 22276, 11583, 220, 777, 1174, 220, 508, 1174, 220, 1691, 7609, 763, 13168, 311, 3766, 7978, 11, 4869, 11, 1057, 3135, 4284, 430, 539, 1193, 27631, 4449, 6344, 1394, 20103, 11, 719, 682, 2536, 1481, 91895, 1122, 1343, 61822, 320, 438, 520, 3325, 19646, 8614, 1154, 315, 682, 6989, 705, 439, 1664, 439, 2860, 4449, 39158, 29283, 11, 44853, 1603, 279, 800, 5757, 1122, 11, 4762, 2949, 264, 3980, 30450, 12309, 2875, 892, 9575, 13, 13516, 18007, 11, 420, 1925, 17102, 374, 22514, 311, 264, 1396, 315, 3682, 32946, 430, 649, 48863, 10383, 279, 15632, 315, 31206, 9042, 7978, 13, 19331, 1226, 13375, 264, 2134, 315, 31467, 31206, 55388, 29060, 1701, 279, 99234, 4488, 869, 29625, 46867, 58870, 320, 44, 10190, 34, 8, 8292, 93682, 385, 23407, 288, 220, 1313, 662, 763, 2015, 311, 8720, 279, 22514, 2136, 315, 1057, 4325, 17989, 311, 264, 1396, 315, 4972, 32946, 11, 584, 10837, 29060, 1234, 320, 16, 8, 459, 57253, 269, 9920, 323, 459, 653, 6133, 9920, 31467, 31206, 55388, 1646, 1389, 279, 4846, 26619, 430, 279, 4478, 315, 31206, 15740, 315, 264, 65009, 374, 49393, 449, 279, 4478, 315, 1202, 6691, 65009, 11, 279, 15629, 10923, 6724, 9678, 7969, 505, 65009, 311, 65009, 26, 320, 17, 8, 2380, 2204, 7437, 315, 31376, 1652, 10892, 811, 369, 5419, 7954, 1389, 832, 38178, 520, 264, 7340, 58321, 315, 1652, 10892, 811, 320, 2638, 362, 7026, 2500, 832, 44878, 1063, 13893, 20733, 81473, 320, 2638, 426, 7026, 323, 264, 4948, 832, 18306, 505, 9939, 7678, 1880, 453, 662, 220, 717, 320, 2638, 356, 7048, 320, 18, 8, 2204, 4972, 32946, 922, 279, 4325, 315, 279, 3789, 315, 279, 37555, 848, 33495, 39838, 8781, 315, 27631, 4449, 10901, 380, 71, 564, 50514, 8, 1389, 220, 4728, 11, 220, 1041, 15, 11, 323, 220, 9795, 15, 11583, 26, 323, 220, 19, 8, 2380, 2204, 10778, 32946, 922, 279, 37555, 86945, 5411, 22165, 315, 356, 2002, 5237, 6347, 320, 82, 1601, 311, 356, 58444, 10649, 11, 13219, 128257, 198, 128256, 78191, 198, 791, 2926, 35530, 315, 10065, 15740, 45374, 10819, 1109, 305, 411, 14200, 10171, 25, 1561, 29060, 4284, 430, 279, 1176, 10065, 1343, 61822, 22763, 304, 11295, 50787, 1389, 4972, 311, 279, 3728, 20534, 13381, 430, 743, 304, 2212, 220, 7007, 3610, 1667, 4227, 13, 578, 31376, 3335, 21667, 430, 4661, 682, 315, 279, 10065, 1343, 61822, 3967, 3432, 1047, 2586, 1139, 14209, 555, 279, 7314, 315, 279, 34896, 7414, 26572, 1063, 220, 17048, 3610, 1667, 4227, 13, 578, 30758, 3967, 10065, 81473, 2736, 31324, 6485, 27448, 9268, 11, 902, 24897, 430, 10099, 2011, 617, 44853, 1317, 1603, 279, 42080, 315, 279, 34896, 7414, 13, 4452, 11, 3827, 14609, 2740, 90547, 81473, 430, 649, 387, 78076, 30105, 311, 864, 7813, 3042, 7414, 3115, 527, 1633, 9024, 13, 763, 2015, 311, 8417, 1148, 279, 3789, 315, 872, 3070, 5021, 7111, 1093, 11, 6160, 22012, 1205, 15062, 5029, 2038, 369, 279, 1455, 14154, 10065, 1207, 17171, 1389, 279, 274, 621, 4282, 11, 13979, 307, 30627, 11, 3698, 503, 616, 552, 323, 29960, 96614, 598, 13, 2999, 13, 11826, 423, 2319, 8892, 1036, 323, 17054, 480, 531, 468, 9603, 383, 579, 315, 279, 14829, 315, 11165, 6043, 63333, 323, 4323, 18843, 2508, 304, 279, 6011, 315, 9420, 323, 25027, 23199, 520, 47514, 52, 47304, 617, 1457, 1511, 264, 502, 8446, 3196, 389, 279, 779, 19434, 31206, 55388, 311, 19874, 279, 27076, 2508, 315, 4216, 10065, 15740, 323, 8356, 264, 502, 16430, 369, 279, 17051, 315, 279, 24417, 10065, 5315, 13, 11205, 14955, 5101, 304, 279, 8486, 38130, 29140, 13, 578, 31206, 9042, 5603, 374, 3196, 389, 279, 17966, 430, 34684, 47376, 304, 279, 85381, 315, 682, 44304, 927, 279, 3388, 315, 892, 13, 578, 13112, 315, 279, 19465, 6811, 1990, 1403, 1584, 1154, 1288, 9093, 6904, 389, 279, 892, 26401, 2533, 814, 37441, 3640, 505, 872, 1566, 4279, 46831, 13, 330, 8140, 4007, 374, 3196, 389, 264, 10824, 315, 19465, 828, 505, 19225, 10099, 323, 2038, 14592, 505, 1664, 30105, 81473, 11, 902, 584, 30239, 449, 279, 1520, 315, 6485, 6500, 26249, 1359, 423, 2319, 8892, 1036, 15100, 13, 1789, 279, 4007, 11, 279, 12074, 1511, 459, 57899, 3544, 10550, 1903, 709, 315, 279, 24630, 315, 220, 4386, 28896, 505, 220, 2131, 9606, 11, 2737, 24005, 315, 682, 279, 3682, 10065, 5315, 11, 21760, 304, 4040, 389, 1884, 430, 37441, 3640, 1633, 4216, 13, 578, 6492, 43496, 279, 17102, 8813, 304, 459, 6931, 4007, 11, 902, 30105, 279, 6371, 315, 10099, 311, 279, 4275, 47026, 466, 96614, 292, 48688, 11, 902, 36513, 505, 220, 1041, 15, 311, 220, 17048, 3610, 1667, 4227, 13, 4452, 11, 1790, 311, 872, 13051, 11, 279, 3135, 1101, 12090, 430, 279, 30758, 1343, 61822, 11, 323, 279, 38618, 315, 682, 52303, 10065, 9606, 320, 1820, 779, 19434, 39158, 29283, 705, 44853, 2949, 279, 1389, 3980, 30450, 12365, 1389, 2875, 892, 65160, 315, 220, 1135, 3610, 1667, 13, 330, 644, 5369, 11, 420, 4216, 10474, 315, 41993, 82258, 8111, 311, 617, 53580, 279, 14560, 10182, 4442, 430, 6197, 311, 19435, 4047, 9420, 11, 264, 4261, 13160, 555, 15748, 1317, 9860, 3728, 80616, 7246, 430, 36513, 505, 922, 220, 13104, 311, 220, 22276, 3610, 1667, 4227, 1359, 423, 2319, 8892, 1036, 2795, 13, 763, 2015, 311, 8720, 279, 628, 12119, 3225, 315, 279, 502, 14955, 11, 279, 12074, 3197, 311, 6920, 704, 4726, 29060, 1701, 810, 16781, 30525, 323, 13241, 29564, 5528, 1210, 2057, 17782, 520, 1664, 83208, 31342, 449, 5201, 311, 279, 79612, 323, 72546, 315, 279, 30758, 10099, 11, 584, 1101, 1205, 311, 1440, 810, 922, 279, 12434, 4787, 430, 85814, 2391, 279, 4275, 47026, 466, 96614, 292, 11, 323, 584, 1205, 810, 81473, 430, 649, 387, 78076, 12893, 311, 3230, 3827, 48228, 5315, 498, 468, 9603, 383, 579, 2795, 13, 220, 128257, 198 ]

2,110

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Scientists’ research interests are often skewed toward charismatic organisms, but quantifying research biases is challenging. By combining bibliometric data with trait-based approaches and using a well-studied alpine flora as a case study, we demonstrate that morphological and colour traits, as well as range size, have significantly more impact on species choice for wild flowering plants than traits related to ecology and rarity. These biases should be taken into account to inform more objective plant conservation efforts. Main Throughout human history, plants have played the role of silent partners in the growth of virtually every civilization 1 . Humans have exploited wild plants and crops as sources of food 2 , used trees as combustible material and to craft manufactured goods 1 , 3 and taken inspiration from the beauty of flowers for poetic and artistic endeavours 4 , 5 . Since the birth of modern science, plants have also become the subjects of intense investigation. As scientists systematically studied the natural history of plants 6 , they soon realized that many of these species could function as model organisms to address fundamental scientific questions 7 . Edward O. Wilson famously stated that ‘[…] for every scientific question, there is the ideal study system to test it’ and thus, the choice of a researcher to study one species or another is often driven by functional criteria (for example, ploidy level for genetics studies and ease of growth under controlled conditions). Still, outside of the laboratory or the greenhouse, field scientists may be challenged in their choice of focus organisms by concerns that exceed strictly scientific research interests. As a result, when plant scientists select to study a specific wild plant among the pool of species available in a given study region, it may be that factors unrelated to the biological question end up influencing species choice and introducing biases in the research outcome. Whereas this is not a problem per se, a disparity in scientific attention towards certain species may become a concern in conservation biology, where it is paramount to ensure a ‘level playing field’ in selecting conservation priorities 8 , 9 . Given their global diversity 10 and ecological importance 11 , 12 , plants should be prominent in conservation biology’s effort to curb species loss under mounting anthropogenic pressures 13 , 14 , 15 . Yet, it is well documented that plants receive less attention and consequently less funding in conservation than do animals 16 , 17 . This particular case of taxonomic bias has been connected to ‘plant blindness’ 18 or ‘plant awareness disparity’ 19 , two terms proposed to indicate the lack of awareness for plants. Associated with both the evolutionary history of human cognition and the effect of cultural, scientific and educational tendencies, this disparity translates into serious real-life impacts, as it affects the knowledge base of conservation and its policies. As addressing this bias is urgent but also often outside the scope of plant sciences, we want to identify more specific biases that can be addressed from within the scientific community dedicated to plants, thereby informing better research practices. With this goal in mind, we chose a well-defined case study in which to consider specific traits and factors that could influence the choice of species studied. By combining the strengths of bibliometrics and trait-based approaches, we asked what kind of biases might operate in plant sciences, resulting in some species being more studied than others. To resolve this question, we chose a model system of 113 species typical of the Southwestern Alps, one of the largest biodiversity hotspots within the Mediterranean region 20 (Fig. 1a ). By focusing on a well-known flora in a delimited area, this study design allowed us to control for several confounding factors related to sampling biases, trait heterogeneity and research interest. Fig. 1: Study workflow and most important factors in explaining research interest. a , Schematic representation of the data collection and the subdivision of the plant traits in three categories of ecology, morphology and rarity. b , Outcomes of the variance partitioning analysis, whereby the relative contribution of traits related to ecology, morphology and rarity is ruled out, as well as the random effect of species’ taxonomic relatedness at family level. T°, temperature. Full size image We tested whether there is a relationship between research focus on a plant species (measured using bibliometric indicators) and species-specific traits related to ecology, morphology and rarity (Fig. 1a ). In the Web of Science, we sourced 280 papers focusing on the selected plant species (average (±s.d.) of 2.15 ± 2.96 scientific papers per plant), published between 1975 and 2020. Given that the number of publications, their average annual number of citations and average h -index were all reciprocally correlated (all Pearson’s r > 0.7; Supplementary Fig. 1 ), we expressed research attention simply as the total number of publications. By means of variance partitioning analysis 21 , we ruled out the relative contribution of ecology, morphology and rarity in determining the observed pattern of research attention. This analysis indicated how the choice of investigated species across the literature in the last 45 years has been strongly influenced by plant traits related to aesthetics. Using marginal R 2 , we observed how morphological and colour traits explain the greater proportion of variance (15.0%), whereas the contribution of ecology and rarity was negligible (Fig. 1b ). However, 75.6% of model variance remained unexplained. When reassessing variance partitioning using conditional R 2 , which describe the proportion of variance explained by both fixed effect and random factors (species taxonomic relatedness), we found that 54% of unexplained variance was due to the random effect. This reveals that certain clusters of closely related plants are more studied than others and share more similar traits than expected from a random pool (examples in Fig. 2a ). Fig. 2: Regression analysis of plant traits. a , Example of representative plant species with different traits and research attention: Gentiana ligustica R. Vilm. & Chopinet (Gentianaceae, blue inflorescence and", "role": "user" }, { "content": "New Curtin University research has found a bias among scientists toward colourful and visually striking plants, means they are more likely to be chosen for scientific study and benefit from subsequent conservation efforts, regardless of their ecological importance. Co-author John Curtin Distinguished Professor Kingsley Dixon from Curtin's School of Molecular and Life Sciences was part of an international team that looked for evidence of an aesthetic bias among scientists by analysing 113 plant species found in global biodiversity hotspot the Southwestern Alps and mentioned in 280 research papers published between 1975 and 2020. Professor Dixon said the study tested whether there was a relationship between research focus on plant species and characteristics such as the colour, shape and prominence of species. \"We found flowers that were accessible and conspicuous were among those that were most studied, while colour also played a big role,\" Professor Dixon said. \"Blue plants, which are relatively rare, received the most research attention and white, red and pink flowers were more likely to feature in research literature than green and brown plants. \"Stem height, which determines a plant's ability to stand out among others, was also a contributing factor, while the rarity of a plant did not significantly influence research attention.\" Professor Dixon said plant traits such as colour and prominence were not indicators of their ecological significance, and so the 'attractiveness bias' could divert important research attention away from more deserving species. \"This bias may have the negative consequence of steering conservation efforts away from plants that, while less visually pleasing, are more important to the health of overall ecosystems,\" Professor Dixon said. \"Our study shows the need to take aesthetic biases more explicitly into consideration in experimental design and choice of species studied, to ensure the best conservation and ecological outcomes.\" The full paper, \"Plant scientists research attention is skewed towards colorful, conspicuous, and broadly distributed flowers\" was published in Nature Plants. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Scientists’ research interests are often skewed toward charismatic organisms, but quantifying research biases is challenging. By combining bibliometric data with trait-based approaches and using a well-studied alpine flora as a case study, we demonstrate that morphological and colour traits, as well as range size, have significantly more impact on species choice for wild flowering plants than traits related to ecology and rarity. These biases should be taken into account to inform more objective plant conservation efforts. Main Throughout human history, plants have played the role of silent partners in the growth of virtually every civilization 1 . Humans have exploited wild plants and crops as sources of food 2 , used trees as combustible material and to craft manufactured goods 1 , 3 and taken inspiration from the beauty of flowers for poetic and artistic endeavours 4 , 5 . Since the birth of modern science, plants have also become the subjects of intense investigation. As scientists systematically studied the natural history of plants 6 , they soon realized that many of these species could function as model organisms to address fundamental scientific questions 7 . Edward O. Wilson famously stated that ‘[…] for every scientific question, there is the ideal study system to test it’ and thus, the choice of a researcher to study one species or another is often driven by functional criteria (for example, ploidy level for genetics studies and ease of growth under controlled conditions). Still, outside of the laboratory or the greenhouse, field scientists may be challenged in their choice of focus organisms by concerns that exceed strictly scientific research interests. As a result, when plant scientists select to study a specific wild plant among the pool of species available in a given study region, it may be that factors unrelated to the biological question end up influencing species choice and introducing biases in the research outcome. Whereas this is not a problem per se, a disparity in scientific attention towards certain species may become a concern in conservation biology, where it is paramount to ensure a ‘level playing field’ in selecting conservation priorities 8 , 9 . Given their global diversity 10 and ecological importance 11 , 12 , plants should be prominent in conservation biology’s effort to curb species loss under mounting anthropogenic pressures 13 , 14 , 15 . Yet, it is well documented that plants receive less attention and consequently less funding in conservation than do animals 16 , 17 . This particular case of taxonomic bias has been connected to ‘plant blindness’ 18 or ‘plant awareness disparity’ 19 , two terms proposed to indicate the lack of awareness for plants. Associated with both the evolutionary history of human cognition and the effect of cultural, scientific and educational tendencies, this disparity translates into serious real-life impacts, as it affects the knowledge base of conservation and its policies. As addressing this bias is urgent but also often outside the scope of plant sciences, we want to identify more specific biases that can be addressed from within the scientific community dedicated to plants, thereby informing better research practices. With this goal in mind, we chose a well-defined case study in which to consider specific traits and factors that could influence the choice of species studied. By combining the strengths of bibliometrics and trait-based approaches, we asked what kind of biases might operate in plant sciences, resulting in some species being more studied than others. To resolve this question, we chose a model system of 113 species typical of the Southwestern Alps, one of the largest biodiversity hotspots within the Mediterranean region 20 (Fig. 1a ). By focusing on a well-known flora in a delimited area, this study design allowed us to control for several confounding factors related to sampling biases, trait heterogeneity and research interest. Fig. 1: Study workflow and most important factors in explaining research interest. a , Schematic representation of the data collection and the subdivision of the plant traits in three categories of ecology, morphology and rarity. b , Outcomes of the variance partitioning analysis, whereby the relative contribution of traits related to ecology, morphology and rarity is ruled out, as well as the random effect of species’ taxonomic relatedness at family level. T°, temperature. Full size image We tested whether there is a relationship between research focus on a plant species (measured using bibliometric indicators) and species-specific traits related to ecology, morphology and rarity (Fig. 1a ). In the Web of Science, we sourced 280 papers focusing on the selected plant species (average (±s.d.) of 2.15 ± 2.96 scientific papers per plant), published between 1975 and 2020. Given that the number of publications, their average annual number of citations and average h -index were all reciprocally correlated (all Pearson’s r > 0.7; Supplementary Fig. 1 ), we expressed research attention simply as the total number of publications. By means of variance partitioning analysis 21 , we ruled out the relative contribution of ecology, morphology and rarity in determining the observed pattern of research attention. This analysis indicated how the choice of investigated species across the literature in the last 45 years has been strongly influenced by plant traits related to aesthetics. Using marginal R 2 , we observed how morphological and colour traits explain the greater proportion of variance (15.0%), whereas the contribution of ecology and rarity was negligible (Fig. 1b ). However, 75.6% of model variance remained unexplained. When reassessing variance partitioning using conditional R 2 , which describe the proportion of variance explained by both fixed effect and random factors (species taxonomic relatedness), we found that 54% of unexplained variance was due to the random effect. This reveals that certain clusters of closely related plants are more studied than others and share more similar traits than expected from a random pool (examples in Fig. 2a ). Fig. 2: Regression analysis of plant traits. a , Example of representative plant species with different traits and research attention: Gentiana ligustica R. Vilm. & Chopinet (Gentianaceae, blue inflorescence and<|im_end|> <|im_start|>assistant New Curtin University research has found a bias among scientists toward colourful and visually striking plants, means they are more likely to be chosen for scientific study and benefit from subsequent conservation efforts, regardless of their ecological importance. Co-author John Curtin Distinguished Professor Kingsley Dixon from Curtin's School of Molecular and Life Sciences was part of an international team that looked for evidence of an aesthetic bias among scientists by analysing 113 plant species found in global biodiversity hotspot the Southwestern Alps and mentioned in 280 research papers published between 1975 and 2020. Professor Dixon said the study tested whether there was a relationship between research focus on plant species and characteristics such as the colour, shape and prominence of species. "We found flowers that were accessible and conspicuous were among those that were most studied, while colour also played a big role," Professor Dixon said. "Blue plants, which are relatively rare, received the most research attention and white, red and pink flowers were more likely to feature in research literature than green and brown plants. "Stem height, which determines a plant's ability to stand out among others, was also a contributing factor, while the rarity of a plant did not significantly influence research attention." Professor Dixon said plant traits such as colour and prominence were not indicators of their ecological significance, and so the 'attractiveness bias' could divert important research attention away from more deserving species. "This bias may have the negative consequence of steering conservation efforts away from plants that, while less visually pleasing, are more important to the health of overall ecosystems," Professor Dixon said. "Our study shows the need to take aesthetic biases more explicitly into consideration in experimental design and choice of species studied, to ensure the best conservation and ecological outcomes." The full paper, "Plant scientists research attention is skewed towards colorful, conspicuous, and broadly distributed flowers" was published in Nature Plants. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 57116, 529, 3495, 12034, 527, 3629, 87572, 9017, 79323, 44304, 11, 719, 10484, 7922, 3495, 50183, 374, 17436, 13, 3296, 35271, 44615, 24264, 828, 449, 18027, 6108, 20414, 323, 1701, 264, 1664, 5594, 664, 1142, 453, 39138, 82088, 439, 264, 1162, 4007, 11, 584, 20461, 430, 27448, 5848, 323, 12745, 25022, 11, 439, 1664, 439, 2134, 1404, 11, 617, 12207, 810, 5536, 389, 9606, 5873, 369, 8545, 82339, 11012, 1109, 25022, 5552, 311, 72546, 323, 59871, 13, 4314, 50183, 1288, 387, 4529, 1139, 2759, 311, 6179, 810, 16945, 6136, 29711, 9045, 13, 4802, 46982, 3823, 3925, 11, 11012, 617, 6476, 279, 3560, 315, 21737, 8717, 304, 279, 6650, 315, 21907, 1475, 36017, 220, 16, 662, 66094, 617, 51763, 8545, 11012, 323, 31665, 439, 8336, 315, 3691, 220, 17, 1174, 1511, 12690, 439, 44545, 1260, 3769, 323, 311, 11003, 28648, 11822, 220, 16, 1174, 220, 18, 323, 4529, 20343, 505, 279, 13444, 315, 19837, 369, 76534, 323, 32692, 29705, 402, 2530, 220, 19, 1174, 220, 20, 662, 8876, 279, 7342, 315, 6617, 8198, 11, 11012, 617, 1101, 3719, 279, 15223, 315, 19428, 8990, 13, 1666, 14248, 60826, 20041, 279, 5933, 3925, 315, 11012, 220, 21, 1174, 814, 5246, 15393, 430, 1690, 315, 1521, 9606, 1436, 734, 439, 1646, 44304, 311, 2686, 16188, 12624, 4860, 220, 22, 662, 22653, 507, 13, 17882, 51287, 11224, 430, 3451, 96332, 369, 1475, 12624, 3488, 11, 1070, 374, 279, 10728, 4007, 1887, 311, 1296, 433, 529, 323, 8617, 11, 279, 5873, 315, 264, 32185, 311, 4007, 832, 9606, 477, 2500, 374, 3629, 16625, 555, 16003, 13186, 320, 2000, 3187, 11, 113042, 43686, 2237, 369, 56104, 7978, 323, 14553, 315, 6650, 1234, 14400, 4787, 570, 16782, 11, 4994, 315, 279, 27692, 477, 279, 37647, 11, 2115, 14248, 1253, 387, 29991, 304, 872, 5873, 315, 5357, 44304, 555, 10742, 430, 12771, 26549, 12624, 3495, 12034, 13, 1666, 264, 1121, 11, 994, 6136, 14248, 3373, 311, 4007, 264, 3230, 8545, 6136, 4315, 279, 7463, 315, 9606, 2561, 304, 264, 2728, 4007, 5654, 11, 433, 1253, 387, 430, 9547, 46305, 311, 279, 24156, 3488, 842, 709, 66700, 9606, 5873, 323, 33018, 50183, 304, 279, 3495, 15632, 13, 61695, 420, 374, 539, 264, 3575, 824, 513, 11, 264, 66949, 304, 12624, 6666, 7119, 3738, 9606, 1253, 3719, 264, 4747, 304, 29711, 34458, 11, 1405, 433, 374, 74510, 311, 6106, 264, 3451, 3374, 5737, 2115, 529, 304, 27397, 29711, 30601, 220, 23, 1174, 220, 24, 662, 16644, 872, 3728, 20057, 220, 605, 323, 50953, 12939, 220, 806, 1174, 220, 717, 1174, 11012, 1288, 387, 21102, 304, 29711, 34458, 753, 5149, 311, 44962, 9606, 4814, 1234, 34739, 41416, 29569, 40850, 220, 1032, 1174, 220, 975, 1174, 220, 868, 662, 14968, 11, 433, 374, 1664, 27470, 430, 11012, 5371, 2753, 6666, 323, 52394, 2753, 11006, 304, 29711, 1109, 656, 10099, 220, 845, 1174, 220, 1114, 662, 1115, 4040, 1162, 315, 3827, 48228, 15837, 706, 1027, 8599, 311, 3451, 21494, 85515, 529, 220, 972, 477, 3451, 21494, 17985, 66949, 529, 220, 777, 1174, 1403, 3878, 11223, 311, 13519, 279, 6996, 315, 17985, 369, 11012, 13, 26475, 449, 2225, 279, 41993, 3925, 315, 3823, 75310, 323, 279, 2515, 315, 13042, 11, 12624, 323, 16627, 61555, 11, 420, 66949, 48018, 1139, 6129, 1972, 26928, 25949, 11, 439, 433, 22223, 279, 6677, 2385, 315, 29711, 323, 1202, 10396, 13, 1666, 28118, 420, 15837, 374, 34771, 719, 1101, 3629, 4994, 279, 7036, 315, 6136, 36788, 11, 584, 1390, 311, 10765, 810, 3230, 50183, 430, 649, 387, 20669, 505, 2949, 279, 12624, 4029, 12514, 311, 11012, 11, 28592, 63025, 2731, 3495, 12659, 13, 3161, 420, 5915, 304, 4059, 11, 584, 14896, 264, 1664, 39817, 1162, 4007, 304, 902, 311, 2980, 3230, 25022, 323, 9547, 430, 1436, 10383, 279, 5873, 315, 9606, 20041, 13, 3296, 35271, 279, 36486, 315, 44615, 92891, 323, 18027, 6108, 20414, 11, 584, 4691, 1148, 3169, 315, 50183, 2643, 14816, 304, 6136, 36788, 11, 13239, 304, 1063, 9606, 1694, 810, 20041, 1109, 3885, 13, 2057, 9006, 420, 3488, 11, 584, 14896, 264, 1646, 1887, 315, 220, 8190, 9606, 14595, 315, 279, 4987, 31382, 94000, 11, 832, 315, 279, 7928, 73119, 4106, 68110, 2949, 279, 38785, 5654, 220, 508, 320, 30035, 13, 220, 16, 64, 7609, 3296, 21760, 389, 264, 1664, 22015, 82088, 304, 264, 86428, 3158, 11, 420, 4007, 2955, 5535, 603, 311, 2585, 369, 3892, 2389, 13900, 9547, 5552, 311, 25936, 50183, 11, 18027, 30548, 76730, 323, 3495, 2802, 13, 23966, 13, 220, 16, 25, 19723, 29388, 323, 1455, 3062, 9547, 304, 26073, 3495, 2802, 13, 264, 1174, 328, 82149, 13340, 315, 279, 828, 4526, 323, 279, 60922, 315, 279, 6136, 25022, 304, 2380, 11306, 315, 72546, 11, 79612, 323, 59871, 13, 293, 1174, 4470, 6716, 315, 279, 33373, 17071, 287, 6492, 11, 49001, 279, 8844, 19035, 315, 25022, 5552, 311, 72546, 11, 79612, 323, 59871, 374, 21989, 704, 11, 439, 1664, 439, 279, 4288, 2515, 315, 9606, 529, 3827, 48228, 5552, 2136, 520, 3070, 2237, 13, 350, 11877, 11, 9499, 13, 8797, 1404, 2217, 1226, 12793, 3508, 1070, 374, 264, 5133, 1990, 3495, 5357, 389, 264, 6136, 9606, 320, 2727, 40412, 1701, 44615, 24264, 34824, 8, 323, 9606, 19440, 25022, 5552, 311, 72546, 11, 79612, 323, 59871, 320, 30035, 13, 220, 16, 64, 7609, 763, 279, 5000, 315, 10170, 11, 584, 42211, 220, 11209, 16064, 21760, 389, 279, 4183, 6136, 9606, 320, 17645, 320, 38121, 82, 962, 6266, 315, 220, 17, 13, 868, 20903, 220, 17, 13, 4161, 12624, 16064, 824, 6136, 705, 4756, 1990, 220, 4468, 20, 323, 220, 2366, 15, 13, 16644, 430, 279, 1396, 315, 29085, 11, 872, 5578, 9974, 1396, 315, 52946, 323, 5578, 305, 482, 1275, 1051, 682, 25455, 28787, 750, 49393, 320, 543, 59642, 753, 436, 871, 220, 15, 13, 22, 26, 99371, 23966, 13, 220, 16, 7026, 584, 13605, 3495, 6666, 5042, 439, 279, 2860, 1396, 315, 29085, 13, 3296, 3445, 315, 33373, 17071, 287, 6492, 220, 1691, 1174, 584, 21989, 704, 279, 8844, 19035, 315, 72546, 11, 79612, 323, 59871, 304, 26679, 279, 13468, 5497, 315, 3495, 6666, 13, 1115, 6492, 16717, 1268, 279, 5873, 315, 27313, 9606, 4028, 279, 17649, 304, 279, 1566, 220, 1774, 1667, 706, 1027, 16917, 28160, 555, 6136, 25022, 5552, 311, 67323, 13, 12362, 32873, 432, 220, 17, 1174, 584, 13468, 1268, 27448, 5848, 323, 12745, 25022, 10552, 279, 7191, 21801, 315, 33373, 320, 868, 13, 15, 34971, 20444, 279, 19035, 315, 72546, 323, 59871, 574, 82802, 320, 30035, 13, 220, 16, 65, 7609, 4452, 11, 220, 2075, 13, 21, 4, 315, 1646, 33373, 14958, 653, 81950, 13, 3277, 32834, 434, 287, 33373, 17071, 287, 1701, 35787, 432, 220, 17, 1174, 902, 7664, 279, 21801, 315, 33373, 11497, 555, 2225, 8521, 2515, 323, 4288, 9547, 320, 43590, 3827, 48228, 5552, 2136, 705, 584, 1766, 430, 220, 4370, 4, 315, 653, 81950, 33373, 574, 4245, 311, 279, 4288, 2515, 13, 1115, 21667, 430, 3738, 28066, 315, 15499, 5552, 11012, 527, 810, 20041, 1109, 3885, 323, 4430, 810, 4528, 25022, 1109, 3685, 505, 264, 4288, 7463, 320, 52768, 304, 23966, 13, 220, 17, 64, 7609, 23966, 13, 220, 17, 25, 48570, 6492, 315, 6136, 25022, 13, 264, 1174, 13688, 315, 18740, 6136, 9606, 449, 2204, 25022, 323, 3495, 6666, 25, 36823, 12699, 29413, 592, 3074, 432, 13, 650, 9672, 13, 612, 65097, 30976, 320, 38, 306, 1122, 114785, 11, 6437, 4225, 385, 417, 36634, 323, 128257, 198, 128256, 78191, 198, 3648, 31523, 258, 3907, 3495, 706, 1766, 264, 15837, 4315, 14248, 9017, 70467, 323, 43395, 21933, 11012, 11, 3445, 814, 527, 810, 4461, 311, 387, 12146, 369, 12624, 4007, 323, 8935, 505, 17876, 29711, 9045, 11, 15851, 315, 872, 50953, 12939, 13, 3623, 43802, 3842, 31523, 258, 423, 80382, 17054, 24980, 3258, 64795, 505, 31523, 258, 596, 6150, 315, 60825, 323, 9601, 23199, 574, 961, 315, 459, 6625, 2128, 430, 7111, 369, 6029, 315, 459, 37637, 15837, 4315, 14248, 555, 22209, 287, 220, 8190, 6136, 9606, 1766, 304, 3728, 73119, 80310, 279, 4987, 31382, 94000, 323, 9932, 304, 220, 11209, 3495, 16064, 4756, 1990, 220, 4468, 20, 323, 220, 2366, 15, 13, 17054, 64795, 1071, 279, 4007, 12793, 3508, 1070, 574, 264, 5133, 1990, 3495, 5357, 389, 6136, 9606, 323, 17910, 1778, 439, 279, 12745, 11, 6211, 323, 71199, 315, 9606, 13, 330, 1687, 1766, 19837, 430, 1051, 15987, 323, 97985, 1051, 4315, 1884, 430, 1051, 1455, 20041, 11, 1418, 12745, 1101, 6476, 264, 2466, 3560, 1359, 17054, 64795, 1071, 13, 330, 10544, 11012, 11, 902, 527, 12309, 9024, 11, 4036, 279, 1455, 3495, 6666, 323, 4251, 11, 2579, 323, 18718, 19837, 1051, 810, 4461, 311, 4668, 304, 3495, 17649, 1109, 6307, 323, 14198, 11012, 13, 330, 626, 336, 2673, 11, 902, 27667, 264, 6136, 596, 5845, 311, 2559, 704, 4315, 3885, 11, 574, 1101, 264, 29820, 8331, 11, 1418, 279, 59871, 315, 264, 6136, 1550, 539, 12207, 10383, 3495, 6666, 1210, 17054, 64795, 1071, 6136, 25022, 1778, 439, 12745, 323, 71199, 1051, 539, 34824, 315, 872, 50953, 26431, 11, 323, 779, 279, 364, 266, 2193, 13071, 15837, 6, 1436, 37098, 3062, 3495, 6666, 3201, 505, 810, 76554, 9606, 13, 330, 2028, 15837, 1253, 617, 279, 8389, 29774, 315, 33277, 29711, 9045, 3201, 505, 11012, 430, 11, 1418, 2753, 43395, 54799, 11, 527, 810, 3062, 311, 279, 2890, 315, 8244, 61951, 1359, 17054, 64795, 1071, 13, 330, 8140, 4007, 5039, 279, 1205, 311, 1935, 37637, 50183, 810, 21650, 1139, 18361, 304, 22772, 2955, 323, 5873, 315, 9606, 20041, 11, 311, 6106, 279, 1888, 29711, 323, 50953, 20124, 1210, 578, 2539, 5684, 11, 330, 55747, 14248, 3495, 6666, 374, 87572, 7119, 34966, 11, 97985, 11, 323, 44029, 4332, 19837, 1, 574, 4756, 304, 22037, 50298, 13, 220, 128257, 198 ]

1,638

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Solution processing is a promising route for the realization of low-cost, large-area, flexible and lightweight photovoltaic devices with short energy payback time and high specific power. However, solar cells based on solution-processed organic, inorganic and hybrid materials reported thus far generally suffer from poor air stability, require an inert-atmosphere processing environment or necessitate high-temperature processing 1 , all of which increase manufacturing complexities and costs. Simultaneously fulfilling the goals of high efficiency, low-temperature fabrication conditions and good atmospheric stability remains a major technical challenge, which may be addressed, as we demonstrate here, with the development of room-temperature solution-processed ZnO/PbS quantum dot solar cells. By engineering the band alignment of the quantum dot layers through the use of different ligand treatments, a certified efficiency of 8.55% has been reached. Furthermore, the performance of unencapsulated devices remains unchanged for over 150 days of storage in air. This material system introduces a new approach towards the goal of high-performance air-stable solar cells compatible with simple solution processes and deposition on flexible substrates. Main Near-infrared PbS quantum dots (QDs) composed of earth-abundant elements 2 have emerged as promising candidates for photovoltaic applications because of a tunable energy bandgap that covers the optimal bandgap range for single and multi-junction solar cells 1 . The QD surface ligands 3 , 4 , 5 , 6 , 7 and the photovoltaic device architecture 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 play crucial roles in determining the optoelectronic properties of QD solar cells. Advances in QD surface passivation, particularly through the use of halide ions as inorganic ligands 4 , have led to rapid improvements in QD solar cell power conversion efficiencies to 7% 5 , 15 , 16 as a result of a lower density of trapped carriers than in their organic ligands counterparts 4 . Furthermore, recent studies have demonstrated the ability to control the band edge energies of QD films through ligand exchange 18 , 19 , 20 . However, fabrication of these recent QD devices requires high-temperature annealing (>500 °C) of the TiO 2 window layer 5 , 16 or two different processing atmospheres, including an inert gas environment 15 . Although good stability has been claimed, the devices still show performance degradation to ~85% of their original efficiencies within one week, even under inert atmosphere 5 , 16 . Here, we demonstrate ZnO/PbS solar cells in which the PbS QD and ZnO nanocrystals are both solution-processed in air and at room temperature. We demonstrate a device architecture that employs layers of QDs treated with different ligands for different functions by tuning their relative band alignment—a layer of inorganic-ligand-passivated QDs serves as the main light-absorbing layer and a layer of organic-ligand-passivated QDs serves as an electron-blocking/hole-extraction layer. The devices show significant improvements in power conversion efficiency and long-term air stability, compared with previously reported devices. Figure 1a shows the schematics of the device structures employed in this work. Oleic-acid-capped PbS QDs with the first exciton absorption peak at λ = 901 nm in solution ( Supplementary Fig. 1 ) are used to fabricate the thin films. Tetrabutylammonium iodide (TBAI) and 1,2-ethanedithiol (EDT) are used as the inorganic and organic ligands for solid-state ligand exchange. After solid-state ligand exchange, the first exciton absorption peak shifts to λ ~ 935 nm, which corresponds to an optical bandgap E g = 1.33 eV. We find that PbS QD films treated with TBAI (PbS-TBAI) exhibit superior air stability compared with PbS QDs treated with EDT (PbS-EDT; Supplementary Fig. 2 ). PbS-TBAI-only devices also show a higher short-circuit current density ( J SC ), whereas PbS-EDT-only devices show a higher open circuit voltage ( V OC ; Supplementary Fig. 3 ). Figure 1: Photovoltaic device architectures and performance. a , Device architectures. b , Representative J – V characteristics of devices with Au anodes under simulated AM1.5G irradiation (100 mW cm −2 ). The PbS-TBAI device consists of 12 layers of PbS-TBAI and the PbS-TBAI/PbS-EDT device consists of 10 layers of PbS-TBAI and 2 layers of PbS-EDT. c , External quantum efficiency (EQE) spectra for the same devices. Full size image The J – V characteristics of photovoltaic devices with Au anodes are shown in Fig. 1b . The device consisting of 12 PbS-TBAI layers (corresponding to a film thickness of ~220 nm) shows a power conversion efficiency of 6.0 ± 0.4%, which is higher than the previously reported TiO 2 /PbS-TBAI devices consisting of PbS QDs with an additional solution phase CdCl 2 treatment and MoO 3 /Au/Ag anode 4 . Although PbS-EDT-only devices show a lower J SC than PbS-TBAI-only devices, replacing the topmost two PbS-TBAI layers with two PbS-EDT layers significantly improves the J SC , V OC and fill factor (FF), resulting in a ~35% improvement in power conversion efficiency to 8.2 ± 0.6%, with a 9.2% lab-champion device ( Table 1 ). Table 1 Solar cell performance parameters. Full size table We attribute the improvement in efficiency to the band offsets between the two PbS QD layers, which effectively block electron flow to the anode while facilitating hole extraction. We use ultraviolet photoelectron spectroscopy (UPS) to determine the band edge energies with respect to vacuum in PbS QD films ( Fig. 2a ). PbS-TBAI exhibits a deeper work function of 4.77 eV (that is, E F = −4.77 eV with respect to vacuum, where E F is the Fermi level energy) than PbS-EDT. We attribute the difference in their work functions to the difference between the Pb-halide anion and the Pb-thiol–carbon interactions, which give rise to different surface dipole moments, as discussed elsewhere 20 . Furthermore, the difference between the Fermi level and valence band edge ( E V ) in PbS-TBAI is greater ( E F − E V = 0.82 eV) than that in PbS-EDT ( E F − E V = 0.63 eV). According to the individually determined band positions, the large conduction band offset (0.68 eV) between", "role": "user" }, { "content": "Solar-cell technology has advanced rapidly, as hundreds of groups around the world pursue more than two dozen approaches using different materials, technologies, and approaches to improve efficiency and reduce costs. Now a team at MIT has set a new record for the most efficient quantum-dot cells—a type of solar cell that is seen as especially promising because of its inherently low cost, versatility, and light weight. While the overall efficiency of this cell is still low compared to other types—about 9 percent of the energy of sunlight is converted to electricity—the rate of improvement of this technology is one of the most rapid seen for a solar technology. The development is described in a paper, published in the journal Nature Materials, by MIT professors Moungi Bawendi and Vladimir Bulović and graduate students Chia-Hao Chuang and Patrick Brown. The new process is an extension of work by Bawendi, the Lester Wolfe Professor of Chemistry, to produce quantum dots with precisely controllable characteristics—and as uniform thin coatings that can be applied to other materials. These minuscule particles are very effective at turning light into electricity, and vice versa. Since the first progress toward the use of quantum dots to make solar cells, Bawendi says, \"The community, in the last few years, has started to understand better how these cells operate, and what the limitations are.\" The new work represents a significant leap in overcoming those limitations, increasing the current flow in the cells and thus boosting their overall efficiency in converting sunlight into electricity. Many approaches to creating low-cost, large-area flexible and lightweight solar cells suffer from serious limitations—such as short operating lifetimes when exposed to air, or the need for high temperatures and vacuum chambers during production. By contrast, the new process does not require an inert atmosphere or high temperatures to grow the active device layers, and the resulting cells show no degradation after more than five months of storage in air. Bulović, the Fariborz Maseeh Professor of Emerging Technology and associate dean for innovation in MIT's School of Engineering, explains that thin coatings of quantum dots \"allow them to do what they do as individuals—to absorb light very well—but also work as a group, to transport charges.\" This allows those charges to be collected at the edge of the film, where they can be harnessed to provide an electric current. The new work brings together developments from several fields to push the technology to unprecedented efficiency for a quantum-dot based system: The paper's four co-authors come from MIT's departments of physics, chemistry, materials science and engineering, and electrical engineering and computer science. The solar cell produced by the team has now been added to the National Renewable Energy Laboratories' listing of record-high efficiencies for each kind of solar-cell technology. The overall efficiency of the cell is still lower than for most other types of solar cells. But Bulović points out, \"Silicon had six decades to get where it is today, and even silicon hasn't reached the theoretical limit yet. You can't hope to have an entirely new technology beat an incumbent in just four years of development.\" And the new technology has important advantages, notably a manufacturing process that is far less energy-intensive than other types. Chuang adds, \"Every part of the cell, except the electrodes for now, can be deposited at room temperature, in air, out of solution. It's really unprecedented.\" The system is so new that it also has potential as a tool for basic research. \"There's a lot to learn about why it is so stable. There's a lot more to be done, to use it as a testbed for physics, to see why the results are sometimes better than we expect,\" Bulović says. A companion paper, written by three members of the same team along with MIT's Jeffrey Grossman, the Carl Richard Soderberg Associate Professor of Power Engineering, and three others, appears this month in the journal ACS Nano, explaining in greater detail the science behind the strategy employed to reach this efficiency breakthrough. The new work represents a turnaround for Bawendi, who had spent much of his career working with quantum dots. \"I was somewhat of a skeptic four years ago,\" he says. But his team's research since then has clearly demonstrated quantum dots' potential in solar cells, he adds. Arthur Nozik, a research professor in chemistry at the University of Colorado who was not involved in this research, says, \"This result represents a significant advance for the applications of quantum-dot films and the technology of low-temperature, solution-processed, quantum-dot photovoltaic cells. … There is still a long way to go before quantum-dot solar cells are commercially viable, but this latest development is a nice step toward this ultimate goal.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Solution processing is a promising route for the realization of low-cost, large-area, flexible and lightweight photovoltaic devices with short energy payback time and high specific power. However, solar cells based on solution-processed organic, inorganic and hybrid materials reported thus far generally suffer from poor air stability, require an inert-atmosphere processing environment or necessitate high-temperature processing 1 , all of which increase manufacturing complexities and costs. Simultaneously fulfilling the goals of high efficiency, low-temperature fabrication conditions and good atmospheric stability remains a major technical challenge, which may be addressed, as we demonstrate here, with the development of room-temperature solution-processed ZnO/PbS quantum dot solar cells. By engineering the band alignment of the quantum dot layers through the use of different ligand treatments, a certified efficiency of 8.55% has been reached. Furthermore, the performance of unencapsulated devices remains unchanged for over 150 days of storage in air. This material system introduces a new approach towards the goal of high-performance air-stable solar cells compatible with simple solution processes and deposition on flexible substrates. Main Near-infrared PbS quantum dots (QDs) composed of earth-abundant elements 2 have emerged as promising candidates for photovoltaic applications because of a tunable energy bandgap that covers the optimal bandgap range for single and multi-junction solar cells 1 . The QD surface ligands 3 , 4 , 5 , 6 , 7 and the photovoltaic device architecture 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 play crucial roles in determining the optoelectronic properties of QD solar cells. Advances in QD surface passivation, particularly through the use of halide ions as inorganic ligands 4 , have led to rapid improvements in QD solar cell power conversion efficiencies to 7% 5 , 15 , 16 as a result of a lower density of trapped carriers than in their organic ligands counterparts 4 . Furthermore, recent studies have demonstrated the ability to control the band edge energies of QD films through ligand exchange 18 , 19 , 20 . However, fabrication of these recent QD devices requires high-temperature annealing (>500 °C) of the TiO 2 window layer 5 , 16 or two different processing atmospheres, including an inert gas environment 15 . Although good stability has been claimed, the devices still show performance degradation to ~85% of their original efficiencies within one week, even under inert atmosphere 5 , 16 . Here, we demonstrate ZnO/PbS solar cells in which the PbS QD and ZnO nanocrystals are both solution-processed in air and at room temperature. We demonstrate a device architecture that employs layers of QDs treated with different ligands for different functions by tuning their relative band alignment—a layer of inorganic-ligand-passivated QDs serves as the main light-absorbing layer and a layer of organic-ligand-passivated QDs serves as an electron-blocking/hole-extraction layer. The devices show significant improvements in power conversion efficiency and long-term air stability, compared with previously reported devices. Figure 1a shows the schematics of the device structures employed in this work. Oleic-acid-capped PbS QDs with the first exciton absorption peak at λ = 901 nm in solution ( Supplementary Fig. 1 ) are used to fabricate the thin films. Tetrabutylammonium iodide (TBAI) and 1,2-ethanedithiol (EDT) are used as the inorganic and organic ligands for solid-state ligand exchange. After solid-state ligand exchange, the first exciton absorption peak shifts to λ ~ 935 nm, which corresponds to an optical bandgap E g = 1.33 eV. We find that PbS QD films treated with TBAI (PbS-TBAI) exhibit superior air stability compared with PbS QDs treated with EDT (PbS-EDT; Supplementary Fig. 2 ). PbS-TBAI-only devices also show a higher short-circuit current density ( J SC ), whereas PbS-EDT-only devices show a higher open circuit voltage ( V OC ; Supplementary Fig. 3 ). Figure 1: Photovoltaic device architectures and performance. a , Device architectures. b , Representative J – V characteristics of devices with Au anodes under simulated AM1.5G irradiation (100 mW cm −2 ). The PbS-TBAI device consists of 12 layers of PbS-TBAI and the PbS-TBAI/PbS-EDT device consists of 10 layers of PbS-TBAI and 2 layers of PbS-EDT. c , External quantum efficiency (EQE) spectra for the same devices. Full size image The J – V characteristics of photovoltaic devices with Au anodes are shown in Fig. 1b . The device consisting of 12 PbS-TBAI layers (corresponding to a film thickness of ~220 nm) shows a power conversion efficiency of 6.0 ± 0.4%, which is higher than the previously reported TiO 2 /PbS-TBAI devices consisting of PbS QDs with an additional solution phase CdCl 2 treatment and MoO 3 /Au/Ag anode 4 . Although PbS-EDT-only devices show a lower J SC than PbS-TBAI-only devices, replacing the topmost two PbS-TBAI layers with two PbS-EDT layers significantly improves the J SC , V OC and fill factor (FF), resulting in a ~35% improvement in power conversion efficiency to 8.2 ± 0.6%, with a 9.2% lab-champion device ( Table 1 ). Table 1 Solar cell performance parameters. Full size table We attribute the improvement in efficiency to the band offsets between the two PbS QD layers, which effectively block electron flow to the anode while facilitating hole extraction. We use ultraviolet photoelectron spectroscopy (UPS) to determine the band edge energies with respect to vacuum in PbS QD films ( Fig. 2a ). PbS-TBAI exhibits a deeper work function of 4.77 eV (that is, E F = −4.77 eV with respect to vacuum, where E F is the Fermi level energy) than PbS-EDT. We attribute the difference in their work functions to the difference between the Pb-halide anion and the Pb-thiol–carbon interactions, which give rise to different surface dipole moments, as discussed elsewhere 20 . Furthermore, the difference between the Fermi level and valence band edge ( E V ) in PbS-TBAI is greater ( E F − E V = 0.82 eV) than that in PbS-EDT ( E F − E V = 0.63 eV). According to the individually determined band positions, the large conduction band offset (0.68 eV) between<|im_end|> <|im_start|>assistant Solar-cell technology has advanced rapidly, as hundreds of groups around the world pursue more than two dozen approaches using different materials, technologies, and approaches to improve efficiency and reduce costs. Now a team at MIT has set a new record for the most efficient quantum-dot cells—a type of solar cell that is seen as especially promising because of its inherently low cost, versatility, and light weight. While the overall efficiency of this cell is still low compared to other types—about 9 percent of the energy of sunlight is converted to electricity—the rate of improvement of this technology is one of the most rapid seen for a solar technology. The development is described in a paper, published in the journal Nature Materials, by MIT professors Moungi Bawendi and Vladimir Bulović and graduate students Chia-Hao Chuang and Patrick Brown. The new process is an extension of work by Bawendi, the Lester Wolfe Professor of Chemistry, to produce quantum dots with precisely controllable characteristics—and as uniform thin coatings that can be applied to other materials. These minuscule particles are very effective at turning light into electricity, and vice versa. Since the first progress toward the use of quantum dots to make solar cells, Bawendi says, "The community, in the last few years, has started to understand better how these cells operate, and what the limitations are." The new work represents a significant leap in overcoming those limitations, increasing the current flow in the cells and thus boosting their overall efficiency in converting sunlight into electricity. Many approaches to creating low-cost, large-area flexible and lightweight solar cells suffer from serious limitations—such as short operating lifetimes when exposed to air, or the need for high temperatures and vacuum chambers during production. By contrast, the new process does not require an inert atmosphere or high temperatures to grow the active device layers, and the resulting cells show no degradation after more than five months of storage in air. Bulović, the Fariborz Maseeh Professor of Emerging Technology and associate dean for innovation in MIT's School of Engineering, explains that thin coatings of quantum dots "allow them to do what they do as individuals—to absorb light very well—but also work as a group, to transport charges." This allows those charges to be collected at the edge of the film, where they can be harnessed to provide an electric current. The new work brings together developments from several fields to push the technology to unprecedented efficiency for a quantum-dot based system: The paper's four co-authors come from MIT's departments of physics, chemistry, materials science and engineering, and electrical engineering and computer science. The solar cell produced by the team has now been added to the National Renewable Energy Laboratories' listing of record-high efficiencies for each kind of solar-cell technology. The overall efficiency of the cell is still lower than for most other types of solar cells. But Bulović points out, "Silicon had six decades to get where it is today, and even silicon hasn't reached the theoretical limit yet. You can't hope to have an entirely new technology beat an incumbent in just four years of development." And the new technology has important advantages, notably a manufacturing process that is far less energy-intensive than other types. Chuang adds, "Every part of the cell, except the electrodes for now, can be deposited at room temperature, in air, out of solution. It's really unprecedented." The system is so new that it also has potential as a tool for basic research. "There's a lot to learn about why it is so stable. There's a lot more to be done, to use it as a testbed for physics, to see why the results are sometimes better than we expect," Bulović says. A companion paper, written by three members of the same team along with MIT's Jeffrey Grossman, the Carl Richard Soderberg Associate Professor of Power Engineering, and three others, appears this month in the journal ACS Nano, explaining in greater detail the science behind the strategy employed to reach this efficiency breakthrough. The new work represents a turnaround for Bawendi, who had spent much of his career working with quantum dots. "I was somewhat of a skeptic four years ago," he says. But his team's research since then has clearly demonstrated quantum dots' potential in solar cells, he adds. Arthur Nozik, a research professor in chemistry at the University of Colorado who was not involved in this research, says, "This result represents a significant advance for the applications of quantum-dot films and the technology of low-temperature, solution-processed, quantum-dot photovoltaic cells. … There is still a long way to go before quantum-dot solar cells are commercially viable, but this latest development is a nice step toward this ultimate goal." <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 12761, 8863, 374, 264, 26455, 6149, 369, 279, 49803, 315, 3428, 41238, 11, 3544, 30122, 11, 19303, 323, 30244, 4604, 93591, 292, 7766, 449, 2875, 4907, 2343, 1445, 892, 323, 1579, 3230, 2410, 13, 4452, 11, 13238, 7917, 3196, 389, 6425, 12, 35122, 17808, 11, 304, 61694, 323, 26038, 7384, 5068, 8617, 3117, 8965, 7831, 505, 8009, 3805, 20334, 11, 1397, 459, 81073, 29883, 8801, 8182, 8863, 4676, 477, 4541, 20227, 1579, 12, 35658, 8863, 220, 16, 1174, 682, 315, 902, 5376, 15266, 84140, 323, 7194, 13, 4567, 495, 20933, 50698, 279, 9021, 315, 1579, 15374, 11, 3428, 12, 35658, 59251, 4787, 323, 1695, 45475, 20334, 8625, 264, 3682, 11156, 8815, 11, 902, 1253, 387, 20669, 11, 439, 584, 20461, 1618, 11, 449, 279, 4500, 315, 3130, 12, 35658, 6425, 12, 35122, 127265, 46, 16744, 65, 50, 31228, 13046, 13238, 7917, 13, 3296, 15009, 279, 7200, 17632, 315, 279, 31228, 13046, 13931, 1555, 279, 1005, 315, 2204, 29413, 438, 22972, 11, 264, 23759, 15374, 315, 220, 23, 13, 2131, 4, 706, 1027, 8813, 13, 24296, 11, 279, 5178, 315, 653, 967, 2690, 7913, 7766, 8625, 35957, 369, 927, 220, 3965, 2919, 315, 5942, 304, 3805, 13, 1115, 3769, 1887, 40019, 264, 502, 5603, 7119, 279, 5915, 315, 1579, 58574, 3805, 5594, 481, 13238, 7917, 18641, 449, 4382, 6425, 11618, 323, 65374, 389, 19303, 16146, 988, 13, 4802, 31494, 3502, 82482, 98454, 50, 31228, 32094, 320, 48, 68050, 8, 24306, 315, 9578, 39130, 1263, 519, 5540, 220, 17, 617, 22763, 439, 26455, 11426, 369, 4604, 93591, 292, 8522, 1606, 315, 264, 11716, 481, 4907, 7200, 42510, 430, 14861, 279, 23669, 7200, 42510, 2134, 369, 3254, 323, 7447, 13636, 600, 13238, 7917, 220, 16, 662, 578, 1229, 35, 7479, 29413, 2914, 220, 18, 1174, 220, 19, 1174, 220, 20, 1174, 220, 21, 1174, 220, 22, 323, 279, 4604, 93591, 292, 3756, 18112, 220, 23, 1174, 220, 24, 1174, 220, 605, 1174, 220, 806, 1174, 220, 717, 1174, 220, 1032, 1174, 220, 975, 1174, 220, 868, 1174, 220, 845, 1174, 220, 1114, 1514, 16996, 13073, 304, 26679, 279, 3469, 4748, 772, 8535, 6012, 315, 1229, 35, 13238, 7917, 13, 91958, 304, 1229, 35, 7479, 1522, 40227, 11, 8104, 1555, 279, 1005, 315, 15104, 579, 65125, 439, 304, 61694, 29413, 2914, 220, 19, 1174, 617, 6197, 311, 11295, 18637, 304, 1229, 35, 13238, 2849, 2410, 14747, 92126, 311, 220, 22, 4, 220, 20, 1174, 220, 868, 1174, 220, 845, 439, 264, 1121, 315, 264, 4827, 17915, 315, 31691, 35991, 1109, 304, 872, 17808, 29413, 2914, 38495, 220, 19, 662, 24296, 11, 3293, 7978, 617, 21091, 279, 5845, 311, 2585, 279, 7200, 6964, 49969, 315, 1229, 35, 12631, 1555, 29413, 438, 9473, 220, 972, 1174, 220, 777, 1174, 220, 508, 662, 4452, 11, 59251, 315, 1521, 3293, 1229, 35, 7766, 7612, 1579, 12, 35658, 86997, 6260, 77952, 2636, 37386, 34, 8, 315, 279, 23126, 46, 220, 17, 3321, 6324, 220, 20, 1174, 220, 845, 477, 1403, 2204, 8863, 14036, 65733, 11, 2737, 459, 81073, 6962, 4676, 220, 868, 662, 10541, 1695, 20334, 706, 1027, 11922, 11, 279, 7766, 2103, 1501, 5178, 53568, 311, 4056, 5313, 4, 315, 872, 4113, 92126, 2949, 832, 2046, 11, 1524, 1234, 81073, 16975, 220, 20, 1174, 220, 845, 662, 5810, 11, 584, 20461, 127265, 46, 16744, 65, 50, 13238, 7917, 304, 902, 279, 98454, 50, 1229, 35, 323, 127265, 46, 20622, 4309, 92475, 527, 2225, 6425, 12, 35122, 304, 3805, 323, 520, 3130, 9499, 13, 1226, 20461, 264, 3756, 18112, 430, 51242, 13931, 315, 1229, 68050, 12020, 449, 2204, 29413, 2914, 369, 2204, 5865, 555, 42438, 872, 8844, 7200, 17632, 29096, 6324, 315, 304, 61694, 2922, 343, 438, 48067, 55786, 1229, 68050, 17482, 439, 279, 1925, 3177, 97510, 269, 7278, 6324, 323, 264, 6324, 315, 17808, 2922, 343, 438, 48067, 55786, 1229, 68050, 17482, 439, 459, 17130, 79861, 7682, 1286, 10397, 27523, 6324, 13, 578, 7766, 1501, 5199, 18637, 304, 2410, 14747, 15374, 323, 1317, 9860, 3805, 20334, 11, 7863, 449, 8767, 5068, 7766, 13, 19575, 220, 16, 64, 5039, 279, 20225, 29470, 315, 279, 3756, 14726, 20011, 304, 420, 990, 13, 33797, 292, 38698, 307, 1824, 5795, 98454, 50, 1229, 68050, 449, 279, 1176, 25435, 263, 44225, 16557, 520, 49438, 284, 220, 19319, 26807, 304, 6425, 320, 99371, 23966, 13, 220, 16, 883, 527, 1511, 311, 13354, 349, 279, 15792, 12631, 13, 350, 17820, 370, 332, 4010, 309, 1677, 2411, 80087, 579, 320, 51, 7209, 40, 8, 323, 220, 16, 11, 17, 12, 774, 52530, 411, 25947, 320, 1507, 51, 8, 527, 1511, 439, 279, 304, 61694, 323, 17808, 29413, 2914, 369, 6573, 21395, 29413, 438, 9473, 13, 4740, 6573, 21395, 29413, 438, 9473, 11, 279, 1176, 25435, 263, 44225, 16557, 29735, 311, 49438, 4056, 220, 26970, 26807, 11, 902, 34310, 311, 459, 29393, 7200, 42510, 469, 342, 284, 220, 16, 13, 1644, 384, 53, 13, 1226, 1505, 430, 98454, 50, 1229, 35, 12631, 12020, 449, 350, 7209, 40, 320, 47, 65, 50, 9469, 7209, 40, 8, 31324, 16757, 3805, 20334, 7863, 449, 98454, 50, 1229, 68050, 12020, 449, 49023, 320, 47, 65, 50, 12, 1507, 51, 26, 99371, 23966, 13, 220, 17, 7609, 98454, 50, 9469, 7209, 40, 15744, 7766, 1101, 1501, 264, 5190, 2875, 1824, 38368, 1510, 17915, 320, 622, 7683, 7026, 20444, 98454, 50, 12, 1507, 51, 15744, 7766, 1501, 264, 5190, 1825, 16622, 22465, 320, 650, 32967, 2652, 99371, 23966, 13, 220, 18, 7609, 19575, 220, 16, 25, 18235, 93591, 292, 3756, 78335, 323, 5178, 13, 264, 1174, 14227, 78335, 13, 293, 1174, 38366, 622, 1389, 650, 17910, 315, 7766, 449, 33150, 459, 2601, 1234, 46836, 6912, 16, 13, 20, 38, 76327, 367, 320, 1041, 296, 54, 10166, 25173, 17, 7609, 578, 98454, 50, 9469, 7209, 40, 3756, 17610, 315, 220, 717, 13931, 315, 98454, 50, 9469, 7209, 40, 323, 279, 98454, 50, 9469, 7209, 40, 16744, 65, 50, 12, 1507, 51, 3756, 17610, 315, 220, 605, 13931, 315, 98454, 50, 9469, 7209, 40, 323, 220, 17, 13931, 315, 98454, 50, 12, 1507, 51, 13, 272, 1174, 32036, 31228, 15374, 320, 55107, 36, 8, 63697, 369, 279, 1890, 7766, 13, 8797, 1404, 2217, 578, 622, 1389, 650, 17910, 315, 4604, 93591, 292, 7766, 449, 33150, 459, 2601, 527, 6982, 304, 23966, 13, 220, 16, 65, 662, 578, 3756, 31706, 315, 220, 717, 98454, 50, 9469, 7209, 40, 13931, 320, 6133, 6961, 287, 311, 264, 4632, 26839, 315, 4056, 8610, 26807, 8, 5039, 264, 2410, 14747, 15374, 315, 220, 21, 13, 15, 20903, 220, 15, 13, 19, 13689, 902, 374, 5190, 1109, 279, 8767, 5068, 23126, 46, 220, 17, 611, 47, 65, 50, 9469, 7209, 40, 7766, 31706, 315, 98454, 50, 1229, 68050, 449, 459, 5217, 6425, 10474, 85090, 5176, 220, 17, 6514, 323, 6178, 46, 220, 18, 611, 66432, 14, 9219, 459, 536, 220, 19, 662, 10541, 98454, 50, 12, 1507, 51, 15744, 7766, 1501, 264, 4827, 622, 7683, 1109, 98454, 50, 9469, 7209, 40, 15744, 7766, 11, 25935, 279, 1948, 3646, 1403, 98454, 50, 9469, 7209, 40, 13931, 449, 1403, 98454, 50, 12, 1507, 51, 13931, 12207, 36050, 279, 622, 7683, 1174, 650, 32967, 323, 5266, 8331, 320, 1785, 705, 13239, 304, 264, 4056, 1758, 4, 16048, 304, 2410, 14747, 15374, 311, 220, 23, 13, 17, 20903, 220, 15, 13, 21, 13689, 449, 264, 220, 24, 13, 17, 4, 10278, 11843, 13580, 3756, 320, 6771, 220, 16, 7609, 6771, 220, 16, 25450, 2849, 5178, 5137, 13, 8797, 1404, 2007, 1226, 7180, 279, 16048, 304, 15374, 311, 279, 7200, 36146, 1990, 279, 1403, 98454, 50, 1229, 35, 13931, 11, 902, 13750, 2565, 17130, 6530, 311, 279, 459, 536, 1418, 68365, 14512, 33289, 13, 1226, 1005, 37232, 85311, 6685, 75603, 66425, 51856, 320, 77283, 8, 311, 8417, 279, 7200, 6964, 49969, 449, 5201, 311, 29302, 304, 98454, 50, 1229, 35, 12631, 320, 23966, 13, 220, 17, 64, 7609, 98454, 50, 9469, 7209, 40, 50829, 264, 19662, 990, 734, 315, 220, 19, 13, 2813, 384, 53, 320, 9210, 374, 11, 469, 435, 284, 25173, 19, 13, 2813, 384, 53, 449, 5201, 311, 29302, 11, 1405, 469, 435, 374, 279, 99362, 72, 2237, 4907, 8, 1109, 98454, 50, 12, 1507, 51, 13, 1226, 7180, 279, 6811, 304, 872, 990, 5865, 311, 279, 6811, 1990, 279, 98454, 2902, 278, 579, 459, 290, 323, 279, 98454, 7716, 25947, 4235, 74441, 22639, 11, 902, 3041, 10205, 311, 2204, 7479, 24522, 1286, 14269, 11, 439, 14407, 18403, 220, 508, 662, 24296, 11, 279, 6811, 1990, 279, 99362, 72, 2237, 323, 1062, 768, 7200, 6964, 320, 469, 650, 883, 304, 98454, 50, 9469, 7209, 40, 374, 7191, 320, 469, 435, 25173, 469, 650, 284, 220, 15, 13, 6086, 384, 53, 8, 1109, 430, 304, 98454, 50, 12, 1507, 51, 320, 469, 435, 25173, 469, 650, 284, 220, 15, 13, 5495, 384, 53, 570, 10771, 311, 279, 32399, 11075, 7200, 10093, 11, 279, 3544, 390, 23985, 7200, 4445, 320, 15, 13, 2614, 384, 53, 8, 1990, 128257, 198, 128256, 78191, 198, 72041, 33001, 5557, 706, 11084, 19019, 11, 439, 11758, 315, 5315, 2212, 279, 1917, 23564, 810, 1109, 1403, 21030, 20414, 1701, 2204, 7384, 11, 14645, 11, 323, 20414, 311, 7417, 15374, 323, 8108, 7194, 13, 4800, 264, 2128, 520, 15210, 706, 743, 264, 502, 3335, 369, 279, 1455, 11297, 31228, 82002, 7917, 29096, 955, 315, 13238, 2849, 430, 374, 3970, 439, 5423, 26455, 1606, 315, 1202, 49188, 3428, 2853, 11, 60112, 11, 323, 3177, 4785, 13, 6104, 279, 8244, 15374, 315, 420, 2849, 374, 2103, 3428, 7863, 311, 1023, 4595, 2345, 9274, 220, 24, 3346, 315, 279, 4907, 315, 40120, 374, 16489, 311, 18200, 22416, 4478, 315, 16048, 315, 420, 5557, 374, 832, 315, 279, 1455, 11295, 3970, 369, 264, 13238, 5557, 13, 578, 4500, 374, 7633, 304, 264, 5684, 11, 4756, 304, 279, 8486, 22037, 32009, 11, 555, 15210, 45724, 73934, 983, 72, 426, 675, 41124, 323, 36011, 13805, 46188, 7886, 323, 19560, 4236, 921, 689, 11529, 3524, 62111, 526, 323, 20199, 10690, 13, 578, 502, 1920, 374, 459, 9070, 315, 990, 555, 426, 675, 41124, 11, 279, 83758, 80652, 17054, 315, 42846, 11, 311, 8356, 31228, 32094, 449, 24559, 687, 69855, 17910, 17223, 439, 14113, 15792, 92025, 430, 649, 387, 9435, 311, 1023, 7384, 13, 4314, 1332, 26089, 1130, 19252, 527, 1633, 7524, 520, 13353, 3177, 1139, 18200, 11, 323, 17192, 46391, 13, 8876, 279, 1176, 5208, 9017, 279, 1005, 315, 31228, 32094, 311, 1304, 13238, 7917, 11, 426, 675, 41124, 2795, 11, 330, 791, 4029, 11, 304, 279, 1566, 2478, 1667, 11, 706, 3940, 311, 3619, 2731, 1268, 1521, 7917, 14816, 11, 323, 1148, 279, 9669, 527, 1210, 578, 502, 990, 11105, 264, 5199, 32571, 304, 74017, 1884, 9669, 11, 7859, 279, 1510, 6530, 304, 279, 7917, 323, 8617, 56028, 872, 8244, 15374, 304, 34537, 40120, 1139, 18200, 13, 9176, 20414, 311, 6968, 3428, 41238, 11, 3544, 30122, 19303, 323, 30244, 13238, 7917, 7831, 505, 6129, 9669, 2345, 21470, 439, 2875, 10565, 10345, 7034, 994, 15246, 311, 3805, 11, 477, 279, 1205, 369, 1579, 20472, 323, 29302, 53279, 2391, 5788, 13, 3296, 13168, 11, 279, 502, 1920, 1587, 539, 1397, 459, 81073, 16975, 477, 1579, 20472, 311, 3139, 279, 4642, 3756, 13931, 11, 323, 279, 13239, 7917, 1501, 912, 53568, 1306, 810, 1109, 4330, 4038, 315, 5942, 304, 3805, 13, 13805, 46188, 7886, 11, 279, 13759, 581, 68423, 386, 521, 2701, 17054, 315, 86148, 12053, 323, 22712, 73962, 369, 19297, 304, 15210, 596, 6150, 315, 17005, 11, 15100, 430, 15792, 92025, 315, 31228, 32094, 330, 7331, 1124, 311, 656, 1148, 814, 656, 439, 7931, 50617, 35406, 3177, 1633, 1664, 38542, 1101, 990, 439, 264, 1912, 11, 311, 7710, 10405, 1210, 1115, 6276, 1884, 10405, 311, 387, 14890, 520, 279, 6964, 315, 279, 4632, 11, 1405, 814, 649, 387, 305, 1923, 22456, 311, 3493, 459, 9249, 1510, 13, 578, 502, 990, 12716, 3871, 26006, 505, 3892, 5151, 311, 4585, 279, 5557, 311, 31069, 15374, 369, 264, 31228, 82002, 3196, 1887, 25, 578, 5684, 596, 3116, 1080, 34603, 1105, 2586, 505, 15210, 596, 26280, 315, 22027, 11, 30903, 11, 7384, 8198, 323, 15009, 11, 323, 20314, 15009, 323, 6500, 8198, 13, 578, 13238, 2849, 9124, 555, 279, 2128, 706, 1457, 1027, 3779, 311, 279, 5165, 93438, 12634, 78717, 6, 15182, 315, 3335, 28661, 92126, 369, 1855, 3169, 315, 13238, 33001, 5557, 13, 578, 8244, 15374, 315, 279, 2849, 374, 2103, 4827, 1109, 369, 1455, 1023, 4595, 315, 13238, 7917, 13, 2030, 13805, 46188, 7886, 3585, 704, 11, 330, 28671, 1965, 1047, 4848, 11026, 311, 636, 1405, 433, 374, 3432, 11, 323, 1524, 51692, 12775, 956, 8813, 279, 32887, 4017, 3686, 13, 1472, 649, 956, 3987, 311, 617, 459, 11622, 502, 5557, 9567, 459, 51382, 304, 1120, 3116, 1667, 315, 4500, 1210, 1628, 279, 502, 5557, 706, 3062, 22934, 11, 35146, 264, 15266, 1920, 430, 374, 3117, 2753, 4907, 88092, 1109, 1023, 4595, 13, 62111, 526, 11621, 11, 330, 11769, 961, 315, 279, 2849, 11, 3734, 279, 80390, 369, 1457, 11, 649, 387, 54568, 520, 3130, 9499, 11, 304, 3805, 11, 704, 315, 6425, 13, 1102, 596, 2216, 31069, 1210, 578, 1887, 374, 779, 502, 430, 433, 1101, 706, 4754, 439, 264, 5507, 369, 6913, 3495, 13, 330, 3947, 596, 264, 2763, 311, 4048, 922, 3249, 433, 374, 779, 15528, 13, 2684, 596, 264, 2763, 810, 311, 387, 2884, 11, 311, 1005, 433, 439, 264, 1296, 2788, 369, 22027, 11, 311, 1518, 3249, 279, 3135, 527, 7170, 2731, 1109, 584, 1755, 1359, 13805, 46188, 7886, 2795, 13, 362, 22489, 5684, 11, 5439, 555, 2380, 3697, 315, 279, 1890, 2128, 3235, 449, 15210, 596, 42107, 43907, 1543, 11, 279, 22770, 12131, 328, 4414, 7881, 33468, 17054, 315, 7572, 17005, 11, 323, 2380, 3885, 11, 8111, 420, 2305, 304, 279, 8486, 79184, 64051, 11, 26073, 304, 7191, 7872, 279, 8198, 4920, 279, 8446, 20011, 311, 5662, 420, 15374, 42445, 13, 578, 502, 990, 11105, 264, 67610, 369, 426, 675, 41124, 11, 889, 1047, 7543, 1790, 315, 813, 7076, 3318, 449, 31228, 32094, 13, 330, 40, 574, 14738, 315, 264, 55950, 3116, 1667, 4227, 1359, 568, 2795, 13, 2030, 813, 2128, 596, 3495, 2533, 1243, 706, 9539, 21091, 31228, 32094, 6, 4754, 304, 13238, 7917, 11, 568, 11621, 13, 28686, 2360, 76574, 11, 264, 3495, 14561, 304, 30903, 520, 279, 3907, 315, 15745, 889, 574, 539, 6532, 304, 420, 3495, 11, 2795, 11, 330, 2028, 1121, 11105, 264, 5199, 12178, 369, 279, 8522, 315, 31228, 82002, 12631, 323, 279, 5557, 315, 3428, 12, 35658, 11, 6425, 12, 35122, 11, 31228, 82002, 4604, 93591, 292, 7917, 13, 4696, 2684, 374, 2103, 264, 1317, 1648, 311, 733, 1603, 31228, 82002, 13238, 7917, 527, 54453, 31528, 11, 719, 420, 5652, 4500, 374, 264, 6555, 3094, 9017, 420, 17139, 5915, 1210, 220, 128257, 198 ]

2,478

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract The field of ‘Valleytronics’ has recently been attracting growing interest as a promising concept for the next generation electronics, because non-dissipative pure valley currents with no accompanying net charge flow can be manipulated for computational use, akin to pure spin currents 1 . Valley is a quantum number defined in an electronic system whose energy bands contain energetically degenerate but non-equivalent local minima (conduction band) or maxima (valence band) due to a certain crystal structure. Specifically, spatial inversion symmetry broken two-dimensional honeycomb lattice systems exhibiting Berry curvature is a subset of possible systems that enable optical 2 , 3 , 4 , 5 , magnetic 6 , 7 , 8 , 9 and electrical control of the valley degree of freedom 10 , 11 , 12 . Here we use dual-gated bilayer graphene to electrically induce and control broken inversion symmetry (or Berry curvature) as well as the carrier density for generating and detecting the pure valley current. In the insulating regime, at zero-magnetic field, we observe a large nonlocal resistance that scales cubically with the local resistivity, which is evidence of pure valley current. Main Charge and spin are both well-defined quantum numbers in solids. Spintronics is a technology that uses the spin degree of freedom. The application range of spintronics has been largely expanded by the development of electrical techniques for generating and detecting the spin current 1 . The valley degree of freedom in solid crystals can be handled by controlling the occupation of the non-equivalent structures in the band, providing the novel concept of so-called valleytronics. Among various material candidates for valleytronics, two-dimensional (2D) honeycomb lattice systems with broken spatial inversion symmetry, such as gapped graphene and transition metal dichalcogenide (TMDC), are predicted to be the most useful. These systems have two valleys, called K and K′. Optical 2 , 3 , 4 , 5 , magnetic 6 , 7 , 8 , 9 and electrical 10 , 11 , 12 control of the valley has been demonstrated. In particular, Berry curvature, which emerges in these honeycomb lattice systems with broken spatial inversion symmetry, enables electrical control of the valley degree of freedom. Berry curvature acts as an out-of-plane pseudo-magnetic field in momentum space and has opposite sign between the two valleys. Therefore, a transverse pure valley current is generated by means of the anomalous velocity, in analogy to a transverse electronic current being generated by means of the Lorentz force due to a magnetic field in real space 13 , 14 (see Fig. 1d ). This phenomenon is called the valley Hall effect 10 and can be used to generate a valley current. The inverse valley Hall effect, which converts the valley current into a transverse electric field, allows the detection of the pure valley current. Figure 1: Scheme for detection of the nonlocal resistance due to valley current flow in BLG. a , Band structure, Berry curvature and valley Hall conductivity of BLG. A band gap 2 Δ and Berry curvature Ω emerge as a result of broken spatial inversion symmetry. The valley Hall conductivity σ xy VH , which is calculated by integrating the Berry curvature, is constant in the bandgap. b , Schematic of the dual-gated BLG device. The top gate is a gold film, and the back gate is a p-doped silicon substrate. Two h-BN layers and a SiO 2 film are used as gate insulators. Using these gates, the carrier density and perpendicular electric field (displacement field) are independently varied. Expanded image: Lattice structure of AB-stacked BLG. In the presence of a displacement field, an energy difference between the top and bottom layer emerges. Therefore spatial inversion symmetry is broken in this system, and both Berry curvature and a bandgap emerge. c , AFM image of the BLG device without the top h-BN. The light blue region indicates the area of the top gate. The BLG has a mobility of ∼ 15,000 cm 2 V −1 s −1 at both 1.5 and 70 K. d , Schematic of the nonlocal resistance measurement and the nonlocal transport mediated by a pure valley current. The electric field driving the charge current in the left-hand circuit generates a pure valley current in the transverse direction by means of the valley Hall effect (VHE). This valley current is converted into an electric field or nonlocal voltage in the right-hand circuit by means of the inverse valley Hall effect (IVHE) to generate the nonlocal resistance. Full size image The valley Hall effect was first reported for photo-generated electrons in monolayer MoS 2 (ref. 11 ). However, the small inter-valley scattering length in this material prevents the detection of the pure valley current, which does not accompany the electronic current. Compared to TMDC, graphene has a much larger inter-valley scattering length owing to its higher crystal quality. Monolayer graphene on h-BN has more recently been used to generate and detect the pure valley current, where the crystal direction of the graphene was aligned to that of the h-BN such that the superlattice potential imposed by the h-BN structurally breaks the spatial inversion symmetry 12 . The valley Hall effect was analysed in detail with the carrier density as a parameter using metallic samples whose resistivity decreases as the temperature is lowered, but leaving unaddressed the insulating regime, which is more appropriate for investigating the pure valley current. In this work we employed bilayer graphene (BLG) to generate and detect the valley current. We used a perpendicular electric field to break the spatial inversion symmetry and induce Berry curvature as well as a bandgap (see Fig. 1a ). The dual-gated structure seen in Fig. 1b allows electrical and independent control of the perpendicular electric field and the carrier density 15 , 16 , 17 , 18 , 19 . This is in contrast to the monolayer graphene samples in ref. 12 , where the monolayer graphene has to be structurally aligned with h-BN through a process of mechanical transfer. BLG valley Hall devices therefore show greater", "role": "user" }, { "content": "University of Tokyo researchers have demonstrated an electrically-controllable valley current device that may pave the way to ultra-low-power \"valleytronics\" devices. On the atomic scale, matter behaves as both a particle and a wave. Electrons, therefore, have an associated wavelength that usually can have many different values. In crystalline systems however, certain wavelengths may be favored. Graphene, for example, has two favored wavelengths known as K and K' (K prime). This means that two electrons in graphene can have the same energy but different wavelengths - or, to put it another way, different \"valley.\" Electronics use charge to represent information, but when charge flows through a material, some energy is dissipated as heat, a problem for all electronic devices in use today. However, if the same quantity of electrons in a channel flow in opposite directions, no net charge is transferred and no heat is dissipated - but in a normal electronic device this would mean that no information was passed either. A valleytronics device transmitting information using pure valley current, where electrons with the same valley flow in one direction, would not have this limitation, and offers a route to realizing extremely low power devices. Experimental studies on valley current have only recently started. Control of valley current in a graphene monolayer has been demonstrated, but only under very specific conditions and with limited control of conversion from charge current to valley current. In order for valley current to be a viable alternative to charge current-based modern electronics, it is necessary to control the conversion between charge current and valley current over a wide range at high temperatures. Now, Professor Seigo Tarucha's research group at the Department of Applied Physics at the Graduate School of Engineering has created an electrically controllable valley current device that converts conventional electrical current to valley current, passes it through a long (3.5 micron) channel, then converts the valley current back into charge current that can be detected by a measurable voltage. The research group used a graphene bilayer sandwiched between two insulator layers, with the whole device sandwiched between two conducting layers or 'gates', allowing for the control of valley. A vertical electric field (green arrows) breaks the symmetry of the bilayer graphene allowing for selective control of valley. A conventional, small electrical current (purple arrow) is converted into valley current via the valley Hall effect (VHE). (The electrons in the K valley, blue, travel to the right; while the electrons in the Kâ€� valley, pink, travel to the left.) Pure valley current travels over a significant distance. At the other side of the device the valley current is converted back to charge current via the inverse valley Hall effect (IVHE) and is detected as a voltage. Credit: (c) 2015 Seigo Tarucha The group transferred valley current over a distance large enough to exclude other possible competing explanations for their results and were able to control the efficiency of valley current conversion over a wide range. The device also operated at temperatures far higher than expected. \"We usually measure our devices at temperatures lower than the liquefaction point of Helium (-268.95 C, just 4.2 K above absolute zero) to detect this type of phenomena,\" says Dr. Yamamoto, a member of the research group. \"We were surprised that the signal could be detected even at -203.15 C (70 K). In the future, it may be possible to develop devices that can operate at room temperature.\" \"Valley current, unlike charge current is non dissipative. This means that no energy is lost during the transfer of information,\" says Professor Tarucha. He continues, \"With power consumption becoming a major issue in modern electronics, valley current based devices open up a new direction for future ultra-low-power consumption computing devices.\" An Atomic Force Microscope image of the valleytronics device. The bright orange area is bilayer graphene. The light blue area shows the area of the top gate. Current is injected from the right side of the device, and converted to valley current. The valley current is converted back to charge current and detected as a voltage signal. Credit: (c) 2015 Seigo Tarucha ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract The field of ‘Valleytronics’ has recently been attracting growing interest as a promising concept for the next generation electronics, because non-dissipative pure valley currents with no accompanying net charge flow can be manipulated for computational use, akin to pure spin currents 1 . Valley is a quantum number defined in an electronic system whose energy bands contain energetically degenerate but non-equivalent local minima (conduction band) or maxima (valence band) due to a certain crystal structure. Specifically, spatial inversion symmetry broken two-dimensional honeycomb lattice systems exhibiting Berry curvature is a subset of possible systems that enable optical 2 , 3 , 4 , 5 , magnetic 6 , 7 , 8 , 9 and electrical control of the valley degree of freedom 10 , 11 , 12 . Here we use dual-gated bilayer graphene to electrically induce and control broken inversion symmetry (or Berry curvature) as well as the carrier density for generating and detecting the pure valley current. In the insulating regime, at zero-magnetic field, we observe a large nonlocal resistance that scales cubically with the local resistivity, which is evidence of pure valley current. Main Charge and spin are both well-defined quantum numbers in solids. Spintronics is a technology that uses the spin degree of freedom. The application range of spintronics has been largely expanded by the development of electrical techniques for generating and detecting the spin current 1 . The valley degree of freedom in solid crystals can be handled by controlling the occupation of the non-equivalent structures in the band, providing the novel concept of so-called valleytronics. Among various material candidates for valleytronics, two-dimensional (2D) honeycomb lattice systems with broken spatial inversion symmetry, such as gapped graphene and transition metal dichalcogenide (TMDC), are predicted to be the most useful. These systems have two valleys, called K and K′. Optical 2 , 3 , 4 , 5 , magnetic 6 , 7 , 8 , 9 and electrical 10 , 11 , 12 control of the valley has been demonstrated. In particular, Berry curvature, which emerges in these honeycomb lattice systems with broken spatial inversion symmetry, enables electrical control of the valley degree of freedom. Berry curvature acts as an out-of-plane pseudo-magnetic field in momentum space and has opposite sign between the two valleys. Therefore, a transverse pure valley current is generated by means of the anomalous velocity, in analogy to a transverse electronic current being generated by means of the Lorentz force due to a magnetic field in real space 13 , 14 (see Fig. 1d ). This phenomenon is called the valley Hall effect 10 and can be used to generate a valley current. The inverse valley Hall effect, which converts the valley current into a transverse electric field, allows the detection of the pure valley current. Figure 1: Scheme for detection of the nonlocal resistance due to valley current flow in BLG. a , Band structure, Berry curvature and valley Hall conductivity of BLG. A band gap 2 Δ and Berry curvature Ω emerge as a result of broken spatial inversion symmetry. The valley Hall conductivity σ xy VH , which is calculated by integrating the Berry curvature, is constant in the bandgap. b , Schematic of the dual-gated BLG device. The top gate is a gold film, and the back gate is a p-doped silicon substrate. Two h-BN layers and a SiO 2 film are used as gate insulators. Using these gates, the carrier density and perpendicular electric field (displacement field) are independently varied. Expanded image: Lattice structure of AB-stacked BLG. In the presence of a displacement field, an energy difference between the top and bottom layer emerges. Therefore spatial inversion symmetry is broken in this system, and both Berry curvature and a bandgap emerge. c , AFM image of the BLG device without the top h-BN. The light blue region indicates the area of the top gate. The BLG has a mobility of ∼ 15,000 cm 2 V −1 s −1 at both 1.5 and 70 K. d , Schematic of the nonlocal resistance measurement and the nonlocal transport mediated by a pure valley current. The electric field driving the charge current in the left-hand circuit generates a pure valley current in the transverse direction by means of the valley Hall effect (VHE). This valley current is converted into an electric field or nonlocal voltage in the right-hand circuit by means of the inverse valley Hall effect (IVHE) to generate the nonlocal resistance. Full size image The valley Hall effect was first reported for photo-generated electrons in monolayer MoS 2 (ref. 11 ). However, the small inter-valley scattering length in this material prevents the detection of the pure valley current, which does not accompany the electronic current. Compared to TMDC, graphene has a much larger inter-valley scattering length owing to its higher crystal quality. Monolayer graphene on h-BN has more recently been used to generate and detect the pure valley current, where the crystal direction of the graphene was aligned to that of the h-BN such that the superlattice potential imposed by the h-BN structurally breaks the spatial inversion symmetry 12 . The valley Hall effect was analysed in detail with the carrier density as a parameter using metallic samples whose resistivity decreases as the temperature is lowered, but leaving unaddressed the insulating regime, which is more appropriate for investigating the pure valley current. In this work we employed bilayer graphene (BLG) to generate and detect the valley current. We used a perpendicular electric field to break the spatial inversion symmetry and induce Berry curvature as well as a bandgap (see Fig. 1a ). The dual-gated structure seen in Fig. 1b allows electrical and independent control of the perpendicular electric field and the carrier density 15 , 16 , 17 , 18 , 19 . This is in contrast to the monolayer graphene samples in ref. 12 , where the monolayer graphene has to be structurally aligned with h-BN through a process of mechanical transfer. BLG valley Hall devices therefore show greater<|im_end|> <|im_start|>assistant University of Tokyo researchers have demonstrated an electrically-controllable valley current device that may pave the way to ultra-low-power "valleytronics" devices. On the atomic scale, matter behaves as both a particle and a wave. Electrons, therefore, have an associated wavelength that usually can have many different values. In crystalline systems however, certain wavelengths may be favored. Graphene, for example, has two favored wavelengths known as K and K' (K prime). This means that two electrons in graphene can have the same energy but different wavelengths - or, to put it another way, different "valley." Electronics use charge to represent information, but when charge flows through a material, some energy is dissipated as heat, a problem for all electronic devices in use today. However, if the same quantity of electrons in a channel flow in opposite directions, no net charge is transferred and no heat is dissipated - but in a normal electronic device this would mean that no information was passed either. A valleytronics device transmitting information using pure valley current, where electrons with the same valley flow in one direction, would not have this limitation, and offers a route to realizing extremely low power devices. Experimental studies on valley current have only recently started. Control of valley current in a graphene monolayer has been demonstrated, but only under very specific conditions and with limited control of conversion from charge current to valley current. In order for valley current to be a viable alternative to charge current-based modern electronics, it is necessary to control the conversion between charge current and valley current over a wide range at high temperatures. Now, Professor Seigo Tarucha's research group at the Department of Applied Physics at the Graduate School of Engineering has created an electrically controllable valley current device that converts conventional electrical current to valley current, passes it through a long (3.5 micron) channel, then converts the valley current back into charge current that can be detected by a measurable voltage. The research group used a graphene bilayer sandwiched between two insulator layers, with the whole device sandwiched between two conducting layers or 'gates', allowing for the control of valley. A vertical electric field (green arrows) breaks the symmetry of the bilayer graphene allowing for selective control of valley. A conventional, small electrical current (purple arrow) is converted into valley current via the valley Hall effect (VHE). (The electrons in the K valley, blue, travel to the right; while the electrons in the Kâ€� valley, pink, travel to the left.) Pure valley current travels over a significant distance. At the other side of the device the valley current is converted back to charge current via the inverse valley Hall effect (IVHE) and is detected as a voltage. Credit: (c) 2015 Seigo Tarucha The group transferred valley current over a distance large enough to exclude other possible competing explanations for their results and were able to control the efficiency of valley current conversion over a wide range. The device also operated at temperatures far higher than expected. "We usually measure our devices at temperatures lower than the liquefaction point of Helium (-268.95 C, just 4.2 K above absolute zero) to detect this type of phenomena," says Dr. Yamamoto, a member of the research group. "We were surprised that the signal could be detected even at -203.15 C (70 K). In the future, it may be possible to develop devices that can operate at room temperature." "Valley current, unlike charge current is non dissipative. This means that no energy is lost during the transfer of information," says Professor Tarucha. He continues, "With power consumption becoming a major issue in modern electronics, valley current based devices open up a new direction for future ultra-low-power consumption computing devices." An Atomic Force Microscope image of the valleytronics device. The bright orange area is bilayer graphene. The light blue area shows the area of the top gate. Current is injected from the right side of the device, and converted to valley current. The valley current is converted back to charge current and detected as a voltage signal. Credit: (c) 2015 Seigo Tarucha <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 578, 2115, 315, 3451, 2257, 3258, 35785, 1233, 529, 706, 6051, 1027, 51647, 7982, 2802, 439, 264, 26455, 7434, 369, 279, 1828, 9659, 31591, 11, 1606, 2536, 1773, 1056, 575, 1413, 10748, 34681, 60701, 449, 912, 24442, 4272, 6900, 6530, 649, 387, 55315, 369, 55580, 1005, 11, 53007, 311, 10748, 12903, 60701, 220, 16, 662, 13345, 374, 264, 31228, 1396, 4613, 304, 459, 14683, 1887, 6832, 4907, 21562, 6782, 38556, 456, 2740, 5367, 13523, 719, 2536, 63359, 12031, 2254, 1332, 7675, 320, 444, 23985, 7200, 8, 477, 1973, 7675, 320, 838, 768, 7200, 8, 4245, 311, 264, 3738, 26110, 6070, 13, 45863, 11, 29079, 47588, 46220, 11102, 1403, 33520, 26828, 22631, 55372, 6067, 87719, 44685, 83233, 374, 264, 27084, 315, 3284, 6067, 430, 7431, 29393, 220, 17, 1174, 220, 18, 1174, 220, 19, 1174, 220, 20, 1174, 24924, 220, 21, 1174, 220, 22, 1174, 220, 23, 1174, 220, 24, 323, 20314, 2585, 315, 279, 34681, 8547, 315, 11542, 220, 605, 1174, 220, 806, 1174, 220, 717, 662, 5810, 584, 1005, 19091, 2427, 660, 20934, 1155, 66192, 311, 9249, 750, 49853, 323, 2585, 11102, 47588, 46220, 320, 269, 44685, 83233, 8, 439, 1664, 439, 279, 19115, 17915, 369, 24038, 323, 54626, 279, 10748, 34681, 1510, 13, 763, 279, 1672, 15853, 17942, 11, 520, 7315, 1474, 39100, 2115, 11, 584, 23846, 264, 3544, 2536, 2497, 13957, 430, 29505, 19250, 2740, 449, 279, 2254, 22884, 1968, 11, 902, 374, 6029, 315, 10748, 34681, 1510, 13, 4802, 37895, 323, 12903, 527, 2225, 1664, 39817, 31228, 5219, 304, 82486, 13, 41785, 35785, 1233, 374, 264, 5557, 430, 5829, 279, 12903, 8547, 315, 11542, 13, 578, 3851, 2134, 315, 12903, 35785, 1233, 706, 1027, 14090, 17626, 555, 279, 4500, 315, 20314, 12823, 369, 24038, 323, 54626, 279, 12903, 1510, 220, 16, 662, 578, 34681, 8547, 315, 11542, 304, 6573, 48473, 649, 387, 18073, 555, 26991, 279, 30747, 315, 279, 2536, 63359, 12031, 14726, 304, 279, 7200, 11, 8405, 279, 11775, 7434, 315, 779, 19434, 34681, 35785, 1233, 13, 22395, 5370, 3769, 11426, 369, 34681, 35785, 1233, 11, 1403, 33520, 320, 17, 35, 8, 26828, 22631, 55372, 6067, 449, 11102, 29079, 47588, 46220, 11, 1778, 439, 342, 5795, 66192, 323, 9320, 9501, 29953, 17356, 11968, 579, 320, 22809, 5744, 705, 527, 19698, 311, 387, 279, 1455, 5505, 13, 4314, 6067, 617, 1403, 86497, 11, 2663, 735, 323, 735, 39615, 13, 75939, 220, 17, 1174, 220, 18, 1174, 220, 19, 1174, 220, 20, 1174, 24924, 220, 21, 1174, 220, 22, 1174, 220, 23, 1174, 220, 24, 323, 20314, 220, 605, 1174, 220, 806, 1174, 220, 717, 2585, 315, 279, 34681, 706, 1027, 21091, 13, 763, 4040, 11, 44685, 83233, 11, 902, 59696, 304, 1521, 26828, 22631, 55372, 6067, 449, 11102, 29079, 47588, 46220, 11, 20682, 20314, 2585, 315, 279, 34681, 8547, 315, 11542, 13, 44685, 83233, 14385, 439, 459, 704, 8838, 90649, 35850, 1474, 39100, 2115, 304, 24151, 3634, 323, 706, 14329, 1879, 1990, 279, 1403, 86497, 13, 15636, 11, 264, 1380, 4550, 10748, 34681, 1510, 374, 8066, 555, 3445, 315, 279, 37782, 30543, 15798, 11, 304, 56203, 311, 264, 1380, 4550, 14683, 1510, 1694, 8066, 555, 3445, 315, 279, 54333, 406, 89, 5457, 4245, 311, 264, 24924, 2115, 304, 1972, 3634, 220, 1032, 1174, 220, 975, 320, 4151, 23966, 13, 220, 16, 67, 7609, 1115, 25885, 374, 2663, 279, 34681, 11166, 2515, 220, 605, 323, 649, 387, 1511, 311, 7068, 264, 34681, 1510, 13, 578, 29049, 34681, 11166, 2515, 11, 902, 33822, 279, 34681, 1510, 1139, 264, 1380, 4550, 9249, 2115, 11, 6276, 279, 18468, 315, 279, 10748, 34681, 1510, 13, 19575, 220, 16, 25, 44881, 369, 18468, 315, 279, 2536, 2497, 13957, 4245, 311, 34681, 1510, 6530, 304, 15195, 38, 13, 264, 1174, 17366, 6070, 11, 44685, 83233, 323, 34681, 11166, 98971, 315, 15195, 38, 13, 362, 7200, 13225, 220, 17, 82263, 323, 44685, 83233, 117336, 34044, 439, 264, 1121, 315, 11102, 29079, 47588, 46220, 13, 578, 34681, 11166, 98971, 48823, 31884, 99122, 1174, 902, 374, 16997, 555, 54952, 279, 44685, 83233, 11, 374, 6926, 304, 279, 7200, 42510, 13, 293, 1174, 328, 82149, 315, 279, 19091, 2427, 660, 15195, 38, 3756, 13, 578, 1948, 18618, 374, 264, 6761, 4632, 11, 323, 279, 1203, 18618, 374, 264, 281, 1773, 16771, 51692, 54057, 13, 9220, 305, 7826, 45, 13931, 323, 264, 12095, 46, 220, 17, 4632, 527, 1511, 439, 18618, 1672, 42391, 13, 12362, 1521, 35634, 11, 279, 19115, 17915, 323, 77933, 9249, 2115, 320, 4338, 16491, 2115, 8, 527, 29235, 28830, 13, 40337, 2217, 25, 445, 32891, 6070, 315, 14469, 5594, 11440, 15195, 38, 13, 763, 279, 9546, 315, 264, 44153, 2115, 11, 459, 4907, 6811, 1990, 279, 1948, 323, 5740, 6324, 59696, 13, 15636, 29079, 47588, 46220, 374, 11102, 304, 420, 1887, 11, 323, 2225, 44685, 83233, 323, 264, 7200, 42510, 34044, 13, 272, 1174, 20479, 44, 2217, 315, 279, 15195, 38, 3756, 2085, 279, 1948, 305, 7826, 45, 13, 578, 3177, 6437, 5654, 15151, 279, 3158, 315, 279, 1948, 18618, 13, 578, 15195, 38, 706, 264, 31139, 315, 12264, 120, 220, 868, 11, 931, 10166, 220, 17, 650, 25173, 16, 274, 25173, 16, 520, 2225, 220, 16, 13, 20, 323, 220, 2031, 735, 13, 294, 1174, 328, 82149, 315, 279, 2536, 2497, 13957, 19179, 323, 279, 2536, 2497, 7710, 78926, 555, 264, 10748, 34681, 1510, 13, 578, 9249, 2115, 10043, 279, 6900, 1510, 304, 279, 2163, 25417, 16622, 27983, 264, 10748, 34681, 1510, 304, 279, 1380, 4550, 5216, 555, 3445, 315, 279, 34681, 11166, 2515, 320, 53, 1837, 570, 1115, 34681, 1510, 374, 16489, 1139, 459, 9249, 2115, 477, 2536, 2497, 22465, 304, 279, 1314, 25417, 16622, 555, 3445, 315, 279, 29049, 34681, 11166, 2515, 320, 3166, 1837, 8, 311, 7068, 279, 2536, 2497, 13957, 13, 8797, 1404, 2217, 578, 34681, 11166, 2515, 574, 1176, 5068, 369, 6685, 16581, 57678, 304, 1647, 337, 1155, 6178, 50, 220, 17, 320, 1116, 13, 220, 806, 7609, 4452, 11, 279, 2678, 958, 46254, 3258, 72916, 3160, 304, 420, 3769, 29034, 279, 18468, 315, 279, 10748, 34681, 1510, 11, 902, 1587, 539, 19780, 279, 14683, 1510, 13, 59813, 311, 24929, 5744, 11, 66192, 706, 264, 1790, 8294, 958, 46254, 3258, 72916, 3160, 56612, 311, 1202, 5190, 26110, 4367, 13, 3206, 337, 1155, 66192, 389, 305, 7826, 45, 706, 810, 6051, 1027, 1511, 311, 7068, 323, 11388, 279, 10748, 34681, 1510, 11, 1405, 279, 26110, 5216, 315, 279, 66192, 574, 27210, 311, 430, 315, 279, 305, 7826, 45, 1778, 430, 279, 2307, 75, 32891, 4754, 27070, 555, 279, 305, 7826, 45, 2080, 43024, 18808, 279, 29079, 47588, 46220, 220, 717, 662, 578, 34681, 11166, 2515, 574, 67458, 304, 7872, 449, 279, 19115, 17915, 439, 264, 5852, 1701, 46258, 10688, 6832, 22884, 1968, 43154, 439, 279, 9499, 374, 39920, 11, 719, 9564, 653, 5102, 291, 279, 1672, 15853, 17942, 11, 902, 374, 810, 8475, 369, 24834, 279, 10748, 34681, 1510, 13, 763, 420, 990, 584, 20011, 20934, 1155, 66192, 320, 9574, 38, 8, 311, 7068, 323, 11388, 279, 34681, 1510, 13, 1226, 1511, 264, 77933, 9249, 2115, 311, 1464, 279, 29079, 47588, 46220, 323, 49853, 44685, 83233, 439, 1664, 439, 264, 7200, 42510, 320, 4151, 23966, 13, 220, 16, 64, 7609, 578, 19091, 2427, 660, 6070, 3970, 304, 23966, 13, 220, 16, 65, 6276, 20314, 323, 9678, 2585, 315, 279, 77933, 9249, 2115, 323, 279, 19115, 17915, 220, 868, 1174, 220, 845, 1174, 220, 1114, 1174, 220, 972, 1174, 220, 777, 662, 1115, 374, 304, 13168, 311, 279, 1647, 337, 1155, 66192, 10688, 304, 2098, 13, 220, 717, 1174, 1405, 279, 1647, 337, 1155, 66192, 706, 311, 387, 2080, 43024, 27210, 449, 305, 7826, 45, 1555, 264, 1920, 315, 22936, 8481, 13, 15195, 38, 34681, 11166, 7766, 9093, 1501, 7191, 128257, 198, 128256, 78191, 198, 31272, 315, 27286, 12074, 617, 21091, 459, 9249, 750, 35172, 69855, 34681, 1510, 3756, 430, 1253, 94123, 279, 1648, 311, 24955, 60369, 27624, 330, 838, 3258, 35785, 1233, 1, 7766, 13, 1952, 279, 25524, 5569, 11, 5030, 74157, 439, 2225, 264, 19320, 323, 264, 12330, 13, 10085, 26692, 11, 9093, 11, 617, 459, 5938, 46406, 430, 6118, 649, 617, 1690, 2204, 2819, 13, 763, 64568, 483, 6067, 4869, 11, 3738, 93959, 1253, 387, 46603, 13, 12441, 1994, 11, 369, 3187, 11, 706, 1403, 46603, 93959, 3967, 439, 735, 323, 735, 6, 320, 42, 10461, 570, 1115, 3445, 430, 1403, 57678, 304, 66192, 649, 617, 279, 1890, 4907, 719, 2204, 93959, 482, 477, 11, 311, 2231, 433, 2500, 1648, 11, 2204, 330, 838, 3258, 1210, 38784, 1005, 6900, 311, 4097, 2038, 11, 719, 994, 6900, 28555, 1555, 264, 3769, 11, 1063, 4907, 374, 14091, 63332, 439, 8798, 11, 264, 3575, 369, 682, 14683, 7766, 304, 1005, 3432, 13, 4452, 11, 422, 279, 1890, 12472, 315, 57678, 304, 264, 5613, 6530, 304, 14329, 18445, 11, 912, 4272, 6900, 374, 23217, 323, 912, 8798, 374, 14091, 63332, 482, 719, 304, 264, 4725, 14683, 3756, 420, 1053, 3152, 430, 912, 2038, 574, 5946, 3060, 13, 362, 34681, 35785, 1233, 3756, 78768, 2038, 1701, 10748, 34681, 1510, 11, 1405, 57678, 449, 279, 1890, 34681, 6530, 304, 832, 5216, 11, 1053, 539, 617, 420, 20893, 11, 323, 6209, 264, 6149, 311, 44114, 9193, 3428, 2410, 7766, 13, 57708, 7978, 389, 34681, 1510, 617, 1193, 6051, 3940, 13, 7935, 315, 34681, 1510, 304, 264, 66192, 1647, 337, 1155, 706, 1027, 21091, 11, 719, 1193, 1234, 1633, 3230, 4787, 323, 449, 7347, 2585, 315, 14747, 505, 6900, 1510, 311, 34681, 1510, 13, 763, 2015, 369, 34681, 1510, 311, 387, 264, 31528, 10778, 311, 6900, 1510, 6108, 6617, 31591, 11, 433, 374, 5995, 311, 2585, 279, 14747, 1990, 6900, 1510, 323, 34681, 1510, 927, 264, 7029, 2134, 520, 1579, 20472, 13, 4800, 11, 17054, 1369, 7992, 24912, 55481, 596, 3495, 1912, 520, 279, 6011, 315, 43608, 28415, 520, 279, 44825, 6150, 315, 17005, 706, 3549, 459, 9249, 750, 687, 69855, 34681, 1510, 3756, 430, 33822, 21349, 20314, 1510, 311, 34681, 1510, 11, 16609, 433, 1555, 264, 1317, 320, 18, 13, 20, 95309, 8, 5613, 11, 1243, 33822, 279, 34681, 1510, 1203, 1139, 6900, 1510, 430, 649, 387, 16914, 555, 264, 66303, 22465, 13, 578, 3495, 1912, 1511, 264, 66192, 20934, 1155, 28974, 291, 1990, 1403, 1672, 10733, 13931, 11, 449, 279, 4459, 3756, 28974, 291, 1990, 1403, 31474, 13931, 477, 364, 70, 988, 518, 10923, 369, 279, 2585, 315, 34681, 13, 362, 12414, 9249, 2115, 320, 13553, 38057, 8, 18808, 279, 46220, 315, 279, 20934, 1155, 66192, 10923, 369, 44010, 2585, 315, 34681, 13, 362, 21349, 11, 2678, 20314, 1510, 320, 57607, 18404, 8, 374, 16489, 1139, 34681, 1510, 4669, 279, 34681, 11166, 2515, 320, 53, 1837, 570, 320, 791, 57678, 304, 279, 735, 34681, 11, 6437, 11, 5944, 311, 279, 1314, 26, 1418, 279, 57678, 304, 279, 735, 9011, 15406, 5809, 34681, 11, 18718, 11, 5944, 311, 279, 2163, 6266, 30688, 34681, 1510, 35292, 927, 264, 5199, 6138, 13, 2468, 279, 1023, 3185, 315, 279, 3756, 279, 34681, 1510, 374, 16489, 1203, 311, 6900, 1510, 4669, 279, 29049, 34681, 11166, 2515, 320, 3166, 1837, 8, 323, 374, 16914, 439, 264, 22465, 13, 16666, 25, 320, 66, 8, 220, 679, 20, 1369, 7992, 24912, 55481, 578, 1912, 23217, 34681, 1510, 927, 264, 6138, 3544, 3403, 311, 22429, 1023, 3284, 27260, 41941, 369, 872, 3135, 323, 1051, 3025, 311, 2585, 279, 15374, 315, 34681, 1510, 14747, 927, 264, 7029, 2134, 13, 578, 3756, 1101, 24026, 520, 20472, 3117, 5190, 1109, 3685, 13, 330, 1687, 6118, 6767, 1057, 7766, 520, 20472, 4827, 1109, 279, 93542, 91409, 1486, 315, 16183, 2411, 10505, 16332, 13, 2721, 356, 11, 1120, 220, 19, 13, 17, 735, 3485, 10973, 7315, 8, 311, 11388, 420, 955, 315, 44247, 1359, 2795, 2999, 13, 34654, 57960, 11, 264, 4562, 315, 279, 3495, 1912, 13, 330, 1687, 1051, 14792, 430, 279, 8450, 1436, 387, 16914, 1524, 520, 482, 9639, 13, 868, 356, 320, 2031, 735, 570, 763, 279, 3938, 11, 433, 1253, 387, 3284, 311, 2274, 7766, 430, 649, 14816, 520, 3130, 9499, 1210, 330, 2257, 3258, 1510, 11, 20426, 6900, 1510, 374, 2536, 93522, 1413, 13, 1115, 3445, 430, 912, 4907, 374, 5675, 2391, 279, 8481, 315, 2038, 1359, 2795, 17054, 24912, 55481, 13, 1283, 9731, 11, 330, 2409, 2410, 15652, 10671, 264, 3682, 4360, 304, 6617, 31591, 11, 34681, 1510, 3196, 7766, 1825, 709, 264, 502, 5216, 369, 3938, 24955, 60369, 27624, 15652, 25213, 7766, 1210, 1556, 31416, 11994, 18654, 4280, 2217, 315, 279, 34681, 35785, 1233, 3756, 13, 578, 10107, 19087, 3158, 374, 20934, 1155, 66192, 13, 578, 3177, 6437, 3158, 5039, 279, 3158, 315, 279, 1948, 18618, 13, 9303, 374, 41772, 505, 279, 1314, 3185, 315, 279, 3756, 11, 323, 16489, 311, 34681, 1510, 13, 578, 34681, 1510, 374, 16489, 1203, 311, 6900, 1510, 323, 16914, 439, 264, 22465, 8450, 13, 16666, 25, 320, 66, 8, 220, 679, 20, 1369, 7992, 24912, 55481, 220, 128257, 198 ]

2,169

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Digital technologies are being harnessed to support the public-health response to COVID-19 worldwide, including population surveillance, case identification, contact tracing and evaluation of interventions on the basis of mobility data and communication with the public. These rapid responses leverage billions of mobile phones, large online datasets, connected devices, relatively low-cost computing resources and advances in machine learning and natural language processing. This Review aims to capture the breadth of digital innovations for the public-health response to COVID-19 worldwide and their limitations, and barriers to their implementation, including legal, ethical and privacy barriers, as well as organizational and workforce barriers. The future of public health is likely to become increasingly digital, and we review the need for the alignment of international strategies for the regulation, evaluation and use of digital technologies to strengthen pandemic management, and future preparedness for COVID-19 and other infectious diseases. Main COVID-19, a previously unknown respiratory illness caused by the coronavirus SARS-CoV-2 1 , 2 , was declared a pandemic by the World Health Organization (WHO) on 11 March 2020, less than 3 months after cases were first detected. With now over 9.8 million confirmed cases and more than 495,000 deaths 3 recorded worldwide, there are grave concerns about the global health, societal and economic effects of this virus, particularly on vulnerable and disadvantaged populations, and in low- and middle-income countries with fragile health systems 4 , 5 . At the time of this writing, 7.1 billion people live in countries that have had substantial travel and social restrictions 6 . As with the control of outbreaks and pandemics before it, controlling the COVID-19 pandemic rests on the detection and containment of clusters of infection and the interruption of community transmission to mitigate the impact on human health. During the plague outbreak that affected 14th-century Europe, isolation of affected communities and restriction of population movement were used to avoid further spread 7 . These public-health measures for outbreak response remain relevant today, including surveillance, rapid case identification, interruption of community transmission and strong public communication. Monitoring how these measures are implemented and their impact on incidence and mortality is essential. All countries are required by the International Health Regulations (2005) 8 to have core capacity to ensure national preparedness for infectious hazards that have the potential to spread internationally. Research and development of new methods and technologies to strengthen these core capacities often occurs during outbreaks, when innovation is an absolute necessity 9 . During the outbreak of severe acute respiratory syndrome in 2003, Hong Kong identified clusters of disease through the use of electronic data systems 10 . During the Ebola outbreaks in West Africa in 2014–2016, mobile phone data were used to model travel patterns 11 , and hand-held sequencing devices permitted more-effective contact tracing and a better understanding of the dynamics of the outbreaks 12 . Similarly, digital technologies also have been deployed in the COVID-19 pandemic 13 , 14 (Table 1 ) to strengthen each of the four public-health measures noted above. Table 1 Digital technologies used in the COVID-19 pandemic Full size table The digital revolution has transformed many aspects of life. As of 2019, 67% of the global population had subscribed to mobile devices, of which 65% were smartphones—with the fastest growth in Sub-Saharan Africa 15 . In 2019, 204 billion apps were downloaded 16 , and as of January 2020, 3.8 billion people actively used social media 17 . Here we critically review how digital technologies are being harnessed for the public-health response to COVID-19 worldwide (Fig. 1 ). We discuss the breadth of innovations and their respective limitations. This systems-level approach is needed to inform how digital strategies can be incorporated into COVID-19-control strategies, and to help prepare for future epidemics. Fig. 1: The interconnected digital technologies used in the public-health response to COVID-19. Many approaches use a combination of digital technologies and may rely on telecommunications infrastructure and internet availability. Machine learning is shown as a separate branch for clarity, although it also underpins many of the other technologies. Much of the data generated from these technologies feeds into data dashboards. SMS, short message service. Full size image Digital epidemiological surveillance A core public-health function of outbreak management is understanding infection transmission in time, place and person, and identifying risk factors for the disease to guide effective interventions. A range of digital data sources are being used to enhance and interpret key epidemiological data gathered by public-health authorities for COVID-19. Online data sources for early disease detection Established population-surveillance systems typically rely on health-related data from laboratories, notifications of cases diagnosed by clinicians and syndromic surveillance networks. Syndromic surveillance networks are based on reports of clinical symptoms, such as ‘influenza-like illness’, rather than a laboratory diagnosis, from hospital and selected sentinel primary and secondary healthcare facilities, which agree to provide regular surveillance data of all cases. These sources, however, ultimately miss cases in which healthcare is not sought. In the UK, for example, where until recently only hospitalized patients and healthcare workers were routinely tested for COVID-19, confirmed cases represent an estimated 4.7% of symptomatic COVID-19 cases 18 . Identifying undetected cases would help elucidate the magnitude and characteristics of the outbreak 19 and reduce onward transmission. In the past two decades, data from online news sites, news-aggregation services, social networks, web searches and participatory longitudinal community cohorts have aimed to fill this gap. Data-aggregation systems, including ProMED-mail 20 , GPHIN 21 , HealthMap 22 and EIOS 23 , which use natural language processing and machine learning to process and filter online data, have been developed to provide epidemiological insight. These data sources are increasingly being integrated into the formal surveillance landscape 24 and have a role in COVID-19 surveillance. The WHO’s platform EPI-BRAIN brings together diverse datasets for infectious-disease emergency preparedness and response, including environmental and meteorological data 25 . Several systems have claimed detection of early disease reports for COVID-19, through the use of crowdsourced data and news reports, before the WHO released a statement", "role": "user" }, { "content": "Digital technologies have an important role to play in responding to future pandemics, a new study in the journal, Nature Medicine reports. During this unique study, researchers from the i-sense project, led by Professor Rachel McKendry from UCL, reviewed how digital technologies have been mobilized in response to COVID-19. The associated concerns with privacy, the effectiveness of such technologies and how they can be used in future pandemics were also examined by the team which includes Professor Vince Emery from the University of Surrey. Researchers found to get the most out of digital technologies, they should be developed collaboratively with governments and healthcare providers, ensuring they meet public health needs and ethical standards. It was recommended that key stakeholders in the digital field, such as technology companies, should be long-term partners in preparedness planning rather than being partners only when emergencies are ongoing. The benefits of digital technologies such as access to faster and more widespread communication, including through social media platforms, TV briefings and text message updates was noted by researchers. The efforts of some technology companies such as Google who have been prioritizing messaging from trusted sources, including the WHO, in their search responses were also recognized. David Heymann, Professor of Infectious Disease Epidemiology at the London School of Hygiene & Tropical Medicine, said: \"We need to ensure new digital technologies go through rigorous evaluation to identify those technologies that prove to be effective so that they can add to our armamentarium for outbreak control, adhere to privacy and ethics frameworks, and are built into online pathways developed in collaboration with end-users.\" However researchers did find some problems with the use of digital technologies during pandemics. During the outbreak of COVID-19, many technologies have been adapted and developed on a scale never seen before, including new apps and data dashboards using anonymised and aggregated data to help inform public health interventions. This has led to concerns about civil liberties and privacy. Chief scientific advisor, Department for International Trade, Dr. Mike Short CBE, said: \"Although times of emergency may call for different data access requirements, any data used for the pandemic response should not be misused beyond this purpose, and systems need to be proofed against invasion of privacy and comply with relevant governance.\" Researchers also noted that the use of data to inform outbreak response should also take into account the digital divide across the globe as although 67 percent of the global population subscribe to a mobile device, 51 percent of the world's population are not mobile internet subscribers. As many of these interventions and surveillance methods rely on connectivity, researchers found many communities may be left behind or missed from statistics. Professor Vince Emery, emeritus professor of translational virology at the University of Surrey, said: \"This review provides further impetus to the deployment of digital technologies to sense pandemics and with the roll-out of 5G new exciting possibilities will develop and contribute to controlling major public health emergencies. Viruses know no borders and, increasingly, neither do digital technologies and data so it is important they are utilized to their full potential.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Digital technologies are being harnessed to support the public-health response to COVID-19 worldwide, including population surveillance, case identification, contact tracing and evaluation of interventions on the basis of mobility data and communication with the public. These rapid responses leverage billions of mobile phones, large online datasets, connected devices, relatively low-cost computing resources and advances in machine learning and natural language processing. This Review aims to capture the breadth of digital innovations for the public-health response to COVID-19 worldwide and their limitations, and barriers to their implementation, including legal, ethical and privacy barriers, as well as organizational and workforce barriers. The future of public health is likely to become increasingly digital, and we review the need for the alignment of international strategies for the regulation, evaluation and use of digital technologies to strengthen pandemic management, and future preparedness for COVID-19 and other infectious diseases. Main COVID-19, a previously unknown respiratory illness caused by the coronavirus SARS-CoV-2 1 , 2 , was declared a pandemic by the World Health Organization (WHO) on 11 March 2020, less than 3 months after cases were first detected. With now over 9.8 million confirmed cases and more than 495,000 deaths 3 recorded worldwide, there are grave concerns about the global health, societal and economic effects of this virus, particularly on vulnerable and disadvantaged populations, and in low- and middle-income countries with fragile health systems 4 , 5 . At the time of this writing, 7.1 billion people live in countries that have had substantial travel and social restrictions 6 . As with the control of outbreaks and pandemics before it, controlling the COVID-19 pandemic rests on the detection and containment of clusters of infection and the interruption of community transmission to mitigate the impact on human health. During the plague outbreak that affected 14th-century Europe, isolation of affected communities and restriction of population movement were used to avoid further spread 7 . These public-health measures for outbreak response remain relevant today, including surveillance, rapid case identification, interruption of community transmission and strong public communication. Monitoring how these measures are implemented and their impact on incidence and mortality is essential. All countries are required by the International Health Regulations (2005) 8 to have core capacity to ensure national preparedness for infectious hazards that have the potential to spread internationally. Research and development of new methods and technologies to strengthen these core capacities often occurs during outbreaks, when innovation is an absolute necessity 9 . During the outbreak of severe acute respiratory syndrome in 2003, Hong Kong identified clusters of disease through the use of electronic data systems 10 . During the Ebola outbreaks in West Africa in 2014–2016, mobile phone data were used to model travel patterns 11 , and hand-held sequencing devices permitted more-effective contact tracing and a better understanding of the dynamics of the outbreaks 12 . Similarly, digital technologies also have been deployed in the COVID-19 pandemic 13 , 14 (Table 1 ) to strengthen each of the four public-health measures noted above. Table 1 Digital technologies used in the COVID-19 pandemic Full size table The digital revolution has transformed many aspects of life. As of 2019, 67% of the global population had subscribed to mobile devices, of which 65% were smartphones—with the fastest growth in Sub-Saharan Africa 15 . In 2019, 204 billion apps were downloaded 16 , and as of January 2020, 3.8 billion people actively used social media 17 . Here we critically review how digital technologies are being harnessed for the public-health response to COVID-19 worldwide (Fig. 1 ). We discuss the breadth of innovations and their respective limitations. This systems-level approach is needed to inform how digital strategies can be incorporated into COVID-19-control strategies, and to help prepare for future epidemics. Fig. 1: The interconnected digital technologies used in the public-health response to COVID-19. Many approaches use a combination of digital technologies and may rely on telecommunications infrastructure and internet availability. Machine learning is shown as a separate branch for clarity, although it also underpins many of the other technologies. Much of the data generated from these technologies feeds into data dashboards. SMS, short message service. Full size image Digital epidemiological surveillance A core public-health function of outbreak management is understanding infection transmission in time, place and person, and identifying risk factors for the disease to guide effective interventions. A range of digital data sources are being used to enhance and interpret key epidemiological data gathered by public-health authorities for COVID-19. Online data sources for early disease detection Established population-surveillance systems typically rely on health-related data from laboratories, notifications of cases diagnosed by clinicians and syndromic surveillance networks. Syndromic surveillance networks are based on reports of clinical symptoms, such as ‘influenza-like illness’, rather than a laboratory diagnosis, from hospital and selected sentinel primary and secondary healthcare facilities, which agree to provide regular surveillance data of all cases. These sources, however, ultimately miss cases in which healthcare is not sought. In the UK, for example, where until recently only hospitalized patients and healthcare workers were routinely tested for COVID-19, confirmed cases represent an estimated 4.7% of symptomatic COVID-19 cases 18 . Identifying undetected cases would help elucidate the magnitude and characteristics of the outbreak 19 and reduce onward transmission. In the past two decades, data from online news sites, news-aggregation services, social networks, web searches and participatory longitudinal community cohorts have aimed to fill this gap. Data-aggregation systems, including ProMED-mail 20 , GPHIN 21 , HealthMap 22 and EIOS 23 , which use natural language processing and machine learning to process and filter online data, have been developed to provide epidemiological insight. These data sources are increasingly being integrated into the formal surveillance landscape 24 and have a role in COVID-19 surveillance. The WHO’s platform EPI-BRAIN brings together diverse datasets for infectious-disease emergency preparedness and response, including environmental and meteorological data 25 . Several systems have claimed detection of early disease reports for COVID-19, through the use of crowdsourced data and news reports, before the WHO released a statement<|im_end|> <|im_start|>assistant Digital technologies have an important role to play in responding to future pandemics, a new study in the journal, Nature Medicine reports. During this unique study, researchers from the i-sense project, led by Professor Rachel McKendry from UCL, reviewed how digital technologies have been mobilized in response to COVID-19. The associated concerns with privacy, the effectiveness of such technologies and how they can be used in future pandemics were also examined by the team which includes Professor Vince Emery from the University of Surrey. Researchers found to get the most out of digital technologies, they should be developed collaboratively with governments and healthcare providers, ensuring they meet public health needs and ethical standards. It was recommended that key stakeholders in the digital field, such as technology companies, should be long-term partners in preparedness planning rather than being partners only when emergencies are ongoing. The benefits of digital technologies such as access to faster and more widespread communication, including through social media platforms, TV briefings and text message updates was noted by researchers. The efforts of some technology companies such as Google who have been prioritizing messaging from trusted sources, including the WHO, in their search responses were also recognized. David Heymann, Professor of Infectious Disease Epidemiology at the London School of Hygiene & Tropical Medicine, said: "We need to ensure new digital technologies go through rigorous evaluation to identify those technologies that prove to be effective so that they can add to our armamentarium for outbreak control, adhere to privacy and ethics frameworks, and are built into online pathways developed in collaboration with end-users." However researchers did find some problems with the use of digital technologies during pandemics. During the outbreak of COVID-19, many technologies have been adapted and developed on a scale never seen before, including new apps and data dashboards using anonymised and aggregated data to help inform public health interventions. This has led to concerns about civil liberties and privacy. Chief scientific advisor, Department for International Trade, Dr. Mike Short CBE, said: "Although times of emergency may call for different data access requirements, any data used for the pandemic response should not be misused beyond this purpose, and systems need to be proofed against invasion of privacy and comply with relevant governance." Researchers also noted that the use of data to inform outbreak response should also take into account the digital divide across the globe as although 67 percent of the global population subscribe to a mobile device, 51 percent of the world's population are not mobile internet subscribers. As many of these interventions and surveillance methods rely on connectivity, researchers found many communities may be left behind or missed from statistics. Professor Vince Emery, emeritus professor of translational virology at the University of Surrey, said: "This review provides further impetus to the deployment of digital technologies to sense pandemics and with the roll-out of 5G new exciting possibilities will develop and contribute to controlling major public health emergencies. Viruses know no borders and, increasingly, neither do digital technologies and data so it is important they are utilized to their full potential." <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 14434, 14645, 527, 1694, 305, 1923, 22456, 311, 1862, 279, 586, 79505, 2077, 311, 20562, 12, 777, 15603, 11, 2737, 7187, 22156, 11, 1162, 22654, 11, 3729, 46515, 323, 16865, 315, 39455, 389, 279, 8197, 315, 31139, 828, 323, 10758, 449, 279, 586, 13, 4314, 11295, 14847, 33164, 33151, 315, 6505, 18084, 11, 3544, 2930, 30525, 11, 8599, 7766, 11, 12309, 3428, 41238, 25213, 5070, 323, 31003, 304, 5780, 6975, 323, 5933, 4221, 8863, 13, 1115, 10506, 22262, 311, 12602, 279, 58321, 315, 7528, 46045, 369, 279, 586, 79505, 2077, 311, 20562, 12, 777, 15603, 323, 872, 9669, 11, 323, 30740, 311, 872, 8292, 11, 2737, 5897, 11, 31308, 323, 12625, 30740, 11, 439, 1664, 439, 41295, 323, 32027, 30740, 13, 578, 3938, 315, 586, 2890, 374, 4461, 311, 3719, 15098, 7528, 11, 323, 584, 3477, 279, 1205, 369, 279, 17632, 315, 6625, 15174, 369, 279, 19812, 11, 16865, 323, 1005, 315, 7528, 14645, 311, 20259, 28522, 6373, 11, 323, 3938, 10235, 2136, 369, 20562, 12, 777, 323, 1023, 50600, 19338, 13, 4802, 20562, 12, 777, 11, 264, 8767, 9987, 42631, 17563, 9057, 555, 279, 33333, 328, 17485, 87271, 53, 12, 17, 220, 16, 1174, 220, 17, 1174, 574, 14610, 264, 28522, 555, 279, 4435, 6401, 21021, 320, 78847, 8, 389, 220, 806, 5587, 220, 2366, 15, 11, 2753, 1109, 220, 18, 4038, 1306, 5157, 1051, 1176, 16914, 13, 3161, 1457, 927, 220, 24, 13, 23, 3610, 11007, 5157, 323, 810, 1109, 220, 21038, 11, 931, 16779, 220, 18, 12715, 15603, 11, 1070, 527, 25165, 10742, 922, 279, 3728, 2890, 11, 59529, 323, 7100, 6372, 315, 420, 17188, 11, 8104, 389, 20134, 323, 80947, 22673, 11, 323, 304, 3428, 12, 323, 6278, 32197, 5961, 449, 45350, 2890, 6067, 220, 19, 1174, 220, 20, 662, 2468, 279, 892, 315, 420, 4477, 11, 220, 22, 13, 16, 7239, 1274, 3974, 304, 5961, 430, 617, 1047, 12190, 5944, 323, 3674, 17294, 220, 21, 662, 1666, 449, 279, 2585, 315, 77871, 323, 12495, 38305, 1603, 433, 11, 26991, 279, 20562, 12, 777, 28522, 54331, 389, 279, 18468, 323, 46311, 315, 28066, 315, 19405, 323, 279, 75103, 315, 4029, 18874, 311, 50460, 279, 5536, 389, 3823, 2890, 13, 12220, 279, 55537, 31188, 430, 11754, 220, 975, 339, 34457, 4606, 11, 31398, 315, 11754, 10977, 323, 20020, 315, 7187, 7351, 1051, 1511, 311, 5766, 4726, 9041, 220, 22, 662, 4314, 586, 79505, 11193, 369, 31188, 2077, 7293, 9959, 3432, 11, 2737, 22156, 11, 11295, 1162, 22654, 11, 75103, 315, 4029, 18874, 323, 3831, 586, 10758, 13, 51803, 1268, 1521, 11193, 527, 11798, 323, 872, 5536, 389, 39775, 323, 29528, 374, 7718, 13, 2052, 5961, 527, 2631, 555, 279, 7327, 6401, 49357, 320, 1049, 20, 8, 220, 23, 311, 617, 6332, 8824, 311, 6106, 5426, 10235, 2136, 369, 50600, 52642, 430, 617, 279, 4754, 311, 9041, 37545, 13, 8483, 323, 4500, 315, 502, 5528, 323, 14645, 311, 20259, 1521, 6332, 59539, 3629, 13980, 2391, 77871, 11, 994, 19297, 374, 459, 10973, 32961, 220, 24, 662, 12220, 279, 31188, 315, 15748, 30883, 42631, 28439, 304, 220, 1049, 18, 11, 19730, 18711, 11054, 28066, 315, 8624, 1555, 279, 1005, 315, 14683, 828, 6067, 220, 605, 662, 12220, 279, 48082, 77871, 304, 4410, 10384, 304, 220, 679, 19, 4235, 679, 21, 11, 6505, 4641, 828, 1051, 1511, 311, 1646, 5944, 12912, 220, 806, 1174, 323, 1450, 58606, 62119, 7766, 15480, 810, 53421, 3729, 46515, 323, 264, 2731, 8830, 315, 279, 30295, 315, 279, 77871, 220, 717, 662, 35339, 11, 7528, 14645, 1101, 617, 1027, 27167, 304, 279, 20562, 12, 777, 28522, 220, 1032, 1174, 220, 975, 320, 2620, 220, 16, 883, 311, 20259, 1855, 315, 279, 3116, 586, 79505, 11193, 10555, 3485, 13, 6771, 220, 16, 14434, 14645, 1511, 304, 279, 20562, 12, 777, 28522, 8797, 1404, 2007, 578, 7528, 14110, 706, 24411, 1690, 13878, 315, 2324, 13, 1666, 315, 220, 679, 24, 11, 220, 3080, 4, 315, 279, 3728, 7187, 1047, 53200, 311, 6505, 7766, 11, 315, 902, 220, 2397, 4, 1051, 36122, 81902, 279, 26731, 6650, 304, 3804, 97519, 10384, 220, 868, 662, 763, 220, 679, 24, 11, 220, 7854, 7239, 10721, 1051, 24174, 220, 845, 1174, 323, 439, 315, 6186, 220, 2366, 15, 11, 220, 18, 13, 23, 7239, 1274, 22815, 1511, 3674, 3772, 220, 1114, 662, 5810, 584, 41440, 3477, 1268, 7528, 14645, 527, 1694, 305, 1923, 22456, 369, 279, 586, 79505, 2077, 311, 20562, 12, 777, 15603, 320, 30035, 13, 220, 16, 7609, 1226, 4358, 279, 58321, 315, 46045, 323, 872, 20081, 9669, 13, 1115, 6067, 11852, 5603, 374, 4460, 311, 6179, 1268, 7528, 15174, 649, 387, 32762, 1139, 20562, 12, 777, 4565, 15174, 11, 323, 311, 1520, 10772, 369, 3938, 28817, 38305, 13, 23966, 13, 220, 16, 25, 578, 83416, 7528, 14645, 1511, 304, 279, 586, 79505, 2077, 311, 20562, 12, 777, 13, 9176, 20414, 1005, 264, 10824, 315, 7528, 14645, 323, 1253, 17631, 389, 62866, 14054, 323, 7757, 18539, 13, 13257, 6975, 374, 6982, 439, 264, 8821, 9046, 369, 32373, 11, 8051, 433, 1101, 1234, 75658, 1690, 315, 279, 1023, 14645, 13, 24191, 315, 279, 828, 8066, 505, 1521, 14645, 35496, 1139, 828, 24858, 19826, 13, 31009, 11, 2875, 1984, 2532, 13, 8797, 1404, 2217, 14434, 62057, 5848, 22156, 362, 6332, 586, 79505, 734, 315, 31188, 6373, 374, 8830, 19405, 18874, 304, 892, 11, 2035, 323, 1732, 11, 323, 25607, 5326, 9547, 369, 279, 8624, 311, 8641, 7524, 39455, 13, 362, 2134, 315, 7528, 828, 8336, 527, 1694, 1511, 311, 18885, 323, 14532, 1401, 62057, 5848, 828, 20802, 555, 586, 79505, 11527, 369, 20562, 12, 777, 13, 8267, 828, 8336, 369, 4216, 8624, 18468, 87350, 7187, 68806, 61400, 6067, 11383, 17631, 389, 2890, 14228, 828, 505, 70760, 11, 22736, 315, 5157, 29704, 555, 78545, 323, 22013, 442, 292, 22156, 14488, 13, 42319, 442, 292, 22156, 14488, 527, 3196, 389, 6821, 315, 14830, 13803, 11, 1778, 439, 3451, 258, 1517, 10529, 4458, 12970, 17563, 20182, 4856, 1109, 264, 27692, 23842, 11, 505, 8952, 323, 4183, 81878, 6156, 323, 14580, 18985, 13077, 11, 902, 7655, 311, 3493, 5912, 22156, 828, 315, 682, 5157, 13, 4314, 8336, 11, 4869, 11, 13967, 3194, 5157, 304, 902, 18985, 374, 539, 16495, 13, 763, 279, 6560, 11, 369, 3187, 11, 1405, 3156, 6051, 1193, 70340, 6978, 323, 18985, 7487, 1051, 40076, 12793, 369, 20562, 12, 777, 11, 11007, 5157, 4097, 459, 13240, 220, 19, 13, 22, 4, 315, 12104, 13795, 20562, 12, 777, 5157, 220, 972, 662, 23322, 7922, 2073, 295, 1599, 5157, 1053, 1520, 97298, 349, 279, 26703, 323, 17910, 315, 279, 31188, 220, 777, 323, 8108, 79287, 18874, 13, 763, 279, 3347, 1403, 11026, 11, 828, 505, 2930, 3754, 6732, 11, 3754, 43085, 35542, 3600, 11, 3674, 14488, 11, 3566, 27573, 323, 5293, 5382, 68102, 4029, 90388, 617, 20034, 311, 5266, 420, 13225, 13, 2956, 43085, 35542, 6067, 11, 2737, 1322, 76206, 11724, 220, 508, 1174, 480, 11079, 691, 220, 1691, 1174, 6401, 2276, 220, 1313, 323, 469, 29236, 220, 1419, 1174, 902, 1005, 5933, 4221, 8863, 323, 5780, 6975, 311, 1920, 323, 4141, 2930, 828, 11, 617, 1027, 8040, 311, 3493, 62057, 5848, 20616, 13, 4314, 828, 8336, 527, 15098, 1694, 18751, 1139, 279, 16287, 22156, 18921, 220, 1187, 323, 617, 264, 3560, 304, 20562, 12, 777, 22156, 13, 578, 40312, 753, 5452, 469, 1932, 7826, 88840, 12716, 3871, 17226, 30525, 369, 50600, 1773, 56407, 13147, 10235, 2136, 323, 2077, 11, 2737, 12434, 323, 42142, 5848, 828, 220, 914, 662, 26778, 6067, 617, 11922, 18468, 315, 4216, 8624, 6821, 369, 20562, 12, 777, 11, 1555, 279, 1005, 315, 35851, 54492, 828, 323, 3754, 6821, 11, 1603, 279, 40312, 6004, 264, 5224, 128257, 198, 128256, 78191, 198, 39212, 14645, 617, 459, 3062, 3560, 311, 1514, 304, 30438, 311, 3938, 12495, 38305, 11, 264, 502, 4007, 304, 279, 8486, 11, 22037, 19152, 6821, 13, 12220, 420, 5016, 4007, 11, 12074, 505, 279, 602, 1355, 1137, 2447, 11, 6197, 555, 17054, 32532, 26718, 408, 894, 505, 549, 3218, 11, 22690, 1268, 7528, 14645, 617, 1027, 29905, 1534, 304, 2077, 311, 20562, 12, 777, 13, 578, 5938, 10742, 449, 12625, 11, 279, 27375, 315, 1778, 14645, 323, 1268, 814, 649, 387, 1511, 304, 3938, 12495, 38305, 1051, 1101, 25078, 555, 279, 2128, 902, 5764, 17054, 56232, 5867, 727, 505, 279, 3907, 315, 68064, 13, 59250, 1766, 311, 636, 279, 1455, 704, 315, 7528, 14645, 11, 814, 1288, 387, 8040, 11430, 8046, 449, 17047, 323, 18985, 12850, 11, 23391, 814, 3449, 586, 2890, 3966, 323, 31308, 10886, 13, 1102, 574, 11349, 430, 1401, 39210, 304, 279, 7528, 2115, 11, 1778, 439, 5557, 5220, 11, 1288, 387, 1317, 9860, 8717, 304, 10235, 2136, 9293, 4856, 1109, 1694, 8717, 1193, 994, 69074, 527, 14529, 13, 578, 7720, 315, 7528, 14645, 1778, 439, 2680, 311, 10819, 323, 810, 24716, 10758, 11, 2737, 1555, 3674, 3772, 15771, 11, 6007, 10015, 826, 323, 1495, 1984, 9013, 574, 10555, 555, 12074, 13, 578, 9045, 315, 1063, 5557, 5220, 1778, 439, 5195, 889, 617, 1027, 45777, 4954, 30622, 505, 22542, 8336, 11, 2737, 279, 40312, 11, 304, 872, 2778, 14847, 1051, 1101, 15324, 13, 6941, 28653, 18022, 11, 17054, 315, 88911, 1245, 31974, 88953, 2508, 520, 279, 7295, 6150, 315, 10320, 43312, 612, 71343, 19152, 11, 1071, 25, 330, 1687, 1205, 311, 6106, 502, 7528, 14645, 733, 1555, 47999, 16865, 311, 10765, 1884, 14645, 430, 12391, 311, 387, 7524, 779, 430, 814, 649, 923, 311, 1057, 6916, 2908, 34765, 369, 31188, 2585, 11, 49553, 311, 12625, 323, 32008, 49125, 11, 323, 527, 5918, 1139, 2930, 44014, 8040, 304, 20632, 449, 842, 44480, 1210, 4452, 12074, 1550, 1505, 1063, 5435, 449, 279, 1005, 315, 7528, 14645, 2391, 12495, 38305, 13, 12220, 279, 31188, 315, 20562, 12, 777, 11, 1690, 14645, 617, 1027, 30464, 323, 8040, 389, 264, 5569, 2646, 3970, 1603, 11, 2737, 502, 10721, 323, 828, 24858, 19826, 1701, 32248, 4147, 323, 71922, 828, 311, 1520, 6179, 586, 2890, 39455, 13, 1115, 706, 6197, 311, 10742, 922, 8431, 58455, 323, 12625, 13, 14681, 12624, 37713, 11, 6011, 369, 7327, 17657, 11, 2999, 13, 11519, 10928, 356, 11855, 11, 1071, 25, 330, 16179, 3115, 315, 13147, 1253, 1650, 369, 2204, 828, 2680, 8670, 11, 904, 828, 1511, 369, 279, 28522, 2077, 1288, 539, 387, 5906, 2656, 7953, 420, 7580, 11, 323, 6067, 1205, 311, 387, 11311, 291, 2403, 30215, 315, 12625, 323, 26069, 449, 9959, 35186, 1210, 59250, 1101, 10555, 430, 279, 1005, 315, 828, 311, 6179, 31188, 2077, 1288, 1101, 1935, 1139, 2759, 279, 7528, 22497, 4028, 279, 24867, 439, 8051, 220, 3080, 3346, 315, 279, 3728, 7187, 18447, 311, 264, 6505, 3756, 11, 220, 3971, 3346, 315, 279, 1917, 596, 7187, 527, 539, 6505, 7757, 31120, 13, 1666, 1690, 315, 1521, 39455, 323, 22156, 5528, 17631, 389, 31357, 11, 12074, 1766, 1690, 10977, 1253, 387, 2163, 4920, 477, 13942, 505, 13443, 13, 17054, 56232, 5867, 727, 11, 991, 261, 36891, 14561, 315, 12215, 1697, 3355, 299, 36781, 520, 279, 3907, 315, 68064, 11, 1071, 25, 330, 2028, 3477, 5825, 4726, 3242, 64476, 311, 279, 24047, 315, 7528, 14645, 311, 5647, 12495, 38305, 323, 449, 279, 6638, 9994, 315, 220, 20, 38, 502, 13548, 24525, 690, 2274, 323, 17210, 311, 26991, 3682, 586, 2890, 69074, 13, 9734, 4881, 1440, 912, 24743, 323, 11, 15098, 11, 14188, 656, 7528, 14645, 323, 828, 779, 433, 374, 3062, 814, 527, 34716, 311, 872, 2539, 4754, 1210, 220, 128257, 198 ]

1,922

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Fear extinction is an adaptive process whereby defensive responses are attenuated following repeated experience of prior fear-related stimuli without harm. The formation of extinction memories involves interactions between various corticolimbic structures, resulting in reduced central amygdala (CEA) output. Recent studies show, however, the CEA is not merely an output relay of fear responses but contains multiple neuronal subpopulations that interact to calibrate levels of fear responding. Here, by integrating behavioural, in vivo electrophysiological, anatomical and optogenetic approaches in mice we demonstrate that fear extinction produces reversible, stimulus- and context-specific changes in neuronal responses to conditioned stimuli in functionally and genetically defined cell types in the lateral (CEl) and medial (CEm) CEA. Moreover, we show these alterations are absent when extinction is deficient and that selective silencing of protein kinase C delta-expressing (PKCδ) CEl neurons impairs fear extinction. Our findings identify CEA inhibitory microcircuits that act as critical elements within the brain networks mediating fear extinction. Introduction The survival of animals depends on their ability to mobilize appropriate defensive behaviours to imminent threats 1 . Yet, animals also need to be able to flexibly adapt to changes in threat contingencies by inhibiting fear responses when threat-related stimuli no longer associate with aversive outcomes, in a process called fear extinction 2 , 3 , 4 . In a typical experimental procedure, an association between conditioned stimuli (CS, a tone or light) and unconditioned stimuli (US, e.g. a foot shock) is first formed (fear conditioning) and then subsequently updated by repeated presentations of the CS in the absence of the US (fear extinction). Fear extinction is thought of as a new learning process wherein animals learn that the CS is no longer predictive of the US 4 . Thus, fear extinction does not reflect the mere erasure of the conditioned fear memory; indeed fear can be spontaneously recovered after fear extinction, or triggered by exposure to the US or a new context 5 , 6 , 7 . Current models posit that neural circuits and cell assemblies for fear and extinction memories compete with one another, in a context-dependent manner, to determine the degree of fear responding to the CS 4 , 8 , 9 . In recent years, there have been major advances in delineating the neural circuity underlying fear conditioning and extinction 10 , 11 , yet key elements of this circuitry remain to be elucidated. Of particular note, the central nucleus of the amygdala (CEA) has long been ascribed an essential role in the expression of conditioned fear responses 1 . However, detailed dissection of CEA circuitry, using in vivo and ex vivo recordings from functionally and/or genetically defined cell types, has recently challenged the view that the CEA is merely an output relay of fear responses. Instead, this work indicates that the CEA contains multiple anatomically, molecularly and functionally defined neuronal subpopulations that interact to calibrate levels of fear responding 12 , 13 , 14 . CEA output neurons located in both the lateral (CEl) and the medial (CEm) subdivision of the CEA project to downstream targets that mediate different components of conditioned defensive behaviours, such as freezing or flight 15 , 16 , 17 . Fear conditioning potentiates excitatory input onto CEl projections to the ventrolateral periaqueductal grey (vlPAG) 18 and CEm output neurons exhibit increased CS responses upon fear conditioning 15 . In turn, the activity of CEm output neurons is thought to be controlled by excitatory glutamatergic afferents from auditory thalamus and the basal amygdala (BA) 19 . Crucially, however, CEm output neurons are also subject to inhibitory control from GABAergic neurons located in the neighbouring intercalated cell clusters (ITCs) and a subset of neurons in the CEl expressing protein-kinase C delta (PKCδ) 15 , 20 , 21 . Thus, following fear conditioning, three functional neuronal subpopulations emerge in the CEl: (1) CS ‘non-responsive’ neurons, (2) CElon neurons that are excited by the CS following fear conditioning and overlap in part with a somatostatin (SST)-expressing population 18 , 22 , 23 and (3) CEloff neurons, which acquire an inhibitory response to the CS and partly overlap with PKCδ neurons 15 . Interestingly, CElon and CEloff neurons can inhibit each other 15 , and SST neurons can inhibit PKCδ neurons 22 , which could result in a switch-like disinhibition of output neurons in CEm or in CEl 12 . Together, these earlier findings show that there is a layer of processing and plasticity within the CEA that can serve to promote and limit fear responding 24 , 25 . This raises the intriguing possibility that the same CEA circuitry could be ideally positioned to mediate fear extinction and act as a substrate for the reductions in fear responding that occur with extinction. The major aim of the current study was to test this hypothesis using a combination of behavioural, in vivo electrophysiological, optogenetic and molecular approaches. Our findings demonstrate that microcircuits within the CEA are crucial for fear extinction. Results Neuronal correlates of fear extinction in subpopulations of CEA neurons To first identify neuronal correlates of fear extinction in CEA circuits, we submitted freely-moving mice ( n = 27, C57BL/6J, hereafter B6) to a fear-conditioning and extinction procedure while chronically recording single-unit activity in CEA (Figs. S1 , S2 ; Supplementary Tables 1 – 4 ; see ‘Methods’) 15 . Following fear conditioning, mice exhibited a selective increase in conditioned freezing to the CS that was reversed to pre-conditioning levels by the end of fear extinction learning (Fig. 1a, b ; Fig. S3 ). Fig. 1: Neuronal correlates of fear extinction in subpopulations of CEA neurons. a Behavioural protocol. FC: fear conditioning. CS: conditioned stimuli. b Behavioural data. B6 mice: n = 27; freezing, habituation, no CS: 19.8 ± 2.6%, CS: 26.1 ± 3.3%, beginning of extinction 1, no CS: 18.5 ± 2.3%, CS: 61.9 ± 4.6%, end of extinction 2, no CS: 25.3 ± 3.1%, CS: 34.1 ± 3.4%, blocks (averages) of 4 CSs. One-way repeated-measures ANOVA F (5,130) = 30.8, p < 0.001, followed", "role": "user" }, { "content": "The brain mechanisms underlying the suppression of fear responses have attracted a lot of attention as they are relevant for therapy of human anxiety disorders. Despite our broad understanding of the different brain regions activated during the experience of fear, how fear responses can be suppressed remains largely elusive. Researchers at the University of Bern and the Friedrich Miescher Institute in Basel have now discovered that the activation of identified central amygdala neurons can suppress fear responses. Fear is an important reaction that warns and protects us from danger. But when fear responses are out of control, this can lead to persistent fears and anxiety disorders. In Europe, about 15 percent of the population is affected by anxiety disorders. Existing therapies remain largely unspecific or are not generally effective, because the detailed neurobiological understanding of these disorders is lacking. What was known so far is that distinct nerve cells interact together to regulate fear responses by promoting or suppressing them. Different circuits of nerve cells are involved in this process. A kind of \"tug-of-war\" takes place, with one brain circuit \"winning\" and overriding the other, depending on the context. If this system is disturbed, for example if fear reactions are no longer suppressed, this can lead to anxiety disorders. Recent studies have shown that certain groups of neurons in the amygdala are crucial for the regulation of fear responses. The amygdala is a small almond-shaped brain structure in the center of the brain that receives information about fearful stimuli and transmits it to other brain regions to generate fear responses. This causes the body to release stress hormones, change heart rate or trigger fight, flight or freezing responses. Subdivision of the mouse amygdala. The cell types studied are located in the central amygdala (red). Credit: Rob Hurt / Wikicommons (CC BY-SA 4.0) Now, a group led by Professors Stéphane Ciocchi of the University of Bern and Andreas Lüthi of the Friedrich Miescher Institute in Basel has discovered that the amygdala plays a much more active role in these processes than previously thought: Not only is the central amygdala a \"hub\" to generate fear responses, but it contains neuronal microcircuits that regulate the suppression of fear responses. In animal models, it has been shown that inhibition of these microcircuits leads to long-lasting fear behaviour. However, when they are activated, behaviour returns to normal despite previous fear responses. This shows that neurons in the central amygdala are highly adaptive and essential for suppressing fear. These results were published in the journal Nature Communications. \"Disturbed\" suppression leads to long-lasting fear The researchers led by Stéphane Ciocchi and Andreas Lüthi studied the activity of neurons of the central amygdala in mice during the suppression of fear responses. They were able to identify different cell types that influence the animals' behaviour. For their study, the researchers used several methods, including a technique called optogenetics with which they could precisely shut down—with pulses of light—the activity of an identified neuronal population within the central amygdala that produces a specific enzyme. This impaired the suppression of fear responses, whereupon animals became excessively fearful. \"We were surprised how strongly our targeted intervention in specific cell types of the central amygdala affected fear responses,\" says Ciocchi, Assistant Professor at the Institute of Physiology, University of Bern. \"The optogenetic silencing of these specific neurons completely abolished the suppression of fear and provoked a state of pathological fear.\" Important for developing more effective therapies In humans, dysfunction of this system, including deficient plasticity in the nerve cells of the central amygdala described here, could contribute to the impaired suppression of fear memories reported in patients with anxiety and trauma-related disorders. A better understanding of these processes will help develop more specific therapies for these disorders. \"However, further studies are necessary to investigate whether discoveries obtained in simple animal models can be extrapolated to human anxiety disorders,\" Ciocchi adds. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Fear extinction is an adaptive process whereby defensive responses are attenuated following repeated experience of prior fear-related stimuli without harm. The formation of extinction memories involves interactions between various corticolimbic structures, resulting in reduced central amygdala (CEA) output. Recent studies show, however, the CEA is not merely an output relay of fear responses but contains multiple neuronal subpopulations that interact to calibrate levels of fear responding. Here, by integrating behavioural, in vivo electrophysiological, anatomical and optogenetic approaches in mice we demonstrate that fear extinction produces reversible, stimulus- and context-specific changes in neuronal responses to conditioned stimuli in functionally and genetically defined cell types in the lateral (CEl) and medial (CEm) CEA. Moreover, we show these alterations are absent when extinction is deficient and that selective silencing of protein kinase C delta-expressing (PKCδ) CEl neurons impairs fear extinction. Our findings identify CEA inhibitory microcircuits that act as critical elements within the brain networks mediating fear extinction. Introduction The survival of animals depends on their ability to mobilize appropriate defensive behaviours to imminent threats 1 . Yet, animals also need to be able to flexibly adapt to changes in threat contingencies by inhibiting fear responses when threat-related stimuli no longer associate with aversive outcomes, in a process called fear extinction 2 , 3 , 4 . In a typical experimental procedure, an association between conditioned stimuli (CS, a tone or light) and unconditioned stimuli (US, e.g. a foot shock) is first formed (fear conditioning) and then subsequently updated by repeated presentations of the CS in the absence of the US (fear extinction). Fear extinction is thought of as a new learning process wherein animals learn that the CS is no longer predictive of the US 4 . Thus, fear extinction does not reflect the mere erasure of the conditioned fear memory; indeed fear can be spontaneously recovered after fear extinction, or triggered by exposure to the US or a new context 5 , 6 , 7 . Current models posit that neural circuits and cell assemblies for fear and extinction memories compete with one another, in a context-dependent manner, to determine the degree of fear responding to the CS 4 , 8 , 9 . In recent years, there have been major advances in delineating the neural circuity underlying fear conditioning and extinction 10 , 11 , yet key elements of this circuitry remain to be elucidated. Of particular note, the central nucleus of the amygdala (CEA) has long been ascribed an essential role in the expression of conditioned fear responses 1 . However, detailed dissection of CEA circuitry, using in vivo and ex vivo recordings from functionally and/or genetically defined cell types, has recently challenged the view that the CEA is merely an output relay of fear responses. Instead, this work indicates that the CEA contains multiple anatomically, molecularly and functionally defined neuronal subpopulations that interact to calibrate levels of fear responding 12 , 13 , 14 . CEA output neurons located in both the lateral (CEl) and the medial (CEm) subdivision of the CEA project to downstream targets that mediate different components of conditioned defensive behaviours, such as freezing or flight 15 , 16 , 17 . Fear conditioning potentiates excitatory input onto CEl projections to the ventrolateral periaqueductal grey (vlPAG) 18 and CEm output neurons exhibit increased CS responses upon fear conditioning 15 . In turn, the activity of CEm output neurons is thought to be controlled by excitatory glutamatergic afferents from auditory thalamus and the basal amygdala (BA) 19 . Crucially, however, CEm output neurons are also subject to inhibitory control from GABAergic neurons located in the neighbouring intercalated cell clusters (ITCs) and a subset of neurons in the CEl expressing protein-kinase C delta (PKCδ) 15 , 20 , 21 . Thus, following fear conditioning, three functional neuronal subpopulations emerge in the CEl: (1) CS ‘non-responsive’ neurons, (2) CElon neurons that are excited by the CS following fear conditioning and overlap in part with a somatostatin (SST)-expressing population 18 , 22 , 23 and (3) CEloff neurons, which acquire an inhibitory response to the CS and partly overlap with PKCδ neurons 15 . Interestingly, CElon and CEloff neurons can inhibit each other 15 , and SST neurons can inhibit PKCδ neurons 22 , which could result in a switch-like disinhibition of output neurons in CEm or in CEl 12 . Together, these earlier findings show that there is a layer of processing and plasticity within the CEA that can serve to promote and limit fear responding 24 , 25 . This raises the intriguing possibility that the same CEA circuitry could be ideally positioned to mediate fear extinction and act as a substrate for the reductions in fear responding that occur with extinction. The major aim of the current study was to test this hypothesis using a combination of behavioural, in vivo electrophysiological, optogenetic and molecular approaches. Our findings demonstrate that microcircuits within the CEA are crucial for fear extinction. Results Neuronal correlates of fear extinction in subpopulations of CEA neurons To first identify neuronal correlates of fear extinction in CEA circuits, we submitted freely-moving mice ( n = 27, C57BL/6J, hereafter B6) to a fear-conditioning and extinction procedure while chronically recording single-unit activity in CEA (Figs. S1 , S2 ; Supplementary Tables 1 – 4 ; see ‘Methods’) 15 . Following fear conditioning, mice exhibited a selective increase in conditioned freezing to the CS that was reversed to pre-conditioning levels by the end of fear extinction learning (Fig. 1a, b ; Fig. S3 ). Fig. 1: Neuronal correlates of fear extinction in subpopulations of CEA neurons. a Behavioural protocol. FC: fear conditioning. CS: conditioned stimuli. b Behavioural data. B6 mice: n = 27; freezing, habituation, no CS: 19.8 ± 2.6%, CS: 26.1 ± 3.3%, beginning of extinction 1, no CS: 18.5 ± 2.3%, CS: 61.9 ± 4.6%, end of extinction 2, no CS: 25.3 ± 3.1%, CS: 34.1 ± 3.4%, blocks (averages) of 4 CSs. One-way repeated-measures ANOVA F (5,130) = 30.8, p < 0.001, followed<|im_end|> <|im_start|>assistant The brain mechanisms underlying the suppression of fear responses have attracted a lot of attention as they are relevant for therapy of human anxiety disorders. Despite our broad understanding of the different brain regions activated during the experience of fear, how fear responses can be suppressed remains largely elusive. Researchers at the University of Bern and the Friedrich Miescher Institute in Basel have now discovered that the activation of identified central amygdala neurons can suppress fear responses. Fear is an important reaction that warns and protects us from danger. But when fear responses are out of control, this can lead to persistent fears and anxiety disorders. In Europe, about 15 percent of the population is affected by anxiety disorders. Existing therapies remain largely unspecific or are not generally effective, because the detailed neurobiological understanding of these disorders is lacking. What was known so far is that distinct nerve cells interact together to regulate fear responses by promoting or suppressing them. Different circuits of nerve cells are involved in this process. A kind of "tug-of-war" takes place, with one brain circuit "winning" and overriding the other, depending on the context. If this system is disturbed, for example if fear reactions are no longer suppressed, this can lead to anxiety disorders. Recent studies have shown that certain groups of neurons in the amygdala are crucial for the regulation of fear responses. The amygdala is a small almond-shaped brain structure in the center of the brain that receives information about fearful stimuli and transmits it to other brain regions to generate fear responses. This causes the body to release stress hormones, change heart rate or trigger fight, flight or freezing responses. Subdivision of the mouse amygdala. The cell types studied are located in the central amygdala (red). Credit: Rob Hurt / Wikicommons (CC BY-SA 4.0) Now, a group led by Professors Stéphane Ciocchi of the University of Bern and Andreas Lüthi of the Friedrich Miescher Institute in Basel has discovered that the amygdala plays a much more active role in these processes than previously thought: Not only is the central amygdala a "hub" to generate fear responses, but it contains neuronal microcircuits that regulate the suppression of fear responses. In animal models, it has been shown that inhibition of these microcircuits leads to long-lasting fear behaviour. However, when they are activated, behaviour returns to normal despite previous fear responses. This shows that neurons in the central amygdala are highly adaptive and essential for suppressing fear. These results were published in the journal Nature Communications. "Disturbed" suppression leads to long-lasting fear The researchers led by Stéphane Ciocchi and Andreas Lüthi studied the activity of neurons of the central amygdala in mice during the suppression of fear responses. They were able to identify different cell types that influence the animals' behaviour. For their study, the researchers used several methods, including a technique called optogenetics with which they could precisely shut down—with pulses of light—the activity of an identified neuronal population within the central amygdala that produces a specific enzyme. This impaired the suppression of fear responses, whereupon animals became excessively fearful. "We were surprised how strongly our targeted intervention in specific cell types of the central amygdala affected fear responses," says Ciocchi, Assistant Professor at the Institute of Physiology, University of Bern. "The optogenetic silencing of these specific neurons completely abolished the suppression of fear and provoked a state of pathological fear." Important for developing more effective therapies In humans, dysfunction of this system, including deficient plasticity in the nerve cells of the central amygdala described here, could contribute to the impaired suppression of fear memories reported in patients with anxiety and trauma-related disorders. A better understanding of these processes will help develop more specific therapies for these disorders. "However, further studies are necessary to investigate whether discoveries obtained in simple animal models can be extrapolated to human anxiety disorders," Ciocchi adds. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 43067, 52609, 374, 459, 48232, 1920, 49001, 16399, 14847, 527, 57732, 660, 2768, 11763, 3217, 315, 4972, 8850, 14228, 56688, 2085, 11682, 13, 578, 18488, 315, 52609, 19459, 18065, 22639, 1990, 5370, 23100, 27561, 21495, 292, 14726, 11, 13239, 304, 11293, 8792, 64383, 29684, 6181, 320, 2152, 32, 8, 2612, 13, 35390, 7978, 1501, 11, 4869, 11, 279, 356, 19657, 374, 539, 16632, 459, 2612, 32951, 315, 8850, 14847, 719, 5727, 5361, 79402, 1207, 8539, 7607, 430, 16681, 311, 1652, 44192, 5990, 315, 8850, 30438, 13, 5810, 11, 555, 54952, 88979, 11, 304, 41294, 4135, 22761, 1065, 41314, 11, 75893, 950, 323, 3469, 11968, 5411, 20414, 304, 24548, 584, 20461, 430, 8850, 52609, 19159, 81193, 11, 39535, 12, 323, 2317, 19440, 4442, 304, 79402, 14847, 311, 66731, 56688, 304, 734, 750, 323, 52033, 4613, 2849, 4595, 304, 279, 45569, 320, 2152, 75, 8, 323, 97348, 320, 2152, 76, 8, 356, 19657, 13, 23674, 11, 584, 1501, 1521, 61086, 527, 28310, 994, 52609, 374, 87544, 323, 430, 44010, 5554, 11627, 315, 13128, 82160, 356, 9665, 10397, 1911, 287, 320, 23037, 34, 86486, 8, 356, 6719, 34313, 3242, 4825, 8850, 52609, 13, 5751, 14955, 10765, 356, 19657, 20747, 10843, 8162, 44398, 12059, 430, 1180, 439, 9200, 5540, 2949, 279, 8271, 14488, 1812, 23747, 8850, 52609, 13, 29438, 578, 20237, 315, 10099, 14117, 389, 872, 5845, 311, 29905, 553, 8475, 16399, 71177, 311, 51551, 18208, 220, 16, 662, 14968, 11, 10099, 1101, 1205, 311, 387, 3025, 311, 5882, 6623, 10737, 311, 4442, 304, 6023, 39639, 6072, 555, 20747, 5977, 8850, 14847, 994, 6023, 14228, 56688, 912, 5129, 22712, 449, 1860, 53453, 20124, 11, 304, 264, 1920, 2663, 8850, 52609, 220, 17, 1174, 220, 18, 1174, 220, 19, 662, 763, 264, 14595, 22772, 10537, 11, 459, 15360, 1990, 66731, 56688, 320, 6546, 11, 264, 16630, 477, 3177, 8, 323, 653, 9233, 291, 56688, 320, 2078, 11, 384, 1326, 13, 264, 4579, 10988, 8, 374, 1176, 14454, 320, 69, 686, 35121, 8, 323, 1243, 28520, 6177, 555, 11763, 38480, 315, 279, 10211, 304, 279, 19821, 315, 279, 2326, 320, 69, 686, 52609, 570, 43067, 52609, 374, 3463, 315, 439, 264, 502, 6975, 1920, 42418, 10099, 4048, 430, 279, 10211, 374, 912, 5129, 60336, 315, 279, 2326, 220, 19, 662, 14636, 11, 8850, 52609, 1587, 539, 8881, 279, 17983, 2781, 4058, 315, 279, 66731, 8850, 5044, 26, 13118, 8850, 649, 387, 88558, 26403, 1306, 8850, 52609, 11, 477, 22900, 555, 14675, 311, 279, 2326, 477, 264, 502, 2317, 220, 20, 1174, 220, 21, 1174, 220, 22, 662, 9303, 4211, 20940, 430, 30828, 46121, 323, 2849, 62407, 369, 8850, 323, 52609, 19459, 20874, 449, 832, 2500, 11, 304, 264, 2317, 43918, 11827, 11, 311, 8417, 279, 8547, 315, 8850, 30438, 311, 279, 10211, 220, 19, 1174, 220, 23, 1174, 220, 24, 662, 763, 3293, 1667, 11, 1070, 617, 1027, 3682, 31003, 304, 91784, 1113, 279, 30828, 4319, 35594, 16940, 8850, 35121, 323, 52609, 220, 605, 1174, 220, 806, 1174, 3686, 1401, 5540, 315, 420, 16622, 894, 7293, 311, 387, 97298, 660, 13, 5046, 4040, 5296, 11, 279, 8792, 62607, 315, 279, 64383, 29684, 6181, 320, 2152, 32, 8, 706, 1317, 1027, 439, 17890, 459, 7718, 3560, 304, 279, 7645, 315, 66731, 8850, 14847, 220, 16, 662, 4452, 11, 11944, 834, 2879, 315, 356, 19657, 16622, 894, 11, 1701, 304, 41294, 323, 506, 41294, 38140, 505, 734, 750, 323, 5255, 52033, 4613, 2849, 4595, 11, 706, 6051, 29991, 279, 1684, 430, 279, 356, 19657, 374, 16632, 459, 2612, 32951, 315, 8850, 14847, 13, 12361, 11, 420, 990, 15151, 430, 279, 356, 19657, 5727, 5361, 75893, 2740, 11, 31206, 398, 323, 734, 750, 4613, 79402, 1207, 8539, 7607, 430, 16681, 311, 1652, 44192, 5990, 315, 8850, 30438, 220, 717, 1174, 220, 1032, 1174, 220, 975, 662, 356, 19657, 2612, 34313, 7559, 304, 2225, 279, 45569, 320, 2152, 75, 8, 323, 279, 97348, 320, 2152, 76, 8, 60922, 315, 279, 356, 19657, 2447, 311, 52452, 11811, 430, 1812, 6629, 2204, 6956, 315, 66731, 16399, 71177, 11, 1778, 439, 43318, 477, 11213, 220, 868, 1174, 220, 845, 1174, 220, 1114, 662, 43067, 35121, 3419, 23202, 988, 25435, 5382, 1988, 8800, 356, 6719, 41579, 311, 279, 10594, 1098, 19715, 824, 689, 447, 81600, 278, 20366, 320, 14878, 47, 1929, 8, 220, 972, 323, 356, 2321, 2612, 34313, 31324, 7319, 10211, 14847, 5304, 8850, 35121, 220, 868, 662, 763, 2543, 11, 279, 5820, 315, 356, 2321, 2612, 34313, 374, 3463, 311, 387, 14400, 555, 25435, 5382, 35169, 309, 977, 70, 292, 264, 3018, 812, 505, 83629, 270, 17243, 355, 323, 279, 80710, 64383, 29684, 6181, 320, 7209, 8, 220, 777, 662, 76104, 34575, 11, 4869, 11, 356, 2321, 2612, 34313, 527, 1101, 3917, 311, 20747, 10843, 2585, 505, 480, 57650, 75439, 34313, 7559, 304, 279, 62027, 958, 5531, 660, 2849, 28066, 320, 964, 34645, 8, 323, 264, 27084, 315, 34313, 304, 279, 356, 6719, 37810, 13128, 12, 8148, 521, 356, 9665, 320, 23037, 34, 86486, 8, 220, 868, 1174, 220, 508, 1174, 220, 1691, 662, 14636, 11, 2768, 8850, 35121, 11, 2380, 16003, 79402, 1207, 8539, 7607, 34044, 304, 279, 356, 6719, 25, 320, 16, 8, 10211, 3451, 6414, 21638, 529, 34313, 11, 320, 17, 8, 356, 6719, 263, 34313, 430, 527, 12304, 555, 279, 10211, 2768, 8850, 35121, 323, 28347, 304, 961, 449, 264, 1794, 266, 537, 15111, 320, 50, 790, 7435, 14107, 287, 7187, 220, 972, 1174, 220, 1313, 1174, 220, 1419, 323, 320, 18, 8, 27809, 94138, 34313, 11, 902, 21953, 459, 20747, 10843, 2077, 311, 279, 10211, 323, 28135, 28347, 449, 25864, 34, 86486, 34313, 220, 868, 662, 58603, 11, 356, 6719, 263, 323, 27809, 94138, 34313, 649, 69033, 1855, 1023, 220, 868, 1174, 323, 92516, 34313, 649, 69033, 25864, 34, 86486, 34313, 220, 1313, 1174, 902, 1436, 1121, 304, 264, 3480, 12970, 64842, 60073, 315, 2612, 34313, 304, 356, 2321, 477, 304, 356, 6719, 220, 717, 662, 32255, 11, 1521, 6931, 14955, 1501, 430, 1070, 374, 264, 6324, 315, 8863, 323, 12466, 488, 2949, 279, 356, 19657, 430, 649, 8854, 311, 12192, 323, 4017, 8850, 30438, 220, 1187, 1174, 220, 914, 662, 1115, 25930, 279, 41765, 13336, 430, 279, 1890, 356, 19657, 16622, 894, 1436, 387, 50663, 35328, 311, 1812, 6629, 8850, 52609, 323, 1180, 439, 264, 54057, 369, 279, 47311, 304, 8850, 30438, 430, 12446, 449, 52609, 13, 578, 3682, 9395, 315, 279, 1510, 4007, 574, 311, 1296, 420, 31178, 1701, 264, 10824, 315, 88979, 11, 304, 41294, 4135, 22761, 1065, 41314, 11, 3469, 11968, 5411, 323, 31206, 20414, 13, 5751, 14955, 20461, 430, 8162, 44398, 12059, 2949, 279, 356, 19657, 527, 16996, 369, 8850, 52609, 13, 18591, 4275, 324, 25180, 97303, 315, 8850, 52609, 304, 1207, 8539, 7607, 315, 356, 19657, 34313, 2057, 1176, 10765, 79402, 97303, 315, 8850, 52609, 304, 356, 19657, 46121, 11, 584, 14976, 26662, 86572, 24548, 320, 308, 284, 220, 1544, 11, 356, 3226, 9574, 14, 21, 41, 11, 1618, 10924, 426, 21, 8, 311, 264, 8850, 59105, 287, 323, 52609, 10537, 1418, 27076, 2740, 14975, 3254, 61675, 5820, 304, 356, 19657, 320, 37, 14801, 13, 328, 16, 1174, 328, 17, 2652, 99371, 43252, 220, 16, 1389, 220, 19, 2652, 1518, 3451, 18337, 96206, 220, 868, 662, 23548, 8850, 35121, 11, 24548, 51713, 264, 44010, 5376, 304, 66731, 43318, 311, 279, 10211, 430, 574, 28537, 311, 864, 59105, 287, 5990, 555, 279, 842, 315, 8850, 52609, 6975, 320, 30035, 13, 220, 16, 64, 11, 293, 2652, 23966, 13, 328, 18, 7609, 23966, 13, 220, 16, 25, 4275, 324, 25180, 97303, 315, 8850, 52609, 304, 1207, 8539, 7607, 315, 356, 19657, 34313, 13, 264, 80354, 278, 11766, 13, 16396, 25, 8850, 35121, 13, 10211, 25, 66731, 56688, 13, 293, 80354, 278, 828, 13, 426, 21, 24548, 25, 308, 284, 220, 1544, 26, 43318, 11, 14464, 4090, 11, 912, 10211, 25, 220, 777, 13, 23, 20903, 220, 17, 13, 21, 13689, 10211, 25, 220, 1627, 13, 16, 20903, 220, 18, 13, 18, 13689, 7314, 315, 52609, 220, 16, 11, 912, 10211, 25, 220, 972, 13, 20, 20903, 220, 17, 13, 18, 13689, 10211, 25, 220, 5547, 13, 24, 20903, 220, 19, 13, 21, 13689, 842, 315, 52609, 220, 17, 11, 912, 10211, 25, 220, 914, 13, 18, 20903, 220, 18, 13, 16, 13689, 10211, 25, 220, 1958, 13, 16, 20903, 220, 18, 13, 19, 13689, 10215, 320, 7403, 1154, 8, 315, 220, 19, 10211, 82, 13, 3861, 27896, 11763, 35073, 24368, 2147, 46, 13114, 435, 320, 20, 11, 5894, 8, 284, 220, 966, 13, 23, 11, 281, 366, 220, 15, 13, 4119, 11, 8272, 128257, 198, 128256, 78191, 198, 791, 8271, 24717, 16940, 279, 46735, 315, 8850, 14847, 617, 29123, 264, 2763, 315, 6666, 439, 814, 527, 9959, 369, 15419, 315, 3823, 18547, 24673, 13, 18185, 1057, 7353, 8830, 315, 279, 2204, 8271, 13918, 22756, 2391, 279, 3217, 315, 8850, 11, 1268, 8850, 14847, 649, 387, 56089, 8625, 14090, 66684, 13, 59250, 520, 279, 3907, 315, 14502, 323, 279, 80474, 386, 552, 9211, 10181, 304, 90558, 617, 1457, 11352, 430, 279, 15449, 315, 11054, 8792, 64383, 29684, 6181, 34313, 649, 28321, 8850, 14847, 13, 43067, 374, 459, 3062, 13010, 430, 49140, 323, 36236, 603, 505, 8137, 13, 2030, 994, 8850, 14847, 527, 704, 315, 2585, 11, 420, 649, 3063, 311, 26048, 24087, 323, 18547, 24673, 13, 763, 4606, 11, 922, 220, 868, 3346, 315, 279, 7187, 374, 11754, 555, 18547, 24673, 13, 69571, 52312, 7293, 14090, 7120, 15934, 477, 527, 539, 8965, 7524, 11, 1606, 279, 11944, 18247, 8385, 5848, 8830, 315, 1521, 24673, 374, 32161, 13, 3639, 574, 3967, 779, 3117, 374, 430, 12742, 32015, 7917, 16681, 3871, 311, 37377, 8850, 14847, 555, 22923, 477, 98795, 1124, 13, 34496, 46121, 315, 32015, 7917, 527, 6532, 304, 420, 1920, 13, 362, 3169, 315, 330, 83, 773, 8838, 48260, 1, 5097, 2035, 11, 449, 832, 8271, 16622, 330, 7678, 1251, 1, 323, 68971, 279, 1023, 11, 11911, 389, 279, 2317, 13, 1442, 420, 1887, 374, 56507, 11, 369, 3187, 422, 8850, 25481, 527, 912, 5129, 56089, 11, 420, 649, 3063, 311, 18547, 24673, 13, 35390, 7978, 617, 6982, 430, 3738, 5315, 315, 34313, 304, 279, 64383, 29684, 6181, 527, 16996, 369, 279, 19812, 315, 8850, 14847, 13, 578, 64383, 29684, 6181, 374, 264, 2678, 63168, 35831, 8271, 6070, 304, 279, 4219, 315, 279, 8271, 430, 21879, 2038, 922, 63757, 56688, 323, 1380, 45803, 433, 311, 1023, 8271, 13918, 311, 7068, 8850, 14847, 13, 1115, 11384, 279, 2547, 311, 4984, 8631, 44315, 11, 2349, 4851, 4478, 477, 8346, 4465, 11, 11213, 477, 43318, 14847, 13, 3804, 29864, 315, 279, 8814, 64383, 29684, 6181, 13, 578, 2849, 4595, 20041, 527, 7559, 304, 279, 8792, 64383, 29684, 6181, 320, 1171, 570, 16666, 25, 4997, 87349, 611, 43205, 55094, 24483, 320, 3791, 7866, 93314, 220, 19, 13, 15, 8, 4800, 11, 264, 1912, 6197, 555, 8626, 434, 1105, 800, 978, 764, 2194, 32744, 511, 14946, 315, 279, 3907, 315, 14502, 323, 51162, 445, 2448, 339, 72, 315, 279, 80474, 386, 552, 9211, 10181, 304, 90558, 706, 11352, 430, 279, 64383, 29684, 6181, 11335, 264, 1790, 810, 4642, 3560, 304, 1521, 11618, 1109, 8767, 3463, 25, 2876, 1193, 374, 279, 8792, 64383, 29684, 6181, 264, 330, 27780, 1, 311, 7068, 8850, 14847, 11, 719, 433, 5727, 79402, 8162, 44398, 12059, 430, 37377, 279, 46735, 315, 8850, 14847, 13, 763, 10065, 4211, 11, 433, 706, 1027, 6982, 430, 61478, 315, 1521, 8162, 44398, 12059, 11767, 311, 1317, 65265, 8850, 17432, 13, 4452, 11, 994, 814, 527, 22756, 11, 17432, 4780, 311, 4725, 8994, 3766, 8850, 14847, 13, 1115, 5039, 430, 34313, 304, 279, 8792, 64383, 29684, 6181, 527, 7701, 48232, 323, 7718, 369, 98795, 8850, 13, 4314, 3135, 1051, 4756, 304, 279, 8486, 22037, 26545, 13, 330, 24243, 75325, 1, 46735, 11767, 311, 1317, 65265, 8850, 578, 12074, 6197, 555, 800, 978, 764, 2194, 32744, 511, 14946, 323, 51162, 445, 2448, 339, 72, 20041, 279, 5820, 315, 34313, 315, 279, 8792, 64383, 29684, 6181, 304, 24548, 2391, 279, 46735, 315, 8850, 14847, 13, 2435, 1051, 3025, 311, 10765, 2204, 2849, 4595, 430, 10383, 279, 10099, 6, 17432, 13, 1789, 872, 4007, 11, 279, 12074, 1511, 3892, 5528, 11, 2737, 264, 15105, 2663, 3469, 11968, 25265, 449, 902, 814, 1436, 24559, 9495, 1523, 81902, 66557, 315, 3177, 22416, 5820, 315, 459, 11054, 79402, 7187, 2949, 279, 8792, 64383, 29684, 6181, 430, 19159, 264, 3230, 49242, 13, 1115, 50160, 279, 46735, 315, 8850, 14847, 11, 1405, 59723, 10099, 6244, 87146, 63757, 13, 330, 1687, 1051, 14792, 1268, 16917, 1057, 17550, 21623, 304, 3230, 2849, 4595, 315, 279, 8792, 64383, 29684, 6181, 11754, 8850, 14847, 1359, 2795, 32744, 511, 14946, 11, 22103, 17054, 520, 279, 10181, 315, 95946, 11, 3907, 315, 14502, 13, 330, 791, 3469, 11968, 5411, 5554, 11627, 315, 1521, 3230, 34313, 6724, 81081, 279, 46735, 315, 8850, 323, 76566, 264, 1614, 315, 89961, 8850, 1210, 44921, 369, 11469, 810, 7524, 52312, 763, 12966, 11, 32403, 315, 420, 1887, 11, 2737, 87544, 12466, 488, 304, 279, 32015, 7917, 315, 279, 8792, 64383, 29684, 6181, 7633, 1618, 11, 1436, 17210, 311, 279, 50160, 46735, 315, 8850, 19459, 5068, 304, 6978, 449, 18547, 323, 30988, 14228, 24673, 13, 362, 2731, 8830, 315, 1521, 11618, 690, 1520, 2274, 810, 3230, 52312, 369, 1521, 24673, 13, 330, 11458, 11, 4726, 7978, 527, 5995, 311, 19874, 3508, 54098, 12457, 304, 4382, 10065, 4211, 649, 387, 71462, 660, 311, 3823, 18547, 24673, 1359, 32744, 511, 14946, 11621, 13, 220, 128257, 198 ]

2,267

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Immunocompromised patients, including those with inborn errors of immunity (IEI), may be at increased risk for severe or prolonged infections with SARS-CoV-2 (Zhu et al. N Engl J Med. 382:727–33, 2020 ; Guan et al. 2020 ; Minotti et al. J Infect. 81:e61–6, 2020 ). While antibody and T cell responses to SARS-CoV-2 structural proteins are well described in healthy convalescent donors, adaptive humoral and cellular immunity has not yet been characterized in patients with antibody deficiency (Grifoni et al. Cell. 181:1489–1501 e1415, 2020 ; Burbelo et al. 2020 ; Long et al. Nat Med. 26:845–8, 2020 ; Braun et al. 2020 ). Herein, we describe the clinical course, antibody, and T cell responses to SARS-CoV-2 structural proteins in a cohort of adult and pediatric patients with antibody deficiencies ( n = 5) and controls (related and unrelated) infected with SARS-CoV-2. Five patients within the same family (3 with antibody deficiency, 2 immunocompetent controls) showed antibody responses to nucleocapsid and spike proteins, as well as SARS-CoV-2 specific T cell immunity at days 65–84 from onset of symptoms. No significant difference was identified between immunocompromised patients and controls. Two additional unrelated, adult patients with common variable immune deficiency were assessed. One did not show antibody response, but both demonstrated SARS-CoV-2-specific T cell immunity when evaluated 33 and 76 days, respectively, following SARS-CoV-2 diagnosis. This report is the first to show robust T cell activity and humoral immunity against SARS-CoV-2 structural proteins in some patients with antibody deficiency. Given the reliance on spike protein in most candidate vaccines (Folegatti et al. Lancet. 396:467–78, 2020 ; Jackson et al. N Engl J Med. 383:1920–31, 2020 ), the responses are encouraging. Additional studies will be needed to further define the timing of onset of immunity, longevity of the immune response, and variability of response in immunocompromised patients. Working on a manuscript? Avoid the common mistakes Introduction Since the start of the COVID-19 pandemic there has been expanding evidence that immunocompromised patients may be at increased risk for severe or prolonged infections with SARS-CoV-2 [ 1 , 2 , 3 ]. Clinical descriptions of COVID-19 in patients with T cell and antibody-specific inborn errors of immunity (IEI) are expanding, including reports of worsened disease course in patients with common variable immunodeficiency (CVID) as compared with pure agammaglobulinemia [ 4 , 5 , 6 , 7 ]. In the largest cohort described to date of patients with IEI and COVID-19, 20% of the cohort required intensive care, with an overall mortality rate of 10%; 6 of 9 deceased patients suffered from an antibody defect [ 6 ]. Their findings represent increased morbidity and mortality, especially at younger ages, as compared with the general population. While antibody and T cell responses to SARS-CoV-2 structural proteins are well described in healthy convalescent donors, adaptive humoral and cellular immunity have not yet been characterized in patients with antibody deficiencies [ 8 , 9 , 10 , 11 ]. Here, we describe five patients affected with antibody deficiencies who developed mild symptoms of COVID-19 and provide comprehensive analysis of their adaptive immune responses. Methods All patients provided written informed consent for clinical data and blood sample collection on protocols approved by the National Institutes of Health Institutional Review Board, in concordance with ethical standards as put forth by the Declaration of Helsinki. Serology Assays SARS-CoV-2 antibody testing was performed via luciferase immunoprecipitation assay on all subjects as previously described [ 9 ]. Briefly, plasma samples were incubated with spike and nucleocapsid proteins fused to Gaussia and Renilla luciferase, respectively. Protein A/G beads were added, and samples were washed prior to addition of coelenterazine substrate (Promega). A Berthold 165 LB 960 Centro Microplate Luminometer was used to measure luciferase activity in light units. Antibody levels were reported as the geometric mean level with 95% confidence interval. As described previously, cutoff limits for determining positive antibodies in the SARS-CoV-2-infected samples were based on the mean plus 3–4 standard deviations of the serum values derived from uninfected blood donor controls for nucleocapsid (125,000 LUs) and spike (45,000 LUs) [ 9 ]. Percentages for categorical variables, median, mean, standard deviation and range, and geometric mean were used to describe the data. Unpaired t tests were used for statistical analysis. T Cell Assays Testing of T cell responses was performed via stimulation of peripheral blood mononuclear cells with peptide libraries encompassing SARS-CoV-2 structural proteins as previously described [ 12 ]. Cells were then cultured for 10 days in 96-well plates with IL-4 (400 IU/mL) and IL-7 (10 ng/mL). On day 10, expanded viral specific T cells (VSTs) were harvested. 2 × 10 5 VSTs were plated in a 96-well plate and re-stimulated with SARS-CoV-2 structural proteins pooled pepmixes or actin (negative control) with CD28/CD49d (BD Biosciences) and anti-CD107a- Pe-Cy7 antibody. After 1 h of stimulation, brefeldin A (Golgiplug; BD Biosciences, San Jose, CA, USA) and monensin (GolgiStop; BD Biosciences, San Jose, CA, USA) were added. Cells were then incubated for an additional 4 h. Cell viability was assessed using Live-Dead Aqua. Cells were surface stained with fluorophore-conjugated antibodies against CD3-BV785, CD4-BV605, CD8- BV421, TCRαβ-PerCP Cy5.5, TCRγδ- APC-Fire750, CCR7-FITC, CD45-RO-PE Dazzle, HLA-DR-Alexaflour700, and CD56-BV650 (Miltenyi Biotec; BioLegend). Cells were fixed, permeabilized with Cytofix/Cytoperm solution (BD Biosciences), and subsequently stained with IFN-γ-APC and TNF-α-PE (Miltenyi Biotec). All samples were acquired on a CytoFLEX cytometer (Beckman Coulter, Brea, CA, USA). The gating strategy for analysis is presented in Supplemental Fig. 2 . Results Clinical History Immunodeficiency History The proband of the kindred (P1) is an 11-year-old boy with CVID, atopy, celiac disease, and recurrent infections beginning in the first year of life. He is currently treated with immunoglobulin replacement therapy with improvement in infections (Supplemental Table 1 ). His twin brother (P2) had a history of periodic fever, apthous stomatitis, pharyngitis, adenitis (PFAPA), recurrent sinusitis, eosinophilic esophagitis, and environmental allergies, as well as hypogammaglobulinemia (Supplemental Fig. 1 ) [ 13 ]. Their younger sister (P3) has history of recurrent sinopulmonary infections, otitis media requiring myringotomy tubes, pharyngitis", "role": "user" }, { "content": "According to data from a cohort of adult and pediatric patients with antibody deficiencies, patients that often fail to make protective immune responses to infections and vaccinations showed robust T-cell activity and humoral immunity against SARS-CoV-2 structural proteins. The new study, led by researchers at Children's National Hospital, is the first to demonstrate a robust T-cell response against SARS-CoV-2 in immunocompromised patients. \"If T-cell responses to SARS-CoV-2 are indeed protective, then it could suggest that adoptive T-cell immunotherapy might benefit more profoundly immunocompromised patients,\" said Michael Keller, M.D., director of the Translational Research Laboratory in the Program for Cell Enhancement and Technologies for Immunotherapy (CETI) at Children's National. \"Through our developing phase I T-cell immunotherapy protocol, we intend to investigate if coronavirus-specific T-cells may be protective following bone marrow transplantation, as well as in other immunodeficient populations.\" The study, published in the Journal of Clinical Immunology, showed that patients with antibody deficiency disorders, including inborn errors of immunity (IEI) and common variable immunodeficiency (CVID), can mount an immune response to SARS-CoV-2. The findings propose that vaccination may still be helpful for this population. \"This data suggests that many patients with antibody deficiency should be capable of responding to COVID-19 vaccines, and current studies at the National Institutes of Health and elsewhere are addressing whether those responses are likely to be protective and lasting,\" said Dr. Keller. The T-cell responses in all the COVID-19 patients were similar in magnitude to healthy adult and pediatric convalescent participants. Kinoshita et al. call for additional studies to further define the quality of the antibody response and the longevity of immune responses against SARS-CoV-2 in immunocompromised patients compared with healthy donors. Currently, there is also very little data on adaptive immune responses to SARS-CoV-2 in these vulnerable populations. The study sheds light on the antibody and T-cell responses to SARS-CoV-2 protein spikes based on a sample size of six patients, including a family group of three children and their mother. All have antibody deficiencies and developed mild COVID-19 symptoms, minus one child who remained asymptomatic. Control participants were the father of the same family, who tested positive for COVID-19, and another incidental adult (not next of kin) experienced mild COVID-19 symptoms. The researchers took blood samples to test the T-cell response in cell cultures and provided comprehensive statistical analysis of the adaptive immune responses. \"This was a small group of patients, but given the high proportion of responses, it does suggest that many of our antibody deficient patients are likely to mount immune responses to SARS-CoV-2,\" said Dr. Keller. \"Additional studies are needed to know whether other patients with primary immunodeficiency develop immunity following COVID-19 infection and will likely be answered by a large international collaboration organized by our collaborators at the Garvan Institute in Sydney.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Immunocompromised patients, including those with inborn errors of immunity (IEI), may be at increased risk for severe or prolonged infections with SARS-CoV-2 (Zhu et al. N Engl J Med. 382:727–33, 2020 ; Guan et al. 2020 ; Minotti et al. J Infect. 81:e61–6, 2020 ). While antibody and T cell responses to SARS-CoV-2 structural proteins are well described in healthy convalescent donors, adaptive humoral and cellular immunity has not yet been characterized in patients with antibody deficiency (Grifoni et al. Cell. 181:1489–1501 e1415, 2020 ; Burbelo et al. 2020 ; Long et al. Nat Med. 26:845–8, 2020 ; Braun et al. 2020 ). Herein, we describe the clinical course, antibody, and T cell responses to SARS-CoV-2 structural proteins in a cohort of adult and pediatric patients with antibody deficiencies ( n = 5) and controls (related and unrelated) infected with SARS-CoV-2. Five patients within the same family (3 with antibody deficiency, 2 immunocompetent controls) showed antibody responses to nucleocapsid and spike proteins, as well as SARS-CoV-2 specific T cell immunity at days 65–84 from onset of symptoms. No significant difference was identified between immunocompromised patients and controls. Two additional unrelated, adult patients with common variable immune deficiency were assessed. One did not show antibody response, but both demonstrated SARS-CoV-2-specific T cell immunity when evaluated 33 and 76 days, respectively, following SARS-CoV-2 diagnosis. This report is the first to show robust T cell activity and humoral immunity against SARS-CoV-2 structural proteins in some patients with antibody deficiency. Given the reliance on spike protein in most candidate vaccines (Folegatti et al. Lancet. 396:467–78, 2020 ; Jackson et al. N Engl J Med. 383:1920–31, 2020 ), the responses are encouraging. Additional studies will be needed to further define the timing of onset of immunity, longevity of the immune response, and variability of response in immunocompromised patients. Working on a manuscript? Avoid the common mistakes Introduction Since the start of the COVID-19 pandemic there has been expanding evidence that immunocompromised patients may be at increased risk for severe or prolonged infections with SARS-CoV-2 [ 1 , 2 , 3 ]. Clinical descriptions of COVID-19 in patients with T cell and antibody-specific inborn errors of immunity (IEI) are expanding, including reports of worsened disease course in patients with common variable immunodeficiency (CVID) as compared with pure agammaglobulinemia [ 4 , 5 , 6 , 7 ]. In the largest cohort described to date of patients with IEI and COVID-19, 20% of the cohort required intensive care, with an overall mortality rate of 10%; 6 of 9 deceased patients suffered from an antibody defect [ 6 ]. Their findings represent increased morbidity and mortality, especially at younger ages, as compared with the general population. While antibody and T cell responses to SARS-CoV-2 structural proteins are well described in healthy convalescent donors, adaptive humoral and cellular immunity have not yet been characterized in patients with antibody deficiencies [ 8 , 9 , 10 , 11 ]. Here, we describe five patients affected with antibody deficiencies who developed mild symptoms of COVID-19 and provide comprehensive analysis of their adaptive immune responses. Methods All patients provided written informed consent for clinical data and blood sample collection on protocols approved by the National Institutes of Health Institutional Review Board, in concordance with ethical standards as put forth by the Declaration of Helsinki. Serology Assays SARS-CoV-2 antibody testing was performed via luciferase immunoprecipitation assay on all subjects as previously described [ 9 ]. Briefly, plasma samples were incubated with spike and nucleocapsid proteins fused to Gaussia and Renilla luciferase, respectively. Protein A/G beads were added, and samples were washed prior to addition of coelenterazine substrate (Promega). A Berthold 165 LB 960 Centro Microplate Luminometer was used to measure luciferase activity in light units. Antibody levels were reported as the geometric mean level with 95% confidence interval. As described previously, cutoff limits for determining positive antibodies in the SARS-CoV-2-infected samples were based on the mean plus 3–4 standard deviations of the serum values derived from uninfected blood donor controls for nucleocapsid (125,000 LUs) and spike (45,000 LUs) [ 9 ]. Percentages for categorical variables, median, mean, standard deviation and range, and geometric mean were used to describe the data. Unpaired t tests were used for statistical analysis. T Cell Assays Testing of T cell responses was performed via stimulation of peripheral blood mononuclear cells with peptide libraries encompassing SARS-CoV-2 structural proteins as previously described [ 12 ]. Cells were then cultured for 10 days in 96-well plates with IL-4 (400 IU/mL) and IL-7 (10 ng/mL). On day 10, expanded viral specific T cells (VSTs) were harvested. 2 × 10 5 VSTs were plated in a 96-well plate and re-stimulated with SARS-CoV-2 structural proteins pooled pepmixes or actin (negative control) with CD28/CD49d (BD Biosciences) and anti-CD107a- Pe-Cy7 antibody. After 1 h of stimulation, brefeldin A (Golgiplug; BD Biosciences, San Jose, CA, USA) and monensin (GolgiStop; BD Biosciences, San Jose, CA, USA) were added. Cells were then incubated for an additional 4 h. Cell viability was assessed using Live-Dead Aqua. Cells were surface stained with fluorophore-conjugated antibodies against CD3-BV785, CD4-BV605, CD8- BV421, TCRαβ-PerCP Cy5.5, TCRγδ- APC-Fire750, CCR7-FITC, CD45-RO-PE Dazzle, HLA-DR-Alexaflour700, and CD56-BV650 (Miltenyi Biotec; BioLegend). Cells were fixed, permeabilized with Cytofix/Cytoperm solution (BD Biosciences), and subsequently stained with IFN-γ-APC and TNF-α-PE (Miltenyi Biotec). All samples were acquired on a CytoFLEX cytometer (Beckman Coulter, Brea, CA, USA). The gating strategy for analysis is presented in Supplemental Fig. 2 . Results Clinical History Immunodeficiency History The proband of the kindred (P1) is an 11-year-old boy with CVID, atopy, celiac disease, and recurrent infections beginning in the first year of life. He is currently treated with immunoglobulin replacement therapy with improvement in infections (Supplemental Table 1 ). His twin brother (P2) had a history of periodic fever, apthous stomatitis, pharyngitis, adenitis (PFAPA), recurrent sinusitis, eosinophilic esophagitis, and environmental allergies, as well as hypogammaglobulinemia (Supplemental Fig. 1 ) [ 13 ]. Their younger sister (P3) has history of recurrent sinopulmonary infections, otitis media requiring myringotomy tubes, pharyngitis<|im_end|> <|im_start|>assistant According to data from a cohort of adult and pediatric patients with antibody deficiencies, patients that often fail to make protective immune responses to infections and vaccinations showed robust T-cell activity and humoral immunity against SARS-CoV-2 structural proteins. The new study, led by researchers at Children's National Hospital, is the first to demonstrate a robust T-cell response against SARS-CoV-2 in immunocompromised patients. "If T-cell responses to SARS-CoV-2 are indeed protective, then it could suggest that adoptive T-cell immunotherapy might benefit more profoundly immunocompromised patients," said Michael Keller, M.D., director of the Translational Research Laboratory in the Program for Cell Enhancement and Technologies for Immunotherapy (CETI) at Children's National. "Through our developing phase I T-cell immunotherapy protocol, we intend to investigate if coronavirus-specific T-cells may be protective following bone marrow transplantation, as well as in other immunodeficient populations." The study, published in the Journal of Clinical Immunology, showed that patients with antibody deficiency disorders, including inborn errors of immunity (IEI) and common variable immunodeficiency (CVID), can mount an immune response to SARS-CoV-2. The findings propose that vaccination may still be helpful for this population. "This data suggests that many patients with antibody deficiency should be capable of responding to COVID-19 vaccines, and current studies at the National Institutes of Health and elsewhere are addressing whether those responses are likely to be protective and lasting," said Dr. Keller. The T-cell responses in all the COVID-19 patients were similar in magnitude to healthy adult and pediatric convalescent participants. Kinoshita et al. call for additional studies to further define the quality of the antibody response and the longevity of immune responses against SARS-CoV-2 in immunocompromised patients compared with healthy donors. Currently, there is also very little data on adaptive immune responses to SARS-CoV-2 in these vulnerable populations. The study sheds light on the antibody and T-cell responses to SARS-CoV-2 protein spikes based on a sample size of six patients, including a family group of three children and their mother. All have antibody deficiencies and developed mild COVID-19 symptoms, minus one child who remained asymptomatic. Control participants were the father of the same family, who tested positive for COVID-19, and another incidental adult (not next of kin) experienced mild COVID-19 symptoms. The researchers took blood samples to test the T-cell response in cell cultures and provided comprehensive statistical analysis of the adaptive immune responses. "This was a small group of patients, but given the high proportion of responses, it does suggest that many of our antibody deficient patients are likely to mount immune responses to SARS-CoV-2," said Dr. Keller. "Additional studies are needed to know whether other patients with primary immunodeficiency develop immunity following COVID-19 infection and will likely be answered by a large international collaboration organized by our collaborators at the Garvan Institute in Sydney." <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 67335, 12255, 25475, 4147, 6978, 11, 2737, 1884, 449, 304, 16381, 6103, 315, 40368, 320, 5484, 40, 705, 1253, 387, 520, 7319, 5326, 369, 15748, 477, 44387, 30020, 449, 328, 17485, 87271, 53, 12, 17, 320, 57, 17156, 1880, 453, 13, 452, 99730, 622, 3344, 13, 220, 18781, 25, 23486, 4235, 1644, 11, 220, 2366, 15, 2652, 4673, 276, 1880, 453, 13, 220, 2366, 15, 2652, 3468, 42327, 1880, 453, 13, 622, 88911, 13, 220, 5932, 57076, 5547, 4235, 21, 11, 220, 2366, 15, 7609, 6104, 63052, 323, 350, 2849, 14847, 311, 328, 17485, 87271, 53, 12, 17, 24693, 28896, 527, 1664, 7633, 304, 9498, 5804, 3916, 1189, 33149, 11, 48232, 2854, 10020, 323, 35693, 40368, 706, 539, 3686, 1027, 32971, 304, 6978, 449, 63052, 48294, 320, 6600, 333, 21446, 1880, 453, 13, 14299, 13, 220, 10562, 25, 10410, 24, 4235, 3965, 16, 384, 9335, 20, 11, 220, 2366, 15, 2652, 92733, 20782, 1880, 453, 13, 220, 2366, 15, 2652, 5843, 1880, 453, 13, 24772, 3344, 13, 220, 1627, 25, 24650, 4235, 23, 11, 220, 2366, 15, 2652, 70703, 1880, 453, 13, 220, 2366, 15, 7609, 5810, 258, 11, 584, 7664, 279, 14830, 3388, 11, 63052, 11, 323, 350, 2849, 14847, 311, 328, 17485, 87271, 53, 12, 17, 24693, 28896, 304, 264, 41944, 315, 6822, 323, 53166, 6978, 449, 63052, 72946, 320, 308, 284, 220, 20, 8, 323, 11835, 320, 9920, 323, 46305, 8, 29374, 449, 328, 17485, 87271, 53, 12, 17, 13, 21594, 6978, 2949, 279, 1890, 3070, 320, 18, 449, 63052, 48294, 11, 220, 17, 33119, 12255, 7005, 306, 11835, 8, 8710, 63052, 14847, 311, 31484, 511, 2690, 307, 323, 37393, 28896, 11, 439, 1664, 439, 328, 17485, 87271, 53, 12, 17, 3230, 350, 2849, 40368, 520, 2919, 220, 2397, 4235, 5833, 505, 42080, 315, 13803, 13, 2360, 5199, 6811, 574, 11054, 1990, 33119, 12255, 25475, 4147, 6978, 323, 11835, 13, 9220, 5217, 46305, 11, 6822, 6978, 449, 4279, 3977, 22852, 48294, 1051, 32448, 13, 3861, 1550, 539, 1501, 63052, 2077, 11, 719, 2225, 21091, 328, 17485, 87271, 53, 12, 17, 19440, 350, 2849, 40368, 994, 26126, 220, 1644, 323, 220, 4767, 2919, 11, 15947, 11, 2768, 328, 17485, 87271, 53, 12, 17, 23842, 13, 1115, 1934, 374, 279, 1176, 311, 1501, 22514, 350, 2849, 5820, 323, 2854, 10020, 40368, 2403, 328, 17485, 87271, 53, 12, 17, 24693, 28896, 304, 1063, 6978, 449, 63052, 48294, 13, 16644, 279, 54180, 389, 37393, 13128, 304, 1455, 9322, 40300, 320, 37, 1286, 70, 32055, 1880, 453, 13, 39634, 295, 13, 220, 19615, 25, 20419, 4235, 2495, 11, 220, 2366, 15, 2652, 13972, 1880, 453, 13, 452, 99730, 622, 3344, 13, 220, 19230, 25, 5926, 15, 4235, 2148, 11, 220, 2366, 15, 7026, 279, 14847, 527, 26921, 13, 24086, 7978, 690, 387, 4460, 311, 4726, 7124, 279, 18912, 315, 42080, 315, 40368, 11, 58219, 315, 279, 22852, 2077, 11, 323, 54709, 315, 2077, 304, 33119, 12255, 25475, 4147, 6978, 13, 22938, 389, 264, 47913, 30, 35106, 279, 4279, 21294, 29438, 8876, 279, 1212, 315, 279, 20562, 12, 777, 28522, 1070, 706, 1027, 24050, 6029, 430, 33119, 12255, 25475, 4147, 6978, 1253, 387, 520, 7319, 5326, 369, 15748, 477, 44387, 30020, 449, 328, 17485, 87271, 53, 12, 17, 510, 220, 16, 1174, 220, 17, 1174, 220, 18, 21087, 33135, 28887, 315, 20562, 12, 777, 304, 6978, 449, 350, 2849, 323, 63052, 19440, 304, 16381, 6103, 315, 40368, 320, 5484, 40, 8, 527, 24050, 11, 2737, 6821, 315, 47293, 6901, 8624, 3388, 304, 6978, 449, 4279, 3977, 33119, 98677, 10603, 320, 34, 7635, 8, 439, 7863, 449, 10748, 945, 8836, 351, 1718, 24292, 22689, 510, 220, 19, 1174, 220, 20, 1174, 220, 21, 1174, 220, 22, 21087, 763, 279, 7928, 41944, 7633, 311, 2457, 315, 6978, 449, 18657, 40, 323, 20562, 12, 777, 11, 220, 508, 4, 315, 279, 41944, 2631, 37295, 2512, 11, 449, 459, 8244, 29528, 4478, 315, 220, 605, 16571, 220, 21, 315, 220, 24, 43720, 6978, 16654, 505, 459, 63052, 23011, 510, 220, 21, 21087, 11205, 14955, 4097, 7319, 93144, 19025, 323, 29528, 11, 5423, 520, 14992, 17051, 11, 439, 7863, 449, 279, 4689, 7187, 13, 6104, 63052, 323, 350, 2849, 14847, 311, 328, 17485, 87271, 53, 12, 17, 24693, 28896, 527, 1664, 7633, 304, 9498, 5804, 3916, 1189, 33149, 11, 48232, 2854, 10020, 323, 35693, 40368, 617, 539, 3686, 1027, 32971, 304, 6978, 449, 63052, 72946, 510, 220, 23, 1174, 220, 24, 1174, 220, 605, 1174, 220, 806, 21087, 5810, 11, 584, 7664, 4330, 6978, 11754, 449, 63052, 72946, 889, 8040, 23900, 13803, 315, 20562, 12, 777, 323, 3493, 16195, 6492, 315, 872, 48232, 22852, 14847, 13, 19331, 2052, 6978, 3984, 5439, 16369, 14771, 369, 14830, 828, 323, 6680, 6205, 4526, 389, 32885, 12054, 555, 279, 5165, 73828, 315, 6401, 98984, 10506, 8925, 11, 304, 3613, 541, 685, 449, 31308, 10886, 439, 2231, 13544, 555, 279, 42021, 315, 77434, 13, 8409, 2508, 2755, 954, 328, 17485, 87271, 53, 12, 17, 63052, 7649, 574, 10887, 4669, 27016, 11691, 521, 33119, 454, 2827, 575, 7709, 65033, 389, 682, 15223, 439, 8767, 7633, 510, 220, 24, 21087, 37618, 398, 11, 32426, 10688, 1051, 49727, 660, 449, 37393, 323, 31484, 511, 2690, 307, 28896, 75754, 311, 18879, 29578, 323, 14094, 6374, 27016, 11691, 521, 11, 15947, 13, 49475, 362, 16169, 55308, 1051, 3779, 11, 323, 10688, 1051, 38593, 4972, 311, 5369, 315, 1080, 301, 1992, 10119, 54057, 320, 36286, 11437, 570, 362, 9084, 339, 820, 220, 10680, 41250, 220, 16415, 57674, 18654, 1787, 445, 10318, 21037, 574, 1511, 311, 6767, 27016, 11691, 521, 5820, 304, 3177, 8316, 13, 95951, 1094, 5990, 1051, 5068, 439, 279, 53584, 3152, 2237, 449, 220, 2721, 4, 12410, 10074, 13, 1666, 7633, 8767, 11, 45379, 13693, 369, 26679, 6928, 59854, 304, 279, 328, 17485, 87271, 53, 12, 17, 48336, 1599, 10688, 1051, 3196, 389, 279, 3152, 5636, 220, 18, 4235, 19, 5410, 86365, 315, 279, 41529, 2819, 14592, 505, 653, 13885, 1599, 6680, 35558, 11835, 369, 31484, 511, 2690, 307, 320, 6549, 11, 931, 445, 3642, 8, 323, 37393, 320, 1774, 11, 931, 445, 3642, 8, 510, 220, 24, 21087, 56448, 1154, 369, 70636, 7482, 11, 23369, 11, 3152, 11, 5410, 38664, 323, 2134, 11, 323, 53584, 3152, 1051, 1511, 311, 7664, 279, 828, 13, 1252, 77267, 259, 7177, 1051, 1511, 369, 29564, 6492, 13, 350, 14299, 2755, 954, 27866, 315, 350, 2849, 14847, 574, 10887, 4669, 41959, 315, 35688, 6680, 1647, 263, 9834, 7917, 449, 72249, 20797, 38632, 287, 328, 17485, 87271, 53, 12, 17, 24693, 28896, 439, 8767, 7633, 510, 220, 717, 21087, 59190, 1051, 1243, 89948, 369, 220, 605, 2919, 304, 220, 4161, 2695, 616, 25485, 449, 11598, 12, 19, 320, 3443, 81725, 93422, 8, 323, 11598, 12, 22, 320, 605, 7933, 93422, 570, 1952, 1938, 220, 605, 11, 17626, 29962, 3230, 350, 7917, 320, 53, 790, 82, 8, 1051, 67572, 13, 220, 17, 25800, 220, 605, 220, 20, 650, 790, 82, 1051, 88233, 304, 264, 220, 4161, 2695, 616, 12235, 323, 312, 5594, 318, 7913, 449, 328, 17485, 87271, 53, 12, 17, 24693, 28896, 76476, 87695, 36171, 288, 477, 1180, 258, 320, 43324, 2585, 8, 449, 11325, 1591, 14, 6620, 2491, 67, 320, 9740, 77948, 5979, 2436, 8, 323, 7294, 12, 6620, 7699, 64, 12, 5250, 7813, 88, 22, 63052, 13, 4740, 220, 16, 305, 315, 41959, 11, 293, 1116, 789, 258, 362, 320, 38, 337, 8376, 48574, 26, 40410, 77948, 5979, 2436, 11, 5960, 11097, 11, 9362, 11, 7427, 8, 323, 1647, 729, 258, 320, 38, 337, 8376, 10903, 26, 40410, 77948, 5979, 2436, 11, 5960, 11097, 11, 9362, 11, 7427, 8, 1051, 3779, 13, 59190, 1051, 1243, 49727, 660, 369, 459, 5217, 220, 19, 305, 13, 14299, 68507, 574, 32448, 1701, 11406, 12, 29420, 72507, 13, 59190, 1051, 7479, 61152, 449, 54736, 5237, 461, 15204, 48802, 660, 59854, 2403, 11325, 18, 7826, 53, 22539, 11, 11325, 19, 7826, 53, 19666, 11, 11325, 23, 12, 41200, 18245, 11, 350, 9150, 19481, 52355, 12, 3976, 7269, 18221, 20, 13, 20, 11, 350, 9150, 60474, 86486, 12, 87341, 7424, 556, 11711, 11, 356, 9150, 22, 7424, 964, 34, 11, 11325, 1774, 12, 1308, 12, 1777, 423, 10002, 273, 11, 473, 18326, 12, 7842, 6830, 2635, 64, 1517, 414, 7007, 11, 323, 11325, 3487, 7826, 53, 13655, 320, 60332, 2002, 39172, 426, 11345, 762, 26, 24432, 40775, 570, 59190, 1051, 8521, 11, 55424, 13052, 1534, 449, 18221, 998, 5862, 11547, 16820, 3376, 76, 6425, 320, 9740, 77948, 5979, 2436, 705, 323, 28520, 61152, 449, 11812, 45, 12, 60474, 12, 2599, 34, 323, 32023, 37, 12, 19481, 12, 1777, 320, 60332, 2002, 39172, 426, 11345, 762, 570, 2052, 10688, 1051, 19426, 389, 264, 18221, 998, 37, 36345, 79909, 21037, 320, 3513, 377, 1543, 67948, 466, 11, 426, 5325, 11, 9362, 11, 7427, 570, 578, 74499, 8446, 369, 6492, 374, 10666, 304, 43491, 278, 23966, 13, 220, 17, 662, 18591, 33135, 11346, 67335, 98677, 10603, 11346, 578, 3650, 438, 315, 279, 3169, 1171, 320, 47, 16, 8, 374, 459, 220, 806, 4771, 6418, 8334, 449, 356, 7635, 11, 520, 1289, 11, 272, 95705, 8624, 11, 323, 65174, 30020, 7314, 304, 279, 1176, 1060, 315, 2324, 13, 1283, 374, 5131, 12020, 449, 33119, 76525, 24292, 14039, 15419, 449, 16048, 304, 30020, 320, 10254, 2833, 278, 6771, 220, 16, 7609, 5414, 28497, 10868, 320, 47, 17, 8, 1047, 264, 3925, 315, 39445, 34653, 11, 1469, 339, 788, 20703, 82801, 11, 1343, 661, 983, 20000, 11, 100213, 20000, 320, 20280, 89769, 705, 65174, 76914, 20000, 11, 62894, 258, 98635, 292, 1560, 5237, 351, 20000, 11, 323, 12434, 58742, 11, 439, 1664, 439, 9950, 540, 8836, 351, 1718, 24292, 22689, 320, 10254, 2833, 278, 23966, 13, 220, 16, 883, 510, 220, 1032, 21087, 11205, 14992, 13219, 320, 47, 18, 8, 706, 3925, 315, 65174, 7589, 454, 360, 55892, 30020, 11, 14479, 20000, 3772, 23537, 856, 12928, 85995, 34083, 11, 1343, 661, 983, 20000, 128257, 198, 128256, 78191, 198, 11439, 311, 828, 505, 264, 41944, 315, 6822, 323, 53166, 6978, 449, 63052, 72946, 11, 6978, 430, 3629, 3775, 311, 1304, 29219, 22852, 14847, 311, 30020, 323, 91971, 8710, 22514, 350, 33001, 5820, 323, 2854, 10020, 40368, 2403, 328, 17485, 87271, 53, 12, 17, 24693, 28896, 13, 578, 502, 4007, 11, 6197, 555, 12074, 520, 15394, 596, 5165, 15429, 11, 374, 279, 1176, 311, 20461, 264, 22514, 350, 33001, 2077, 2403, 328, 17485, 87271, 53, 12, 17, 304, 33119, 12255, 25475, 4147, 6978, 13, 330, 2746, 350, 33001, 14847, 311, 328, 17485, 87271, 53, 12, 17, 527, 13118, 29219, 11, 1243, 433, 1436, 4284, 430, 11142, 535, 350, 33001, 33119, 42811, 2643, 8935, 810, 66278, 33119, 12255, 25475, 4147, 6978, 1359, 1071, 8096, 66603, 11, 386, 920, 2637, 7690, 315, 279, 4149, 75, 1697, 8483, 32184, 304, 279, 6826, 369, 14299, 53617, 323, 25579, 369, 67335, 42811, 320, 34, 1372, 40, 8, 520, 15394, 596, 5165, 13, 330, 24798, 1057, 11469, 10474, 358, 350, 33001, 33119, 42811, 11766, 11, 584, 30730, 311, 19874, 422, 33333, 19440, 350, 1824, 6572, 1253, 387, 29219, 2768, 17685, 83748, 98702, 11, 439, 1664, 439, 304, 1023, 33119, 98677, 5499, 22673, 1210, 578, 4007, 11, 4756, 304, 279, 10139, 315, 33135, 67335, 2508, 11, 8710, 430, 6978, 449, 63052, 48294, 24673, 11, 2737, 304, 16381, 6103, 315, 40368, 320, 5484, 40, 8, 323, 4279, 3977, 33119, 98677, 10603, 320, 34, 7635, 705, 649, 6606, 459, 22852, 2077, 311, 328, 17485, 87271, 53, 12, 17, 13, 578, 14955, 30714, 430, 47165, 1253, 2103, 387, 11190, 369, 420, 7187, 13, 330, 2028, 828, 13533, 430, 1690, 6978, 449, 63052, 48294, 1288, 387, 13171, 315, 30438, 311, 20562, 12, 777, 40300, 11, 323, 1510, 7978, 520, 279, 5165, 73828, 315, 6401, 323, 18403, 527, 28118, 3508, 1884, 14847, 527, 4461, 311, 387, 29219, 323, 29869, 1359, 1071, 2999, 13, 66603, 13, 578, 350, 33001, 14847, 304, 682, 279, 20562, 12, 777, 6978, 1051, 4528, 304, 26703, 311, 9498, 6822, 323, 53166, 5804, 3916, 1189, 13324, 13, 31991, 9451, 6388, 1880, 453, 13, 1650, 369, 5217, 7978, 311, 4726, 7124, 279, 4367, 315, 279, 63052, 2077, 323, 279, 58219, 315, 22852, 14847, 2403, 328, 17485, 87271, 53, 12, 17, 304, 33119, 12255, 25475, 4147, 6978, 7863, 449, 9498, 33149, 13, 25122, 11, 1070, 374, 1101, 1633, 2697, 828, 389, 48232, 22852, 14847, 311, 328, 17485, 87271, 53, 12, 17, 304, 1521, 20134, 22673, 13, 578, 4007, 77039, 3177, 389, 279, 63052, 323, 350, 33001, 14847, 311, 328, 17485, 87271, 53, 12, 17, 13128, 51760, 3196, 389, 264, 6205, 1404, 315, 4848, 6978, 11, 2737, 264, 3070, 1912, 315, 2380, 2911, 323, 872, 6691, 13, 2052, 617, 63052, 72946, 323, 8040, 23900, 20562, 12, 777, 13803, 11, 28382, 832, 1716, 889, 14958, 97354, 13795, 13, 7935, 13324, 1051, 279, 7126, 315, 279, 1890, 3070, 11, 889, 12793, 6928, 369, 20562, 12, 777, 11, 323, 2500, 84316, 6822, 320, 1962, 1828, 315, 24890, 8, 10534, 23900, 20562, 12, 777, 13803, 13, 578, 12074, 3952, 6680, 10688, 311, 1296, 279, 350, 33001, 2077, 304, 2849, 27833, 323, 3984, 16195, 29564, 6492, 315, 279, 48232, 22852, 14847, 13, 330, 2028, 574, 264, 2678, 1912, 315, 6978, 11, 719, 2728, 279, 1579, 21801, 315, 14847, 11, 433, 1587, 4284, 430, 1690, 315, 1057, 63052, 87544, 6978, 527, 4461, 311, 6606, 22852, 14847, 311, 328, 17485, 87271, 53, 12, 17, 1359, 1071, 2999, 13, 66603, 13, 330, 30119, 7978, 527, 4460, 311, 1440, 3508, 1023, 6978, 449, 6156, 33119, 98677, 10603, 2274, 40368, 2768, 20562, 12, 777, 19405, 323, 690, 4461, 387, 19089, 555, 264, 3544, 6625, 20632, 17057, 555, 1057, 79119, 520, 279, 12471, 16023, 10181, 304, 21972, 1210, 220, 128257, 198 ]

2,298

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Metaplastic breast carcinoma is an aggressive form of invasive breast cancer with histological evidence of epithelial to mesenchymal transition (EMT). However, the defining molecular events are unknown. Here we show that CCN6 (WISP3), a secreted matricellular protein of the CCN (CYR61/CTGF/NOV) family, is significantly downregulated in clinical samples of human spindle cell metaplastic breast carcinoma. We generated a mouse model of mammary epithelial-specific Ccn6 deletion by developing a floxed Ccn6 mouse which was bred with an MMTV-Cre mouse. Ccn6 fl/fl ;MMTV-Cre mice displayed severe defects in ductal branching and abnormal age-related involution compared to littermate controls. Ccn6 fl/fl ;MMTV-Cre mice developed invasive high grade mammary carcinomas with bona fide EMT, histologically similar to human metaplastic breast carcinomas. Global gene expression profiling of Ccn6 fl/fl mammary carcinomas and comparison of orthologous genes with a human metaplastic carcinoma signature revealed a significant overlap of 87 genes ( P =5 × 10 −11 ). Among the shared deregulated genes between mouse and human are important regulators of epithelial morphogenesis including Cdh1, Ck19, Cldn3 and 4, Ddr1, and Wnt10a . These results document a causal role for Ccn6 deletion in the pathogenesis of metaplastic carcinomas with histological and molecular similarities with human disease. We provide a platform to study new targets in the diagnosis and treatment of human metaplastic carcinomas, and a new disease relevant model in which to test new treatment strategies. Introduction Metaplastic breast carcinomas constitute approximately 1% of invasive carcinomas and are characterized by histological evidence of epithelial to mesenchymal transition (EMT) towards spindle, squamous, and less frequently heterologous elements including chondroid and osseous differentiation. 1 Metaplastic carcinomas are a subtype of triple negative breast cancer (TNBC) that are poorly responsive to chemotherapy, with high propensity for distant metastasis. 2 , 3 Recent comprehensive genomic analyses revealed that metaplastic carcinomas belong to the mesenchymal-like subtype of TNBC, with a distinct transcriptional profile than other invasive breast carcinomas. 4 , 5 , 6 However, the molecular determinants of metaplastic carcinomas needed to inform effective treatments are still incompletely understood. Metaplasia is the reversible change in which one adult cell type is replaced by another adult cell type. Epithelial cells may undergo metaplasia through EMT, which during tumorigenesis results in the acquisition of molecular and phenotypic changes towards a spindle cell morphology and dysfunctional cell-cell adhesion, leading to invasion and metastasis. 7 Of all human cancers, metaplastic carcinomas provide the clearest evidence of morphological and molecular EMT with deregulation of genes involved in cell adhesion and low expression of claudins. 4 , 5 , 6 CCN6 (WISP3) is a secreted matricellular protein of the CCN family, which includes six members that play regulatory rather than structural roles in embryonic development, cell attachment and growth. 8 CCN proteins act in a cell and tissue-specific manner primarily through direct binding to cell surface receptors including integrins and by modulating the effect of extracellular growth factors on epithelial cells. 9 , 10 , 11 , 12 , 13 , 14 Located at 6q21-22, CCN6 was first identified as a novel gene downregulated in the highly aggressive inflammatory breast cancers. 15 We have shown that CCN6 is secreted by ductal epithelial cells in the breast, and that CCN6 downregulation in nontumorigenic breast cells is a robust inducer of EMT and is sufficient to confer growth factor independent survival and resistance to anoikis, a property of metastatic cancer cells. 9 , 11 , 12 , 13 , 14 , 15 Despite this knowledge, a direct role of CCN6 in breast tumorigenesis and the underlying mechanisms have remained elusive in part due to the lack of a physiologically relevant genetically engineered mouse model. Results CCN6 protein is reduced in human metaplastic carcinomas Based on our previous studies showing that CCN6 regulates the transition between epithelial and mesenchymal states in breast cells, we set out to investigate CCN6 expression in breast tissues. Immunohistochemical evaluation revealed that CCN6 level is significantly reduced in spindle metaplastic carcinomas compared to normal breast and invasive ductal carcinomas ( Figure 1a ). All normal breast lobules examined, and 67% of invasive ductal carcinomas maintained high levels of CCN6. This distribution was shifted in metaplastic carcinomas, among which 67.9% had low CCN6 expression ( Figure 1b ). Figure 1 CCN6 protein is reduced in human spindle metaplastic carcinomas of the breast compared to invasive ductal carcinoma and normal breast lobules. ( a ) images of a normal breast lobule, an invasive ductal carcinoma with no special features, and a spindle metaplastic carcinoma stained with hematoxylin and eosin (H&E) and CCN6 immunostaining (magnification × 400). ( b ) Invasive metaplastic and ductal carcinomas with high or low CCN6 protein. Chi-square test P =0.0018. (Scale bars, 20 μm.) Full size image Mammary epithelial specific Ccn6 deletion causes abnormal mammary gland development To directly investigate whether loss of Ccn6 in vivo triggers the development of carcinomas that recapitulate human metaplastic carcinomas, we generated a new model of epithelial cell specific Ccn6 deletion in the mammary gland using Cre/loxp-mediated recombination ( Figures 2a and b ). We specifically inactivated the Ccn6 gene in the mammary epithelium, by intercrossing the floxed Ccn6 mice with the MMTV-Cre mice. The offspring were genotyped using primers specific for various Ccn6 alleles (that is, floxed, wild type and deleted) and with primers specific for Cre ( Figure 2c ). We confirmed the presence of Ccn6 deletion in the mammary glands by quantitative reverse transcriptase-PCR and Western blots using whole mammary gland protein extracts, and by immunohistochemistry in mammary gland tissue samples ( Figures 2d–f ). Figure 2 Conditional deletion of Ccn6 in the mammary epithelium using the Cre-Lox system. ( a ) Mouse Ccn6 containing exons 2 and 3. Pictured: wild-type allele; targeted allele after homologous recombination in embryonic stem (ES) cells; the floxed allele in which exons 2 and 3 are flanked by loxP sites and the neomycin cassette has been excised; the allele in which exons 2 and 3 have been deleted in Ccn6 fl/fl ;MMTV-Cre mice. 5′ homology arm (~5.6 kb),", "role": "user" }, { "content": "For more than a decade, Celina Kleer, M.D., has been studying how a poorly understood protein called CCN6 affects breast cancer. To learn more about its role in breast cancer development, Kleer's lab designed a special mouse model - which led to something unexpected. They deleted CCN6 from the mammary gland in the mice. This type of model allows researchers to study effects specific to the loss of the protein. As Kleer and her team checked in at different ages, they found delayed development and mammary glands that did not develop properly. \"After a year, the mice started to form mammary gland tumors. These tumors looked identical to human metaplastic breast cancer, with the same characteristics. That was very exciting,\" says Kleer, Harold A. Oberman Collegiate Professor of Pathology and director of the Breast Pathology Program at the University of Michigan Comprehensive Cancer Center. Metaplastic breast cancer is a very rare and aggressive subtype of triple-negative breast cancer - a type considered rare and aggressive of its own. Up to 20 percent of all breast cancers are triple-negative. Only 1 percent are metaplastic. \"Metaplastic breast cancers are challenging to diagnose and treat. In part, the difficulties stem from the lack of mouse models to study this disease,\" Kleer says. So not only did Kleer gain a better understanding of CCN6, but her lab's findings open the door to a better understanding of this very challenging subtype of breast cancer. The study is published in Oncogene. \"Our hypothesis, based on years of experiments in our lab, was that knocking out this gene would induce breast cancer. But we didn't know if knocking out CCN6 would be enough to unleash tumors, and if so, when, or what kind,\" Kleer says. \"Now we have a new mouse model, and a new way of studying metaplastic carcinomas, for which there's no other model.\" One of the hallmarks of metaplastic breast cancer is that the cells are more mesenchymal, a cell state that enables them to move and invade. Likewise, researchers saw this in their mouse model: knocking down CCN6 induced the process known as the epithelial to mesenchymal transition. \"This process is hard to see in tumors under a microscope. It's exciting that we see this in the mouse model as well as in patient samples and cell lines,\" Kleer says. The researchers looked at the tumors developed by mice in their new model and identified several potential genes to target with therapeutics. Some of the options, such as p38, already have antibodies or inhibitors against them. The team's next steps will be to test these potential therapeutics in the lab, in combination with existing chemotherapies. They will also use the mouse model to gain a better understanding of metaplastic breast cancer and discover new genes that play a role it its development. \"Understanding the disease may lead us to better ways to attack it,\" Kleer says. \"For patients with metaplastic breast cancer, it doesn't matter that it's rare. They want - and they deserve - better treatments.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Metaplastic breast carcinoma is an aggressive form of invasive breast cancer with histological evidence of epithelial to mesenchymal transition (EMT). However, the defining molecular events are unknown. Here we show that CCN6 (WISP3), a secreted matricellular protein of the CCN (CYR61/CTGF/NOV) family, is significantly downregulated in clinical samples of human spindle cell metaplastic breast carcinoma. We generated a mouse model of mammary epithelial-specific Ccn6 deletion by developing a floxed Ccn6 mouse which was bred with an MMTV-Cre mouse. Ccn6 fl/fl ;MMTV-Cre mice displayed severe defects in ductal branching and abnormal age-related involution compared to littermate controls. Ccn6 fl/fl ;MMTV-Cre mice developed invasive high grade mammary carcinomas with bona fide EMT, histologically similar to human metaplastic breast carcinomas. Global gene expression profiling of Ccn6 fl/fl mammary carcinomas and comparison of orthologous genes with a human metaplastic carcinoma signature revealed a significant overlap of 87 genes ( P =5 × 10 −11 ). Among the shared deregulated genes between mouse and human are important regulators of epithelial morphogenesis including Cdh1, Ck19, Cldn3 and 4, Ddr1, and Wnt10a . These results document a causal role for Ccn6 deletion in the pathogenesis of metaplastic carcinomas with histological and molecular similarities with human disease. We provide a platform to study new targets in the diagnosis and treatment of human metaplastic carcinomas, and a new disease relevant model in which to test new treatment strategies. Introduction Metaplastic breast carcinomas constitute approximately 1% of invasive carcinomas and are characterized by histological evidence of epithelial to mesenchymal transition (EMT) towards spindle, squamous, and less frequently heterologous elements including chondroid and osseous differentiation. 1 Metaplastic carcinomas are a subtype of triple negative breast cancer (TNBC) that are poorly responsive to chemotherapy, with high propensity for distant metastasis. 2 , 3 Recent comprehensive genomic analyses revealed that metaplastic carcinomas belong to the mesenchymal-like subtype of TNBC, with a distinct transcriptional profile than other invasive breast carcinomas. 4 , 5 , 6 However, the molecular determinants of metaplastic carcinomas needed to inform effective treatments are still incompletely understood. Metaplasia is the reversible change in which one adult cell type is replaced by another adult cell type. Epithelial cells may undergo metaplasia through EMT, which during tumorigenesis results in the acquisition of molecular and phenotypic changes towards a spindle cell morphology and dysfunctional cell-cell adhesion, leading to invasion and metastasis. 7 Of all human cancers, metaplastic carcinomas provide the clearest evidence of morphological and molecular EMT with deregulation of genes involved in cell adhesion and low expression of claudins. 4 , 5 , 6 CCN6 (WISP3) is a secreted matricellular protein of the CCN family, which includes six members that play regulatory rather than structural roles in embryonic development, cell attachment and growth. 8 CCN proteins act in a cell and tissue-specific manner primarily through direct binding to cell surface receptors including integrins and by modulating the effect of extracellular growth factors on epithelial cells. 9 , 10 , 11 , 12 , 13 , 14 Located at 6q21-22, CCN6 was first identified as a novel gene downregulated in the highly aggressive inflammatory breast cancers. 15 We have shown that CCN6 is secreted by ductal epithelial cells in the breast, and that CCN6 downregulation in nontumorigenic breast cells is a robust inducer of EMT and is sufficient to confer growth factor independent survival and resistance to anoikis, a property of metastatic cancer cells. 9 , 11 , 12 , 13 , 14 , 15 Despite this knowledge, a direct role of CCN6 in breast tumorigenesis and the underlying mechanisms have remained elusive in part due to the lack of a physiologically relevant genetically engineered mouse model. Results CCN6 protein is reduced in human metaplastic carcinomas Based on our previous studies showing that CCN6 regulates the transition between epithelial and mesenchymal states in breast cells, we set out to investigate CCN6 expression in breast tissues. Immunohistochemical evaluation revealed that CCN6 level is significantly reduced in spindle metaplastic carcinomas compared to normal breast and invasive ductal carcinomas ( Figure 1a ). All normal breast lobules examined, and 67% of invasive ductal carcinomas maintained high levels of CCN6. This distribution was shifted in metaplastic carcinomas, among which 67.9% had low CCN6 expression ( Figure 1b ). Figure 1 CCN6 protein is reduced in human spindle metaplastic carcinomas of the breast compared to invasive ductal carcinoma and normal breast lobules. ( a ) images of a normal breast lobule, an invasive ductal carcinoma with no special features, and a spindle metaplastic carcinoma stained with hematoxylin and eosin (H&E) and CCN6 immunostaining (magnification × 400). ( b ) Invasive metaplastic and ductal carcinomas with high or low CCN6 protein. Chi-square test P =0.0018. (Scale bars, 20 μm.) Full size image Mammary epithelial specific Ccn6 deletion causes abnormal mammary gland development To directly investigate whether loss of Ccn6 in vivo triggers the development of carcinomas that recapitulate human metaplastic carcinomas, we generated a new model of epithelial cell specific Ccn6 deletion in the mammary gland using Cre/loxp-mediated recombination ( Figures 2a and b ). We specifically inactivated the Ccn6 gene in the mammary epithelium, by intercrossing the floxed Ccn6 mice with the MMTV-Cre mice. The offspring were genotyped using primers specific for various Ccn6 alleles (that is, floxed, wild type and deleted) and with primers specific for Cre ( Figure 2c ). We confirmed the presence of Ccn6 deletion in the mammary glands by quantitative reverse transcriptase-PCR and Western blots using whole mammary gland protein extracts, and by immunohistochemistry in mammary gland tissue samples ( Figures 2d–f ). Figure 2 Conditional deletion of Ccn6 in the mammary epithelium using the Cre-Lox system. ( a ) Mouse Ccn6 containing exons 2 and 3. Pictured: wild-type allele; targeted allele after homologous recombination in embryonic stem (ES) cells; the floxed allele in which exons 2 and 3 are flanked by loxP sites and the neomycin cassette has been excised; the allele in which exons 2 and 3 have been deleted in Ccn6 fl/fl ;MMTV-Cre mice. 5′ homology arm (~5.6 kb),<|im_end|> <|im_start|>assistant For more than a decade, Celina Kleer, M.D., has been studying how a poorly understood protein called CCN6 affects breast cancer. To learn more about its role in breast cancer development, Kleer's lab designed a special mouse model - which led to something unexpected. They deleted CCN6 from the mammary gland in the mice. This type of model allows researchers to study effects specific to the loss of the protein. As Kleer and her team checked in at different ages, they found delayed development and mammary glands that did not develop properly. "After a year, the mice started to form mammary gland tumors. These tumors looked identical to human metaplastic breast cancer, with the same characteristics. That was very exciting," says Kleer, Harold A. Oberman Collegiate Professor of Pathology and director of the Breast Pathology Program at the University of Michigan Comprehensive Cancer Center. Metaplastic breast cancer is a very rare and aggressive subtype of triple-negative breast cancer - a type considered rare and aggressive of its own. Up to 20 percent of all breast cancers are triple-negative. Only 1 percent are metaplastic. "Metaplastic breast cancers are challenging to diagnose and treat. In part, the difficulties stem from the lack of mouse models to study this disease," Kleer says. So not only did Kleer gain a better understanding of CCN6, but her lab's findings open the door to a better understanding of this very challenging subtype of breast cancer. The study is published in Oncogene. "Our hypothesis, based on years of experiments in our lab, was that knocking out this gene would induce breast cancer. But we didn't know if knocking out CCN6 would be enough to unleash tumors, and if so, when, or what kind," Kleer says. "Now we have a new mouse model, and a new way of studying metaplastic carcinomas, for which there's no other model." One of the hallmarks of metaplastic breast cancer is that the cells are more mesenchymal, a cell state that enables them to move and invade. Likewise, researchers saw this in their mouse model: knocking down CCN6 induced the process known as the epithelial to mesenchymal transition. "This process is hard to see in tumors under a microscope. It's exciting that we see this in the mouse model as well as in patient samples and cell lines," Kleer says. The researchers looked at the tumors developed by mice in their new model and identified several potential genes to target with therapeutics. Some of the options, such as p38, already have antibodies or inhibitors against them. The team's next steps will be to test these potential therapeutics in the lab, in combination with existing chemotherapies. They will also use the mouse model to gain a better understanding of metaplastic breast cancer and discover new genes that play a role it its development. "Understanding the disease may lead us to better ways to attack it," Kleer says. "For patients with metaplastic breast cancer, it doesn't matter that it's rare. They want - and they deserve - better treatments." <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 6344, 391, 52279, 17659, 89468, 374, 459, 19738, 1376, 315, 53354, 17659, 9572, 449, 13034, 5848, 6029, 315, 64779, 59544, 311, 11083, 20345, 1631, 278, 9320, 320, 2783, 51, 570, 4452, 11, 279, 27409, 31206, 4455, 527, 9987, 13, 5810, 584, 1501, 430, 13844, 45, 21, 320, 54, 56606, 18, 705, 264, 6367, 291, 5634, 2265, 54230, 13128, 315, 279, 13844, 45, 320, 35625, 49, 5547, 14, 1182, 37432, 14, 9173, 53, 8, 3070, 11, 374, 12207, 1523, 81722, 304, 14830, 10688, 315, 3823, 99291, 2849, 2322, 391, 52279, 17659, 89468, 13, 1226, 8066, 264, 8814, 1646, 315, 33820, 1563, 64779, 59544, 19440, 356, 14606, 21, 37166, 555, 11469, 264, 9943, 52419, 356, 14606, 21, 8814, 902, 574, 55187, 449, 459, 386, 8673, 53, 7813, 265, 8814, 13, 356, 14606, 21, 1344, 59403, 2652, 8195, 16027, 7813, 265, 24548, 12882, 15748, 42655, 304, 45339, 278, 86567, 323, 35663, 4325, 14228, 1558, 3294, 7863, 311, 39682, 18543, 11835, 13, 356, 14606, 21, 1344, 59403, 2652, 8195, 16027, 7813, 265, 24548, 8040, 53354, 1579, 12239, 33820, 1563, 52788, 23063, 449, 94169, 282, 579, 469, 8673, 11, 13034, 30450, 4528, 311, 3823, 2322, 391, 52279, 17659, 52788, 23063, 13, 8121, 15207, 7645, 56186, 315, 356, 14606, 21, 1344, 59403, 33820, 1563, 52788, 23063, 323, 12593, 315, 30299, 1640, 788, 21389, 449, 264, 3823, 2322, 391, 52279, 89468, 12223, 10675, 264, 5199, 28347, 315, 220, 4044, 21389, 320, 393, 284, 20, 25800, 220, 605, 25173, 806, 7609, 22395, 279, 6222, 72915, 7913, 21389, 1990, 8814, 323, 3823, 527, 3062, 40242, 315, 64779, 59544, 27448, 52379, 2737, 356, 31721, 16, 11, 356, 74, 777, 11, 356, 509, 77, 18, 323, 220, 19, 11, 423, 3696, 16, 11, 323, 468, 406, 605, 64, 662, 4314, 3135, 2246, 264, 59557, 3560, 369, 356, 14606, 21, 37166, 304, 279, 1853, 52379, 315, 2322, 391, 52279, 52788, 23063, 449, 13034, 5848, 323, 31206, 43874, 449, 3823, 8624, 13, 1226, 3493, 264, 5452, 311, 4007, 502, 11811, 304, 279, 23842, 323, 6514, 315, 3823, 2322, 391, 52279, 52788, 23063, 11, 323, 264, 502, 8624, 9959, 1646, 304, 902, 311, 1296, 502, 6514, 15174, 13, 29438, 6344, 391, 52279, 17659, 52788, 23063, 35256, 13489, 220, 16, 4, 315, 53354, 52788, 23063, 323, 527, 32971, 555, 13034, 5848, 6029, 315, 64779, 59544, 311, 11083, 20345, 1631, 278, 9320, 320, 2783, 51, 8, 7119, 99291, 11, 8330, 23333, 11, 323, 2753, 14134, 30548, 1640, 788, 5540, 2737, 523, 2159, 1607, 323, 2709, 325, 788, 60038, 13, 220, 16, 6344, 391, 52279, 52788, 23063, 527, 264, 53582, 315, 24657, 8389, 17659, 9572, 320, 30271, 5002, 8, 430, 527, 31555, 27078, 311, 62730, 11, 449, 1579, 95323, 369, 29827, 68370, 10949, 13, 220, 17, 1174, 220, 18, 35390, 16195, 81064, 29060, 10675, 430, 2322, 391, 52279, 52788, 23063, 9352, 311, 279, 11083, 20345, 1631, 278, 12970, 53582, 315, 32023, 5002, 11, 449, 264, 12742, 46940, 278, 5643, 1109, 1023, 53354, 17659, 52788, 23063, 13, 220, 19, 1174, 220, 20, 1174, 220, 21, 4452, 11, 279, 31206, 6449, 1821, 315, 2322, 391, 52279, 52788, 23063, 4460, 311, 6179, 7524, 22972, 527, 2103, 53990, 50268, 16365, 13, 6344, 391, 14833, 689, 374, 279, 81193, 2349, 304, 902, 832, 6822, 2849, 955, 374, 12860, 555, 2500, 6822, 2849, 955, 13, 11266, 411, 59544, 7917, 1253, 37771, 2322, 391, 14833, 689, 1555, 469, 8673, 11, 902, 2391, 15756, 4775, 268, 14093, 3135, 304, 279, 24279, 315, 31206, 323, 14345, 37941, 292, 4442, 7119, 264, 99291, 2849, 79612, 323, 88804, 2849, 33001, 1008, 59738, 11, 6522, 311, 30215, 323, 68370, 10949, 13, 220, 22, 5046, 682, 3823, 51423, 11, 2322, 391, 52279, 52788, 23063, 3493, 279, 11551, 15795, 6029, 315, 27448, 5848, 323, 31206, 469, 8673, 449, 72915, 2987, 315, 21389, 6532, 304, 2849, 1008, 59738, 323, 3428, 7645, 315, 1206, 8039, 1354, 13, 220, 19, 1174, 220, 20, 1174, 220, 21, 13844, 45, 21, 320, 54, 56606, 18, 8, 374, 264, 6367, 291, 5634, 2265, 54230, 13128, 315, 279, 13844, 45, 3070, 11, 902, 5764, 4848, 3697, 430, 1514, 23331, 4856, 1109, 24693, 13073, 304, 44481, 14338, 4500, 11, 2849, 20581, 323, 6650, 13, 220, 23, 13844, 45, 28896, 1180, 304, 264, 2849, 323, 20438, 19440, 11827, 15871, 1555, 2167, 11212, 311, 2849, 7479, 44540, 2737, 8936, 1354, 323, 555, 1491, 15853, 279, 2515, 315, 11741, 65441, 6650, 9547, 389, 64779, 59544, 7917, 13, 220, 24, 1174, 220, 605, 1174, 220, 806, 1174, 220, 717, 1174, 220, 1032, 1174, 220, 975, 42867, 520, 220, 21, 80, 1691, 12, 1313, 11, 13844, 45, 21, 574, 1176, 11054, 439, 264, 11775, 15207, 1523, 81722, 304, 279, 7701, 19738, 47288, 17659, 51423, 13, 220, 868, 1226, 617, 6982, 430, 13844, 45, 21, 374, 6367, 291, 555, 45339, 278, 64779, 59544, 7917, 304, 279, 17659, 11, 323, 430, 13844, 45, 21, 1523, 1610, 2987, 304, 308, 546, 372, 4775, 56989, 17659, 7917, 374, 264, 22514, 4507, 3913, 315, 469, 8673, 323, 374, 14343, 311, 49843, 6650, 8331, 9678, 20237, 323, 13957, 311, 39124, 1609, 285, 11, 264, 3424, 315, 68370, 780, 9572, 7917, 13, 220, 24, 1174, 220, 806, 1174, 220, 717, 1174, 220, 1032, 1174, 220, 975, 1174, 220, 868, 18185, 420, 6677, 11, 264, 2167, 3560, 315, 13844, 45, 21, 304, 17659, 15756, 4775, 268, 14093, 323, 279, 16940, 24717, 617, 14958, 66684, 304, 961, 4245, 311, 279, 6996, 315, 264, 4571, 72, 30450, 9959, 52033, 46036, 8814, 1646, 13, 18591, 13844, 45, 21, 13128, 374, 11293, 304, 3823, 2322, 391, 52279, 52788, 23063, 20817, 389, 1057, 3766, 7978, 9204, 430, 13844, 45, 21, 80412, 279, 9320, 1990, 64779, 59544, 323, 11083, 20345, 1631, 278, 5415, 304, 17659, 7917, 11, 584, 743, 704, 311, 19874, 13844, 45, 21, 7645, 304, 17659, 39881, 13, 67335, 2319, 26407, 32056, 16865, 10675, 430, 13844, 45, 21, 2237, 374, 12207, 11293, 304, 99291, 2322, 391, 52279, 52788, 23063, 7863, 311, 4725, 17659, 323, 53354, 45339, 278, 52788, 23063, 320, 19575, 220, 16, 64, 7609, 2052, 4725, 17659, 41253, 2482, 25078, 11, 323, 220, 3080, 4, 315, 53354, 45339, 278, 52788, 23063, 18908, 1579, 5990, 315, 13844, 45, 21, 13, 1115, 8141, 574, 30073, 304, 2322, 391, 52279, 52788, 23063, 11, 4315, 902, 220, 3080, 13, 24, 4, 1047, 3428, 13844, 45, 21, 7645, 320, 19575, 220, 16, 65, 7609, 19575, 220, 16, 13844, 45, 21, 13128, 374, 11293, 304, 3823, 99291, 2322, 391, 52279, 52788, 23063, 315, 279, 17659, 7863, 311, 53354, 45339, 278, 89468, 323, 4725, 17659, 41253, 2482, 13, 320, 264, 883, 5448, 315, 264, 4725, 17659, 41253, 1130, 11, 459, 53354, 45339, 278, 89468, 449, 912, 3361, 4519, 11, 323, 264, 99291, 2322, 391, 52279, 89468, 61152, 449, 17728, 4428, 4223, 3817, 323, 62894, 258, 320, 39, 69248, 8, 323, 13844, 45, 21, 33119, 537, 2101, 320, 76, 3326, 2461, 25800, 220, 3443, 570, 320, 293, 883, 763, 78134, 2322, 391, 52279, 323, 45339, 278, 52788, 23063, 449, 1579, 477, 3428, 13844, 45, 21, 13128, 13, 34382, 34047, 1296, 393, 284, 15, 13, 4119, 23, 13, 320, 7092, 16283, 11, 220, 508, 33983, 76, 6266, 8797, 1404, 2217, 48869, 1563, 64779, 59544, 3230, 356, 14606, 21, 37166, 11384, 35663, 33820, 1563, 67169, 4500, 2057, 6089, 19874, 3508, 4814, 315, 356, 14606, 21, 304, 41294, 31854, 279, 4500, 315, 52788, 23063, 430, 55099, 275, 6468, 3823, 2322, 391, 52279, 52788, 23063, 11, 584, 8066, 264, 502, 1646, 315, 64779, 59544, 2849, 3230, 356, 14606, 21, 37166, 304, 279, 33820, 1563, 67169, 1701, 7948, 107861, 36825, 82076, 312, 76128, 320, 69356, 220, 17, 64, 323, 293, 7609, 1226, 11951, 304, 31262, 279, 356, 14606, 21, 15207, 304, 279, 33820, 1563, 64779, 301, 2411, 11, 555, 958, 29942, 287, 279, 9943, 52419, 356, 14606, 21, 24548, 449, 279, 386, 8673, 53, 7813, 265, 24548, 13, 578, 46471, 1051, 4173, 354, 33601, 1701, 9036, 388, 3230, 369, 5370, 356, 14606, 21, 98260, 320, 9210, 374, 11, 9943, 52419, 11, 8545, 955, 323, 11309, 8, 323, 449, 9036, 388, 3230, 369, 7948, 320, 19575, 220, 17, 66, 7609, 1226, 11007, 279, 9546, 315, 356, 14606, 21, 37166, 304, 279, 33820, 1563, 82375, 555, 47616, 10134, 36815, 521, 12, 74256, 323, 11104, 1529, 2469, 1701, 4459, 33820, 1563, 67169, 13128, 49062, 11, 323, 555, 33119, 2319, 26407, 52755, 304, 33820, 1563, 67169, 20438, 10688, 320, 69356, 220, 17, 67, 4235, 69, 7609, 19575, 220, 17, 93073, 37166, 315, 356, 14606, 21, 304, 279, 33820, 1563, 64779, 301, 2411, 1701, 279, 7948, 12, 4357, 87, 1887, 13, 320, 264, 883, 18191, 356, 14606, 21, 8649, 506, 2439, 220, 17, 323, 220, 18, 13, 393, 30375, 25, 8545, 10827, 70510, 26, 17550, 70510, 1306, 5105, 1640, 788, 312, 76128, 304, 44481, 14338, 19646, 320, 1600, 8, 7917, 26, 279, 9943, 52419, 70510, 304, 902, 506, 2439, 220, 17, 323, 220, 18, 527, 1344, 41872, 555, 781, 87, 47, 6732, 323, 279, 841, 316, 65156, 82358, 706, 1027, 3521, 4147, 26, 279, 70510, 304, 902, 506, 2439, 220, 17, 323, 220, 18, 617, 1027, 11309, 304, 356, 14606, 21, 1344, 59403, 2652, 8195, 16027, 7813, 265, 24548, 13, 220, 20, 39615, 5105, 2508, 6916, 31857, 20, 13, 21, 39753, 705, 128257, 198, 128256, 78191, 198, 2520, 810, 1109, 264, 13515, 11, 47643, 2259, 27446, 261, 11, 386, 920, 2637, 706, 1027, 21630, 1268, 264, 31555, 16365, 13128, 2663, 13844, 45, 21, 22223, 17659, 9572, 13, 2057, 4048, 810, 922, 1202, 3560, 304, 17659, 9572, 4500, 11, 27446, 261, 596, 10278, 6319, 264, 3361, 8814, 1646, 482, 902, 6197, 311, 2555, 16907, 13, 2435, 11309, 13844, 45, 21, 505, 279, 33820, 1563, 67169, 304, 279, 24548, 13, 1115, 955, 315, 1646, 6276, 12074, 311, 4007, 6372, 3230, 311, 279, 4814, 315, 279, 13128, 13, 1666, 27446, 261, 323, 1077, 2128, 10273, 304, 520, 2204, 17051, 11, 814, 1766, 23540, 4500, 323, 33820, 1563, 82375, 430, 1550, 539, 2274, 10489, 13, 330, 6153, 264, 1060, 11, 279, 24548, 3940, 311, 1376, 33820, 1563, 67169, 56071, 13, 4314, 56071, 7111, 20086, 311, 3823, 2322, 391, 52279, 17659, 9572, 11, 449, 279, 1890, 17910, 13, 3011, 574, 1633, 13548, 1359, 2795, 27446, 261, 11, 53215, 362, 13, 52245, 1543, 57665, 6629, 17054, 315, 8092, 2508, 323, 7690, 315, 279, 57598, 8092, 2508, 6826, 520, 279, 3907, 315, 14972, 67963, 26211, 5955, 13, 6344, 391, 52279, 17659, 9572, 374, 264, 1633, 9024, 323, 19738, 53582, 315, 24657, 62035, 17659, 9572, 482, 264, 955, 6646, 9024, 323, 19738, 315, 1202, 1866, 13, 3216, 311, 220, 508, 3346, 315, 682, 17659, 51423, 527, 24657, 62035, 13, 8442, 220, 16, 3346, 527, 2322, 391, 52279, 13, 330, 35773, 391, 52279, 17659, 51423, 527, 17436, 311, 58681, 323, 4322, 13, 763, 961, 11, 279, 27129, 19646, 505, 279, 6996, 315, 8814, 4211, 311, 4007, 420, 8624, 1359, 27446, 261, 2795, 13, 2100, 539, 1193, 1550, 27446, 261, 8895, 264, 2731, 8830, 315, 13844, 45, 21, 11, 719, 1077, 10278, 596, 14955, 1825, 279, 6134, 311, 264, 2731, 8830, 315, 420, 1633, 17436, 53582, 315, 17659, 9572, 13, 578, 4007, 374, 4756, 304, 77854, 34224, 13, 330, 8140, 31178, 11, 3196, 389, 1667, 315, 21896, 304, 1057, 10278, 11, 574, 430, 50244, 704, 420, 15207, 1053, 49853, 17659, 9572, 13, 2030, 584, 3287, 956, 1440, 422, 50244, 704, 13844, 45, 21, 1053, 387, 3403, 311, 78535, 56071, 11, 323, 422, 779, 11, 994, 11, 477, 1148, 3169, 1359, 27446, 261, 2795, 13, 330, 7184, 584, 617, 264, 502, 8814, 1646, 11, 323, 264, 502, 1648, 315, 21630, 2322, 391, 52279, 52788, 23063, 11, 369, 902, 1070, 596, 912, 1023, 1646, 1210, 3861, 315, 279, 14321, 15914, 315, 2322, 391, 52279, 17659, 9572, 374, 430, 279, 7917, 527, 810, 11083, 20345, 1631, 278, 11, 264, 2849, 1614, 430, 20682, 1124, 311, 3351, 323, 75272, 13, 50487, 11, 12074, 5602, 420, 304, 872, 8814, 1646, 25, 50244, 1523, 13844, 45, 21, 36572, 279, 1920, 3967, 439, 279, 64779, 59544, 311, 11083, 20345, 1631, 278, 9320, 13, 330, 2028, 1920, 374, 2653, 311, 1518, 304, 56071, 1234, 264, 73757, 13, 1102, 596, 13548, 430, 584, 1518, 420, 304, 279, 8814, 1646, 439, 1664, 439, 304, 8893, 10688, 323, 2849, 5238, 1359, 27446, 261, 2795, 13, 578, 12074, 7111, 520, 279, 56071, 8040, 555, 24548, 304, 872, 502, 1646, 323, 11054, 3892, 4754, 21389, 311, 2218, 449, 9139, 88886, 13, 4427, 315, 279, 2671, 11, 1778, 439, 281, 1987, 11, 2736, 617, 59854, 477, 68642, 2403, 1124, 13, 578, 2128, 596, 1828, 7504, 690, 387, 311, 1296, 1521, 4754, 9139, 88886, 304, 279, 10278, 11, 304, 10824, 449, 6484, 8590, 1605, 391, 552, 13, 2435, 690, 1101, 1005, 279, 8814, 1646, 311, 8895, 264, 2731, 8830, 315, 2322, 391, 52279, 17659, 9572, 323, 7142, 502, 21389, 430, 1514, 264, 3560, 433, 1202, 4500, 13, 330, 71251, 279, 8624, 1253, 3063, 603, 311, 2731, 5627, 311, 3440, 433, 1359, 27446, 261, 2795, 13, 330, 2520, 6978, 449, 2322, 391, 52279, 17659, 9572, 11, 433, 3250, 956, 5030, 430, 433, 596, 9024, 13, 2435, 1390, 482, 323, 814, 23528, 482, 2731, 22972, 1210, 220, 128257, 198 ]

2,203

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Facial mimicry is a central feature of human social interactions. Although it has been evidenced in other mammals, no study has yet shown that this phenomenon can reach the level of precision seem in humans and gorillas. Here, we studied the facial complexity of group-housed sun bears, a typically solitary species, with special focus on testing for exact facial mimicry. Our results provided evidence that the bears have the ability to mimic the expressions of their conspecifics and that they do so by matching the exact facial variants they interact with. In addition, the data showed the bears produced the open-mouth faces predominantly when they received the recipient’s attention, suggesting a degree of social sensitivity. Our finding questions the relationship between communicative complexity and social complexity, and suggests the possibility that the capacity for complex facial communication is phylogenetically more widespread than previously thought. Introduction Behavioural mimicry pervades human social interactions 1 . Facial, postural and vocal signals are regularly automatically shared by others, sometimes resulting in or from emotional contagion 2 . There has been a vast literature on facial mimicry 3 , leading to the view that humans are capable of matching the facial expressions of others with great precision 4 (hereafter, “exact facial mimicry”), with benefits during social interactions such as strengthened social bonds and sharing detailed emotional information 2 , 5 . Although it has been shown that facial mimicry is also present in non-human mammals 6 , 7 , 8 , only one study of gorillas ( Gorilla gorilla gorilla ) 9 has so far demonstrated the precision as seen in humans, i.e., by mimicking one variant of a facial display over another. In this study, we examined facial expressions in spontaneous social play of group-housed sun bears ( Helarctos malayanus ). Many basic facts of sun bear biology are unknown, due to the difficulties of studying this elusive species in the wild 10 , 11 . Nonetheless, it is known that sun bears feed on an omnivorous diet in tropical rainforests 12 , and a study on adult sun bears in Ulu Segama Forest Reserve showed that they seldom participate in social interactions with one another outside of mating contexts despite home ranges overlapping by up to 20% 10 , indicating a largely solitary lifestyle. Notably, mothers often raise two offspring simultaneously, which are highly altricial for the first 3 months and interact with the mother extensively during this period 11 . Facial expressions in sun bears have not been studied, but open-mouth expressions are shown mostly by juveniles and during play in the closely related American black bears ( Ursus americanus ) 13 . Sun bears use two distinct variants of open-mouth faces during play (personal observations), similar to American black bears 13 and other carnivorans 14 . This observation is intriguing because it raises the possibility that sun bears exhibit complex forms of facial communication comparable to those that have been shown mostly in species with strong social tendencies 6 , 7 , 8 , 9 . In turn, this implies that complex forms of communication cannot be explained only as evolved adaptations to a demanding social environment 15 . Hallmarks of complex facial communication include for instance muscular variation in expressions 15 , facial mimicry 1 , 3 , 4 , and social sensitivity to the attentional states of others during expression production 16 , 17 , 18 . As facial mimicry occurs in phylogenetically distanced mammalian species during play (primates 6 , 7 , 9 ; dogs 8 ) and sun bears produce distinct facial variants during social play which is an essential precondition for exact mimicry, our hypothesis is that facial mimicry and exact facial mimicry are present in sun bears during social play. Additionally, social sensitivity was also measured as a component of such complexity. Social sensitivity via facial communication was previously suggested for dogs ( Canis familiaris ) 16 and apes 17 , 18 , mammalian taxa that are closely associated with humans on a social and phylogenetic level, respectively. Social sensitivity is essential to effective facial communication, particularly during play wherein the absence of play signalling often escalates play into aggression 19 . Given that bears are known to engage in play 13 , we therefore expect sun bears show social sensitivity in their facial expression production. Material and Method Sun bears and data collection Twenty-two group-housed rehabilitant sun bears (aged 2–12 years; mean age = 6.0 ± 2.9 SD) of the Bornean Sun Bear Conservation Centre (Malaysia) were studied. All bears were unrelated. The bears were video-recorded using 3-minute focal recordings and ad libitum recordings from January 2015 to September 2016 and from August to December 2017. Recordings of the bears were collected in three outdoor forest enclosures, ranging from 0.13–0.32 hectares, meaning enclosures were large enough that bears did not have to socially interact by necessity. Group compositions were changed throughout the data collection of this study, but the group sizes within enclosures did not exceed six bears. For further details about these bears (see Table S1 ), study site and recording equipment, see Supplementary Methods. Behavioural coding Social play involved one bear directing a play action towards another bear, and the other bear responding with a play action. Social play began with the first play action and ended when play actions stopped for 10 seconds or more. Three-hundred seventy-two social play bouts were identified. Within these play bouts, scenes of rough play were observed 135 times and scenes of gentle play were observed 333 times (see supplementary electronic materials for examples and definitions of rough and gentle play). A single play bout could include both rough and gentle play at different points. Nine-hundred and thirty-one open-mouth facial expressions were coded during these bouts when the mouth opened widely and the jaw dropped. All observed expressions were coded. Two variants were identified: WUI (With Upper Incisors) occurred when the upper lip and nose were raised, which resulted in the wrinkling of the muzzle", "role": "user" }, { "content": "The world's smallest bears can exactly mimic another bear's facial expressions, casting doubt on humans and other primates' supremacy at this subtle form of communication. It is the first time such exact facial mimicry has been seen outside of humans and gorillas. The research, by Dr. Marina Davila-Ross and Ph.D. candidate Derry Taylor, both at the University of Portsmouth, is published in Scientific Reports. The researchers studied sun bears—a solitary species in the wild, but also surprisingly playful—for more than two years. They found bears can use facial expressions to communicate with others in a similar way to humans and apes, strongly suggesting other mammals might also be masters of this complex social skill and, in addition, have a degree of social sensitivity. Dr. Davila-Ross said: \"Mimicking the facial expressions of others in exact ways is one of the pillars of human communication. Other primates and dogs are known to mimic each other, but only great apes and humans, and now sun bears, were previously known to show such complexity in their facial mimicry. \"Because sun bears appear to have facial communication of such complexity and because they have no special evolutionary link to humans like monkeys are apes, nor are they domesticated animals like dogs, we are confident that this more advanced form of mimicry is present in various other species. This, however, needs to be further investigated. \"What's most surprising is the sun bear is not a social animal. In the wild, it's a relatively solitary animal, so this suggests the ability to communicate via complex facial expressions could be a pervasive trait in mammals, allowing them to navigate their societies.\" Facial mimicry is when an animal responds to another's facial expression with the same or similar expression. Mr Taylor coded the facial expressions of 22 sun bears in spontaneous social play sessions. The bears, aged 2-12, were housed in Bornean Sun Bear Conservation Centre in Malaysia in which enclosures were large enough to allow bears to choose whether to interact or not. Despite the bears' preference in the wild for a solitary life, the bears in this study took part in hundreds of play bouts, with more than twice as many gentle play sessions compared to rough play. During these encounters, the research team coded two distinct expressions—one involving a display of the upper incisor teeth, and one without. The bears were most likely to show precise facial mimicry during gentle play. Mr Taylor said such subtle mimicking could be to help two bears signal that they are ready to play more roughly, or to strengthen social bonds. He said: \"It is widely believed that we only find complex forms of communication in species with complex social systems. As sun bears are a largely solitary species, our study of their facial communication questions this belief, because it shows a complex form of facial communication that until now was known only in more social species. \"Sun bears are an elusive species in the wild and so very little is known about them. We know they live in tropical rainforests, eat almost everything, and that outside of the mating season adults have little to do with one another. \"That's what makes these results so fascinating—they are a non-social species who when face to face can communicate subtly and precisely.\" Sun bears, also known as honey bears, stand at 120-150 cm tall and weigh up to 80kg. They are endangered and live in the tropical forests of south-east Asia. Social sophistication aside, sun bear numbers are dwindling due to deforestation, poaching and being killed by farmers for eating crops. Increasingly, new mother bears are killed so their cub can be taken and raised as a pet or kept in captivity as 'bile bears' where their bile is harvested for use in some Chinese medicines. The field research was funded by the Royal Society and the Leakey Foundation. Previous research at the University of Portsmouth showed dogs alter their facial expressions if they know someone is looking at them. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Facial mimicry is a central feature of human social interactions. Although it has been evidenced in other mammals, no study has yet shown that this phenomenon can reach the level of precision seem in humans and gorillas. Here, we studied the facial complexity of group-housed sun bears, a typically solitary species, with special focus on testing for exact facial mimicry. Our results provided evidence that the bears have the ability to mimic the expressions of their conspecifics and that they do so by matching the exact facial variants they interact with. In addition, the data showed the bears produced the open-mouth faces predominantly when they received the recipient’s attention, suggesting a degree of social sensitivity. Our finding questions the relationship between communicative complexity and social complexity, and suggests the possibility that the capacity for complex facial communication is phylogenetically more widespread than previously thought. Introduction Behavioural mimicry pervades human social interactions 1 . Facial, postural and vocal signals are regularly automatically shared by others, sometimes resulting in or from emotional contagion 2 . There has been a vast literature on facial mimicry 3 , leading to the view that humans are capable of matching the facial expressions of others with great precision 4 (hereafter, “exact facial mimicry”), with benefits during social interactions such as strengthened social bonds and sharing detailed emotional information 2 , 5 . Although it has been shown that facial mimicry is also present in non-human mammals 6 , 7 , 8 , only one study of gorillas ( Gorilla gorilla gorilla ) 9 has so far demonstrated the precision as seen in humans, i.e., by mimicking one variant of a facial display over another. In this study, we examined facial expressions in spontaneous social play of group-housed sun bears ( Helarctos malayanus ). Many basic facts of sun bear biology are unknown, due to the difficulties of studying this elusive species in the wild 10 , 11 . Nonetheless, it is known that sun bears feed on an omnivorous diet in tropical rainforests 12 , and a study on adult sun bears in Ulu Segama Forest Reserve showed that they seldom participate in social interactions with one another outside of mating contexts despite home ranges overlapping by up to 20% 10 , indicating a largely solitary lifestyle. Notably, mothers often raise two offspring simultaneously, which are highly altricial for the first 3 months and interact with the mother extensively during this period 11 . Facial expressions in sun bears have not been studied, but open-mouth expressions are shown mostly by juveniles and during play in the closely related American black bears ( Ursus americanus ) 13 . Sun bears use two distinct variants of open-mouth faces during play (personal observations), similar to American black bears 13 and other carnivorans 14 . This observation is intriguing because it raises the possibility that sun bears exhibit complex forms of facial communication comparable to those that have been shown mostly in species with strong social tendencies 6 , 7 , 8 , 9 . In turn, this implies that complex forms of communication cannot be explained only as evolved adaptations to a demanding social environment 15 . Hallmarks of complex facial communication include for instance muscular variation in expressions 15 , facial mimicry 1 , 3 , 4 , and social sensitivity to the attentional states of others during expression production 16 , 17 , 18 . As facial mimicry occurs in phylogenetically distanced mammalian species during play (primates 6 , 7 , 9 ; dogs 8 ) and sun bears produce distinct facial variants during social play which is an essential precondition for exact mimicry, our hypothesis is that facial mimicry and exact facial mimicry are present in sun bears during social play. Additionally, social sensitivity was also measured as a component of such complexity. Social sensitivity via facial communication was previously suggested for dogs ( Canis familiaris ) 16 and apes 17 , 18 , mammalian taxa that are closely associated with humans on a social and phylogenetic level, respectively. Social sensitivity is essential to effective facial communication, particularly during play wherein the absence of play signalling often escalates play into aggression 19 . Given that bears are known to engage in play 13 , we therefore expect sun bears show social sensitivity in their facial expression production. Material and Method Sun bears and data collection Twenty-two group-housed rehabilitant sun bears (aged 2–12 years; mean age = 6.0 ± 2.9 SD) of the Bornean Sun Bear Conservation Centre (Malaysia) were studied. All bears were unrelated. The bears were video-recorded using 3-minute focal recordings and ad libitum recordings from January 2015 to September 2016 and from August to December 2017. Recordings of the bears were collected in three outdoor forest enclosures, ranging from 0.13–0.32 hectares, meaning enclosures were large enough that bears did not have to socially interact by necessity. Group compositions were changed throughout the data collection of this study, but the group sizes within enclosures did not exceed six bears. For further details about these bears (see Table S1 ), study site and recording equipment, see Supplementary Methods. Behavioural coding Social play involved one bear directing a play action towards another bear, and the other bear responding with a play action. Social play began with the first play action and ended when play actions stopped for 10 seconds or more. Three-hundred seventy-two social play bouts were identified. Within these play bouts, scenes of rough play were observed 135 times and scenes of gentle play were observed 333 times (see supplementary electronic materials for examples and definitions of rough and gentle play). A single play bout could include both rough and gentle play at different points. Nine-hundred and thirty-one open-mouth facial expressions were coded during these bouts when the mouth opened widely and the jaw dropped. All observed expressions were coded. Two variants were identified: WUI (With Upper Incisors) occurred when the upper lip and nose were raised, which resulted in the wrinkling of the muzzle<|im_end|> <|im_start|>assistant The world's smallest bears can exactly mimic another bear's facial expressions, casting doubt on humans and other primates' supremacy at this subtle form of communication. It is the first time such exact facial mimicry has been seen outside of humans and gorillas. The research, by Dr. Marina Davila-Ross and Ph.D. candidate Derry Taylor, both at the University of Portsmouth, is published in Scientific Reports. The researchers studied sun bears—a solitary species in the wild, but also surprisingly playful—for more than two years. They found bears can use facial expressions to communicate with others in a similar way to humans and apes, strongly suggesting other mammals might also be masters of this complex social skill and, in addition, have a degree of social sensitivity. Dr. Davila-Ross said: "Mimicking the facial expressions of others in exact ways is one of the pillars of human communication. Other primates and dogs are known to mimic each other, but only great apes and humans, and now sun bears, were previously known to show such complexity in their facial mimicry. "Because sun bears appear to have facial communication of such complexity and because they have no special evolutionary link to humans like monkeys are apes, nor are they domesticated animals like dogs, we are confident that this more advanced form of mimicry is present in various other species. This, however, needs to be further investigated. "What's most surprising is the sun bear is not a social animal. In the wild, it's a relatively solitary animal, so this suggests the ability to communicate via complex facial expressions could be a pervasive trait in mammals, allowing them to navigate their societies." Facial mimicry is when an animal responds to another's facial expression with the same or similar expression. Mr Taylor coded the facial expressions of 22 sun bears in spontaneous social play sessions. The bears, aged 2-12, were housed in Bornean Sun Bear Conservation Centre in Malaysia in which enclosures were large enough to allow bears to choose whether to interact or not. Despite the bears' preference in the wild for a solitary life, the bears in this study took part in hundreds of play bouts, with more than twice as many gentle play sessions compared to rough play. During these encounters, the research team coded two distinct expressions—one involving a display of the upper incisor teeth, and one without. The bears were most likely to show precise facial mimicry during gentle play. Mr Taylor said such subtle mimicking could be to help two bears signal that they are ready to play more roughly, or to strengthen social bonds. He said: "It is widely believed that we only find complex forms of communication in species with complex social systems. As sun bears are a largely solitary species, our study of their facial communication questions this belief, because it shows a complex form of facial communication that until now was known only in more social species. "Sun bears are an elusive species in the wild and so very little is known about them. We know they live in tropical rainforests, eat almost everything, and that outside of the mating season adults have little to do with one another. "That's what makes these results so fascinating—they are a non-social species who when face to face can communicate subtly and precisely." Sun bears, also known as honey bears, stand at 120-150 cm tall and weigh up to 80kg. They are endangered and live in the tropical forests of south-east Asia. Social sophistication aside, sun bear numbers are dwindling due to deforestation, poaching and being killed by farmers for eating crops. Increasingly, new mother bears are killed so their cub can be taken and raised as a pet or kept in captivity as 'bile bears' where their bile is harvested for use in some Chinese medicines. The field research was funded by the Royal Society and the Leakey Foundation. Previous research at the University of Portsmouth showed dogs alter their facial expressions if they know someone is looking at them. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 75622, 56459, 894, 374, 264, 8792, 4668, 315, 3823, 3674, 22639, 13, 10541, 433, 706, 1027, 69457, 304, 1023, 56669, 11, 912, 4007, 706, 3686, 6982, 430, 420, 25885, 649, 5662, 279, 2237, 315, 16437, 2873, 304, 12966, 323, 46298, 34344, 13, 5810, 11, 584, 20041, 279, 28900, 23965, 315, 1912, 2902, 37588, 7160, 30824, 11, 264, 11383, 58229, 9606, 11, 449, 3361, 5357, 389, 7649, 369, 4839, 28900, 56459, 894, 13, 5751, 3135, 3984, 6029, 430, 279, 30824, 617, 279, 5845, 311, 56459, 279, 24282, 315, 872, 1615, 15934, 82, 323, 430, 814, 656, 779, 555, 12864, 279, 4839, 28900, 27103, 814, 16681, 449, 13, 763, 5369, 11, 279, 828, 8710, 279, 30824, 9124, 279, 1825, 92139, 12580, 47904, 994, 814, 4036, 279, 22458, 753, 6666, 11, 23377, 264, 8547, 315, 3674, 27541, 13, 5751, 9455, 4860, 279, 5133, 1990, 6057, 1413, 23965, 323, 3674, 23965, 11, 323, 13533, 279, 13336, 430, 279, 8824, 369, 6485, 28900, 10758, 374, 37555, 86945, 37774, 810, 24716, 1109, 8767, 3463, 13, 29438, 80354, 278, 56459, 894, 47274, 3536, 3823, 3674, 22639, 220, 16, 662, 75622, 11, 1772, 4269, 323, 26480, 17738, 527, 15870, 9651, 6222, 555, 3885, 11, 7170, 13239, 304, 477, 505, 14604, 64915, 290, 220, 17, 662, 2684, 706, 1027, 264, 13057, 17649, 389, 28900, 56459, 894, 220, 18, 1174, 6522, 311, 279, 1684, 430, 12966, 527, 13171, 315, 12864, 279, 28900, 24282, 315, 3885, 449, 2294, 16437, 220, 19, 320, 6881, 10924, 11, 1054, 47485, 28900, 56459, 894, 56955, 449, 7720, 2391, 3674, 22639, 1778, 439, 60862, 3674, 27460, 323, 11821, 11944, 14604, 2038, 220, 17, 1174, 220, 20, 662, 10541, 433, 706, 1027, 6982, 430, 28900, 56459, 894, 374, 1101, 3118, 304, 2536, 70095, 56669, 220, 21, 1174, 220, 22, 1174, 220, 23, 1174, 1193, 832, 4007, 315, 46298, 34344, 320, 47247, 6374, 46298, 6374, 46298, 6374, 883, 220, 24, 706, 779, 3117, 21091, 279, 16437, 439, 3970, 304, 12966, 11, 602, 1770, 2637, 555, 28003, 16671, 832, 11678, 315, 264, 28900, 3113, 927, 2500, 13, 763, 420, 4007, 11, 584, 25078, 28900, 24282, 304, 54557, 3674, 1514, 315, 1912, 2902, 37588, 7160, 30824, 320, 16183, 277, 302, 437, 8811, 44957, 355, 7609, 9176, 6913, 13363, 315, 7160, 11984, 34458, 527, 9987, 11, 4245, 311, 279, 27129, 315, 21630, 420, 66684, 9606, 304, 279, 8545, 220, 605, 1174, 220, 806, 662, 56733, 11, 433, 374, 3967, 430, 7160, 30824, 5510, 389, 459, 50197, 344, 20857, 10173, 304, 35148, 11422, 1348, 37379, 220, 717, 1174, 323, 264, 4007, 389, 6822, 7160, 30824, 304, 549, 10036, 17652, 3105, 20585, 25820, 8710, 430, 814, 56452, 16136, 304, 3674, 22639, 449, 832, 2500, 4994, 315, 73219, 38697, 8994, 2162, 21986, 50917, 555, 709, 311, 220, 508, 4, 220, 605, 1174, 19392, 264, 14090, 58229, 19433, 13, 2876, 2915, 11, 27698, 3629, 4933, 1403, 46471, 25291, 11, 902, 527, 7701, 453, 376, 7235, 369, 279, 1176, 220, 18, 4038, 323, 16681, 449, 279, 6691, 42817, 2391, 420, 4261, 220, 806, 662, 75622, 24282, 304, 7160, 30824, 617, 539, 1027, 20041, 11, 719, 1825, 92139, 24282, 527, 6982, 10213, 555, 99545, 3742, 323, 2391, 1514, 304, 279, 15499, 5552, 3778, 3776, 30824, 320, 71138, 355, 39542, 355, 883, 220, 1032, 662, 8219, 30824, 1005, 1403, 12742, 27103, 315, 1825, 92139, 12580, 2391, 1514, 320, 30712, 24654, 705, 4528, 311, 3778, 3776, 30824, 220, 1032, 323, 1023, 39438, 50775, 598, 220, 975, 662, 1115, 22695, 374, 41765, 1606, 433, 25930, 279, 13336, 430, 7160, 30824, 31324, 6485, 7739, 315, 28900, 10758, 30139, 311, 1884, 430, 617, 1027, 6982, 10213, 304, 9606, 449, 3831, 3674, 61555, 220, 21, 1174, 220, 22, 1174, 220, 23, 1174, 220, 24, 662, 763, 2543, 11, 420, 24897, 430, 6485, 7739, 315, 10758, 4250, 387, 11497, 1193, 439, 28995, 77765, 311, 264, 26192, 3674, 4676, 220, 868, 662, 11166, 15914, 315, 6485, 28900, 10758, 2997, 369, 2937, 52192, 23851, 304, 24282, 220, 868, 1174, 28900, 56459, 894, 220, 16, 1174, 220, 18, 1174, 220, 19, 1174, 323, 3674, 27541, 311, 279, 6666, 278, 5415, 315, 3885, 2391, 7645, 5788, 220, 845, 1174, 220, 1114, 1174, 220, 972, 662, 1666, 28900, 56459, 894, 13980, 304, 37555, 86945, 37774, 1612, 4979, 36041, 10700, 9606, 2391, 1514, 320, 18375, 988, 220, 21, 1174, 220, 22, 1174, 220, 24, 2652, 12875, 220, 23, 883, 323, 7160, 30824, 8356, 12742, 28900, 27103, 2391, 3674, 1514, 902, 374, 459, 7718, 80538, 369, 4839, 56459, 894, 11, 1057, 31178, 374, 430, 28900, 56459, 894, 323, 4839, 28900, 56459, 894, 527, 3118, 304, 7160, 30824, 2391, 3674, 1514, 13, 23212, 11, 3674, 27541, 574, 1101, 17303, 439, 264, 3777, 315, 1778, 23965, 13, 9983, 27541, 4669, 28900, 10758, 574, 8767, 12090, 369, 12875, 320, 3053, 285, 11537, 285, 883, 220, 845, 323, 1469, 288, 220, 1114, 1174, 220, 972, 1174, 36041, 10700, 77314, 430, 527, 15499, 5938, 449, 12966, 389, 264, 3674, 323, 37555, 86945, 5411, 2237, 11, 15947, 13, 9983, 27541, 374, 7718, 311, 7524, 28900, 10758, 11, 8104, 2391, 1514, 42418, 279, 19821, 315, 1514, 91977, 3629, 27533, 988, 1514, 1139, 40307, 220, 777, 662, 16644, 430, 30824, 527, 3967, 311, 16988, 304, 1514, 220, 1032, 1174, 584, 9093, 1755, 7160, 30824, 1501, 3674, 27541, 304, 872, 28900, 7645, 5788, 13, 10441, 323, 6872, 8219, 30824, 323, 828, 4526, 44956, 38502, 1912, 2902, 37588, 89266, 519, 7160, 30824, 320, 3359, 220, 17, 4235, 717, 1667, 26, 3152, 4325, 284, 220, 21, 13, 15, 20903, 220, 17, 13, 24, 8189, 8, 315, 279, 426, 17334, 276, 8219, 24941, 45435, 14821, 320, 30700, 59185, 8, 1051, 20041, 13, 2052, 30824, 1051, 46305, 13, 578, 30824, 1051, 2835, 57263, 291, 1701, 220, 18, 24401, 42199, 38140, 323, 1008, 3127, 275, 372, 38140, 505, 6186, 220, 679, 20, 311, 6250, 220, 679, 21, 323, 505, 6287, 311, 6790, 220, 679, 22, 13, 13896, 826, 315, 279, 30824, 1051, 14890, 304, 2380, 16166, 13952, 3289, 42306, 11, 24950, 505, 220, 15, 13, 1032, 4235, 15, 13, 843, 81743, 11, 7438, 3289, 42306, 1051, 3544, 3403, 430, 30824, 1550, 539, 617, 311, 40418, 16681, 555, 32961, 13, 5856, 62644, 1051, 5614, 6957, 279, 828, 4526, 315, 420, 4007, 11, 719, 279, 1912, 12562, 2949, 3289, 42306, 1550, 539, 12771, 4848, 30824, 13, 1789, 4726, 3649, 922, 1521, 30824, 320, 4151, 6771, 328, 16, 7026, 4007, 2816, 323, 14975, 7241, 11, 1518, 99371, 19331, 13, 80354, 278, 11058, 9983, 1514, 6532, 832, 11984, 46090, 264, 1514, 1957, 7119, 2500, 11984, 11, 323, 279, 1023, 11984, 30438, 449, 264, 1514, 1957, 13, 9983, 1514, 6137, 449, 279, 1176, 1514, 1957, 323, 9670, 994, 1514, 6299, 10717, 369, 220, 605, 6622, 477, 810, 13, 14853, 2902, 7259, 71049, 38502, 3674, 1514, 96271, 1051, 11054, 13, 25218, 1521, 1514, 96271, 11, 16451, 315, 11413, 1514, 1051, 13468, 220, 8878, 3115, 323, 16451, 315, 22443, 1514, 1051, 13468, 220, 8765, 3115, 320, 4151, 80506, 14683, 7384, 369, 10507, 323, 17931, 315, 11413, 323, 22443, 1514, 570, 362, 3254, 1514, 25646, 1436, 2997, 2225, 11413, 323, 22443, 1514, 520, 2204, 3585, 13, 38166, 2902, 7259, 323, 27219, 19101, 1825, 92139, 28900, 24282, 1051, 47773, 2391, 1521, 96271, 994, 279, 11013, 9107, 13882, 323, 279, 16942, 12504, 13, 2052, 13468, 24282, 1051, 47773, 13, 9220, 27103, 1051, 11054, 25, 468, 2327, 320, 2409, 31714, 4953, 42314, 8, 10222, 994, 279, 8582, 19588, 323, 19689, 1051, 9408, 11, 902, 19543, 304, 279, 58370, 2785, 315, 279, 75329, 128257, 198, 128256, 78191, 198, 791, 1917, 596, 25655, 30824, 649, 7041, 56459, 2500, 11984, 596, 28900, 24282, 11, 25146, 10712, 389, 12966, 323, 1023, 9036, 988, 6, 65503, 520, 420, 27545, 1376, 315, 10758, 13, 1102, 374, 279, 1176, 892, 1778, 4839, 28900, 56459, 894, 706, 1027, 3970, 4994, 315, 12966, 323, 46298, 34344, 13, 578, 3495, 11, 555, 2999, 13, 52636, 5460, 10746, 11151, 3746, 323, 2405, 920, 13, 9322, 423, 5515, 16844, 11, 2225, 520, 279, 3907, 315, 87670, 11, 374, 4756, 304, 38130, 29140, 13, 578, 12074, 20041, 7160, 30824, 29096, 58229, 9606, 304, 279, 8545, 11, 719, 1101, 29392, 57169, 72318, 810, 1109, 1403, 1667, 13, 2435, 1766, 30824, 649, 1005, 28900, 24282, 311, 19570, 449, 3885, 304, 264, 4528, 1648, 311, 12966, 323, 1469, 288, 11, 16917, 23377, 1023, 56669, 2643, 1101, 387, 36467, 315, 420, 6485, 3674, 10151, 323, 11, 304, 5369, 11, 617, 264, 8547, 315, 3674, 27541, 13, 2999, 13, 5460, 10746, 11151, 3746, 1071, 25, 330, 44, 318, 16671, 279, 28900, 24282, 315, 3885, 304, 4839, 5627, 374, 832, 315, 279, 64982, 315, 3823, 10758, 13, 7089, 9036, 988, 323, 12875, 527, 3967, 311, 56459, 1855, 1023, 11, 719, 1193, 2294, 1469, 288, 323, 12966, 11, 323, 1457, 7160, 30824, 11, 1051, 8767, 3967, 311, 1501, 1778, 23965, 304, 872, 28900, 56459, 894, 13, 330, 18433, 7160, 30824, 5101, 311, 617, 28900, 10758, 315, 1778, 23965, 323, 1606, 814, 617, 912, 3361, 41993, 2723, 311, 12966, 1093, 61820, 527, 1469, 288, 11, 6463, 527, 814, 13018, 660, 10099, 1093, 12875, 11, 584, 527, 16913, 430, 420, 810, 11084, 1376, 315, 56459, 894, 374, 3118, 304, 5370, 1023, 9606, 13, 1115, 11, 4869, 11, 3966, 311, 387, 4726, 27313, 13, 330, 3923, 596, 1455, 15206, 374, 279, 7160, 11984, 374, 539, 264, 3674, 10065, 13, 763, 279, 8545, 11, 433, 596, 264, 12309, 58229, 10065, 11, 779, 420, 13533, 279, 5845, 311, 19570, 4669, 6485, 28900, 24282, 1436, 387, 264, 71867, 18027, 304, 56669, 11, 10923, 1124, 311, 21546, 872, 34775, 1210, 75622, 56459, 894, 374, 994, 459, 10065, 31680, 311, 2500, 596, 28900, 7645, 449, 279, 1890, 477, 4528, 7645, 13, 4491, 16844, 47773, 279, 28900, 24282, 315, 220, 1313, 7160, 30824, 304, 54557, 3674, 1514, 16079, 13, 578, 30824, 11, 20330, 220, 17, 12, 717, 11, 1051, 52258, 304, 426, 17334, 276, 8219, 24941, 45435, 14821, 304, 28796, 304, 902, 3289, 42306, 1051, 3544, 3403, 311, 2187, 30824, 311, 5268, 3508, 311, 16681, 477, 539, 13, 18185, 279, 30824, 6, 22698, 304, 279, 8545, 369, 264, 58229, 2324, 11, 279, 30824, 304, 420, 4007, 3952, 961, 304, 11758, 315, 1514, 96271, 11, 449, 810, 1109, 11157, 439, 1690, 22443, 1514, 16079, 7863, 311, 11413, 1514, 13, 12220, 1521, 35006, 11, 279, 3495, 2128, 47773, 1403, 12742, 24282, 87671, 16239, 264, 3113, 315, 279, 8582, 3709, 16220, 18311, 11, 323, 832, 2085, 13, 578, 30824, 1051, 1455, 4461, 311, 1501, 24473, 28900, 56459, 894, 2391, 22443, 1514, 13, 4491, 16844, 1071, 1778, 27545, 28003, 16671, 1436, 387, 311, 1520, 1403, 30824, 8450, 430, 814, 527, 5644, 311, 1514, 810, 17715, 11, 477, 311, 20259, 3674, 27460, 13, 1283, 1071, 25, 330, 2181, 374, 13882, 11846, 430, 584, 1193, 1505, 6485, 7739, 315, 10758, 304, 9606, 449, 6485, 3674, 6067, 13, 1666, 7160, 30824, 527, 264, 14090, 58229, 9606, 11, 1057, 4007, 315, 872, 28900, 10758, 4860, 420, 16801, 11, 1606, 433, 5039, 264, 6485, 1376, 315, 28900, 10758, 430, 3156, 1457, 574, 3967, 1193, 304, 810, 3674, 9606, 13, 330, 31192, 30824, 527, 459, 66684, 9606, 304, 279, 8545, 323, 779, 1633, 2697, 374, 3967, 922, 1124, 13, 1226, 1440, 814, 3974, 304, 35148, 11422, 1348, 37379, 11, 8343, 4661, 4395, 11, 323, 430, 4994, 315, 279, 73219, 3280, 12884, 617, 2697, 311, 656, 449, 832, 2500, 13, 330, 4897, 596, 1148, 3727, 1521, 3135, 779, 27387, 71201, 527, 264, 2536, 43129, 9606, 889, 994, 3663, 311, 3663, 649, 19570, 87417, 323, 24559, 1210, 8219, 30824, 11, 1101, 3967, 439, 26828, 30824, 11, 2559, 520, 220, 4364, 12, 3965, 10166, 16615, 323, 17988, 709, 311, 220, 1490, 7501, 13, 2435, 527, 52356, 323, 3974, 304, 279, 35148, 36658, 315, 10007, 40607, 13936, 13, 9983, 85536, 16038, 11, 7160, 11984, 5219, 527, 83222, 2785, 4245, 311, 711, 97893, 11, 3273, 12092, 323, 1694, 7577, 555, 20957, 369, 12459, 31665, 13, 74540, 398, 11, 502, 6691, 30824, 527, 7577, 779, 872, 19250, 649, 387, 4529, 323, 9408, 439, 264, 6896, 477, 8774, 304, 84019, 439, 364, 65, 458, 30824, 6, 1405, 872, 73394, 374, 67572, 369, 1005, 304, 1063, 8620, 39653, 13, 578, 2115, 3495, 574, 24853, 555, 279, 16591, 13581, 323, 279, 2009, 731, 88, 5114, 13, 30013, 3495, 520, 279, 3907, 315, 87670, 8710, 12875, 11857, 872, 28900, 24282, 422, 814, 1440, 4423, 374, 3411, 520, 1124, 13, 220, 128257, 198 ]

2,081

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract The hypothesis that oviraptorosaurs used tail-feather displays in courtship behavior previously predicted that oviraptorosaurs would be found to display sexually dimorphic caudal osteology. MPC-D 100/1002 and MPC-D 100/1127 are two specimens of the oviraptorosaur Khaan mckennai . Although similar in absolute size and in virtually all other anatomical details, the anterior haemal spines of MPC-D 100/1002 exceed those of MPC-D 100/1127 in ventral depth and develop a hitherto unreported “spearhead” shape. This dissimilarity cannot be readily explained as pathologic and is too extreme to be reasonably attributed to the amount of individual variation expected among con-specifics. Instead, this discrepancy in haemal spine morphology may be attributable to sexual dimorphism. The haemal spine form of MPC-D 100/1002 offers greater surface area for caudal muscle insertions. On this basis, MPC-D 100/1002 is regarded as most probably male and MPC-D 100/1127 is regarded as most probably female. Introduction As in all major vertebrate groups, dinosaurs must have included many species with gross anatomical traits that were sexually dimorphic. However, the identification of sexual dimorphism in dinosaurs is hindered by the limitations of an ancient fossil record, which restricts comparative sample size, degrades the quality of available specimens and usually precludes the observation of non-osteological features. Among non-avian theropod dinosaurs, previous attempts to recognize sexual dimorphism have been controversial and inconclusive. Here we describe a possible instance of sexual dimorphism based on chevron morphology in the oviraptorosaur Khaan mckennai . Two specimens of Khaan mckennai (Paleontological Center of the Mongolian Academy of Sciences MPC-D 100/1002 and MPC-D 100/1127) were excavated from the same Upper Cretaceous locality in the Djadokhta Formation (Ukhaa Tolgod, Gurvan Tes Somon, Omnogov Aimak, Gobi Desert, Mongolia) and were found in close proximity to each other (approximately 20 cm away) and in the same bedding plane 1 . Geological work at Ukhaa Tolgod indicates that the preserved animals were buried alive by catastrophic dune collapses, precipitated by heavy rains 2 , 3 . MPC-D 100/1002 and MPC-D 100/1127 were likely killed by a single collapse event and appear to have been near each other prior to death. The two specimens were collectively given the informal, but perhaps fortuitous, nicknames of “Romeo and Juliet” or, occasionally, “Sid and Nancy”. MPC-D 100/1002 is slightly larger than MPC-D 100/1127 (femur lengths of 195 mm and 190 mm, respectively). MPC-D 100/1127 – the holotype of Khaan mckennai 1 – is a complete skeleton. MPC-D 100/1002 is a nearly complete skeleton, missing only the middle and posterior portions of the tail. It nevertheless displays all diagnostic characteristics of Khaan mckennai , including a proximally narrow metacarpal III that does not contact the distal carpals (for a full description of both specimens and their taxonomic assignment see Clark et al. 1 and Balanoff and Norell 4 ). In both individuals, all vertebral neural arches and centra are fully fused, indicating that both had reached adulthood before death 5 , 6 , although histological evidence is still wanting. Based on the similarities in size and proportions, both individuals also appear to have reached roughly the same level of maturity. However, the chevrons of MPC-D 100/1002 and MPC-D 100/1127 show a striking disparity in morphology. Description The anterior chevrons of MPC-D 100/1127 have an overall form that is typical of non-avian theropods, including that previously reported from other oviraptorosaurs ( Figure 1 ). The anterior haemal spines are flat laterally and are simple finger-like projections. In terms of dorsoventral depth, the haemal spine of the second chevron is the deepest and all more posterior haemal spines sequentially decrease in depth. At roughly the middle of the tail, the haemal spines gradually transition into a more boot-shaped form, with weak anterior projections and strong posterior projections ( Figure 1 and 2 ). Although the posterior haemal spines of some oviraptorosaurs (such as Anzu wyliei CM 78000 and 78001, Gigantoraptor erlianensis LH V0011 and Nomingia gobiensis MPC-D 100/119) are rectangular 7 , the general pattern of gradual chevron shape change seen in MPC-D 100/1127 is typical, not only of oviraptorosaurs, but of most non-avian coelurosaurs 8 . As in MPC-D 100/1127, the first chevron of MPC-D 100/1002 lies between the second and third caudal vertebrae; it also has a lateromedially flat haemal spine that is a simple finger-like projection, although the ventral tip is proportionately wider anteroposteriorly than that of the first chevron of MPC-D 100/1127. The second chevron of MPC-D 100/1002 has a haemal spine that is transversely flat and has a prominent posterior heel-like projection located roughly two thirds the way down the central shaft. The haemal spines of the third and fourth chevrons resemble that of the second, but are sequentially shorter and have an increasingly more prominent posterior projection. Each also has a smaller, but increasingly prominent, anterior projection that is slightly ventral to the posterior projection. The haemal spine of the fourth chevron has a distinctive ventrally-projecting spear-head shape ( Figure 1 and 2 ). Unfortunately, only the first four chevrons of MPC-D 100/1002 are preserved and it is impossible to determine if the shape of the haemal spine form of the fourth chevron is representative of more posterior chevrons, or if the haemal spine shape changed posteriorly. Relative to the proportions of the vertebrae, the anterior haemal spines of MPC-D 100/1002 all exceed those of MPC-D 100/1127 in ventral depth ( Figure 1 and 2 , Table 1 ). Table 1 Caudal vertebra and chevron measurements of MPC-D 100/1002 and MPC-D 100/1127 -- “???” indicates measurements that were obscured and could not be reliably measured Full size table Discussion The dissimilarity among the anterior chevrons of MPC-D 100/1002 and MPC-D 100/1127 cannot be readily explained as pathologic. In both specimens, the chevrons show no signs of rugosities or of bilateral asymmetries and neither form is limited to a single chevron. The finger-like form of MPC-D 100/1127 is shared by all anterior haemal spines and the more unusual spear-head haemal spine form of MPC-D 100/1002 manifests progressively across the second, third and fourth haemal spines", "role": "user" }, { "content": "Paleontologists at the University of Alberta have discovered evidence of a prehistoric romance and the secret to sexing some dinosaurs. \"Determining a dinosaur's gender is really hard,\" says graduate student Scott Persons, lead author of the research. \"Because soft anatomy seldom fossilizes, a dinosaur fossil usually provides no direct evidence of whether it was a male or a female.\" Instead, the new research focuses on indirect evidence. Modern birds, the living descendants of dinosaurs, frequently show sexually dimorphic display structures. Such structures—like the fans of peacocks, the tall crests of roosters or the long tail feathers of some birds of paradise—are used to attract and court mates, and are almost always much larger in males (who do the courting) than in females (who do the choosing). Back in 2011, Persons and his colleagues published research on the tails of a group of birdlike dinosaurs called oviraptors. Oviraptors were strictly land-bound animals, but according to the study, they possessed fans of long feathers on the ends of their tails. If these dinosaurs weren't able to fly, what good were their tail feathers? Scott Persons \"Our theory,\" explains Persons, \"was that these large feather fans were used for the same purpose as the feather fans of many modern ground birds, like turkeys, peacocks and prairie chickens: they were used to enhance courtship displays. My analysis of the tail skeletons supported this theory, because the skeletons showed adaptations for both high tail flexibility and enlarged tail musculature—both traits that would have helped an oviraptor to flaunt its tail fan in a mating dance.\" The U of A researchers took the idea a step further. \"The greatest test of any scientific theory is its predictive power,\" says Persons. \"If we were right, and oviraptors really were using their tail fans to court mates, then, just as in modern birds, the display structures ought to be sexually dimorphic. We published the prediction that careful analysis of more oviraptor tails would reveal male and female differences within the same species.\" That prediction has come home to roost. In the new study, published this week in the journal Scientific Reports, Persons and his team have confirmed sexual dimorphism, after meticulous observation of two oviraptor specimens. The two raptors were discovered in the Gobi Desert of Mongolia. Both died and were buried next to each other when a large sand dune collapsed on top of them. When they were first unearthed, the two oviraptors were given the nicknames \"Romeo and Juliet,\" because they seemed reminiscent of Shakespeare's famously doomed lovers. It turns out that the nickname may have been entirely appropriate. \"We discovered that, although both oviraptors were roughly the same size, the same age and otherwise identical in all anatomical regards, 'Romeo' had larger and specially shaped tail bones,\" says Persons. \"This indicates that it had a greater capacity for courtship displays and was likely a male.\" By comparison, the second specimen, \"Juliet,\" had shorter and simpler tail bones, suggesting a lesser capacity for peacocking, and has been interpreted as a female. According to Persons, the two may very well have been a mated pair, making for an altogether romantic story, as the dinosaur couple was preserved side by side for more than 75 million years. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract The hypothesis that oviraptorosaurs used tail-feather displays in courtship behavior previously predicted that oviraptorosaurs would be found to display sexually dimorphic caudal osteology. MPC-D 100/1002 and MPC-D 100/1127 are two specimens of the oviraptorosaur Khaan mckennai . Although similar in absolute size and in virtually all other anatomical details, the anterior haemal spines of MPC-D 100/1002 exceed those of MPC-D 100/1127 in ventral depth and develop a hitherto unreported “spearhead” shape. This dissimilarity cannot be readily explained as pathologic and is too extreme to be reasonably attributed to the amount of individual variation expected among con-specifics. Instead, this discrepancy in haemal spine morphology may be attributable to sexual dimorphism. The haemal spine form of MPC-D 100/1002 offers greater surface area for caudal muscle insertions. On this basis, MPC-D 100/1002 is regarded as most probably male and MPC-D 100/1127 is regarded as most probably female. Introduction As in all major vertebrate groups, dinosaurs must have included many species with gross anatomical traits that were sexually dimorphic. However, the identification of sexual dimorphism in dinosaurs is hindered by the limitations of an ancient fossil record, which restricts comparative sample size, degrades the quality of available specimens and usually precludes the observation of non-osteological features. Among non-avian theropod dinosaurs, previous attempts to recognize sexual dimorphism have been controversial and inconclusive. Here we describe a possible instance of sexual dimorphism based on chevron morphology in the oviraptorosaur Khaan mckennai . Two specimens of Khaan mckennai (Paleontological Center of the Mongolian Academy of Sciences MPC-D 100/1002 and MPC-D 100/1127) were excavated from the same Upper Cretaceous locality in the Djadokhta Formation (Ukhaa Tolgod, Gurvan Tes Somon, Omnogov Aimak, Gobi Desert, Mongolia) and were found in close proximity to each other (approximately 20 cm away) and in the same bedding plane 1 . Geological work at Ukhaa Tolgod indicates that the preserved animals were buried alive by catastrophic dune collapses, precipitated by heavy rains 2 , 3 . MPC-D 100/1002 and MPC-D 100/1127 were likely killed by a single collapse event and appear to have been near each other prior to death. The two specimens were collectively given the informal, but perhaps fortuitous, nicknames of “Romeo and Juliet” or, occasionally, “Sid and Nancy”. MPC-D 100/1002 is slightly larger than MPC-D 100/1127 (femur lengths of 195 mm and 190 mm, respectively). MPC-D 100/1127 – the holotype of Khaan mckennai 1 – is a complete skeleton. MPC-D 100/1002 is a nearly complete skeleton, missing only the middle and posterior portions of the tail. It nevertheless displays all diagnostic characteristics of Khaan mckennai , including a proximally narrow metacarpal III that does not contact the distal carpals (for a full description of both specimens and their taxonomic assignment see Clark et al. 1 and Balanoff and Norell 4 ). In both individuals, all vertebral neural arches and centra are fully fused, indicating that both had reached adulthood before death 5 , 6 , although histological evidence is still wanting. Based on the similarities in size and proportions, both individuals also appear to have reached roughly the same level of maturity. However, the chevrons of MPC-D 100/1002 and MPC-D 100/1127 show a striking disparity in morphology. Description The anterior chevrons of MPC-D 100/1127 have an overall form that is typical of non-avian theropods, including that previously reported from other oviraptorosaurs ( Figure 1 ). The anterior haemal spines are flat laterally and are simple finger-like projections. In terms of dorsoventral depth, the haemal spine of the second chevron is the deepest and all more posterior haemal spines sequentially decrease in depth. At roughly the middle of the tail, the haemal spines gradually transition into a more boot-shaped form, with weak anterior projections and strong posterior projections ( Figure 1 and 2 ). Although the posterior haemal spines of some oviraptorosaurs (such as Anzu wyliei CM 78000 and 78001, Gigantoraptor erlianensis LH V0011 and Nomingia gobiensis MPC-D 100/119) are rectangular 7 , the general pattern of gradual chevron shape change seen in MPC-D 100/1127 is typical, not only of oviraptorosaurs, but of most non-avian coelurosaurs 8 . As in MPC-D 100/1127, the first chevron of MPC-D 100/1002 lies between the second and third caudal vertebrae; it also has a lateromedially flat haemal spine that is a simple finger-like projection, although the ventral tip is proportionately wider anteroposteriorly than that of the first chevron of MPC-D 100/1127. The second chevron of MPC-D 100/1002 has a haemal spine that is transversely flat and has a prominent posterior heel-like projection located roughly two thirds the way down the central shaft. The haemal spines of the third and fourth chevrons resemble that of the second, but are sequentially shorter and have an increasingly more prominent posterior projection. Each also has a smaller, but increasingly prominent, anterior projection that is slightly ventral to the posterior projection. The haemal spine of the fourth chevron has a distinctive ventrally-projecting spear-head shape ( Figure 1 and 2 ). Unfortunately, only the first four chevrons of MPC-D 100/1002 are preserved and it is impossible to determine if the shape of the haemal spine form of the fourth chevron is representative of more posterior chevrons, or if the haemal spine shape changed posteriorly. Relative to the proportions of the vertebrae, the anterior haemal spines of MPC-D 100/1002 all exceed those of MPC-D 100/1127 in ventral depth ( Figure 1 and 2 , Table 1 ). Table 1 Caudal vertebra and chevron measurements of MPC-D 100/1002 and MPC-D 100/1127 -- “???” indicates measurements that were obscured and could not be reliably measured Full size table Discussion The dissimilarity among the anterior chevrons of MPC-D 100/1002 and MPC-D 100/1127 cannot be readily explained as pathologic. In both specimens, the chevrons show no signs of rugosities or of bilateral asymmetries and neither form is limited to a single chevron. The finger-like form of MPC-D 100/1127 is shared by all anterior haemal spines and the more unusual spear-head haemal spine form of MPC-D 100/1002 manifests progressively across the second, third and fourth haemal spines<|im_end|> <|im_start|>assistant Paleontologists at the University of Alberta have discovered evidence of a prehistoric romance and the secret to sexing some dinosaurs. "Determining a dinosaur's gender is really hard," says graduate student Scott Persons, lead author of the research. "Because soft anatomy seldom fossilizes, a dinosaur fossil usually provides no direct evidence of whether it was a male or a female." Instead, the new research focuses on indirect evidence. Modern birds, the living descendants of dinosaurs, frequently show sexually dimorphic display structures. Such structures—like the fans of peacocks, the tall crests of roosters or the long tail feathers of some birds of paradise—are used to attract and court mates, and are almost always much larger in males (who do the courting) than in females (who do the choosing). Back in 2011, Persons and his colleagues published research on the tails of a group of birdlike dinosaurs called oviraptors. Oviraptors were strictly land-bound animals, but according to the study, they possessed fans of long feathers on the ends of their tails. If these dinosaurs weren't able to fly, what good were their tail feathers? Scott Persons "Our theory," explains Persons, "was that these large feather fans were used for the same purpose as the feather fans of many modern ground birds, like turkeys, peacocks and prairie chickens: they were used to enhance courtship displays. My analysis of the tail skeletons supported this theory, because the skeletons showed adaptations for both high tail flexibility and enlarged tail musculature—both traits that would have helped an oviraptor to flaunt its tail fan in a mating dance." The U of A researchers took the idea a step further. "The greatest test of any scientific theory is its predictive power," says Persons. "If we were right, and oviraptors really were using their tail fans to court mates, then, just as in modern birds, the display structures ought to be sexually dimorphic. We published the prediction that careful analysis of more oviraptor tails would reveal male and female differences within the same species." That prediction has come home to roost. In the new study, published this week in the journal Scientific Reports, Persons and his team have confirmed sexual dimorphism, after meticulous observation of two oviraptor specimens. The two raptors were discovered in the Gobi Desert of Mongolia. Both died and were buried next to each other when a large sand dune collapsed on top of them. When they were first unearthed, the two oviraptors were given the nicknames "Romeo and Juliet," because they seemed reminiscent of Shakespeare's famously doomed lovers. It turns out that the nickname may have been entirely appropriate. "We discovered that, although both oviraptors were roughly the same size, the same age and otherwise identical in all anatomical regards, 'Romeo' had larger and specially shaped tail bones," says Persons. "This indicates that it had a greater capacity for courtship displays and was likely a male." By comparison, the second specimen, "Juliet," had shorter and simpler tail bones, suggesting a lesser capacity for peacocking, and has been interpreted as a female. According to Persons, the two may very well have been a mated pair, making for an altogether romantic story, as the dinosaur couple was preserved side by side for more than 75 million years. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 578, 31178, 430, 25568, 404, 33757, 53356, 1511, 9986, 34303, 1894, 19207, 304, 5590, 5383, 7865, 8767, 19698, 430, 25568, 404, 33757, 53356, 1053, 387, 1766, 311, 3113, 27681, 5213, 41969, 2211, 664, 278, 52368, 2508, 13, 92698, 9607, 220, 1041, 14, 1041, 17, 323, 92698, 9607, 220, 1041, 14, 7261, 22, 527, 1403, 57749, 315, 279, 25568, 404, 33757, 59076, 735, 4317, 276, 296, 377, 52024, 662, 10541, 4528, 304, 10973, 1404, 323, 304, 21907, 682, 1023, 75893, 950, 3649, 11, 279, 37229, 6520, 336, 278, 993, 1572, 315, 92698, 9607, 220, 1041, 14, 1041, 17, 12771, 1884, 315, 92698, 9607, 220, 1041, 14, 7261, 22, 304, 10594, 3545, 8149, 323, 2274, 264, 305, 411, 14200, 653, 76833, 1054, 82, 8174, 2025, 863, 6211, 13, 1115, 14091, 318, 49325, 4250, 387, 31368, 11497, 439, 1853, 39227, 323, 374, 2288, 14560, 311, 387, 29546, 30706, 311, 279, 3392, 315, 3927, 23851, 3685, 4315, 390, 19440, 82, 13, 12361, 11, 420, 79105, 304, 6520, 336, 278, 35776, 79612, 1253, 387, 71526, 311, 7392, 5213, 53907, 13, 578, 6520, 336, 278, 35776, 1376, 315, 92698, 9607, 220, 1041, 14, 1041, 17, 6209, 7191, 7479, 3158, 369, 2211, 664, 278, 16124, 5774, 919, 13, 1952, 420, 8197, 11, 92698, 9607, 220, 1041, 14, 1041, 17, 374, 27458, 439, 1455, 4762, 8762, 323, 92698, 9607, 220, 1041, 14, 7261, 22, 374, 27458, 439, 1455, 4762, 8954, 13, 29438, 1666, 304, 682, 3682, 67861, 65216, 5315, 11, 65375, 2011, 617, 5343, 1690, 9606, 449, 20547, 75893, 950, 25022, 430, 1051, 27681, 5213, 41969, 13, 4452, 11, 279, 22654, 315, 7392, 5213, 53907, 304, 65375, 374, 57780, 291, 555, 279, 9669, 315, 459, 14154, 31376, 3335, 11, 902, 9067, 82, 55394, 6205, 1404, 11, 409, 23142, 279, 4367, 315, 2561, 57749, 323, 6118, 864, 7548, 279, 22695, 315, 2536, 12, 85223, 5848, 4519, 13, 22395, 2536, 12, 60278, 9139, 454, 347, 65375, 11, 3766, 13865, 311, 15641, 7392, 5213, 53907, 617, 1027, 20733, 323, 28093, 8500, 13, 5810, 584, 7664, 264, 3284, 2937, 315, 7392, 5213, 53907, 3196, 389, 3091, 30579, 79612, 304, 279, 25568, 404, 33757, 59076, 735, 4317, 276, 296, 377, 52024, 662, 9220, 57749, 315, 735, 4317, 276, 296, 377, 52024, 320, 78666, 546, 5848, 5955, 315, 279, 44539, 89108, 16192, 315, 23199, 92698, 9607, 220, 1041, 14, 1041, 17, 323, 92698, 9607, 220, 1041, 14, 7261, 22, 8, 1051, 45215, 660, 505, 279, 1890, 31714, 356, 2171, 77140, 69187, 304, 279, 52162, 329, 564, 76909, 72466, 320, 52, 74, 4317, 64, 59602, 40811, 11, 62033, 16023, 23971, 18024, 263, 11, 90934, 540, 869, 71715, 587, 11, 480, 18843, 43286, 11, 91850, 8, 323, 1051, 1766, 304, 3345, 37843, 311, 1855, 1023, 320, 97836, 220, 508, 10166, 3201, 8, 323, 304, 279, 1890, 61253, 11277, 220, 16, 662, 80850, 990, 520, 60413, 4317, 64, 59602, 40811, 15151, 430, 279, 34683, 10099, 1051, 28016, 13989, 555, 54677, 294, 2957, 87458, 11, 36841, 33337, 555, 8987, 62555, 220, 17, 1174, 220, 18, 662, 92698, 9607, 220, 1041, 14, 1041, 17, 323, 92698, 9607, 220, 1041, 14, 7261, 22, 1051, 4461, 7577, 555, 264, 3254, 18678, 1567, 323, 5101, 311, 617, 1027, 3221, 1855, 1023, 4972, 311, 4648, 13, 578, 1403, 57749, 1051, 45925, 2728, 279, 42887, 11, 719, 8530, 12108, 3159, 788, 11, 16370, 11654, 315, 1054, 49, 638, 78, 323, 72124, 863, 477, 11, 23781, 11, 1054, 68753, 323, 35336, 11453, 92698, 9607, 220, 1041, 14, 1041, 17, 374, 10284, 8294, 1109, 92698, 9607, 220, 1041, 14, 7261, 22, 320, 69, 336, 324, 29416, 315, 220, 6280, 9653, 323, 220, 7028, 9653, 11, 15947, 570, 92698, 9607, 220, 1041, 14, 7261, 22, 1389, 279, 24429, 4249, 315, 735, 4317, 276, 296, 377, 52024, 220, 16, 1389, 374, 264, 4686, 30535, 13, 92698, 9607, 220, 1041, 14, 1041, 17, 374, 264, 7154, 4686, 30535, 11, 7554, 1193, 279, 6278, 323, 46000, 19885, 315, 279, 9986, 13, 1102, 38330, 19207, 682, 15439, 17910, 315, 735, 4317, 276, 296, 377, 52024, 1174, 2737, 264, 22267, 318, 750, 15376, 2322, 582, 8035, 278, 14767, 430, 1587, 539, 3729, 279, 1612, 278, 39739, 1147, 320, 2000, 264, 2539, 4096, 315, 2225, 57749, 323, 872, 3827, 48228, 16720, 1518, 22010, 1880, 453, 13, 220, 16, 323, 19984, 276, 1885, 323, 452, 461, 657, 220, 19, 7609, 763, 2225, 7931, 11, 682, 67861, 42743, 30828, 5438, 288, 323, 2960, 969, 527, 7373, 75754, 11, 19392, 430, 2225, 1047, 8813, 64033, 1603, 4648, 220, 20, 1174, 220, 21, 1174, 8051, 13034, 5848, 6029, 374, 2103, 19762, 13, 20817, 389, 279, 43874, 304, 1404, 323, 49892, 11, 2225, 7931, 1101, 5101, 311, 617, 8813, 17715, 279, 1890, 2237, 315, 48261, 13, 4452, 11, 279, 3091, 85, 26692, 315, 92698, 9607, 220, 1041, 14, 1041, 17, 323, 92698, 9607, 220, 1041, 14, 7261, 22, 1501, 264, 21933, 66949, 304, 79612, 13, 7817, 578, 37229, 3091, 85, 26692, 315, 92698, 9607, 220, 1041, 14, 7261, 22, 617, 459, 8244, 1376, 430, 374, 14595, 315, 2536, 12, 60278, 9139, 454, 30797, 11, 2737, 430, 8767, 5068, 505, 1023, 25568, 404, 33757, 53356, 320, 19575, 220, 16, 7609, 578, 37229, 6520, 336, 278, 993, 1572, 527, 10269, 3010, 750, 323, 527, 4382, 14654, 12970, 41579, 13, 763, 3878, 315, 53403, 708, 688, 3545, 8149, 11, 279, 6520, 336, 278, 35776, 315, 279, 2132, 3091, 30579, 374, 279, 51621, 323, 682, 810, 46000, 6520, 336, 278, 993, 1572, 95659, 18979, 304, 8149, 13, 2468, 17715, 279, 6278, 315, 279, 9986, 11, 279, 6520, 336, 278, 993, 1572, 27115, 9320, 1139, 264, 810, 10677, 35831, 1376, 11, 449, 7621, 37229, 41579, 323, 3831, 46000, 41579, 320, 19575, 220, 16, 323, 220, 17, 7609, 10541, 279, 46000, 6520, 336, 278, 993, 1572, 315, 1063, 25568, 404, 33757, 53356, 320, 21470, 439, 1556, 26738, 289, 67577, 72, 18582, 220, 19423, 410, 323, 220, 19423, 1721, 11, 45234, 89267, 33757, 2781, 92898, 87778, 83863, 650, 4119, 16, 323, 452, 18238, 689, 342, 18843, 87778, 92698, 9607, 220, 1041, 14, 9079, 8, 527, 52524, 220, 22, 1174, 279, 4689, 5497, 315, 53722, 3091, 30579, 6211, 2349, 3970, 304, 92698, 9607, 220, 1041, 14, 7261, 22, 374, 14595, 11, 539, 1193, 315, 25568, 404, 33757, 53356, 11, 719, 315, 1455, 2536, 12, 60278, 1080, 301, 2868, 9258, 1759, 220, 23, 662, 1666, 304, 92698, 9607, 220, 1041, 14, 7261, 22, 11, 279, 1176, 3091, 30579, 315, 92698, 9607, 220, 1041, 14, 1041, 17, 15812, 1990, 279, 2132, 323, 4948, 2211, 664, 278, 5309, 51313, 68, 26, 433, 1101, 706, 264, 3010, 25111, 34575, 10269, 6520, 336, 278, 35776, 430, 374, 264, 4382, 14654, 12970, 22343, 11, 8051, 279, 10594, 3545, 11813, 374, 21801, 2718, 22622, 3276, 261, 454, 11975, 2521, 398, 1109, 430, 315, 279, 1176, 3091, 30579, 315, 92698, 9607, 220, 1041, 14, 7261, 22, 13, 578, 2132, 3091, 30579, 315, 92698, 9607, 220, 1041, 14, 1041, 17, 706, 264, 6520, 336, 278, 35776, 430, 374, 1380, 3078, 989, 10269, 323, 706, 264, 21102, 46000, 35428, 12970, 22343, 7559, 17715, 1403, 94237, 279, 1648, 1523, 279, 8792, 31468, 13, 578, 6520, 336, 278, 993, 1572, 315, 279, 4948, 323, 11999, 3091, 85, 26692, 52280, 430, 315, 279, 2132, 11, 719, 527, 95659, 24210, 323, 617, 459, 15098, 810, 21102, 46000, 22343, 13, 9062, 1101, 706, 264, 9333, 11, 719, 15098, 21102, 11, 37229, 22343, 430, 374, 10284, 10594, 3545, 311, 279, 46000, 22343, 13, 578, 6520, 336, 278, 35776, 315, 279, 11999, 3091, 30579, 706, 264, 35947, 10594, 81, 750, 34796, 287, 41963, 27488, 6211, 320, 19575, 220, 16, 323, 220, 17, 7609, 19173, 11, 1193, 279, 1176, 3116, 3091, 85, 26692, 315, 92698, 9607, 220, 1041, 14, 1041, 17, 527, 34683, 323, 433, 374, 12266, 311, 8417, 422, 279, 6211, 315, 279, 6520, 336, 278, 35776, 1376, 315, 279, 11999, 3091, 30579, 374, 18740, 315, 810, 46000, 3091, 85, 26692, 11, 477, 422, 279, 6520, 336, 278, 35776, 6211, 5614, 46000, 398, 13, 40502, 311, 279, 49892, 315, 279, 5309, 51313, 68, 11, 279, 37229, 6520, 336, 278, 993, 1572, 315, 92698, 9607, 220, 1041, 14, 1041, 17, 682, 12771, 1884, 315, 92698, 9607, 220, 1041, 14, 7261, 22, 304, 10594, 3545, 8149, 320, 19575, 220, 16, 323, 220, 17, 1174, 6771, 220, 16, 7609, 6771, 220, 16, 356, 8039, 278, 5309, 51313, 323, 3091, 30579, 22323, 315, 92698, 9607, 220, 1041, 14, 1041, 17, 323, 92698, 9607, 220, 1041, 14, 7261, 22, 1198, 1054, 7801, 12671, 15151, 22323, 430, 1051, 96801, 323, 1436, 539, 387, 57482, 17303, 8797, 1404, 2007, 36613, 578, 14091, 318, 49325, 4315, 279, 37229, 3091, 85, 26692, 315, 92698, 9607, 220, 1041, 14, 1041, 17, 323, 92698, 9607, 220, 1041, 14, 7261, 22, 4250, 387, 31368, 11497, 439, 1853, 39227, 13, 763, 2225, 57749, 11, 279, 3091, 85, 26692, 1501, 912, 12195, 315, 29742, 437, 1385, 477, 315, 52303, 54395, 4150, 4108, 323, 14188, 1376, 374, 7347, 311, 264, 3254, 3091, 30579, 13, 578, 14654, 12970, 1376, 315, 92698, 9607, 220, 1041, 14, 7261, 22, 374, 6222, 555, 682, 37229, 6520, 336, 278, 993, 1572, 323, 279, 810, 19018, 41963, 27488, 6520, 336, 278, 35776, 1376, 315, 92698, 9607, 220, 1041, 14, 1041, 17, 84332, 72859, 4028, 279, 2132, 11, 4948, 323, 11999, 6520, 336, 278, 993, 1572, 128257, 198, 128256, 78191, 198, 78666, 546, 22012, 520, 279, 3907, 315, 33654, 617, 11352, 6029, 315, 264, 864, 74416, 30363, 323, 279, 6367, 311, 1877, 287, 1063, 65375, 13, 330, 93748, 287, 264, 63989, 596, 10026, 374, 2216, 2653, 1359, 2795, 19560, 5575, 10016, 63030, 11, 3063, 3229, 315, 279, 3495, 13, 330, 18433, 8579, 62690, 56452, 31376, 4861, 11, 264, 63989, 31376, 6118, 5825, 912, 2167, 6029, 315, 3508, 433, 574, 264, 8762, 477, 264, 8954, 1210, 12361, 11, 279, 502, 3495, 24400, 389, 25636, 6029, 13, 18766, 20229, 11, 279, 5496, 49446, 315, 65375, 11, 14134, 1501, 27681, 5213, 41969, 3113, 14726, 13, 15483, 14726, 2345, 4908, 279, 7359, 315, 1069, 582, 26246, 11, 279, 16615, 1922, 37379, 315, 938, 537, 388, 477, 279, 1317, 9986, 56994, 315, 1063, 20229, 315, 50852, 83872, 1511, 311, 9504, 323, 5590, 55616, 11, 323, 527, 4661, 2744, 1790, 8294, 304, 25000, 320, 14965, 656, 279, 2126, 1303, 8, 1109, 304, 28585, 320, 14965, 656, 279, 19301, 570, 6984, 304, 220, 679, 16, 11, 63030, 323, 813, 18105, 4756, 3495, 389, 279, 64614, 315, 264, 1912, 315, 12224, 4908, 65375, 2663, 25568, 404, 58512, 13, 507, 46957, 58512, 1051, 26549, 4363, 50962, 10099, 11, 719, 4184, 311, 279, 4007, 11, 814, 43890, 7359, 315, 1317, 56994, 389, 279, 10548, 315, 872, 64614, 13, 1442, 1521, 65375, 15058, 956, 3025, 311, 11722, 11, 1148, 1695, 1051, 872, 9986, 56994, 30, 10016, 63030, 330, 8140, 10334, 1359, 15100, 63030, 11, 330, 16514, 430, 1521, 3544, 50876, 7359, 1051, 1511, 369, 279, 1890, 7580, 439, 279, 50876, 7359, 315, 1690, 6617, 5015, 20229, 11, 1093, 13535, 10786, 11, 1069, 582, 26246, 323, 550, 75690, 54623, 25, 814, 1051, 1511, 311, 18885, 5590, 5383, 19207, 13, 3092, 6492, 315, 279, 9986, 75407, 7396, 420, 10334, 11, 1606, 279, 75407, 8710, 77765, 369, 2225, 1579, 9986, 25152, 323, 74117, 9986, 3167, 3395, 1598, 2345, 21704, 25022, 430, 1053, 617, 9087, 459, 25568, 404, 33757, 311, 97228, 3935, 1202, 9986, 8571, 304, 264, 73219, 15612, 1210, 578, 549, 315, 362, 12074, 3952, 279, 4623, 264, 3094, 4726, 13, 330, 791, 12474, 1296, 315, 904, 12624, 10334, 374, 1202, 60336, 2410, 1359, 2795, 63030, 13, 330, 2746, 584, 1051, 1314, 11, 323, 25568, 404, 58512, 2216, 1051, 1701, 872, 9986, 7359, 311, 5590, 55616, 11, 1243, 11, 1120, 439, 304, 6617, 20229, 11, 279, 3113, 14726, 22525, 311, 387, 27681, 5213, 41969, 13, 1226, 4756, 279, 20212, 430, 16994, 6492, 315, 810, 25568, 404, 33757, 64614, 1053, 16805, 8762, 323, 8954, 12062, 2949, 279, 1890, 9606, 1210, 3011, 20212, 706, 2586, 2162, 311, 938, 537, 13, 763, 279, 502, 4007, 11, 4756, 420, 2046, 304, 279, 8486, 38130, 29140, 11, 63030, 323, 813, 2128, 617, 11007, 7392, 5213, 53907, 11, 1306, 96278, 22695, 315, 1403, 25568, 404, 33757, 57749, 13, 578, 1403, 436, 58512, 1051, 11352, 304, 279, 480, 18843, 43286, 315, 91850, 13, 11995, 8636, 323, 1051, 28016, 1828, 311, 1855, 1023, 994, 264, 3544, 9462, 294, 2957, 29368, 389, 1948, 315, 1124, 13, 3277, 814, 1051, 1176, 79675, 291, 11, 279, 1403, 25568, 404, 58512, 1051, 2728, 279, 16370, 11654, 330, 49, 638, 78, 323, 72124, 1359, 1606, 814, 9508, 56085, 315, 42482, 596, 51287, 58737, 33218, 13, 1102, 10800, 704, 430, 279, 30499, 1253, 617, 1027, 11622, 8475, 13, 330, 1687, 11352, 430, 11, 8051, 2225, 25568, 404, 58512, 1051, 17715, 279, 1890, 1404, 11, 279, 1890, 4325, 323, 6062, 20086, 304, 682, 75893, 950, 24886, 11, 364, 49, 638, 78, 6, 1047, 8294, 323, 35426, 27367, 9986, 25896, 1359, 2795, 63030, 13, 330, 2028, 15151, 430, 433, 1047, 264, 7191, 8824, 369, 5590, 5383, 19207, 323, 574, 4461, 264, 8762, 1210, 3296, 12593, 11, 279, 2132, 58184, 11, 330, 29185, 3978, 1359, 1047, 24210, 323, 35388, 9986, 25896, 11, 23377, 264, 32415, 8824, 369, 1069, 582, 71191, 11, 323, 706, 1027, 33398, 439, 264, 8954, 13, 10771, 311, 63030, 11, 279, 1403, 1253, 1633, 1664, 617, 1027, 264, 296, 660, 6857, 11, 3339, 369, 459, 31155, 24364, 3446, 11, 439, 279, 63989, 5743, 574, 34683, 3185, 555, 3185, 369, 810, 1109, 220, 2075, 3610, 1667, 13, 220, 128257, 198 ]

2,270

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract The ability to form memories is a prerequisite for an organism's behavioral adaptation to environmental changes. At the molecular level, the acquisition and maintenance of memory requires changes in chromatin modifications. In an effort to unravel the epigenetic network underlying both short- and long-term memory, we examined chromatin modification changes in two distinct mouse brain regions, two cell types and three time points before and after contextual learning. We found that histone modifications predominantly changed during memory acquisition and correlated surprisingly little with changes in gene expression. Although long-lasting changes were almost exclusive to neurons, learning-related histone modification and DNA methylation changes also occurred in non-neuronal cell types, suggesting a functional role for non-neuronal cells in epigenetic learning. Finally, our data provide evidence for a molecular framework of memory acquisition and maintenance, wherein DNA methylation could alter the expression and splicing of genes involved in functional plasticity and synaptic wiring. Main An organism's ability to learn and establish memory is essential for its behavioral adaptation to environmental changes. On a cellular level, learning and memory is mediated by structural and functional changes of cells in the nervous system. These changes, also termed plasticity, change a neuron's response to an external stimulus 1 . At the molecular level, these structural changes are dependent on intracellular signaling networks that regulate the synthesis of proteins and the activity of genes 1 . In addition to transcriptional and translational changes, a large body of evidence suggests that chromatin modifications are an important part of learning and memory processes 2 , 3 , 4 , 5 . In brief, genetic and pharmacological evidence indicates that changes in the activity of chromatin modifying enzymes influence cognitive abilities in animals and humans 5 . Furthermore, correlational evidence links bulk changes in histone post-translational modifications (HPTMs), predominantly histone acetylation, to the formation of short- (cellular consolidation) and long-term (systems consolidation) memory 5 , 6 , 7 . Dynamic and stable changes of HPTM and 5-methylcytosine DNA methylation (DNAme) have been reported for the learning-relevant genes Reelin , Calcineurin and Bdnf during cellular consolidation, systems consolidation and memory maintenance 3 , 8 , 9 . Consistent with the 'histone code' theory 10 , this evidence suggests that chromatin modifications, specifically histone acetylation and DNAme, might be a molecular correlate of long-term memory (mnemonic substrate) by modulating the stimulus-dependent activation of learning-relevant genes in memory-forming cellular networks 3 , 11 , 12 . In addition to a potential role as mnemonic substrate, chromatin modifications might be functionally important during cellular and systems consolidation. Although this theoretical framework highlights the potential dual role of chromatin modifications in learning and memory processes, the spatio-temporal extent of DNAme and HPTM changes and their functional implications remain unclear 5 . We set out to clarify the functional roles of chromatin modification changes in short- and long-term memory formation and maintenance. Results Cell type – specific chromatin modification data To identify DNAme and HPTM changes that are associated with short- and long-term memory consolidation and maintenance, we charted an unbiased, genome-wide profile of chromatin modifications, brain region and cell type specifically, over time ( Supplementary Fig. 1 and Online Methods ). In brief, we chose contextual fear conditioning (CFC) as the learning procedure given its robustness and its wide application 13 . The areas that we investigated were the hippocampal CA1 region, a region that is crucial for the short-term memory formation during CFC 14 , and the anterior cingulate cortex (ACC), a region important for associative memory acquisition and maintenance 15 , 16 . To decipher the role of neuronal and non-neuronal cells, we optimized the BiTS-ChIP (batch isolation of tissue-specific chromatin and ChIP) protocol 17 , 18 , 19 to murine brain tissue, sorting for NeuN-positive neuronal and NeuN-negative non-neuronal cells ( Fig. 1a ). In addition, we substantially reduced the amounts of starting material needed for high-quality ChIP- and MeDIP-seq (methylated DNA immunoprecipitation) experiments ( Supplementary Table 1 , Supplementary Fig. 2 and Online Methods ). To allow for comparisons between chromatin modification and gene expression levels, we performed RNA-seq on unsorted samples ( Supplementary Table 2 ). Figure 1: High-resolution brain region– and cell type–specific chromatin modification data. ( a ) Method outline. The hippocampal CA1 or cortical ACC were dissected from wild-type mice and nuclei were fixed during isolation, resulting in high-confidence in vivo chromatin modification data. Nuclei were stained with antibody to the neuronal marker NeuN, sorted into NeuN-positive (+) and NeuN-negative (−) nuclei via fluorescence-activated cell sorting, and chromatin was sheared. ChIP or MeDIP experiments were performed on neuronal and non-neuronal samples under naive or learning conditions. Notably, all experiments shown are in a naive state in which the animals performed baseline cognitive tasks and correspond to data from the hippocampal CA1 region. ( b ) Cell type–specific chromatin modification enrichment on the neuronally expressed Camk2a gene locus. Promoter arrows indicate the direction of transcription. Neuronal data (+) showed strong enrichment, whereas non-neuronal data (−) showed an absence of activity-linked chromatin modifications (for example, H3K4me3). ( c ) Aggregate plot of H3K79me3 using merged neuronal (green, D+) and non-neuronal data (blue, D−) for genes that are known to be expressed only in neurons (G+) or in non-neurons (G−). Shaded areas represent 95% confidence intervals. Full size image Many chromatin modifications have been linked to learning and memory processes and we chose to examine a subset of these in our experiments. Of the seven modifications investigated, three were previously found to be differentially regulated during CFC (DNAme, H3K9ac and H3K4me3) 7 , 8 , 9 , 20 . In addition to these learning-associated modifications, we examined four chromatin modifications that were not previously linked to learning and memory (H3K4me1, H3K79me3, H3K27ac and H3K27me3). All of these chromatin modifications have been studied extensively and are well correlated with gene and/or enhancer activity 17 , 21 , 22 . In brief, H3K4me3, H3K9ac, H3K79me3 and H3K27ac demarcate active genes, H3K27ac and H3K4me1 are found on active enhancers, and H3K27me3 and", "role": "user" }, { "content": "Scientists from the German Center for Neurodegenerative Diseases have shed new light on the molecular basis of memory. Their study confirms that the formation of memories is accompanied by an altered activity of specific genes. In addition, they found an unprecedented amount of evidence that supports the hypothesis that chemical labels on the backbone of the DNA (so-called DNA methylation) may be the molecular basis of long-term memory. These findings are reported in Nature Neuroscience. The brain still harbours many unknowns. Basically, it is believed that it stores experiences by altering the connections between brain cells. This ability to adapt—which is also called \"plasticity\"—provides the basis for memory and learning, which is the ability to draw conclusions from memories. On a molecular scale, these changes are mediated by modifications of expression of specific genes that strengthen or weaken the connections between the brain cells as required. In the current study, a research team led by Dr. Stefan Bonn and Prof. André Fischer from Göttingen, joined forces with colleagues from the DZNE's Munich site to examine how the activity of such genes is regulated. The scientists stimulated long-term memory in mice by training the animals to recognise a specific test environment. Based on tissue samples, the researchers could discern the extent to which this learning task triggered changes in the activity of the genes in the mice's brain cells. Their focus was directed on so-called epigenetic modifications. These modifications involve the DNA and DNA-associated proteins. Epigenetic modifications \"The cell makes use of various mechanisms in order to turn genes on or off, without altering the DNA sequence itself. It's called 'epigenetics',\" explains Dr. Magali Hennion, a staff member of the research group of Stefan Bonn. In principle, gene regulation can happen through methylation, whereby the backbone of the DNA is chemically labeled at specific sites. Changes in the proteins called histones that are packaging the DNA may also occur. Hennion: \"Research on epigenetic changes that are related to memory processes is still at an early stage. We look at such features not only for the purpose of a better understanding of how memory works—we also look for potential targets for drugs that may counteract memory decline. Ultimately, our research is about therapies against Alzheimer's and similar brain diseases.\" A code for memory contents? In the current study, the researchers found modifications, both of the histones as well as of the methylation of the DNA. However, histone modifications had little effect on the activity of genes involved in neuroplasticity. Furthermore, Bonn and his colleagues not only discovered epigenetic modifications in nerve cells, but also in non-neuronal cells of the brain. \"The relevance of non-neuronal cells for memory is an interesting topic that we will continue to pursue,\" says André Fischer, site speaker for the DZNE in Göttingen and professor at the University Medical Center Göttingen (UMG). \"Furthermore, our observations suggest that neuroplasticity is, to a large extent, regulated by DNA methylation. Although this is not a new hypothesis, our study provides an unprecedented amount of supporting evidence for this. Thus, methylation may indeed be an important molecular constituent of long-term memory. In such a case, methylation could be a sort of code for memory content and a potential target for therapies against Alzheimer's disease. This is an aspect that we specifically want to focus on, in further studies.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract The ability to form memories is a prerequisite for an organism's behavioral adaptation to environmental changes. At the molecular level, the acquisition and maintenance of memory requires changes in chromatin modifications. In an effort to unravel the epigenetic network underlying both short- and long-term memory, we examined chromatin modification changes in two distinct mouse brain regions, two cell types and three time points before and after contextual learning. We found that histone modifications predominantly changed during memory acquisition and correlated surprisingly little with changes in gene expression. Although long-lasting changes were almost exclusive to neurons, learning-related histone modification and DNA methylation changes also occurred in non-neuronal cell types, suggesting a functional role for non-neuronal cells in epigenetic learning. Finally, our data provide evidence for a molecular framework of memory acquisition and maintenance, wherein DNA methylation could alter the expression and splicing of genes involved in functional plasticity and synaptic wiring. Main An organism's ability to learn and establish memory is essential for its behavioral adaptation to environmental changes. On a cellular level, learning and memory is mediated by structural and functional changes of cells in the nervous system. These changes, also termed plasticity, change a neuron's response to an external stimulus 1 . At the molecular level, these structural changes are dependent on intracellular signaling networks that regulate the synthesis of proteins and the activity of genes 1 . In addition to transcriptional and translational changes, a large body of evidence suggests that chromatin modifications are an important part of learning and memory processes 2 , 3 , 4 , 5 . In brief, genetic and pharmacological evidence indicates that changes in the activity of chromatin modifying enzymes influence cognitive abilities in animals and humans 5 . Furthermore, correlational evidence links bulk changes in histone post-translational modifications (HPTMs), predominantly histone acetylation, to the formation of short- (cellular consolidation) and long-term (systems consolidation) memory 5 , 6 , 7 . Dynamic and stable changes of HPTM and 5-methylcytosine DNA methylation (DNAme) have been reported for the learning-relevant genes Reelin , Calcineurin and Bdnf during cellular consolidation, systems consolidation and memory maintenance 3 , 8 , 9 . Consistent with the 'histone code' theory 10 , this evidence suggests that chromatin modifications, specifically histone acetylation and DNAme, might be a molecular correlate of long-term memory (mnemonic substrate) by modulating the stimulus-dependent activation of learning-relevant genes in memory-forming cellular networks 3 , 11 , 12 . In addition to a potential role as mnemonic substrate, chromatin modifications might be functionally important during cellular and systems consolidation. Although this theoretical framework highlights the potential dual role of chromatin modifications in learning and memory processes, the spatio-temporal extent of DNAme and HPTM changes and their functional implications remain unclear 5 . We set out to clarify the functional roles of chromatin modification changes in short- and long-term memory formation and maintenance. Results Cell type – specific chromatin modification data To identify DNAme and HPTM changes that are associated with short- and long-term memory consolidation and maintenance, we charted an unbiased, genome-wide profile of chromatin modifications, brain region and cell type specifically, over time ( Supplementary Fig. 1 and Online Methods ). In brief, we chose contextual fear conditioning (CFC) as the learning procedure given its robustness and its wide application 13 . The areas that we investigated were the hippocampal CA1 region, a region that is crucial for the short-term memory formation during CFC 14 , and the anterior cingulate cortex (ACC), a region important for associative memory acquisition and maintenance 15 , 16 . To decipher the role of neuronal and non-neuronal cells, we optimized the BiTS-ChIP (batch isolation of tissue-specific chromatin and ChIP) protocol 17 , 18 , 19 to murine brain tissue, sorting for NeuN-positive neuronal and NeuN-negative non-neuronal cells ( Fig. 1a ). In addition, we substantially reduced the amounts of starting material needed for high-quality ChIP- and MeDIP-seq (methylated DNA immunoprecipitation) experiments ( Supplementary Table 1 , Supplementary Fig. 2 and Online Methods ). To allow for comparisons between chromatin modification and gene expression levels, we performed RNA-seq on unsorted samples ( Supplementary Table 2 ). Figure 1: High-resolution brain region– and cell type–specific chromatin modification data. ( a ) Method outline. The hippocampal CA1 or cortical ACC were dissected from wild-type mice and nuclei were fixed during isolation, resulting in high-confidence in vivo chromatin modification data. Nuclei were stained with antibody to the neuronal marker NeuN, sorted into NeuN-positive (+) and NeuN-negative (−) nuclei via fluorescence-activated cell sorting, and chromatin was sheared. ChIP or MeDIP experiments were performed on neuronal and non-neuronal samples under naive or learning conditions. Notably, all experiments shown are in a naive state in which the animals performed baseline cognitive tasks and correspond to data from the hippocampal CA1 region. ( b ) Cell type–specific chromatin modification enrichment on the neuronally expressed Camk2a gene locus. Promoter arrows indicate the direction of transcription. Neuronal data (+) showed strong enrichment, whereas non-neuronal data (−) showed an absence of activity-linked chromatin modifications (for example, H3K4me3). ( c ) Aggregate plot of H3K79me3 using merged neuronal (green, D+) and non-neuronal data (blue, D−) for genes that are known to be expressed only in neurons (G+) or in non-neurons (G−). Shaded areas represent 95% confidence intervals. Full size image Many chromatin modifications have been linked to learning and memory processes and we chose to examine a subset of these in our experiments. Of the seven modifications investigated, three were previously found to be differentially regulated during CFC (DNAme, H3K9ac and H3K4me3) 7 , 8 , 9 , 20 . In addition to these learning-associated modifications, we examined four chromatin modifications that were not previously linked to learning and memory (H3K4me1, H3K79me3, H3K27ac and H3K27me3). All of these chromatin modifications have been studied extensively and are well correlated with gene and/or enhancer activity 17 , 21 , 22 . In brief, H3K4me3, H3K9ac, H3K79me3 and H3K27ac demarcate active genes, H3K27ac and H3K4me1 are found on active enhancers, and H3K27me3 and<|im_end|> <|im_start|>assistant Scientists from the German Center for Neurodegenerative Diseases have shed new light on the molecular basis of memory. Their study confirms that the formation of memories is accompanied by an altered activity of specific genes. In addition, they found an unprecedented amount of evidence that supports the hypothesis that chemical labels on the backbone of the DNA (so-called DNA methylation) may be the molecular basis of long-term memory. These findings are reported in Nature Neuroscience. The brain still harbours many unknowns. Basically, it is believed that it stores experiences by altering the connections between brain cells. This ability to adapt—which is also called "plasticity"—provides the basis for memory and learning, which is the ability to draw conclusions from memories. On a molecular scale, these changes are mediated by modifications of expression of specific genes that strengthen or weaken the connections between the brain cells as required. In the current study, a research team led by Dr. Stefan Bonn and Prof. André Fischer from Göttingen, joined forces with colleagues from the DZNE's Munich site to examine how the activity of such genes is regulated. The scientists stimulated long-term memory in mice by training the animals to recognise a specific test environment. Based on tissue samples, the researchers could discern the extent to which this learning task triggered changes in the activity of the genes in the mice's brain cells. Their focus was directed on so-called epigenetic modifications. These modifications involve the DNA and DNA-associated proteins. Epigenetic modifications "The cell makes use of various mechanisms in order to turn genes on or off, without altering the DNA sequence itself. It's called 'epigenetics'," explains Dr. Magali Hennion, a staff member of the research group of Stefan Bonn. In principle, gene regulation can happen through methylation, whereby the backbone of the DNA is chemically labeled at specific sites. Changes in the proteins called histones that are packaging the DNA may also occur. Hennion: "Research on epigenetic changes that are related to memory processes is still at an early stage. We look at such features not only for the purpose of a better understanding of how memory works—we also look for potential targets for drugs that may counteract memory decline. Ultimately, our research is about therapies against Alzheimer's and similar brain diseases." A code for memory contents? In the current study, the researchers found modifications, both of the histones as well as of the methylation of the DNA. However, histone modifications had little effect on the activity of genes involved in neuroplasticity. Furthermore, Bonn and his colleagues not only discovered epigenetic modifications in nerve cells, but also in non-neuronal cells of the brain. "The relevance of non-neuronal cells for memory is an interesting topic that we will continue to pursue," says André Fischer, site speaker for the DZNE in Göttingen and professor at the University Medical Center Göttingen (UMG). "Furthermore, our observations suggest that neuroplasticity is, to a large extent, regulated by DNA methylation. Although this is not a new hypothesis, our study provides an unprecedented amount of supporting evidence for this. Thus, methylation may indeed be an important molecular constituent of long-term memory. In such a case, methylation could be a sort of code for memory content and a potential target for therapies against Alzheimer's disease. This is an aspect that we specifically want to focus on, in further studies." <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 578, 5845, 311, 1376, 19459, 374, 264, 80884, 369, 459, 47120, 596, 36695, 34185, 311, 12434, 4442, 13, 2468, 279, 31206, 2237, 11, 279, 24279, 323, 13709, 315, 5044, 7612, 4442, 304, 22083, 15111, 29882, 13, 763, 459, 5149, 311, 75073, 279, 4248, 6569, 5411, 4009, 16940, 2225, 2875, 12, 323, 1317, 9860, 5044, 11, 584, 25078, 22083, 15111, 17466, 4442, 304, 1403, 12742, 8814, 8271, 13918, 11, 1403, 2849, 4595, 323, 2380, 892, 3585, 1603, 323, 1306, 66251, 6975, 13, 1226, 1766, 430, 13034, 606, 29882, 47904, 5614, 2391, 5044, 24279, 323, 49393, 29392, 2697, 449, 4442, 304, 15207, 7645, 13, 10541, 1317, 65265, 4442, 1051, 4661, 14079, 311, 34313, 11, 6975, 14228, 13034, 606, 17466, 323, 15922, 21747, 79933, 4442, 1101, 10222, 304, 2536, 41078, 324, 25180, 2849, 4595, 11, 23377, 264, 16003, 3560, 369, 2536, 41078, 324, 25180, 7917, 304, 4248, 6569, 5411, 6975, 13, 17830, 11, 1057, 828, 3493, 6029, 369, 264, 31206, 12914, 315, 5044, 24279, 323, 13709, 11, 42418, 15922, 21747, 79933, 1436, 11857, 279, 7645, 323, 993, 90214, 315, 21389, 6532, 304, 16003, 12466, 488, 323, 99827, 19358, 13, 4802, 1556, 47120, 596, 5845, 311, 4048, 323, 5813, 5044, 374, 7718, 369, 1202, 36695, 34185, 311, 12434, 4442, 13, 1952, 264, 35693, 2237, 11, 6975, 323, 5044, 374, 78926, 555, 24693, 323, 16003, 4442, 315, 7917, 304, 279, 23418, 1887, 13, 4314, 4442, 11, 1101, 61937, 12466, 488, 11, 2349, 264, 49384, 596, 2077, 311, 459, 9434, 39535, 220, 16, 662, 2468, 279, 31206, 2237, 11, 1521, 24693, 4442, 527, 18222, 389, 10805, 65441, 43080, 14488, 430, 37377, 279, 39975, 315, 28896, 323, 279, 5820, 315, 21389, 220, 16, 662, 763, 5369, 311, 46940, 278, 323, 12215, 1697, 4442, 11, 264, 3544, 2547, 315, 6029, 13533, 430, 22083, 15111, 29882, 527, 459, 3062, 961, 315, 6975, 323, 5044, 11618, 220, 17, 1174, 220, 18, 1174, 220, 19, 1174, 220, 20, 662, 763, 10015, 11, 19465, 323, 36449, 5848, 6029, 15151, 430, 4442, 304, 279, 5820, 315, 22083, 15111, 47141, 56067, 10383, 25702, 18000, 304, 10099, 323, 12966, 220, 20, 662, 24296, 11, 35983, 1697, 6029, 7902, 20155, 4442, 304, 13034, 606, 1772, 39160, 75, 1697, 29882, 320, 39, 2898, 22365, 705, 47904, 13034, 606, 1645, 2676, 2354, 11, 311, 279, 18488, 315, 2875, 12, 320, 5997, 1299, 60732, 8, 323, 1317, 9860, 320, 46654, 60732, 8, 5044, 220, 20, 1174, 220, 21, 1174, 220, 22, 662, 22648, 323, 15528, 4442, 315, 473, 2898, 44, 323, 220, 20, 1474, 42972, 11377, 43681, 483, 15922, 21747, 79933, 320, 56420, 2727, 8, 617, 1027, 5068, 369, 279, 6975, 5621, 8532, 21389, 1050, 33830, 1174, 35315, 483, 324, 258, 323, 426, 17851, 69, 2391, 35693, 60732, 11, 6067, 60732, 323, 5044, 13709, 220, 18, 1174, 220, 23, 1174, 220, 24, 662, 7440, 18620, 449, 279, 364, 21843, 606, 2082, 6, 10334, 220, 605, 1174, 420, 6029, 13533, 430, 22083, 15111, 29882, 11, 11951, 13034, 606, 1645, 2676, 2354, 323, 15922, 2727, 11, 2643, 387, 264, 31206, 81584, 315, 1317, 9860, 5044, 320, 22524, 39901, 54057, 8, 555, 1491, 15853, 279, 39535, 43918, 15449, 315, 6975, 5621, 8532, 21389, 304, 5044, 8627, 287, 35693, 14488, 220, 18, 1174, 220, 806, 1174, 220, 717, 662, 763, 5369, 311, 264, 4754, 3560, 439, 87901, 54057, 11, 22083, 15111, 29882, 2643, 387, 734, 750, 3062, 2391, 35693, 323, 6067, 60732, 13, 10541, 420, 32887, 12914, 22020, 279, 4754, 19091, 3560, 315, 22083, 15111, 29882, 304, 6975, 323, 5044, 11618, 11, 279, 993, 6400, 69290, 10020, 13112, 315, 15922, 2727, 323, 473, 2898, 44, 4442, 323, 872, 16003, 25127, 7293, 25420, 220, 20, 662, 1226, 743, 704, 311, 38263, 279, 16003, 13073, 315, 22083, 15111, 17466, 4442, 304, 2875, 12, 323, 1317, 9860, 5044, 18488, 323, 13709, 13, 18591, 14299, 955, 1389, 3230, 22083, 15111, 17466, 828, 2057, 10765, 15922, 2727, 323, 473, 2898, 44, 4442, 430, 527, 5938, 449, 2875, 12, 323, 1317, 9860, 5044, 60732, 323, 13709, 11, 584, 9676, 291, 459, 74315, 11, 33869, 25480, 5643, 315, 22083, 15111, 29882, 11, 8271, 5654, 323, 2849, 955, 11951, 11, 927, 892, 320, 99371, 23966, 13, 220, 16, 323, 8267, 19331, 7609, 763, 10015, 11, 584, 14896, 66251, 8850, 35121, 320, 34, 6897, 8, 439, 279, 6975, 10537, 2728, 1202, 22514, 2136, 323, 1202, 7029, 3851, 220, 1032, 662, 578, 5789, 430, 584, 27313, 1051, 279, 71206, 1141, 278, 9362, 16, 5654, 11, 264, 5654, 430, 374, 16996, 369, 279, 2875, 9860, 5044, 18488, 2391, 356, 6897, 220, 975, 1174, 323, 279, 37229, 272, 287, 6468, 49370, 320, 30542, 705, 264, 5654, 3062, 369, 70003, 5044, 24279, 323, 13709, 220, 868, 1174, 220, 845, 662, 2057, 75277, 279, 3560, 315, 79402, 323, 2536, 41078, 324, 25180, 7917, 11, 584, 34440, 279, 12371, 10155, 30653, 3378, 320, 14377, 31398, 315, 20438, 19440, 22083, 15111, 323, 921, 3378, 8, 11766, 220, 1114, 1174, 220, 972, 1174, 220, 777, 311, 8309, 483, 8271, 20438, 11, 29373, 369, 45950, 45, 69788, 79402, 323, 45950, 45, 62035, 2536, 41078, 324, 25180, 7917, 320, 23966, 13, 220, 16, 64, 7609, 763, 5369, 11, 584, 32302, 11293, 279, 15055, 315, 6041, 3769, 4460, 369, 1579, 22867, 921, 3378, 12, 323, 2206, 35, 3378, 7962, 80, 320, 76, 42972, 660, 15922, 33119, 454, 2827, 575, 7709, 8, 21896, 320, 99371, 6771, 220, 16, 1174, 99371, 23966, 13, 220, 17, 323, 8267, 19331, 7609, 2057, 2187, 369, 36595, 1990, 22083, 15111, 17466, 323, 15207, 7645, 5990, 11, 584, 10887, 41214, 7962, 80, 389, 653, 29398, 10688, 320, 99371, 6771, 220, 17, 7609, 19575, 220, 16, 25, 5234, 64036, 8271, 5654, 4235, 323, 2849, 955, 4235, 52340, 22083, 15111, 17466, 828, 13, 320, 264, 883, 6872, 21782, 13, 578, 71206, 1141, 278, 9362, 16, 477, 83619, 26925, 1051, 75050, 291, 505, 8545, 10827, 24548, 323, 97192, 1051, 8521, 2391, 31398, 11, 13239, 304, 1579, 91980, 304, 41294, 22083, 15111, 17466, 828, 13, 452, 22935, 72, 1051, 61152, 449, 63052, 311, 279, 79402, 11381, 45950, 45, 11, 10839, 1139, 45950, 45, 69788, 18457, 8, 323, 45950, 45, 62035, 320, 34363, 8, 97192, 4669, 97332, 12, 31262, 2849, 29373, 11, 323, 22083, 15111, 574, 1364, 1636, 13, 921, 3378, 477, 2206, 35, 3378, 21896, 1051, 10887, 389, 79402, 323, 2536, 41078, 324, 25180, 10688, 1234, 50765, 477, 6975, 4787, 13, 2876, 2915, 11, 682, 21896, 6982, 527, 304, 264, 50765, 1614, 304, 902, 279, 10099, 10887, 26954, 25702, 9256, 323, 8024, 311, 828, 505, 279, 71206, 1141, 278, 9362, 16, 5654, 13, 320, 293, 883, 14299, 955, 4235, 52340, 22083, 15111, 17466, 70272, 389, 279, 49384, 750, 13605, 8215, 74, 17, 64, 15207, 79257, 13, 18042, 26464, 38057, 13519, 279, 5216, 315, 46940, 13, 4275, 324, 25180, 828, 18457, 8, 8710, 3831, 70272, 11, 20444, 2536, 41078, 324, 25180, 828, 320, 34363, 8, 8710, 459, 19821, 315, 5820, 55514, 22083, 15111, 29882, 320, 2000, 3187, 11, 473, 18, 42, 19, 2727, 18, 570, 320, 272, 883, 58022, 7234, 315, 473, 18, 42, 4643, 2727, 18, 1701, 27092, 79402, 320, 13553, 11, 423, 37297, 323, 2536, 41078, 324, 25180, 828, 320, 12481, 11, 423, 34363, 8, 369, 21389, 430, 527, 3967, 311, 387, 13605, 1193, 304, 34313, 320, 38, 37297, 477, 304, 2536, 41078, 54769, 320, 38, 34363, 570, 1443, 14589, 5789, 4097, 220, 2721, 4, 12410, 28090, 13, 8797, 1404, 2217, 9176, 22083, 15111, 29882, 617, 1027, 10815, 311, 6975, 323, 5044, 11618, 323, 584, 14896, 311, 21635, 264, 27084, 315, 1521, 304, 1057, 21896, 13, 5046, 279, 8254, 29882, 27313, 11, 2380, 1051, 8767, 1766, 311, 387, 2204, 34575, 35319, 2391, 356, 6897, 320, 56420, 2727, 11, 473, 18, 42, 24, 582, 323, 473, 18, 42, 19, 2727, 18, 8, 220, 22, 1174, 220, 23, 1174, 220, 24, 1174, 220, 508, 662, 763, 5369, 311, 1521, 6975, 75968, 29882, 11, 584, 25078, 3116, 22083, 15111, 29882, 430, 1051, 539, 8767, 10815, 311, 6975, 323, 5044, 320, 39, 18, 42, 19, 2727, 16, 11, 473, 18, 42, 4643, 2727, 18, 11, 473, 18, 42, 1544, 582, 323, 473, 18, 42, 1544, 2727, 18, 570, 2052, 315, 1521, 22083, 15111, 29882, 617, 1027, 20041, 42817, 323, 527, 1664, 49393, 449, 15207, 323, 5255, 8833, 11967, 5820, 220, 1114, 1174, 220, 1691, 1174, 220, 1313, 662, 763, 10015, 11, 473, 18, 42, 19, 2727, 18, 11, 473, 18, 42, 24, 582, 11, 473, 18, 42, 4643, 2727, 18, 323, 473, 18, 42, 1544, 582, 2486, 8362, 349, 4642, 21389, 11, 473, 18, 42, 1544, 582, 323, 473, 18, 42, 19, 2727, 16, 527, 1766, 389, 4642, 8833, 32842, 11, 323, 473, 18, 42, 1544, 2727, 18, 323, 128257, 198, 128256, 78191, 198, 72326, 505, 279, 6063, 5955, 369, 32359, 451, 7642, 1413, 70674, 617, 25351, 502, 3177, 389, 279, 31206, 8197, 315, 5044, 13, 11205, 4007, 43496, 430, 279, 18488, 315, 19459, 374, 24895, 555, 459, 29852, 5820, 315, 3230, 21389, 13, 763, 5369, 11, 814, 1766, 459, 31069, 3392, 315, 6029, 430, 11815, 279, 31178, 430, 11742, 9382, 389, 279, 56527, 315, 279, 15922, 320, 708, 19434, 15922, 21747, 79933, 8, 1253, 387, 279, 31206, 8197, 315, 1317, 9860, 5044, 13, 4314, 14955, 527, 5068, 304, 22037, 85879, 13, 578, 8271, 2103, 69566, 2530, 1690, 9987, 82, 13, 41812, 11, 433, 374, 11846, 430, 433, 10756, 11704, 555, 60923, 279, 13537, 1990, 8271, 7917, 13, 1115, 5845, 311, 10737, 50004, 374, 1101, 2663, 330, 501, 5174, 488, 66101, 782, 68254, 279, 8197, 369, 5044, 323, 6975, 11, 902, 374, 279, 5845, 311, 4128, 31342, 505, 19459, 13, 1952, 264, 31206, 5569, 11, 1521, 4442, 527, 78926, 555, 29882, 315, 7645, 315, 3230, 21389, 430, 20259, 477, 33556, 279, 13537, 1990, 279, 8271, 7917, 439, 2631, 13, 763, 279, 1510, 4007, 11, 264, 3495, 2128, 6197, 555, 2999, 13, 50002, 13789, 77, 323, 8626, 13, 85900, 63016, 505, 480, 45326, 1303, 268, 11, 11096, 8603, 449, 18105, 505, 279, 423, 57, 4031, 596, 47304, 2816, 311, 21635, 1268, 279, 5820, 315, 1778, 21389, 374, 35319, 13, 578, 14248, 81471, 1317, 9860, 5044, 304, 24548, 555, 4967, 279, 10099, 311, 44917, 264, 3230, 1296, 4676, 13, 20817, 389, 20438, 10688, 11, 279, 12074, 1436, 42645, 279, 13112, 311, 902, 420, 6975, 3465, 22900, 4442, 304, 279, 5820, 315, 279, 21389, 304, 279, 24548, 596, 8271, 7917, 13, 11205, 5357, 574, 15910, 389, 779, 19434, 4248, 6569, 5411, 29882, 13, 4314, 29882, 21736, 279, 15922, 323, 15922, 75968, 28896, 13, 11266, 6569, 5411, 29882, 330, 791, 2849, 3727, 1005, 315, 5370, 24717, 304, 2015, 311, 2543, 21389, 389, 477, 1022, 11, 2085, 60923, 279, 15922, 8668, 5196, 13, 1102, 596, 2663, 364, 752, 6569, 25265, 38687, 15100, 2999, 13, 7023, 8115, 473, 2734, 290, 11, 264, 5687, 4562, 315, 279, 3495, 1912, 315, 50002, 13789, 77, 13, 763, 17966, 11, 15207, 19812, 649, 3621, 1555, 21747, 79933, 11, 49001, 279, 56527, 315, 279, 15922, 374, 8590, 2740, 30929, 520, 3230, 6732, 13, 29240, 304, 279, 28896, 2663, 13034, 3233, 430, 527, 24066, 279, 15922, 1253, 1101, 12446, 13, 473, 2734, 290, 25, 330, 28528, 389, 4248, 6569, 5411, 4442, 430, 527, 5552, 311, 5044, 11618, 374, 2103, 520, 459, 4216, 6566, 13, 1226, 1427, 520, 1778, 4519, 539, 1193, 369, 279, 7580, 315, 264, 2731, 8830, 315, 1268, 5044, 4375, 86319, 1101, 1427, 369, 4754, 11811, 369, 11217, 430, 1253, 5663, 533, 5044, 18174, 13, 55106, 11, 1057, 3495, 374, 922, 52312, 2403, 44531, 596, 323, 4528, 8271, 19338, 1210, 362, 2082, 369, 5044, 8970, 30, 763, 279, 1510, 4007, 11, 279, 12074, 1766, 29882, 11, 2225, 315, 279, 13034, 3233, 439, 1664, 439, 315, 279, 21747, 79933, 315, 279, 15922, 13, 4452, 11, 13034, 606, 29882, 1047, 2697, 2515, 389, 279, 5820, 315, 21389, 6532, 304, 18247, 501, 5174, 488, 13, 24296, 11, 13789, 77, 323, 813, 18105, 539, 1193, 11352, 4248, 6569, 5411, 29882, 304, 32015, 7917, 11, 719, 1101, 304, 2536, 41078, 324, 25180, 7917, 315, 279, 8271, 13, 330, 791, 41961, 315, 2536, 41078, 324, 25180, 7917, 369, 5044, 374, 459, 7185, 8712, 430, 584, 690, 3136, 311, 23564, 1359, 2795, 85900, 63016, 11, 2816, 19114, 369, 279, 423, 57, 4031, 304, 480, 45326, 1303, 268, 323, 14561, 520, 279, 3907, 13235, 5955, 480, 45326, 1303, 268, 320, 2864, 38, 570, 330, 57417, 11, 1057, 24654, 4284, 430, 18247, 501, 5174, 488, 374, 11, 311, 264, 3544, 13112, 11, 35319, 555, 15922, 21747, 79933, 13, 10541, 420, 374, 539, 264, 502, 31178, 11, 1057, 4007, 5825, 459, 31069, 3392, 315, 12899, 6029, 369, 420, 13, 14636, 11, 21747, 79933, 1253, 13118, 387, 459, 3062, 31206, 75164, 315, 1317, 9860, 5044, 13, 763, 1778, 264, 1162, 11, 21747, 79933, 1436, 387, 264, 3460, 315, 2082, 369, 5044, 2262, 323, 264, 4754, 2218, 369, 52312, 2403, 44531, 596, 8624, 13, 1115, 374, 459, 13189, 430, 584, 11951, 1390, 311, 5357, 389, 11, 304, 4726, 7978, 1210, 220, 128257, 198 ]

2,178

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Background Prior research has shown that artificial intelligence (AI) systems often encode biases against minority subgroups. However, little work has focused on ways to mitigate the harm discriminatory algorithms can cause in high-stakes settings such as medicine. Methods In this study, we experimentally evaluated the impact biased AI recommendations have on emergency decisions, where participants respond to mental health crises by calling for either medical or police assistance. We recruited 438 clinicians and 516 non-experts to participate in our web-based experiment. We evaluated participant decision-making with and without advice from biased and unbiased AI systems. We also varied the style of the AI advice, framing it either as prescriptive recommendations or descriptive flags. Results Participant decisions are unbiased without AI advice. However, both clinicians and non-experts are influenced by prescriptive recommendations from a biased algorithm, choosing police help more often in emergencies involving African-American or Muslim men. Crucially, using descriptive flags rather than prescriptive recommendations allows respondents to retain their original, unbiased decision-making. Conclusions Our work demonstrates the practical danger of using biased models in health contexts, and suggests that appropriately framing decision support can mitigate the effects of AI bias. These findings must be carefully considered in the many real-world clinical scenarios where inaccurate or biased models may be used to inform important decisions. Plain language summary Artificial intelligence (AI) systems that make decisions based on historical data are increasingly common in health care settings. However, many AI models exhibit problematic biases, as data often reflect human prejudices against minority groups. In this study, we used a web-based experiment to evaluate the impact biased models can have when used to inform human decisions. We found that though participants were not inherently biased, they were strongly influenced by advice from a biased model if it was offered prescriptively (i.e., “you should do X”). This adherence led their decisions to be biased against African-American and Muslims individuals. However, framing the same advice descriptively (i.e., without recommending a specific action) allowed participants to remain fair. These results demonstrate that though discriminatory AI can lead to poor outcomes for minority groups, appropriately framing advice can help mitigate its effects. Introduction Machine learning (ML) and artificial intelligence (AI) are increasingly being used to support decision-making in a variety of health care applications 1 , 2 . However, the potential impact of deploying AI in heterogeneous health contexts is not well understood. As these tools proliferate, it is vital to study how AI can be used to improve expert practice—even when models inevitably make mistakes. Recent work has demonstrated that inaccurate recommendations from AI systems can significantly worsen the quality of clinical treatment decisions 3 , 4 . Other research has shown that even though experts may believe the quality of ML-given advice to be lower, they show similar levels of error as non-experts when presented with incorrect recommendations 5 . Increasing model explainability and interpretability does not resolve this issue, and in some cases, may worsen human ability to detect mistakes 6 , 7 . These human-AI interaction shortcomings are especially concerning in the context of a body of literature that has established that ML models often exhibit biases against racial, gender, and religious subgroups 8 . Large language models like BERT 9 and GPT-3 10 —which are powerful and easy to deploy—exhibit problematic prejudices, such as persistently associating Muslims with violence in sentence-completion tasks 11 . Even variants of the BERT architecture trained on scientific abstracts and clinical notes favor majority groups in many clinical-prediction tasks 12 . While previous work has established these biases, it is unclear how the actual use of a biased model might affect decision-making in a practical health care setting. This interaction is especially vital to understand now, as language models begin to be used in health applications like triage 13 and therapy chatbots 14 . In this study, we evaluated the impact biased AI can have in a decision setting involving a mental health emergency. We conducted a web-based experiment with 954 consented subjects: 438 clinicians and 516 non-experts. We found that though participant decisions were unbiased without AI advice, they were highly influenced by prescriptive recommendations from a biased AI system. This algorithmic adherence created racial and religious disparities in their decisions. However, we found that using descriptive rather than prescriptive recommendations allowed participants to retain their original, unbiased decision-making. These results demonstrate that though using discriminatory AI in a realistic health setting can lead to poor outcomes for marginalized subgroups, appropriately framing model advice can help mitigate the underlying bias of the AI system. Methods Participant recruitment We adopted an experimental approach to evaluate the impact that biased AI can have in a decision setting involving a mental health emergency. We recruited 438 clinicians and 516 non-experts to participate in our experiment, which was conducted online through Qualtrics between May 2021 and December 2021. Clinicians were recruited by emailing staff and residents at hospitals in the United States and Canada, while non-experts were recruited through social media (Facebook, Reddit) and university email lists. Informed consent was obtained from all participants. This study was exempt from a full ethical review by COUHES, the Institutional Review Board for the Massachusetts Institute of Technology (MIT), because it met the criteria for exemption defined in Federal regulation 45 CFR 46. Participants were asked to complete a short complete a short demographic survey after completing the main experiment. We summarize key participant demographics in Supplementary Table 1 , additional measures in Supplementary Table 2 , and clinician-specific characteristics in Supplementary Table 3 . Note that we excluded participants who Qualtrics identified as bots, as well as those who rushed through our survey (finishing in under 5 min). We also excluded duplicate responses from the same participant, which removed 15 clinician and 2347 non-expert responses. Experimental design Participants were shown a series of eight call summaries to a fictitious crisis hotline, each of which described a male individual experiencing a mental health emergency. In addition to specifics about the situation,", "role": "user" }, { "content": "It's no secret that people harbor biases—some unconscious, perhaps, and others painfully overt. The average person might suppose that computers—machines typically made of plastic, steel, glass, silicon, and various metals—are free of prejudice. While that assumption may hold for computer hardware, the same is not always true for computer software, which is programmed by fallible humans and can be fed data that is, itself, compromised in certain respects. Artificial intelligence (AI) systems—those based on machine learning, in particular—are seeing increased use in medicine for diagnosing specific diseases, for example, or evaluating X-rays. These systems are also being relied on to support decision-making in other areas of health care. Recent research has shown, however, that machine learning models can encode biases against minority subgroups, and the recommendations they make may consequently reflect those same biases. A new study by researchers from MIT's Computer Science and Artificial Intelligence Laboratory (CSAIL) and the MIT Jameel Clinic, which was published last month in Communications Medicine, assesses the impact that discriminatory AI models can have, especially for systems that are intended to provide advice in urgent situations. \"We found that the manner in which the advice is framed can have significant repercussions,\" explains the paper's lead author, Hammaad Adam, a Ph.D. student at MIT's Institute for Data Systems and Society. \"Fortunately, the harm caused by biased models can be limited (though not necessarily eliminated) when the advice is presented in a different way.\" The other co-authors of the paper are Aparna Balagopalan and Emily Alsentzer, both Ph.D. students, and the professors Fotini Christia and Marzyeh Ghassemi. AI models used in medicine can suffer from inaccuracies and inconsistencies, in part because the data used to train the models are often not representative of real-world settings. Different kinds of X-ray machines, for instance, can record things differently and hence yield different results. Models trained predominately on white people, moreover, may not be as accurate when applied to other groups. The Communications Medicine paper is not focused on issues of that sort but instead addresses problems that stem from biases and on ways to mitigate the adverse consequences. A group of 954 people (438 clinicians and 516 nonexperts) took part in an experiment to see how AI biases can affect decision-making. The participants were presented with call summaries from a fictitious crisis hotline, each involving a male individual undergoing a mental health emergency. The summaries contained information as to whether the individual was Caucasian or African American and would also mention his religion if he happened to be Muslim. A typical call summary might describe a circumstance in which an African American man was found at home in a delirious state, indicating that \"he has not consumed any drugs or alcohol, as he is a practicing Muslim.\" Study participants were instructed to call the police if they thought the patient was likely to turn violent; otherwise, they were encouraged to seek medical help. The participants were randomly divided into a control or \"baseline\" group plus four other groups designed to test responses under slightly different conditions. \"We want to understand how biased models can influence decisions, but we first need to understand how human biases can affect the decision-making process,\" Adam notes. What they found in their analysis of the baseline group was rather surprising: \"In the setting we considered, human participants did not exhibit any biases. That doesn't mean that humans are not biased, but the way we conveyed information about a person's race and religion, evidently, was not strong enough to elicit their biases.\" The other four groups in the experiment were given advice that either came from a biased or unbiased model, and that advice was presented in either a \"prescriptive\" or a \"descriptive\" form. A biased model would be more likely to recommend police help in a situation involving an African American or Muslim person than would an unbiased model. Participants in the study, however, did not know which kind of model their advice came from, or even that models delivering the advice could be biased at all. Prescriptive advice spells out what a participant should do in unambiguous terms, telling them they should call the police in one instance or seek medical help in another. Descriptive advice is less direct: A flag is displayed to show that the AI system perceives a risk of violence associated with a particular call; no flag is shown if the threat of violence is deemed small. A key takeaway of the experiment is that participants \"were highly influenced by prescriptive recommendations from a biased AI system,\" the authors wrote. But they also found that \"using descriptive rather than prescriptive recommendations allowed participants to retain their original, unbiased decision-making.\" In other words, the bias incorporated within an AI model can be diminished by appropriately framing the advice that's rendered. Why the different outcomes, depending on how advice is posed? When someone is told to do something, like call the police, that leaves little room for doubt, Adam explains. However, when the situation is merely described—classified with or without the presence of a flag—\"that leaves room for a participant's own interpretation; it allows them to be more flexible and consider the situation for themselves.\" Second, the researchers found that the language models that are typically used to offer advice are easy to bias. Language models represent a class of machine learning systems that are trained on text, such as the entire contents of Wikipedia and other web material. When these models are \"fine-tuned\" by relying on a much smaller subset of data for training purposes—just 2,000 sentences, as opposed to 8 million web pages—the resultant models can be readily biased. Third, the MIT team discovered that decision-makers who are themselves unbiased can still be misled by the recommendations provided by biased models. Medical training (or the lack thereof) did not change responses in a discernible way. \"Clinicians were influenced by biased models as much as non-experts were,\" the authors stated. \"These findings could be applicable to other settings,\" Adam says, and are not necessarily restricted to health care situations. When it comes to deciding which people should receive a job interview, a biased model could be more likely to turn down Black applicants. The results could be different, however, if instead of explicitly (and prescriptively) telling an employer to \"reject this applicant,\" a descriptive flag is attached to the file to indicate the applicant's \"possible lack of experience.\" The implications of this work are broader than just figuring out how to deal with individuals in the midst of mental health crises, Adam maintains. \"Our ultimate goal is to make sure that machine learning models are used in a fair, safe, and robust way.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Background Prior research has shown that artificial intelligence (AI) systems often encode biases against minority subgroups. However, little work has focused on ways to mitigate the harm discriminatory algorithms can cause in high-stakes settings such as medicine. Methods In this study, we experimentally evaluated the impact biased AI recommendations have on emergency decisions, where participants respond to mental health crises by calling for either medical or police assistance. We recruited 438 clinicians and 516 non-experts to participate in our web-based experiment. We evaluated participant decision-making with and without advice from biased and unbiased AI systems. We also varied the style of the AI advice, framing it either as prescriptive recommendations or descriptive flags. Results Participant decisions are unbiased without AI advice. However, both clinicians and non-experts are influenced by prescriptive recommendations from a biased algorithm, choosing police help more often in emergencies involving African-American or Muslim men. Crucially, using descriptive flags rather than prescriptive recommendations allows respondents to retain their original, unbiased decision-making. Conclusions Our work demonstrates the practical danger of using biased models in health contexts, and suggests that appropriately framing decision support can mitigate the effects of AI bias. These findings must be carefully considered in the many real-world clinical scenarios where inaccurate or biased models may be used to inform important decisions. Plain language summary Artificial intelligence (AI) systems that make decisions based on historical data are increasingly common in health care settings. However, many AI models exhibit problematic biases, as data often reflect human prejudices against minority groups. In this study, we used a web-based experiment to evaluate the impact biased models can have when used to inform human decisions. We found that though participants were not inherently biased, they were strongly influenced by advice from a biased model if it was offered prescriptively (i.e., “you should do X”). This adherence led their decisions to be biased against African-American and Muslims individuals. However, framing the same advice descriptively (i.e., without recommending a specific action) allowed participants to remain fair. These results demonstrate that though discriminatory AI can lead to poor outcomes for minority groups, appropriately framing advice can help mitigate its effects. Introduction Machine learning (ML) and artificial intelligence (AI) are increasingly being used to support decision-making in a variety of health care applications 1 , 2 . However, the potential impact of deploying AI in heterogeneous health contexts is not well understood. As these tools proliferate, it is vital to study how AI can be used to improve expert practice—even when models inevitably make mistakes. Recent work has demonstrated that inaccurate recommendations from AI systems can significantly worsen the quality of clinical treatment decisions 3 , 4 . Other research has shown that even though experts may believe the quality of ML-given advice to be lower, they show similar levels of error as non-experts when presented with incorrect recommendations 5 . Increasing model explainability and interpretability does not resolve this issue, and in some cases, may worsen human ability to detect mistakes 6 , 7 . These human-AI interaction shortcomings are especially concerning in the context of a body of literature that has established that ML models often exhibit biases against racial, gender, and religious subgroups 8 . Large language models like BERT 9 and GPT-3 10 —which are powerful and easy to deploy—exhibit problematic prejudices, such as persistently associating Muslims with violence in sentence-completion tasks 11 . Even variants of the BERT architecture trained on scientific abstracts and clinical notes favor majority groups in many clinical-prediction tasks 12 . While previous work has established these biases, it is unclear how the actual use of a biased model might affect decision-making in a practical health care setting. This interaction is especially vital to understand now, as language models begin to be used in health applications like triage 13 and therapy chatbots 14 . In this study, we evaluated the impact biased AI can have in a decision setting involving a mental health emergency. We conducted a web-based experiment with 954 consented subjects: 438 clinicians and 516 non-experts. We found that though participant decisions were unbiased without AI advice, they were highly influenced by prescriptive recommendations from a biased AI system. This algorithmic adherence created racial and religious disparities in their decisions. However, we found that using descriptive rather than prescriptive recommendations allowed participants to retain their original, unbiased decision-making. These results demonstrate that though using discriminatory AI in a realistic health setting can lead to poor outcomes for marginalized subgroups, appropriately framing model advice can help mitigate the underlying bias of the AI system. Methods Participant recruitment We adopted an experimental approach to evaluate the impact that biased AI can have in a decision setting involving a mental health emergency. We recruited 438 clinicians and 516 non-experts to participate in our experiment, which was conducted online through Qualtrics between May 2021 and December 2021. Clinicians were recruited by emailing staff and residents at hospitals in the United States and Canada, while non-experts were recruited through social media (Facebook, Reddit) and university email lists. Informed consent was obtained from all participants. This study was exempt from a full ethical review by COUHES, the Institutional Review Board for the Massachusetts Institute of Technology (MIT), because it met the criteria for exemption defined in Federal regulation 45 CFR 46. Participants were asked to complete a short complete a short demographic survey after completing the main experiment. We summarize key participant demographics in Supplementary Table 1 , additional measures in Supplementary Table 2 , and clinician-specific characteristics in Supplementary Table 3 . Note that we excluded participants who Qualtrics identified as bots, as well as those who rushed through our survey (finishing in under 5 min). We also excluded duplicate responses from the same participant, which removed 15 clinician and 2347 non-expert responses. Experimental design Participants were shown a series of eight call summaries to a fictitious crisis hotline, each of which described a male individual experiencing a mental health emergency. In addition to specifics about the situation,<|im_end|> <|im_start|>assistant It's no secret that people harbor biases—some unconscious, perhaps, and others painfully overt. The average person might suppose that computers—machines typically made of plastic, steel, glass, silicon, and various metals—are free of prejudice. While that assumption may hold for computer hardware, the same is not always true for computer software, which is programmed by fallible humans and can be fed data that is, itself, compromised in certain respects. Artificial intelligence (AI) systems—those based on machine learning, in particular—are seeing increased use in medicine for diagnosing specific diseases, for example, or evaluating X-rays. These systems are also being relied on to support decision-making in other areas of health care. Recent research has shown, however, that machine learning models can encode biases against minority subgroups, and the recommendations they make may consequently reflect those same biases. A new study by researchers from MIT's Computer Science and Artificial Intelligence Laboratory (CSAIL) and the MIT Jameel Clinic, which was published last month in Communications Medicine, assesses the impact that discriminatory AI models can have, especially for systems that are intended to provide advice in urgent situations. "We found that the manner in which the advice is framed can have significant repercussions," explains the paper's lead author, Hammaad Adam, a Ph.D. student at MIT's Institute for Data Systems and Society. "Fortunately, the harm caused by biased models can be limited (though not necessarily eliminated) when the advice is presented in a different way." The other co-authors of the paper are Aparna Balagopalan and Emily Alsentzer, both Ph.D. students, and the professors Fotini Christia and Marzyeh Ghassemi. AI models used in medicine can suffer from inaccuracies and inconsistencies, in part because the data used to train the models are often not representative of real-world settings. Different kinds of X-ray machines, for instance, can record things differently and hence yield different results. Models trained predominately on white people, moreover, may not be as accurate when applied to other groups. The Communications Medicine paper is not focused on issues of that sort but instead addresses problems that stem from biases and on ways to mitigate the adverse consequences. A group of 954 people (438 clinicians and 516 nonexperts) took part in an experiment to see how AI biases can affect decision-making. The participants were presented with call summaries from a fictitious crisis hotline, each involving a male individual undergoing a mental health emergency. The summaries contained information as to whether the individual was Caucasian or African American and would also mention his religion if he happened to be Muslim. A typical call summary might describe a circumstance in which an African American man was found at home in a delirious state, indicating that "he has not consumed any drugs or alcohol, as he is a practicing Muslim." Study participants were instructed to call the police if they thought the patient was likely to turn violent; otherwise, they were encouraged to seek medical help. The participants were randomly divided into a control or "baseline" group plus four other groups designed to test responses under slightly different conditions. "We want to understand how biased models can influence decisions, but we first need to understand how human biases can affect the decision-making process," Adam notes. What they found in their analysis of the baseline group was rather surprising: "In the setting we considered, human participants did not exhibit any biases. That doesn't mean that humans are not biased, but the way we conveyed information about a person's race and religion, evidently, was not strong enough to elicit their biases." The other four groups in the experiment were given advice that either came from a biased or unbiased model, and that advice was presented in either a "prescriptive" or a "descriptive" form. A biased model would be more likely to recommend police help in a situation involving an African American or Muslim person than would an unbiased model. Participants in the study, however, did not know which kind of model their advice came from, or even that models delivering the advice could be biased at all. Prescriptive advice spells out what a participant should do in unambiguous terms, telling them they should call the police in one instance or seek medical help in another. Descriptive advice is less direct: A flag is displayed to show that the AI system perceives a risk of violence associated with a particular call; no flag is shown if the threat of violence is deemed small. A key takeaway of the experiment is that participants "were highly influenced by prescriptive recommendations from a biased AI system," the authors wrote. But they also found that "using descriptive rather than prescriptive recommendations allowed participants to retain their original, unbiased decision-making." In other words, the bias incorporated within an AI model can be diminished by appropriately framing the advice that's rendered. Why the different outcomes, depending on how advice is posed? When someone is told to do something, like call the police, that leaves little room for doubt, Adam explains. However, when the situation is merely described—classified with or without the presence of a flag—"that leaves room for a participant's own interpretation; it allows them to be more flexible and consider the situation for themselves." Second, the researchers found that the language models that are typically used to offer advice are easy to bias. Language models represent a class of machine learning systems that are trained on text, such as the entire contents of Wikipedia and other web material. When these models are "fine-tuned" by relying on a much smaller subset of data for training purposes—just 2,000 sentences, as opposed to 8 million web pages—the resultant models can be readily biased. Third, the MIT team discovered that decision-makers who are themselves unbiased can still be misled by the recommendations provided by biased models. Medical training (or the lack thereof) did not change responses in a discernible way. "Clinicians were influenced by biased models as much as non-experts were," the authors stated. "These findings could be applicable to other settings," Adam says, and are not necessarily restricted to health care situations. When it comes to deciding which people should receive a job interview, a biased model could be more likely to turn down Black applicants. The results could be different, however, if instead of explicitly (and prescriptively) telling an employer to "reject this applicant," a descriptive flag is attached to the file to indicate the applicant's "possible lack of experience." The implications of this work are broader than just figuring out how to deal with individuals in the midst of mental health crises, Adam maintains. "Our ultimate goal is to make sure that machine learning models are used in a fair, safe, and robust way." <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 25837, 32499, 3495, 706, 6982, 430, 21075, 11478, 320, 15836, 8, 6067, 3629, 16559, 50183, 2403, 23413, 1207, 17171, 13, 4452, 11, 2697, 990, 706, 10968, 389, 5627, 311, 50460, 279, 11682, 68763, 26249, 649, 5353, 304, 1579, 5594, 2094, 5110, 1778, 439, 16088, 13, 19331, 763, 420, 4007, 11, 584, 9526, 750, 26126, 279, 5536, 48761, 15592, 19075, 617, 389, 13147, 11429, 11, 1405, 13324, 6013, 311, 10723, 2890, 58187, 555, 8260, 369, 3060, 6593, 477, 4379, 13291, 13, 1226, 45425, 220, 20596, 78545, 323, 220, 20571, 2536, 18882, 15916, 311, 16136, 304, 1057, 3566, 6108, 9526, 13, 1226, 26126, 25923, 5597, 28846, 449, 323, 2085, 9650, 505, 48761, 323, 74315, 15592, 6067, 13, 1226, 1101, 28830, 279, 1742, 315, 279, 15592, 9650, 11, 59049, 433, 3060, 439, 1685, 41419, 19075, 477, 53944, 8202, 13, 18591, 47476, 11429, 527, 74315, 2085, 15592, 9650, 13, 4452, 11, 2225, 78545, 323, 2536, 18882, 15916, 527, 28160, 555, 1685, 41419, 19075, 505, 264, 48761, 12384, 11, 19301, 4379, 1520, 810, 3629, 304, 69074, 16239, 11904, 24145, 477, 10451, 3026, 13, 76104, 34575, 11, 1701, 53944, 8202, 4856, 1109, 1685, 41419, 19075, 6276, 34281, 311, 14389, 872, 4113, 11, 74315, 5597, 28846, 13, 1221, 24436, 5751, 990, 32216, 279, 15325, 8137, 315, 1701, 48761, 4211, 304, 2890, 38697, 11, 323, 13533, 430, 36001, 59049, 5597, 1862, 649, 50460, 279, 6372, 315, 15592, 15837, 13, 4314, 14955, 2011, 387, 15884, 6646, 304, 279, 1690, 1972, 31184, 14830, 26350, 1405, 50504, 477, 48761, 4211, 1253, 387, 1511, 311, 6179, 3062, 11429, 13, 44299, 4221, 12399, 59294, 11478, 320, 15836, 8, 6067, 430, 1304, 11429, 3196, 389, 13970, 828, 527, 15098, 4279, 304, 2890, 2512, 5110, 13, 4452, 11, 1690, 15592, 4211, 31324, 36033, 50183, 11, 439, 828, 3629, 8881, 3823, 99876, 2403, 23413, 5315, 13, 763, 420, 4007, 11, 584, 1511, 264, 3566, 6108, 9526, 311, 15806, 279, 5536, 48761, 4211, 649, 617, 994, 1511, 311, 6179, 3823, 11429, 13, 1226, 1766, 430, 3582, 13324, 1051, 539, 49188, 48761, 11, 814, 1051, 16917, 28160, 555, 9650, 505, 264, 48761, 1646, 422, 433, 574, 9076, 1685, 1250, 3210, 320, 72, 1770, 2637, 1054, 9514, 1288, 656, 1630, 65312, 1115, 71628, 6197, 872, 11429, 311, 387, 48761, 2403, 11904, 24145, 323, 20071, 7931, 13, 4452, 11, 59049, 279, 1890, 9650, 951, 1250, 3210, 320, 72, 1770, 2637, 2085, 65774, 264, 3230, 1957, 8, 5535, 13324, 311, 7293, 6762, 13, 4314, 3135, 20461, 430, 3582, 68763, 15592, 649, 3063, 311, 8009, 20124, 369, 23413, 5315, 11, 36001, 59049, 9650, 649, 1520, 50460, 1202, 6372, 13, 29438, 13257, 6975, 320, 2735, 8, 323, 21075, 11478, 320, 15836, 8, 527, 15098, 1694, 1511, 311, 1862, 5597, 28846, 304, 264, 8205, 315, 2890, 2512, 8522, 220, 16, 1174, 220, 17, 662, 4452, 11, 279, 4754, 5536, 315, 61417, 15592, 304, 98882, 2890, 38697, 374, 539, 1664, 16365, 13, 1666, 1521, 7526, 43036, 349, 11, 433, 374, 16595, 311, 4007, 1268, 15592, 649, 387, 1511, 311, 7417, 6335, 6725, 80078, 994, 4211, 40605, 1304, 21294, 13, 35390, 990, 706, 21091, 430, 50504, 19075, 505, 15592, 6067, 649, 12207, 47293, 268, 279, 4367, 315, 14830, 6514, 11429, 220, 18, 1174, 220, 19, 662, 7089, 3495, 706, 6982, 430, 1524, 3582, 11909, 1253, 4510, 279, 4367, 315, 20187, 2427, 2116, 9650, 311, 387, 4827, 11, 814, 1501, 4528, 5990, 315, 1493, 439, 2536, 18882, 15916, 994, 10666, 449, 15465, 19075, 220, 20, 662, 74540, 1646, 10552, 2968, 323, 14532, 2968, 1587, 539, 9006, 420, 4360, 11, 323, 304, 1063, 5157, 11, 1253, 47293, 268, 3823, 5845, 311, 11388, 21294, 220, 21, 1174, 220, 22, 662, 4314, 3823, 6830, 40, 16628, 73021, 527, 5423, 18815, 304, 279, 2317, 315, 264, 2547, 315, 17649, 430, 706, 9749, 430, 20187, 4211, 3629, 31324, 50183, 2403, 19739, 11, 10026, 11, 323, 10597, 1207, 17171, 220, 23, 662, 20902, 4221, 4211, 1093, 426, 3481, 220, 24, 323, 480, 2898, 12, 18, 220, 605, 2001, 8370, 527, 8147, 323, 4228, 311, 10739, 2345, 327, 66917, 36033, 99876, 11, 1778, 439, 23135, 4501, 4189, 1113, 20071, 449, 9349, 304, 11914, 11733, 14723, 9256, 220, 806, 662, 7570, 27103, 315, 279, 426, 3481, 18112, 16572, 389, 12624, 8278, 82, 323, 14830, 8554, 4799, 8857, 5315, 304, 1690, 14830, 2320, 1171, 2538, 9256, 220, 717, 662, 6104, 3766, 990, 706, 9749, 1521, 50183, 11, 433, 374, 25420, 1268, 279, 5150, 1005, 315, 264, 48761, 1646, 2643, 7958, 5597, 28846, 304, 264, 15325, 2890, 2512, 6376, 13, 1115, 16628, 374, 5423, 16595, 311, 3619, 1457, 11, 439, 4221, 4211, 3240, 311, 387, 1511, 304, 2890, 8522, 1093, 2463, 425, 220, 1032, 323, 15419, 6369, 63005, 220, 975, 662, 763, 420, 4007, 11, 584, 26126, 279, 5536, 48761, 15592, 649, 617, 304, 264, 5597, 6376, 16239, 264, 10723, 2890, 13147, 13, 1226, 13375, 264, 3566, 6108, 9526, 449, 220, 25741, 14771, 291, 15223, 25, 220, 20596, 78545, 323, 220, 20571, 2536, 18882, 15916, 13, 1226, 1766, 430, 3582, 25923, 11429, 1051, 74315, 2085, 15592, 9650, 11, 814, 1051, 7701, 28160, 555, 1685, 41419, 19075, 505, 264, 48761, 15592, 1887, 13, 1115, 12384, 292, 71628, 3549, 19739, 323, 10597, 83057, 304, 872, 11429, 13, 4452, 11, 584, 1766, 430, 1701, 53944, 4856, 1109, 1685, 41419, 19075, 5535, 13324, 311, 14389, 872, 4113, 11, 74315, 5597, 28846, 13, 4314, 3135, 20461, 430, 3582, 1701, 68763, 15592, 304, 264, 26569, 2890, 6376, 649, 3063, 311, 8009, 20124, 369, 76820, 1207, 17171, 11, 36001, 59049, 1646, 9650, 649, 1520, 50460, 279, 16940, 15837, 315, 279, 15592, 1887, 13, 19331, 47476, 34102, 1226, 18306, 459, 22772, 5603, 311, 15806, 279, 5536, 430, 48761, 15592, 649, 617, 304, 264, 5597, 6376, 16239, 264, 10723, 2890, 13147, 13, 1226, 45425, 220, 20596, 78545, 323, 220, 20571, 2536, 18882, 15916, 311, 16136, 304, 1057, 9526, 11, 902, 574, 13375, 2930, 1555, 20143, 376, 1233, 1990, 3297, 220, 2366, 16, 323, 6790, 220, 2366, 16, 13, 18905, 9818, 1051, 45425, 555, 92801, 5687, 323, 11062, 520, 24461, 304, 279, 3723, 4273, 323, 7008, 11, 1418, 2536, 18882, 15916, 1051, 45425, 1555, 3674, 3772, 320, 21124, 11, 27728, 8, 323, 12374, 2613, 11725, 13, 763, 10365, 14771, 574, 12457, 505, 682, 13324, 13, 1115, 4007, 574, 39028, 505, 264, 2539, 31308, 3477, 555, 7432, 52, 39, 1600, 11, 279, 98984, 10506, 8925, 369, 279, 22108, 10181, 315, 12053, 320, 18836, 705, 1606, 433, 2322, 279, 13186, 369, 45798, 4613, 304, 12411, 19812, 220, 1774, 70921, 220, 2790, 13, 52878, 1051, 4691, 311, 4686, 264, 2875, 4686, 264, 2875, 38462, 10795, 1306, 27666, 279, 1925, 9526, 13, 1226, 63179, 1401, 25923, 63334, 304, 99371, 6771, 220, 16, 1174, 5217, 11193, 304, 99371, 6771, 220, 17, 1174, 323, 9400, 12734, 19440, 17910, 304, 99371, 6771, 220, 18, 662, 7181, 430, 584, 28544, 13324, 889, 20143, 376, 1233, 11054, 439, 50629, 11, 439, 1664, 439, 1884, 889, 33341, 1555, 1057, 10795, 320, 5589, 11218, 304, 1234, 220, 20, 1332, 570, 1226, 1101, 28544, 23329, 14847, 505, 279, 1890, 25923, 11, 902, 7108, 220, 868, 9400, 12734, 323, 220, 11727, 22, 2536, 18882, 531, 14847, 13, 57708, 2955, 52878, 1051, 6982, 264, 4101, 315, 8223, 1650, 70022, 311, 264, 89207, 65795, 11501, 92975, 11, 1855, 315, 902, 7633, 264, 8762, 3927, 25051, 264, 10723, 2890, 13147, 13, 763, 5369, 311, 49449, 922, 279, 6671, 11, 128257, 198, 128256, 78191, 198, 2181, 596, 912, 6367, 430, 1274, 57511, 50183, 2345, 15031, 40711, 11, 8530, 11, 323, 3885, 76699, 43661, 13, 578, 5578, 1732, 2643, 23289, 430, 19002, 2345, 55377, 1572, 11383, 1903, 315, 12466, 11, 9699, 11, 9168, 11, 51692, 11, 323, 5370, 37182, 83872, 1949, 315, 48786, 13, 6104, 430, 25329, 1253, 3412, 369, 6500, 12035, 11, 279, 1890, 374, 539, 2744, 837, 369, 6500, 3241, 11, 902, 374, 56168, 555, 4498, 1260, 12966, 323, 649, 387, 23114, 828, 430, 374, 11, 5196, 11, 44500, 304, 3738, 43666, 13, 59294, 11478, 320, 15836, 8, 6067, 2345, 54719, 3196, 389, 5780, 6975, 11, 304, 4040, 83872, 9298, 7319, 1005, 304, 16088, 369, 13493, 14759, 3230, 19338, 11, 369, 3187, 11, 477, 38663, 1630, 82817, 13, 4314, 6067, 527, 1101, 1694, 41013, 389, 311, 1862, 5597, 28846, 304, 1023, 5789, 315, 2890, 2512, 13, 35390, 3495, 706, 6982, 11, 4869, 11, 430, 5780, 6975, 4211, 649, 16559, 50183, 2403, 23413, 1207, 17171, 11, 323, 279, 19075, 814, 1304, 1253, 52394, 8881, 1884, 1890, 50183, 13, 362, 502, 4007, 555, 12074, 505, 15210, 596, 17863, 10170, 323, 59294, 22107, 32184, 320, 6546, 6093, 8, 323, 279, 15210, 93188, 301, 40324, 11, 902, 574, 4756, 1566, 2305, 304, 26545, 19152, 11, 8720, 288, 279, 5536, 430, 68763, 15592, 4211, 649, 617, 11, 5423, 369, 6067, 430, 527, 10825, 311, 3493, 9650, 304, 34771, 15082, 13, 330, 1687, 1766, 430, 279, 11827, 304, 902, 279, 9650, 374, 47093, 649, 617, 5199, 81909, 1359, 15100, 279, 5684, 596, 3063, 3229, 11, 9777, 1764, 329, 15387, 11, 264, 2405, 920, 13, 5575, 520, 15210, 596, 10181, 369, 2956, 15264, 323, 13581, 13, 330, 73055, 11, 279, 11682, 9057, 555, 48761, 4211, 649, 387, 7347, 320, 4636, 539, 14647, 34373, 8, 994, 279, 9650, 374, 10666, 304, 264, 2204, 1648, 1210, 578, 1023, 1080, 34603, 1105, 315, 279, 5684, 527, 362, 1768, 3458, 19984, 351, 454, 33383, 323, 35266, 1708, 25526, 7215, 11, 2225, 2405, 920, 13, 4236, 11, 323, 279, 45724, 74311, 6729, 3771, 689, 323, 2947, 4341, 2701, 480, 4752, 87698, 13, 15592, 4211, 1511, 304, 16088, 649, 7831, 505, 42025, 27121, 323, 92922, 11, 304, 961, 1606, 279, 828, 1511, 311, 5542, 279, 4211, 527, 3629, 539, 18740, 315, 1972, 31184, 5110, 13, 34496, 13124, 315, 1630, 30630, 12933, 11, 369, 2937, 11, 649, 3335, 2574, 22009, 323, 16472, 7692, 2204, 3135, 13, 27972, 16572, 35064, 2718, 389, 4251, 1274, 11, 44643, 11, 1253, 539, 387, 439, 13687, 994, 9435, 311, 1023, 5315, 13, 578, 26545, 19152, 5684, 374, 539, 10968, 389, 4819, 315, 430, 3460, 719, 4619, 14564, 5435, 430, 19646, 505, 50183, 323, 389, 5627, 311, 50460, 279, 31959, 16296, 13, 362, 1912, 315, 220, 25741, 1274, 320, 20596, 78545, 323, 220, 20571, 2536, 4683, 15916, 8, 3952, 961, 304, 459, 9526, 311, 1518, 1268, 15592, 50183, 649, 7958, 5597, 28846, 13, 578, 13324, 1051, 10666, 449, 1650, 70022, 505, 264, 89207, 65795, 11501, 92975, 11, 1855, 16239, 264, 8762, 3927, 47397, 264, 10723, 2890, 13147, 13, 578, 70022, 13282, 2038, 439, 311, 3508, 279, 3927, 574, 85519, 477, 11904, 3778, 323, 1053, 1101, 6420, 813, 13901, 422, 568, 7077, 311, 387, 10451, 13, 362, 14595, 1650, 12399, 2643, 7664, 264, 53237, 304, 902, 459, 11904, 3778, 893, 574, 1766, 520, 2162, 304, 264, 1624, 404, 1245, 1614, 11, 19392, 430, 330, 383, 706, 539, 27073, 904, 11217, 477, 13200, 11, 439, 568, 374, 264, 36666, 10451, 1210, 19723, 13324, 1051, 42075, 311, 1650, 279, 4379, 422, 814, 3463, 279, 8893, 574, 4461, 311, 2543, 16806, 26, 6062, 11, 814, 1051, 21190, 311, 6056, 6593, 1520, 13, 578, 13324, 1051, 27716, 18255, 1139, 264, 2585, 477, 330, 77058, 1, 1912, 5636, 3116, 1023, 5315, 6319, 311, 1296, 14847, 1234, 10284, 2204, 4787, 13, 330, 1687, 1390, 311, 3619, 1268, 48761, 4211, 649, 10383, 11429, 11, 719, 584, 1176, 1205, 311, 3619, 1268, 3823, 50183, 649, 7958, 279, 5597, 28846, 1920, 1359, 15387, 8554, 13, 3639, 814, 1766, 304, 872, 6492, 315, 279, 26954, 1912, 574, 4856, 15206, 25, 330, 644, 279, 6376, 584, 6646, 11, 3823, 13324, 1550, 539, 31324, 904, 50183, 13, 3011, 3250, 956, 3152, 430, 12966, 527, 539, 48761, 11, 719, 279, 1648, 584, 73897, 2038, 922, 264, 1732, 596, 7102, 323, 13901, 11, 67170, 11, 574, 539, 3831, 3403, 311, 658, 19195, 872, 50183, 1210, 578, 1023, 3116, 5315, 304, 279, 9526, 1051, 2728, 9650, 430, 3060, 3782, 505, 264, 48761, 477, 74315, 1646, 11, 323, 430, 9650, 574, 10666, 304, 3060, 264, 330, 24544, 41419, 1, 477, 264, 330, 5919, 41419, 1, 1376, 13, 362, 48761, 1646, 1053, 387, 810, 4461, 311, 7079, 4379, 1520, 304, 264, 6671, 16239, 459, 11904, 3778, 477, 10451, 1732, 1109, 1053, 459, 74315, 1646, 13, 52878, 304, 279, 4007, 11, 4869, 11, 1550, 539, 1440, 902, 3169, 315, 1646, 872, 9650, 3782, 505, 11, 477, 1524, 430, 4211, 24944, 279, 9650, 1436, 387, 48761, 520, 682, 13, 4203, 41419, 9650, 26701, 704, 1148, 264, 25923, 1288, 656, 304, 653, 91313, 3878, 11, 11890, 1124, 814, 1288, 1650, 279, 4379, 304, 832, 2937, 477, 6056, 6593, 1520, 304, 2500, 13, 3959, 41419, 9650, 374, 2753, 2167, 25, 362, 5292, 374, 12882, 311, 1501, 430, 279, 15592, 1887, 62822, 1924, 264, 5326, 315, 9349, 5938, 449, 264, 4040, 1650, 26, 912, 5292, 374, 6982, 422, 279, 6023, 315, 9349, 374, 25660, 2678, 13, 362, 1401, 89474, 315, 279, 9526, 374, 430, 13324, 330, 52898, 7701, 28160, 555, 1685, 41419, 19075, 505, 264, 48761, 15592, 1887, 1359, 279, 12283, 6267, 13, 2030, 814, 1101, 1766, 430, 330, 985, 53944, 4856, 1109, 1685, 41419, 19075, 5535, 13324, 311, 14389, 872, 4113, 11, 74315, 5597, 28846, 1210, 763, 1023, 4339, 11, 279, 15837, 32762, 2949, 459, 15592, 1646, 649, 387, 54182, 555, 36001, 59049, 279, 9650, 430, 596, 23188, 13, 8595, 279, 2204, 20124, 11, 11911, 389, 1268, 9650, 374, 37260, 30, 3277, 4423, 374, 3309, 311, 656, 2555, 11, 1093, 1650, 279, 4379, 11, 430, 11141, 2697, 3130, 369, 10712, 11, 15387, 15100, 13, 4452, 11, 994, 279, 6671, 374, 16632, 7633, 2345, 65974, 449, 477, 2085, 279, 9546, 315, 264, 5292, 93830, 9210, 11141, 3130, 369, 264, 25923, 596, 1866, 23692, 26, 433, 6276, 1124, 311, 387, 810, 19303, 323, 2980, 279, 6671, 369, 5694, 1210, 10657, 11, 279, 12074, 1766, 430, 279, 4221, 4211, 430, 527, 11383, 1511, 311, 3085, 9650, 527, 4228, 311, 15837, 13, 11688, 4211, 4097, 264, 538, 315, 5780, 6975, 6067, 430, 527, 16572, 389, 1495, 11, 1778, 439, 279, 4553, 8970, 315, 27685, 323, 1023, 3566, 3769, 13, 3277, 1521, 4211, 527, 330, 63157, 2442, 49983, 1, 555, 39661, 389, 264, 1790, 9333, 27084, 315, 828, 369, 4967, 10096, 2345, 4345, 220, 17, 11, 931, 23719, 11, 439, 16475, 311, 220, 23, 3610, 3566, 6959, 22416, 84913, 4211, 649, 387, 31368, 48761, 13, 21530, 11, 279, 15210, 2128, 11352, 430, 5597, 76170, 889, 527, 5694, 74315, 649, 2103, 387, 99525, 555, 279, 19075, 3984, 555, 48761, 4211, 13, 13235, 4967, 320, 269, 279, 6996, 34366, 8, 1550, 539, 2349, 14847, 304, 264, 42645, 1260, 1648, 13, 330, 68133, 9818, 1051, 28160, 555, 48761, 4211, 439, 1790, 439, 2536, 18882, 15916, 1051, 1359, 279, 12283, 11224, 13, 330, 9673, 14955, 1436, 387, 8581, 311, 1023, 5110, 1359, 15387, 2795, 11, 323, 527, 539, 14647, 22486, 311, 2890, 2512, 15082, 13, 3277, 433, 4131, 311, 30230, 902, 1274, 1288, 5371, 264, 2683, 7274, 11, 264, 48761, 1646, 1436, 387, 810, 4461, 311, 2543, 1523, 5348, 32177, 13, 578, 3135, 1436, 387, 2204, 11, 4869, 11, 422, 4619, 315, 21650, 320, 438, 1685, 1250, 3210, 8, 11890, 459, 19683, 311, 330, 48096, 420, 32368, 1359, 264, 53944, 5292, 374, 12673, 311, 279, 1052, 311, 13519, 279, 32368, 596, 330, 10236, 6996, 315, 3217, 1210, 578, 25127, 315, 420, 990, 527, 27927, 1109, 1120, 48309, 704, 1268, 311, 3568, 449, 7931, 304, 279, 35446, 315, 10723, 2890, 58187, 11, 15387, 33095, 13, 330, 8140, 17139, 5915, 374, 311, 1304, 2771, 430, 5780, 6975, 4211, 527, 1511, 304, 264, 6762, 11, 6220, 11, 323, 22514, 1648, 1210, 220, 128257, 198 ]

2,611

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Neuropil is a fundamental form of tissue organization within the brain 1 , in which densely packed neurons synaptically interconnect into precise circuit architecture 2 , 3 . However, the structural and developmental principles that govern this nanoscale precision remain largely unknown 4 , 5 . Here we use an iterative data coarse-graining algorithm termed ‘diffusion condensation’ 6 to identify nested circuit structures within the Caenorhabditis elegans neuropil, which is known as the nerve ring. We show that the nerve ring neuropil is largely organized into four strata that are composed of related behavioural circuits. The stratified architecture of the neuropil is a geometrical representation of the functional segregation of sensory information and motor outputs, with specific sensory organs and muscle quadrants mapping onto particular neuropil strata. We identify groups of neurons with unique morphologies that integrate information across strata and that create neural structures that cage the strata within the nerve ring. We use high resolution light-sheet microscopy 7 , 8 coupled with lineage-tracing and cell-tracking algorithms 9 , 10 to resolve the developmental sequence and reveal principles of cell position, migration and outgrowth that guide stratified neuropil organization. Our results uncover conserved structural design principles that underlie the architecture and function of the nerve ring neuropil, and reveal a temporal progression of outgrowth—based on pioneer neurons—that guides the hierarchical development of the layered neuropil. Our findings provide a systematic blueprint for using structural and developmental approaches to understand neuropil organization within the brain. Main To elucidate the structural and developmental principles that govern neuropil assembly, we examined the C. elegans nerve ring neuropil, a major site of neuronal integration that contains 181 of the 282 somatic neurons in the adult hermaphrodite 3 . The lineage, morphology and synaptic connectivity of all 181 neurons is known 3 , 11 . Network principles and circuit motifs 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 as well as cellular and molecular mechanisms of nerve ring formation 21 , 22 , 23 , 24 have been elucidated. However, we lack an understanding of the structural design principles that underlie the architecture and function of the nerve ring neuropil, and the developmental sequence that forms this functional structure. Quantitative analyses of neuropil organization To systematically dissect the organization of the nerve ring neuropil, we analysed previously segmented data 18 , 19 in which more than 100,000 instances of neurite–neurite contacts had been quantified for two published C. elegans electron microscopy neuropil datasets 3 (Fig. 1a ). We focused on contact profiles instead of synaptic connections to reveal both functional and structural neuropil relationships. Fig. 1: Computational detection of a hierarchical tree of neurite organization in the C. elegans neuropil. a , Pipeline for analyses of the C. elegans neuropil. We used published serial section electron microscopy (EM) data 3 and previously quantified neuron–neuron contacts 18 , 19 to generate an adjacency matrix, which was analysed by diffusion condensation (DC) 6 and visualized using C-PHATE 28 . L4 and adult worm outputs were quantitatively compared and stereotypical clusters and outliers identified. b , C-PHATE plot of diffusion condensation analysis for an L4 worm. Individual neurons are located at the edges of the graph and condense as they move towards the centre. The four clusters identified are individually coloured. C3 and C4 are more closely related than C1 and C2 (Extended Data Fig. 2a–d , Supplementary Videos 1 , 2 ). c , Top, volumetric reconstruction of the L4 C. elegans neuropil (from electron microscopy serial sections 3 ) with the four strata individually coloured. S1–S4 are stacked along the anterior–posterior axis, and S3 is basal to S4. Bottom, representations of individual strata (Extended Data Fig. 1c–h , Supplementary Video 3 ). d , Volumetric reconstruction of S1 perpendicular looping neurons (highlighted in red). A, anterior; D, dorsal. e , Schematic of d with the trajectory of S2 (in c ) through specific S1 loops. f , As e , but with the trajectories of S3 and S4. g , The looping structure formed by 32 of the 45 S1 neurons, with loops coloured according to encased strata (in c ) (Extended Data Fig. 4 , Supplementary Videos 4 , 5 ). Scale bars, 5 μm ( c , d ). Full size image We generated an adjacency matrix by summing all contact surface areas for each possible neuron pair, and applied a new diffusion condensation 6 (DC) clustering algorithm to iteratively cluster neurons on the basis of the quantitative similarity of the contact profile of each neuron (Fig. 1a ). Unlike other clustering algorithms 25 , 26 , 27 , diffusion condensation condenses data without assuming underlying data structure or forcing a k -way partition. At each iteration, diffusion condensation clusters the data by merging neurons that are within a threshold distance of each other. We then applied C-PHATE, an extension of the PHATE 28 visualization method, to generate an interactive 3D visualization of the iterative diffusion condensation clustering (Fig. 1a, b , Supplementary Methods). By iteratively condensing data points closer to their neighbours, DC/C-PHATE outputs dynamically unveil relationships among the data at varying scales of granularity, from cell–cell to circuit–circuit interactions. Quantitative comparisons of DC/C-PHATE outputs revealed similar—but not identical—clustering patterns between a larva stage 4 (L4) and an adult hermaphrodite nerve ring reconstruction (adjusted Rand index (ARI) of 0.7) (Extended Data Figs. 1a, b , 2f, m, n ), which is consistent with previous qualitative descriptions of the stereotyped C. elegans nerve ring 3 and with recent analyses of neurite adjacency differences 18 , 19 (Extended Data Fig. 2e ). Our quantitative analyses of the differences in diffusion condensation output between the larva and adult electron microscopy reconstructions also revealed that the differences were underpinned by biologically relevant changes that occur between these developmental stages (Extended Data Fig. 2a–f, q–s , Supplementary Discussion 3 ). The results of the diffusion condensation analysis of the contact profiles differed from those of the synaptic", "role": "user" }, { "content": "Understanding how the brain works is a paramount goal of medical science. But with its billions of tightly packed, intermingled neurons, the human brain is dauntingly difficult to visualize and map, which can provide the route to therapies for long-intractable disorders. In a major advance published next week in Nature, scientists for the first time report the structure of a fundamental type of tissue organization in brains, called neuropil, as well as the developmental pathways that lead to neuropil assembly in the roundworm C. elegans. This multidisciplinary study was a collaboration between five laboratories, including scientists at the Marine Biological Laboratory (MBL), Woods Hole, which hosted much of the collaboration. \"Neuropil is a tissue-level organization seen in many different types of brains, from worms to humans,\" says senior author and MBL Fellow Daniel Colón-Ramos of Yale School of Medicine. \"When things are that conserved in nature, they are important.\" \"But trying to understand neuropil structure and function is very challenging. It's like looking at a spaghetti bowl,\" Colón-Ramos says. \"Hundreds of neurons are on top of each other, touching each other, making thousands of choices as they intermingle through different sections of the animal's brain. How can you describe neuropil organization in a way that's comprehensible? That is one of the contributions of this paper.\" The authors focused on the neuropil in the C. elegans nerve ring, a tangled bundle of 181 neurons that serves as the worm's central processing unit. Through an innovative melding of network analysis and imaging strategies, they revealed that the nerve ring is organized into four layers, or strata. These strata, they showed, contain distinct domains for processing sensory information and motor behaviors. They were able to map the worm's sensory organs and muscle quadrants onto the relevant strata. The team also discovered unique neurons that integrate information across strata and build a type of \"cage\" around the layers. Finally, they showed how the layered structure of the neuropil emerges in the developing worm embryo, using high-resolution light-sheet microscopy developed by MBL Fellow Hari Shroff of the National Institute of Biomedical Imaging and Bioengineering, and MBL Investigator Abhishek Kumar. \"This is a paradigm shift where we combined two fields—computational biology and developmental biology—that don't often go together,\" says first author Mark Moyle, associate research scientist in neuroscience at Yale School of Medicine. \"We showed that by using computational approaches, we could understand the neuropil structure, and we could then use that knowledge to identify the developmental processes leading to the correct assembly of that structure.\" This approach can serve as a blueprint for understanding neuropil organization in other animal brains, the authors state. Volumetric reconstruction of the L4 C. elegans neuropil (from EM serial sections) with neurons from the four strata highlighted (S1-Red, S2-Purple, S3-Blue, S4-Green). Credit: Mark Moyle et al., Nature, 2021. From Buildings to Boroughs to New York City C. elegans has the best understood nervous system of all animals. More than 30 years ago, John White, Sydney Brenner, and colleagues published the worm's \"connectome\"—a wiring diagram of its 302 neurons and the ~7,000 synaptic connections between them. Since that pioneering study, nearly every neuron in C. elegans has been characterized: its shape, functional category, the neural circuits it participates in, and its developmental cell lineage. What was missing, though, was a picture of how these cells and circuits integrate in space and over time. Colón-Ramos and team analyzed published data on all the membrane contacts between the 181 neurons in the nerve ring. They then applied novel network analyses to group cells into \"neighborhoods\" based on their contact profiles—similar in principle to algorithms that Facebook uses to suggest friends based on people's common contacts. This revealed the neuropil's layered structure and enabled the team to understand cell-cell interactions in the context of functional circuits, and functional circuits in the context of higher-order neuropil structure (See video 1). \"All of a sudden, when you see the architecture, you realize that all this knowledge that was out there about the animal's behaviors has a home in the structure of the brain,\" Colón-Ramos says. \"By analogy, rather than just having knowledge of the East Side of New York and the West Side, Brooklyn and Queens, suddenly you see how the city fits together and you understand the relationships between the neighborhoods.\" \"So now we could see, 'OK, this is why these behaviors are reflex-like, because they are direct circuits that go into the muscles. And this is how they integrate with other parts of the motor program.' Having the structure allows you to generate new models regarding how information is being processed and parceled out to lead to behaviors,\" Colón-Ramos says. Time-lapse of the outgrowth dynamics of the C. elegans nerve ring followed by a 3D rotation of the last timepoint to highlight the neuropil, which is the bright ring structure in the anterior part of the embryo (top). Embryo twitches during later development. Neuropil intensity increases in overtime, probably due to an increase in the number of neurons entering the neuropil. Images are deconvolved diSPIM maximum intensity projections. Credit: Mark Moyle et al, Nature, 2021 Reconstructing the Birth and Development of the Nerve Ring The brain is a product of development, starting with one embryonic cell division and ending with a complete organ. \"An order emerges through time. So our next question was, how can you instruct the formation of a layered structure? How are all these decisions simultaneously occurring in hundreds of cells, but resulting in organized layers? How are the decisions coordinated through time and space?\" Colón-Ramos says. \"Layered structures are a fundamental unit of brain organization—the retina is a layer, and the cortex is a layer. If we could understand it for the worm, it would allow us to create models that might help us understand the development of layers in other vertebrate organs, like the eye,\" Colón-Ramos says. This part of the research began in 2014 when Colón-Ramos and Moyle began collaborating with microscope developers Shroff and Kumar at the MBL. \"We started by building a microscope (the diSPIM) that let us look at the embryo with better spatial and temporal resolution than the tools of the time,\" Shroff says. They then identified every cell in the C. elegans embryo using lineaging approaches developed by co-author Zhirong Bao of Sloan Kettering Institute (these findings are catalogued at WormGUIDES.org). \"This was a painful process, but very important to do,\" Shroff says. After years of sharing a lab at the MBL, numerous adjustments to the diSPIM system, integrations with other critically important technology, and plenty of frustration, the collaborators succeeded in resolving the developmental sequence of the C. elegans neuropil and revealing principles that guide its stratified organization (see video 2). \"This would have been impossible without the long-term, gentle imaging of the diSPIM,\" Colón-Ramos says. \"In developing the technology, many changes seemed incremental but in fact were very enabling, allowing us to do something we couldn't do before. Often the changes we needed fell between two disciplines with different vocabularies, and it required prolonged, focused, exhaustive conversations to identify them. That is what our collaboration at the MBL enabled.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Neuropil is a fundamental form of tissue organization within the brain 1 , in which densely packed neurons synaptically interconnect into precise circuit architecture 2 , 3 . However, the structural and developmental principles that govern this nanoscale precision remain largely unknown 4 , 5 . Here we use an iterative data coarse-graining algorithm termed ‘diffusion condensation’ 6 to identify nested circuit structures within the Caenorhabditis elegans neuropil, which is known as the nerve ring. We show that the nerve ring neuropil is largely organized into four strata that are composed of related behavioural circuits. The stratified architecture of the neuropil is a geometrical representation of the functional segregation of sensory information and motor outputs, with specific sensory organs and muscle quadrants mapping onto particular neuropil strata. We identify groups of neurons with unique morphologies that integrate information across strata and that create neural structures that cage the strata within the nerve ring. We use high resolution light-sheet microscopy 7 , 8 coupled with lineage-tracing and cell-tracking algorithms 9 , 10 to resolve the developmental sequence and reveal principles of cell position, migration and outgrowth that guide stratified neuropil organization. Our results uncover conserved structural design principles that underlie the architecture and function of the nerve ring neuropil, and reveal a temporal progression of outgrowth—based on pioneer neurons—that guides the hierarchical development of the layered neuropil. Our findings provide a systematic blueprint for using structural and developmental approaches to understand neuropil organization within the brain. Main To elucidate the structural and developmental principles that govern neuropil assembly, we examined the C. elegans nerve ring neuropil, a major site of neuronal integration that contains 181 of the 282 somatic neurons in the adult hermaphrodite 3 . The lineage, morphology and synaptic connectivity of all 181 neurons is known 3 , 11 . Network principles and circuit motifs 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 as well as cellular and molecular mechanisms of nerve ring formation 21 , 22 , 23 , 24 have been elucidated. However, we lack an understanding of the structural design principles that underlie the architecture and function of the nerve ring neuropil, and the developmental sequence that forms this functional structure. Quantitative analyses of neuropil organization To systematically dissect the organization of the nerve ring neuropil, we analysed previously segmented data 18 , 19 in which more than 100,000 instances of neurite–neurite contacts had been quantified for two published C. elegans electron microscopy neuropil datasets 3 (Fig. 1a ). We focused on contact profiles instead of synaptic connections to reveal both functional and structural neuropil relationships. Fig. 1: Computational detection of a hierarchical tree of neurite organization in the C. elegans neuropil. a , Pipeline for analyses of the C. elegans neuropil. We used published serial section electron microscopy (EM) data 3 and previously quantified neuron–neuron contacts 18 , 19 to generate an adjacency matrix, which was analysed by diffusion condensation (DC) 6 and visualized using C-PHATE 28 . L4 and adult worm outputs were quantitatively compared and stereotypical clusters and outliers identified. b , C-PHATE plot of diffusion condensation analysis for an L4 worm. Individual neurons are located at the edges of the graph and condense as they move towards the centre. The four clusters identified are individually coloured. C3 and C4 are more closely related than C1 and C2 (Extended Data Fig. 2a–d , Supplementary Videos 1 , 2 ). c , Top, volumetric reconstruction of the L4 C. elegans neuropil (from electron microscopy serial sections 3 ) with the four strata individually coloured. S1–S4 are stacked along the anterior–posterior axis, and S3 is basal to S4. Bottom, representations of individual strata (Extended Data Fig. 1c–h , Supplementary Video 3 ). d , Volumetric reconstruction of S1 perpendicular looping neurons (highlighted in red). A, anterior; D, dorsal. e , Schematic of d with the trajectory of S2 (in c ) through specific S1 loops. f , As e , but with the trajectories of S3 and S4. g , The looping structure formed by 32 of the 45 S1 neurons, with loops coloured according to encased strata (in c ) (Extended Data Fig. 4 , Supplementary Videos 4 , 5 ). Scale bars, 5 μm ( c , d ). Full size image We generated an adjacency matrix by summing all contact surface areas for each possible neuron pair, and applied a new diffusion condensation 6 (DC) clustering algorithm to iteratively cluster neurons on the basis of the quantitative similarity of the contact profile of each neuron (Fig. 1a ). Unlike other clustering algorithms 25 , 26 , 27 , diffusion condensation condenses data without assuming underlying data structure or forcing a k -way partition. At each iteration, diffusion condensation clusters the data by merging neurons that are within a threshold distance of each other. We then applied C-PHATE, an extension of the PHATE 28 visualization method, to generate an interactive 3D visualization of the iterative diffusion condensation clustering (Fig. 1a, b , Supplementary Methods). By iteratively condensing data points closer to their neighbours, DC/C-PHATE outputs dynamically unveil relationships among the data at varying scales of granularity, from cell–cell to circuit–circuit interactions. Quantitative comparisons of DC/C-PHATE outputs revealed similar—but not identical—clustering patterns between a larva stage 4 (L4) and an adult hermaphrodite nerve ring reconstruction (adjusted Rand index (ARI) of 0.7) (Extended Data Figs. 1a, b , 2f, m, n ), which is consistent with previous qualitative descriptions of the stereotyped C. elegans nerve ring 3 and with recent analyses of neurite adjacency differences 18 , 19 (Extended Data Fig. 2e ). Our quantitative analyses of the differences in diffusion condensation output between the larva and adult electron microscopy reconstructions also revealed that the differences were underpinned by biologically relevant changes that occur between these developmental stages (Extended Data Fig. 2a–f, q–s , Supplementary Discussion 3 ). The results of the diffusion condensation analysis of the contact profiles differed from those of the synaptic<|im_end|> <|im_start|>assistant Understanding how the brain works is a paramount goal of medical science. But with its billions of tightly packed, intermingled neurons, the human brain is dauntingly difficult to visualize and map, which can provide the route to therapies for long-intractable disorders. In a major advance published next week in Nature, scientists for the first time report the structure of a fundamental type of tissue organization in brains, called neuropil, as well as the developmental pathways that lead to neuropil assembly in the roundworm C. elegans. This multidisciplinary study was a collaboration between five laboratories, including scientists at the Marine Biological Laboratory (MBL), Woods Hole, which hosted much of the collaboration. "Neuropil is a tissue-level organization seen in many different types of brains, from worms to humans," says senior author and MBL Fellow Daniel Colón-Ramos of Yale School of Medicine. "When things are that conserved in nature, they are important." "But trying to understand neuropil structure and function is very challenging. It's like looking at a spaghetti bowl," Colón-Ramos says. "Hundreds of neurons are on top of each other, touching each other, making thousands of choices as they intermingle through different sections of the animal's brain. How can you describe neuropil organization in a way that's comprehensible? That is one of the contributions of this paper." The authors focused on the neuropil in the C. elegans nerve ring, a tangled bundle of 181 neurons that serves as the worm's central processing unit. Through an innovative melding of network analysis and imaging strategies, they revealed that the nerve ring is organized into four layers, or strata. These strata, they showed, contain distinct domains for processing sensory information and motor behaviors. They were able to map the worm's sensory organs and muscle quadrants onto the relevant strata. The team also discovered unique neurons that integrate information across strata and build a type of "cage" around the layers. Finally, they showed how the layered structure of the neuropil emerges in the developing worm embryo, using high-resolution light-sheet microscopy developed by MBL Fellow Hari Shroff of the National Institute of Biomedical Imaging and Bioengineering, and MBL Investigator Abhishek Kumar. "This is a paradigm shift where we combined two fields—computational biology and developmental biology—that don't often go together," says first author Mark Moyle, associate research scientist in neuroscience at Yale School of Medicine. "We showed that by using computational approaches, we could understand the neuropil structure, and we could then use that knowledge to identify the developmental processes leading to the correct assembly of that structure." This approach can serve as a blueprint for understanding neuropil organization in other animal brains, the authors state. Volumetric reconstruction of the L4 C. elegans neuropil (from EM serial sections) with neurons from the four strata highlighted (S1-Red, S2-Purple, S3-Blue, S4-Green). Credit: Mark Moyle et al., Nature, 2021. From Buildings to Boroughs to New York City C. elegans has the best understood nervous system of all animals. More than 30 years ago, John White, Sydney Brenner, and colleagues published the worm's "connectome"—a wiring diagram of its 302 neurons and the ~7,000 synaptic connections between them. Since that pioneering study, nearly every neuron in C. elegans has been characterized: its shape, functional category, the neural circuits it participates in, and its developmental cell lineage. What was missing, though, was a picture of how these cells and circuits integrate in space and over time. Colón-Ramos and team analyzed published data on all the membrane contacts between the 181 neurons in the nerve ring. They then applied novel network analyses to group cells into "neighborhoods" based on their contact profiles—similar in principle to algorithms that Facebook uses to suggest friends based on people's common contacts. This revealed the neuropil's layered structure and enabled the team to understand cell-cell interactions in the context of functional circuits, and functional circuits in the context of higher-order neuropil structure (See video 1). "All of a sudden, when you see the architecture, you realize that all this knowledge that was out there about the animal's behaviors has a home in the structure of the brain," Colón-Ramos says. "By analogy, rather than just having knowledge of the East Side of New York and the West Side, Brooklyn and Queens, suddenly you see how the city fits together and you understand the relationships between the neighborhoods." "So now we could see, 'OK, this is why these behaviors are reflex-like, because they are direct circuits that go into the muscles. And this is how they integrate with other parts of the motor program.' Having the structure allows you to generate new models regarding how information is being processed and parceled out to lead to behaviors," Colón-Ramos says. Time-lapse of the outgrowth dynamics of the C. elegans nerve ring followed by a 3D rotation of the last timepoint to highlight the neuropil, which is the bright ring structure in the anterior part of the embryo (top). Embryo twitches during later development. Neuropil intensity increases in overtime, probably due to an increase in the number of neurons entering the neuropil. Images are deconvolved diSPIM maximum intensity projections. Credit: Mark Moyle et al, Nature, 2021 Reconstructing the Birth and Development of the Nerve Ring The brain is a product of development, starting with one embryonic cell division and ending with a complete organ. "An order emerges through time. So our next question was, how can you instruct the formation of a layered structure? How are all these decisions simultaneously occurring in hundreds of cells, but resulting in organized layers? How are the decisions coordinated through time and space?" Colón-Ramos says. "Layered structures are a fundamental unit of brain organization—the retina is a layer, and the cortex is a layer. If we could understand it for the worm, it would allow us to create models that might help us understand the development of layers in other vertebrate organs, like the eye," Colón-Ramos says. This part of the research began in 2014 when Colón-Ramos and Moyle began collaborating with microscope developers Shroff and Kumar at the MBL. "We started by building a microscope (the diSPIM) that let us look at the embryo with better spatial and temporal resolution than the tools of the time," Shroff says. They then identified every cell in the C. elegans embryo using lineaging approaches developed by co-author Zhirong Bao of Sloan Kettering Institute (these findings are catalogued at WormGUIDES.org). "This was a painful process, but very important to do," Shroff says. After years of sharing a lab at the MBL, numerous adjustments to the diSPIM system, integrations with other critically important technology, and plenty of frustration, the collaborators succeeded in resolving the developmental sequence of the C. elegans neuropil and revealing principles that guide its stratified organization (see video 2). "This would have been impossible without the long-term, gentle imaging of the diSPIM," Colón-Ramos says. "In developing the technology, many changes seemed incremental but in fact were very enabling, allowing us to do something we couldn't do before. Often the changes we needed fell between two disciplines with different vocabularies, and it required prolonged, focused, exhaustive conversations to identify them. That is what our collaboration at the MBL enabled." <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 45950, 897, 321, 374, 264, 16188, 1376, 315, 20438, 7471, 2949, 279, 8271, 220, 16, 1174, 304, 902, 97617, 19937, 34313, 6925, 2756, 2740, 958, 6595, 1139, 24473, 16622, 18112, 220, 17, 1174, 220, 18, 662, 4452, 11, 279, 24693, 323, 48006, 16565, 430, 2633, 420, 20622, 437, 2296, 16437, 7293, 14090, 9987, 220, 19, 1174, 220, 20, 662, 5810, 584, 1005, 459, 87975, 828, 50347, 25313, 2101, 12384, 61937, 3451, 13798, 7713, 9955, 42725, 529, 220, 21, 311, 10765, 24997, 16622, 14726, 2949, 279, 14751, 99831, 10796, 18225, 285, 18190, 598, 98666, 321, 11, 902, 374, 3967, 439, 279, 32015, 10264, 13, 1226, 1501, 430, 279, 32015, 10264, 98666, 321, 374, 14090, 17057, 1139, 3116, 610, 460, 430, 527, 24306, 315, 5552, 88979, 46121, 13, 578, 44397, 1908, 18112, 315, 279, 98666, 321, 374, 264, 69086, 12381, 13340, 315, 279, 16003, 64244, 315, 49069, 2038, 323, 9048, 16674, 11, 449, 3230, 49069, 36853, 323, 16124, 30236, 1821, 13021, 8800, 4040, 98666, 321, 610, 460, 13, 1226, 10765, 5315, 315, 34313, 449, 5016, 27448, 9268, 430, 32172, 2038, 4028, 610, 460, 323, 430, 1893, 30828, 14726, 430, 36460, 279, 610, 460, 2949, 279, 32015, 10264, 13, 1226, 1005, 1579, 11175, 3177, 90066, 92914, 220, 22, 1174, 220, 23, 34356, 449, 65009, 10398, 4628, 323, 2849, 94949, 26249, 220, 24, 1174, 220, 605, 311, 9006, 279, 48006, 8668, 323, 16805, 16565, 315, 2849, 2361, 11, 12172, 323, 704, 74189, 430, 8641, 44397, 1908, 98666, 321, 7471, 13, 5751, 3135, 45063, 1615, 2841, 24693, 2955, 16565, 430, 1234, 11828, 279, 18112, 323, 734, 315, 279, 32015, 10264, 98666, 321, 11, 323, 16805, 264, 37015, 33824, 315, 704, 74189, 2345, 31039, 389, 54047, 34313, 41128, 28292, 279, 70994, 4500, 315, 279, 64241, 98666, 321, 13, 5751, 14955, 3493, 264, 37538, 54029, 369, 1701, 24693, 323, 48006, 20414, 311, 3619, 98666, 321, 7471, 2949, 279, 8271, 13, 4802, 2057, 97298, 349, 279, 24693, 323, 48006, 16565, 430, 2633, 98666, 321, 14956, 11, 584, 25078, 279, 356, 13, 18190, 598, 32015, 10264, 98666, 321, 11, 264, 3682, 2816, 315, 79402, 18052, 430, 5727, 220, 10562, 315, 279, 220, 16544, 1794, 780, 34313, 304, 279, 6822, 1077, 76, 1366, 24409, 635, 220, 18, 662, 578, 65009, 11, 79612, 323, 99827, 31357, 315, 682, 220, 10562, 34313, 374, 3967, 220, 18, 1174, 220, 806, 662, 8304, 16565, 323, 16622, 84989, 220, 717, 1174, 220, 1032, 1174, 220, 975, 1174, 220, 868, 1174, 220, 845, 1174, 220, 1114, 1174, 220, 972, 1174, 220, 777, 1174, 220, 508, 439, 1664, 439, 35693, 323, 31206, 24717, 315, 32015, 10264, 18488, 220, 1691, 1174, 220, 1313, 1174, 220, 1419, 1174, 220, 1187, 617, 1027, 97298, 660, 13, 4452, 11, 584, 6996, 459, 8830, 315, 279, 24693, 2955, 16565, 430, 1234, 11828, 279, 18112, 323, 734, 315, 279, 32015, 10264, 98666, 321, 11, 323, 279, 48006, 8668, 430, 7739, 420, 16003, 6070, 13, 32541, 22018, 29060, 315, 98666, 321, 7471, 2057, 60826, 75050, 279, 7471, 315, 279, 32015, 10264, 98666, 321, 11, 584, 67458, 8767, 86045, 828, 220, 972, 1174, 220, 777, 304, 902, 810, 1109, 220, 1041, 11, 931, 13422, 315, 21850, 635, 4235, 818, 324, 635, 19015, 1047, 1027, 10484, 1908, 369, 1403, 4756, 356, 13, 18190, 598, 17130, 92914, 98666, 321, 30525, 220, 18, 320, 30035, 13, 220, 16, 64, 7609, 1226, 10968, 389, 3729, 21542, 4619, 315, 99827, 13537, 311, 16805, 2225, 16003, 323, 24693, 98666, 321, 12135, 13, 23966, 13, 220, 16, 25, 93028, 18468, 315, 264, 70994, 5021, 315, 21850, 635, 7471, 304, 279, 356, 13, 18190, 598, 98666, 321, 13, 264, 1174, 42007, 369, 29060, 315, 279, 356, 13, 18190, 598, 98666, 321, 13, 1226, 1511, 4756, 6275, 3857, 17130, 92914, 320, 2783, 8, 828, 220, 18, 323, 8767, 10484, 1908, 49384, 4235, 818, 37190, 19015, 220, 972, 1174, 220, 777, 311, 7068, 459, 74949, 6303, 11, 902, 574, 67458, 555, 58430, 9955, 42725, 320, 5744, 8, 220, 21, 323, 9302, 1534, 1701, 356, 9483, 39, 2390, 220, 1591, 662, 445, 19, 323, 6822, 35311, 16674, 1051, 10484, 275, 8046, 7863, 323, 23473, 88167, 28066, 323, 87763, 11054, 13, 293, 1174, 356, 9483, 39, 2390, 7234, 315, 58430, 9955, 42725, 6492, 369, 459, 445, 19, 35311, 13, 30440, 34313, 527, 7559, 520, 279, 13116, 315, 279, 4876, 323, 9955, 1137, 439, 814, 3351, 7119, 279, 12541, 13, 578, 3116, 28066, 11054, 527, 32399, 58919, 13, 356, 18, 323, 356, 19, 527, 810, 15499, 5552, 1109, 356, 16, 323, 356, 17, 320, 54290, 2956, 23966, 13, 220, 17, 64, 4235, 67, 1174, 99371, 20114, 220, 16, 1174, 220, 17, 7609, 272, 1174, 7054, 11, 63920, 16743, 43738, 315, 279, 445, 19, 356, 13, 18190, 598, 98666, 321, 320, 1527, 17130, 92914, 6275, 14491, 220, 18, 883, 449, 279, 3116, 610, 460, 32399, 58919, 13, 328, 16, 4235, 50, 19, 527, 42415, 3235, 279, 37229, 4235, 2252, 14917, 8183, 11, 323, 328, 18, 374, 80710, 311, 328, 19, 13, 26821, 11, 44713, 315, 3927, 610, 460, 320, 54290, 2956, 23966, 13, 220, 16, 66, 4235, 71, 1174, 99371, 8519, 220, 18, 7609, 294, 1174, 650, 1152, 16743, 43738, 315, 328, 16, 77933, 63687, 34313, 320, 36298, 291, 304, 2579, 570, 362, 11, 37229, 26, 423, 11, 96146, 13, 384, 1174, 328, 82149, 315, 294, 449, 279, 35782, 315, 328, 17, 320, 258, 272, 883, 1555, 3230, 328, 16, 30853, 13, 282, 1174, 1666, 384, 1174, 719, 449, 279, 86648, 315, 328, 18, 323, 328, 19, 13, 342, 1174, 578, 63687, 6070, 14454, 555, 220, 843, 315, 279, 220, 1774, 328, 16, 34313, 11, 449, 30853, 58919, 4184, 311, 3289, 1503, 610, 460, 320, 258, 272, 883, 320, 54290, 2956, 23966, 13, 220, 19, 1174, 99371, 20114, 220, 19, 1174, 220, 20, 7609, 25635, 16283, 11, 220, 20, 33983, 76, 320, 272, 1174, 294, 7609, 8797, 1404, 2217, 1226, 8066, 459, 74949, 6303, 555, 2694, 5424, 682, 3729, 7479, 5789, 369, 1855, 3284, 49384, 6857, 11, 323, 9435, 264, 502, 58430, 9955, 42725, 220, 21, 320, 5744, 8, 59454, 12384, 311, 5480, 8046, 10879, 34313, 389, 279, 8197, 315, 279, 47616, 38723, 315, 279, 3729, 5643, 315, 1855, 49384, 320, 30035, 13, 220, 16, 64, 7609, 27140, 1023, 59454, 26249, 220, 914, 1174, 220, 1627, 1174, 220, 1544, 1174, 58430, 9955, 42725, 9955, 4377, 828, 2085, 26619, 16940, 828, 6070, 477, 25957, 264, 597, 482, 3195, 17071, 13, 2468, 1855, 20140, 11, 58430, 9955, 42725, 28066, 279, 828, 555, 54477, 34313, 430, 527, 2949, 264, 12447, 6138, 315, 1855, 1023, 13, 1226, 1243, 9435, 356, 9483, 39, 2390, 11, 459, 9070, 315, 279, 15001, 2390, 220, 1591, 42148, 1749, 11, 311, 7068, 459, 21416, 220, 18, 35, 42148, 315, 279, 87975, 58430, 9955, 42725, 59454, 320, 30035, 13, 220, 16, 64, 11, 293, 1174, 99371, 19331, 570, 3296, 5480, 8046, 9955, 49205, 828, 3585, 12401, 311, 872, 36956, 11, 11162, 11547, 9483, 39, 2390, 16674, 43111, 92131, 12135, 4315, 279, 828, 520, 29865, 29505, 315, 97097, 11, 505, 2849, 4235, 5997, 311, 16622, 4235, 66, 38368, 22639, 13, 32541, 22018, 36595, 315, 11162, 11547, 9483, 39, 2390, 16674, 10675, 4528, 38542, 539, 20086, 2345, 566, 37794, 12912, 1990, 264, 45555, 6723, 6566, 220, 19, 320, 43, 19, 8, 323, 459, 6822, 1077, 76, 1366, 24409, 635, 32015, 10264, 43738, 320, 88897, 24916, 1963, 320, 16412, 8, 315, 220, 15, 13, 22, 8, 320, 54290, 2956, 435, 14801, 13, 220, 16, 64, 11, 293, 1174, 220, 17, 69, 11, 296, 11, 308, 7026, 902, 374, 13263, 449, 3766, 62129, 28887, 315, 279, 23473, 354, 33601, 356, 13, 18190, 598, 32015, 10264, 220, 18, 323, 449, 3293, 29060, 315, 21850, 635, 74949, 12062, 220, 972, 1174, 220, 777, 320, 54290, 2956, 23966, 13, 220, 17, 68, 7609, 5751, 47616, 29060, 315, 279, 12062, 304, 58430, 9955, 42725, 2612, 1990, 279, 45555, 6723, 323, 6822, 17130, 92914, 16456, 20232, 1101, 10675, 430, 279, 12062, 1051, 1234, 79, 21203, 555, 6160, 30450, 9959, 4442, 430, 12446, 1990, 1521, 48006, 18094, 320, 54290, 2956, 23966, 13, 220, 17, 64, 4235, 69, 11, 2874, 4235, 82, 1174, 99371, 36613, 220, 18, 7609, 578, 3135, 315, 279, 58430, 9955, 42725, 6492, 315, 279, 3729, 21542, 89075, 505, 1884, 315, 279, 99827, 128257, 198, 128256, 78191, 198, 71251, 1268, 279, 8271, 4375, 374, 264, 74510, 5915, 315, 6593, 8198, 13, 2030, 449, 1202, 33151, 315, 40069, 19937, 11, 958, 5424, 839, 34313, 11, 279, 3823, 8271, 374, 57697, 398, 5107, 311, 51187, 323, 2472, 11, 902, 649, 3493, 279, 6149, 311, 52312, 369, 1317, 3502, 2193, 481, 24673, 13, 763, 264, 3682, 12178, 4756, 1828, 2046, 304, 22037, 11, 14248, 369, 279, 1176, 892, 1934, 279, 6070, 315, 264, 16188, 955, 315, 20438, 7471, 304, 35202, 11, 2663, 98666, 321, 11, 439, 1664, 439, 279, 48006, 44014, 430, 3063, 311, 98666, 321, 14956, 304, 279, 4883, 56741, 356, 13, 18190, 598, 13, 1115, 64486, 3510, 44550, 4007, 574, 264, 20632, 1990, 4330, 70760, 11, 2737, 14248, 520, 279, 23820, 63711, 32184, 320, 8578, 43, 705, 35848, 52029, 11, 902, 21685, 1790, 315, 279, 20632, 13, 330, 8989, 84, 897, 321, 374, 264, 20438, 11852, 7471, 3970, 304, 1690, 2204, 4595, 315, 35202, 11, 505, 63000, 311, 12966, 1359, 2795, 10195, 3229, 323, 386, 9574, 37946, 15469, 4349, 3244, 11151, 10808, 315, 44552, 6150, 315, 19152, 13, 330, 4599, 2574, 527, 430, 1615, 2841, 304, 7138, 11, 814, 527, 3062, 1210, 330, 4071, 4560, 311, 3619, 98666, 321, 6070, 323, 734, 374, 1633, 17436, 13, 1102, 596, 1093, 3411, 520, 264, 88010, 19763, 1359, 4349, 3244, 11151, 10808, 2795, 13, 330, 91722, 315, 34313, 527, 389, 1948, 315, 1855, 1023, 11, 31687, 1855, 1023, 11, 3339, 9214, 315, 11709, 439, 814, 958, 76, 2222, 1555, 2204, 14491, 315, 279, 10065, 596, 8271, 13, 2650, 649, 499, 7664, 98666, 321, 7471, 304, 264, 1648, 430, 596, 12963, 37864, 30, 3011, 374, 832, 315, 279, 19564, 315, 420, 5684, 1210, 578, 12283, 10968, 389, 279, 98666, 321, 304, 279, 356, 13, 18190, 598, 32015, 10264, 11, 264, 93941, 13190, 315, 220, 10562, 34313, 430, 17482, 439, 279, 35311, 596, 8792, 8863, 5089, 13, 17331, 459, 18699, 71530, 287, 315, 4009, 6492, 323, 32758, 15174, 11, 814, 10675, 430, 279, 32015, 10264, 374, 17057, 1139, 3116, 13931, 11, 477, 610, 460, 13, 4314, 610, 460, 11, 814, 8710, 11, 6782, 12742, 31576, 369, 8863, 49069, 2038, 323, 9048, 28198, 13, 2435, 1051, 3025, 311, 2472, 279, 35311, 596, 49069, 36853, 323, 16124, 30236, 1821, 8800, 279, 9959, 610, 460, 13, 578, 2128, 1101, 11352, 5016, 34313, 430, 32172, 2038, 4028, 610, 460, 323, 1977, 264, 955, 315, 330, 66, 425, 1, 2212, 279, 13931, 13, 17830, 11, 814, 8710, 1268, 279, 64241, 6070, 315, 279, 98666, 321, 59696, 304, 279, 11469, 35311, 87701, 11, 1701, 1579, 64036, 3177, 90066, 92914, 8040, 555, 386, 9574, 37946, 98545, 1443, 299, 544, 315, 279, 5165, 10181, 315, 12371, 61860, 65606, 323, 24432, 99015, 11, 323, 386, 9574, 33180, 859, 3765, 26301, 92180, 41240, 13, 330, 2028, 374, 264, 49340, 6541, 1405, 584, 11093, 1403, 5151, 2345, 66047, 1697, 34458, 323, 48006, 34458, 41128, 1541, 956, 3629, 733, 3871, 1359, 2795, 1176, 3229, 4488, 6178, 982, 11, 22712, 3495, 28568, 304, 93048, 520, 44552, 6150, 315, 19152, 13, 330, 1687, 8710, 430, 555, 1701, 55580, 20414, 11, 584, 1436, 3619, 279, 98666, 321, 6070, 11, 323, 584, 1436, 1243, 1005, 430, 6677, 311, 10765, 279, 48006, 11618, 6522, 311, 279, 4495, 14956, 315, 430, 6070, 1210, 1115, 5603, 649, 8854, 439, 264, 54029, 369, 8830, 98666, 321, 7471, 304, 1023, 10065, 35202, 11, 279, 12283, 1614, 13, 650, 1152, 16743, 43738, 315, 279, 445, 19, 356, 13, 18190, 598, 98666, 321, 320, 1527, 17329, 6275, 14491, 8, 449, 34313, 505, 279, 3116, 610, 460, 27463, 320, 50, 16, 12, 6161, 11, 328, 17, 9483, 36805, 11, 328, 18, 12, 10544, 11, 328, 19, 12279, 4542, 570, 16666, 25, 4488, 6178, 982, 1880, 453, 2637, 22037, 11, 220, 2366, 16, 13, 5659, 74248, 311, 85303, 82, 311, 1561, 4356, 4409, 356, 13, 18190, 598, 706, 279, 1888, 16365, 23418, 1887, 315, 682, 10099, 13, 4497, 1109, 220, 966, 1667, 4227, 11, 3842, 5929, 11, 21972, 44808, 1215, 11, 323, 18105, 4756, 279, 35311, 596, 330, 6595, 638, 66101, 64, 19358, 13861, 315, 1202, 220, 13121, 34313, 323, 279, 4056, 22, 11, 931, 99827, 13537, 1990, 1124, 13, 8876, 430, 71674, 4007, 11, 7154, 1475, 49384, 304, 356, 13, 18190, 598, 706, 1027, 32971, 25, 1202, 6211, 11, 16003, 5699, 11, 279, 30828, 46121, 433, 91287, 304, 11, 323, 1202, 48006, 2849, 65009, 13, 3639, 574, 7554, 11, 3582, 11, 574, 264, 6945, 315, 1268, 1521, 7917, 323, 46121, 32172, 304, 3634, 323, 927, 892, 13, 4349, 3244, 11151, 10808, 323, 2128, 30239, 4756, 828, 389, 682, 279, 39654, 19015, 1990, 279, 220, 10562, 34313, 304, 279, 32015, 10264, 13, 2435, 1243, 9435, 11775, 4009, 29060, 311, 1912, 7917, 1139, 330, 37569, 5812, 82, 1, 3196, 389, 872, 3729, 21542, 2345, 65387, 304, 17966, 311, 26249, 430, 5690, 5829, 311, 4284, 4885, 3196, 389, 1274, 596, 4279, 19015, 13, 1115, 10675, 279, 98666, 321, 596, 64241, 6070, 323, 9147, 279, 2128, 311, 3619, 2849, 33001, 22639, 304, 279, 2317, 315, 16003, 46121, 11, 323, 16003, 46121, 304, 279, 2317, 315, 5190, 24747, 98666, 321, 6070, 320, 10031, 2835, 220, 16, 570, 330, 2460, 315, 264, 11210, 11, 994, 499, 1518, 279, 18112, 11, 499, 13383, 430, 682, 420, 6677, 430, 574, 704, 1070, 922, 279, 10065, 596, 28198, 706, 264, 2162, 304, 279, 6070, 315, 279, 8271, 1359, 4349, 3244, 11151, 10808, 2795, 13, 330, 1383, 56203, 11, 4856, 1109, 1120, 3515, 6677, 315, 279, 6460, 17072, 315, 1561, 4356, 323, 279, 4410, 17072, 11, 26832, 323, 28162, 11, 15187, 499, 1518, 1268, 279, 3363, 18809, 3871, 323, 499, 3619, 279, 12135, 1990, 279, 33100, 1210, 330, 4516, 1457, 584, 1436, 1518, 11, 364, 4012, 11, 420, 374, 3249, 1521, 28198, 527, 33766, 12970, 11, 1606, 814, 527, 2167, 46121, 430, 733, 1139, 279, 24569, 13, 1628, 420, 374, 1268, 814, 32172, 449, 1023, 5596, 315, 279, 9048, 2068, 3238, 20636, 279, 6070, 6276, 499, 311, 7068, 502, 4211, 9002, 1268, 2038, 374, 1694, 15590, 323, 1370, 34283, 704, 311, 3063, 311, 28198, 1359, 4349, 3244, 11151, 10808, 2795, 13, 4212, 2922, 7629, 315, 279, 704, 74189, 30295, 315, 279, 356, 13, 18190, 598, 32015, 10264, 8272, 555, 264, 220, 18, 35, 12984, 315, 279, 1566, 892, 2837, 311, 11415, 279, 98666, 321, 11, 902, 374, 279, 10107, 10264, 6070, 304, 279, 37229, 961, 315, 279, 87701, 320, 3565, 570, 30227, 97234, 4483, 26286, 2391, 3010, 4500, 13, 45950, 897, 321, 21261, 12992, 304, 39599, 11, 4762, 4245, 311, 459, 5376, 304, 279, 1396, 315, 34313, 16661, 279, 98666, 321, 13, 12041, 527, 409, 12296, 8905, 1891, 4695, 1829, 7340, 21261, 41579, 13, 16666, 25, 4488, 6178, 982, 1880, 453, 11, 22037, 11, 220, 2366, 16, 1050, 7750, 287, 279, 36127, 323, 11050, 315, 279, 452, 5976, 22249, 578, 8271, 374, 264, 2027, 315, 4500, 11, 6041, 449, 832, 44481, 14338, 2849, 13096, 323, 13696, 449, 264, 4686, 2942, 13, 330, 2127, 2015, 59696, 1555, 892, 13, 2100, 1057, 1828, 3488, 574, 11, 1268, 649, 499, 21745, 279, 18488, 315, 264, 64241, 6070, 30, 2650, 527, 682, 1521, 11429, 25291, 31965, 304, 11758, 315, 7917, 11, 719, 13239, 304, 17057, 13931, 30, 2650, 527, 279, 11429, 47672, 1555, 892, 323, 3634, 7673, 4349, 3244, 11151, 10808, 2795, 13, 330, 9368, 291, 14726, 527, 264, 16188, 5089, 315, 8271, 7471, 22416, 84827, 374, 264, 6324, 11, 323, 279, 49370, 374, 264, 6324, 13, 1442, 584, 1436, 3619, 433, 369, 279, 35311, 11, 433, 1053, 2187, 603, 311, 1893, 4211, 430, 2643, 1520, 603, 3619, 279, 4500, 315, 13931, 304, 1023, 67861, 65216, 36853, 11, 1093, 279, 8071, 1359, 4349, 3244, 11151, 10808, 2795, 13, 1115, 961, 315, 279, 3495, 6137, 304, 220, 679, 19, 994, 4349, 3244, 11151, 10808, 323, 6178, 982, 6137, 73301, 449, 73757, 13707, 1443, 299, 544, 323, 41240, 520, 279, 386, 9574, 13, 330, 1687, 3940, 555, 4857, 264, 73757, 320, 1820, 1891, 4695, 1829, 8, 430, 1095, 603, 1427, 520, 279, 87701, 449, 2731, 29079, 323, 37015, 11175, 1109, 279, 7526, 315, 279, 892, 1359, 1443, 299, 544, 2795, 13, 2435, 1243, 11054, 1475, 2849, 304, 279, 356, 13, 18190, 598, 87701, 1701, 1584, 4210, 20414, 8040, 555, 1080, 43802, 1901, 30728, 647, 426, 3524, 315, 94193, 735, 22120, 287, 10181, 320, 45010, 14955, 527, 16808, 3340, 520, 74130, 42878, 1600, 2726, 570, 330, 2028, 574, 264, 26175, 1920, 11, 719, 1633, 3062, 311, 656, 1359, 1443, 299, 544, 2795, 13, 4740, 1667, 315, 11821, 264, 10278, 520, 279, 386, 9574, 11, 12387, 34074, 311, 279, 1891, 4695, 1829, 1887, 11, 8936, 811, 449, 1023, 41440, 3062, 5557, 11, 323, 11510, 315, 33086, 11, 279, 79119, 26399, 304, 53583, 279, 48006, 8668, 315, 279, 356, 13, 18190, 598, 98666, 321, 323, 31720, 16565, 430, 8641, 1202, 44397, 1908, 7471, 320, 4151, 2835, 220, 17, 570, 330, 2028, 1053, 617, 1027, 12266, 2085, 279, 1317, 9860, 11, 22443, 32758, 315, 279, 1891, 4695, 1829, 1359, 4349, 3244, 11151, 10808, 2795, 13, 330, 644, 11469, 279, 5557, 11, 1690, 4442, 9508, 53399, 719, 304, 2144, 1051, 1633, 28462, 11, 10923, 603, 311, 656, 2555, 584, 7846, 956, 656, 1603, 13, 36016, 279, 4442, 584, 4460, 11299, 1990, 1403, 49255, 449, 2204, 24757, 1299, 552, 11, 323, 433, 2631, 44387, 11, 10968, 11, 73603, 21633, 311, 10765, 1124, 13, 3011, 374, 1148, 1057, 20632, 520, 279, 386, 9574, 9147, 1210, 220, 128257, 198 ]

2,972

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Glass is inherently unstable to crystallization. However, how this transformation occurs while the dynamics in the glass stay frozen at the particle scale is poorly understood. Here, through single-particle-resolved imaging experiments, we show that due to frozen-in density inhomogeneities, a soft colloidal glass crystallizes via two distinct pathways. In the poorly packed regions of the glass, crystallinity grew smoothly due to local particle shuffles, whereas in the well-packed regions, we observed abrupt jumps in crystallinity that were triggered by avalanches—cooperative rearrangements involving many tens of particles. Importantly, we show that softness—a structural-order parameter determined through machine-learning methods—not only predicts where crystallization initiates in a glass but is also sensitive to the crystallization pathway. Such a causal connection between the structure and stability of a glass has so far remained elusive. Devising strategies to manipulate softness may thus prove invaluable in realizing long-lived glassy states. Main Elucidating the microscopic underpinnings of devitrification—the transformation of a glass to a crystal—besides being of fundamental interest in many branches of science 1 , 2 , 3 , 4 , 5 , is essential for the formulation of stable glasses that find numerous applications in industry 6 , 7 . Unlike the more conventional process of crystallization from a supercooled liquid 8 , 9 , 10 , 11 , 12 , 13 , which requires macroscopic particle diffusion, the pathways through which a system that is structurally arrested at the particle scale crystallizes remain unclear, largely due to the slow and seemingly stochastic nature of the dynamics 14 , 15 . In a system of monodisperse hard spheres, simulations 14 have found that crystallization in poorly annealed glasses began soon after quench and was autocatalytic: local particle shuffles, without cage-breaking, helped transform amorphous regions into compact crystals that subsequently enhanced mobility in nearby regions, thus creating a positive feedback that aided further growth. Conversely, simulations on well-annealed/mature hard-sphere glasses have uncovered a qualitatively different behaviour 15 , 16 , 17 , 18 . Long quiescent periods were interspersed with abrupt increases in crystallinity, and these jumps were concurrent with avalanches in nearby regions, in which many tens to a few hundred particles participated in cooperative rearrangements. Avalanche particles underwent displacements about a third of their size, and these were mostly not the ones that crystallized. Since avalanches occurred even in a polydisperse system, where crystallization was well suppressed, it was concluded that avalanches mediate crystallization, and not vice versa. This crystallization pathway has now been found in simulations of glasses with Lennard-Jones 17 and soft 18 particle interactions as well. Some of these studies also found that devitrification is linked to the underlying structure. Not only does crystallization preferentially occur in regions that already possess a form of partial order called medium-range crystalline order (MRCO) 15 , 17 , avalanches themselves were found to be spatially correlated with ‘soft spots’: regions where rearrangements are likely to occur in a glass 19 . In fact, simulations have found avalanche initiator particles with lower values of local density and bond-orientational order than the rest of the system 17 . A correlation between structural and dynamical heterogeneities and crystal nucleation has indeed been found in scattering experiments on deeply supercooled colloidal hard-sphere liquids 20 . However, in these studies, no crystallization was seen in the glassy regime. Never has devitrification been directly observed in experiments at the single-particle level. Direct imaging of this process is not possible in atomic and molecular systems. While micrometre colloidal hard spheres have proven invaluable as experimental models in probing many condensed-matter phenomena 12 , 13 , in the context of devitrification, this is not the system of choice. Avalanches are thought to help the system navigate from metabasin to metabasin 21 , and because these transitions are rare events, capturing them already requires long and continuous imaging experiments. In hard spheres, where particles cannot overlap, numerical studies have found that avalanches are even rarer than in soft spheres where some small degree of overlap is possible 18 . The crystallization mechanism, nevertheless, was identical in both of these systems. Guided by these observations, here, we investigate the devitrification of colloidal glasses made of micrometre monodisperse soft particles. To capture the elusive avalanche events, we performed particle-resolved confocal microscope imaging of large systems for long times. In our two-dimensional (2D) imaging experiments, a horizontal slice in the bulk of the three-dimensional (3D) glass sample contained at least N ≈ 10 4 particles (depending on the particle volume fraction ϕ ), while in our 3D experiments, we imaged in excess of N ≈ 6 × 10 4 particles (see Materials and methods). Our experiments typically spanned 5 × 10 5 τ B to 2 × 10 6 τ B , where \${\\tau }_{{\\mathrm{B}}}=\\frac{{\\sigma }^{3}\\uppi \\eta }{8{k}_{{\\mathrm{B}}}T}\$ is the Brownian time of a freely diffusing particle. Here, η is the solvent viscosity, k B is the Boltzmann constant, T is the temperature and σ is the diameter of the particle. Even though soft inter-particle interactions probably hasten devitrification 18 , both the system size studied and the experiment duration exceeded simulations, even on hard spheres 15 , 17 . Since there can be appreciable particle overlap in soft spheres, the glass transition volume fraction in these systems is larger than in colloidal hard spheres. Recent experiments and simulations on soft colloids have identified a critical volume fraction, ϕ o , below which the structural relaxation time, τ α , grows in a manner identical to that in liquids of hard spheres 22 , 23 . Where these two systems differ is for ϕ ≥ ϕ o . In this regime, τ α is infinite for the hard-sphere case, while for soft spheres, it remains finite and grows weakly with ϕ due to intermittent internal stress relaxation events 23 . While there is as yet no consensus on whether ϕ o corresponds to the glass or the jamming transition of soft spheres 22 , the operational definition of a glass transition defined in ref. 23", "role": "user" }, { "content": "Glass is amorphous in nature—its atomic structure does not involve the repetitive arrangement seen in crystalline materials. But occasionally, it undergoes a process called devitrification, which is the transformation of a glass into a crystal—often an unwanted process in industries. The dynamics of devitrification remain poorly understood because the process can be extremely slow, spanning decades or more. Now, a team of researchers led by Rajesh Ganapathy, Associate Professor at the Jawaharlal Nehru Center for Advanced Scientific Research (JNCASR), in collaboration with Ajay Sood, DST Year of Science Chair and Professor at the Indian Institute of Science (IISc), and their Ph.D. student Divya Ganapathi (IISc) has visualized devitrification for the first time in experiments. The results of this study have been published in Nature Physics. \"The trick was to work with a glass made of colloidal particles. Since each colloidal particle can be thought of as a substitute for a single atom, but being ten thousand times bigger than the atom, its dynamics can be watched in real-time with an optical microscope. Also, to hasten the process we tweaked the interaction between particles so that it is soft and rearrangements in the glass occurred frequently,\" says Divya Ganapathi. In order to make a glass, Divya Ganapathi and the team jammed the colloids together to reach high densities. The researchers observed different regions of the glass following two routes to crystallization: an avalanche-mediated route involving rapid rearrangements in the structure, and a smooth growth route with rearrangements happening gradually over time. To gain insights into these findings, the researchers then used machine learning methods to determine if there was some subtle structural feature hidden in the glass that apriori decides which regions would later crystallize and through what route. Despite the glass being disordered, the machine learning model was able to identify a structural feature called \"softness\" that had earlier been found to decide which particles in the glass rearrange and which do not. The researchers then found that regions in the glass which had particle clusters with large \"softness\" values were the ones that crystallized and that \"softness\" was also sensitive to the crystallization route. Perhaps the most striking finding emerging from the study was that the authors fed their machine learning model pictures of a colloidal glass and the model accurately predicted the regions that crystallized days in advance. \"This paves the way for a powerful technique to identify and tune 'softness' well in advance and avoid devitrification,\" says Ajay Sood. Understanding devitrification is crucial in areas like the pharmaceutical industry, which strives to produce stable amorphous drugs as they dissolve faster in the body than their crystalline counterparts. Even liquid nuclear waste is vitrified as a solid in a glass matrix to safely dispose it of deep underground and prevent hazardous materials from leaking into the environment. The authors believe that this study is a significant step forward in understanding the connection between the underlying structure and stability of glass. \"It is really cool that a machine learning algorithm can predict where the glass is going to crystallize and where it is going to stay glassy. This could be the initial step for designing more stable glasses like the gorilla glass on mobile phones, which is ubiquitous in modern technology,\" says Rajesh Ganapathy. The ability to manipulate structural parameters could usher in new ways to realize technologically significant long-lived glassy states. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Glass is inherently unstable to crystallization. However, how this transformation occurs while the dynamics in the glass stay frozen at the particle scale is poorly understood. Here, through single-particle-resolved imaging experiments, we show that due to frozen-in density inhomogeneities, a soft colloidal glass crystallizes via two distinct pathways. In the poorly packed regions of the glass, crystallinity grew smoothly due to local particle shuffles, whereas in the well-packed regions, we observed abrupt jumps in crystallinity that were triggered by avalanches—cooperative rearrangements involving many tens of particles. Importantly, we show that softness—a structural-order parameter determined through machine-learning methods—not only predicts where crystallization initiates in a glass but is also sensitive to the crystallization pathway. Such a causal connection between the structure and stability of a glass has so far remained elusive. Devising strategies to manipulate softness may thus prove invaluable in realizing long-lived glassy states. Main Elucidating the microscopic underpinnings of devitrification—the transformation of a glass to a crystal—besides being of fundamental interest in many branches of science 1 , 2 , 3 , 4 , 5 , is essential for the formulation of stable glasses that find numerous applications in industry 6 , 7 . Unlike the more conventional process of crystallization from a supercooled liquid 8 , 9 , 10 , 11 , 12 , 13 , which requires macroscopic particle diffusion, the pathways through which a system that is structurally arrested at the particle scale crystallizes remain unclear, largely due to the slow and seemingly stochastic nature of the dynamics 14 , 15 . In a system of monodisperse hard spheres, simulations 14 have found that crystallization in poorly annealed glasses began soon after quench and was autocatalytic: local particle shuffles, without cage-breaking, helped transform amorphous regions into compact crystals that subsequently enhanced mobility in nearby regions, thus creating a positive feedback that aided further growth. Conversely, simulations on well-annealed/mature hard-sphere glasses have uncovered a qualitatively different behaviour 15 , 16 , 17 , 18 . Long quiescent periods were interspersed with abrupt increases in crystallinity, and these jumps were concurrent with avalanches in nearby regions, in which many tens to a few hundred particles participated in cooperative rearrangements. Avalanche particles underwent displacements about a third of their size, and these were mostly not the ones that crystallized. Since avalanches occurred even in a polydisperse system, where crystallization was well suppressed, it was concluded that avalanches mediate crystallization, and not vice versa. This crystallization pathway has now been found in simulations of glasses with Lennard-Jones 17 and soft 18 particle interactions as well. Some of these studies also found that devitrification is linked to the underlying structure. Not only does crystallization preferentially occur in regions that already possess a form of partial order called medium-range crystalline order (MRCO) 15 , 17 , avalanches themselves were found to be spatially correlated with ‘soft spots’: regions where rearrangements are likely to occur in a glass 19 . In fact, simulations have found avalanche initiator particles with lower values of local density and bond-orientational order than the rest of the system 17 . A correlation between structural and dynamical heterogeneities and crystal nucleation has indeed been found in scattering experiments on deeply supercooled colloidal hard-sphere liquids 20 . However, in these studies, no crystallization was seen in the glassy regime. Never has devitrification been directly observed in experiments at the single-particle level. Direct imaging of this process is not possible in atomic and molecular systems. While micrometre colloidal hard spheres have proven invaluable as experimental models in probing many condensed-matter phenomena 12 , 13 , in the context of devitrification, this is not the system of choice. Avalanches are thought to help the system navigate from metabasin to metabasin 21 , and because these transitions are rare events, capturing them already requires long and continuous imaging experiments. In hard spheres, where particles cannot overlap, numerical studies have found that avalanches are even rarer than in soft spheres where some small degree of overlap is possible 18 . The crystallization mechanism, nevertheless, was identical in both of these systems. Guided by these observations, here, we investigate the devitrification of colloidal glasses made of micrometre monodisperse soft particles. To capture the elusive avalanche events, we performed particle-resolved confocal microscope imaging of large systems for long times. In our two-dimensional (2D) imaging experiments, a horizontal slice in the bulk of the three-dimensional (3D) glass sample contained at least N ≈ 10 4 particles (depending on the particle volume fraction ϕ ), while in our 3D experiments, we imaged in excess of N ≈ 6 × 10 4 particles (see Materials and methods). Our experiments typically spanned 5 × 10 5 τ B to 2 × 10 6 τ B , where ${\tau }_{{\mathrm{B}}}=\frac{{\sigma }^{3}\uppi \eta }{8{k}_{{\mathrm{B}}}T}$ is the Brownian time of a freely diffusing particle. Here, η is the solvent viscosity, k B is the Boltzmann constant, T is the temperature and σ is the diameter of the particle. Even though soft inter-particle interactions probably hasten devitrification 18 , both the system size studied and the experiment duration exceeded simulations, even on hard spheres 15 , 17 . Since there can be appreciable particle overlap in soft spheres, the glass transition volume fraction in these systems is larger than in colloidal hard spheres. Recent experiments and simulations on soft colloids have identified a critical volume fraction, ϕ o , below which the structural relaxation time, τ α , grows in a manner identical to that in liquids of hard spheres 22 , 23 . Where these two systems differ is for ϕ ≥ ϕ o . In this regime, τ α is infinite for the hard-sphere case, while for soft spheres, it remains finite and grows weakly with ϕ due to intermittent internal stress relaxation events 23 . While there is as yet no consensus on whether ϕ o corresponds to the glass or the jamming transition of soft spheres 22 , the operational definition of a glass transition defined in ref. 23<|im_end|> <|im_start|>assistant Glass is amorphous in nature—its atomic structure does not involve the repetitive arrangement seen in crystalline materials. But occasionally, it undergoes a process called devitrification, which is the transformation of a glass into a crystal—often an unwanted process in industries. The dynamics of devitrification remain poorly understood because the process can be extremely slow, spanning decades or more. Now, a team of researchers led by Rajesh Ganapathy, Associate Professor at the Jawaharlal Nehru Center for Advanced Scientific Research (JNCASR), in collaboration with Ajay Sood, DST Year of Science Chair and Professor at the Indian Institute of Science (IISc), and their Ph.D. student Divya Ganapathi (IISc) has visualized devitrification for the first time in experiments. The results of this study have been published in Nature Physics. "The trick was to work with a glass made of colloidal particles. Since each colloidal particle can be thought of as a substitute for a single atom, but being ten thousand times bigger than the atom, its dynamics can be watched in real-time with an optical microscope. Also, to hasten the process we tweaked the interaction between particles so that it is soft and rearrangements in the glass occurred frequently," says Divya Ganapathi. In order to make a glass, Divya Ganapathi and the team jammed the colloids together to reach high densities. The researchers observed different regions of the glass following two routes to crystallization: an avalanche-mediated route involving rapid rearrangements in the structure, and a smooth growth route with rearrangements happening gradually over time. To gain insights into these findings, the researchers then used machine learning methods to determine if there was some subtle structural feature hidden in the glass that apriori decides which regions would later crystallize and through what route. Despite the glass being disordered, the machine learning model was able to identify a structural feature called "softness" that had earlier been found to decide which particles in the glass rearrange and which do not. The researchers then found that regions in the glass which had particle clusters with large "softness" values were the ones that crystallized and that "softness" was also sensitive to the crystallization route. Perhaps the most striking finding emerging from the study was that the authors fed their machine learning model pictures of a colloidal glass and the model accurately predicted the regions that crystallized days in advance. "This paves the way for a powerful technique to identify and tune 'softness' well in advance and avoid devitrification," says Ajay Sood. Understanding devitrification is crucial in areas like the pharmaceutical industry, which strives to produce stable amorphous drugs as they dissolve faster in the body than their crystalline counterparts. Even liquid nuclear waste is vitrified as a solid in a glass matrix to safely dispose it of deep underground and prevent hazardous materials from leaking into the environment. The authors believe that this study is a significant step forward in understanding the connection between the underlying structure and stability of glass. "It is really cool that a machine learning algorithm can predict where the glass is going to crystallize and where it is going to stay glassy. This could be the initial step for designing more stable glasses like the gorilla glass on mobile phones, which is ubiquitous in modern technology," says Rajesh Ganapathy. The ability to manipulate structural parameters could usher in new ways to realize technologically significant long-lived glassy states. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 21396, 374, 49188, 45311, 311, 64568, 2065, 13, 4452, 11, 1268, 420, 18475, 13980, 1418, 279, 30295, 304, 279, 9168, 4822, 20268, 520, 279, 19320, 5569, 374, 31555, 16365, 13, 5810, 11, 1555, 3254, 2320, 7203, 11849, 8905, 32758, 21896, 11, 584, 1501, 430, 4245, 311, 20268, 3502, 17915, 304, 35940, 34224, 1385, 11, 264, 8579, 82048, 26966, 9168, 64568, 4861, 4669, 1403, 12742, 44014, 13, 763, 279, 31555, 19937, 13918, 315, 279, 9168, 11, 64568, 13797, 14264, 39511, 4245, 311, 2254, 19320, 559, 78553, 11, 20444, 304, 279, 1664, 71004, 13918, 11, 584, 13468, 44077, 35308, 304, 64568, 13797, 430, 1051, 22900, 555, 41635, 83281, 2345, 1030, 43719, 56427, 526, 3808, 16239, 1690, 22781, 315, 19252, 13, 13516, 18007, 11, 584, 1501, 430, 8579, 2136, 29096, 24693, 24747, 5852, 11075, 1555, 5780, 71856, 5528, 63938, 1193, 56978, 1405, 64568, 2065, 12961, 988, 304, 264, 9168, 719, 374, 1101, 16614, 311, 279, 64568, 2065, 38970, 13, 15483, 264, 59557, 3717, 1990, 279, 6070, 323, 20334, 315, 264, 9168, 706, 779, 3117, 14958, 66684, 13, 1611, 2749, 287, 15174, 311, 37735, 8579, 2136, 1253, 8617, 12391, 56193, 304, 44114, 1317, 62954, 9168, 88, 5415, 13, 4802, 4072, 73787, 1113, 279, 90090, 1234, 79, 6258, 826, 315, 3567, 22288, 2461, 22416, 18475, 315, 264, 9168, 311, 264, 26110, 2345, 9620, 3422, 1694, 315, 16188, 2802, 304, 1690, 23962, 315, 8198, 220, 16, 1174, 220, 17, 1174, 220, 18, 1174, 220, 19, 1174, 220, 20, 1174, 374, 7718, 369, 279, 55986, 315, 15528, 29247, 430, 1505, 12387, 8522, 304, 5064, 220, 21, 1174, 220, 22, 662, 27140, 279, 810, 21349, 1920, 315, 64568, 2065, 505, 264, 2307, 1030, 42831, 14812, 220, 23, 1174, 220, 24, 1174, 220, 605, 1174, 220, 806, 1174, 220, 717, 1174, 220, 1032, 1174, 902, 7612, 18563, 58510, 19320, 58430, 11, 279, 44014, 1555, 902, 264, 1887, 430, 374, 2080, 43024, 12800, 520, 279, 19320, 5569, 64568, 4861, 7293, 25420, 11, 14090, 4245, 311, 279, 6435, 323, 23490, 96340, 7138, 315, 279, 30295, 220, 975, 1174, 220, 868, 662, 763, 264, 1887, 315, 1647, 347, 28470, 325, 2653, 66818, 11, 47590, 220, 975, 617, 1766, 430, 64568, 2065, 304, 31555, 86997, 5962, 29247, 6137, 5246, 1306, 934, 20345, 323, 574, 57253, 4306, 70504, 25, 2254, 19320, 559, 78553, 11, 2085, 36460, 55407, 11, 9087, 5276, 1097, 16751, 788, 13918, 1139, 17251, 48473, 430, 28520, 24872, 31139, 304, 14373, 13918, 11, 8617, 6968, 264, 6928, 11302, 430, 63957, 4726, 6650, 13, 82671, 11, 47590, 389, 1664, 19415, 818, 5962, 3262, 1598, 2653, 1355, 8182, 29247, 617, 43522, 264, 5965, 275, 8046, 2204, 17432, 220, 868, 1174, 220, 845, 1174, 220, 1114, 1174, 220, 972, 662, 5843, 934, 552, 1189, 18852, 1051, 82019, 32390, 291, 449, 44077, 12992, 304, 64568, 13797, 11, 323, 1521, 35308, 1051, 35135, 449, 41635, 83281, 304, 14373, 13918, 11, 304, 902, 1690, 22781, 311, 264, 2478, 7895, 19252, 31408, 304, 48566, 56427, 526, 3808, 13, 99807, 19252, 55093, 13770, 34178, 922, 264, 4948, 315, 872, 1404, 11, 323, 1521, 1051, 10213, 539, 279, 6305, 430, 64568, 1534, 13, 8876, 41635, 83281, 10222, 1524, 304, 264, 10062, 4338, 82344, 1887, 11, 1405, 64568, 2065, 574, 1664, 56089, 11, 433, 574, 20536, 430, 41635, 83281, 1812, 6629, 64568, 2065, 11, 323, 539, 17192, 46391, 13, 1115, 64568, 2065, 38970, 706, 1457, 1027, 1766, 304, 47590, 315, 29247, 449, 445, 2734, 569, 12278, 3233, 220, 1114, 323, 8579, 220, 972, 19320, 22639, 439, 1664, 13, 4427, 315, 1521, 7978, 1101, 1766, 430, 3567, 22288, 2461, 374, 10815, 311, 279, 16940, 6070, 13, 2876, 1193, 1587, 64568, 2065, 10932, 31668, 12446, 304, 13918, 430, 2736, 15575, 264, 1376, 315, 7276, 2015, 2663, 11298, 31608, 64568, 483, 2015, 320, 44, 7532, 46, 8, 220, 868, 1174, 220, 1114, 1174, 41635, 83281, 5694, 1051, 1766, 311, 387, 29079, 398, 49393, 449, 3451, 3594, 19300, 89213, 13918, 1405, 56427, 526, 3808, 527, 4461, 311, 12446, 304, 264, 9168, 220, 777, 662, 763, 2144, 11, 47590, 617, 1766, 96694, 99140, 19252, 449, 4827, 2819, 315, 2254, 17915, 323, 11049, 12, 15226, 1697, 2015, 1109, 279, 2800, 315, 279, 1887, 220, 1114, 662, 362, 26670, 1990, 24693, 323, 18003, 950, 30548, 34224, 1385, 323, 26110, 31484, 367, 706, 13118, 1027, 1766, 304, 72916, 21896, 389, 17693, 2307, 1030, 42831, 82048, 26966, 2653, 1355, 8182, 67849, 220, 508, 662, 4452, 11, 304, 1521, 7978, 11, 912, 64568, 2065, 574, 3970, 304, 279, 9168, 88, 17942, 13, 15037, 706, 3567, 22288, 2461, 1027, 6089, 13468, 304, 21896, 520, 279, 3254, 2320, 7203, 2237, 13, 7286, 32758, 315, 420, 1920, 374, 539, 3284, 304, 25524, 323, 31206, 6067, 13, 6104, 19748, 442, 47987, 82048, 26966, 2653, 66818, 617, 17033, 56193, 439, 22772, 4211, 304, 84072, 1690, 75826, 1474, 1683, 44247, 220, 717, 1174, 220, 1032, 1174, 304, 279, 2317, 315, 3567, 22288, 2461, 11, 420, 374, 539, 279, 1887, 315, 5873, 13, 50078, 83281, 527, 3463, 311, 1520, 279, 1887, 21546, 505, 20208, 51410, 311, 20208, 51410, 220, 1691, 1174, 323, 1606, 1521, 34692, 527, 9024, 4455, 11, 40880, 1124, 2736, 7612, 1317, 323, 19815, 32758, 21896, 13, 763, 2653, 66818, 11, 1405, 19252, 4250, 28347, 11, 35876, 7978, 617, 1766, 430, 41635, 83281, 527, 1524, 436, 61570, 1109, 304, 8579, 66818, 1405, 1063, 2678, 8547, 315, 28347, 374, 3284, 220, 972, 662, 578, 64568, 2065, 17383, 11, 38330, 11, 574, 20086, 304, 2225, 315, 1521, 6067, 13, 12433, 291, 555, 1521, 24654, 11, 1618, 11, 584, 19874, 279, 3567, 22288, 2461, 315, 82048, 26966, 29247, 1903, 315, 19748, 442, 47987, 1647, 347, 28470, 325, 8579, 19252, 13, 2057, 12602, 279, 66684, 96694, 4455, 11, 584, 10887, 19320, 11849, 8905, 2389, 3768, 73757, 32758, 315, 3544, 6067, 369, 1317, 3115, 13, 763, 1057, 1403, 33520, 320, 17, 35, 8, 32758, 21896, 11, 264, 16600, 16363, 304, 279, 20155, 315, 279, 2380, 33520, 320, 18, 35, 8, 9168, 6205, 13282, 520, 3325, 452, 118792, 220, 605, 220, 19, 19252, 320, 81580, 389, 279, 19320, 8286, 19983, 17839, 243, 7026, 1418, 304, 1057, 220, 18, 35, 21896, 11, 584, 737, 3359, 304, 13937, 315, 452, 118792, 220, 21, 25800, 220, 605, 220, 19, 19252, 320, 4151, 32009, 323, 5528, 570, 5751, 21896, 11383, 9575, 19212, 220, 20, 25800, 220, 605, 220, 20, 39570, 426, 311, 220, 17, 25800, 220, 605, 220, 21, 39570, 426, 1174, 1405, 1144, 2358, 59, 30243, 335, 62, 3052, 59, 92650, 90, 33, 76642, 35533, 38118, 3052, 59, 25956, 335, 48922, 18, 11281, 455, 2554, 1144, 1955, 335, 90, 23, 70194, 20009, 3052, 59, 92650, 90, 33, 76642, 51, 11281, 8, 374, 279, 10690, 1122, 892, 315, 264, 26662, 3722, 985, 19320, 13, 5810, 11, 101034, 374, 279, 69996, 99530, 11, 597, 426, 374, 279, 47047, 89, 18022, 6926, 11, 350, 374, 279, 9499, 323, 48823, 374, 279, 23899, 315, 279, 19320, 13, 7570, 3582, 8579, 958, 2320, 7203, 22639, 4762, 34143, 268, 3567, 22288, 2461, 220, 972, 1174, 2225, 279, 1887, 1404, 20041, 323, 279, 9526, 8250, 34908, 47590, 11, 1524, 389, 2653, 66818, 220, 868, 1174, 220, 1114, 662, 8876, 1070, 649, 387, 9989, 2205, 19320, 28347, 304, 8579, 66818, 11, 279, 9168, 9320, 8286, 19983, 304, 1521, 6067, 374, 8294, 1109, 304, 82048, 26966, 2653, 66818, 13, 35390, 21896, 323, 47590, 389, 8579, 82048, 3447, 617, 11054, 264, 9200, 8286, 19983, 11, 17839, 243, 297, 1174, 3770, 902, 279, 24693, 43685, 892, 11, 39570, 19581, 1174, 28815, 304, 264, 11827, 20086, 311, 430, 304, 67849, 315, 2653, 66818, 220, 1313, 1174, 220, 1419, 662, 11208, 1521, 1403, 6067, 1782, 374, 369, 17839, 243, 63247, 17839, 243, 297, 662, 763, 420, 17942, 11, 39570, 19581, 374, 24746, 369, 279, 2653, 1355, 8182, 1162, 11, 1418, 369, 8579, 66818, 11, 433, 8625, 35326, 323, 28815, 7621, 398, 449, 17839, 243, 4245, 311, 75568, 5419, 8631, 43685, 4455, 220, 1419, 662, 6104, 1070, 374, 439, 3686, 912, 24811, 389, 3508, 17839, 243, 297, 34310, 311, 279, 9168, 477, 279, 20673, 5424, 9320, 315, 8579, 66818, 220, 1313, 1174, 279, 25605, 7419, 315, 264, 9168, 9320, 4613, 304, 2098, 13, 220, 1419, 128257, 198, 128256, 78191, 198, 85103, 374, 1097, 16751, 788, 304, 7138, 2345, 1220, 25524, 6070, 1587, 539, 21736, 279, 59177, 27204, 3970, 304, 64568, 483, 7384, 13, 2030, 23781, 11, 433, 37771, 288, 264, 1920, 2663, 3567, 22288, 2461, 11, 902, 374, 279, 18475, 315, 264, 9168, 1139, 264, 26110, 2345, 61917, 459, 36021, 1920, 304, 19647, 13, 578, 30295, 315, 3567, 22288, 2461, 7293, 31555, 16365, 1606, 279, 1920, 649, 387, 9193, 6435, 11, 56886, 11026, 477, 810, 13, 4800, 11, 264, 2128, 315, 12074, 6197, 555, 26291, 4385, 50181, 391, 19682, 11, 33468, 17054, 520, 279, 34294, 1494, 49358, 278, 73536, 2739, 5955, 369, 21844, 38130, 8483, 320, 41, 10153, 1950, 49, 705, 304, 20632, 449, 41757, 352, 328, 1411, 11, 78200, 9941, 315, 10170, 16478, 323, 17054, 520, 279, 7904, 10181, 315, 10170, 320, 40, 1669, 66, 705, 323, 872, 2405, 920, 13, 5575, 8940, 7911, 50181, 391, 67631, 320, 40, 1669, 66, 8, 706, 9302, 1534, 3567, 22288, 2461, 369, 279, 1176, 892, 304, 21896, 13, 578, 3135, 315, 420, 4007, 617, 1027, 4756, 304, 22037, 28415, 13, 330, 791, 14397, 574, 311, 990, 449, 264, 9168, 1903, 315, 82048, 26966, 19252, 13, 8876, 1855, 82048, 26966, 19320, 649, 387, 3463, 315, 439, 264, 28779, 369, 264, 3254, 19670, 11, 719, 1694, 5899, 16579, 3115, 11493, 1109, 279, 19670, 11, 1202, 30295, 649, 387, 15746, 304, 1972, 7394, 449, 459, 29393, 73757, 13, 7429, 11, 311, 34143, 268, 279, 1920, 584, 89560, 279, 16628, 1990, 19252, 779, 430, 433, 374, 8579, 323, 56427, 526, 3808, 304, 279, 9168, 10222, 14134, 1359, 2795, 8940, 7911, 50181, 391, 67631, 13, 763, 2015, 311, 1304, 264, 9168, 11, 8940, 7911, 50181, 391, 67631, 323, 279, 2128, 20673, 2106, 279, 82048, 3447, 3871, 311, 5662, 1579, 90816, 13, 578, 12074, 13468, 2204, 13918, 315, 279, 9168, 2768, 1403, 11543, 311, 64568, 2065, 25, 459, 96694, 82076, 6149, 16239, 11295, 56427, 526, 3808, 304, 279, 6070, 11, 323, 264, 11113, 6650, 6149, 449, 56427, 526, 3808, 12765, 27115, 927, 892, 13, 2057, 8895, 26793, 1139, 1521, 14955, 11, 279, 12074, 1243, 1511, 5780, 6975, 5528, 311, 8417, 422, 1070, 574, 1063, 27545, 24693, 4668, 8340, 304, 279, 9168, 430, 1469, 3334, 72, 28727, 902, 13918, 1053, 3010, 64568, 553, 323, 1555, 1148, 6149, 13, 18185, 279, 9168, 1694, 834, 10767, 11, 279, 5780, 6975, 1646, 574, 3025, 311, 10765, 264, 24693, 4668, 2663, 330, 3594, 2136, 1, 430, 1047, 6931, 1027, 1766, 311, 10491, 902, 19252, 304, 279, 9168, 56427, 853, 323, 902, 656, 539, 13, 578, 12074, 1243, 1766, 430, 13918, 304, 279, 9168, 902, 1047, 19320, 28066, 449, 3544, 330, 3594, 2136, 1, 2819, 1051, 279, 6305, 430, 64568, 1534, 323, 430, 330, 3594, 2136, 1, 574, 1101, 16614, 311, 279, 64568, 2065, 6149, 13, 19292, 279, 1455, 21933, 9455, 24084, 505, 279, 4007, 574, 430, 279, 12283, 23114, 872, 5780, 6975, 1646, 9364, 315, 264, 82048, 26966, 9168, 323, 279, 1646, 30357, 19698, 279, 13918, 430, 64568, 1534, 2919, 304, 12178, 13, 330, 2028, 281, 4798, 279, 1648, 369, 264, 8147, 15105, 311, 10765, 323, 26306, 364, 3594, 2136, 6, 1664, 304, 12178, 323, 5766, 3567, 22288, 2461, 1359, 2795, 41757, 352, 328, 1411, 13, 46551, 3567, 22288, 2461, 374, 16996, 304, 5789, 1093, 279, 35410, 5064, 11, 902, 75651, 311, 8356, 15528, 1097, 16751, 788, 11217, 439, 814, 73739, 10819, 304, 279, 2547, 1109, 872, 64568, 483, 38495, 13, 7570, 14812, 11499, 12571, 374, 13458, 81, 1908, 439, 264, 6573, 304, 264, 9168, 6303, 311, 21676, 28490, 433, 315, 5655, 26326, 323, 5471, 51024, 7384, 505, 52929, 1139, 279, 4676, 13, 578, 12283, 4510, 430, 420, 4007, 374, 264, 5199, 3094, 4741, 304, 8830, 279, 3717, 1990, 279, 16940, 6070, 323, 20334, 315, 9168, 13, 330, 2181, 374, 2216, 7155, 430, 264, 5780, 6975, 12384, 649, 7168, 1405, 279, 9168, 374, 2133, 311, 64568, 553, 323, 1405, 433, 374, 2133, 311, 4822, 9168, 88, 13, 1115, 1436, 387, 279, 2926, 3094, 369, 30829, 810, 15528, 29247, 1093, 279, 46298, 6374, 9168, 389, 6505, 18084, 11, 902, 374, 64564, 304, 6617, 5557, 1359, 2795, 26291, 4385, 50181, 391, 19682, 13, 578, 5845, 311, 37735, 24693, 5137, 1436, 64260, 304, 502, 5627, 311, 13383, 2869, 30450, 5199, 1317, 62954, 9168, 88, 5415, 13, 220, 128257, 198 ]

2,097

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Modern tomatoes have narrow genetic diversity limiting their improvement potential. We present a tomato pan-genome constructed using genome sequences of 725 phylogenetically and geographically representative accessions, revealing 4,873 genes absent from the reference genome. Presence/absence variation analyses reveal substantial gene loss and intense negative selection of genes and promoters during tomato domestication and improvement. Lost or negatively selected genes are enriched for important traits, especially disease resistance. We identify a rare allele in the TomLoxC promoter selected against during domestication. Quantitative trait locus mapping and analysis of transgenic plants reveal a role for TomLoxC in apocarotenoid production, which contributes to desirable tomato flavor. In orange-stage fruit, accessions harboring both the rare and common TomLoxC alleles (heterozygotes) have higher TomLoxC expression than those homozygous for either and are resurgent in modern tomatoes. The tomato pan-genome adds depth and completeness to the reference genome, and is useful for future biological discovery and breeding. Main Tomato is one of the most consumed vegetables worldwide with a total production of 182 million tons worth more than US$60 billion in 2017 ( ). A reference genome sequence was released 1 and has greatly facilitated scientific discoveries and molecular breeding of this important crop. Cultivated tomato ( Solanum lycopersicum L.) has experienced severe bottlenecks during its breeding history, resulting in a narrow genetic base 2 . However, modern cultivated tomatoes exhibit a wide range of phenotypic variation 3 and metabolic diversity 4 , mainly because of natural and human breeding-mediated introgressions from wild relatives 5 , in addition to spontaneous mutations that have also contributed to this seeming paradox 3 . Consequently, individual cultivars are expected to contain alleles or loci that are absent in the reference genome 6 . S. lycopersicum L. can be further divided into two botanical types: large-fruited tomatoes S. lycopersicum var. lycopersicum (SLL) and cherry-sized early domesticates S. lycopersicum var. cerasiforme (SLC). Following the release of the tomato reference genome, hundreds of diverse cultivated and wild tomato accessions have been resequenced, and the resulting data have been analyzed to reveal genomic changes through the history of tomato breeding. This has led to identifying specific genome regions targeted by human selection 7 , 8 , 9 , 10 . Notably, in these studies, reported genomic variation was revealed through mapping of short reads to the reference genome, an activity whose very nature ignores sequence information that is absent from the reference genome, precluding the discovery of previously unknown loci and highly divergent alleles. A pan-genome comprising all genetic elements from cultivated tomatoes and their wild progenitors is crucial for comprehensive exploration of domestication, assessment of breeding histories, optimal utilization of breeding resources and a more complete characterization of tomato gene function and potential. We constructed a tomato pan-genome using the ‘map-to-pan’ strategy 11 , based on resequencing data of 725 accessions belonging to the Lycopersicon clade, which consists of S. lycopersicum L. and its close wild relatives, Solanum pimpinellifolium (SP), and S. cheesmaniae and S. galapagense (SCG). The pan-genome captured 4,873 additional genes not in the reference genome. Comparative analyses using the constructed pan-genome revealed abundant presence/absence variations (PAVs) of functionally important genes under selection and identified a rare allele defined by promoter variation in the tomato lipoxygenase gene, TomLoxC . TomLoxC is known to influence fruit flavor by catalyzing the synthesis of lipid-derived C5 and C6 volatiles. Further characterization reveals a role of TomLoxC in apocarotenoid production. The rare allele of TomLoxC may have undergone negative selection in the early domesticates, followed by more recent reintroduction. The PAV dynamics presented here provide a case model of the profound impact of human selection on the gene repertoire of an important modern crop, in addition to a more complete picture of the genome potential of tomato that will guide breeding for targeted traits. Results Pan-genome of cultivated tomato and close wild relatives Genome sequences were collected/generated for a total of 725 tomato accessions in the Lycopersicon clade, including 372 SLL, 267 SLC, 78 SP and 8 SCG (3 S. cheesmaniae and 5 S. galapagense ) (Supplementary Tables 1 and 2 ). Among these accessions, genome sequences of 561 were available from previous reports 1 , 7 , 8 , 9 , 12 , 13 , 14 , whereas genomes of 166 accessions (of which 2 were also sequenced previously), including 121 SLC, 26 SP and 19 SLL, were sequenced in this study to obtain broader regional and global representation. Among the 725 accessions, 98 and 242 had sequence coverage of more than 20× and 10×, respectively. The genome for each accession was de novo assembled, producing a total of 306 Gb of contigs longer than 500 base pairs (bp) with an N50 value (the minimum contig length needed to cover 50% of the assembly) of 3,180 bp (Supplementary Table 2 , Supplementary Fig. 1 and Supplementary Note ). All assembled contigs were compared with the reference genome to identify previously unknown sequences. A total of 4.87 Gb of nonreference sequence with identity <90% to the reference genome was obtained (Supplementary Table 2 , Supplementary Fig. 2 and Supplementary Note ). After removing redundancies, 449,614 sequences with a total length of 351 Mb comprising the nonreference genome remained. Approximately 78.2% of the nonreference genome comprised repetitive elements, which was higher than that of the reference genome (63.5%) 1 . A total of 4,873 protein-coding genes were predicted in the nonreference genome (Supplementary Table 3 ). The reference ‘Heinz 1706’ genome contains 35,768 protein-coding genes (version ITAG3.2), of which 272 were potential contaminations and thus were removed (Supplementary Table 4 and Supplementary Note ). The tomato pan-genome, including reference and nonreference genome sequences, had a total size of 1,179 Mb and contained 40,369 protein-coding genes. Among the nonreference genes, 2,933 could be annotated with gene ontology (GO) terms or Pfam domains. A total of 332 nonreference genes were covered by ‘Heinz 1706’ reads with a coverage fraction greater than 95%, and 170 were fully covered, suggesting that they were not assembled in the reference", "role": "user" }, { "content": "Tomato breeders have traditionally emphasized traits that improve production, like larger fruits and more fruits per plant. As a result, some traits that improved other important qualities, such as flavor and disease resistance, were lost. Researchers from Boyce Thompson Institute and colleagues from partnering institutions have created a pan-genome that captures all of the genetic information of 725 cultivated and closely related wild tomatoes, establishing a resource that promises to help breeders develop more flavorful and sustainable varieties. As described in a paper published in Nature Genetics on May 13, the researchers found 4,873 new genes and identified a rare version of a gene that can make tomatoes tastier. \"The pan-genome essentially provides a reservoir of additional genes not present in the reference genome,\" said BTI faculty member Zhangjun Fei. \"Breeders can explore the pan-genome for genes of interest, and potentially select for them as they do further breeding to improve their tomatoes.\"The first tomato genome sequence was a large modern variety published in 2012, revealing approximately 35,000 genes and facilitating crop improvement efforts. Since then, several hundred additional tomato genotypes have been sequenced.The current study is the first to mine all of these genome sequences—as well as another 166 new sequences generated by the researchers—to hunt for genes that were absent from the reference genome. \"During the domestication and improvement of the tomato, people mostly focused on traits that would increase production, like fruit size and shelf-life,\" Fei said, \"so some genes involved in other important fruit quality traits and stress tolerance were lost during this process.\" Indeed, the researchers found that genes involved in defense responses to different pathogens were the most common group of genes that were missing in the domesticated varieties of tomato. \"These new genes could enable plant breeders to develop elite varieties of tomatoes that have genetic resistance to diseases that we currently address by treating the plants with pesticides or other cost-intensive and environmentally unfriendly measures,\" added James Giovannoni, a BTI faculty member and USDA scientist. The new tomato pan-genome found about 5,000 previously undocumented tomato genes, including for flavor. Credit: Agricultural Research Service-USDA Giovannoni and Fei are co-corresponding authors on the paper and adjunct professors in Cornell University's School of Integrative Plant Science. In addition to recovering these \"lost\" genes, the researchers also analyzed the pan-genome to find genes and gene mutations that are rare among the modern cultivars. This analysis identified a rare version of a gene, called TomLoxC, which contributes to a desirable tomato flavor. The rare version is present in 91.2% of wild tomatoes but only 2.2% of older domesticated tomatoes. \"The rare version of TomLoxC now has a frequency of 7% in modern tomato varieties, so clearly the breeders have started selecting for it, probably as they have focused more on flavor in the recent decades,\" Giovannoni said. The researchers also discovered a new role for the TomLoxC gene. \"TomLoxC appears, based on its sequence, to be involved in producing compounds from fats,\" said Giovannoni. \"We found it also produces flavor compounds from carotenoids, which are the pigments that make a tomato red. So it had an additional function beyond what we expected, and an outcome that is interesting to people who enjoy eating flavorful tomatoes.\" Ultimately, the tomato pan-genome could benefit the economy and the consumer, according to Clifford Weil, program director of the NSF's Plant Genome Research Program, which supported the work. \"How many times do you hear someone say that tomatoes from the store just don't quite measure up to heirloom varieties?\" Weil asked. \"This study gets to why that might be the case and shows that better tasting tomatoes appear to be on their way back.\" Tomatoes are one of the most consumed vegetables in the world—although technically we eat their fruit—with 182 million tons worth more than $60 billion produced each year. Tomatoes also are the second most-consumed vegetable in the U.S., with each American consuming an average of 20.3 pounds of fresh tomatoes and 73.3 pounds of processed tomatoes each year. Researchers from the University of Florida, Cornell, the U.S. Department of Agriculture, the Pennsylvania State University, the Polytechnic University of Valencia, the University of Georgia and the Chinese Academy of Agricultural Sciences also participated in the study. This research was supported by grants from the U.S. National Science Foundation, the European Research Area Network for Coordinating Action in Plant Sciences, the USDA-ARS and the U.S.-Israel Binational Agricultural Research and Development Fund. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Modern tomatoes have narrow genetic diversity limiting their improvement potential. We present a tomato pan-genome constructed using genome sequences of 725 phylogenetically and geographically representative accessions, revealing 4,873 genes absent from the reference genome. Presence/absence variation analyses reveal substantial gene loss and intense negative selection of genes and promoters during tomato domestication and improvement. Lost or negatively selected genes are enriched for important traits, especially disease resistance. We identify a rare allele in the TomLoxC promoter selected against during domestication. Quantitative trait locus mapping and analysis of transgenic plants reveal a role for TomLoxC in apocarotenoid production, which contributes to desirable tomato flavor. In orange-stage fruit, accessions harboring both the rare and common TomLoxC alleles (heterozygotes) have higher TomLoxC expression than those homozygous for either and are resurgent in modern tomatoes. The tomato pan-genome adds depth and completeness to the reference genome, and is useful for future biological discovery and breeding. Main Tomato is one of the most consumed vegetables worldwide with a total production of 182 million tons worth more than US$60 billion in 2017 ( ). A reference genome sequence was released 1 and has greatly facilitated scientific discoveries and molecular breeding of this important crop. Cultivated tomato ( Solanum lycopersicum L.) has experienced severe bottlenecks during its breeding history, resulting in a narrow genetic base 2 . However, modern cultivated tomatoes exhibit a wide range of phenotypic variation 3 and metabolic diversity 4 , mainly because of natural and human breeding-mediated introgressions from wild relatives 5 , in addition to spontaneous mutations that have also contributed to this seeming paradox 3 . Consequently, individual cultivars are expected to contain alleles or loci that are absent in the reference genome 6 . S. lycopersicum L. can be further divided into two botanical types: large-fruited tomatoes S. lycopersicum var. lycopersicum (SLL) and cherry-sized early domesticates S. lycopersicum var. cerasiforme (SLC). Following the release of the tomato reference genome, hundreds of diverse cultivated and wild tomato accessions have been resequenced, and the resulting data have been analyzed to reveal genomic changes through the history of tomato breeding. This has led to identifying specific genome regions targeted by human selection 7 , 8 , 9 , 10 . Notably, in these studies, reported genomic variation was revealed through mapping of short reads to the reference genome, an activity whose very nature ignores sequence information that is absent from the reference genome, precluding the discovery of previously unknown loci and highly divergent alleles. A pan-genome comprising all genetic elements from cultivated tomatoes and their wild progenitors is crucial for comprehensive exploration of domestication, assessment of breeding histories, optimal utilization of breeding resources and a more complete characterization of tomato gene function and potential. We constructed a tomato pan-genome using the ‘map-to-pan’ strategy 11 , based on resequencing data of 725 accessions belonging to the Lycopersicon clade, which consists of S. lycopersicum L. and its close wild relatives, Solanum pimpinellifolium (SP), and S. cheesmaniae and S. galapagense (SCG). The pan-genome captured 4,873 additional genes not in the reference genome. Comparative analyses using the constructed pan-genome revealed abundant presence/absence variations (PAVs) of functionally important genes under selection and identified a rare allele defined by promoter variation in the tomato lipoxygenase gene, TomLoxC . TomLoxC is known to influence fruit flavor by catalyzing the synthesis of lipid-derived C5 and C6 volatiles. Further characterization reveals a role of TomLoxC in apocarotenoid production. The rare allele of TomLoxC may have undergone negative selection in the early domesticates, followed by more recent reintroduction. The PAV dynamics presented here provide a case model of the profound impact of human selection on the gene repertoire of an important modern crop, in addition to a more complete picture of the genome potential of tomato that will guide breeding for targeted traits. Results Pan-genome of cultivated tomato and close wild relatives Genome sequences were collected/generated for a total of 725 tomato accessions in the Lycopersicon clade, including 372 SLL, 267 SLC, 78 SP and 8 SCG (3 S. cheesmaniae and 5 S. galapagense ) (Supplementary Tables 1 and 2 ). Among these accessions, genome sequences of 561 were available from previous reports 1 , 7 , 8 , 9 , 12 , 13 , 14 , whereas genomes of 166 accessions (of which 2 were also sequenced previously), including 121 SLC, 26 SP and 19 SLL, were sequenced in this study to obtain broader regional and global representation. Among the 725 accessions, 98 and 242 had sequence coverage of more than 20× and 10×, respectively. The genome for each accession was de novo assembled, producing a total of 306 Gb of contigs longer than 500 base pairs (bp) with an N50 value (the minimum contig length needed to cover 50% of the assembly) of 3,180 bp (Supplementary Table 2 , Supplementary Fig. 1 and Supplementary Note ). All assembled contigs were compared with the reference genome to identify previously unknown sequences. A total of 4.87 Gb of nonreference sequence with identity <90% to the reference genome was obtained (Supplementary Table 2 , Supplementary Fig. 2 and Supplementary Note ). After removing redundancies, 449,614 sequences with a total length of 351 Mb comprising the nonreference genome remained. Approximately 78.2% of the nonreference genome comprised repetitive elements, which was higher than that of the reference genome (63.5%) 1 . A total of 4,873 protein-coding genes were predicted in the nonreference genome (Supplementary Table 3 ). The reference ‘Heinz 1706’ genome contains 35,768 protein-coding genes (version ITAG3.2), of which 272 were potential contaminations and thus were removed (Supplementary Table 4 and Supplementary Note ). The tomato pan-genome, including reference and nonreference genome sequences, had a total size of 1,179 Mb and contained 40,369 protein-coding genes. Among the nonreference genes, 2,933 could be annotated with gene ontology (GO) terms or Pfam domains. A total of 332 nonreference genes were covered by ‘Heinz 1706’ reads with a coverage fraction greater than 95%, and 170 were fully covered, suggesting that they were not assembled in the reference<|im_end|> <|im_start|>assistant Tomato breeders have traditionally emphasized traits that improve production, like larger fruits and more fruits per plant. As a result, some traits that improved other important qualities, such as flavor and disease resistance, were lost. Researchers from Boyce Thompson Institute and colleagues from partnering institutions have created a pan-genome that captures all of the genetic information of 725 cultivated and closely related wild tomatoes, establishing a resource that promises to help breeders develop more flavorful and sustainable varieties. As described in a paper published in Nature Genetics on May 13, the researchers found 4,873 new genes and identified a rare version of a gene that can make tomatoes tastier. "The pan-genome essentially provides a reservoir of additional genes not present in the reference genome," said BTI faculty member Zhangjun Fei. "Breeders can explore the pan-genome for genes of interest, and potentially select for them as they do further breeding to improve their tomatoes."The first tomato genome sequence was a large modern variety published in 2012, revealing approximately 35,000 genes and facilitating crop improvement efforts. Since then, several hundred additional tomato genotypes have been sequenced.The current study is the first to mine all of these genome sequences—as well as another 166 new sequences generated by the researchers—to hunt for genes that were absent from the reference genome. "During the domestication and improvement of the tomato, people mostly focused on traits that would increase production, like fruit size and shelf-life," Fei said, "so some genes involved in other important fruit quality traits and stress tolerance were lost during this process." Indeed, the researchers found that genes involved in defense responses to different pathogens were the most common group of genes that were missing in the domesticated varieties of tomato. "These new genes could enable plant breeders to develop elite varieties of tomatoes that have genetic resistance to diseases that we currently address by treating the plants with pesticides or other cost-intensive and environmentally unfriendly measures," added James Giovannoni, a BTI faculty member and USDA scientist. The new tomato pan-genome found about 5,000 previously undocumented tomato genes, including for flavor. Credit: Agricultural Research Service-USDA Giovannoni and Fei are co-corresponding authors on the paper and adjunct professors in Cornell University's School of Integrative Plant Science. In addition to recovering these "lost" genes, the researchers also analyzed the pan-genome to find genes and gene mutations that are rare among the modern cultivars. This analysis identified a rare version of a gene, called TomLoxC, which contributes to a desirable tomato flavor. The rare version is present in 91.2% of wild tomatoes but only 2.2% of older domesticated tomatoes. "The rare version of TomLoxC now has a frequency of 7% in modern tomato varieties, so clearly the breeders have started selecting for it, probably as they have focused more on flavor in the recent decades," Giovannoni said. The researchers also discovered a new role for the TomLoxC gene. "TomLoxC appears, based on its sequence, to be involved in producing compounds from fats," said Giovannoni. "We found it also produces flavor compounds from carotenoids, which are the pigments that make a tomato red. So it had an additional function beyond what we expected, and an outcome that is interesting to people who enjoy eating flavorful tomatoes." Ultimately, the tomato pan-genome could benefit the economy and the consumer, according to Clifford Weil, program director of the NSF's Plant Genome Research Program, which supported the work. "How many times do you hear someone say that tomatoes from the store just don't quite measure up to heirloom varieties?" Weil asked. "This study gets to why that might be the case and shows that better tasting tomatoes appear to be on their way back." Tomatoes are one of the most consumed vegetables in the world—although technically we eat their fruit—with 182 million tons worth more than $60 billion produced each year. Tomatoes also are the second most-consumed vegetable in the U.S., with each American consuming an average of 20.3 pounds of fresh tomatoes and 73.3 pounds of processed tomatoes each year. Researchers from the University of Florida, Cornell, the U.S. Department of Agriculture, the Pennsylvania State University, the Polytechnic University of Valencia, the University of Georgia and the Chinese Academy of Agricultural Sciences also participated in the study. This research was supported by grants from the U.S. National Science Foundation, the European Research Area Network for Coordinating Action in Plant Sciences, the USDA-ARS and the U.S.-Israel Binational Agricultural Research and Development Fund. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 18766, 41613, 617, 15376, 19465, 20057, 33994, 872, 16048, 4754, 13, 1226, 3118, 264, 42120, 7363, 37564, 638, 20968, 1701, 33869, 24630, 315, 220, 23309, 37555, 86945, 37774, 323, 3980, 65031, 18740, 2680, 919, 11, 31720, 220, 19, 11, 25747, 21389, 28310, 505, 279, 5905, 33869, 13, 79723, 14, 3518, 768, 23851, 29060, 16805, 12190, 15207, 4814, 323, 19428, 8389, 6727, 315, 21389, 323, 95260, 2391, 42120, 13018, 367, 323, 16048, 13, 28351, 477, 48291, 4183, 21389, 527, 69671, 369, 3062, 25022, 11, 5423, 8624, 13957, 13, 1226, 10765, 264, 9024, 70510, 304, 279, 8529, 4357, 12398, 66642, 4183, 2403, 2391, 13018, 367, 13, 32541, 22018, 18027, 79257, 13021, 323, 6492, 315, 1380, 89305, 11012, 16805, 264, 3560, 369, 8529, 4357, 12398, 304, 1469, 511, 277, 66728, 590, 5788, 11, 902, 44072, 311, 35946, 42120, 17615, 13, 763, 19087, 51256, 14098, 11, 2680, 919, 69566, 5620, 2225, 279, 9024, 323, 4279, 8529, 4357, 12398, 98260, 320, 71, 1430, 76523, 70, 6429, 8, 617, 5190, 8529, 4357, 12398, 7645, 1109, 1884, 55513, 4341, 70, 788, 369, 3060, 323, 527, 594, 86153, 304, 6617, 41613, 13, 578, 42120, 7363, 37564, 638, 11621, 8149, 323, 80414, 311, 279, 5905, 33869, 11, 323, 374, 5505, 369, 3938, 24156, 18841, 323, 40308, 13, 4802, 94091, 374, 832, 315, 279, 1455, 27073, 24822, 15603, 449, 264, 2860, 5788, 315, 220, 10828, 3610, 20181, 5922, 810, 1109, 2326, 3, 1399, 7239, 304, 220, 679, 22, 320, 7609, 362, 5905, 33869, 8668, 574, 6004, 220, 16, 323, 706, 19407, 72849, 12624, 54098, 323, 31206, 40308, 315, 420, 3062, 19641, 13, 26676, 55786, 42120, 320, 11730, 276, 372, 326, 3418, 52187, 86231, 445, 6266, 706, 10534, 15748, 11176, 35291, 14895, 2391, 1202, 40308, 3925, 11, 13239, 304, 264, 15376, 19465, 2385, 220, 17, 662, 4452, 11, 6617, 67166, 41613, 31324, 264, 7029, 2134, 315, 14345, 37941, 292, 23851, 220, 18, 323, 41861, 20057, 220, 19, 1174, 14918, 1606, 315, 5933, 323, 3823, 40308, 82076, 20285, 2542, 919, 505, 8545, 29658, 220, 20, 1174, 304, 5369, 311, 54557, 34684, 430, 617, 1101, 20162, 311, 420, 76795, 52313, 220, 18, 662, 53123, 11, 3927, 27981, 1590, 527, 3685, 311, 6782, 98260, 477, 1353, 72, 430, 527, 28310, 304, 279, 5905, 33869, 220, 21, 662, 328, 13, 326, 3418, 52187, 86231, 445, 13, 649, 387, 4726, 18255, 1139, 1403, 98302, 4595, 25, 3544, 51478, 84, 1639, 41613, 328, 13, 326, 3418, 52187, 86231, 767, 13, 326, 3418, 52187, 86231, 320, 50, 4178, 8, 323, 41980, 28935, 4216, 13018, 988, 328, 13, 326, 3418, 52187, 86231, 767, 13, 272, 9431, 7398, 68, 320, 8143, 34, 570, 23548, 279, 4984, 315, 279, 42120, 5905, 33869, 11, 11758, 315, 17226, 67166, 323, 8545, 42120, 2680, 919, 617, 1027, 312, 6741, 5886, 11, 323, 279, 13239, 828, 617, 1027, 30239, 311, 16805, 81064, 4442, 1555, 279, 3925, 315, 42120, 40308, 13, 1115, 706, 6197, 311, 25607, 3230, 33869, 13918, 17550, 555, 3823, 6727, 220, 22, 1174, 220, 23, 1174, 220, 24, 1174, 220, 605, 662, 2876, 2915, 11, 304, 1521, 7978, 11, 5068, 81064, 23851, 574, 10675, 1555, 13021, 315, 2875, 16181, 311, 279, 5905, 33869, 11, 459, 5820, 6832, 1633, 7138, 49378, 8668, 2038, 430, 374, 28310, 505, 279, 5905, 33869, 11, 864, 11150, 279, 18841, 315, 8767, 9987, 1353, 72, 323, 7701, 37441, 16149, 98260, 13, 362, 7363, 37564, 638, 46338, 682, 19465, 5540, 505, 67166, 41613, 323, 872, 8545, 84360, 12170, 374, 16996, 369, 16195, 27501, 315, 13018, 367, 11, 15813, 315, 40308, 53210, 11, 23669, 50549, 315, 40308, 5070, 323, 264, 810, 4686, 60993, 315, 42120, 15207, 734, 323, 4754, 13, 1226, 20968, 264, 42120, 7363, 37564, 638, 1701, 279, 3451, 2235, 4791, 12, 857, 529, 8446, 220, 806, 1174, 3196, 389, 312, 6741, 11627, 828, 315, 220, 23309, 2680, 919, 33152, 311, 279, 445, 3418, 52187, 1965, 1206, 1037, 11, 902, 17610, 315, 328, 13, 326, 3418, 52187, 86231, 445, 13, 323, 1202, 3345, 8545, 29658, 11, 11730, 276, 372, 85448, 258, 616, 333, 337, 2411, 320, 4695, 705, 323, 328, 13, 43932, 52668, 68, 323, 328, 13, 15730, 391, 351, 1137, 320, 3624, 38, 570, 578, 7363, 37564, 638, 17439, 220, 19, 11, 25747, 5217, 21389, 539, 304, 279, 5905, 33869, 13, 97280, 29060, 1701, 279, 20968, 7363, 37564, 638, 10675, 44611, 9546, 14, 3518, 768, 27339, 320, 8201, 52837, 8, 315, 734, 750, 3062, 21389, 1234, 6727, 323, 11054, 264, 9024, 70510, 4613, 555, 66642, 23851, 304, 279, 42120, 326, 7088, 19472, 521, 15207, 11, 8529, 4357, 12398, 662, 8529, 4357, 12398, 374, 3967, 311, 10383, 14098, 17615, 555, 34454, 18854, 287, 279, 39975, 315, 68700, 72286, 356, 20, 323, 356, 21, 4499, 266, 3742, 13, 15903, 60993, 21667, 264, 3560, 315, 8529, 4357, 12398, 304, 1469, 511, 277, 66728, 590, 5788, 13, 578, 9024, 70510, 315, 8529, 4357, 12398, 1253, 617, 64238, 8389, 6727, 304, 279, 4216, 13018, 988, 11, 8272, 555, 810, 3293, 76267, 17158, 13, 578, 393, 8253, 30295, 10666, 1618, 3493, 264, 1162, 1646, 315, 279, 28254, 5536, 315, 3823, 6727, 389, 279, 15207, 77768, 315, 459, 3062, 6617, 19641, 11, 304, 5369, 311, 264, 810, 4686, 6945, 315, 279, 33869, 4754, 315, 42120, 430, 690, 8641, 40308, 369, 17550, 25022, 13, 18591, 11233, 37564, 638, 315, 67166, 42120, 323, 3345, 8545, 29658, 82917, 24630, 1051, 14890, 80472, 369, 264, 2860, 315, 220, 23309, 42120, 2680, 919, 304, 279, 445, 3418, 52187, 1965, 1206, 1037, 11, 2737, 220, 17662, 328, 4178, 11, 220, 16567, 328, 8724, 11, 220, 2495, 9440, 323, 220, 23, 7683, 38, 320, 18, 328, 13, 43932, 52668, 68, 323, 220, 20, 328, 13, 15730, 391, 351, 1137, 883, 320, 10254, 67082, 43252, 220, 16, 323, 220, 17, 7609, 22395, 1521, 2680, 919, 11, 33869, 24630, 315, 220, 20460, 1051, 2561, 505, 3766, 6821, 220, 16, 1174, 220, 22, 1174, 220, 23, 1174, 220, 24, 1174, 220, 717, 1174, 220, 1032, 1174, 220, 975, 1174, 20444, 85381, 315, 220, 11247, 2680, 919, 320, 1073, 902, 220, 17, 1051, 1101, 11506, 5886, 8767, 705, 2737, 220, 7994, 328, 8724, 11, 220, 1627, 9440, 323, 220, 777, 328, 4178, 11, 1051, 11506, 5886, 304, 420, 4007, 311, 6994, 27927, 15481, 323, 3728, 13340, 13, 22395, 279, 220, 23309, 2680, 919, 11, 220, 3264, 323, 220, 12754, 1047, 8668, 10401, 315, 810, 1109, 220, 508, 18028, 323, 220, 605, 18028, 11, 15947, 13, 578, 33869, 369, 1855, 85045, 574, 409, 39423, 35105, 11, 17843, 264, 2860, 315, 220, 12879, 480, 65, 315, 687, 14801, 5129, 1109, 220, 2636, 2385, 13840, 320, 18287, 8, 449, 459, 452, 1135, 907, 320, 1820, 8187, 687, 343, 3160, 4460, 311, 3504, 220, 1135, 4, 315, 279, 14956, 8, 315, 220, 18, 11, 5245, 27783, 320, 10254, 67082, 6771, 220, 17, 1174, 99371, 23966, 13, 220, 16, 323, 99371, 7181, 7609, 2052, 35105, 687, 14801, 1051, 7863, 449, 279, 5905, 33869, 311, 10765, 8767, 9987, 24630, 13, 362, 2860, 315, 220, 19, 13, 4044, 480, 65, 315, 2536, 16690, 8668, 449, 9764, 366, 1954, 4, 311, 279, 5905, 33869, 574, 12457, 320, 10254, 67082, 6771, 220, 17, 1174, 99371, 23966, 13, 220, 17, 323, 99371, 7181, 7609, 4740, 18054, 37673, 32737, 11, 220, 21125, 11, 22638, 24630, 449, 264, 2860, 3160, 315, 220, 18113, 51365, 46338, 279, 2536, 16690, 33869, 14958, 13, 79904, 220, 2495, 13, 17, 4, 315, 279, 2536, 16690, 33869, 40056, 59177, 5540, 11, 902, 574, 5190, 1109, 430, 315, 279, 5905, 33869, 320, 5495, 13, 20, 11587, 220, 16, 662, 362, 2860, 315, 220, 19, 11, 25747, 13128, 1824, 3785, 21389, 1051, 19698, 304, 279, 2536, 16690, 33869, 320, 10254, 67082, 6771, 220, 18, 7609, 578, 5905, 3451, 1548, 41622, 220, 8258, 21, 529, 33869, 5727, 220, 1758, 11, 17521, 13128, 1824, 3785, 21389, 320, 4464, 8871, 1929, 18, 13, 17, 705, 315, 902, 220, 15741, 1051, 4754, 35522, 811, 323, 8617, 1051, 7108, 320, 10254, 67082, 6771, 220, 19, 323, 99371, 7181, 7609, 578, 42120, 7363, 37564, 638, 11, 2737, 5905, 323, 2536, 16690, 33869, 24630, 11, 1047, 264, 2860, 1404, 315, 220, 16, 11, 11128, 51365, 323, 13282, 220, 1272, 11, 19929, 13128, 1824, 3785, 21389, 13, 22395, 279, 2536, 16690, 21389, 11, 220, 17, 11, 25806, 1436, 387, 63951, 449, 15207, 84369, 320, 15881, 8, 3878, 477, 43168, 309, 31576, 13, 362, 2860, 315, 220, 17079, 2536, 16690, 21389, 1051, 9960, 555, 3451, 1548, 41622, 220, 8258, 21, 529, 16181, 449, 264, 10401, 19983, 7191, 1109, 220, 2721, 13689, 323, 220, 8258, 1051, 7373, 9960, 11, 23377, 430, 814, 1051, 539, 35105, 304, 279, 5905, 128257, 198, 128256, 78191, 198, 25763, 4428, 28875, 388, 617, 36342, 46728, 25022, 430, 7417, 5788, 11, 1093, 8294, 26390, 323, 810, 26390, 824, 6136, 13, 1666, 264, 1121, 11, 1063, 25022, 430, 13241, 1023, 3062, 29600, 11, 1778, 439, 17615, 323, 8624, 13957, 11, 1051, 5675, 13, 59250, 505, 16576, 346, 26224, 10181, 323, 18105, 505, 70220, 14673, 617, 3549, 264, 7363, 37564, 638, 430, 41255, 682, 315, 279, 19465, 2038, 315, 220, 23309, 67166, 323, 15499, 5552, 8545, 41613, 11, 31692, 264, 5211, 430, 21300, 311, 1520, 28875, 388, 2274, 810, 94631, 323, 22556, 36680, 13, 1666, 7633, 304, 264, 5684, 4756, 304, 22037, 84386, 389, 3297, 220, 1032, 11, 279, 12074, 1766, 220, 19, 11, 25747, 502, 21389, 323, 11054, 264, 9024, 2373, 315, 264, 15207, 430, 649, 1304, 41613, 58172, 1291, 13, 330, 791, 7363, 37564, 638, 16168, 5825, 264, 45512, 315, 5217, 21389, 539, 3118, 304, 279, 5905, 33869, 1359, 1071, 21795, 40, 22291, 4562, 37120, 58781, 3926, 72, 13, 330, 33, 29616, 388, 649, 13488, 279, 7363, 37564, 638, 369, 21389, 315, 2802, 11, 323, 13893, 3373, 369, 1124, 439, 814, 656, 4726, 40308, 311, 7417, 872, 41613, 1210, 791, 1176, 42120, 33869, 8668, 574, 264, 3544, 6617, 8205, 4756, 304, 220, 679, 17, 11, 31720, 13489, 220, 1758, 11, 931, 21389, 323, 68365, 19641, 16048, 9045, 13, 8876, 1243, 11, 3892, 7895, 5217, 42120, 4173, 22583, 617, 1027, 11506, 5886, 11829, 1510, 4007, 374, 279, 1176, 311, 10705, 682, 315, 1521, 33869, 24630, 60654, 1664, 439, 2500, 220, 11247, 502, 24630, 8066, 555, 279, 12074, 50617, 19614, 369, 21389, 430, 1051, 28310, 505, 279, 5905, 33869, 13, 330, 16397, 279, 13018, 367, 323, 16048, 315, 279, 42120, 11, 1274, 10213, 10968, 389, 25022, 430, 1053, 5376, 5788, 11, 1093, 14098, 1404, 323, 28745, 26928, 1359, 3926, 72, 1071, 11, 330, 708, 1063, 21389, 6532, 304, 1023, 3062, 14098, 4367, 25022, 323, 8631, 25065, 1051, 5675, 2391, 420, 1920, 1210, 23150, 11, 279, 12074, 1766, 430, 21389, 6532, 304, 9232, 14847, 311, 2204, 78284, 1051, 279, 1455, 4279, 1912, 315, 21389, 430, 1051, 7554, 304, 279, 13018, 660, 36680, 315, 42120, 13, 330, 9673, 502, 21389, 1436, 7431, 6136, 28875, 388, 311, 2274, 21342, 36680, 315, 41613, 430, 617, 19465, 13957, 311, 19338, 430, 584, 5131, 2686, 555, 27723, 279, 11012, 449, 61257, 477, 1023, 2853, 88092, 323, 57340, 9662, 18260, 11193, 1359, 3779, 7957, 61678, 17893, 72, 11, 264, 21795, 40, 22291, 4562, 323, 61091, 28568, 13, 578, 502, 42120, 7363, 37564, 638, 1766, 922, 220, 20, 11, 931, 8767, 47757, 42120, 21389, 11, 2737, 369, 17615, 13, 16666, 25, 60134, 8483, 5475, 33440, 6486, 61678, 17893, 72, 323, 3926, 72, 527, 1080, 46713, 6961, 287, 12283, 389, 279, 5684, 323, 90695, 45724, 304, 56819, 3907, 596, 6150, 315, 30101, 1413, 18317, 10170, 13, 763, 5369, 311, 42386, 1521, 330, 55437, 1, 21389, 11, 279, 12074, 1101, 30239, 279, 7363, 37564, 638, 311, 1505, 21389, 323, 15207, 34684, 430, 527, 9024, 4315, 279, 6617, 27981, 1590, 13, 1115, 6492, 11054, 264, 9024, 2373, 315, 264, 15207, 11, 2663, 8529, 4357, 12398, 11, 902, 44072, 311, 264, 35946, 42120, 17615, 13, 578, 9024, 2373, 374, 3118, 304, 220, 5925, 13, 17, 4, 315, 8545, 41613, 719, 1193, 220, 17, 13, 17, 4, 315, 9191, 13018, 660, 41613, 13, 330, 791, 9024, 2373, 315, 8529, 4357, 12398, 1457, 706, 264, 11900, 315, 220, 22, 4, 304, 6617, 42120, 36680, 11, 779, 9539, 279, 28875, 388, 617, 3940, 27397, 369, 433, 11, 4762, 439, 814, 617, 10968, 810, 389, 17615, 304, 279, 3293, 11026, 1359, 61678, 17893, 72, 1071, 13, 578, 12074, 1101, 11352, 264, 502, 3560, 369, 279, 8529, 4357, 12398, 15207, 13, 330, 25763, 4357, 12398, 8111, 11, 3196, 389, 1202, 8668, 11, 311, 387, 6532, 304, 17843, 32246, 505, 50127, 1359, 1071, 61678, 17893, 72, 13, 330, 1687, 1766, 433, 1101, 19159, 17615, 32246, 505, 1841, 66728, 17390, 11, 902, 527, 279, 24623, 1392, 430, 1304, 264, 42120, 2579, 13, 2100, 433, 1047, 459, 5217, 734, 7953, 1148, 584, 3685, 11, 323, 459, 15632, 430, 374, 7185, 311, 1274, 889, 4774, 12459, 94631, 41613, 1210, 55106, 11, 279, 42120, 7363, 37564, 638, 1436, 8935, 279, 8752, 323, 279, 11761, 11, 4184, 311, 86783, 1226, 321, 11, 2068, 7690, 315, 279, 80628, 596, 18317, 82917, 8483, 6826, 11, 902, 7396, 279, 990, 13, 330, 4438, 1690, 3115, 656, 499, 6865, 4423, 2019, 430, 41613, 505, 279, 3637, 1120, 1541, 956, 5115, 6767, 709, 311, 51543, 18981, 36680, 7673, 1226, 321, 4691, 13, 330, 2028, 4007, 5334, 311, 3249, 430, 2643, 387, 279, 1162, 323, 5039, 430, 2731, 47500, 41613, 5101, 311, 387, 389, 872, 1648, 1203, 1210, 8529, 20798, 527, 832, 315, 279, 1455, 27073, 24822, 304, 279, 1917, 2345, 37241, 32654, 584, 8343, 872, 14098, 81902, 220, 10828, 3610, 20181, 5922, 810, 1109, 400, 1399, 7239, 9124, 1855, 1060, 13, 8529, 20798, 1101, 527, 279, 2132, 1455, 15204, 1264, 291, 36581, 304, 279, 549, 815, 2637, 449, 1855, 3778, 35208, 459, 5578, 315, 220, 508, 13, 18, 16701, 315, 7878, 41613, 323, 220, 5958, 13, 18, 16701, 315, 15590, 41613, 1855, 1060, 13, 59250, 505, 279, 3907, 315, 9784, 11, 56819, 11, 279, 549, 815, 13, 6011, 315, 37963, 11, 279, 20355, 3314, 3907, 11, 279, 19294, 26522, 292, 3907, 315, 61349, 11, 279, 3907, 315, 16272, 323, 279, 8620, 16192, 315, 60134, 23199, 1101, 31408, 304, 279, 4007, 13, 1115, 3495, 574, 7396, 555, 25076, 505, 279, 549, 815, 13, 5165, 10170, 5114, 11, 279, 7665, 8483, 12299, 8304, 369, 3623, 6114, 1113, 5703, 304, 18317, 23199, 11, 279, 61091, 12, 17485, 323, 279, 549, 815, 12898, 34627, 30444, 1697, 60134, 8483, 323, 11050, 13492, 13, 220, 128257, 198 ]

2,413

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Accurately modeling cellular response to perturbations is a central goal of computational biology. While such modeling has been based on statistical, mechanistic and machine learning models in specific settings, no generalization of predictions to phenomena absent from training data (out-of-sample) has yet been demonstrated. Here, we present scGen ( ), a model combining variational autoencoders and latent space vector arithmetics for high-dimensional single-cell gene expression data. We show that scGen accurately models perturbation and infection response of cells across cell types, studies and species. In particular, we demonstrate that scGen learns cell-type and species-specific responses implying that it captures features that distinguish responding from non-responding genes and cells. With the upcoming availability of large-scale atlases of organs in a healthy state, we envision scGen to become a tool for experimental design through in silico screening of perturbation response in the context of disease and drug treatment. Main Single-cell transcriptomics has become an established tool for the unbiased profiling of complex and heterogeneous systems 1 , 2 . The generated data sets are typically used for explaining phenotypes through cellular composition and dynamics. Of particular interest are the dynamics of single cells in response to perturbations, be it to dose 3 , treatment 4 , 5 or the knockout of genes 6 , 7 , 8 . Although advances in single-cell differential expression analysis 9 , 10 have enabled the identification of genes associated with a perturbation, generative modeling of perturbation response takes a step further in that it enables the generation of data in silico. The ability to generate data that cover phenomena not seen during training is particularly challenging and referred to as out-of-sample prediction. While dynamic mechanistic models have been suggested for predicting low-dimensional quantities that characterize cellular response 11 , 12 , such as a scalar measure of proliferation, they face fundamental problems. These models cannot easily be formulated in a data-driven way and require temporal resolution of the experimental data. Due to the typically small number of time points available, parameters are often hard to identify. Resorting to linear statistical models for modeling perturbation response 6 , 8 leads to low predictive power for the complicated non-linear effects that single-cell data display. In contrast, neural network models do not face these limits. Recently, such models have been suggested for the analysis of single-cell RNA sequencing (scRNA-seq) data 13 , 14 , 15 , 16 , 17 . In particular, generative adversarial networks (GANs) have been proposed for simulating single-cell differentiation through so-called latent space interpolation 16 . While providing an interesting alternative to established pseudotemporal ordering algorithms 18 , this analysis does not demonstrate the capability of GANs for out-of-sample prediction. The use of GANs for the harder task of out-of-sample prediction is hindered by fundamental difficulties: (1) GANs are hard to train for structured high-dimensional data, leading to high-variance predictions with large errors in extrapolation, and (2) GANs do not allow for the direct mapping of a gene expression vector x on a latent space vector z , making it difficult or impossible to generate a cell with a set of desired properties. In addition, for structured data, GANs have not yet shown advantages over the simpler variational autoencoders (VAE) 19 ( Methods ). To overcome these problems, we built scGen, which is based on a VAE combined with vector arithmetics, with an architecture adapted for scRNA-seq data. scGen enables predictions of dose and infection response of cells for phenomena absent from training data across cell types, studies and species. In a broad benchmark, it outperforms other potential modeling approaches, such as linear methods, conditional variational autoencoders (CVAE) 20 and style transfer GANs. The benchmark of several generative neural network models should present a valuable resource for the community showing opportunities and limitations for such models when applied to scRNA-seq data. scGen is based on Tensorflow 21 and on the single-cell analysis toolkit Scanpy 22 . Results scGen accurately predicts single-cell perturbation response out-of-sample High-dimensional scRNA-seq data is typically assumed to be well parametrized by a low-dimensional manifold arising from the constraints of the underlying gene regulatory networks. Current analysis algorithms mostly focus on characterizing the manifold using graph-based techniques 23 , 24 in the space spanned by a few principal components. More recently, the manifold has been modeled using neural networks 13 , 14 , 15 , 16 , 17 . As in other application fields 25 , 26 , in the latent spaces of these models, the manifolds display astonishingly simple properties, such as approximately linear axes of variation for latent variables explaining a major part of the variability in the data. Hence, linear extrapolations of the low-dimensional manifold could in principle capture variability related to perturbation and other covariates (Supplementary Note 1 and Supplemental Fig. 1 ). Let every cell i with expression profile x i be characterized by a variable p i , which represents a discrete attribute across the whole manifold, such as perturbation, species or batch. To start with, we assume only two conditions 0 (unperturbed) and 1 (perturbed). Let us further consider the conditional distribution \${\\it{P}}\\left( {x_i{\\mathrm{|}}z_i,p_i} \\right)\$ , which assumes that each cell x i comes from a low-dimensional representation z i in condition p i . We use a VAE to model \${\\it{P}}\\left( {x_i{\\mathrm{|}}z_i,p_i} \\right)\$ in its dependence on z i and vector arithmetics in the latent space of VAE to model the dependence on p i (Fig. 1 ). Fig. 1: scGen, a method to predict single-cell perturbation response. Given a set of observed cell types in control and stimulation, we aim to predict the perturbation response of a new cell type A (blue) by training a model that learns to generalize the response of the cells in the training set. Within scGen, the model is a variational autoencoder, and the predictions are obtained using vector arithmetics in the latent space of the autoencoder. Specifically, we project gene expression measurements into a latent space using an encoder network and obtain a vector δ that", "role": "user" }, { "content": "Large-scale atlases of organs in a healthy state are soon going to be available, in particular, the Human Cell Atlas. This is a significant step in better understanding cells, tissues and organs in healthy state and provides a reference when diagnosing, monitoring and treating disease. However, due to the sheer number of possible combinations of treatment and disease conditions, expanding these data to characterize disease and disease treatment in traditional life science laboratories is labor-intensive and costly, and therefore not scalable. Accurately modeling cellular response to perturbations (e.g., disease, compounds, genetic interventions) is a central goal of computational biology. Although models based on statistical and mechanistic approaches exist, no machine-learning-based solution viable for unobserved high-dimensional phenomena has yet been available. In addition, scGen is the first tool that predicts cellular response out-of-sample. This means that scGen, if trained on data that capture the effect of perturbations for a given system, is able to make reliable predictions for a different system. \"For the first time, we have the opportunity to use data generated in one model system such as mouse and use the data to predict disease or therapy response in human patients,\" said Mohammad Lotfollahi, Ph.D. student (Helmholtz Zentrum München and Technische Universität München). scGen is a generative deep learning model that leverages ideas from image, sequence and language processing, and, for the first time, applies these ideas to model the behavior of a cell in silico. The next step for the team concerns the improving scGen to a fully data-driven formulation, increasing its predictive power to enable the study of combinations of perturbations. \"We can now start optimizing scGen to answer more and more complex questions about diseases,\" said Alex Wolf, Team Leader, and Fabian Theis, Director of the Institute of Computational Biology and Chair of Mathematical Modeling of Biological Systems at Technische Universität München. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Accurately modeling cellular response to perturbations is a central goal of computational biology. While such modeling has been based on statistical, mechanistic and machine learning models in specific settings, no generalization of predictions to phenomena absent from training data (out-of-sample) has yet been demonstrated. Here, we present scGen ( ), a model combining variational autoencoders and latent space vector arithmetics for high-dimensional single-cell gene expression data. We show that scGen accurately models perturbation and infection response of cells across cell types, studies and species. In particular, we demonstrate that scGen learns cell-type and species-specific responses implying that it captures features that distinguish responding from non-responding genes and cells. With the upcoming availability of large-scale atlases of organs in a healthy state, we envision scGen to become a tool for experimental design through in silico screening of perturbation response in the context of disease and drug treatment. Main Single-cell transcriptomics has become an established tool for the unbiased profiling of complex and heterogeneous systems 1 , 2 . The generated data sets are typically used for explaining phenotypes through cellular composition and dynamics. Of particular interest are the dynamics of single cells in response to perturbations, be it to dose 3 , treatment 4 , 5 or the knockout of genes 6 , 7 , 8 . Although advances in single-cell differential expression analysis 9 , 10 have enabled the identification of genes associated with a perturbation, generative modeling of perturbation response takes a step further in that it enables the generation of data in silico. The ability to generate data that cover phenomena not seen during training is particularly challenging and referred to as out-of-sample prediction. While dynamic mechanistic models have been suggested for predicting low-dimensional quantities that characterize cellular response 11 , 12 , such as a scalar measure of proliferation, they face fundamental problems. These models cannot easily be formulated in a data-driven way and require temporal resolution of the experimental data. Due to the typically small number of time points available, parameters are often hard to identify. Resorting to linear statistical models for modeling perturbation response 6 , 8 leads to low predictive power for the complicated non-linear effects that single-cell data display. In contrast, neural network models do not face these limits. Recently, such models have been suggested for the analysis of single-cell RNA sequencing (scRNA-seq) data 13 , 14 , 15 , 16 , 17 . In particular, generative adversarial networks (GANs) have been proposed for simulating single-cell differentiation through so-called latent space interpolation 16 . While providing an interesting alternative to established pseudotemporal ordering algorithms 18 , this analysis does not demonstrate the capability of GANs for out-of-sample prediction. The use of GANs for the harder task of out-of-sample prediction is hindered by fundamental difficulties: (1) GANs are hard to train for structured high-dimensional data, leading to high-variance predictions with large errors in extrapolation, and (2) GANs do not allow for the direct mapping of a gene expression vector x on a latent space vector z , making it difficult or impossible to generate a cell with a set of desired properties. In addition, for structured data, GANs have not yet shown advantages over the simpler variational autoencoders (VAE) 19 ( Methods ). To overcome these problems, we built scGen, which is based on a VAE combined with vector arithmetics, with an architecture adapted for scRNA-seq data. scGen enables predictions of dose and infection response of cells for phenomena absent from training data across cell types, studies and species. In a broad benchmark, it outperforms other potential modeling approaches, such as linear methods, conditional variational autoencoders (CVAE) 20 and style transfer GANs. The benchmark of several generative neural network models should present a valuable resource for the community showing opportunities and limitations for such models when applied to scRNA-seq data. scGen is based on Tensorflow 21 and on the single-cell analysis toolkit Scanpy 22 . Results scGen accurately predicts single-cell perturbation response out-of-sample High-dimensional scRNA-seq data is typically assumed to be well parametrized by a low-dimensional manifold arising from the constraints of the underlying gene regulatory networks. Current analysis algorithms mostly focus on characterizing the manifold using graph-based techniques 23 , 24 in the space spanned by a few principal components. More recently, the manifold has been modeled using neural networks 13 , 14 , 15 , 16 , 17 . As in other application fields 25 , 26 , in the latent spaces of these models, the manifolds display astonishingly simple properties, such as approximately linear axes of variation for latent variables explaining a major part of the variability in the data. Hence, linear extrapolations of the low-dimensional manifold could in principle capture variability related to perturbation and other covariates (Supplementary Note 1 and Supplemental Fig. 1 ). Let every cell i with expression profile x i be characterized by a variable p i , which represents a discrete attribute across the whole manifold, such as perturbation, species or batch. To start with, we assume only two conditions 0 (unperturbed) and 1 (perturbed). Let us further consider the conditional distribution ${\it{P}}\left( {x_i{\mathrm{|}}z_i,p_i} \right)$ , which assumes that each cell x i comes from a low-dimensional representation z i in condition p i . We use a VAE to model ${\it{P}}\left( {x_i{\mathrm{|}}z_i,p_i} \right)$ in its dependence on z i and vector arithmetics in the latent space of VAE to model the dependence on p i (Fig. 1 ). Fig. 1: scGen, a method to predict single-cell perturbation response. Given a set of observed cell types in control and stimulation, we aim to predict the perturbation response of a new cell type A (blue) by training a model that learns to generalize the response of the cells in the training set. Within scGen, the model is a variational autoencoder, and the predictions are obtained using vector arithmetics in the latent space of the autoencoder. Specifically, we project gene expression measurements into a latent space using an encoder network and obtain a vector δ that<|im_end|> <|im_start|>assistant Large-scale atlases of organs in a healthy state are soon going to be available, in particular, the Human Cell Atlas. This is a significant step in better understanding cells, tissues and organs in healthy state and provides a reference when diagnosing, monitoring and treating disease. However, due to the sheer number of possible combinations of treatment and disease conditions, expanding these data to characterize disease and disease treatment in traditional life science laboratories is labor-intensive and costly, and therefore not scalable. Accurately modeling cellular response to perturbations (e.g., disease, compounds, genetic interventions) is a central goal of computational biology. Although models based on statistical and mechanistic approaches exist, no machine-learning-based solution viable for unobserved high-dimensional phenomena has yet been available. In addition, scGen is the first tool that predicts cellular response out-of-sample. This means that scGen, if trained on data that capture the effect of perturbations for a given system, is able to make reliable predictions for a different system. "For the first time, we have the opportunity to use data generated in one model system such as mouse and use the data to predict disease or therapy response in human patients," said Mohammad Lotfollahi, Ph.D. student (Helmholtz Zentrum München and Technische Universität München). scGen is a generative deep learning model that leverages ideas from image, sequence and language processing, and, for the first time, applies these ideas to model the behavior of a cell in silico. The next step for the team concerns the improving scGen to a fully data-driven formulation, increasing its predictive power to enable the study of combinations of perturbations. "We can now start optimizing scGen to answer more and more complex questions about diseases," said Alex Wolf, Team Leader, and Fabian Theis, Director of the Institute of Computational Biology and Chair of Mathematical Modeling of Biological Systems at Technische Universität München. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 11683, 324, 2718, 34579, 35693, 2077, 311, 18713, 9225, 811, 374, 264, 8792, 5915, 315, 55580, 34458, 13, 6104, 1778, 34579, 706, 1027, 3196, 389, 29564, 11, 7852, 4633, 323, 5780, 6975, 4211, 304, 3230, 5110, 11, 912, 4689, 2065, 315, 20492, 311, 44247, 28310, 505, 4967, 828, 320, 412, 8838, 84979, 8, 706, 3686, 1027, 21091, 13, 5810, 11, 584, 3118, 1156, 10172, 320, 7026, 264, 1646, 35271, 4244, 1697, 3313, 967, 53598, 323, 42767, 3634, 4724, 802, 411, 46366, 369, 1579, 33520, 3254, 33001, 15207, 7645, 828, 13, 1226, 1501, 430, 1156, 10172, 30357, 4211, 18713, 65916, 323, 19405, 2077, 315, 7917, 4028, 2849, 4595, 11, 7978, 323, 9606, 13, 763, 4040, 11, 584, 20461, 430, 1156, 10172, 47310, 2849, 10827, 323, 9606, 19440, 14847, 73967, 430, 433, 41255, 4519, 430, 33137, 30438, 505, 2536, 12, 6961, 287, 21389, 323, 7917, 13, 3161, 279, 14827, 18539, 315, 3544, 13230, 71554, 2315, 315, 36853, 304, 264, 9498, 1614, 11, 584, 48146, 1156, 10172, 311, 3719, 264, 5507, 369, 22772, 2955, 1555, 304, 5554, 4042, 23061, 315, 18713, 65916, 2077, 304, 279, 2317, 315, 8624, 323, 5623, 6514, 13, 4802, 11579, 33001, 36815, 24203, 706, 3719, 459, 9749, 5507, 369, 279, 74315, 56186, 315, 6485, 323, 98882, 6067, 220, 16, 1174, 220, 17, 662, 578, 8066, 828, 7437, 527, 11383, 1511, 369, 26073, 14345, 22583, 1555, 35693, 18528, 323, 30295, 13, 5046, 4040, 2802, 527, 279, 30295, 315, 3254, 7917, 304, 2077, 311, 18713, 9225, 811, 11, 387, 433, 311, 19660, 220, 18, 1174, 6514, 220, 19, 1174, 220, 20, 477, 279, 77173, 315, 21389, 220, 21, 1174, 220, 22, 1174, 220, 23, 662, 10541, 31003, 304, 3254, 33001, 41264, 7645, 6492, 220, 24, 1174, 220, 605, 617, 9147, 279, 22654, 315, 21389, 5938, 449, 264, 18713, 65916, 11, 1803, 1413, 34579, 315, 18713, 65916, 2077, 5097, 264, 3094, 4726, 304, 430, 433, 20682, 279, 9659, 315, 828, 304, 5554, 4042, 13, 578, 5845, 311, 7068, 828, 430, 3504, 44247, 539, 3970, 2391, 4967, 374, 8104, 17436, 323, 14183, 311, 439, 704, 8838, 84979, 20212, 13, 6104, 8915, 7852, 4633, 4211, 617, 1027, 12090, 369, 52997, 3428, 33520, 33776, 430, 70755, 35693, 2077, 220, 806, 1174, 220, 717, 1174, 1778, 439, 264, 17722, 6767, 315, 53840, 11, 814, 3663, 16188, 5435, 13, 4314, 4211, 4250, 6847, 387, 60394, 304, 264, 828, 32505, 1648, 323, 1397, 37015, 11175, 315, 279, 22772, 828, 13, 24586, 311, 279, 11383, 2678, 1396, 315, 892, 3585, 2561, 11, 5137, 527, 3629, 2653, 311, 10765, 13, 34937, 287, 311, 13790, 29564, 4211, 369, 34579, 18713, 65916, 2077, 220, 21, 1174, 220, 23, 11767, 311, 3428, 60336, 2410, 369, 279, 17395, 2536, 62399, 6372, 430, 3254, 33001, 828, 3113, 13, 763, 13168, 11, 30828, 4009, 4211, 656, 539, 3663, 1521, 13693, 13, 42096, 11, 1778, 4211, 617, 1027, 12090, 369, 279, 6492, 315, 3254, 33001, 41214, 62119, 320, 2445, 31820, 7962, 80, 8, 828, 220, 1032, 1174, 220, 975, 1174, 220, 868, 1174, 220, 845, 1174, 220, 1114, 662, 763, 4040, 11, 1803, 1413, 29511, 43821, 14488, 320, 59587, 82, 8, 617, 1027, 11223, 369, 1675, 15853, 3254, 33001, 60038, 1555, 779, 19434, 42767, 3634, 37587, 220, 845, 662, 6104, 8405, 459, 7185, 10778, 311, 9749, 51743, 354, 3342, 10020, 22106, 26249, 220, 972, 1174, 420, 6492, 1587, 539, 20461, 279, 23099, 315, 480, 1111, 82, 369, 704, 8838, 84979, 20212, 13, 578, 1005, 315, 480, 1111, 82, 369, 279, 16127, 3465, 315, 704, 8838, 84979, 20212, 374, 57780, 291, 555, 16188, 27129, 25, 320, 16, 8, 480, 1111, 82, 527, 2653, 311, 5542, 369, 34030, 1579, 33520, 828, 11, 6522, 311, 1579, 86515, 5397, 20492, 449, 3544, 6103, 304, 71462, 367, 11, 323, 320, 17, 8, 480, 1111, 82, 656, 539, 2187, 369, 279, 2167, 13021, 315, 264, 15207, 7645, 4724, 865, 389, 264, 42767, 3634, 4724, 1167, 1174, 3339, 433, 5107, 477, 12266, 311, 7068, 264, 2849, 449, 264, 743, 315, 12974, 6012, 13, 763, 5369, 11, 369, 34030, 828, 11, 480, 1111, 82, 617, 539, 3686, 6982, 22934, 927, 279, 35388, 4244, 1697, 3313, 967, 53598, 320, 13114, 36, 8, 220, 777, 320, 19331, 7609, 2057, 23075, 1521, 5435, 11, 584, 5918, 1156, 10172, 11, 902, 374, 3196, 389, 264, 650, 13983, 11093, 449, 4724, 802, 411, 46366, 11, 449, 459, 18112, 30464, 369, 1156, 31820, 7962, 80, 828, 13, 1156, 10172, 20682, 20492, 315, 19660, 323, 19405, 2077, 315, 7917, 369, 44247, 28310, 505, 4967, 828, 4028, 2849, 4595, 11, 7978, 323, 9606, 13, 763, 264, 7353, 29531, 11, 433, 704, 716, 10008, 1023, 4754, 34579, 20414, 11, 1778, 439, 13790, 5528, 11, 35787, 4244, 1697, 3313, 967, 53598, 320, 34, 13114, 36, 8, 220, 508, 323, 1742, 8481, 480, 1111, 82, 13, 578, 29531, 315, 3892, 1803, 1413, 30828, 4009, 4211, 1288, 3118, 264, 15525, 5211, 369, 279, 4029, 9204, 10708, 323, 9669, 369, 1778, 4211, 994, 9435, 311, 1156, 31820, 7962, 80, 828, 13, 1156, 10172, 374, 3196, 389, 27127, 5072, 220, 1691, 323, 389, 279, 3254, 33001, 6492, 66994, 32208, 3368, 220, 1313, 662, 18591, 1156, 10172, 30357, 56978, 3254, 33001, 18713, 65916, 2077, 704, 8838, 84979, 5234, 33520, 1156, 31820, 7962, 80, 828, 374, 11383, 19655, 311, 387, 1664, 1719, 17820, 1534, 555, 264, 3428, 33520, 73929, 40986, 505, 279, 17413, 315, 279, 16940, 15207, 23331, 14488, 13, 9303, 6492, 26249, 10213, 5357, 389, 3752, 4954, 279, 73929, 1701, 4876, 6108, 12823, 220, 1419, 1174, 220, 1187, 304, 279, 3634, 9575, 19212, 555, 264, 2478, 12717, 6956, 13, 4497, 6051, 11, 279, 73929, 706, 1027, 62653, 1701, 30828, 14488, 220, 1032, 1174, 220, 975, 1174, 220, 868, 1174, 220, 845, 1174, 220, 1114, 662, 1666, 304, 1023, 3851, 5151, 220, 914, 1174, 220, 1627, 1174, 304, 279, 42767, 12908, 315, 1521, 4211, 11, 279, 893, 333, 18938, 3113, 50013, 398, 4382, 6012, 11, 1778, 439, 13489, 13790, 25776, 315, 23851, 369, 42767, 7482, 26073, 264, 3682, 961, 315, 279, 54709, 304, 279, 828, 13, 32140, 11, 13790, 71462, 811, 315, 279, 3428, 33520, 73929, 1436, 304, 17966, 12602, 54709, 5552, 311, 18713, 65916, 323, 1023, 22590, 2850, 988, 320, 10254, 67082, 7181, 220, 16, 323, 43491, 278, 23966, 13, 220, 16, 7609, 6914, 1475, 2849, 602, 449, 7645, 5643, 865, 602, 387, 32971, 555, 264, 3977, 281, 602, 1174, 902, 11105, 264, 44279, 7180, 4028, 279, 4459, 73929, 11, 1778, 439, 18713, 65916, 11, 9606, 477, 7309, 13, 2057, 1212, 449, 11, 584, 9855, 1193, 1403, 4787, 220, 15, 320, 359, 77468, 75325, 8, 323, 220, 16, 320, 77468, 75325, 570, 6914, 603, 4726, 2980, 279, 35787, 8141, 1144, 2358, 59, 275, 90, 47, 3500, 59, 2414, 7, 314, 87, 5431, 36802, 92650, 47215, 3500, 89, 5431, 7385, 5431, 92, 1144, 1315, 10929, 8, 1174, 902, 22204, 430, 1855, 2849, 865, 602, 4131, 505, 264, 3428, 33520, 13340, 1167, 602, 304, 3044, 281, 602, 662, 1226, 1005, 264, 650, 13983, 311, 1646, 1144, 2358, 59, 275, 90, 47, 3500, 59, 2414, 7, 314, 87, 5431, 36802, 92650, 47215, 3500, 89, 5431, 7385, 5431, 92, 1144, 1315, 10929, 8, 304, 1202, 44393, 389, 1167, 602, 323, 4724, 802, 411, 46366, 304, 279, 42767, 3634, 315, 650, 13983, 311, 1646, 279, 44393, 389, 281, 602, 320, 30035, 13, 220, 16, 7609, 23966, 13, 220, 16, 25, 1156, 10172, 11, 264, 1749, 311, 7168, 3254, 33001, 18713, 65916, 2077, 13, 16644, 264, 743, 315, 13468, 2849, 4595, 304, 2585, 323, 41959, 11, 584, 9395, 311, 7168, 279, 18713, 65916, 2077, 315, 264, 502, 2849, 955, 362, 320, 12481, 8, 555, 4967, 264, 1646, 430, 47310, 311, 93640, 279, 2077, 315, 279, 7917, 304, 279, 4967, 743, 13, 25218, 1156, 10172, 11, 279, 1646, 374, 264, 4244, 1697, 3313, 28106, 11, 323, 279, 20492, 527, 12457, 1701, 4724, 802, 411, 46366, 304, 279, 42767, 3634, 315, 279, 3313, 28106, 13, 45863, 11, 584, 2447, 15207, 7645, 22323, 1139, 264, 42767, 3634, 1701, 459, 24592, 4009, 323, 6994, 264, 4724, 70434, 430, 128257, 198, 128256, 78191, 198, 35353, 13230, 71554, 2315, 315, 36853, 304, 264, 9498, 1614, 527, 5246, 2133, 311, 387, 2561, 11, 304, 4040, 11, 279, 11344, 14299, 43443, 13, 1115, 374, 264, 5199, 3094, 304, 2731, 8830, 7917, 11, 39881, 323, 36853, 304, 9498, 1614, 323, 5825, 264, 5905, 994, 13493, 14759, 11, 16967, 323, 27723, 8624, 13, 4452, 11, 4245, 311, 279, 33638, 1396, 315, 3284, 28559, 315, 6514, 323, 8624, 4787, 11, 24050, 1521, 828, 311, 70755, 8624, 323, 8624, 6514, 304, 8776, 2324, 8198, 70760, 374, 9511, 88092, 323, 34348, 11, 323, 9093, 539, 69311, 13, 11683, 324, 2718, 34579, 35693, 2077, 311, 18713, 9225, 811, 320, 68, 1326, 2637, 8624, 11, 32246, 11, 19465, 39455, 8, 374, 264, 8792, 5915, 315, 55580, 34458, 13, 10541, 4211, 3196, 389, 29564, 323, 7852, 4633, 20414, 3073, 11, 912, 5780, 71856, 6108, 6425, 31528, 369, 653, 5598, 2841, 1579, 33520, 44247, 706, 3686, 1027, 2561, 13, 763, 5369, 11, 1156, 10172, 374, 279, 1176, 5507, 430, 56978, 35693, 2077, 704, 8838, 84979, 13, 1115, 3445, 430, 1156, 10172, 11, 422, 16572, 389, 828, 430, 12602, 279, 2515, 315, 18713, 9225, 811, 369, 264, 2728, 1887, 11, 374, 3025, 311, 1304, 15062, 20492, 369, 264, 2204, 1887, 13, 330, 2520, 279, 1176, 892, 11, 584, 617, 279, 6776, 311, 1005, 828, 8066, 304, 832, 1646, 1887, 1778, 439, 8814, 323, 1005, 279, 828, 311, 7168, 8624, 477, 15419, 2077, 304, 3823, 6978, 1359, 1071, 65552, 22503, 69, 48955, 72, 11, 2405, 920, 13, 5575, 320, 39, 24037, 71, 6312, 89, 1901, 306, 10952, 90366, 323, 7146, 10782, 15915, 37714, 90366, 570, 1156, 10172, 374, 264, 1803, 1413, 5655, 6975, 1646, 430, 28605, 1154, 6848, 505, 2217, 11, 8668, 323, 4221, 8863, 11, 323, 11, 369, 279, 1176, 892, 11, 17208, 1521, 6848, 311, 1646, 279, 7865, 315, 264, 2849, 304, 5554, 4042, 13, 578, 1828, 3094, 369, 279, 2128, 10742, 279, 18899, 1156, 10172, 311, 264, 7373, 828, 32505, 55986, 11, 7859, 1202, 60336, 2410, 311, 7431, 279, 4007, 315, 28559, 315, 18713, 9225, 811, 13, 330, 1687, 649, 1457, 1212, 74142, 1156, 10172, 311, 4320, 810, 323, 810, 6485, 4860, 922, 19338, 1359, 1071, 8683, 26296, 11, 8068, 23896, 11, 323, 19797, 1122, 578, 285, 11, 10783, 315, 279, 10181, 315, 93028, 40023, 323, 16478, 315, 92102, 77349, 315, 63711, 15264, 520, 7146, 10782, 15915, 37714, 90366, 13, 220, 128257, 198 ]

1,765

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract We present a new 4D printing approach that can create high resolution (up to a few microns), multimaterial shape memory polymer (SMP) architectures. The approach is based on high resolution projection microstereolithography (PμSL) and uses a family of photo-curable methacrylate based copolymer networks. We designed the constituents and compositions to exhibit desired thermomechanical behavior (including rubbery modulus, glass transition temperature and failure strain which is more than 300% and larger than any existing printable materials) to enable controlled shape memory behavior. We used a high resolution, high contrast digital micro display to ensure high resolution of photo-curing methacrylate based SMPs that requires higher exposure energy than more common acrylate based polymers. An automated material exchange process enables the manufacture of 3D composite architectures from multiple photo-curable SMPs. In order to understand the behavior of the 3D composite microarchitectures, we carry out high fidelity computational simulations of their complex nonlinear, time-dependent behavior and study important design considerations including local deformation, shape fixity and free recovery rate. Simulations are in good agreement with experiments for a series of single and multimaterial components and can be used to facilitate the design of SMP 3D structures. Introduction Three-dimension (3D) printing technology allows the creation of complex geometries with precisely prescribed microarchitectures that enable new functionality or improved and even optimal performance. While 3D printing has largely emphasized manufacturing with a single material, recent advances in multimaterial printing enable the creation of heterogeneous structures or composites that have myriad scientific and technological applications 1 , 2 , 3 , 4 , 5 . Commercial printing systems with these capabilities have been used in many innovative applications, but are limited because their development has largely proceeded with objectives of creating printed components with reliable mechanical properties and applications have generally emphasized linear elastic behavior with small deformations where the innovation arises from the sophisticated geometry. Independently, soft active materials (SAMs) as a class of emerging materials with the capability of exhibiting large elastic deformation in response to environmental stimuli such as heat 6 , 7 , light 8 , 9 and electricity 10 , 11 , are enabling the creation of functional active components. SAMs including shape memory polymers (SMPs), hydrogels, dielectric elastomers have been used to fabricate biomedical devices 7 , 12 , 13 , wearable devices 14 , 15 , artificial muscles 10 , 11 and other smart products 16 , 17 , 18 . However, applications of SAMs are limited by the current manufacturing approaches which constrain active structures and devices to simple geometries, often created with a single material and they have yet to broadly exploit the potential of tailored microarchitectures. This picture is changing as 3D printing and SAMs are being integrated. The most notable example is the recently developed “4D printing” technology 2 , 3 in which the printed 3D structures are able to actively transform configurations over time in response to environmental stimuli. There are two types of SAMs mainly used to realize 4D printing: hydrogels that swell when solvent molecules diffuse into polymer network and shape memory polymers (SMPs) that are capable of fixing temporary shapes and recovering to the permanent shape upon heating. The examples of the hydrogel-based 4D printing include complex self-evolving structures actuated by multilayer joints 5 , active valves made of thermally sensitive hydrogel 19 , pattern transformation realized by heat-shrinkable polymer 20 and biominic 4D printing achieved by anisotropic hydrogel composites with cellulose fibrils 21 . However, the low modulus of hydrogels ranging from ∼ kPa to ∼ 100 kPa 19 , 21 and the solvent diffusion based slow response rates in the time scale of a few ten minutes, hours and even days 5 , 21 , 22 make the hydrogel based 4D printing not suitable for structural and actuation applications. Compared to hydrogels, SMPs have higher modulus ranging ∼ MPa to ∼ GPa 7 , 23 and faster response rates (in the scale of seconds to minutes depending on actuation temperature) 24 , 25 . The examples of the SMP based 4D printing include printed active composites where precisely prescribed SMP fibers were used to activate the complex shape change 2 , 3 , sequential self-folding structured where SMP hinges with different responding rates were deliberately placed at different positions 4 and multi-shape active composites where two SMP fibers with different glass transition temperatures 26 . To date, the SMP based 4D printing were mainly realized by commercial Polyjet 3D printer (Stratasys, Objet) which create materials with properties ranging between rigid and elastomeric by mixing the two base resins. The fact that users are not allowed to freely tune the thermomechanical properties beyond the realm of available resins impedes this 4D printing technology to advance to a wider range of applications. For example, the capability of 4D printed actuation is limited as the printed digital materials break at 10–25% 27 ; the printed structures could not be used in high temperature applications as the highest glass transition temperature of the available resin is about ∼ 70 °C 4 . In addition, this technology is not suitable for microscale applications as the lateral printing resolution is up to 200 μm inherently limited by the Polyjet printing method 28 . In this paper we report a new approach that enables high resolution multimaterial 4D printing by printing highly tailorable SMPs on a projection microstereolithography (PμSL) based additive manufacturing system. We synthesize photo-curable methacrylate based copolymer networks using commercially-available materials. By tuning the material constituents and compositions, the flexibility of the methacrylate based copolymer networks enables highly tailorable SMP thermomechanical properties including rubbery modulus (from ∼ MPa to ∼ 100 MPa), glass transition temperature (from ∼ −50 °C to ∼ 180 °C) and the failure strain (up to ∼ 300%). Methacrylate based SMPs with different constituents or compositions form strong interface bonds with each other and enable fabrication of 3D structures made of multiple SMPs that can exhibit new functionality resulting from their dynamic thermomechanical properties. The PμSL based additive manufacturing system with", "role": "user" }, { "content": "Engineers from MIT and Singapore University of Technology and Design (SUTD) are using light to print three-dimensional structures that \"remember\" their original shapes. Even after being stretched, twisted, and bent at extreme angles, the structures—from small coils and multimaterial flowers, to an inch-tall replica of the Eiffel tower—sprang back to their original forms within seconds of being heated to a certain temperature \"sweet spot.\" For some structures, the researchers were able to print micron-scale features as small as the diameter of a human hair—dimensions that are at least one-tenth as big as what others have been able to achieve with printable shape-memory materials. The team's results were published earlier this month in the online journal Scientific Reports. Nicholas X. Fang, associate professor of mechanical engineering at MIT, says shape-memory polymers that can predictably morph in response to temperature can be useful for a number of applications, from soft actuators that turn solar panels toward the sun, to tiny drug capsules that open upon early signs of infection. \"We ultimately want to use body temperature as a trigger,\" Fang says. \"If we can design these polymers properly, we may be able to form a drug delivery device that will only release medicine at the sign of a fever.\" Fang's coauthors include former MIT-SUTD research fellow Qi \"Kevin\" Ge, now an assistant professor at SUTD; former MIT research associate Howon Lee, now an assistant professor at Rutgers University; and others from SUTD and Georgia Institute of Technology. Ge says the process of 3-D printing shape-memory materials can also be thought of as 4-D printing, as the structures are designed to change over the fourth dimension—time. \"Our method not only enables 4-D printing at the micron-scale, but also suggests recipes to print shape-memory polymers that can be stretched 10 times larger than those printed by commercial 3-D printers,\" Ge says. \"This will advance 4-D printing into a wide variety of practical applications, including biomedical devices, deployable aerospace structures, and shape-changing photovoltaic solar cells.\" Need for speed Fang and others have been exploring the use of soft, active materials as reliable, pliable tools. These new and emerging materials, which include shape-memory polymers, can stretch and deform dramatically in response to environmental stimuli such as heat, light, and electricity—properties that researchers have been investigating for use in biomedical devices, soft robotics, wearable sensors, and artificial muscles. A shape-memory Eiffel tower was 3-D printed using projection microstereolithography. It is shown recovering from being bent, after toughening on a heated Singapore dollar coin. Credit: Qi (Kevin) Ge Shape-memory polymers are particularly intriguing: These materials can switch between two states—a harder, low-temperature, amorphous state, and a soft, high-temperature, rubbery state. The bent and stretched shapes can be \"frozen\" at room temperature, and when heated the materials will \"remember\" and snap back to their original sturdy form. To fabricate shape-memory structures, some researchers have looked to 3-D printing, as the technology allows them to custom-design structures with relatively fine detail. However, using conventional 3-D printers, researchers have only been able to design structures with details no smaller than a few millimeters. Fang says this size restriction also limits how fast the material can recover its original shape. \"The reality is that, if you're able to make it to much smaller dimensions, these materials can actually respond very quickly, within seconds,\" Fang says. \"For example, a flower can release pollen in milliseconds. It can only do that because its actuation mechanisms are at the micron scale.\" Printing with light To print shape-memory structures with even finer details, Fang and his colleagues used a 3-D printing process they have pioneered, called microstereolithography, in which they use light from a projector to print patterns on successive layers of resin. The researchers first create a model of a structure using computer-aided design (CAD) software, then divide the model into hundreds of slices, each of which they send through the projector as a bitmap—an image file format that represents each layer as an arrangement of very fine pixels. The projector then shines light in the pattern of the bitmap, onto a liquid resin, or polymer solution, etching the pattern into the resin, which then solidifies. \"We're printing with light, layer by layer,\" Fang says. \"It's almost like how dentists form replicas of teeth and fill cavities, except that we're doing it with high-resolution lenses that come from the semiconductor industry, which give us intricate parts, with dimensions comparable to the diameter of a human hair.\" The researchers then looked through the scientific literature to identify an ideal mix of polymers to create a shape-memory material on which to print their light patterns. They picked two polymers, one composed of long-chain polymers, or spaghetti-like strands, and the other resembling more of a stiff scaffold. When mixed together and cured, the material can be stretched and twisted dramatically without breaking. What's more, the material can bounce back to its original printed form, within a specific temperature range—in this case, between 40 and 180 degrees Celsius (104 to 356 degrees Fahrenheit). Credit: Massachusetts Institute of Technology The team printed a variety of structures, including coils, flowers, and the miniature Eiffel tower, whose full-size counterpart is known for its intricate steel and beam patterns. Fang found that the structures could be stretched to three times their original length without breaking. When they were exposed to heat within the range of 40 C to 180 C, they snapped back to their original shapes within seconds. \"Because we're using our own printers that offer much smaller pixel size, we're seeing much faster response, on the order of seconds,\" Fang says. \"If we can push to even smaller dimensions, we may also be able to push their response time, to milliseconds.\" \"This is a very advanced 3-D printing method compared to traditional nozzle or ink-jet based printers,\" says Shaochen Chen, professor of nano-engineering at the University of California at San Diego, who was not involved in the research. \"The method's main advantages are faster printing and better structural integrity.\" Soft grip To demonstrate a simple application for the shape-memory structures, Fang and his colleagues printed a small, rubbery, claw-like gripper. They attached a thin handle to the base of the gripper, then stretched the gripper's claws open. When they cranked the temperature of the surrounding air to at least 40 C, the gripper closed around whatever the engineers placed beneath it. \"The grippers are a nice example of how manipulation can be done with soft materials,\" Fang says. \"We showed that it is possible to pick up a small bolt, and also even fish eggs and soft tofu. That type of soft grip is probably very unique and beneficial.\" Going forward, he hopes to find combinations of polymers to make shape-memory materials that react to slightly lower temperatures, approaching the range of human body temperatures, to design soft, active, controllable drug delivery capsules. He says the material may also be printed as soft, responsive hinges to help solar panels track the sun. \"Very often, excessive heat will build up on the back side of the solar cell, so you could use [shape-memory materials] as an actuation mechanism to tune the inclination angle of the solar cell,\" Fang says. \"So we think there will probably be more applications that we can demonstrate.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract We present a new 4D printing approach that can create high resolution (up to a few microns), multimaterial shape memory polymer (SMP) architectures. The approach is based on high resolution projection microstereolithography (PμSL) and uses a family of photo-curable methacrylate based copolymer networks. We designed the constituents and compositions to exhibit desired thermomechanical behavior (including rubbery modulus, glass transition temperature and failure strain which is more than 300% and larger than any existing printable materials) to enable controlled shape memory behavior. We used a high resolution, high contrast digital micro display to ensure high resolution of photo-curing methacrylate based SMPs that requires higher exposure energy than more common acrylate based polymers. An automated material exchange process enables the manufacture of 3D composite architectures from multiple photo-curable SMPs. In order to understand the behavior of the 3D composite microarchitectures, we carry out high fidelity computational simulations of their complex nonlinear, time-dependent behavior and study important design considerations including local deformation, shape fixity and free recovery rate. Simulations are in good agreement with experiments for a series of single and multimaterial components and can be used to facilitate the design of SMP 3D structures. Introduction Three-dimension (3D) printing technology allows the creation of complex geometries with precisely prescribed microarchitectures that enable new functionality or improved and even optimal performance. While 3D printing has largely emphasized manufacturing with a single material, recent advances in multimaterial printing enable the creation of heterogeneous structures or composites that have myriad scientific and technological applications 1 , 2 , 3 , 4 , 5 . Commercial printing systems with these capabilities have been used in many innovative applications, but are limited because their development has largely proceeded with objectives of creating printed components with reliable mechanical properties and applications have generally emphasized linear elastic behavior with small deformations where the innovation arises from the sophisticated geometry. Independently, soft active materials (SAMs) as a class of emerging materials with the capability of exhibiting large elastic deformation in response to environmental stimuli such as heat 6 , 7 , light 8 , 9 and electricity 10 , 11 , are enabling the creation of functional active components. SAMs including shape memory polymers (SMPs), hydrogels, dielectric elastomers have been used to fabricate biomedical devices 7 , 12 , 13 , wearable devices 14 , 15 , artificial muscles 10 , 11 and other smart products 16 , 17 , 18 . However, applications of SAMs are limited by the current manufacturing approaches which constrain active structures and devices to simple geometries, often created with a single material and they have yet to broadly exploit the potential of tailored microarchitectures. This picture is changing as 3D printing and SAMs are being integrated. The most notable example is the recently developed “4D printing” technology 2 , 3 in which the printed 3D structures are able to actively transform configurations over time in response to environmental stimuli. There are two types of SAMs mainly used to realize 4D printing: hydrogels that swell when solvent molecules diffuse into polymer network and shape memory polymers (SMPs) that are capable of fixing temporary shapes and recovering to the permanent shape upon heating. The examples of the hydrogel-based 4D printing include complex self-evolving structures actuated by multilayer joints 5 , active valves made of thermally sensitive hydrogel 19 , pattern transformation realized by heat-shrinkable polymer 20 and biominic 4D printing achieved by anisotropic hydrogel composites with cellulose fibrils 21 . However, the low modulus of hydrogels ranging from ∼ kPa to ∼ 100 kPa 19 , 21 and the solvent diffusion based slow response rates in the time scale of a few ten minutes, hours and even days 5 , 21 , 22 make the hydrogel based 4D printing not suitable for structural and actuation applications. Compared to hydrogels, SMPs have higher modulus ranging ∼ MPa to ∼ GPa 7 , 23 and faster response rates (in the scale of seconds to minutes depending on actuation temperature) 24 , 25 . The examples of the SMP based 4D printing include printed active composites where precisely prescribed SMP fibers were used to activate the complex shape change 2 , 3 , sequential self-folding structured where SMP hinges with different responding rates were deliberately placed at different positions 4 and multi-shape active composites where two SMP fibers with different glass transition temperatures 26 . To date, the SMP based 4D printing were mainly realized by commercial Polyjet 3D printer (Stratasys, Objet) which create materials with properties ranging between rigid and elastomeric by mixing the two base resins. The fact that users are not allowed to freely tune the thermomechanical properties beyond the realm of available resins impedes this 4D printing technology to advance to a wider range of applications. For example, the capability of 4D printed actuation is limited as the printed digital materials break at 10–25% 27 ; the printed structures could not be used in high temperature applications as the highest glass transition temperature of the available resin is about ∼ 70 °C 4 . In addition, this technology is not suitable for microscale applications as the lateral printing resolution is up to 200 μm inherently limited by the Polyjet printing method 28 . In this paper we report a new approach that enables high resolution multimaterial 4D printing by printing highly tailorable SMPs on a projection microstereolithography (PμSL) based additive manufacturing system. We synthesize photo-curable methacrylate based copolymer networks using commercially-available materials. By tuning the material constituents and compositions, the flexibility of the methacrylate based copolymer networks enables highly tailorable SMP thermomechanical properties including rubbery modulus (from ∼ MPa to ∼ 100 MPa), glass transition temperature (from ∼ −50 °C to ∼ 180 °C) and the failure strain (up to ∼ 300%). Methacrylate based SMPs with different constituents or compositions form strong interface bonds with each other and enable fabrication of 3D structures made of multiple SMPs that can exhibit new functionality resulting from their dynamic thermomechanical properties. The PμSL based additive manufacturing system with<|im_end|> <|im_start|>assistant Engineers from MIT and Singapore University of Technology and Design (SUTD) are using light to print three-dimensional structures that "remember" their original shapes. Even after being stretched, twisted, and bent at extreme angles, the structures—from small coils and multimaterial flowers, to an inch-tall replica of the Eiffel tower—sprang back to their original forms within seconds of being heated to a certain temperature "sweet spot." For some structures, the researchers were able to print micron-scale features as small as the diameter of a human hair—dimensions that are at least one-tenth as big as what others have been able to achieve with printable shape-memory materials. The team's results were published earlier this month in the online journal Scientific Reports. Nicholas X. Fang, associate professor of mechanical engineering at MIT, says shape-memory polymers that can predictably morph in response to temperature can be useful for a number of applications, from soft actuators that turn solar panels toward the sun, to tiny drug capsules that open upon early signs of infection. "We ultimately want to use body temperature as a trigger," Fang says. "If we can design these polymers properly, we may be able to form a drug delivery device that will only release medicine at the sign of a fever." Fang's coauthors include former MIT-SUTD research fellow Qi "Kevin" Ge, now an assistant professor at SUTD; former MIT research associate Howon Lee, now an assistant professor at Rutgers University; and others from SUTD and Georgia Institute of Technology. Ge says the process of 3-D printing shape-memory materials can also be thought of as 4-D printing, as the structures are designed to change over the fourth dimension—time. "Our method not only enables 4-D printing at the micron-scale, but also suggests recipes to print shape-memory polymers that can be stretched 10 times larger than those printed by commercial 3-D printers," Ge says. "This will advance 4-D printing into a wide variety of practical applications, including biomedical devices, deployable aerospace structures, and shape-changing photovoltaic solar cells." Need for speed Fang and others have been exploring the use of soft, active materials as reliable, pliable tools. These new and emerging materials, which include shape-memory polymers, can stretch and deform dramatically in response to environmental stimuli such as heat, light, and electricity—properties that researchers have been investigating for use in biomedical devices, soft robotics, wearable sensors, and artificial muscles. A shape-memory Eiffel tower was 3-D printed using projection microstereolithography. It is shown recovering from being bent, after toughening on a heated Singapore dollar coin. Credit: Qi (Kevin) Ge Shape-memory polymers are particularly intriguing: These materials can switch between two states—a harder, low-temperature, amorphous state, and a soft, high-temperature, rubbery state. The bent and stretched shapes can be "frozen" at room temperature, and when heated the materials will "remember" and snap back to their original sturdy form. To fabricate shape-memory structures, some researchers have looked to 3-D printing, as the technology allows them to custom-design structures with relatively fine detail. However, using conventional 3-D printers, researchers have only been able to design structures with details no smaller than a few millimeters. Fang says this size restriction also limits how fast the material can recover its original shape. "The reality is that, if you're able to make it to much smaller dimensions, these materials can actually respond very quickly, within seconds," Fang says. "For example, a flower can release pollen in milliseconds. It can only do that because its actuation mechanisms are at the micron scale." Printing with light To print shape-memory structures with even finer details, Fang and his colleagues used a 3-D printing process they have pioneered, called microstereolithography, in which they use light from a projector to print patterns on successive layers of resin. The researchers first create a model of a structure using computer-aided design (CAD) software, then divide the model into hundreds of slices, each of which they send through the projector as a bitmap—an image file format that represents each layer as an arrangement of very fine pixels. The projector then shines light in the pattern of the bitmap, onto a liquid resin, or polymer solution, etching the pattern into the resin, which then solidifies. "We're printing with light, layer by layer," Fang says. "It's almost like how dentists form replicas of teeth and fill cavities, except that we're doing it with high-resolution lenses that come from the semiconductor industry, which give us intricate parts, with dimensions comparable to the diameter of a human hair." The researchers then looked through the scientific literature to identify an ideal mix of polymers to create a shape-memory material on which to print their light patterns. They picked two polymers, one composed of long-chain polymers, or spaghetti-like strands, and the other resembling more of a stiff scaffold. When mixed together and cured, the material can be stretched and twisted dramatically without breaking. What's more, the material can bounce back to its original printed form, within a specific temperature range—in this case, between 40 and 180 degrees Celsius (104 to 356 degrees Fahrenheit). Credit: Massachusetts Institute of Technology The team printed a variety of structures, including coils, flowers, and the miniature Eiffel tower, whose full-size counterpart is known for its intricate steel and beam patterns. Fang found that the structures could be stretched to three times their original length without breaking. When they were exposed to heat within the range of 40 C to 180 C, they snapped back to their original shapes within seconds. "Because we're using our own printers that offer much smaller pixel size, we're seeing much faster response, on the order of seconds," Fang says. "If we can push to even smaller dimensions, we may also be able to push their response time, to milliseconds." "This is a very advanced 3-D printing method compared to traditional nozzle or ink-jet based printers," says Shaochen Chen, professor of nano-engineering at the University of California at San Diego, who was not involved in the research. "The method's main advantages are faster printing and better structural integrity." Soft grip To demonstrate a simple application for the shape-memory structures, Fang and his colleagues printed a small, rubbery, claw-like gripper. They attached a thin handle to the base of the gripper, then stretched the gripper's claws open. When they cranked the temperature of the surrounding air to at least 40 C, the gripper closed around whatever the engineers placed beneath it. "The grippers are a nice example of how manipulation can be done with soft materials," Fang says. "We showed that it is possible to pick up a small bolt, and also even fish eggs and soft tofu. That type of soft grip is probably very unique and beneficial." Going forward, he hopes to find combinations of polymers to make shape-memory materials that react to slightly lower temperatures, approaching the range of human body temperatures, to design soft, active, controllable drug delivery capsules. He says the material may also be printed as soft, responsive hinges to help solar panels track the sun. "Very often, excessive heat will build up on the back side of the solar cell, so you could use [shape-memory materials] as an actuation mechanism to tune the inclination angle of the solar cell," Fang says. "So we think there will probably be more applications that we can demonstrate." <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 1226, 3118, 264, 502, 220, 19, 35, 18991, 5603, 430, 649, 1893, 1579, 11175, 320, 455, 311, 264, 2478, 19748, 26692, 705, 80149, 2229, 6211, 5044, 47393, 320, 50, 5901, 8, 78335, 13, 578, 5603, 374, 3196, 389, 1579, 11175, 22343, 8162, 267, 486, 48218, 5814, 320, 47, 44223, 8143, 8, 323, 5829, 264, 3070, 315, 6685, 1824, 18835, 21747, 582, 894, 5185, 3196, 6293, 5849, 1195, 14488, 13, 1226, 6319, 279, 51720, 323, 62644, 311, 31324, 12974, 30945, 638, 5776, 950, 7865, 320, 16564, 23506, 88, 75124, 11, 9168, 9320, 9499, 323, 8060, 26800, 902, 374, 810, 1109, 220, 3101, 4, 323, 8294, 1109, 904, 6484, 43095, 7384, 8, 311, 7431, 14400, 6211, 5044, 7865, 13, 1226, 1511, 264, 1579, 11175, 11, 1579, 13168, 7528, 8162, 3113, 311, 6106, 1579, 11175, 315, 6685, 1824, 1711, 21747, 582, 894, 5185, 3196, 93900, 82, 430, 7612, 5190, 14675, 4907, 1109, 810, 4279, 1645, 894, 5185, 3196, 46033, 388, 13, 1556, 28598, 3769, 9473, 1920, 20682, 279, 30847, 315, 220, 18, 35, 28814, 78335, 505, 5361, 6685, 1824, 18835, 93900, 82, 13, 763, 2015, 311, 3619, 279, 7865, 315, 279, 220, 18, 35, 28814, 8162, 1132, 8525, 1439, 11, 584, 6920, 704, 1579, 83604, 55580, 47590, 315, 872, 6485, 75098, 11, 892, 43918, 7865, 323, 4007, 3062, 2955, 38864, 2737, 2254, 91621, 11, 6211, 5155, 488, 323, 1949, 13654, 4478, 13, 4567, 7607, 527, 304, 1695, 9306, 449, 21896, 369, 264, 4101, 315, 3254, 323, 80149, 2229, 6956, 323, 649, 387, 1511, 311, 28696, 279, 2955, 315, 93900, 220, 18, 35, 14726, 13, 29438, 14853, 1773, 18658, 320, 18, 35, 8, 18991, 5557, 6276, 279, 9886, 315, 6485, 69086, 4108, 449, 24559, 32031, 8162, 1132, 8525, 1439, 430, 7431, 502, 15293, 477, 13241, 323, 1524, 23669, 5178, 13, 6104, 220, 18, 35, 18991, 706, 14090, 46728, 15266, 449, 264, 3254, 3769, 11, 3293, 31003, 304, 80149, 2229, 18991, 7431, 279, 9886, 315, 98882, 14726, 477, 470, 81239, 430, 617, 52909, 12624, 323, 30116, 8522, 220, 16, 1174, 220, 17, 1174, 220, 18, 1174, 220, 19, 1174, 220, 20, 662, 28943, 18991, 6067, 449, 1521, 17357, 617, 1027, 1511, 304, 1690, 18699, 8522, 11, 719, 527, 7347, 1606, 872, 4500, 706, 14090, 45374, 449, 26470, 315, 6968, 17124, 6956, 449, 15062, 22936, 6012, 323, 8522, 617, 8965, 46728, 13790, 36573, 7865, 449, 2678, 79212, 811, 1405, 279, 19297, 48282, 505, 279, 27877, 17484, 13, 17565, 4501, 11, 8579, 4642, 7384, 320, 87434, 82, 8, 439, 264, 538, 315, 24084, 7384, 449, 279, 23099, 315, 87719, 3544, 36573, 91621, 304, 2077, 311, 12434, 56688, 1778, 439, 8798, 220, 21, 1174, 220, 22, 1174, 3177, 220, 23, 1174, 220, 24, 323, 18200, 220, 605, 1174, 220, 806, 1174, 527, 28462, 279, 9886, 315, 16003, 4642, 6956, 13, 47687, 82, 2737, 6211, 5044, 46033, 388, 320, 50, 5901, 82, 705, 17055, 70, 2053, 11, 2815, 47262, 92185, 69638, 617, 1027, 1511, 311, 13354, 349, 94612, 7766, 220, 22, 1174, 220, 717, 1174, 220, 1032, 1174, 78348, 7766, 220, 975, 1174, 220, 868, 1174, 21075, 24569, 220, 605, 1174, 220, 806, 323, 1023, 7941, 3956, 220, 845, 1174, 220, 1114, 1174, 220, 972, 662, 4452, 11, 8522, 315, 47687, 82, 527, 7347, 555, 279, 1510, 15266, 20414, 902, 80799, 4642, 14726, 323, 7766, 311, 4382, 69086, 4108, 11, 3629, 3549, 449, 264, 3254, 3769, 323, 814, 617, 3686, 311, 44029, 33294, 279, 4754, 315, 41891, 8162, 1132, 8525, 1439, 13, 1115, 6945, 374, 10223, 439, 220, 18, 35, 18991, 323, 47687, 82, 527, 1694, 18751, 13, 578, 1455, 28289, 3187, 374, 279, 6051, 8040, 1054, 19, 35, 18991, 863, 5557, 220, 17, 1174, 220, 18, 304, 902, 279, 17124, 220, 18, 35, 14726, 527, 3025, 311, 22815, 5276, 33483, 927, 892, 304, 2077, 311, 12434, 56688, 13, 2684, 527, 1403, 4595, 315, 47687, 82, 14918, 1511, 311, 13383, 220, 19, 35, 18991, 25, 17055, 70, 2053, 430, 78353, 994, 69996, 35715, 55517, 1139, 47393, 4009, 323, 6211, 5044, 46033, 388, 320, 50, 5901, 82, 8, 430, 527, 13171, 315, 36351, 13643, 21483, 323, 42386, 311, 279, 15690, 6211, 5304, 24494, 13, 578, 10507, 315, 279, 17055, 29952, 6108, 220, 19, 35, 18991, 2997, 6485, 659, 91345, 20222, 14726, 1180, 13148, 555, 2814, 321, 1155, 35358, 220, 20, 1174, 4642, 64100, 1903, 315, 30945, 750, 16614, 17055, 29952, 220, 777, 1174, 5497, 18475, 15393, 555, 8798, 7666, 35465, 481, 47393, 220, 508, 323, 6160, 8129, 292, 220, 19, 35, 18991, 17427, 555, 459, 285, 79432, 17055, 29952, 470, 81239, 449, 70002, 974, 95235, 8839, 220, 1691, 662, 4452, 11, 279, 3428, 75124, 315, 17055, 70, 2053, 24950, 505, 12264, 120, 597, 20908, 311, 12264, 120, 220, 1041, 597, 20908, 220, 777, 1174, 220, 1691, 323, 279, 69996, 58430, 3196, 6435, 2077, 7969, 304, 279, 892, 5569, 315, 264, 2478, 5899, 4520, 11, 4207, 323, 1524, 2919, 220, 20, 1174, 220, 1691, 1174, 220, 1313, 1304, 279, 17055, 29952, 3196, 220, 19, 35, 18991, 539, 14791, 369, 24693, 323, 1180, 4090, 8522, 13, 59813, 311, 17055, 70, 2053, 11, 93900, 82, 617, 5190, 75124, 24950, 12264, 120, 9599, 64, 311, 12264, 120, 480, 20908, 220, 22, 1174, 220, 1419, 323, 10819, 2077, 7969, 320, 258, 279, 5569, 315, 6622, 311, 4520, 11911, 389, 1180, 4090, 9499, 8, 220, 1187, 1174, 220, 914, 662, 578, 10507, 315, 279, 93900, 3196, 220, 19, 35, 18991, 2997, 17124, 4642, 470, 81239, 1405, 24559, 32031, 93900, 49774, 1051, 1511, 311, 20891, 279, 6485, 6211, 2349, 220, 17, 1174, 220, 18, 1174, 52100, 659, 2269, 15345, 34030, 1405, 93900, 80934, 449, 2204, 30438, 7969, 1051, 36192, 9277, 520, 2204, 10093, 220, 19, 323, 7447, 7666, 2070, 4642, 470, 81239, 1405, 1403, 93900, 49774, 449, 2204, 9168, 9320, 20472, 220, 1627, 662, 2057, 2457, 11, 279, 93900, 3196, 220, 19, 35, 18991, 1051, 14918, 15393, 555, 8518, 19294, 15769, 220, 18, 35, 23185, 320, 2645, 19907, 1065, 11, 4761, 15769, 8, 902, 1893, 7384, 449, 6012, 24950, 1990, 33956, 323, 92185, 316, 11893, 555, 27890, 279, 1403, 2385, 594, 1354, 13, 578, 2144, 430, 3932, 527, 539, 5535, 311, 26662, 26306, 279, 30945, 638, 5776, 950, 6012, 7953, 279, 22651, 315, 2561, 594, 1354, 50502, 288, 420, 220, 19, 35, 18991, 5557, 311, 12178, 311, 264, 22622, 2134, 315, 8522, 13, 1789, 3187, 11, 279, 23099, 315, 220, 19, 35, 17124, 1180, 4090, 374, 7347, 439, 279, 17124, 7528, 7384, 1464, 520, 220, 605, 4235, 914, 4, 220, 1544, 2652, 279, 17124, 14726, 1436, 539, 387, 1511, 304, 1579, 9499, 8522, 439, 279, 8592, 9168, 9320, 9499, 315, 279, 2561, 54614, 374, 922, 12264, 120, 220, 2031, 37386, 34, 220, 19, 662, 763, 5369, 11, 420, 5557, 374, 539, 14791, 369, 8162, 12727, 8522, 439, 279, 45569, 18991, 11175, 374, 709, 311, 220, 1049, 33983, 76, 49188, 7347, 555, 279, 19294, 15769, 18991, 1749, 220, 1591, 662, 763, 420, 5684, 584, 1934, 264, 502, 5603, 430, 20682, 1579, 11175, 80149, 2229, 220, 19, 35, 18991, 555, 18991, 7701, 9986, 25745, 93900, 82, 389, 264, 22343, 8162, 267, 486, 48218, 5814, 320, 47, 44223, 8143, 8, 3196, 64338, 15266, 1887, 13, 1226, 6925, 27985, 6685, 1824, 18835, 21747, 582, 894, 5185, 3196, 6293, 5849, 1195, 14488, 1701, 54453, 94832, 7384, 13, 3296, 42438, 279, 3769, 51720, 323, 62644, 11, 279, 25152, 315, 279, 21747, 582, 894, 5185, 3196, 6293, 5849, 1195, 14488, 20682, 7701, 9986, 25745, 93900, 30945, 638, 5776, 950, 6012, 2737, 23506, 88, 75124, 320, 1527, 12264, 120, 9599, 64, 311, 12264, 120, 220, 1041, 9599, 64, 705, 9168, 9320, 9499, 320, 1527, 12264, 120, 25173, 1135, 37386, 34, 311, 12264, 120, 220, 5245, 37386, 34, 8, 323, 279, 8060, 26800, 320, 455, 311, 12264, 120, 220, 3101, 53172, 57175, 582, 894, 5185, 3196, 93900, 82, 449, 2204, 51720, 477, 62644, 1376, 3831, 3834, 27460, 449, 1855, 1023, 323, 7431, 59251, 315, 220, 18, 35, 14726, 1903, 315, 5361, 93900, 82, 430, 649, 31324, 502, 15293, 13239, 505, 872, 8915, 30945, 638, 5776, 950, 6012, 13, 578, 393, 44223, 8143, 3196, 64338, 15266, 1887, 449, 128257, 198, 128256, 78191, 198, 4674, 388, 505, 15210, 323, 21181, 3907, 315, 12053, 323, 7127, 320, 50, 1406, 35, 8, 527, 1701, 3177, 311, 1194, 2380, 33520, 14726, 430, 330, 30380, 1, 872, 4113, 21483, 13, 7570, 1306, 1694, 41398, 11, 38817, 11, 323, 30280, 520, 14560, 27030, 11, 279, 14726, 88958, 2678, 71860, 323, 80149, 2229, 19837, 11, 311, 459, 17560, 2442, 543, 38054, 315, 279, 469, 3168, 301, 21970, 2345, 52773, 526, 1203, 311, 872, 4113, 7739, 2949, 6622, 315, 1694, 32813, 311, 264, 3738, 9499, 330, 95928, 7858, 1210, 1789, 1063, 14726, 11, 279, 12074, 1051, 3025, 311, 1194, 95309, 13230, 4519, 439, 2678, 439, 279, 23899, 315, 264, 3823, 7013, 2345, 60339, 430, 527, 520, 3325, 832, 2442, 21341, 439, 2466, 439, 1148, 3885, 617, 1027, 3025, 311, 11322, 449, 43095, 6211, 65196, 7384, 13, 578, 2128, 596, 3135, 1051, 4756, 6931, 420, 2305, 304, 279, 2930, 8486, 38130, 29140, 13, 40796, 1630, 13, 59027, 11, 22712, 14561, 315, 22936, 15009, 520, 15210, 11, 2795, 6211, 65196, 46033, 388, 430, 649, 7168, 2915, 27448, 304, 2077, 311, 9499, 649, 387, 5505, 369, 264, 1396, 315, 8522, 11, 505, 8579, 81553, 3046, 430, 2543, 13238, 21988, 9017, 279, 7160, 11, 311, 13987, 5623, 65879, 430, 1825, 5304, 4216, 12195, 315, 19405, 13, 330, 1687, 13967, 1390, 311, 1005, 2547, 9499, 439, 264, 8346, 1359, 59027, 2795, 13, 330, 2746, 584, 649, 2955, 1521, 46033, 388, 10489, 11, 584, 1253, 387, 3025, 311, 1376, 264, 5623, 9889, 3756, 430, 690, 1193, 4984, 16088, 520, 279, 1879, 315, 264, 34653, 1210, 59027, 596, 1080, 48105, 2997, 4846, 15210, 6354, 1406, 35, 3495, 12637, 58094, 330, 48781, 1, 4323, 11, 1457, 459, 18328, 14561, 520, 328, 1406, 35, 26, 4846, 15210, 3495, 22712, 2650, 263, 12336, 11, 1457, 459, 18328, 14561, 520, 72091, 3907, 26, 323, 3885, 505, 328, 1406, 35, 323, 16272, 10181, 315, 12053, 13, 4323, 2795, 279, 1920, 315, 220, 18, 9607, 18991, 6211, 65196, 7384, 649, 1101, 387, 3463, 315, 439, 220, 19, 9607, 18991, 11, 439, 279, 14726, 527, 6319, 311, 2349, 927, 279, 11999, 13167, 2345, 1712, 13, 330, 8140, 1749, 539, 1193, 20682, 220, 19, 9607, 18991, 520, 279, 95309, 13230, 11, 719, 1101, 13533, 19141, 311, 1194, 6211, 65196, 46033, 388, 430, 649, 387, 41398, 220, 605, 3115, 8294, 1109, 1884, 17124, 555, 8518, 220, 18, 9607, 57053, 1359, 4323, 2795, 13, 330, 2028, 690, 12178, 220, 19, 9607, 18991, 1139, 264, 7029, 8205, 315, 15325, 8522, 11, 2737, 94612, 7766, 11, 10739, 481, 78164, 14726, 11, 323, 6211, 49961, 4604, 93591, 292, 13238, 7917, 1210, 14998, 369, 4732, 59027, 323, 3885, 617, 1027, 24919, 279, 1005, 315, 8579, 11, 4642, 7384, 439, 15062, 11, 628, 2205, 7526, 13, 4314, 502, 323, 24084, 7384, 11, 902, 2997, 6211, 65196, 46033, 388, 11, 649, 14841, 323, 79212, 29057, 304, 2077, 311, 12434, 56688, 1778, 439, 8798, 11, 3177, 11, 323, 18200, 2345, 13495, 430, 12074, 617, 1027, 24834, 369, 1005, 304, 94612, 7766, 11, 8579, 74706, 11, 78348, 26148, 11, 323, 21075, 24569, 13, 362, 6211, 65196, 469, 3168, 301, 21970, 574, 220, 18, 9607, 17124, 1701, 22343, 8162, 267, 486, 48218, 5814, 13, 1102, 374, 6982, 42386, 505, 1694, 30280, 11, 1306, 11292, 6147, 389, 264, 32813, 21181, 18160, 16652, 13, 16666, 25, 58094, 320, 48781, 8, 4323, 23342, 65196, 46033, 388, 527, 8104, 41765, 25, 4314, 7384, 649, 3480, 1990, 1403, 5415, 29096, 16127, 11, 3428, 12, 35658, 11, 1097, 16751, 788, 1614, 11, 323, 264, 8579, 11, 1579, 12, 35658, 11, 23506, 88, 1614, 13, 578, 30280, 323, 41398, 21483, 649, 387, 330, 69, 43340, 1, 520, 3130, 9499, 11, 323, 994, 32813, 279, 7384, 690, 330, 30380, 1, 323, 10885, 1203, 311, 872, 4113, 45652, 1376, 13, 2057, 13354, 349, 6211, 65196, 14726, 11, 1063, 12074, 617, 7111, 311, 220, 18, 9607, 18991, 11, 439, 279, 5557, 6276, 1124, 311, 2587, 47117, 14726, 449, 12309, 7060, 7872, 13, 4452, 11, 1701, 21349, 220, 18, 9607, 57053, 11, 12074, 617, 1193, 1027, 3025, 311, 2955, 14726, 449, 3649, 912, 9333, 1109, 264, 2478, 2606, 55336, 13, 59027, 2795, 420, 1404, 20020, 1101, 13693, 1268, 5043, 279, 3769, 649, 11993, 1202, 4113, 6211, 13, 330, 791, 8903, 374, 430, 11, 422, 499, 2351, 3025, 311, 1304, 433, 311, 1790, 9333, 15696, 11, 1521, 7384, 649, 3604, 6013, 1633, 6288, 11, 2949, 6622, 1359, 59027, 2795, 13, 330, 2520, 3187, 11, 264, 23153, 649, 4984, 79784, 304, 31604, 13, 1102, 649, 1193, 656, 430, 1606, 1202, 1180, 4090, 24717, 527, 520, 279, 95309, 5569, 1210, 51869, 449, 3177, 2057, 1194, 6211, 65196, 14726, 449, 1524, 73886, 3649, 11, 59027, 323, 813, 18105, 1511, 264, 220, 18, 9607, 18991, 1920, 814, 617, 96734, 11, 2663, 8162, 267, 486, 48218, 5814, 11, 304, 902, 814, 1005, 3177, 505, 264, 69085, 311, 1194, 12912, 389, 50024, 13931, 315, 54614, 13, 578, 12074, 1176, 1893, 264, 1646, 315, 264, 6070, 1701, 6500, 12, 3864, 291, 2955, 320, 49670, 8, 3241, 11, 1243, 22497, 279, 1646, 1139, 11758, 315, 35354, 11, 1855, 315, 902, 814, 3708, 1555, 279, 69085, 439, 264, 20327, 85366, 2217, 1052, 3645, 430, 11105, 1855, 6324, 439, 459, 27204, 315, 1633, 7060, 16128, 13, 578, 69085, 1243, 65880, 3177, 304, 279, 5497, 315, 279, 20327, 11, 8800, 264, 14812, 54614, 11, 477, 47393, 6425, 11, 1880, 28075, 279, 5497, 1139, 279, 54614, 11, 902, 1243, 6573, 9803, 13, 330, 1687, 2351, 18991, 449, 3177, 11, 6324, 555, 6324, 1359, 59027, 2795, 13, 330, 2181, 596, 4661, 1093, 1268, 18653, 1705, 1376, 81901, 315, 18311, 323, 5266, 57709, 1385, 11, 3734, 430, 584, 2351, 3815, 433, 449, 1579, 64036, 36057, 430, 2586, 505, 279, 87836, 5064, 11, 902, 3041, 603, 57216, 5596, 11, 449, 15696, 30139, 311, 279, 23899, 315, 264, 3823, 7013, 1210, 578, 12074, 1243, 7111, 1555, 279, 12624, 17649, 311, 10765, 459, 10728, 6651, 315, 46033, 388, 311, 1893, 264, 6211, 65196, 3769, 389, 902, 311, 1194, 872, 3177, 12912, 13, 2435, 13061, 1403, 46033, 388, 11, 832, 24306, 315, 1317, 66286, 46033, 388, 11, 477, 88010, 12970, 69864, 11, 323, 279, 1023, 71707, 810, 315, 264, 31161, 85552, 13, 3277, 9709, 3871, 323, 64688, 11, 279, 3769, 649, 387, 41398, 323, 38817, 29057, 2085, 15061, 13, 3639, 596, 810, 11, 279, 3769, 649, 34782, 1203, 311, 1202, 4113, 17124, 1376, 11, 2949, 264, 3230, 9499, 2134, 49525, 420, 1162, 11, 1990, 220, 1272, 323, 220, 5245, 12628, 62447, 320, 6849, 311, 220, 18349, 12628, 69823, 570, 16666, 25, 22108, 10181, 315, 12053, 578, 2128, 17124, 264, 8205, 315, 14726, 11, 2737, 71860, 11, 19837, 11, 323, 279, 57863, 469, 3168, 301, 21970, 11, 6832, 2539, 7321, 45116, 374, 3967, 369, 1202, 57216, 9699, 323, 24310, 12912, 13, 59027, 1766, 430, 279, 14726, 1436, 387, 41398, 311, 2380, 3115, 872, 4113, 3160, 2085, 15061, 13, 3277, 814, 1051, 15246, 311, 8798, 2949, 279, 2134, 315, 220, 1272, 356, 311, 220, 5245, 356, 11, 814, 48110, 1203, 311, 872, 4113, 21483, 2949, 6622, 13, 330, 18433, 584, 2351, 1701, 1057, 1866, 57053, 430, 3085, 1790, 9333, 13252, 1404, 11, 584, 2351, 9298, 1790, 10819, 2077, 11, 389, 279, 2015, 315, 6622, 1359, 59027, 2795, 13, 330, 2746, 584, 649, 4585, 311, 1524, 9333, 15696, 11, 584, 1253, 1101, 387, 3025, 311, 4585, 872, 2077, 892, 11, 311, 31604, 1210, 330, 2028, 374, 264, 1633, 11084, 220, 18, 9607, 18991, 1749, 7863, 311, 8776, 82981, 477, 27513, 13636, 295, 3196, 57053, 1359, 2795, 1443, 3524, 7674, 25507, 11, 14561, 315, 51593, 50725, 4776, 520, 279, 3907, 315, 7188, 520, 5960, 18842, 11, 889, 574, 539, 6532, 304, 279, 3495, 13, 330, 791, 1749, 596, 1925, 22934, 527, 10819, 18991, 323, 2731, 24693, 17025, 1210, 25046, 25703, 2057, 20461, 264, 4382, 3851, 369, 279, 6211, 65196, 14726, 11, 59027, 323, 813, 18105, 17124, 264, 2678, 11, 23506, 88, 11, 57590, 12970, 23854, 7067, 13, 2435, 12673, 264, 15792, 3790, 311, 279, 2385, 315, 279, 23854, 7067, 11, 1243, 41398, 279, 23854, 7067, 596, 68550, 1825, 13, 3277, 814, 1589, 41872, 279, 9499, 315, 279, 14932, 3805, 311, 520, 3325, 220, 1272, 356, 11, 279, 23854, 7067, 8036, 2212, 8996, 279, 25175, 9277, 24923, 433, 13, 330, 791, 23854, 36623, 527, 264, 6555, 3187, 315, 1268, 34786, 649, 387, 2884, 449, 8579, 7384, 1359, 59027, 2795, 13, 330, 1687, 8710, 430, 433, 374, 3284, 311, 3820, 709, 264, 2678, 32942, 11, 323, 1101, 1524, 7795, 19335, 323, 8579, 80247, 13, 3011, 955, 315, 8579, 25703, 374, 4762, 1633, 5016, 323, 24629, 1210, 35971, 4741, 11, 568, 16388, 311, 1505, 28559, 315, 46033, 388, 311, 1304, 6211, 65196, 7384, 430, 14085, 311, 10284, 4827, 20472, 11, 31047, 279, 2134, 315, 3823, 2547, 20472, 11, 311, 2955, 8579, 11, 4642, 11, 687, 69855, 5623, 9889, 65879, 13, 1283, 2795, 279, 3769, 1253, 1101, 387, 17124, 439, 8579, 11, 27078, 80934, 311, 1520, 13238, 21988, 3839, 279, 7160, 13, 330, 26840, 3629, 11, 27639, 8798, 690, 1977, 709, 389, 279, 1203, 3185, 315, 279, 13238, 2849, 11, 779, 499, 1436, 1005, 510, 12510, 65196, 7384, 60, 439, 459, 1180, 4090, 17383, 311, 26306, 279, 77004, 9392, 315, 279, 13238, 2849, 1359, 59027, 2795, 13, 330, 4516, 584, 1781, 1070, 690, 4762, 387, 810, 8522, 430, 584, 649, 20461, 1210, 220, 128257, 198 ]

2,930

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract A long-standing paradigm in astrophysics is that collisions—or mergers—of two neutron stars form highly relativistic and collimated outflows (jets) that power γ-ray bursts of short (less than two seconds) duration 1 , 2 , 3 . The observational support for this model, however, is only indirect 4 , 5 . A hitherto outstanding prediction is that gravitational-wave events from such mergers should be associated with γ-ray bursts, and that a majority of these bursts should be seen off-axis, that is, they should point away from Earth 6 , 7 . Here we report the discovery observations of the X-ray counterpart associated with the gravitational-wave event GW170817. Although the electromagnetic counterpart at optical and infrared frequencies is dominated by the radioactive glow (known as a ‘kilonova’) from freshly synthesized rapid neutron capture (r-process) material in the merger ejecta 8 , 9 , 10 , observations at X-ray and, later, radio frequencies are consistent with a short γ-ray burst viewed off-axis 7 , 11 . Our detection of X-ray emission at a location coincident with the kilonova transient provides the missing observational link between short γ-ray bursts and gravitational waves from neutron-star mergers, and gives independent confirmation of the collimated nature of the γ-ray-burst emission. Main On 17 August 2017 at 12:41:04 universal time ( ut ; hereafter T 0 ), the Advanced Laser Interferometer Gravitational-Wave Observatory (LIGO) detected a gravitational-wave transient from the merger of two neutron stars at a distance 12 of 40 ± 8 Mpc. Approximately two seconds later, a weak γ-ray burst (GRB) of short duration (<2 s) was observed by the Fermi Gamma-ray Space Telescope 13 and INTEGRAL 14 . The low luminosity of this γ-ray transient was unusual compared to the population of short GRBs at cosmological distances 15 , and its physical connection with the gravitational-wave event remained unclear. A vigorous observing campaign targeted the localization region of the gravitational-wave transient, and rapidly identified a source of bright optical, infrared and ultraviolet emission in the early-type galaxy NGC 4993 16 , 17 . This source was designated ‘SSS17a’ by the Swope team 16 , but here we use the official IAU designation, AT 2017gfo. AT 2017gfo was initially not visible at radio and X-ray wavelengths. However, on 26 August 2017, we observed the field with the Chandra X-ray Observatory and detected X-ray emission at the position of AT 2017gfo ( Fig. 1 ). The observed X-ray flux (see Methods) implies an isotropic luminosity of 9 × 10 38 erg s −1 if located in NGC 4993 at a distance of about 40 Mpc. Further Chandra observations, performed between 1 and 2 September 2017, confirmed the presence of continued X-ray activity, and hinted at a slight increase in luminosity to L X,iso ≈ 1.1 × 10 39 erg s −1 . At a similar epoch the onset of radio emission was also detected 18 . Figure 1: Optical/infrared and X-ray images of the counterpart of GW170817. a , Hubble Space Telescope observations show a bright and red transient in the early-type galaxy NGC 4993, at a projected physical offset of about 2 kpc from its nucleus. A similar small offset is observed in less than a quarter of short GRBs 5 . Dust lanes are visible in the inner regions, suggestive of a past merger activity (see Methods). b , Chandra observations revealed a faint X-ray source at the position of the optical/infrared transient. X-ray emission from the galaxy nucleus is also visible. PowerPoint slide Full size image The evolution of AT 2017gfo across the electromagnetic spectrum shows multiple components dominating the observed emission. Simple modelling of the optical–infrared photometry as a blackbody in linear expansion suggests mildly relativistic (≥0.2 c , where c is the speed of light in vacuum) velocities and cool (<10,000 K) temperatures. We find a hot blue component, mainly contributing at optical wavelengths, and a colder infrared component, which progressively becomes redder ( Extended Data Fig. 1 ). The low peak luminosity ( M V ≈ −16) and featureless optical spectrum ( Fig. 2 ) disfavour a supernova explosion (see Methods), while the broad (Δ λ / λ ≈ 0.1) features in the infrared spectra are consistent with expectations for rapidly expanding dynamical ejecta 9 , 10 , rich in lanthanides and actinides formed via rapid neutron capture nucleosynthesis (the r-process). The overall properties of the host galaxy, such as its stellar mass, evolved stellar population and low star formation (see Methods), are consistent with the typical environment of short GRBs and in line with the predictions for compact binary mergers 5 . When combined, these data point to a kilonova emission, consisting of the superposition of radioactive-powered emission from both neutron-rich dynamical ejecta expanding with velocity v ≈ 0.2 c and a slower, sub-relativistic wind with a higher electron fraction 19 . The former component radiates most of its energy in the infrared, while the latter dominates the optical and ultraviolet spectrum. The optical/infrared data set therefore provides convincing evidence that AT 2017gfo was a kilonova produced by the merger of two compact objects, at a time and location consistent with GW170817. Figure 2: Optical and infrared spectra of the kilonova associated with GW170817. The optical spectrum, acquired on 21 August 2017 ( T 0 + 3.5 d) with the Gemini South 8-m telescope, is dominated by a featureless continuum with a rapid turnover above a wavelength of about 0.75 μm. At later times, this feature is no longer visible. Near-infrared spectra, taken with the Hubble Space Telescope between 22 and 28 August 2017, show prominent broad (Δ λ / λ ≈ 0.1) features and a slow evolution towards redder colours. These spectral features are consistent with the ejection of high-velocity, neutron-rich material during a neutron-star merger. The colour-coded numbers indicate the epoch of each spectrum. A spectrum of the broad-lined type Ic supernova SN 1998bw (8 days post-maximum; arbitrarily rescaled) is shown for comparison. Error bars are 1 σ . PowerPoint slide Full size image Our Chandra observations", "role": "user" }, { "content": "Astrophysicist Chris Fryer was enjoying an evening with friends on August 25, 2017, when he got the news of a gravitational-wave detection by LIGO, the Laser Interferometer Gravitational-wave Observatory. The event appeared to be a merger of two neutron stars—a specialty for the Los Alamos National Laboratory team of astrophysicists that Fryer leads. As the distant cosmic cataclysm unfolded, fresh observational data was pouring in from the observation—only the fifth published since the observatory began operating almost two years ago. \"As soon as I heard the news, I knew that understanding all of the implications would require input from a broad, multi-disciplinary set of scientists,\" said Fryer, who leads Los Alamos' Center for Theoretical Astrophysics. Fryer's colleagues, Ryan Wollaeger and Oleg Korobkin, outlined a series of radiation transport calculations and were given priority on Los Alamos' supercomputers to run them. \"Within a few hours, we were up and running.\" They soon discovered the LIGO data showed more ejected mass from the merger than the simulations accounted for. Other researchers at Los Alamos began processing data from a variety of telescopes capturing optical, ultraviolet, x-ray, and gamma-ray signals at observatories around the world (and in space) that had all been quickly directed to the general location of the LIGO discovery. The theorists tweaked their models and, to their delight, the new LIGO data confirmed that heavy elements beyond iron were formed by the r-process (rapid process) in the neutron-star merger. The gravitational wave observation was having a major impact on theory. They also quickly noticed that, within seconds of the time of the gravitational waves, the Fermi spacecraft reported a burst of gamma rays from the same part of the sky. This is the first time that a gravitational wave source has been detected in any other way. It confirms Einstein's prediction that gravitational waves travel at the same speed as gamma rays: the speed of light. When neutron stars collide The gravitational wave emission and related electromagnetic outburst came from the merger of two neutron stars in a galaxy called NGC 4993, about 130 million light-years away in the constellation Hydra. The neutron stars are the crushed remains of massive stars that once blew up in tremendous explosions known as supernovas. With masses 10 and 20 percent greater than the sun's and a footprint the size of Washington, D.C., the neutron stars whirled around each other toward their demise, spinning hundreds of times per second. As they drew closer like a spinning ice skater pulling in her arms, their mutual gravitational attraction smashed the stars apart in a high-energy flash called a short gamma-ray burst and emitted the tell-tale gravitational wave signal. Although short gamma-ray bursts have long been theorized to be produced through neutron star mergers, this event—with both gamma-ray and gravity wave observations—provides the first definitive evidence. With Los Alamos's cross-disciplinary, multi-science expertise, the Los Alamos team was geared up and ready for just such an event. Laboratory researcher Oleg Korobkin is the lead theory author on a paper released yesterday in Science, while the Lab's Ryan Wollaeger is the second theory author on a paper released yesterday in Nature. Beyond that theory work, though, Los Alamos scientists were engaged in a broad range of observations, astronomy, and data analysis tasks in support of the LIGO neutron-star discovery. Because the Laboratory's primary mission centers on the nation's nuclear stockpile, Los Alamos maintains deep expertise in nuclear physics and its cousin astrophysics, the physics of radiation transport, data analysis, and the computer codes that run massive nuclear simulations on world-leading supercomputers. In other words, the Laboratory is a logical partner for extending LIGO discoveries into theories and models and for confirming the conclusions about what the observatory discovers. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract A long-standing paradigm in astrophysics is that collisions—or mergers—of two neutron stars form highly relativistic and collimated outflows (jets) that power γ-ray bursts of short (less than two seconds) duration 1 , 2 , 3 . The observational support for this model, however, is only indirect 4 , 5 . A hitherto outstanding prediction is that gravitational-wave events from such mergers should be associated with γ-ray bursts, and that a majority of these bursts should be seen off-axis, that is, they should point away from Earth 6 , 7 . Here we report the discovery observations of the X-ray counterpart associated with the gravitational-wave event GW170817. Although the electromagnetic counterpart at optical and infrared frequencies is dominated by the radioactive glow (known as a ‘kilonova’) from freshly synthesized rapid neutron capture (r-process) material in the merger ejecta 8 , 9 , 10 , observations at X-ray and, later, radio frequencies are consistent with a short γ-ray burst viewed off-axis 7 , 11 . Our detection of X-ray emission at a location coincident with the kilonova transient provides the missing observational link between short γ-ray bursts and gravitational waves from neutron-star mergers, and gives independent confirmation of the collimated nature of the γ-ray-burst emission. Main On 17 August 2017 at 12:41:04 universal time ( ut ; hereafter T 0 ), the Advanced Laser Interferometer Gravitational-Wave Observatory (LIGO) detected a gravitational-wave transient from the merger of two neutron stars at a distance 12 of 40 ± 8 Mpc. Approximately two seconds later, a weak γ-ray burst (GRB) of short duration (<2 s) was observed by the Fermi Gamma-ray Space Telescope 13 and INTEGRAL 14 . The low luminosity of this γ-ray transient was unusual compared to the population of short GRBs at cosmological distances 15 , and its physical connection with the gravitational-wave event remained unclear. A vigorous observing campaign targeted the localization region of the gravitational-wave transient, and rapidly identified a source of bright optical, infrared and ultraviolet emission in the early-type galaxy NGC 4993 16 , 17 . This source was designated ‘SSS17a’ by the Swope team 16 , but here we use the official IAU designation, AT 2017gfo. AT 2017gfo was initially not visible at radio and X-ray wavelengths. However, on 26 August 2017, we observed the field with the Chandra X-ray Observatory and detected X-ray emission at the position of AT 2017gfo ( Fig. 1 ). The observed X-ray flux (see Methods) implies an isotropic luminosity of 9 × 10 38 erg s −1 if located in NGC 4993 at a distance of about 40 Mpc. Further Chandra observations, performed between 1 and 2 September 2017, confirmed the presence of continued X-ray activity, and hinted at a slight increase in luminosity to L X,iso ≈ 1.1 × 10 39 erg s −1 . At a similar epoch the onset of radio emission was also detected 18 . Figure 1: Optical/infrared and X-ray images of the counterpart of GW170817. a , Hubble Space Telescope observations show a bright and red transient in the early-type galaxy NGC 4993, at a projected physical offset of about 2 kpc from its nucleus. A similar small offset is observed in less than a quarter of short GRBs 5 . Dust lanes are visible in the inner regions, suggestive of a past merger activity (see Methods). b , Chandra observations revealed a faint X-ray source at the position of the optical/infrared transient. X-ray emission from the galaxy nucleus is also visible. PowerPoint slide Full size image The evolution of AT 2017gfo across the electromagnetic spectrum shows multiple components dominating the observed emission. Simple modelling of the optical–infrared photometry as a blackbody in linear expansion suggests mildly relativistic (≥0.2 c , where c is the speed of light in vacuum) velocities and cool (<10,000 K) temperatures. We find a hot blue component, mainly contributing at optical wavelengths, and a colder infrared component, which progressively becomes redder ( Extended Data Fig. 1 ). The low peak luminosity ( M V ≈ −16) and featureless optical spectrum ( Fig. 2 ) disfavour a supernova explosion (see Methods), while the broad (Δ λ / λ ≈ 0.1) features in the infrared spectra are consistent with expectations for rapidly expanding dynamical ejecta 9 , 10 , rich in lanthanides and actinides formed via rapid neutron capture nucleosynthesis (the r-process). The overall properties of the host galaxy, such as its stellar mass, evolved stellar population and low star formation (see Methods), are consistent with the typical environment of short GRBs and in line with the predictions for compact binary mergers 5 . When combined, these data point to a kilonova emission, consisting of the superposition of radioactive-powered emission from both neutron-rich dynamical ejecta expanding with velocity v ≈ 0.2 c and a slower, sub-relativistic wind with a higher electron fraction 19 . The former component radiates most of its energy in the infrared, while the latter dominates the optical and ultraviolet spectrum. The optical/infrared data set therefore provides convincing evidence that AT 2017gfo was a kilonova produced by the merger of two compact objects, at a time and location consistent with GW170817. Figure 2: Optical and infrared spectra of the kilonova associated with GW170817. The optical spectrum, acquired on 21 August 2017 ( T 0 + 3.5 d) with the Gemini South 8-m telescope, is dominated by a featureless continuum with a rapid turnover above a wavelength of about 0.75 μm. At later times, this feature is no longer visible. Near-infrared spectra, taken with the Hubble Space Telescope between 22 and 28 August 2017, show prominent broad (Δ λ / λ ≈ 0.1) features and a slow evolution towards redder colours. These spectral features are consistent with the ejection of high-velocity, neutron-rich material during a neutron-star merger. The colour-coded numbers indicate the epoch of each spectrum. A spectrum of the broad-lined type Ic supernova SN 1998bw (8 days post-maximum; arbitrarily rescaled) is shown for comparison. Error bars are 1 σ . PowerPoint slide Full size image Our Chandra observations<|im_end|> <|im_start|>assistant Astrophysicist Chris Fryer was enjoying an evening with friends on August 25, 2017, when he got the news of a gravitational-wave detection by LIGO, the Laser Interferometer Gravitational-wave Observatory. The event appeared to be a merger of two neutron stars—a specialty for the Los Alamos National Laboratory team of astrophysicists that Fryer leads. As the distant cosmic cataclysm unfolded, fresh observational data was pouring in from the observation—only the fifth published since the observatory began operating almost two years ago. "As soon as I heard the news, I knew that understanding all of the implications would require input from a broad, multi-disciplinary set of scientists," said Fryer, who leads Los Alamos' Center for Theoretical Astrophysics. Fryer's colleagues, Ryan Wollaeger and Oleg Korobkin, outlined a series of radiation transport calculations and were given priority on Los Alamos' supercomputers to run them. "Within a few hours, we were up and running." They soon discovered the LIGO data showed more ejected mass from the merger than the simulations accounted for. Other researchers at Los Alamos began processing data from a variety of telescopes capturing optical, ultraviolet, x-ray, and gamma-ray signals at observatories around the world (and in space) that had all been quickly directed to the general location of the LIGO discovery. The theorists tweaked their models and, to their delight, the new LIGO data confirmed that heavy elements beyond iron were formed by the r-process (rapid process) in the neutron-star merger. The gravitational wave observation was having a major impact on theory. They also quickly noticed that, within seconds of the time of the gravitational waves, the Fermi spacecraft reported a burst of gamma rays from the same part of the sky. This is the first time that a gravitational wave source has been detected in any other way. It confirms Einstein's prediction that gravitational waves travel at the same speed as gamma rays: the speed of light. When neutron stars collide The gravitational wave emission and related electromagnetic outburst came from the merger of two neutron stars in a galaxy called NGC 4993, about 130 million light-years away in the constellation Hydra. The neutron stars are the crushed remains of massive stars that once blew up in tremendous explosions known as supernovas. With masses 10 and 20 percent greater than the sun's and a footprint the size of Washington, D.C., the neutron stars whirled around each other toward their demise, spinning hundreds of times per second. As they drew closer like a spinning ice skater pulling in her arms, their mutual gravitational attraction smashed the stars apart in a high-energy flash called a short gamma-ray burst and emitted the tell-tale gravitational wave signal. Although short gamma-ray bursts have long been theorized to be produced through neutron star mergers, this event—with both gamma-ray and gravity wave observations—provides the first definitive evidence. With Los Alamos's cross-disciplinary, multi-science expertise, the Los Alamos team was geared up and ready for just such an event. Laboratory researcher Oleg Korobkin is the lead theory author on a paper released yesterday in Science, while the Lab's Ryan Wollaeger is the second theory author on a paper released yesterday in Nature. Beyond that theory work, though, Los Alamos scientists were engaged in a broad range of observations, astronomy, and data analysis tasks in support of the LIGO neutron-star discovery. Because the Laboratory's primary mission centers on the nation's nuclear stockpile, Los Alamos maintains deep expertise in nuclear physics and its cousin astrophysics, the physics of radiation transport, data analysis, and the computer codes that run massive nuclear simulations on world-leading supercomputers. In other words, the Laboratory is a logical partner for extending LIGO discoveries into theories and models and for confirming the conclusions about what the observatory discovers. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 362, 1317, 56703, 49340, 304, 12025, 22761, 17688, 374, 430, 48453, 51749, 18970, 388, 2345, 1073, 1403, 73404, 9958, 1376, 7701, 59425, 4633, 323, 4631, 7292, 704, 39240, 320, 75004, 8, 430, 2410, 63127, 30630, 66801, 315, 2875, 320, 1752, 1109, 1403, 6622, 8, 8250, 220, 16, 1174, 220, 17, 1174, 220, 18, 662, 578, 90380, 1862, 369, 420, 1646, 11, 4869, 11, 374, 1193, 25636, 220, 19, 1174, 220, 20, 662, 362, 305, 411, 14200, 19310, 20212, 374, 430, 71019, 89354, 4455, 505, 1778, 18970, 388, 1288, 387, 5938, 449, 63127, 30630, 66801, 11, 323, 430, 264, 8857, 315, 1521, 66801, 1288, 387, 3970, 1022, 36421, 11, 430, 374, 11, 814, 1288, 1486, 3201, 505, 9420, 220, 21, 1174, 220, 22, 662, 5810, 584, 1934, 279, 18841, 24654, 315, 279, 1630, 30630, 45116, 5938, 449, 279, 71019, 89354, 1567, 42353, 8258, 25528, 13, 10541, 279, 66669, 45116, 520, 29393, 323, 59141, 34873, 374, 30801, 555, 279, 59862, 37066, 320, 5391, 439, 264, 3451, 74, 17346, 12949, 96206, 505, 50999, 92106, 11295, 73404, 12602, 320, 81, 51194, 8, 3769, 304, 279, 47112, 90574, 64, 220, 23, 1174, 220, 24, 1174, 220, 605, 1174, 24654, 520, 1630, 30630, 323, 11, 3010, 11, 9063, 34873, 527, 13263, 449, 264, 2875, 63127, 30630, 21165, 19894, 1022, 36421, 220, 22, 1174, 220, 806, 662, 5751, 18468, 315, 1630, 30630, 41353, 520, 264, 3813, 23828, 1748, 449, 279, 15395, 263, 12949, 41658, 5825, 279, 7554, 90380, 2723, 1990, 2875, 63127, 30630, 66801, 323, 71019, 17301, 505, 73404, 21337, 18970, 388, 11, 323, 6835, 9678, 20109, 315, 279, 4631, 7292, 7138, 315, 279, 63127, 30630, 1481, 33712, 41353, 13, 4802, 1952, 220, 1114, 6287, 220, 679, 22, 520, 220, 717, 25, 3174, 25, 2371, 20789, 892, 320, 8791, 2652, 1618, 10924, 350, 220, 15, 7026, 279, 21844, 40708, 5783, 809, 21037, 2895, 44210, 1697, 13299, 525, 58974, 320, 43, 61589, 8, 16914, 264, 71019, 89354, 41658, 505, 279, 47112, 315, 1403, 73404, 9958, 520, 264, 6138, 220, 717, 315, 220, 1272, 20903, 220, 23, 386, 4080, 13, 79904, 1403, 6622, 3010, 11, 264, 7621, 63127, 30630, 21165, 320, 8796, 33, 8, 315, 2875, 8250, 23246, 17, 274, 8, 574, 13468, 555, 279, 99362, 72, 58782, 30630, 11746, 87062, 220, 1032, 323, 2006, 69103, 984, 220, 975, 662, 578, 3428, 46058, 22828, 315, 420, 63127, 30630, 41658, 574, 19018, 7863, 311, 279, 7187, 315, 2875, 15116, 75307, 520, 56754, 5848, 27650, 220, 868, 1174, 323, 1202, 7106, 3717, 449, 279, 71019, 89354, 1567, 14958, 25420, 13, 362, 71920, 46071, 4901, 17550, 279, 53404, 5654, 315, 279, 71019, 89354, 41658, 11, 323, 19019, 11054, 264, 2592, 315, 10107, 29393, 11, 59141, 323, 37232, 85311, 41353, 304, 279, 4216, 10827, 34261, 120233, 220, 18162, 18, 220, 845, 1174, 220, 1114, 662, 1115, 2592, 574, 24073, 3451, 1242, 50, 1114, 64, 529, 555, 279, 328, 1146, 375, 2128, 220, 845, 1174, 719, 1618, 584, 1005, 279, 4033, 358, 36128, 43851, 11, 7520, 220, 679, 22, 70, 831, 13, 7520, 220, 679, 22, 70, 831, 574, 15453, 539, 9621, 520, 9063, 323, 1630, 30630, 93959, 13, 4452, 11, 389, 220, 1627, 6287, 220, 679, 22, 11, 584, 13468, 279, 2115, 449, 279, 921, 24155, 1630, 30630, 58974, 323, 16914, 1630, 30630, 41353, 520, 279, 2361, 315, 7520, 220, 679, 22, 70, 831, 320, 23966, 13, 220, 16, 7609, 578, 13468, 1630, 30630, 31405, 320, 4151, 19331, 8, 24897, 459, 69551, 45036, 46058, 22828, 315, 220, 24, 25800, 220, 605, 220, 1987, 36376, 274, 25173, 16, 422, 7559, 304, 120233, 220, 18162, 18, 520, 264, 6138, 315, 922, 220, 1272, 386, 4080, 13, 15903, 921, 24155, 24654, 11, 10887, 1990, 220, 16, 323, 220, 17, 6250, 220, 679, 22, 11, 11007, 279, 9546, 315, 8738, 1630, 30630, 5820, 11, 323, 67469, 520, 264, 8275, 5376, 304, 46058, 22828, 311, 445, 1630, 11, 15782, 118792, 220, 16, 13, 16, 25800, 220, 605, 220, 2137, 36376, 274, 25173, 16, 662, 2468, 264, 4528, 16746, 279, 42080, 315, 9063, 41353, 574, 1101, 16914, 220, 972, 662, 19575, 220, 16, 25, 75939, 18480, 82482, 323, 1630, 30630, 5448, 315, 279, 45116, 315, 42353, 8258, 25528, 13, 264, 1174, 473, 14942, 11746, 87062, 24654, 1501, 264, 10107, 323, 2579, 41658, 304, 279, 4216, 10827, 34261, 120233, 220, 18162, 18, 11, 520, 264, 28448, 7106, 4445, 315, 922, 220, 17, 597, 4080, 505, 1202, 62607, 13, 362, 4528, 2678, 4445, 374, 13468, 304, 2753, 1109, 264, 8502, 315, 2875, 15116, 75307, 220, 20, 662, 33093, 34125, 527, 9621, 304, 279, 9358, 13918, 11, 99578, 315, 264, 3347, 47112, 5820, 320, 4151, 19331, 570, 293, 1174, 921, 24155, 24654, 10675, 264, 38678, 1630, 30630, 2592, 520, 279, 2361, 315, 279, 29393, 18480, 82482, 41658, 13, 1630, 30630, 41353, 505, 279, 34261, 62607, 374, 1101, 9621, 13, 54600, 15332, 8797, 1404, 2217, 578, 15740, 315, 7520, 220, 679, 22, 70, 831, 4028, 279, 66669, 20326, 5039, 5361, 6956, 68366, 279, 13468, 41353, 13, 9170, 61966, 315, 279, 29393, 4235, 258, 82482, 4604, 7133, 439, 264, 3776, 2664, 304, 13790, 14800, 13533, 76949, 59425, 4633, 320, 120156, 15, 13, 17, 272, 1174, 1405, 272, 374, 279, 4732, 315, 3177, 304, 29302, 8, 75157, 323, 7155, 23246, 605, 11, 931, 735, 8, 20472, 13, 1226, 1505, 264, 4106, 6437, 3777, 11, 14918, 29820, 520, 29393, 93959, 11, 323, 264, 76214, 59141, 3777, 11, 902, 72859, 9221, 63244, 261, 320, 41665, 2956, 23966, 13, 220, 16, 7609, 578, 3428, 16557, 46058, 22828, 320, 386, 650, 118792, 25173, 845, 8, 323, 4668, 1752, 29393, 20326, 320, 23966, 13, 220, 17, 883, 834, 69, 27089, 264, 39887, 12949, 25176, 320, 4151, 19331, 705, 1418, 279, 7353, 320, 101561, 49438, 611, 49438, 118792, 220, 15, 13, 16, 8, 4519, 304, 279, 59141, 63697, 527, 13263, 449, 17078, 369, 19019, 24050, 18003, 950, 90574, 64, 220, 24, 1174, 220, 605, 1174, 9257, 304, 31791, 54895, 3422, 323, 1180, 258, 3422, 14454, 4669, 11295, 73404, 12602, 31484, 437, 74767, 320, 1820, 436, 51194, 570, 578, 8244, 6012, 315, 279, 3552, 34261, 11, 1778, 439, 1202, 48317, 3148, 11, 28995, 48317, 7187, 323, 3428, 6917, 18488, 320, 4151, 19331, 705, 527, 13263, 449, 279, 14595, 4676, 315, 2875, 15116, 75307, 323, 304, 1584, 449, 279, 20492, 369, 17251, 8026, 18970, 388, 220, 20, 662, 3277, 11093, 11, 1521, 828, 1486, 311, 264, 15395, 263, 12949, 41353, 11, 31706, 315, 279, 2307, 3571, 315, 59862, 41503, 41353, 505, 2225, 73404, 41947, 18003, 950, 90574, 64, 24050, 449, 15798, 348, 118792, 220, 15, 13, 17, 272, 323, 264, 29493, 11, 1207, 48712, 20053, 4633, 10160, 449, 264, 5190, 17130, 19983, 220, 777, 662, 578, 4846, 3777, 12164, 988, 1455, 315, 1202, 4907, 304, 279, 59141, 11, 1418, 279, 15629, 83978, 279, 29393, 323, 37232, 85311, 20326, 13, 578, 29393, 18480, 82482, 828, 743, 9093, 5825, 40661, 6029, 430, 7520, 220, 679, 22, 70, 831, 574, 264, 15395, 263, 12949, 9124, 555, 279, 47112, 315, 1403, 17251, 6302, 11, 520, 264, 892, 323, 3813, 13263, 449, 42353, 8258, 25528, 13, 19575, 220, 17, 25, 75939, 323, 59141, 63697, 315, 279, 15395, 263, 12949, 5938, 449, 42353, 8258, 25528, 13, 578, 29393, 20326, 11, 19426, 389, 220, 1691, 6287, 220, 679, 22, 320, 350, 220, 15, 489, 220, 18, 13, 20, 294, 8, 449, 279, 86811, 4987, 220, 23, 1474, 56925, 11, 374, 30801, 555, 264, 4668, 1752, 86901, 449, 264, 11295, 48639, 3485, 264, 46406, 315, 922, 220, 15, 13, 2075, 33983, 76, 13, 2468, 3010, 3115, 11, 420, 4668, 374, 912, 5129, 9621, 13, 31494, 3502, 82482, 63697, 11, 4529, 449, 279, 473, 14942, 11746, 87062, 1990, 220, 1313, 323, 220, 1591, 6287, 220, 679, 22, 11, 1501, 21102, 7353, 320, 101561, 49438, 611, 49438, 118792, 220, 15, 13, 16, 8, 4519, 323, 264, 6435, 15740, 7119, 63244, 261, 27230, 13, 4314, 57077, 4519, 527, 13263, 449, 279, 384, 7761, 315, 1579, 12, 14982, 11, 73404, 41947, 3769, 2391, 264, 73404, 21337, 47112, 13, 578, 12745, 87411, 5219, 13519, 279, 16746, 315, 1855, 20326, 13, 362, 20326, 315, 279, 7353, 90059, 955, 358, 66, 39887, 12949, 18407, 220, 2550, 23, 40924, 320, 23, 2919, 1772, 45173, 3375, 26, 86757, 594, 26294, 8, 374, 6982, 369, 12593, 13, 4703, 16283, 527, 220, 16, 48823, 662, 54600, 15332, 8797, 1404, 2217, 5751, 921, 24155, 24654, 128257, 198, 128256, 78191, 198, 62152, 22761, 1065, 292, 380, 11517, 53517, 261, 574, 22128, 459, 11714, 449, 4885, 389, 6287, 220, 914, 11, 220, 679, 22, 11, 994, 568, 2751, 279, 3754, 315, 264, 71019, 89354, 18468, 555, 445, 61589, 11, 279, 40708, 5783, 809, 21037, 2895, 44210, 1697, 89354, 58974, 13, 578, 1567, 9922, 311, 387, 264, 47112, 315, 1403, 73404, 9958, 29096, 36974, 369, 279, 9853, 1708, 10808, 5165, 32184, 2128, 315, 12025, 22761, 1065, 292, 1705, 430, 53517, 261, 11767, 13, 1666, 279, 29827, 55801, 31179, 85245, 3647, 76782, 11, 7878, 90380, 828, 574, 51513, 304, 505, 279, 22695, 2345, 3323, 279, 18172, 4756, 2533, 279, 9466, 5382, 6137, 10565, 4661, 1403, 1667, 4227, 13, 330, 2170, 5246, 439, 358, 6755, 279, 3754, 11, 358, 7020, 430, 8830, 682, 315, 279, 25127, 1053, 1397, 1988, 505, 264, 7353, 11, 7447, 52765, 44550, 743, 315, 14248, 1359, 1071, 53517, 261, 11, 889, 11767, 9853, 1708, 10808, 6, 5955, 369, 578, 91867, 94202, 17688, 13, 53517, 261, 596, 18105, 11, 13960, 468, 43783, 1916, 323, 507, 1978, 36170, 677, 8148, 11, 33740, 264, 4101, 315, 25407, 7710, 29217, 323, 1051, 2728, 10844, 389, 9853, 1708, 10808, 6, 2307, 66047, 388, 311, 1629, 1124, 13, 330, 43061, 264, 2478, 4207, 11, 584, 1051, 709, 323, 4401, 1210, 2435, 5246, 11352, 279, 445, 61589, 828, 8710, 810, 95503, 3148, 505, 279, 47112, 1109, 279, 47590, 41853, 369, 13, 7089, 12074, 520, 9853, 1708, 10808, 6137, 8863, 828, 505, 264, 8205, 315, 78513, 19031, 40880, 29393, 11, 37232, 85311, 11, 865, 30630, 11, 323, 22350, 30630, 17738, 520, 9466, 38270, 2212, 279, 1917, 320, 438, 304, 3634, 8, 430, 1047, 682, 1027, 6288, 15910, 311, 279, 4689, 3813, 315, 279, 445, 61589, 18841, 13, 578, 84062, 89560, 872, 4211, 323, 11, 311, 872, 18454, 11, 279, 502, 445, 61589, 828, 11007, 430, 8987, 5540, 7953, 11245, 1051, 14454, 555, 279, 436, 51194, 320, 86812, 1920, 8, 304, 279, 73404, 21337, 47112, 13, 578, 71019, 12330, 22695, 574, 3515, 264, 3682, 5536, 389, 10334, 13, 2435, 1101, 6288, 14000, 430, 11, 2949, 6622, 315, 279, 892, 315, 279, 71019, 17301, 11, 279, 99362, 72, 42640, 5068, 264, 21165, 315, 22350, 45220, 505, 279, 1890, 961, 315, 279, 13180, 13, 1115, 374, 279, 1176, 892, 430, 264, 71019, 12330, 2592, 706, 1027, 16914, 304, 904, 1023, 1648, 13, 1102, 43496, 55152, 596, 20212, 430, 71019, 17301, 5944, 520, 279, 1890, 4732, 439, 22350, 45220, 25, 279, 4732, 315, 3177, 13, 3277, 73404, 9958, 67190, 578, 71019, 12330, 41353, 323, 5552, 66669, 704, 58838, 3782, 505, 279, 47112, 315, 1403, 73404, 9958, 304, 264, 34261, 2663, 120233, 220, 18162, 18, 11, 922, 220, 5894, 3610, 3177, 57188, 3201, 304, 279, 83486, 87961, 13, 578, 73404, 9958, 527, 279, 33745, 8625, 315, 11191, 9958, 430, 3131, 42423, 709, 304, 28040, 56506, 3967, 439, 39887, 869, 300, 13, 3161, 32738, 220, 605, 323, 220, 508, 3346, 7191, 1109, 279, 7160, 596, 323, 264, 43972, 279, 1404, 315, 6652, 11, 423, 732, 2637, 279, 73404, 9958, 421, 404, 839, 2212, 1855, 1023, 9017, 872, 58964, 11, 38960, 11758, 315, 3115, 824, 2132, 13, 1666, 814, 24465, 12401, 1093, 264, 38960, 10054, 1940, 977, 23062, 304, 1077, 11977, 11, 872, 27848, 71019, 33464, 57520, 279, 9958, 10980, 304, 264, 1579, 65487, 8381, 2663, 264, 2875, 22350, 30630, 21165, 323, 48042, 279, 3371, 2442, 1604, 71019, 12330, 8450, 13, 10541, 2875, 22350, 30630, 66801, 617, 1317, 1027, 46820, 1534, 311, 387, 9124, 1555, 73404, 6917, 18970, 388, 11, 420, 1567, 81902, 2225, 22350, 30630, 323, 24128, 12330, 24654, 2345, 782, 68254, 279, 1176, 45813, 6029, 13, 3161, 9853, 1708, 10808, 596, 5425, 52765, 44550, 11, 7447, 31419, 1873, 19248, 11, 279, 9853, 1708, 10808, 2128, 574, 59547, 709, 323, 5644, 369, 1120, 1778, 459, 1567, 13, 32184, 32185, 507, 1978, 36170, 677, 8148, 374, 279, 3063, 10334, 3229, 389, 264, 5684, 6004, 13985, 304, 10170, 11, 1418, 279, 11868, 596, 13960, 468, 43783, 1916, 374, 279, 2132, 10334, 3229, 389, 264, 5684, 6004, 13985, 304, 22037, 13, 31886, 430, 10334, 990, 11, 3582, 11, 9853, 1708, 10808, 14248, 1051, 17045, 304, 264, 7353, 2134, 315, 24654, 11, 82213, 11, 323, 828, 6492, 9256, 304, 1862, 315, 279, 445, 61589, 73404, 21337, 18841, 13, 9393, 279, 32184, 596, 6156, 9131, 19169, 389, 279, 7140, 596, 11499, 5708, 12470, 11, 9853, 1708, 10808, 33095, 5655, 19248, 304, 11499, 22027, 323, 1202, 36271, 12025, 22761, 17688, 11, 279, 22027, 315, 25407, 7710, 11, 828, 6492, 11, 323, 279, 6500, 14236, 430, 1629, 11191, 11499, 47590, 389, 1917, 69475, 2307, 66047, 388, 13, 763, 1023, 4339, 11, 279, 32184, 374, 264, 20406, 8427, 369, 33459, 445, 61589, 54098, 1139, 26018, 323, 4211, 323, 369, 50096, 279, 31342, 922, 1148, 279, 9466, 5382, 52114, 13, 220, 128257, 198 ]

2,220

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Integrating costs and benefits is crucial for optimal decision-making. Although much is known about decisions that involve outcome-related costs (e.g., delay, risk), many of our choices are attached to actions and require an evaluation of the associated motor costs. Yet how the brain incorporates motor costs into choices remains largely unclear. We used human fMRI during choices involving monetary reward and physical effort to identify brain regions that serve as a choice comparator for effort-reward trade-offs. By independently varying both options' effort and reward levels, we were able to identify the neural signature of a comparator mechanism. A network involving supplementary motor area and the caudal portion of dorsal anterior cingulate cortex encoded the difference in reward (positively) and effort levels (negatively) between chosen and unchosen choice options. We next modeled effort-discounted subjective values using a novel behavioral model. This revealed that the same network of regions involving dorsal anterior cingulate cortex and supplementary motor area encoded the difference between the chosen and unchosen options' subjective values, and that activity was best described using a concave model of effort-discounting. In addition, this signal reflected how precisely value determined participants' choices. By contrast, separate signals in supplementary motor area and ventromedial prefrontal cortex correlated with participants' tendency to avoid effort and seek reward, respectively. This suggests that the critical neural signature of decision-making for choices involving motor costs is found in human cingulate cortex and not ventromedial prefrontal cortex as typically reported for outcome-based choice. Furthermore, distinct frontal circuits seem to drive behavior toward reward maximization and effort minimization. SIGNIFICANCE STATEMENT The neural processes that govern the trade-off between expected benefits and motor costs remain largely unknown. This is striking because energetic requirements play an integral role in our day-to-day choices and instrumental behavior, and a diminished willingness to exert effort is a characteristic feature of a range of neurological disorders. We use a new behavioral characterization of how humans trade off reward maximization with effort minimization to examine the neural signatures that underpin such choices, using BOLD MRI neuroimaging data. We find the critical neural signature of decision-making, a signal that reflects the comparison of value between choice options, in human cingulate cortex, whereas two distinct brain circuits drive behavior toward reward maximization or effort minimization. cingulate cortex cost-benefit decision making fMRI motor cost physical effort value comparison Introduction Cost-benefit decisions are a central aspect of flexible goal-directed behavior. One particularly well-studied neural system concerns choices where costs are tied to the reward outcomes (e.g., risk, delay) ( Kable and Glimcher, 2007 ; Boorman et al., 2009 ; Philiastides et al., 2010 ). Much less is known about choices tied to physical effort costs, despite their ubiquitous presence in human and animal behavior. The intrinsic relationship between effort and action may engage neural circuits distinct from those involved in other value-based choice computations. There is growing consensus that different types of value-guided decisions are underpinned by distinct neural systems, depending on the type of information that needs to be processed (e.g., Rudebeck et al., 2008 ; Camille et al., 2011b ; Kennerley et al., 2011 ; Pastor-Bernier and Cisek, 2011 ; Rushworth et al., 2012 ). For example, activity in the ventromedial prefrontal cortex (vmPFC) carries a signature of choice comparison (chosen-unchosen value) for decisions between abstract goods or when costs are tied to the outcome ( Kable and Glimcher, 2007 ; Boorman et al., 2009 ; FitzGerald et al., 2009 ; Philiastides et al., 2010 ; Hunt et al., 2012 ; Kolling et al., 2012 ; Clithero and Rangel, 2014 ; Strait et al., 2014 ). By contrast, such value difference signals are found more dorsally in medial frontal cortex when deciding between exploration versus exploitation ( Kolling et al., 2012 ). Choices requiring the evaluation of physical effort rest on representations of the required actions and their energetic costs, and thus likely require an evaluation of the internal state of the agent. This is distinct from choices based solely on reward outcomes ( Rangel and Hare, 2010 ). Indeed, the proposed network for evaluating motor costs comprises brain regions involved in action planning and execution, including the cingulate cortex, putamen, and supplementary motor area (SMA) ( Croxson et al., 2009 ; Kurniawan et al., 2010 ; Prévost et al., 2010 ; Burke et al., 2013 ; Kurniawan et al., 2013 ; Bonnelle et al., 2016 ). Neurons in anterior cingulate cortex (ACC) encode information about rewards, effort costs, and actions ( Matsumoto et al., 2003 ; Kennerley and Wallis, 2009 ; Luk and Wallis, 2009 ; Hayden and Platt, 2010 ), and integrate this information into an economic value signal ( Hillman and Bilkey, 2010 ; Hosokawa et al., 2013 ). Moreover, lesions to ACC profoundly impair choices of effortful options and between action values ( Walton et al., 2003 , 2006 , 2009 ; Schweimer and Hauber, 2005 ; Kennerley et al., 2006 ; Rudebeck et al., 2006 , 2008 ; Camille et al., 2011b ). While these studies highlight the importance of motor-related structures in representing effort information, it remains unclear whether computations in these regions are indeed related to comparing effort values (or effort-discounted net values), the essential neural signature, which would implicate these areas in decision making. Indeed, these regions could simply represent effort, which is then passed onto other regions for value comparison processes. A number of questions thus arise. First, is information about reward and effort compared in separate neural structures, or is this information fed to a region that compares options based on their integrated value? Second, do regions that preferably encode reward or effort have a direct influence on determining choice? Finally, assuming separate neural systems are present for influencing choices based on reward versus effort, how does the brain arbitrate between these signals when reward and effort information support opposing choices? Here we used a task designed to identify signatures of a choice comparison for effort-based decisions in humans using fMRI and to test whether different neural circuits", "role": "user" }, { "content": "How do we decide if something is worth the effort? A team of researchers from Oxford University and UCL have been finding out. Every action we take involves a cost to us in physical energy, yet studies about decision-making have tended to look at how we weight up external costs like risks or time. However, being unwilling to exert effort is a symptom for a range of mental disorders, so understanding how the brain processes decisions about effort versus reward could provide insights into these conditions. In a study supported by the Wellcome Trust and European Research Council, the research team therefore decided to see if there was a distinct brain system involved in weighing up physical costs. Researcher Dr Miriam Klein-Flügge said: \"We asked volunteers to make choices involving different levels of monetary reward and physical effort, while they were placed in a MRI scanner. \"We found that the decisions they made were influenced by both reward size and effort required, with – unsurprisingly – higher reward, lower effort options being particularly favoured. We then looked for particular brain regions involved in the decision-making.\" The team found a relevant pattern of activity in three areas of the brain, the supplementary motor area (SMA), dorsal anterior cingulate cortex (dACC) and putamen. Further analysis showed that assessment of effort was centred on the SMA and putamen, with a separate network in the ventromedial prefrontal cortex assessing reward. The dACC encoded the difference between effort and reward as a single value, likely drawing together the results of the two separate neural circuits, and activity in this area was linked with the degree to which each volunteer's choices were driven by the overall value. Dr Miriam Klein-Flügge said: \"This research fits with and adds to findings from other studies. There is not one single decision-making system in the brain but a set of them that are combined flexibly depending on the decision we are faced with. We have identified the system related to effort, a common factor in many decisions. \"It offers an insight for research into a number of disorders including depression, apathy and negative symptom schizophrenia. Patients with these disorders often show a reduced ability to do something effortful to obtain a reward. Our volunteers were different in their sensitivity to effort, and showed different levels of neural activity, suggesting that people can have different balances between their reward and effort systems. \"While further research is needed, it may be that some disorders involve a particularly acute imbalance between these different decision systems.\" Dr Raliza Stoyanova, in the Neuroscience and Mental Health team at Wellcome, said: \"There are many situations that require us to weigh up effort and reward, for instance deciding whether the extra long walk to get our favourite type of sandwich is worth more than a shorter walk for a less favoured sandwich. \"Although we know a lot about how the brain reacts to rewards of different sizes, the current study is the first to shed light on a brain region that is involved in comparing the size of a reward and the physical effort required to get it. Given that a range of psychiatric conditions involve difficulties in reaching rewards when they require effort, these results open up a number of avenues for future research to test more precisely if, and how, the reward/effort balance may go awry.\" The paper, Neural Signatures of value comparison in human cingulate cortex during decisions requiring an effort-reward trade-off, is published in the Journal of Neuroscience. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Integrating costs and benefits is crucial for optimal decision-making. Although much is known about decisions that involve outcome-related costs (e.g., delay, risk), many of our choices are attached to actions and require an evaluation of the associated motor costs. Yet how the brain incorporates motor costs into choices remains largely unclear. We used human fMRI during choices involving monetary reward and physical effort to identify brain regions that serve as a choice comparator for effort-reward trade-offs. By independently varying both options' effort and reward levels, we were able to identify the neural signature of a comparator mechanism. A network involving supplementary motor area and the caudal portion of dorsal anterior cingulate cortex encoded the difference in reward (positively) and effort levels (negatively) between chosen and unchosen choice options. We next modeled effort-discounted subjective values using a novel behavioral model. This revealed that the same network of regions involving dorsal anterior cingulate cortex and supplementary motor area encoded the difference between the chosen and unchosen options' subjective values, and that activity was best described using a concave model of effort-discounting. In addition, this signal reflected how precisely value determined participants' choices. By contrast, separate signals in supplementary motor area and ventromedial prefrontal cortex correlated with participants' tendency to avoid effort and seek reward, respectively. This suggests that the critical neural signature of decision-making for choices involving motor costs is found in human cingulate cortex and not ventromedial prefrontal cortex as typically reported for outcome-based choice. Furthermore, distinct frontal circuits seem to drive behavior toward reward maximization and effort minimization. SIGNIFICANCE STATEMENT The neural processes that govern the trade-off between expected benefits and motor costs remain largely unknown. This is striking because energetic requirements play an integral role in our day-to-day choices and instrumental behavior, and a diminished willingness to exert effort is a characteristic feature of a range of neurological disorders. We use a new behavioral characterization of how humans trade off reward maximization with effort minimization to examine the neural signatures that underpin such choices, using BOLD MRI neuroimaging data. We find the critical neural signature of decision-making, a signal that reflects the comparison of value between choice options, in human cingulate cortex, whereas two distinct brain circuits drive behavior toward reward maximization or effort minimization. cingulate cortex cost-benefit decision making fMRI motor cost physical effort value comparison Introduction Cost-benefit decisions are a central aspect of flexible goal-directed behavior. One particularly well-studied neural system concerns choices where costs are tied to the reward outcomes (e.g., risk, delay) ( Kable and Glimcher, 2007 ; Boorman et al., 2009 ; Philiastides et al., 2010 ). Much less is known about choices tied to physical effort costs, despite their ubiquitous presence in human and animal behavior. The intrinsic relationship between effort and action may engage neural circuits distinct from those involved in other value-based choice computations. There is growing consensus that different types of value-guided decisions are underpinned by distinct neural systems, depending on the type of information that needs to be processed (e.g., Rudebeck et al., 2008 ; Camille et al., 2011b ; Kennerley et al., 2011 ; Pastor-Bernier and Cisek, 2011 ; Rushworth et al., 2012 ). For example, activity in the ventromedial prefrontal cortex (vmPFC) carries a signature of choice comparison (chosen-unchosen value) for decisions between abstract goods or when costs are tied to the outcome ( Kable and Glimcher, 2007 ; Boorman et al., 2009 ; FitzGerald et al., 2009 ; Philiastides et al., 2010 ; Hunt et al., 2012 ; Kolling et al., 2012 ; Clithero and Rangel, 2014 ; Strait et al., 2014 ). By contrast, such value difference signals are found more dorsally in medial frontal cortex when deciding between exploration versus exploitation ( Kolling et al., 2012 ). Choices requiring the evaluation of physical effort rest on representations of the required actions and their energetic costs, and thus likely require an evaluation of the internal state of the agent. This is distinct from choices based solely on reward outcomes ( Rangel and Hare, 2010 ). Indeed, the proposed network for evaluating motor costs comprises brain regions involved in action planning and execution, including the cingulate cortex, putamen, and supplementary motor area (SMA) ( Croxson et al., 2009 ; Kurniawan et al., 2010 ; Prévost et al., 2010 ; Burke et al., 2013 ; Kurniawan et al., 2013 ; Bonnelle et al., 2016 ). Neurons in anterior cingulate cortex (ACC) encode information about rewards, effort costs, and actions ( Matsumoto et al., 2003 ; Kennerley and Wallis, 2009 ; Luk and Wallis, 2009 ; Hayden and Platt, 2010 ), and integrate this information into an economic value signal ( Hillman and Bilkey, 2010 ; Hosokawa et al., 2013 ). Moreover, lesions to ACC profoundly impair choices of effortful options and between action values ( Walton et al., 2003 , 2006 , 2009 ; Schweimer and Hauber, 2005 ; Kennerley et al., 2006 ; Rudebeck et al., 2006 , 2008 ; Camille et al., 2011b ). While these studies highlight the importance of motor-related structures in representing effort information, it remains unclear whether computations in these regions are indeed related to comparing effort values (or effort-discounted net values), the essential neural signature, which would implicate these areas in decision making. Indeed, these regions could simply represent effort, which is then passed onto other regions for value comparison processes. A number of questions thus arise. First, is information about reward and effort compared in separate neural structures, or is this information fed to a region that compares options based on their integrated value? Second, do regions that preferably encode reward or effort have a direct influence on determining choice? Finally, assuming separate neural systems are present for influencing choices based on reward versus effort, how does the brain arbitrate between these signals when reward and effort information support opposing choices? Here we used a task designed to identify signatures of a choice comparison for effort-based decisions in humans using fMRI and to test whether different neural circuits<|im_end|> <|im_start|>assistant How do we decide if something is worth the effort? A team of researchers from Oxford University and UCL have been finding out. Every action we take involves a cost to us in physical energy, yet studies about decision-making have tended to look at how we weight up external costs like risks or time. However, being unwilling to exert effort is a symptom for a range of mental disorders, so understanding how the brain processes decisions about effort versus reward could provide insights into these conditions. In a study supported by the Wellcome Trust and European Research Council, the research team therefore decided to see if there was a distinct brain system involved in weighing up physical costs. Researcher Dr Miriam Klein-Flügge said: "We asked volunteers to make choices involving different levels of monetary reward and physical effort, while they were placed in a MRI scanner. "We found that the decisions they made were influenced by both reward size and effort required, with – unsurprisingly – higher reward, lower effort options being particularly favoured. We then looked for particular brain regions involved in the decision-making." The team found a relevant pattern of activity in three areas of the brain, the supplementary motor area (SMA), dorsal anterior cingulate cortex (dACC) and putamen. Further analysis showed that assessment of effort was centred on the SMA and putamen, with a separate network in the ventromedial prefrontal cortex assessing reward. The dACC encoded the difference between effort and reward as a single value, likely drawing together the results of the two separate neural circuits, and activity in this area was linked with the degree to which each volunteer's choices were driven by the overall value. Dr Miriam Klein-Flügge said: "This research fits with and adds to findings from other studies. There is not one single decision-making system in the brain but a set of them that are combined flexibly depending on the decision we are faced with. We have identified the system related to effort, a common factor in many decisions. "It offers an insight for research into a number of disorders including depression, apathy and negative symptom schizophrenia. Patients with these disorders often show a reduced ability to do something effortful to obtain a reward. Our volunteers were different in their sensitivity to effort, and showed different levels of neural activity, suggesting that people can have different balances between their reward and effort systems. "While further research is needed, it may be that some disorders involve a particularly acute imbalance between these different decision systems." Dr Raliza Stoyanova, in the Neuroscience and Mental Health team at Wellcome, said: "There are many situations that require us to weigh up effort and reward, for instance deciding whether the extra long walk to get our favourite type of sandwich is worth more than a shorter walk for a less favoured sandwich. "Although we know a lot about how the brain reacts to rewards of different sizes, the current study is the first to shed light on a brain region that is involved in comparing the size of a reward and the physical effort required to get it. Given that a range of psychiatric conditions involve difficulties in reaching rewards when they require effort, these results open up a number of avenues for future research to test more precisely if, and how, the reward/effort balance may go awry." The paper, Neural Signatures of value comparison in human cingulate cortex during decisions requiring an effort-reward trade-off, is published in the Journal of Neuroscience. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 30101, 1113, 7194, 323, 7720, 374, 16996, 369, 23669, 5597, 28846, 13, 10541, 1790, 374, 3967, 922, 11429, 430, 21736, 15632, 14228, 7194, 320, 68, 1326, 2637, 7781, 11, 5326, 705, 1690, 315, 1057, 11709, 527, 12673, 311, 6299, 323, 1397, 459, 16865, 315, 279, 5938, 9048, 7194, 13, 14968, 1268, 279, 8271, 52924, 9048, 7194, 1139, 11709, 8625, 14090, 25420, 13, 1226, 1511, 3823, 282, 79770, 2391, 11709, 16239, 33384, 11565, 323, 7106, 5149, 311, 10765, 8271, 13918, 430, 8854, 439, 264, 5873, 53140, 369, 5149, 5621, 1637, 6696, 65039, 13, 3296, 29235, 29865, 2225, 2671, 6, 5149, 323, 11565, 5990, 11, 584, 1051, 3025, 311, 10765, 279, 30828, 12223, 315, 264, 53140, 17383, 13, 362, 4009, 16239, 80506, 9048, 3158, 323, 279, 2211, 664, 278, 13651, 315, 96146, 37229, 272, 287, 6468, 49370, 21136, 279, 6811, 304, 11565, 320, 2792, 3210, 8, 323, 5149, 5990, 320, 29875, 8046, 8, 1990, 12146, 323, 653, 64175, 5873, 2671, 13, 1226, 1828, 62653, 5149, 10694, 1868, 291, 44122, 2819, 1701, 264, 11775, 36695, 1646, 13, 1115, 10675, 430, 279, 1890, 4009, 315, 13918, 16239, 96146, 37229, 272, 287, 6468, 49370, 323, 80506, 9048, 3158, 21136, 279, 6811, 1990, 279, 12146, 323, 653, 64175, 2671, 6, 44122, 2819, 11, 323, 430, 5820, 574, 1888, 7633, 1701, 264, 3613, 525, 1646, 315, 5149, 10694, 1868, 287, 13, 763, 5369, 11, 420, 8450, 27000, 1268, 24559, 907, 11075, 13324, 6, 11709, 13, 3296, 13168, 11, 8821, 17738, 304, 80506, 9048, 3158, 323, 10594, 442, 291, 532, 864, 7096, 278, 49370, 49393, 449, 13324, 6, 31954, 311, 5766, 5149, 323, 6056, 11565, 11, 15947, 13, 1115, 13533, 430, 279, 9200, 30828, 12223, 315, 5597, 28846, 369, 11709, 16239, 9048, 7194, 374, 1766, 304, 3823, 272, 287, 6468, 49370, 323, 539, 10594, 442, 291, 532, 864, 7096, 278, 49370, 439, 11383, 5068, 369, 15632, 6108, 5873, 13, 24296, 11, 12742, 66746, 46121, 2873, 311, 6678, 7865, 9017, 11565, 31127, 2065, 323, 5149, 21877, 2065, 13, 44272, 34735, 8606, 23233, 5441, 578, 30828, 11618, 430, 2633, 279, 6696, 12744, 1990, 3685, 7720, 323, 9048, 7194, 7293, 14090, 9987, 13, 1115, 374, 21933, 1606, 45955, 8670, 1514, 459, 26154, 3560, 304, 1057, 1938, 4791, 11477, 11709, 323, 42045, 7865, 11, 323, 264, 54182, 39375, 311, 43844, 5149, 374, 264, 29683, 4668, 315, 264, 2134, 315, 64908, 24673, 13, 1226, 1005, 264, 502, 36695, 60993, 315, 1268, 12966, 6696, 1022, 11565, 31127, 2065, 449, 5149, 21877, 2065, 311, 21635, 279, 30828, 33728, 430, 1234, 13576, 1778, 11709, 11, 1701, 426, 8021, 52460, 18247, 318, 4210, 828, 13, 1226, 1505, 279, 9200, 30828, 12223, 315, 5597, 28846, 11, 264, 8450, 430, 27053, 279, 12593, 315, 907, 1990, 5873, 2671, 11, 304, 3823, 272, 287, 6468, 49370, 11, 20444, 1403, 12742, 8271, 46121, 6678, 7865, 9017, 11565, 31127, 2065, 477, 5149, 21877, 2065, 13, 272, 287, 6468, 49370, 2853, 1481, 89729, 5597, 3339, 282, 79770, 9048, 2853, 7106, 5149, 907, 12593, 29438, 11443, 1481, 89729, 11429, 527, 264, 8792, 13189, 315, 19303, 5915, 86855, 7865, 13, 3861, 8104, 1664, 5594, 664, 1142, 30828, 1887, 10742, 11709, 1405, 7194, 527, 17791, 311, 279, 11565, 20124, 320, 68, 1326, 2637, 5326, 11, 7781, 8, 320, 735, 481, 323, 480, 4763, 9211, 11, 220, 1049, 22, 2652, 2577, 63975, 1880, 453, 2637, 220, 1049, 24, 2652, 2405, 4008, 561, 3422, 1880, 453, 2637, 220, 679, 15, 7609, 24191, 2753, 374, 3967, 922, 11709, 17791, 311, 7106, 5149, 7194, 11, 8994, 872, 64564, 9546, 304, 3823, 323, 10065, 7865, 13, 578, 47701, 5133, 1990, 5149, 323, 1957, 1253, 16988, 30828, 46121, 12742, 505, 1884, 6532, 304, 1023, 907, 6108, 5873, 83699, 13, 2684, 374, 7982, 24811, 430, 2204, 4595, 315, 907, 84792, 291, 11429, 527, 1234, 79, 21203, 555, 12742, 30828, 6067, 11, 11911, 389, 279, 955, 315, 2038, 430, 3966, 311, 387, 15590, 320, 68, 1326, 2637, 432, 799, 55177, 1880, 453, 2637, 220, 1049, 23, 2652, 8215, 4618, 1880, 453, 2637, 220, 679, 16, 65, 2652, 14594, 1215, 3258, 1880, 453, 2637, 220, 679, 16, 2652, 59766, 7826, 944, 1291, 323, 356, 1082, 74, 11, 220, 679, 16, 2652, 35175, 20069, 1880, 453, 2637, 220, 679, 17, 7609, 1789, 3187, 11, 5820, 304, 279, 10594, 442, 291, 532, 864, 7096, 278, 49370, 320, 7488, 47, 6897, 8, 24266, 264, 12223, 315, 5873, 12593, 320, 64175, 12, 3265, 8477, 907, 8, 369, 11429, 1990, 8278, 11822, 477, 994, 7194, 527, 17791, 311, 279, 15632, 320, 735, 481, 323, 480, 4763, 9211, 11, 220, 1049, 22, 2652, 2577, 63975, 1880, 453, 2637, 220, 1049, 24, 2652, 37778, 38, 25380, 1880, 453, 2637, 220, 1049, 24, 2652, 2405, 4008, 561, 3422, 1880, 453, 2637, 220, 679, 15, 2652, 27690, 1880, 453, 2637, 220, 679, 17, 2652, 735, 980, 287, 1880, 453, 2637, 220, 679, 17, 2652, 2493, 411, 2382, 323, 432, 17729, 11, 220, 679, 19, 2652, 83163, 1880, 453, 2637, 220, 679, 19, 7609, 3296, 13168, 11, 1778, 907, 6811, 17738, 527, 1766, 810, 77389, 750, 304, 97348, 66746, 49370, 994, 30230, 1990, 27501, 19579, 40761, 320, 735, 980, 287, 1880, 453, 2637, 220, 679, 17, 7609, 79291, 23537, 279, 16865, 315, 7106, 5149, 2800, 389, 44713, 315, 279, 2631, 6299, 323, 872, 45955, 7194, 11, 323, 8617, 4461, 1397, 459, 16865, 315, 279, 5419, 1614, 315, 279, 8479, 13, 1115, 374, 12742, 505, 11709, 3196, 21742, 389, 11565, 20124, 320, 432, 17729, 323, 473, 548, 11, 220, 679, 15, 7609, 23150, 11, 279, 11223, 4009, 369, 38663, 9048, 7194, 41095, 8271, 13918, 6532, 304, 1957, 9293, 323, 11572, 11, 2737, 279, 272, 287, 6468, 49370, 11, 2231, 25807, 11, 323, 80506, 9048, 3158, 320, 50, 4940, 8, 320, 25611, 87, 942, 1880, 453, 2637, 220, 1049, 24, 2652, 735, 399, 72, 42029, 1880, 453, 2637, 220, 679, 15, 2652, 2394, 118904, 537, 1880, 453, 2637, 220, 679, 15, 2652, 50723, 1880, 453, 2637, 220, 679, 18, 2652, 735, 399, 72, 42029, 1880, 453, 2637, 220, 679, 18, 2652, 13789, 64829, 1880, 453, 2637, 220, 679, 21, 7609, 4275, 54769, 304, 37229, 272, 287, 6468, 49370, 320, 30542, 8, 16559, 2038, 922, 21845, 11, 5149, 7194, 11, 323, 6299, 320, 7011, 1264, 2117, 1880, 453, 2637, 220, 1049, 18, 2652, 14594, 1215, 3258, 323, 9935, 285, 11, 220, 1049, 24, 2652, 55757, 323, 9935, 285, 11, 220, 1049, 24, 2652, 77285, 323, 95778, 11, 220, 679, 15, 7026, 323, 32172, 420, 2038, 1139, 459, 7100, 907, 8450, 320, 8270, 1543, 323, 39158, 798, 11, 220, 679, 15, 2652, 65090, 564, 14406, 1880, 453, 2637, 220, 679, 18, 7609, 23674, 11, 63324, 311, 26925, 66278, 38974, 11709, 315, 5149, 1285, 2671, 323, 1990, 1957, 2819, 320, 71509, 1880, 453, 2637, 220, 1049, 18, 1174, 220, 1049, 21, 1174, 220, 1049, 24, 2652, 56834, 3212, 323, 14433, 30970, 11, 220, 1049, 20, 2652, 14594, 1215, 3258, 1880, 453, 2637, 220, 1049, 21, 2652, 432, 799, 55177, 1880, 453, 2637, 220, 1049, 21, 1174, 220, 1049, 23, 2652, 8215, 4618, 1880, 453, 2637, 220, 679, 16, 65, 7609, 6104, 1521, 7978, 11415, 279, 12939, 315, 9048, 14228, 14726, 304, 14393, 5149, 2038, 11, 433, 8625, 25420, 3508, 83699, 304, 1521, 13918, 527, 13118, 5552, 311, 27393, 5149, 2819, 320, 269, 5149, 10694, 1868, 291, 4272, 2819, 705, 279, 7718, 30828, 12223, 11, 902, 1053, 3242, 49895, 1521, 5789, 304, 5597, 3339, 13, 23150, 11, 1521, 13918, 1436, 5042, 4097, 5149, 11, 902, 374, 1243, 5946, 8800, 1023, 13918, 369, 907, 12593, 11618, 13, 362, 1396, 315, 4860, 8617, 31889, 13, 5629, 11, 374, 2038, 922, 11565, 323, 5149, 7863, 304, 8821, 30828, 14726, 11, 477, 374, 420, 2038, 23114, 311, 264, 5654, 430, 43565, 2671, 3196, 389, 872, 18751, 907, 30, 10657, 11, 656, 13918, 430, 52754, 16559, 11565, 477, 5149, 617, 264, 2167, 10383, 389, 26679, 5873, 30, 17830, 11, 26619, 8821, 30828, 6067, 527, 3118, 369, 66700, 11709, 3196, 389, 11565, 19579, 5149, 11, 1268, 1587, 279, 8271, 17114, 7853, 1990, 1521, 17738, 994, 11565, 323, 5149, 2038, 1862, 31322, 11709, 30, 5810, 584, 1511, 264, 3465, 6319, 311, 10765, 33728, 315, 264, 5873, 12593, 369, 5149, 6108, 11429, 304, 12966, 1701, 282, 79770, 323, 311, 1296, 3508, 2204, 30828, 46121, 128257, 198, 128256, 78191, 198, 4438, 656, 584, 10491, 422, 2555, 374, 5922, 279, 5149, 30, 362, 2128, 315, 12074, 505, 26275, 3907, 323, 549, 3218, 617, 1027, 9455, 704, 13, 7357, 1957, 584, 1935, 18065, 264, 2853, 311, 603, 304, 7106, 4907, 11, 3686, 7978, 922, 5597, 28846, 617, 49890, 311, 1427, 520, 1268, 584, 4785, 709, 9434, 7194, 1093, 15635, 477, 892, 13, 4452, 11, 1694, 46243, 311, 43844, 5149, 374, 264, 49648, 369, 264, 2134, 315, 10723, 24673, 11, 779, 8830, 1268, 279, 8271, 11618, 11429, 922, 5149, 19579, 11565, 1436, 3493, 26793, 1139, 1521, 4787, 13, 763, 264, 4007, 7396, 555, 279, 8489, 2063, 17236, 323, 7665, 8483, 9251, 11, 279, 3495, 2128, 9093, 6773, 311, 1518, 422, 1070, 574, 264, 12742, 8271, 1887, 6532, 304, 47826, 709, 7106, 7194, 13, 8483, 261, 2999, 14603, 5038, 43241, 12, 3968, 2448, 70, 713, 1071, 25, 330, 1687, 4691, 23872, 311, 1304, 11709, 16239, 2204, 5990, 315, 33384, 11565, 323, 7106, 5149, 11, 1418, 814, 1051, 9277, 304, 264, 52460, 21438, 13, 330, 1687, 1766, 430, 279, 11429, 814, 1903, 1051, 28160, 555, 2225, 11565, 1404, 323, 5149, 2631, 11, 449, 1389, 69217, 49264, 1389, 5190, 11565, 11, 4827, 5149, 2671, 1694, 8104, 92867, 13, 1226, 1243, 7111, 369, 4040, 8271, 13918, 6532, 304, 279, 5597, 28846, 1210, 578, 2128, 1766, 264, 9959, 5497, 315, 5820, 304, 2380, 5789, 315, 279, 8271, 11, 279, 80506, 9048, 3158, 320, 50, 4940, 705, 96146, 37229, 272, 287, 6468, 49370, 320, 67, 30542, 8, 323, 2231, 25807, 13, 15903, 6492, 8710, 430, 15813, 315, 5149, 574, 2960, 1171, 389, 279, 96996, 323, 2231, 25807, 11, 449, 264, 8821, 4009, 304, 279, 10594, 442, 291, 532, 864, 7096, 278, 49370, 47614, 11565, 13, 578, 294, 30542, 21136, 279, 6811, 1990, 5149, 323, 11565, 439, 264, 3254, 907, 11, 4461, 13633, 3871, 279, 3135, 315, 279, 1403, 8821, 30828, 46121, 11, 323, 5820, 304, 420, 3158, 574, 10815, 449, 279, 8547, 311, 902, 1855, 26202, 596, 11709, 1051, 16625, 555, 279, 8244, 907, 13, 2999, 14603, 5038, 43241, 12, 3968, 2448, 70, 713, 1071, 25, 330, 2028, 3495, 18809, 449, 323, 11621, 311, 14955, 505, 1023, 7978, 13, 2684, 374, 539, 832, 3254, 5597, 28846, 1887, 304, 279, 8271, 719, 264, 743, 315, 1124, 430, 527, 11093, 5882, 6623, 11911, 389, 279, 5597, 584, 527, 17011, 449, 13, 1226, 617, 11054, 279, 1887, 5552, 311, 5149, 11, 264, 4279, 8331, 304, 1690, 11429, 13, 330, 2181, 6209, 459, 20616, 369, 3495, 1139, 264, 1396, 315, 24673, 2737, 18710, 11, 1469, 19682, 323, 8389, 49648, 58533, 13, 44430, 449, 1521, 24673, 3629, 1501, 264, 11293, 5845, 311, 656, 2555, 5149, 1285, 311, 6994, 264, 11565, 13, 5751, 23872, 1051, 2204, 304, 872, 27541, 311, 5149, 11, 323, 8710, 2204, 5990, 315, 30828, 5820, 11, 23377, 430, 1274, 649, 617, 2204, 39954, 1990, 872, 11565, 323, 5149, 6067, 13, 330, 8142, 4726, 3495, 374, 4460, 11, 433, 1253, 387, 430, 1063, 24673, 21736, 264, 8104, 30883, 68331, 1990, 1521, 2204, 5597, 6067, 1210, 2999, 432, 278, 17528, 800, 2303, 86563, 11, 304, 279, 85879, 323, 38895, 6401, 2128, 520, 8489, 2063, 11, 1071, 25, 330, 3947, 527, 1690, 15082, 430, 1397, 603, 311, 17988, 709, 5149, 323, 11565, 11, 369, 2937, 30230, 3508, 279, 5066, 1317, 4321, 311, 636, 1057, 19214, 955, 315, 28974, 374, 5922, 810, 1109, 264, 24210, 4321, 369, 264, 2753, 92867, 28974, 13, 330, 16179, 584, 1440, 264, 2763, 922, 1268, 279, 8271, 69945, 311, 21845, 315, 2204, 12562, 11, 279, 1510, 4007, 374, 279, 1176, 311, 25351, 3177, 389, 264, 8271, 5654, 430, 374, 6532, 304, 27393, 279, 1404, 315, 264, 11565, 323, 279, 7106, 5149, 2631, 311, 636, 433, 13, 16644, 430, 264, 2134, 315, 47657, 4787, 21736, 27129, 304, 19261, 21845, 994, 814, 1397, 5149, 11, 1521, 3135, 1825, 709, 264, 1396, 315, 73234, 369, 3938, 3495, 311, 1296, 810, 24559, 422, 11, 323, 1268, 11, 279, 11565, 14, 6581, 371, 8335, 1253, 733, 1384, 894, 1210, 578, 5684, 11, 61577, 7220, 2859, 315, 907, 12593, 304, 3823, 272, 287, 6468, 49370, 2391, 11429, 23537, 459, 5149, 5621, 1637, 6696, 12744, 11, 374, 4756, 304, 279, 10139, 315, 85879, 13, 220, 128257, 198 ]

2,104

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract The role of individual subunits in the targeting and function of the mammalian BRG1-associated factors (BAF) complex in embryonic stem cell (ESC) pluripotency maintenance has not yet been elucidated. Here we find that the Bromodomain containing protein 9 (BRD9) and Glioma tumor suppressor candidate region gene 1 (GLTSCR1) or its paralog GLTSCR1-like (GLTSCR1L) define a smaller, non-canonical BAF complex (GBAF complex) in mouse ESCs that is distinct from the canonical ESC BAF complex (esBAF). GBAF and esBAF complexes are targeted to different genomic features, with GBAF co-localizing with key regulators of naive pluripotency, which is consistent with its specific function in maintaining naive pluripotency gene expression. BRD9 interacts with BRD4 in a bromodomain-dependent fashion, which leads to the recruitment of GBAF complexes to chromatin, explaining the functional similarity between these epigenetic regulators. Together, our results highlight the biological importance of BAF complex heterogeneity in maintaining the transcriptional network of pluripotency. Introduction Embryonic stem cells (ESCs) have the remarkable ability to self-renew and give rise to any of the over 200 different mature cell types, the property of pluripotency. To maintain ESC identity, the genome is precisely controlled so that only stem cell-specific transcription programs are turned on while lineage-specific programs are silenced 1 , 2 . This control is in part achieved by ATP-dependent chromatin remodeling complexes, which regulate chromatin structure 3 , 4 . In particular, several subunits of the mammalian BRG1-associated factors (BAF) chromatin remodeling complex are required for formation of the inner cell mass (ICM) of the embryo and for maintenance of ESCs in vitro 5 , 6 , 7 , 8 . In mouse ESCs, a specialized BAF complex exists in the form of esBAF, a ~2 MDa complex composed of 9–11 subunits including BRG1, BAF155, BAF47, ARID1A, BAF45A/D, BAF53A, BAF57, SS18, and BAF60A/C 9 , 10 . Genome sequencing studies using conditional deletion of BRG1, the ATPase component of the complex, revealed that esBAF collaborates with the master pluripotency regulators OCT4, SOX2, and NANOG in modulating the expression of ESC-specific genes while repressing genes associated with differentiation 11 , 12 . In addition to esBAF, the related polybromo-associated BAF (PBAF) complex is also present, which contains distinct components including BRD7, ARID2, and PBRM1 13 , 14 , 15 . Upon differentiation, the BAF complex becomes even more diversified, assembling the different subunits in a combinatorial manner, which imparts to the complex its cell type- and developmental stage-specific activities 16 , 17 , 18 . However, it is unclear how distinct BAF complex assemblies and the unique subunits therein contribute to BAF-dependent functions. Mass spectrometric studies in mouse ESCs identified BRD9 as a novel BRG1-interacting partner 9 and was subsequently shown to be a dedicated BAF complex subunit in a leukemic cancer cell line 19 . BRD9 harbors a single bromodomain (BD), an epigenetic reader domain that recognizes acetylated lysines on histones and non-histone proteins 20 , 21 . However, the role of BRD9 in BAF complex targeting and activity remains uncharacterized. Here we find that in mouse ESCs, BRD9 and GLTSCR1/1L are defining members of the smaller, non-canonical GLTSCR1/1L-containing BAF complex or GBAF complex 22 . We perform IP-mass spectrometry characterization of the GBAF complex in mouse ESCs to define shared and unique subunits. GBAF is distinct from esBAF as it lacks BAF47, BAF57, and ARID1A. Chromatin IP (ChIP)-Seq analyses show that esBAF and GBAF are uniquely targeted to sites across the genome and are co-bound with distinct sets of pluripotency transcription factors (TFs). The genomic binding of the GBAF complex is consistent with its role in maintaining the naive pluripotent state, as inhibition of BRD9 results in transcriptional changes representative of a primed epiblast-like state. Conditional deletion of esBAF subunit ARID1A is not highly correlated with this transition, indicating that GBAF complexes have a functionally specific role in regulating this pathway. We demonstrate that BRD9 is targeted to chromatin via its BD, highlighting the role of this reader domain in GBAF complex targeting. Finally, we provide evidence for BD and extra-terminal protein 4 (BRD4)-mediated targeting of the GBAF complex that is BD-dependent, which accounts for their complementary roles in regulating the naive pluripotency transcriptional network. Our studies not only provide important insight into BRD9 function but also add to our understanding of how diversity in BAF complex assembly contributes to the intricate control of the ESC transcription program. Results BRD9 regulates transcription for the maintenance of ESCs To determine the specific role of BRD9 in the maintenance of ESC pluripotency, we made use of the BRD9-BD inhibitor, I-BRD9, which specifically inhibits binding of the BRD9-BD to acetylated residues 23 . By assaying for cell number at different time points, we found a time- and I-BRD9 concentration-dependent decrease in cell proliferation, pointing to a BD-dependent role for BRD9 in maintaining mouse ESCs in serum/leukemia inhibitory factor (LIF) conditions (Fig. 1a ). Because I-BRD9 has been shown to also inhibit BRD4 in vitro 23 , we tested two other BRD9-BD inhibitors (BRD9i), BI-9564 and TP472, which also yielded similar concentration-dependent growth defects in ESCs (Fig. 1b and Supplementary Figure 1a ). Consistent with the specific activity of the BRD9i, short hairpin RNA (shRNA)-mediated knockdown of Brd9 in mouse ESCs with three independent shRNAs resulted in a near complete loss of BRD9 protein expression relative to that of a scrambled control (Supplementary Figures 1 b, 1c ), leading to significant reduction in ESC growth at 2 and 4 days post shRNA transduction (Fig. 1c ). Fig. 1 BRD9 is part of the ESC pluripotency transcriptional regulatory network. a Time course experiment assessing mouse ES cell number after treatment with DMSO or I-BRD9 at either 1.11 or 3.33 µM. Error bars represent one standard deviation from the mean of biological replicates, n = 9. Two-tailed t -test was performed to obtain the p values. * p < 0.05, ** p < 0.01, *** p < 0.001. b As in a , but for ESCs treated with DMSO or BI-9564 at either 300 nM or 1 µM; n", "role": "user" }, { "content": "Embryonic stem cells (ESCs) are the very definition of being full of potential, given that they can become any type of cell in the body. Once they start down any particular path toward a type of tissue, they lose their unlimited potential. Scientists have been trying to understand why and how this happens in order to create regenerative therapies that can, for example, coax a person's own cells to replace damaged or diseased organs. Scientists from the Salk Institute discovered a new protein complex that keeps the brakes on stem cells, allowing them to maintain their indefinite potential. The new complex, called GBAF and detailed in Nature Communications on December 3, 2018, could provide a future target for regenerative medicine. \"This project started as an exploration of embryonic stem cell pluripotency, which is this property that allows ESCs to become all different cell types in the body,\" says Diana Hargreaves, an assistant professor in Salk's Molecular and Cell Biology Laboratory and the senior author of the paper. \"It's very important to know how various networks of genes control pluripotency, so finding a previously unknown protein complex that plays such an important regulatory role was very exciting.\" Every cell in the body has the same set of DNA, which contains the instructions for making every possible cell type. Teams of large protein complexes (known as chromatin remodelers) activate or silence genes, directing an embryonic stem cell down a particular path. Like a team of contractors planning to renovate a house, these protein complexes contain varying subunits, the combination of which changes the physical shape of DNA and determines which genes can be accessed to direct the cell to become, for example, a lung cell or brain cell. Hargreaves's team wanted to better understand how these subunits come together and how particular subunits might dictate a complex's function. So they turned to a protein called BRD9, which was known to associate with the BAF family of chromatin remodelers and was suspected to be a subunit. The team applied a chemical inhibitor of BRD9 to dishes of embryonic stem cells and performed a series of experiments to comprehensively analyze the cells' pluripotency in association with changes in BAF complex activity. Scientists from the Salk Institute discovered a new protein complex that keeps the brakes on stem cells, allowing them to maintain their indefinite potential. Credit: Salk Institute The group was surprised to discover that BRD9 acts as a brake on embryonic stem cell development. When BRD9 is working, cells retain their pluripotency, whereas when its activity is inhibited cells start moving on to the next stage of development. Further work to identify which BAF complexes were at work in the cells revealed another surprise: BRD9 was part of an as-yet-unknown BAF complex. \"For me, what was most exciting about our study was the fact that we had discovered a new BAF complex in embryonic stem cells,\" says Jovylyn Gatchalian, a Salk research associate and the paper's first author. Adds Hargreaves, \"What we see with this work is that there's biochemical diversity at the level of individual variants of the BAF complex that allows for greater regulatory control. Understanding the complexities of that control is going to be key to any regenerative therapies.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract The role of individual subunits in the targeting and function of the mammalian BRG1-associated factors (BAF) complex in embryonic stem cell (ESC) pluripotency maintenance has not yet been elucidated. Here we find that the Bromodomain containing protein 9 (BRD9) and Glioma tumor suppressor candidate region gene 1 (GLTSCR1) or its paralog GLTSCR1-like (GLTSCR1L) define a smaller, non-canonical BAF complex (GBAF complex) in mouse ESCs that is distinct from the canonical ESC BAF complex (esBAF). GBAF and esBAF complexes are targeted to different genomic features, with GBAF co-localizing with key regulators of naive pluripotency, which is consistent with its specific function in maintaining naive pluripotency gene expression. BRD9 interacts with BRD4 in a bromodomain-dependent fashion, which leads to the recruitment of GBAF complexes to chromatin, explaining the functional similarity between these epigenetic regulators. Together, our results highlight the biological importance of BAF complex heterogeneity in maintaining the transcriptional network of pluripotency. Introduction Embryonic stem cells (ESCs) have the remarkable ability to self-renew and give rise to any of the over 200 different mature cell types, the property of pluripotency. To maintain ESC identity, the genome is precisely controlled so that only stem cell-specific transcription programs are turned on while lineage-specific programs are silenced 1 , 2 . This control is in part achieved by ATP-dependent chromatin remodeling complexes, which regulate chromatin structure 3 , 4 . In particular, several subunits of the mammalian BRG1-associated factors (BAF) chromatin remodeling complex are required for formation of the inner cell mass (ICM) of the embryo and for maintenance of ESCs in vitro 5 , 6 , 7 , 8 . In mouse ESCs, a specialized BAF complex exists in the form of esBAF, a ~2 MDa complex composed of 9–11 subunits including BRG1, BAF155, BAF47, ARID1A, BAF45A/D, BAF53A, BAF57, SS18, and BAF60A/C 9 , 10 . Genome sequencing studies using conditional deletion of BRG1, the ATPase component of the complex, revealed that esBAF collaborates with the master pluripotency regulators OCT4, SOX2, and NANOG in modulating the expression of ESC-specific genes while repressing genes associated with differentiation 11 , 12 . In addition to esBAF, the related polybromo-associated BAF (PBAF) complex is also present, which contains distinct components including BRD7, ARID2, and PBRM1 13 , 14 , 15 . Upon differentiation, the BAF complex becomes even more diversified, assembling the different subunits in a combinatorial manner, which imparts to the complex its cell type- and developmental stage-specific activities 16 , 17 , 18 . However, it is unclear how distinct BAF complex assemblies and the unique subunits therein contribute to BAF-dependent functions. Mass spectrometric studies in mouse ESCs identified BRD9 as a novel BRG1-interacting partner 9 and was subsequently shown to be a dedicated BAF complex subunit in a leukemic cancer cell line 19 . BRD9 harbors a single bromodomain (BD), an epigenetic reader domain that recognizes acetylated lysines on histones and non-histone proteins 20 , 21 . However, the role of BRD9 in BAF complex targeting and activity remains uncharacterized. Here we find that in mouse ESCs, BRD9 and GLTSCR1/1L are defining members of the smaller, non-canonical GLTSCR1/1L-containing BAF complex or GBAF complex 22 . We perform IP-mass spectrometry characterization of the GBAF complex in mouse ESCs to define shared and unique subunits. GBAF is distinct from esBAF as it lacks BAF47, BAF57, and ARID1A. Chromatin IP (ChIP)-Seq analyses show that esBAF and GBAF are uniquely targeted to sites across the genome and are co-bound with distinct sets of pluripotency transcription factors (TFs). The genomic binding of the GBAF complex is consistent with its role in maintaining the naive pluripotent state, as inhibition of BRD9 results in transcriptional changes representative of a primed epiblast-like state. Conditional deletion of esBAF subunit ARID1A is not highly correlated with this transition, indicating that GBAF complexes have a functionally specific role in regulating this pathway. We demonstrate that BRD9 is targeted to chromatin via its BD, highlighting the role of this reader domain in GBAF complex targeting. Finally, we provide evidence for BD and extra-terminal protein 4 (BRD4)-mediated targeting of the GBAF complex that is BD-dependent, which accounts for their complementary roles in regulating the naive pluripotency transcriptional network. Our studies not only provide important insight into BRD9 function but also add to our understanding of how diversity in BAF complex assembly contributes to the intricate control of the ESC transcription program. Results BRD9 regulates transcription for the maintenance of ESCs To determine the specific role of BRD9 in the maintenance of ESC pluripotency, we made use of the BRD9-BD inhibitor, I-BRD9, which specifically inhibits binding of the BRD9-BD to acetylated residues 23 . By assaying for cell number at different time points, we found a time- and I-BRD9 concentration-dependent decrease in cell proliferation, pointing to a BD-dependent role for BRD9 in maintaining mouse ESCs in serum/leukemia inhibitory factor (LIF) conditions (Fig. 1a ). Because I-BRD9 has been shown to also inhibit BRD4 in vitro 23 , we tested two other BRD9-BD inhibitors (BRD9i), BI-9564 and TP472, which also yielded similar concentration-dependent growth defects in ESCs (Fig. 1b and Supplementary Figure 1a ). Consistent with the specific activity of the BRD9i, short hairpin RNA (shRNA)-mediated knockdown of Brd9 in mouse ESCs with three independent shRNAs resulted in a near complete loss of BRD9 protein expression relative to that of a scrambled control (Supplementary Figures 1 b, 1c ), leading to significant reduction in ESC growth at 2 and 4 days post shRNA transduction (Fig. 1c ). Fig. 1 BRD9 is part of the ESC pluripotency transcriptional regulatory network. a Time course experiment assessing mouse ES cell number after treatment with DMSO or I-BRD9 at either 1.11 or 3.33 µM. Error bars represent one standard deviation from the mean of biological replicates, n = 9. Two-tailed t -test was performed to obtain the p values. * p < 0.05, ** p < 0.01, *** p < 0.001. b As in a , but for ESCs treated with DMSO or BI-9564 at either 300 nM or 1 µM; n<|im_end|> <|im_start|>assistant Embryonic stem cells (ESCs) are the very definition of being full of potential, given that they can become any type of cell in the body. Once they start down any particular path toward a type of tissue, they lose their unlimited potential. Scientists have been trying to understand why and how this happens in order to create regenerative therapies that can, for example, coax a person's own cells to replace damaged or diseased organs. Scientists from the Salk Institute discovered a new protein complex that keeps the brakes on stem cells, allowing them to maintain their indefinite potential. The new complex, called GBAF and detailed in Nature Communications on December 3, 2018, could provide a future target for regenerative medicine. "This project started as an exploration of embryonic stem cell pluripotency, which is this property that allows ESCs to become all different cell types in the body," says Diana Hargreaves, an assistant professor in Salk's Molecular and Cell Biology Laboratory and the senior author of the paper. "It's very important to know how various networks of genes control pluripotency, so finding a previously unknown protein complex that plays such an important regulatory role was very exciting." Every cell in the body has the same set of DNA, which contains the instructions for making every possible cell type. Teams of large protein complexes (known as chromatin remodelers) activate or silence genes, directing an embryonic stem cell down a particular path. Like a team of contractors planning to renovate a house, these protein complexes contain varying subunits, the combination of which changes the physical shape of DNA and determines which genes can be accessed to direct the cell to become, for example, a lung cell or brain cell. Hargreaves's team wanted to better understand how these subunits come together and how particular subunits might dictate a complex's function. So they turned to a protein called BRD9, which was known to associate with the BAF family of chromatin remodelers and was suspected to be a subunit. The team applied a chemical inhibitor of BRD9 to dishes of embryonic stem cells and performed a series of experiments to comprehensively analyze the cells' pluripotency in association with changes in BAF complex activity. Scientists from the Salk Institute discovered a new protein complex that keeps the brakes on stem cells, allowing them to maintain their indefinite potential. Credit: Salk Institute The group was surprised to discover that BRD9 acts as a brake on embryonic stem cell development. When BRD9 is working, cells retain their pluripotency, whereas when its activity is inhibited cells start moving on to the next stage of development. Further work to identify which BAF complexes were at work in the cells revealed another surprise: BRD9 was part of an as-yet-unknown BAF complex. "For me, what was most exciting about our study was the fact that we had discovered a new BAF complex in embryonic stem cells," says Jovylyn Gatchalian, a Salk research associate and the paper's first author. Adds Hargreaves, "What we see with this work is that there's biochemical diversity at the level of individual variants of the BAF complex that allows for greater regulatory control. Understanding the complexities of that control is going to be key to any regenerative therapies." <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 578, 3560, 315, 3927, 1207, 26726, 304, 279, 25103, 323, 734, 315, 279, 36041, 10700, 19333, 38, 16, 75968, 9547, 320, 7209, 37, 8, 6485, 304, 44481, 14338, 19646, 2849, 320, 54814, 8, 60217, 575, 354, 2301, 13709, 706, 539, 3686, 1027, 97298, 660, 13, 5810, 584, 1505, 430, 279, 65698, 347, 3199, 8649, 13128, 220, 24, 320, 13396, 35, 24, 8, 323, 480, 747, 7942, 36254, 28321, 269, 9322, 5654, 15207, 220, 16, 320, 3910, 51, 38409, 16, 8, 477, 1202, 1370, 32051, 5705, 51, 38409, 16, 12970, 320, 3910, 51, 38409, 16, 43, 8, 7124, 264, 9333, 11, 2536, 72314, 23197, 426, 8440, 6485, 320, 5494, 8440, 6485, 8, 304, 8814, 44374, 82, 430, 374, 12742, 505, 279, 43553, 44374, 426, 8440, 6485, 320, 288, 7209, 37, 570, 480, 7209, 37, 323, 1560, 7209, 37, 69125, 527, 17550, 311, 2204, 81064, 4519, 11, 449, 480, 7209, 37, 1080, 41160, 4954, 449, 1401, 40242, 315, 50765, 60217, 575, 354, 2301, 11, 902, 374, 13263, 449, 1202, 3230, 734, 304, 20958, 50765, 60217, 575, 354, 2301, 15207, 7645, 13, 19333, 35, 24, 84261, 449, 19333, 35, 19, 304, 264, 94571, 347, 3199, 43918, 11401, 11, 902, 11767, 311, 279, 34102, 315, 480, 7209, 37, 69125, 311, 22083, 15111, 11, 26073, 279, 16003, 38723, 1990, 1521, 4248, 6569, 5411, 40242, 13, 32255, 11, 1057, 3135, 11415, 279, 24156, 12939, 315, 426, 8440, 6485, 30548, 76730, 304, 20958, 279, 46940, 278, 4009, 315, 60217, 575, 354, 2301, 13, 29438, 30227, 894, 14338, 19646, 7917, 320, 1600, 34645, 8, 617, 279, 23649, 5845, 311, 659, 5621, 943, 323, 3041, 10205, 311, 904, 315, 279, 927, 220, 1049, 2204, 15196, 2849, 4595, 11, 279, 3424, 315, 60217, 575, 354, 2301, 13, 2057, 10519, 44374, 9764, 11, 279, 33869, 374, 24559, 14400, 779, 430, 1193, 19646, 2849, 19440, 46940, 7620, 527, 6656, 389, 1418, 65009, 19440, 7620, 527, 92781, 220, 16, 1174, 220, 17, 662, 1115, 2585, 374, 304, 961, 17427, 555, 67656, 43918, 22083, 15111, 70430, 69125, 11, 902, 37377, 22083, 15111, 6070, 220, 18, 1174, 220, 19, 662, 763, 4040, 11, 3892, 1207, 26726, 315, 279, 36041, 10700, 19333, 38, 16, 75968, 9547, 320, 7209, 37, 8, 22083, 15111, 70430, 6485, 527, 2631, 369, 18488, 315, 279, 9358, 2849, 3148, 320, 1341, 44, 8, 315, 279, 87701, 323, 369, 13709, 315, 44374, 82, 304, 55004, 220, 20, 1174, 220, 21, 1174, 220, 22, 1174, 220, 23, 662, 763, 8814, 44374, 82, 11, 264, 28175, 426, 8440, 6485, 6866, 304, 279, 1376, 315, 1560, 7209, 37, 11, 264, 4056, 17, 14306, 64, 6485, 24306, 315, 220, 24, 4235, 806, 1207, 26726, 2737, 19333, 38, 16, 11, 426, 8440, 9992, 11, 426, 8440, 2618, 11, 6395, 926, 16, 32, 11, 426, 8440, 1774, 32, 15302, 11, 426, 8440, 4331, 32, 11, 426, 8440, 3226, 11, 18679, 972, 11, 323, 426, 8440, 1399, 32, 11547, 220, 24, 1174, 220, 605, 662, 82917, 62119, 7978, 1701, 35787, 37166, 315, 19333, 38, 16, 11, 279, 67656, 521, 3777, 315, 279, 6485, 11, 10675, 430, 1560, 7209, 37, 11430, 988, 449, 279, 7491, 60217, 575, 354, 2301, 40242, 67277, 19, 11, 5745, 55, 17, 11, 323, 93229, 12501, 304, 1491, 15853, 279, 7645, 315, 44374, 19440, 21389, 1418, 312, 1911, 287, 21389, 5938, 449, 60038, 220, 806, 1174, 220, 717, 662, 763, 5369, 311, 1560, 7209, 37, 11, 279, 5552, 10062, 65, 99639, 75968, 426, 8440, 320, 47, 7209, 37, 8, 6485, 374, 1101, 3118, 11, 902, 5727, 12742, 6956, 2737, 19333, 35, 22, 11, 6395, 926, 17, 11, 323, 393, 13396, 44, 16, 220, 1032, 1174, 220, 975, 1174, 220, 868, 662, 30538, 60038, 11, 279, 426, 8440, 6485, 9221, 1524, 810, 85957, 11, 81759, 279, 2204, 1207, 26726, 304, 264, 3698, 17720, 532, 11827, 11, 902, 3242, 7183, 311, 279, 6485, 1202, 2849, 955, 12, 323, 48006, 6566, 19440, 7640, 220, 845, 1174, 220, 1114, 1174, 220, 972, 662, 4452, 11, 433, 374, 25420, 1268, 12742, 426, 8440, 6485, 62407, 323, 279, 5016, 1207, 26726, 58179, 17210, 311, 426, 8440, 43918, 5865, 13, 9346, 9618, 442, 16743, 7978, 304, 8814, 44374, 82, 11054, 19333, 35, 24, 439, 264, 11775, 19333, 38, 16, 45994, 36022, 8427, 220, 24, 323, 574, 28520, 6982, 311, 387, 264, 12514, 426, 8440, 6485, 1207, 3928, 304, 264, 57381, 8274, 9572, 2849, 1584, 220, 777, 662, 19333, 35, 24, 69566, 1105, 264, 3254, 94571, 347, 3199, 320, 9740, 705, 459, 4248, 6569, 5411, 6742, 8106, 430, 45799, 1645, 2676, 22851, 84495, 1572, 389, 13034, 3233, 323, 2536, 2902, 380, 606, 28896, 220, 508, 1174, 220, 1691, 662, 4452, 11, 279, 3560, 315, 19333, 35, 24, 304, 426, 8440, 6485, 25103, 323, 5820, 8625, 653, 19740, 1534, 13, 5810, 584, 1505, 430, 304, 8814, 44374, 82, 11, 19333, 35, 24, 323, 5705, 51, 38409, 16, 14, 16, 43, 527, 27409, 3697, 315, 279, 9333, 11, 2536, 72314, 23197, 5705, 51, 38409, 16, 14, 16, 43, 93871, 426, 8440, 6485, 477, 480, 7209, 37, 6485, 220, 1313, 662, 1226, 2804, 6933, 1474, 395, 9618, 442, 15501, 60993, 315, 279, 480, 7209, 37, 6485, 304, 8814, 44374, 82, 311, 7124, 6222, 323, 5016, 1207, 26726, 13, 480, 7209, 37, 374, 12742, 505, 1560, 7209, 37, 439, 433, 37856, 426, 8440, 2618, 11, 426, 8440, 3226, 11, 323, 6395, 926, 16, 32, 13, 35318, 15111, 6933, 320, 1163, 3378, 7435, 20794, 29060, 1501, 430, 1560, 7209, 37, 323, 480, 7209, 37, 527, 42329, 17550, 311, 6732, 4028, 279, 33869, 323, 527, 1080, 50962, 449, 12742, 7437, 315, 60217, 575, 354, 2301, 46940, 9547, 320, 11042, 82, 570, 578, 81064, 11212, 315, 279, 480, 7209, 37, 6485, 374, 13263, 449, 1202, 3560, 304, 20958, 279, 50765, 60217, 575, 64632, 1614, 11, 439, 61478, 315, 19333, 35, 24, 3135, 304, 46940, 278, 4442, 18740, 315, 264, 9036, 291, 4248, 581, 4354, 12970, 1614, 13, 93073, 37166, 315, 1560, 7209, 37, 1207, 3928, 6395, 926, 16, 32, 374, 539, 7701, 49393, 449, 420, 9320, 11, 19392, 430, 480, 7209, 37, 69125, 617, 264, 734, 750, 3230, 3560, 304, 58499, 420, 38970, 13, 1226, 20461, 430, 19333, 35, 24, 374, 17550, 311, 22083, 15111, 4669, 1202, 40410, 11, 39686, 279, 3560, 315, 420, 6742, 8106, 304, 480, 7209, 37, 6485, 25103, 13, 17830, 11, 584, 3493, 6029, 369, 40410, 323, 5066, 91723, 13128, 220, 19, 320, 13396, 35, 19, 7435, 4503, 660, 25103, 315, 279, 480, 7209, 37, 6485, 430, 374, 40410, 43918, 11, 902, 9815, 369, 872, 58535, 13073, 304, 58499, 279, 50765, 60217, 575, 354, 2301, 46940, 278, 4009, 13, 5751, 7978, 539, 1193, 3493, 3062, 20616, 1139, 19333, 35, 24, 734, 719, 1101, 923, 311, 1057, 8830, 315, 1268, 20057, 304, 426, 8440, 6485, 14956, 44072, 311, 279, 57216, 2585, 315, 279, 44374, 46940, 2068, 13, 18591, 19333, 35, 24, 80412, 46940, 369, 279, 13709, 315, 44374, 82, 2057, 8417, 279, 3230, 3560, 315, 19333, 35, 24, 304, 279, 13709, 315, 44374, 60217, 575, 354, 2301, 11, 584, 1903, 1005, 315, 279, 19333, 35, 24, 7826, 35, 70785, 11, 358, 7826, 37790, 24, 11, 902, 11951, 20747, 1220, 11212, 315, 279, 19333, 35, 24, 7826, 35, 311, 1645, 2676, 22851, 71783, 220, 1419, 662, 3296, 1089, 17718, 369, 2849, 1396, 520, 2204, 892, 3585, 11, 584, 1766, 264, 892, 12, 323, 358, 7826, 37790, 24, 20545, 43918, 18979, 304, 2849, 53840, 11, 22364, 311, 264, 40410, 43918, 3560, 369, 19333, 35, 24, 304, 20958, 8814, 44374, 82, 304, 41529, 14, 273, 3178, 22689, 20747, 10843, 8331, 320, 43, 2843, 8, 4787, 320, 30035, 13, 220, 16, 64, 7609, 9393, 358, 7826, 37790, 24, 706, 1027, 6982, 311, 1101, 69033, 19333, 35, 19, 304, 55004, 220, 1419, 1174, 584, 12793, 1403, 1023, 19333, 35, 24, 7826, 35, 68642, 320, 13396, 35, 24, 72, 705, 48153, 12, 26067, 19, 323, 30170, 21757, 11, 902, 1101, 58487, 4528, 20545, 43918, 6650, 42655, 304, 44374, 82, 320, 30035, 13, 220, 16, 65, 323, 99371, 19575, 220, 16, 64, 7609, 7440, 18620, 449, 279, 3230, 5820, 315, 279, 19333, 35, 24, 72, 11, 2875, 7013, 13576, 41214, 320, 939, 31820, 7435, 4503, 660, 14459, 2996, 315, 3320, 67, 24, 304, 8814, 44374, 82, 449, 2380, 9678, 559, 51295, 2170, 19543, 304, 264, 3221, 4686, 4814, 315, 19333, 35, 24, 13128, 7645, 8844, 311, 430, 315, 264, 71578, 2585, 320, 10254, 67082, 69356, 220, 16, 293, 11, 220, 16, 66, 7026, 6522, 311, 5199, 14278, 304, 44374, 6650, 520, 220, 17, 323, 220, 19, 2919, 1772, 559, 31820, 1380, 23985, 320, 30035, 13, 220, 16, 66, 7609, 23966, 13, 220, 16, 19333, 35, 24, 374, 961, 315, 279, 44374, 60217, 575, 354, 2301, 46940, 278, 23331, 4009, 13, 264, 4212, 3388, 9526, 47614, 8814, 19844, 2849, 1396, 1306, 6514, 449, 423, 4931, 46, 477, 358, 7826, 37790, 24, 520, 3060, 220, 16, 13, 806, 477, 220, 18, 13, 1644, 64012, 44, 13, 4703, 16283, 4097, 832, 5410, 38664, 505, 279, 3152, 315, 24156, 29641, 988, 11, 308, 284, 220, 24, 13, 9220, 2442, 5805, 259, 482, 1985, 574, 10887, 311, 6994, 279, 281, 2819, 13, 353, 281, 366, 220, 15, 13, 2304, 11, 3146, 281, 366, 220, 15, 13, 1721, 11, 17601, 281, 366, 220, 15, 13, 4119, 13, 293, 1666, 304, 264, 1174, 719, 369, 44374, 82, 12020, 449, 423, 4931, 46, 477, 48153, 12, 26067, 19, 520, 3060, 220, 3101, 308, 44, 477, 220, 16, 64012, 44, 26, 308, 128257, 198, 128256, 78191, 198, 99886, 894, 14338, 19646, 7917, 320, 1600, 34645, 8, 527, 279, 1633, 7419, 315, 1694, 2539, 315, 4754, 11, 2728, 430, 814, 649, 3719, 904, 955, 315, 2849, 304, 279, 2547, 13, 9843, 814, 1212, 1523, 904, 4040, 1853, 9017, 264, 955, 315, 20438, 11, 814, 9229, 872, 27862, 4754, 13, 57116, 617, 1027, 4560, 311, 3619, 3249, 323, 1268, 420, 8741, 304, 2015, 311, 1893, 1239, 75989, 52312, 430, 649, 11, 369, 3187, 11, 91966, 264, 1732, 596, 1866, 7917, 311, 8454, 20727, 477, 6759, 1503, 36853, 13, 57116, 505, 279, 328, 1727, 10181, 11352, 264, 502, 13128, 6485, 430, 13912, 279, 45664, 389, 19646, 7917, 11, 10923, 1124, 311, 10519, 872, 81956, 4754, 13, 578, 502, 6485, 11, 2663, 480, 7209, 37, 323, 11944, 304, 22037, 26545, 389, 6790, 220, 18, 11, 220, 679, 23, 11, 1436, 3493, 264, 3938, 2218, 369, 1239, 75989, 16088, 13, 330, 2028, 2447, 3940, 439, 459, 27501, 315, 44481, 14338, 19646, 2849, 60217, 575, 354, 2301, 11, 902, 374, 420, 3424, 430, 6276, 44374, 82, 311, 3719, 682, 2204, 2849, 4595, 304, 279, 2547, 1359, 2795, 45509, 473, 867, 265, 4798, 11, 459, 18328, 14561, 304, 328, 1727, 596, 60825, 323, 14299, 40023, 32184, 323, 279, 10195, 3229, 315, 279, 5684, 13, 330, 2181, 596, 1633, 3062, 311, 1440, 1268, 5370, 14488, 315, 21389, 2585, 60217, 575, 354, 2301, 11, 779, 9455, 264, 8767, 9987, 13128, 6485, 430, 11335, 1778, 459, 3062, 23331, 3560, 574, 1633, 13548, 1210, 7357, 2849, 304, 279, 2547, 706, 279, 1890, 743, 315, 15922, 11, 902, 5727, 279, 11470, 369, 3339, 1475, 3284, 2849, 955, 13, 40713, 315, 3544, 13128, 69125, 320, 5391, 439, 22083, 15111, 47086, 388, 8, 20891, 477, 21847, 21389, 11, 46090, 459, 44481, 14338, 19646, 2849, 1523, 264, 4040, 1853, 13, 9086, 264, 2128, 315, 33840, 9293, 311, 32652, 349, 264, 3838, 11, 1521, 13128, 69125, 6782, 29865, 1207, 26726, 11, 279, 10824, 315, 902, 4442, 279, 7106, 6211, 315, 15922, 323, 27667, 902, 21389, 649, 387, 25790, 311, 2167, 279, 2849, 311, 3719, 11, 369, 3187, 11, 264, 21271, 2849, 477, 8271, 2849, 13, 473, 867, 265, 4798, 596, 2128, 4934, 311, 2731, 3619, 1268, 1521, 1207, 26726, 2586, 3871, 323, 1268, 4040, 1207, 26726, 2643, 62974, 264, 6485, 596, 734, 13, 2100, 814, 6656, 311, 264, 13128, 2663, 19333, 35, 24, 11, 902, 574, 3967, 311, 22712, 449, 279, 426, 8440, 3070, 315, 22083, 15111, 47086, 388, 323, 574, 24740, 311, 387, 264, 1207, 3928, 13, 578, 2128, 9435, 264, 11742, 70785, 315, 19333, 35, 24, 311, 26863, 315, 44481, 14338, 19646, 7917, 323, 10887, 264, 4101, 315, 21896, 311, 12963, 28014, 24564, 279, 7917, 6, 60217, 575, 354, 2301, 304, 15360, 449, 4442, 304, 426, 8440, 6485, 5820, 13, 57116, 505, 279, 328, 1727, 10181, 11352, 264, 502, 13128, 6485, 430, 13912, 279, 45664, 389, 19646, 7917, 11, 10923, 1124, 311, 10519, 872, 81956, 4754, 13, 16666, 25, 328, 1727, 10181, 578, 1912, 574, 14792, 311, 7142, 430, 19333, 35, 24, 14385, 439, 264, 35718, 389, 44481, 14338, 19646, 2849, 4500, 13, 3277, 19333, 35, 24, 374, 3318, 11, 7917, 14389, 872, 60217, 575, 354, 2301, 11, 20444, 994, 1202, 5820, 374, 99669, 7917, 1212, 7366, 389, 311, 279, 1828, 6566, 315, 4500, 13, 15903, 990, 311, 10765, 902, 426, 8440, 69125, 1051, 520, 990, 304, 279, 7917, 10675, 2500, 13051, 25, 19333, 35, 24, 574, 961, 315, 459, 439, 12303, 295, 12, 16476, 426, 8440, 6485, 13, 330, 2520, 757, 11, 1148, 574, 1455, 13548, 922, 1057, 4007, 574, 279, 2144, 430, 584, 1047, 11352, 264, 502, 426, 8440, 6485, 304, 44481, 14338, 19646, 7917, 1359, 2795, 622, 62615, 18499, 480, 759, 10700, 11, 264, 328, 1727, 3495, 22712, 323, 279, 5684, 596, 1176, 3229, 13, 25483, 473, 867, 265, 4798, 11, 330, 3923, 584, 1518, 449, 420, 990, 374, 430, 1070, 596, 93532, 20057, 520, 279, 2237, 315, 3927, 27103, 315, 279, 426, 8440, 6485, 430, 6276, 369, 7191, 23331, 2585, 13, 46551, 279, 84140, 315, 430, 2585, 374, 2133, 311, 387, 1401, 311, 904, 1239, 75989, 52312, 1210, 220, 128257, 198 ]

2,290

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract In humans and chimpanzees, most intraspecific killing occurs during coalitionary intergroup conflict. In the closely related genus Gorilla, such behavior has not been described. We report three cases of multi-male, multi-female wild mountain gorilla ( G. beringei ) groups attacking extra-group males. The behavior was strikingly similar to reports in chimpanzees, but was never observed in gorillas until after a demographic transition left ~25% of the population living in large social groups with multiple (3+) males. Resource competition is generally considered a motivator of great apes’ (including humans) violent intergroup conflict, but mountain gorillas are non-territorial herbivores with low feeding competition. While adult male gorillas have a defensible resource (i.e. females) and nursing/pregnant females are likely motivated to drive off potentially infanticidal intruders, the participation of others (e.g. juveniles, sub-adults, cycling females) is harder to explain. We speculate that the potential for severe group disruption when current alpha males are severely injured or killed may provide sufficient motivation when the costs to participants are low. These observations suggest that the gorilla population’s recent increase in multi-male groups facilitated the emergence of such behavior, and indicates social structure is a key predictor of coalitionary aggression even in the absence of meaningful resource stress. Introduction Intergroup coalitionary aggression is rare in the animal kingdom, but has particularly notable evolutionary and social significance in Homo sapiens 1 . It is therefore unsurprising that the vertebrate animal behavior corollary best approximating human warfare occurs in one of humans’ closest extant relative, chimpanzees 2 , 3 . As is true for humans, rates of such encounters vary widely across sites and social groups 4 , but lethal chimpanzee ‘raids’ and other forms of cooperative intergroup attacks have been regularly reported at multiple long-term field sites 2 , 5 , 6 , 7 , 8 , 9 , 10 , 11 . Between and within species, violent intergroup conflict is most likely to occur when important resources are defensible and demographic power imbalances reduce the cost to individual participants 4 , 11 , 12 , 13 , 14 . These socioecological conditions help explain differences in relative rates of both human and chimpanzee ‘warfare,’ across sites and groups, as well as its near-absence in other close relatives including bonobos 2 , 3 , 4 and orangutans 15 . Ultimate explanations for the evolution of coalitionary aggression include direct benefits via improved resource access 11 , 12 , 13 , 14 or status maintenance/elevation 16 , 17 , or indirect benefits via kin selection and reciprocal altruism 18 , 19 . Mountain gorillas ( Gorilla beringei ) have been continuously observed in the wild for nearly the same length of time as chimpanzees (~50 years 20 ). Very little coalitionary aggression, either intra or intergroup, has been reported despite the species’ close relationship to humans and chimpanzees 21 . Published examples are limited to small intragroup female alliances, male intervention in such alliances, and reports of individual males supporting either other males, or females 22 , 23 , 24 , 25 . The purported absence of meaningful coalitionary aggression is unsurprising for two reasons. First, the modal group type is one male with multiple females and their offspring, which limits opportunities for coalitions 26 . Second, resource defense is often considered an important motivator of such behavior in great apes 3 , 4 , 11 , but unlike chimpanzees and (historically) humans, mountain gorillas are herbivores with an abundant year-round food supply 27 , 28 . Far less is known about the behavior of more frugivorous western lowland gorillas ( G. gorilla ), but since they also primarily occur in single-male groups opportunities for male coalitions are limited, and benefits of female coalitions are probably minimal 29 . To date no coalitions have been reported for either sex in the western lowland subspecies. Mountain gorilla groups maintain overlapping home ranges, and social units frequently encounter one another in the forest 30 . Interactions can be risky even for animals that do not actively participate. Sexually selected infanticide is an important source of infant mortality in this population 31 , and intergroup interactions expose young animals to potentially infanticidal males. However, as in many primate species, most intergroup interactions are characterized primarily by chasing, aggressive vocalizations, and sometimes minor wounding, but do not usually end in serious injury and may even involve affiliative behavior 13 . In a typical interaction between gorilla groups or between a group and a solitary adult male, young adult and/or fully adult males engage in repeated bluff displays that may or may not escalate to physical contact 32 , 33 . Females and younger group members typically watch from a distance, though females may use interactions to transfer between social groups, and males will herd them to prevent transfers 32 . Involvement of animals other than young adult and fully adult males is usually limited to vocal aggression, if they participate at all (Karisoke Research Center long-term records, pers. obs.). Gorillas’ morphology (extreme sexual dimorphism 34 , well-developed male weaponry 35 , and small testes relative to body size 36 ) strongly suggests they have a long evolutionary history of male contest competition and a one male, multi-female social structure. This was largely supported by demographic and behavioral data collected from the mid 1950’s to the early 1990’s on the mountain gorilla population living in central Africa’s Virunga Massif, one of only two remaining populations in the world. While groups containing two or occasionally three adult males (likely fathers and sons) were reported as far back as the 1950s 37 , 38 , most mountain gorilla groups contained only one adult male 20 , 26 , 38 . However starting in the mid to late 1990’s, the habituated gorilla groups, particularly those monitored by the Dian Fossey Gorilla Fund’s Karisoke Research Center (KRC), grew dramatically larger and increasingly multi-male (hereafter defined as groups containing 3+ adult males). In this system either sex can disperse (females can join established groups or solitary adult", "role": "user" }, { "content": "(Phys.org)—A trio of researchers studying gorillas in Karisoke Research Center in Rwanda has reported on a developing trend observed in mountain gorillas—mobs attacking single individuals for unknown reasons. In their paper published in Scientific Reports, Stacy Rosenbaum, Veronica Vecellio and Tara Stoinski describe three mob attacks that have been observed by several human witnesses over the past decade and offer some possible explanations. For most of the modern study of gorillas in their native environment, the consensus has been that they are generally docile with one another—there have been observations of males fighting, sometimes to the death, but for the most part, the life of the gorilla was thought to be one of mostly peaceful. But now, it appears that the peace can be disturbed by the occasional mob attack on a single individual or, as the researchers note, two individuals. In the first witnessed attack, back in 2004, Rosenbaum was actually one of the witnesses. She describes the incident as arising seemingly out of nowhere. A single male the team had named Inshuti approached a group of gorillas the researchers had named the Beetsme. After some initial rebuffs, the lone male continued to seek acceptance. Then one of the gorillas screamed—the witnesses could not say if it was Inshuti or a member of the group. That was followed by three adult males chasing Inshuti until they caught him and pinned him to the ground. Soon thereafter, the rest of the Beetsme group arrived and all of them (including females and youngsters) participated in causing harm to Inshuti—from pulling hair to scratching and kicking. The leader of the Beetsme sunk his teeth into the gorilla's flesh and shook it like a fighting dog. The mob attack continued for just a few minutes, but then stopped just as quickly as it had started. The attackers walked away and Inshuti slunk into the underbrush to attend to his wounds. The researchers report on two other similar incidents, one of which included an attack on Inshuti and another male. They note that mob attacks by other apes, including chimps, is common, as in humans, but until these recent incidents, it was thought gorillas were gentle giants, unlikely to engage in such violence. The team admits they do not know why the gorillas have begun acting like mobs at times but note that it has occurred during a time when the mountain gorilla population has grown due to conservation efforts. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract In humans and chimpanzees, most intraspecific killing occurs during coalitionary intergroup conflict. In the closely related genus Gorilla, such behavior has not been described. We report three cases of multi-male, multi-female wild mountain gorilla ( G. beringei ) groups attacking extra-group males. The behavior was strikingly similar to reports in chimpanzees, but was never observed in gorillas until after a demographic transition left ~25% of the population living in large social groups with multiple (3+) males. Resource competition is generally considered a motivator of great apes’ (including humans) violent intergroup conflict, but mountain gorillas are non-territorial herbivores with low feeding competition. While adult male gorillas have a defensible resource (i.e. females) and nursing/pregnant females are likely motivated to drive off potentially infanticidal intruders, the participation of others (e.g. juveniles, sub-adults, cycling females) is harder to explain. We speculate that the potential for severe group disruption when current alpha males are severely injured or killed may provide sufficient motivation when the costs to participants are low. These observations suggest that the gorilla population’s recent increase in multi-male groups facilitated the emergence of such behavior, and indicates social structure is a key predictor of coalitionary aggression even in the absence of meaningful resource stress. Introduction Intergroup coalitionary aggression is rare in the animal kingdom, but has particularly notable evolutionary and social significance in Homo sapiens 1 . It is therefore unsurprising that the vertebrate animal behavior corollary best approximating human warfare occurs in one of humans’ closest extant relative, chimpanzees 2 , 3 . As is true for humans, rates of such encounters vary widely across sites and social groups 4 , but lethal chimpanzee ‘raids’ and other forms of cooperative intergroup attacks have been regularly reported at multiple long-term field sites 2 , 5 , 6 , 7 , 8 , 9 , 10 , 11 . Between and within species, violent intergroup conflict is most likely to occur when important resources are defensible and demographic power imbalances reduce the cost to individual participants 4 , 11 , 12 , 13 , 14 . These socioecological conditions help explain differences in relative rates of both human and chimpanzee ‘warfare,’ across sites and groups, as well as its near-absence in other close relatives including bonobos 2 , 3 , 4 and orangutans 15 . Ultimate explanations for the evolution of coalitionary aggression include direct benefits via improved resource access 11 , 12 , 13 , 14 or status maintenance/elevation 16 , 17 , or indirect benefits via kin selection and reciprocal altruism 18 , 19 . Mountain gorillas ( Gorilla beringei ) have been continuously observed in the wild for nearly the same length of time as chimpanzees (~50 years 20 ). Very little coalitionary aggression, either intra or intergroup, has been reported despite the species’ close relationship to humans and chimpanzees 21 . Published examples are limited to small intragroup female alliances, male intervention in such alliances, and reports of individual males supporting either other males, or females 22 , 23 , 24 , 25 . The purported absence of meaningful coalitionary aggression is unsurprising for two reasons. First, the modal group type is one male with multiple females and their offspring, which limits opportunities for coalitions 26 . Second, resource defense is often considered an important motivator of such behavior in great apes 3 , 4 , 11 , but unlike chimpanzees and (historically) humans, mountain gorillas are herbivores with an abundant year-round food supply 27 , 28 . Far less is known about the behavior of more frugivorous western lowland gorillas ( G. gorilla ), but since they also primarily occur in single-male groups opportunities for male coalitions are limited, and benefits of female coalitions are probably minimal 29 . To date no coalitions have been reported for either sex in the western lowland subspecies. Mountain gorilla groups maintain overlapping home ranges, and social units frequently encounter one another in the forest 30 . Interactions can be risky even for animals that do not actively participate. Sexually selected infanticide is an important source of infant mortality in this population 31 , and intergroup interactions expose young animals to potentially infanticidal males. However, as in many primate species, most intergroup interactions are characterized primarily by chasing, aggressive vocalizations, and sometimes minor wounding, but do not usually end in serious injury and may even involve affiliative behavior 13 . In a typical interaction between gorilla groups or between a group and a solitary adult male, young adult and/or fully adult males engage in repeated bluff displays that may or may not escalate to physical contact 32 , 33 . Females and younger group members typically watch from a distance, though females may use interactions to transfer between social groups, and males will herd them to prevent transfers 32 . Involvement of animals other than young adult and fully adult males is usually limited to vocal aggression, if they participate at all (Karisoke Research Center long-term records, pers. obs.). Gorillas’ morphology (extreme sexual dimorphism 34 , well-developed male weaponry 35 , and small testes relative to body size 36 ) strongly suggests they have a long evolutionary history of male contest competition and a one male, multi-female social structure. This was largely supported by demographic and behavioral data collected from the mid 1950’s to the early 1990’s on the mountain gorilla population living in central Africa’s Virunga Massif, one of only two remaining populations in the world. While groups containing two or occasionally three adult males (likely fathers and sons) were reported as far back as the 1950s 37 , 38 , most mountain gorilla groups contained only one adult male 20 , 26 , 38 . However starting in the mid to late 1990’s, the habituated gorilla groups, particularly those monitored by the Dian Fossey Gorilla Fund’s Karisoke Research Center (KRC), grew dramatically larger and increasingly multi-male (hereafter defined as groups containing 3+ adult males). In this system either sex can disperse (females can join established groups or solitary adult<|im_end|> <|im_start|>assistant (Phys.org)—A trio of researchers studying gorillas in Karisoke Research Center in Rwanda has reported on a developing trend observed in mountain gorillas—mobs attacking single individuals for unknown reasons. In their paper published in Scientific Reports, Stacy Rosenbaum, Veronica Vecellio and Tara Stoinski describe three mob attacks that have been observed by several human witnesses over the past decade and offer some possible explanations. For most of the modern study of gorillas in their native environment, the consensus has been that they are generally docile with one another—there have been observations of males fighting, sometimes to the death, but for the most part, the life of the gorilla was thought to be one of mostly peaceful. But now, it appears that the peace can be disturbed by the occasional mob attack on a single individual or, as the researchers note, two individuals. In the first witnessed attack, back in 2004, Rosenbaum was actually one of the witnesses. She describes the incident as arising seemingly out of nowhere. A single male the team had named Inshuti approached a group of gorillas the researchers had named the Beetsme. After some initial rebuffs, the lone male continued to seek acceptance. Then one of the gorillas screamed—the witnesses could not say if it was Inshuti or a member of the group. That was followed by three adult males chasing Inshuti until they caught him and pinned him to the ground. Soon thereafter, the rest of the Beetsme group arrived and all of them (including females and youngsters) participated in causing harm to Inshuti—from pulling hair to scratching and kicking. The leader of the Beetsme sunk his teeth into the gorilla's flesh and shook it like a fighting dog. The mob attack continued for just a few minutes, but then stopped just as quickly as it had started. The attackers walked away and Inshuti slunk into the underbrush to attend to his wounds. The researchers report on two other similar incidents, one of which included an attack on Inshuti and another male. They note that mob attacks by other apes, including chimps, is common, as in humans, but until these recent incidents, it was thought gorillas were gentle giants, unlikely to engage in such violence. The team admits they do not know why the gorillas have begun acting like mobs at times but note that it has occurred during a time when the mountain gorilla population has grown due to conservation efforts. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 763, 12966, 323, 99425, 3059, 288, 11, 1455, 10805, 300, 15934, 13419, 13980, 2391, 26283, 661, 958, 4166, 12324, 13, 763, 279, 15499, 5552, 64677, 47247, 6374, 11, 1778, 7865, 706, 539, 1027, 7633, 13, 1226, 1934, 2380, 5157, 315, 7447, 1474, 1604, 11, 7447, 2269, 12011, 8545, 16700, 46298, 6374, 320, 480, 13, 293, 4776, 20568, 883, 5315, 23664, 5066, 4449, 25000, 13, 578, 7865, 574, 21933, 398, 4528, 311, 6821, 304, 99425, 3059, 288, 11, 719, 574, 2646, 13468, 304, 46298, 34344, 3156, 1306, 264, 38462, 9320, 2163, 4056, 914, 4, 315, 279, 7187, 5496, 304, 3544, 3674, 5315, 449, 5361, 320, 18, 37297, 25000, 13, 12027, 10937, 374, 8965, 6646, 264, 12521, 859, 315, 2294, 1469, 288, 529, 320, 16564, 12966, 8, 16806, 958, 4166, 12324, 11, 719, 16700, 46298, 34344, 527, 2536, 12, 96315, 22676, 39999, 344, 4692, 449, 3428, 26040, 10937, 13, 6104, 6822, 8762, 46298, 34344, 617, 264, 711, 37864, 5211, 320, 72, 1770, 13, 28585, 8, 323, 28456, 4420, 40381, 519, 28585, 527, 4461, 27762, 311, 6678, 1022, 13893, 4225, 8322, 26966, 10805, 664, 388, 11, 279, 20852, 315, 3885, 320, 68, 1326, 13, 99545, 3742, 11, 1207, 26831, 122761, 11, 33162, 28585, 8, 374, 16127, 311, 10552, 13, 1226, 64601, 430, 279, 4754, 369, 15748, 1912, 44219, 994, 1510, 8451, 25000, 527, 35906, 15902, 477, 7577, 1253, 3493, 14343, 25835, 994, 279, 7194, 311, 13324, 527, 3428, 13, 4314, 24654, 4284, 430, 279, 46298, 6374, 7187, 753, 3293, 5376, 304, 7447, 1474, 1604, 5315, 72849, 279, 49179, 315, 1778, 7865, 11, 323, 15151, 3674, 6070, 374, 264, 1401, 62254, 315, 26283, 661, 40307, 1524, 304, 279, 19821, 315, 23222, 5211, 8631, 13, 29438, 1357, 2431, 896, 26283, 661, 40307, 374, 9024, 304, 279, 10065, 26135, 11, 719, 706, 8104, 28289, 41993, 323, 3674, 26431, 304, 84497, 82295, 729, 220, 16, 662, 1102, 374, 9093, 69217, 34754, 430, 279, 67861, 65216, 10065, 7865, 1867, 980, 661, 1888, 10049, 79448, 3823, 39307, 13980, 304, 832, 315, 12966, 529, 18585, 1327, 519, 8844, 11, 99425, 3059, 288, 220, 17, 1174, 220, 18, 662, 1666, 374, 837, 369, 12966, 11, 7969, 315, 1778, 35006, 13592, 13882, 4028, 6732, 323, 3674, 5315, 220, 19, 1174, 719, 45089, 99425, 99066, 3451, 969, 3447, 529, 323, 1023, 7739, 315, 48566, 958, 4166, 8951, 617, 1027, 15870, 5068, 520, 5361, 1317, 9860, 2115, 6732, 220, 17, 1174, 220, 20, 1174, 220, 21, 1174, 220, 22, 1174, 220, 23, 1174, 220, 24, 1174, 220, 605, 1174, 220, 806, 662, 28232, 323, 2949, 9606, 11, 16806, 958, 4166, 12324, 374, 1455, 4461, 311, 12446, 994, 3062, 5070, 527, 711, 37864, 323, 38462, 2410, 737, 76527, 8108, 279, 2853, 311, 3927, 13324, 220, 19, 1174, 220, 806, 1174, 220, 717, 1174, 220, 1032, 1174, 220, 975, 662, 4314, 41589, 762, 5848, 4787, 1520, 10552, 12062, 304, 8844, 7969, 315, 2225, 3823, 323, 99425, 99066, 3451, 11710, 23920, 23189, 4028, 6732, 323, 5315, 11, 439, 1664, 439, 1202, 3221, 97510, 768, 304, 1023, 3345, 29658, 2737, 7970, 677, 437, 220, 17, 1174, 220, 18, 1174, 220, 19, 323, 50707, 332, 598, 220, 868, 662, 29950, 41941, 369, 279, 15740, 315, 26283, 661, 40307, 2997, 2167, 7720, 4669, 13241, 5211, 2680, 220, 806, 1174, 220, 717, 1174, 220, 1032, 1174, 220, 975, 477, 2704, 13709, 16954, 44857, 220, 845, 1174, 220, 1114, 1174, 477, 25636, 7720, 4669, 24890, 6727, 323, 87298, 93592, 2191, 220, 972, 1174, 220, 777, 662, 19149, 46298, 34344, 320, 47247, 6374, 293, 4776, 20568, 883, 617, 1027, 31978, 13468, 304, 279, 8545, 369, 7154, 279, 1890, 3160, 315, 892, 439, 99425, 3059, 288, 31857, 1135, 1667, 220, 508, 7609, 15668, 2697, 26283, 661, 40307, 11, 3060, 50938, 477, 958, 4166, 11, 706, 1027, 5068, 8994, 279, 9606, 529, 3345, 5133, 311, 12966, 323, 99425, 3059, 288, 220, 1691, 662, 30114, 10507, 527, 7347, 311, 2678, 10805, 351, 896, 8954, 70800, 11, 8762, 21623, 304, 1778, 70800, 11, 323, 6821, 315, 3927, 25000, 12899, 3060, 1023, 25000, 11, 477, 28585, 220, 1313, 1174, 220, 1419, 1174, 220, 1187, 1174, 220, 914, 662, 578, 59860, 19821, 315, 23222, 26283, 661, 40307, 374, 69217, 34754, 369, 1403, 8125, 13, 5629, 11, 279, 13531, 1912, 955, 374, 832, 8762, 449, 5361, 28585, 323, 872, 46471, 11, 902, 13693, 10708, 369, 11756, 6055, 220, 1627, 662, 10657, 11, 5211, 9232, 374, 3629, 6646, 459, 3062, 12521, 859, 315, 1778, 7865, 304, 2294, 1469, 288, 220, 18, 1174, 220, 19, 1174, 220, 806, 1174, 719, 20426, 99425, 3059, 288, 323, 320, 44541, 2740, 8, 12966, 11, 16700, 46298, 34344, 527, 39999, 344, 4692, 449, 459, 44611, 1060, 21691, 3691, 8312, 220, 1544, 1174, 220, 1591, 662, 13759, 2753, 374, 3967, 922, 279, 7865, 315, 810, 1448, 773, 344, 20857, 19001, 3428, 1974, 46298, 34344, 320, 480, 13, 46298, 6374, 7026, 719, 2533, 814, 1101, 15871, 12446, 304, 3254, 1474, 1604, 5315, 10708, 369, 8762, 11756, 6055, 527, 7347, 11, 323, 7720, 315, 8954, 11756, 6055, 527, 4762, 17832, 220, 1682, 662, 2057, 2457, 912, 11756, 6055, 617, 1027, 5068, 369, 3060, 1877, 304, 279, 19001, 3428, 1974, 5258, 89721, 13, 19149, 46298, 6374, 5315, 10519, 50917, 2162, 21986, 11, 323, 3674, 8316, 14134, 13123, 832, 2500, 304, 279, 13952, 220, 966, 662, 5783, 4109, 649, 387, 41273, 1524, 369, 10099, 430, 656, 539, 22815, 16136, 13, 6834, 1870, 4183, 4225, 8322, 579, 374, 459, 3062, 2592, 315, 31383, 29528, 304, 420, 7187, 220, 2148, 1174, 323, 958, 4166, 22639, 29241, 3995, 10099, 311, 13893, 4225, 8322, 26966, 25000, 13, 4452, 11, 439, 304, 1690, 550, 3509, 9606, 11, 1455, 958, 4166, 22639, 527, 32971, 15871, 555, 43931, 11, 19738, 26480, 8200, 11, 323, 7170, 9099, 289, 13900, 11, 719, 656, 539, 6118, 842, 304, 6129, 11134, 323, 1253, 1524, 21736, 12204, 1413, 7865, 220, 1032, 662, 763, 264, 14595, 16628, 1990, 46298, 6374, 5315, 477, 1990, 264, 1912, 323, 264, 58229, 6822, 8762, 11, 3995, 6822, 323, 5255, 7373, 6822, 25000, 16988, 304, 11763, 97388, 19207, 430, 1253, 477, 1253, 539, 89690, 311, 7106, 3729, 220, 843, 1174, 220, 1644, 662, 35295, 3916, 323, 14992, 1912, 3697, 11383, 3821, 505, 264, 6138, 11, 3582, 28585, 1253, 1005, 22639, 311, 8481, 1990, 3674, 5315, 11, 323, 25000, 690, 59213, 1124, 311, 5471, 31711, 220, 843, 662, 763, 12821, 7986, 315, 10099, 1023, 1109, 3995, 6822, 323, 7373, 6822, 25000, 374, 6118, 7347, 311, 26480, 40307, 11, 422, 814, 16136, 520, 682, 320, 42, 42960, 4845, 8483, 5955, 1317, 9860, 7576, 11, 7565, 13, 7600, 36434, 47247, 34344, 529, 79612, 320, 428, 9831, 7392, 5213, 53907, 220, 1958, 1174, 1664, 49061, 291, 8762, 78122, 220, 1758, 1174, 323, 2678, 1296, 288, 8844, 311, 2547, 1404, 220, 1927, 883, 16917, 13533, 814, 617, 264, 1317, 41993, 3925, 315, 8762, 14130, 10937, 323, 264, 832, 8762, 11, 7447, 2269, 12011, 3674, 6070, 13, 1115, 574, 14090, 7396, 555, 38462, 323, 36695, 828, 14890, 505, 279, 5209, 220, 6280, 15, 753, 311, 279, 4216, 220, 2550, 15, 753, 389, 279, 16700, 46298, 6374, 7187, 5496, 304, 8792, 10384, 753, 9734, 92945, 9346, 333, 11, 832, 315, 1193, 1403, 9861, 22673, 304, 279, 1917, 13, 6104, 5315, 8649, 1403, 477, 23781, 2380, 6822, 25000, 320, 14617, 40317, 323, 26419, 8, 1051, 5068, 439, 3117, 1203, 439, 279, 220, 6280, 15, 82, 220, 1806, 1174, 220, 1987, 1174, 1455, 16700, 46298, 6374, 5315, 13282, 1193, 832, 6822, 8762, 220, 508, 1174, 220, 1627, 1174, 220, 1987, 662, 4452, 6041, 304, 279, 5209, 311, 3389, 220, 2550, 15, 753, 11, 279, 14464, 13148, 46298, 6374, 5315, 11, 8104, 1884, 41223, 555, 279, 423, 1122, 435, 437, 8674, 47247, 6374, 13492, 753, 13528, 285, 4845, 8483, 5955, 320, 42, 7532, 705, 14264, 29057, 8294, 323, 15098, 7447, 1474, 1604, 320, 6881, 10924, 4613, 439, 5315, 8649, 220, 18, 10, 6822, 25000, 570, 763, 420, 1887, 3060, 1877, 649, 834, 82344, 320, 69, 87503, 649, 5249, 9749, 5315, 477, 58229, 6822, 128257, 198, 128256, 78191, 198, 7, 67171, 2726, 68850, 32, 35062, 315, 12074, 21630, 46298, 34344, 304, 13528, 285, 4845, 8483, 5955, 304, 79204, 706, 5068, 389, 264, 11469, 9327, 13468, 304, 16700, 46298, 34344, 2345, 76, 5598, 23664, 3254, 7931, 369, 9987, 8125, 13, 763, 872, 5684, 4756, 304, 38130, 29140, 11, 98425, 35120, 59611, 11, 83621, 11564, 616, 822, 323, 70797, 71883, 53977, 7664, 2380, 12881, 8951, 430, 617, 1027, 13468, 555, 3892, 3823, 28823, 927, 279, 3347, 13515, 323, 3085, 1063, 3284, 41941, 13, 1789, 1455, 315, 279, 6617, 4007, 315, 46298, 34344, 304, 872, 10068, 4676, 11, 279, 24811, 706, 1027, 430, 814, 527, 8965, 4733, 458, 449, 832, 2500, 2345, 19041, 617, 1027, 24654, 315, 25000, 11039, 11, 7170, 311, 279, 4648, 11, 719, 369, 279, 1455, 961, 11, 279, 2324, 315, 279, 46298, 6374, 574, 3463, 311, 387, 832, 315, 10213, 26733, 13, 2030, 1457, 11, 433, 8111, 430, 279, 9096, 649, 387, 56507, 555, 279, 28961, 12881, 3440, 389, 264, 3254, 3927, 477, 11, 439, 279, 12074, 5296, 11, 1403, 7931, 13, 763, 279, 1176, 32126, 3440, 11, 1203, 304, 220, 1049, 19, 11, 35120, 59611, 574, 3604, 832, 315, 279, 28823, 13, 3005, 16964, 279, 10672, 439, 40986, 23490, 704, 315, 28211, 13, 362, 3254, 8762, 279, 2128, 1047, 7086, 763, 939, 32973, 25735, 264, 1912, 315, 46298, 34344, 279, 12074, 1047, 7086, 279, 2893, 1441, 2727, 13, 4740, 1063, 2926, 12646, 33668, 11, 279, 47766, 8762, 8738, 311, 6056, 26586, 13, 5112, 832, 315, 279, 46298, 34344, 61466, 22416, 28823, 1436, 539, 2019, 422, 433, 574, 763, 939, 32973, 477, 264, 4562, 315, 279, 1912, 13, 3011, 574, 8272, 555, 2380, 6822, 25000, 43931, 763, 939, 32973, 3156, 814, 10791, 1461, 323, 48809, 1461, 311, 279, 5015, 13, 32862, 46095, 11, 279, 2800, 315, 279, 2893, 1441, 2727, 1912, 11721, 323, 682, 315, 1124, 320, 16564, 28585, 323, 61095, 8, 31408, 304, 14718, 11682, 311, 763, 939, 32973, 88958, 23062, 7013, 311, 73019, 323, 40294, 13, 578, 7808, 315, 279, 2893, 1441, 2727, 68265, 813, 18311, 1139, 279, 46298, 6374, 596, 26000, 323, 36014, 433, 1093, 264, 11039, 5679, 13, 578, 12881, 3440, 8738, 369, 1120, 264, 2478, 4520, 11, 719, 1243, 10717, 1120, 439, 6288, 439, 433, 1047, 3940, 13, 578, 42065, 15203, 3201, 323, 763, 939, 32973, 1776, 3200, 1139, 279, 1234, 37161, 311, 9604, 311, 813, 34254, 13, 578, 12074, 1934, 389, 1403, 1023, 4528, 24455, 11, 832, 315, 902, 5343, 459, 3440, 389, 763, 939, 32973, 323, 2500, 8762, 13, 2435, 5296, 430, 12881, 8951, 555, 1023, 1469, 288, 11, 2737, 38094, 1725, 11, 374, 4279, 11, 439, 304, 12966, 11, 719, 3156, 1521, 3293, 24455, 11, 433, 574, 3463, 46298, 34344, 1051, 22443, 46309, 11, 17821, 311, 16988, 304, 1778, 9349, 13, 578, 2128, 38239, 814, 656, 539, 1440, 3249, 279, 46298, 34344, 617, 22088, 15718, 1093, 73492, 520, 3115, 719, 5296, 430, 433, 706, 10222, 2391, 264, 892, 994, 279, 16700, 46298, 6374, 7187, 706, 15042, 4245, 311, 29711, 9045, 13, 220, 128257, 198 ]

1,867

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract In the past decade, membraneless assemblies known as biomolecular condensates have been reported to play key roles in many cellular functions by compartmentalizing specific proteins and nucleic acids in subcellular environments with distinct properties. Furthermore, growing evidence supports the view that biomolecular condensates often form by phase separation, in which a single-phase system demixes into a two-phase system consisting of a condensed phase and a dilute phase of particular biomolecules. Emerging understanding of condensate function in normal and aberrant cellular states, and of the mechanisms of condensate formation, is providing new insights into human disease and revealing novel therapeutic opportunities. In this Perspective, we propose that such insights could enable a previously unexplored drug discovery approach based on identifying condensate-modifying therapeutics (c-mods), and we discuss the strategies, techniques and challenges involved. Introduction For more than a century, scientists have speculated on the structure and organization of the protoplasm 1 , 2 , 3 , 4 . In addition to membrane-bound organelles such as the nucleus and mitochondria, microscopists also observed organelles lacking membranes. For instance, the nucleolus was first described in the 1830s 5 . Additional membraneless organelles were identified at the turn of the twentieth century 6 , 7 , 8 , 9 , 10 , and many others have since been reported. Although the functions of these assemblies — now known as biomolecular condensates — have been described in some cases (Table 1 ), the mechanisms that control their formation, structure, dynamics, composition and activity are only now being studied intensively (Fig. 1 ). Table 1 Functional roles of biomolecular condensates Full size table Fig. 1: Examples of complex composition of biomolecular condensates. The molecular community defines the identity of a biomolecular condensate. Examples of three biomolecular condensates and selected components. The centrosome is the central organizer of microtubules and is involved in regulation of mitosis; the image shows a mitotic SiHa cell, with the centrosome structural protein CDK5RAP2 stained green, the nucleus blue and microtubules red. The nucleolus is the site of ribosome biogenesis; the image shows U2OS cells with the nucleolar scaffold protein NPM1 stained green and microtubules red. Stress granules; the image shows stress granules in HeLa cells, visualized via G3BP1 immunofluorescence. lncRNA, long non-coding RNA; rRNA, ribosomal RNA; snoRNA, small nucleolar RNA. The centrosome image is reproduced from , and the nucleolus image is reproduced from . Full size image Experimental evidence to support the hypothesis that biomolecular condensates form by aqueous phase separation was first generated by Cliff Brangwynne, Tony Hyman, Frank Jülicher and colleagues. They demonstrated that P granules — protein–RNA assemblies found in Caenorhabditis elegans — exhibit liquid-like behaviour in cells, including dripping, wetting and fusion, implicating phase separation in their formation 11 . Subsequent work from Brangwynne and Hyman showed that nucleoli in Xenopus oocytes also behave as liquids, exhibiting rapid ATP-dependent dynamics 12 . Publications from other laboratories soon provided additional support for the concept of biological phase separation. The Rosen laboratory was first to recognize the role and importance of weak multivalent interactions in driving phase separation and speculated that cellular organization and regulation across all of biology might be critically dependent upon such phase transitions 13 . Work from the McKnight laboratory showed that proteins containing low-complexity, intrinsically disordered regions (IDRs) phase separate into hydrogels capable of partitioning ribonucleoprotein (RNP) granule components 14 , 15 . Hanazawa, Yonetani and Sugimoto revealed that just two condensate components can reconstitute P granules in cells, supporting the idea that some proteins are necessary and sufficient to promote condensate assembly 16 . This early work was captured in a series of reviews 17 , 18 , 19 , 20 , 21 . The biomolecular condensates field reached an inflexion point in 2015, with multiple publications reporting breakthrough findings (reviewed in ref. 22 ); since then, research in the field has grown rapidly. Several lines of evidence emerging from such research support the relevance of biomolecular condensates for drug discovery. There are a growing number of examples of ‘aberrant behaviours’ of condensates that are associated with disease states, including neurodegeneration 23 , cancer (for example, prostate cancer) 24 , viral infections (for example, respiratory syncytial virus (RSV)) 25 and cardiac disease 26 , 27 (Table 2 ). Proteins of high therapeutic interest in neurodegenerative disease such as TDP43 and FUS have been identified inside condensates 28 , 29 . The anticancer drugs cisplatin and tamoxifen can partition into transcriptional condensates, altering their composition in cultured cells and in vitro reconstituted model condensates 30 ; initial reports show that small molecules can alter condensate behaviours with functional consequences in cell-based studies 31 , 32 . Finally, the tools to study condensates are rapidly maturing, increasing their applicability to efforts to identify condensate-modifying therapeutics ( c-mods ). Table 2 Dysregulation of biomolecular condensates in disease Full size table Several components are crucial to the basis of a c-mod discovery campaign. First, observed associations between condensate characteristics and diseases should be rigorously validated, with the aim of identifying associations that are causal. Furthermore, it should be established that molecular and mechanistic aspects of biomolecular condensates identified through in vitro studies are relevant in vivo. Second, assays that reliably reflect disease-relevant aspects of the biology of condensates need to be developed. In contrast to classical drugs that typically target unique macromolecules, the target for c-mods is a community of molecules engaged in an extended network. Major challenges include identifying the biomolecule(s) required for condensate assembly, as well as understanding the thermodynamics of the extended network and the kinetics of processes that disrupt the equilibrium. As discussed in detail in refs. 33 , 34 , caution needs to be exercised to not over-interpret qualitative data and results obtained from simplified (for example, in vitro reconstitution) or artificial (for example, overexpression) systems. Nevertheless, these model systems can be leveraged to obtain insights into the structural ensemble and mesoscale organization of a subset of macromolecules inside a condensate-like milieu (reviewed in ref. 35 ) and the effects of", "role": "user" }, { "content": "A new perspective published in Nature Reviews Drug Discovery examines the potential of biomolecular condensates to transform drug discovery. Condensates are membrane-less organelles that form dynamically throughout the cell via a process called phase separation. Over the last decade scientists have recognized the role of biomolecular condensates in cellular organization and disease, marking one of the most revolutionary areas of biology. In \"Modulating biomolecular condensates: a novel approach to drug discovery,\" a Dewpoint Therapeutics perspective, the authors discuss the largely untapped opportunities for targeting biomolecular condensates to develop therapeutic agents for various diseases. \"To our knowledge, this is the first time that a cohesive logic has been assembled outlining how a deep understanding of condensate biology can revolutionize the drug discovery process across therapeutic areas,\" commented Dr. Isaac Klein, Chief Scientific Officer at Dewpoint Therapeutics and corresponding author. The authors propose that condensate dysregulation may represent a node of disease origination in patients with different genetic background and environmental exposures, and that these nodes can be leveraged as drug targets. Classical drug discovery focuses on modifying the function of a single target biomolecule. By reimagining the drug target as the molecular community that resides within a condensate, researchers can modify the function of biological pathways and biomolecules that were previously considered \"undruggable.\" Another promising aspect of condensate drug discovery is that by targeting a disease node, a single therapeutic agent might help treat a larger patient population. \"Condensates are unlike anything seen before in drug discovery. Dewpoint is leading the understanding of condensates and the diverse ways new medicines could be developed to restore aberrant condensate function. No one has previously published the potential of biomolecular condensates from a drug discovery perspective, and Dewpoint scientists are bringing forward a groundbreaking perspective to the field,\" commented Dr. Mark Murcko, Dewpoint Therapeutics Board and Scientific Advisory Board member, and co-corresponding author. The perspective summarizes the rules that underlie the formation, dissolution, and regulation of biomolecular condensates, which have emerged in the last decade. Based on these rules, the authors discuss how condensate dysfunction drives various diseases, including neurodegeneration, cancer, cardiomyopathy and viral infection. Klein comments, \"Dewpoint has developed a platform and drug discovery pipeline that exploits cutting-edge technology and a deep understanding of condensate biology to discover novel condensate modifiers, or c-mods. These molecules have the ability to tackle the root cause of complex diseases and address previously undruggable targets.\" Condensate-targeted drug discovery was pioneered by Dewpoint Therapeutics as the first biotech company to enter the field, in 2018. New rules for the design of condensate modifying therapeutics are continuously evolving along with the new discoveries in the field. Similarly, discovery pipelines are actively under development, bringing hope for new life-saving treatments for patients suffering from debilitating, uncurable diseases. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract In the past decade, membraneless assemblies known as biomolecular condensates have been reported to play key roles in many cellular functions by compartmentalizing specific proteins and nucleic acids in subcellular environments with distinct properties. Furthermore, growing evidence supports the view that biomolecular condensates often form by phase separation, in which a single-phase system demixes into a two-phase system consisting of a condensed phase and a dilute phase of particular biomolecules. Emerging understanding of condensate function in normal and aberrant cellular states, and of the mechanisms of condensate formation, is providing new insights into human disease and revealing novel therapeutic opportunities. In this Perspective, we propose that such insights could enable a previously unexplored drug discovery approach based on identifying condensate-modifying therapeutics (c-mods), and we discuss the strategies, techniques and challenges involved. Introduction For more than a century, scientists have speculated on the structure and organization of the protoplasm 1 , 2 , 3 , 4 . In addition to membrane-bound organelles such as the nucleus and mitochondria, microscopists also observed organelles lacking membranes. For instance, the nucleolus was first described in the 1830s 5 . Additional membraneless organelles were identified at the turn of the twentieth century 6 , 7 , 8 , 9 , 10 , and many others have since been reported. Although the functions of these assemblies — now known as biomolecular condensates — have been described in some cases (Table 1 ), the mechanisms that control their formation, structure, dynamics, composition and activity are only now being studied intensively (Fig. 1 ). Table 1 Functional roles of biomolecular condensates Full size table Fig. 1: Examples of complex composition of biomolecular condensates. The molecular community defines the identity of a biomolecular condensate. Examples of three biomolecular condensates and selected components. The centrosome is the central organizer of microtubules and is involved in regulation of mitosis; the image shows a mitotic SiHa cell, with the centrosome structural protein CDK5RAP2 stained green, the nucleus blue and microtubules red. The nucleolus is the site of ribosome biogenesis; the image shows U2OS cells with the nucleolar scaffold protein NPM1 stained green and microtubules red. Stress granules; the image shows stress granules in HeLa cells, visualized via G3BP1 immunofluorescence. lncRNA, long non-coding RNA; rRNA, ribosomal RNA; snoRNA, small nucleolar RNA. The centrosome image is reproduced from , and the nucleolus image is reproduced from . Full size image Experimental evidence to support the hypothesis that biomolecular condensates form by aqueous phase separation was first generated by Cliff Brangwynne, Tony Hyman, Frank Jülicher and colleagues. They demonstrated that P granules — protein–RNA assemblies found in Caenorhabditis elegans — exhibit liquid-like behaviour in cells, including dripping, wetting and fusion, implicating phase separation in their formation 11 . Subsequent work from Brangwynne and Hyman showed that nucleoli in Xenopus oocytes also behave as liquids, exhibiting rapid ATP-dependent dynamics 12 . Publications from other laboratories soon provided additional support for the concept of biological phase separation. The Rosen laboratory was first to recognize the role and importance of weak multivalent interactions in driving phase separation and speculated that cellular organization and regulation across all of biology might be critically dependent upon such phase transitions 13 . Work from the McKnight laboratory showed that proteins containing low-complexity, intrinsically disordered regions (IDRs) phase separate into hydrogels capable of partitioning ribonucleoprotein (RNP) granule components 14 , 15 . Hanazawa, Yonetani and Sugimoto revealed that just two condensate components can reconstitute P granules in cells, supporting the idea that some proteins are necessary and sufficient to promote condensate assembly 16 . This early work was captured in a series of reviews 17 , 18 , 19 , 20 , 21 . The biomolecular condensates field reached an inflexion point in 2015, with multiple publications reporting breakthrough findings (reviewed in ref. 22 ); since then, research in the field has grown rapidly. Several lines of evidence emerging from such research support the relevance of biomolecular condensates for drug discovery. There are a growing number of examples of ‘aberrant behaviours’ of condensates that are associated with disease states, including neurodegeneration 23 , cancer (for example, prostate cancer) 24 , viral infections (for example, respiratory syncytial virus (RSV)) 25 and cardiac disease 26 , 27 (Table 2 ). Proteins of high therapeutic interest in neurodegenerative disease such as TDP43 and FUS have been identified inside condensates 28 , 29 . The anticancer drugs cisplatin and tamoxifen can partition into transcriptional condensates, altering their composition in cultured cells and in vitro reconstituted model condensates 30 ; initial reports show that small molecules can alter condensate behaviours with functional consequences in cell-based studies 31 , 32 . Finally, the tools to study condensates are rapidly maturing, increasing their applicability to efforts to identify condensate-modifying therapeutics ( c-mods ). Table 2 Dysregulation of biomolecular condensates in disease Full size table Several components are crucial to the basis of a c-mod discovery campaign. First, observed associations between condensate characteristics and diseases should be rigorously validated, with the aim of identifying associations that are causal. Furthermore, it should be established that molecular and mechanistic aspects of biomolecular condensates identified through in vitro studies are relevant in vivo. Second, assays that reliably reflect disease-relevant aspects of the biology of condensates need to be developed. In contrast to classical drugs that typically target unique macromolecules, the target for c-mods is a community of molecules engaged in an extended network. Major challenges include identifying the biomolecule(s) required for condensate assembly, as well as understanding the thermodynamics of the extended network and the kinetics of processes that disrupt the equilibrium. As discussed in detail in refs. 33 , 34 , caution needs to be exercised to not over-interpret qualitative data and results obtained from simplified (for example, in vitro reconstitution) or artificial (for example, overexpression) systems. Nevertheless, these model systems can be leveraged to obtain insights into the structural ensemble and mesoscale organization of a subset of macromolecules inside a condensate-like milieu (reviewed in ref. 35 ) and the effects of<|im_end|> <|im_start|>assistant A new perspective published in Nature Reviews Drug Discovery examines the potential of biomolecular condensates to transform drug discovery. Condensates are membrane-less organelles that form dynamically throughout the cell via a process called phase separation. Over the last decade scientists have recognized the role of biomolecular condensates in cellular organization and disease, marking one of the most revolutionary areas of biology. In "Modulating biomolecular condensates: a novel approach to drug discovery," a Dewpoint Therapeutics perspective, the authors discuss the largely untapped opportunities for targeting biomolecular condensates to develop therapeutic agents for various diseases. "To our knowledge, this is the first time that a cohesive logic has been assembled outlining how a deep understanding of condensate biology can revolutionize the drug discovery process across therapeutic areas," commented Dr. Isaac Klein, Chief Scientific Officer at Dewpoint Therapeutics and corresponding author. The authors propose that condensate dysregulation may represent a node of disease origination in patients with different genetic background and environmental exposures, and that these nodes can be leveraged as drug targets. Classical drug discovery focuses on modifying the function of a single target biomolecule. By reimagining the drug target as the molecular community that resides within a condensate, researchers can modify the function of biological pathways and biomolecules that were previously considered "undruggable." Another promising aspect of condensate drug discovery is that by targeting a disease node, a single therapeutic agent might help treat a larger patient population. "Condensates are unlike anything seen before in drug discovery. Dewpoint is leading the understanding of condensates and the diverse ways new medicines could be developed to restore aberrant condensate function. No one has previously published the potential of biomolecular condensates from a drug discovery perspective, and Dewpoint scientists are bringing forward a groundbreaking perspective to the field," commented Dr. Mark Murcko, Dewpoint Therapeutics Board and Scientific Advisory Board member, and co-corresponding author. The perspective summarizes the rules that underlie the formation, dissolution, and regulation of biomolecular condensates, which have emerged in the last decade. Based on these rules, the authors discuss how condensate dysfunction drives various diseases, including neurodegeneration, cancer, cardiomyopathy and viral infection. Klein comments, "Dewpoint has developed a platform and drug discovery pipeline that exploits cutting-edge technology and a deep understanding of condensate biology to discover novel condensate modifiers, or c-mods. These molecules have the ability to tackle the root cause of complex diseases and address previously undruggable targets." Condensate-targeted drug discovery was pioneered by Dewpoint Therapeutics as the first biotech company to enter the field, in 2018. New rules for the design of condensate modifying therapeutics are continuously evolving along with the new discoveries in the field. Similarly, discovery pipelines are actively under development, bringing hope for new life-saving treatments for patients suffering from debilitating, uncurable diseases. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 763, 279, 3347, 13515, 11, 39654, 1752, 62407, 3967, 439, 39538, 43943, 9955, 729, 988, 617, 1027, 5068, 311, 1514, 1401, 13073, 304, 1690, 35693, 5865, 555, 44598, 278, 4954, 3230, 28896, 323, 31484, 292, 33969, 304, 1207, 5997, 1299, 22484, 449, 12742, 6012, 13, 24296, 11, 7982, 6029, 11815, 279, 1684, 430, 39538, 43943, 9955, 729, 988, 3629, 1376, 555, 10474, 25768, 11, 304, 902, 264, 3254, 82710, 1887, 2486, 953, 288, 1139, 264, 1403, 82710, 1887, 31706, 315, 264, 75826, 10474, 323, 264, 19371, 1088, 10474, 315, 4040, 39538, 82206, 13, 86148, 8830, 315, 9955, 729, 349, 734, 304, 4725, 323, 82102, 519, 35693, 5415, 11, 323, 315, 279, 24717, 315, 9955, 729, 349, 18488, 11, 374, 8405, 502, 26793, 1139, 3823, 8624, 323, 31720, 11775, 37471, 10708, 13, 763, 420, 70288, 11, 584, 30714, 430, 1778, 26793, 1436, 7431, 264, 8767, 653, 69331, 1171, 5623, 18841, 5603, 3196, 389, 25607, 9955, 729, 349, 17515, 7922, 9139, 88886, 320, 66, 17515, 82, 705, 323, 584, 4358, 279, 15174, 11, 12823, 323, 11774, 6532, 13, 29438, 1789, 810, 1109, 264, 9478, 11, 14248, 617, 74877, 389, 279, 6070, 323, 7471, 315, 279, 1760, 56178, 10753, 220, 16, 1174, 220, 17, 1174, 220, 18, 1174, 220, 19, 662, 763, 5369, 311, 39654, 50962, 1262, 2444, 645, 1778, 439, 279, 62607, 323, 55042, 4298, 11, 8162, 2445, 454, 1705, 1101, 13468, 1262, 2444, 645, 32161, 79348, 13, 1789, 2937, 11, 279, 31484, 337, 355, 574, 1176, 7633, 304, 279, 220, 10750, 15, 82, 220, 20, 662, 24086, 39654, 1752, 1262, 2444, 645, 1051, 11054, 520, 279, 2543, 315, 279, 62520, 9478, 220, 21, 1174, 220, 22, 1174, 220, 23, 1174, 220, 24, 1174, 220, 605, 1174, 323, 1690, 3885, 617, 2533, 1027, 5068, 13, 10541, 279, 5865, 315, 1521, 62407, 2001, 1457, 3967, 439, 39538, 43943, 9955, 729, 988, 2001, 617, 1027, 7633, 304, 1063, 5157, 320, 2620, 220, 16, 7026, 279, 24717, 430, 2585, 872, 18488, 11, 6070, 11, 30295, 11, 18528, 323, 5820, 527, 1193, 1457, 1694, 20041, 25228, 3210, 320, 30035, 13, 220, 16, 7609, 6771, 220, 16, 55550, 13073, 315, 39538, 43943, 9955, 729, 988, 8797, 1404, 2007, 23966, 13, 220, 16, 25, 26379, 315, 6485, 18528, 315, 39538, 43943, 9955, 729, 988, 13, 578, 31206, 4029, 19170, 279, 9764, 315, 264, 39538, 43943, 9955, 729, 349, 13, 26379, 315, 2380, 39538, 43943, 9955, 729, 988, 323, 4183, 6956, 13, 578, 2960, 3714, 638, 374, 279, 8792, 47302, 315, 8162, 83, 392, 2482, 323, 374, 6532, 304, 19812, 315, 5568, 10934, 26, 279, 2217, 5039, 264, 5568, 14546, 12095, 34042, 2849, 11, 449, 279, 2960, 3714, 638, 24693, 13128, 11325, 42, 20, 60546, 17, 61152, 6307, 11, 279, 62607, 6437, 323, 8162, 83, 392, 2482, 2579, 13, 578, 31484, 337, 355, 374, 279, 2816, 315, 20735, 32554, 6160, 52379, 26, 279, 2217, 5039, 549, 17, 3204, 7917, 449, 279, 31484, 7569, 85552, 13128, 452, 8971, 16, 61152, 6307, 323, 8162, 83, 392, 2482, 2579, 13, 51568, 16109, 2482, 26, 279, 2217, 5039, 8631, 16109, 2482, 304, 1283, 8921, 7917, 11, 9302, 1534, 4669, 480, 18, 27187, 16, 33119, 1073, 10036, 4692, 36634, 13, 326, 1031, 31820, 11, 1317, 2536, 1824, 3785, 41214, 26, 436, 31820, 11, 20735, 96108, 41214, 26, 66184, 31820, 11, 2678, 31484, 7569, 41214, 13, 578, 2960, 3714, 638, 2217, 374, 55717, 505, 1174, 323, 279, 31484, 337, 355, 2217, 374, 55717, 505, 662, 8797, 1404, 2217, 57708, 6029, 311, 1862, 279, 31178, 430, 39538, 43943, 9955, 729, 988, 1376, 555, 66300, 788, 10474, 25768, 574, 1176, 8066, 555, 48952, 3320, 526, 54756, 818, 11, 19036, 10320, 1543, 11, 9454, 622, 2448, 51195, 323, 18105, 13, 2435, 21091, 430, 393, 16109, 2482, 2001, 13128, 4235, 31820, 62407, 1766, 304, 14751, 99831, 10796, 18225, 285, 18190, 598, 2001, 31324, 14812, 12970, 17432, 304, 7917, 11, 2737, 77315, 11, 14739, 1303, 323, 37608, 11, 92195, 1113, 10474, 25768, 304, 872, 18488, 220, 806, 662, 3804, 72457, 990, 505, 3320, 526, 54756, 818, 323, 10320, 1543, 8710, 430, 31484, 14559, 304, 49329, 46970, 297, 57878, 1101, 36792, 439, 67849, 11, 87719, 11295, 67656, 43918, 30295, 220, 717, 662, 62770, 505, 1023, 70760, 5246, 3984, 5217, 1862, 369, 279, 7434, 315, 24156, 10474, 25768, 13, 578, 35120, 27692, 574, 1176, 311, 15641, 279, 3560, 323, 12939, 315, 7621, 2814, 12031, 22639, 304, 10043, 10474, 25768, 323, 74877, 430, 35693, 7471, 323, 19812, 4028, 682, 315, 34458, 2643, 387, 41440, 18222, 5304, 1778, 10474, 34692, 220, 1032, 662, 5664, 505, 279, 26718, 9471, 27692, 8710, 430, 28896, 8649, 3428, 11733, 9289, 488, 11, 10805, 1354, 2740, 834, 10767, 13918, 320, 926, 43427, 8, 10474, 8821, 1139, 17055, 70, 2053, 13171, 315, 17071, 287, 20735, 263, 22935, 454, 91748, 320, 49, 27321, 8, 16109, 1130, 6956, 220, 975, 1174, 220, 868, 662, 21296, 1394, 14406, 11, 816, 69786, 5676, 323, 84867, 97258, 10675, 430, 1120, 1403, 9955, 729, 349, 6956, 649, 312, 1040, 275, 1088, 393, 16109, 2482, 304, 7917, 11, 12899, 279, 4623, 430, 1063, 28896, 527, 5995, 323, 14343, 311, 12192, 9955, 729, 349, 14956, 220, 845, 662, 1115, 4216, 990, 574, 17439, 304, 264, 4101, 315, 8544, 220, 1114, 1174, 220, 972, 1174, 220, 777, 1174, 220, 508, 1174, 220, 1691, 662, 578, 39538, 43943, 9955, 729, 988, 2115, 8813, 459, 4225, 2635, 290, 1486, 304, 220, 679, 20, 11, 449, 5361, 29085, 13122, 42445, 14955, 320, 19981, 291, 304, 2098, 13, 220, 1313, 7048, 2533, 1243, 11, 3495, 304, 279, 2115, 706, 15042, 19019, 13, 26778, 5238, 315, 6029, 24084, 505, 1778, 3495, 1862, 279, 41961, 315, 39538, 43943, 9955, 729, 988, 369, 5623, 18841, 13, 2684, 527, 264, 7982, 1396, 315, 10507, 315, 3451, 370, 618, 519, 71177, 529, 315, 9955, 729, 988, 430, 527, 5938, 449, 8624, 5415, 11, 2737, 18247, 451, 81157, 220, 1419, 1174, 9572, 320, 2000, 3187, 11, 47447, 9572, 8, 220, 1187, 1174, 29962, 30020, 320, 2000, 3187, 11, 42631, 13105, 16820, 532, 17188, 320, 11706, 53, 595, 220, 914, 323, 47345, 8624, 220, 1627, 1174, 220, 1544, 320, 2620, 220, 17, 7609, 15542, 1354, 315, 1579, 37471, 2802, 304, 18247, 451, 7642, 1413, 8624, 1778, 439, 350, 10510, 3391, 323, 435, 2078, 617, 1027, 11054, 4871, 9955, 729, 988, 220, 1591, 1174, 220, 1682, 662, 578, 88143, 11967, 11217, 67504, 501, 15111, 323, 26555, 5241, 56439, 649, 17071, 1139, 46940, 278, 9955, 729, 988, 11, 60923, 872, 18528, 304, 89948, 7917, 323, 304, 55004, 312, 1040, 275, 2844, 1646, 9955, 729, 988, 220, 966, 2652, 2926, 6821, 1501, 430, 2678, 35715, 649, 11857, 9955, 729, 349, 71177, 449, 16003, 16296, 304, 2849, 6108, 7978, 220, 2148, 1174, 220, 843, 662, 17830, 11, 279, 7526, 311, 4007, 9955, 729, 988, 527, 19019, 5634, 1711, 11, 7859, 872, 4666, 2968, 311, 9045, 311, 10765, 9955, 729, 349, 17515, 7922, 9139, 88886, 320, 272, 17515, 82, 7609, 6771, 220, 17, 65142, 1610, 2987, 315, 39538, 43943, 9955, 729, 988, 304, 8624, 8797, 1404, 2007, 26778, 6956, 527, 16996, 311, 279, 8197, 315, 264, 272, 17515, 18841, 4901, 13, 5629, 11, 13468, 30257, 1990, 9955, 729, 349, 17910, 323, 19338, 1288, 387, 78477, 7162, 33432, 11, 449, 279, 9395, 315, 25607, 30257, 430, 527, 59557, 13, 24296, 11, 433, 1288, 387, 9749, 430, 31206, 323, 7852, 4633, 13878, 315, 39538, 43943, 9955, 729, 988, 11054, 1555, 304, 55004, 7978, 527, 9959, 304, 41294, 13, 10657, 11, 99592, 430, 57482, 8881, 8624, 5621, 8532, 13878, 315, 279, 34458, 315, 9955, 729, 988, 1205, 311, 387, 8040, 13, 763, 13168, 311, 29924, 11217, 430, 11383, 2218, 5016, 9155, 442, 82206, 11, 279, 2218, 369, 272, 17515, 82, 374, 264, 4029, 315, 35715, 17045, 304, 459, 11838, 4009, 13, 17559, 11774, 2997, 25607, 279, 39538, 55269, 1161, 8, 2631, 369, 9955, 729, 349, 14956, 11, 439, 1664, 439, 8830, 279, 30945, 80011, 315, 279, 11838, 4009, 323, 279, 91468, 315, 11618, 430, 24927, 279, 56411, 13, 1666, 14407, 304, 7872, 304, 44243, 13, 220, 1644, 1174, 220, 1958, 1174, 28930, 3966, 311, 387, 62113, 311, 539, 927, 12, 17324, 62129, 828, 323, 3135, 12457, 505, 44899, 320, 2000, 3187, 11, 304, 55004, 312, 44103, 8, 477, 21075, 320, 2000, 3187, 11, 927, 29199, 8, 6067, 13, 35053, 11, 1521, 1646, 6067, 649, 387, 28605, 3359, 311, 6994, 26793, 1139, 279, 24693, 40126, 323, 11083, 437, 2296, 7471, 315, 264, 27084, 315, 9155, 442, 82206, 4871, 264, 9955, 729, 349, 12970, 83259, 320, 19981, 291, 304, 2098, 13, 220, 1758, 883, 323, 279, 6372, 315, 128257, 198, 128256, 78191, 198, 32, 502, 13356, 4756, 304, 22037, 19832, 26166, 39193, 49095, 279, 4754, 315, 39538, 43943, 9955, 729, 988, 311, 5276, 5623, 18841, 13, 45926, 729, 988, 527, 39654, 56009, 1262, 2444, 645, 430, 1376, 43111, 6957, 279, 2849, 4669, 264, 1920, 2663, 10474, 25768, 13, 6193, 279, 1566, 13515, 14248, 617, 15324, 279, 3560, 315, 39538, 43943, 9955, 729, 988, 304, 35693, 7471, 323, 8624, 11, 36024, 832, 315, 279, 1455, 30191, 5789, 315, 34458, 13, 763, 330, 4559, 15853, 39538, 43943, 9955, 729, 988, 25, 264, 11775, 5603, 311, 5623, 18841, 1359, 264, 50400, 2837, 23258, 88886, 13356, 11, 279, 12283, 4358, 279, 14090, 13365, 5795, 10708, 369, 25103, 39538, 43943, 9955, 729, 988, 311, 2274, 37471, 13307, 369, 5370, 19338, 13, 330, 1271, 1057, 6677, 11, 420, 374, 279, 1176, 892, 430, 264, 87516, 12496, 706, 1027, 35105, 79774, 1268, 264, 5655, 8830, 315, 9955, 729, 349, 34458, 649, 14110, 553, 279, 5623, 18841, 1920, 4028, 37471, 5789, 1359, 29786, 2999, 13, 42608, 43241, 11, 14681, 38130, 20148, 520, 50400, 2837, 23258, 88886, 323, 12435, 3229, 13, 578, 12283, 30714, 430, 9955, 729, 349, 22709, 1610, 2987, 1253, 4097, 264, 2494, 315, 8624, 2780, 2617, 304, 6978, 449, 2204, 19465, 4092, 323, 12434, 70530, 11, 323, 430, 1521, 7954, 649, 387, 28605, 3359, 439, 5623, 11811, 13, 68533, 5623, 18841, 24400, 389, 47141, 279, 734, 315, 264, 3254, 2218, 39538, 55269, 13, 3296, 312, 29116, 5859, 279, 5623, 2218, 439, 279, 31206, 4029, 430, 54068, 2949, 264, 9955, 729, 349, 11, 12074, 649, 5719, 279, 734, 315, 24156, 44014, 323, 39538, 82206, 430, 1051, 8767, 6646, 330, 1263, 81, 2661, 481, 1210, 13596, 26455, 13189, 315, 9955, 729, 349, 5623, 18841, 374, 430, 555, 25103, 264, 8624, 2494, 11, 264, 3254, 37471, 8479, 2643, 1520, 4322, 264, 8294, 8893, 7187, 13, 330, 50796, 729, 988, 527, 20426, 4205, 3970, 1603, 304, 5623, 18841, 13, 50400, 2837, 374, 6522, 279, 8830, 315, 9955, 729, 988, 323, 279, 17226, 5627, 502, 39653, 1436, 387, 8040, 311, 15301, 82102, 519, 9955, 729, 349, 734, 13, 2360, 832, 706, 8767, 4756, 279, 4754, 315, 39538, 43943, 9955, 729, 988, 505, 264, 5623, 18841, 13356, 11, 323, 50400, 2837, 14248, 527, 12967, 4741, 264, 64955, 13356, 311, 279, 2115, 1359, 29786, 2999, 13, 4488, 15356, 32563, 11, 50400, 2837, 23258, 88886, 8925, 323, 38130, 45013, 8925, 4562, 11, 323, 1080, 46713, 6961, 287, 3229, 13, 578, 13356, 94594, 279, 5718, 430, 1234, 11828, 279, 18488, 11, 81359, 11, 323, 19812, 315, 39538, 43943, 9955, 729, 988, 11, 902, 617, 22763, 304, 279, 1566, 13515, 13, 20817, 389, 1521, 5718, 11, 279, 12283, 4358, 1268, 9955, 729, 349, 32403, 20722, 5370, 19338, 11, 2737, 18247, 451, 81157, 11, 9572, 11, 73151, 5650, 54042, 323, 29962, 19405, 13, 43241, 6170, 11, 330, 35, 365, 2837, 706, 8040, 264, 5452, 323, 5623, 18841, 15660, 430, 63488, 14713, 48448, 5557, 323, 264, 5655, 8830, 315, 9955, 729, 349, 34458, 311, 7142, 11775, 9955, 729, 349, 36770, 11, 477, 272, 17515, 82, 13, 4314, 35715, 617, 279, 5845, 311, 22118, 279, 3789, 5353, 315, 6485, 19338, 323, 2686, 8767, 2073, 81, 2661, 481, 11811, 1210, 45926, 729, 349, 18996, 291, 5623, 18841, 574, 96734, 555, 50400, 2837, 23258, 88886, 439, 279, 1176, 6160, 59196, 2883, 311, 3810, 279, 2115, 11, 304, 220, 679, 23, 13, 1561, 5718, 369, 279, 2955, 315, 9955, 729, 349, 47141, 9139, 88886, 527, 31978, 42028, 3235, 449, 279, 502, 54098, 304, 279, 2115, 13, 35339, 11, 18841, 58773, 527, 22815, 1234, 4500, 11, 12967, 3987, 369, 502, 2324, 59085, 22972, 369, 6978, 16066, 505, 92890, 11, 653, 2407, 481, 19338, 13, 220, 128257, 198 ]

2,068

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Solid-state nanopores can act as single-molecule sensors and could potentially be used to rapidly sequence DNA molecules. However, nanopores are typically fabricated in insulating membranes that are as thick as 15 bases, which makes it difficult for the devices to read individual bases. Graphene is only 0.335 nm thick (equivalent to the spacing between two bases in a DNA chain) and could therefore provide a suitable membrane for sequencing applications. Here, we show that a solid-state nanopore can be integrated with a graphene nanoribbon transistor to create a sensor for DNA translocation. As DNA molecules move through the pore, the device can simultaneously measure drops in ionic current and changes in local voltage in the transistor, which can both be used to detect the molecules. We examine the correlation between these two signals and use the ionic current measurements as a real-time control of the graphene-based sensing device. Main Solid-state nanopores 1 can be used to sense 2 , 3 , 4 , 5 , 6 , 7 , 8 and manipulate 9 , 10 DNA molecules by threading the molecules through the pore under an applied potential and monitoring the ionic current passing through the pore. Although the size of the pore can be tuned 11 and the devices can be integrated with other single-molecule techniques 9 , 10 , 12 and detection mechanisms 13 , 14 , 15 , 16 , they have yet to deliver sequencing data. One reason for this is that the nanopores are typically fabricated in SiN x or SiO 2 membranes, which have thicknesses that are large compared to the size of a DNA base. Graphene 17 nanopores have recently been used as an alternative to traditional solid-state nanopores 18 , 19 , 20 . In these devices, graphene acts as the membrane material, which allows, in principle, single-base resolution in the ionic current due to its single-atom thickness. However, the relatively large dimensions of the graphene layer in this proposed geometry mean it cannot be used as a sensing electrode, and the reliance on ionic current measurements precludes multiplexing. A complementary approach is to integrate the standard, relatively thick SiN x membrane with a sensing electrode. A variety of sensing electrodes have been theoretically proposed for this purpose, including metallic tunnelling electrodes 21 , graphene nanogaps 22 and graphene nanoribbons (GNRs) 23 . The detection of single translocation events has also been demonstrated experimentally using metallic nanogaps and electrical tunnelling measurements 24 . Although tunnelling detection could in principle be used to achieve single base resolution, the alignment of the active tunnelling area with the nanopore remains a significant issue. Alternatively, silicon nanowire field-effect transistors have previously been combined with a solid-state nanopore to detect DNA translocation 16 . Nanopore with a GNR device To fabricate our devices ( Fig. 1 ) we began by creating a 20-nm-thick SiN x membrane ( ∼ 20 µm × 20 µm in size), followed by the transfer of a chemical vapour deposition (CVD)-grown graphene monolayer ( Fig. 2b,e ). Graphene nanoribbons were defined using electron-beam lithography (EBL) and oxygen reactive ion etching (RIE). Next, electrical contacts were fabricated by EBL, electron-beam evaporation of a Cr (5 nm)/Au (50 nm) metal double layer and lift-off ( Fig. 2c,f ). To minimize the ionic cross-conductance we carried out atomic layer deposition (ALD) of 5 nm Al 2 O 3 , which was expected to isolate the electrodes from the electrolyte solution 16 . Finally, nanopore drilling was performed in a transmission electron microscope (TEM) working in scanning mode 25 , as shown in Fig. 2d,h (for more details see ‘Device fabrication’ section of the Methods ). The resulting structure is a GNR defined on the SiN x membrane with a nanopore located in its centre. Figure 1: Schematics and characterization of the GNR transistor–nanopore measuring set-up. a , Schematic of the set-up (side view). A single DNA molecule is translocating through a nanopore fabricated in a SiN x membrane. b , Artistic representation of the device. c , Photograph of the fluidic cell. d , I – V G characteristics of a liquid-gated GNR with a nanopore in 10 mM KCl. Gating is performed by changing the transmembrane voltage while V sd = 5 mV. e , I – V characteristic of a 10 nm nanopore in 10 mM KCl buffer after connecting the GNR. Dots are experimental points, and the continuous line is the fit from which the value of the conductance is extrapolated. f , I – V characteristic of a GNR in 10 mM KCl (same device as in e ). Dots are experimental points, and the continuous line is the fit from which the value of the resistance is extrapolated. R wet means in buffer conditions as opposed to dry conditions. Full size image Figure 2: Fabrication of a solid-state nanopore with a GNR transistor. a – d , Schematics of device fabrication steps: fabrication of SiN x membrane ( a ); transfer of CVD graphene monolayer ( b ); graphene nanoribbon pattering and electrode fabrication ( c ); pore drilling ( d ). e , Optical micrograph of a SiN x membrane with a transferred CVD graphene monolayer on top. The dashed line highlights the transferred CVD graphene monolayer. Image dimensions, 250 µm × 250 µm. f , Optical micrograph of Cr/Au electrodes contacting four GNRs on the SiN x membrane. From four GNRs we select one for drilling. Image dimensions, 120 µm × 120 µm. g , TEM micrographs of a GNR before (left) and after (right) drilling. h , TEM image of a nanopore (same device as in Fig. 1e ). Full size image To perform device characterization and experiments, we placed our chips in a custom-made microfluidic chamber ( Fig. 1c ) in order to carry out simultaneous measurements of the current flowing through the GNR and the ionic current flowing through the nanopore (for more details see ‘Experimental set-up’ section of the Methods ). We performed our", "role": "user" }, { "content": "If we wanted to count the number of people in a crowd, we could make on the fly estimates, very likely to be imprecise, or we could ask each person to pass through a turnstile. The latter resembles the model that EPFL researchers have used for creating a \"DNA reader\" that is able to detect the passage of individual DNA molecules through a tiny hole: a nanopore with integrated graphene transistor. The DNA molecules are diluted in a solution containing ions and are driven by an electric field through a membrane with a nanopore. When the molecule goes through the orifice, it provokes a slight perturbation to the field, detectable not only by the modulations in ionic current but also by concomitant modulation in the graphene transistor current. Based on this information, it is possible to determine whether a DNA molecule has passed through the membrane or not. This system is based on a method that has been known for over a dozen years. The original technique was not as reliable since it presented a number of shortcomings such as clogging pores and lack of precision, among others. \"We thought that we would be able to solve these problems by creating a membrane as thin as possible while maintaining the orifice's strength\", said Aleksandra Radenovic from the Laboratory of Nanoscale Biology at EPFL. Together with Floriano Traversi, postdoctoral student, and colleagues from the Laboratory of Nanoscale Electronics and Structures, she came across the material that turned out to be both the strongest and most resilient: graphene, which consists of a single layer of carbon molecules. The strips of graphene or nanoribbons used in the experiment were produced at EPFL, thanks to the work carried out at the Center for Micro Nanotechnology (CMI) and the Center for Electron Microscopy (CIME). \"Through an amazing coincidence, continued the researcher, the graphene layer's thickness measures 0.335 nm, which exactly fits the gap existing between two DNA bases, whereas in the materials used so far there was a 15 nm thickness.\" As a result, while previously it was not possible to individually analyze the passage of DNA bases through these \"long\" tunnels – at a molecular scale –, the new method is likely to provide a much higher precision. Eventually, it could be used for DNA sequencing. However they are not there yet. In only 5 milliseconds, up to 50'000 DNA bases can pass through the pores. The electric output signal is not clear enough for \"reading\" the live sequence of the DNA strand passage. \"However, the possibility of detecting the passage of DNA with graphene nanoribbons is a breakthrough as well as a significant opportunity\", said Aleksandra Radenovic. She noted that, for example, the device is also able to detect the passage of other kinds of proteins and provide information on their size and/or shape. This crucial step towards new methods of molecular analysis has received an ERC grant and is featured in an article published in Nature Nanotechnology. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Solid-state nanopores can act as single-molecule sensors and could potentially be used to rapidly sequence DNA molecules. However, nanopores are typically fabricated in insulating membranes that are as thick as 15 bases, which makes it difficult for the devices to read individual bases. Graphene is only 0.335 nm thick (equivalent to the spacing between two bases in a DNA chain) and could therefore provide a suitable membrane for sequencing applications. Here, we show that a solid-state nanopore can be integrated with a graphene nanoribbon transistor to create a sensor for DNA translocation. As DNA molecules move through the pore, the device can simultaneously measure drops in ionic current and changes in local voltage in the transistor, which can both be used to detect the molecules. We examine the correlation between these two signals and use the ionic current measurements as a real-time control of the graphene-based sensing device. Main Solid-state nanopores 1 can be used to sense 2 , 3 , 4 , 5 , 6 , 7 , 8 and manipulate 9 , 10 DNA molecules by threading the molecules through the pore under an applied potential and monitoring the ionic current passing through the pore. Although the size of the pore can be tuned 11 and the devices can be integrated with other single-molecule techniques 9 , 10 , 12 and detection mechanisms 13 , 14 , 15 , 16 , they have yet to deliver sequencing data. One reason for this is that the nanopores are typically fabricated in SiN x or SiO 2 membranes, which have thicknesses that are large compared to the size of a DNA base. Graphene 17 nanopores have recently been used as an alternative to traditional solid-state nanopores 18 , 19 , 20 . In these devices, graphene acts as the membrane material, which allows, in principle, single-base resolution in the ionic current due to its single-atom thickness. However, the relatively large dimensions of the graphene layer in this proposed geometry mean it cannot be used as a sensing electrode, and the reliance on ionic current measurements precludes multiplexing. A complementary approach is to integrate the standard, relatively thick SiN x membrane with a sensing electrode. A variety of sensing electrodes have been theoretically proposed for this purpose, including metallic tunnelling electrodes 21 , graphene nanogaps 22 and graphene nanoribbons (GNRs) 23 . The detection of single translocation events has also been demonstrated experimentally using metallic nanogaps and electrical tunnelling measurements 24 . Although tunnelling detection could in principle be used to achieve single base resolution, the alignment of the active tunnelling area with the nanopore remains a significant issue. Alternatively, silicon nanowire field-effect transistors have previously been combined with a solid-state nanopore to detect DNA translocation 16 . Nanopore with a GNR device To fabricate our devices ( Fig. 1 ) we began by creating a 20-nm-thick SiN x membrane ( ∼ 20 µm × 20 µm in size), followed by the transfer of a chemical vapour deposition (CVD)-grown graphene monolayer ( Fig. 2b,e ). Graphene nanoribbons were defined using electron-beam lithography (EBL) and oxygen reactive ion etching (RIE). Next, electrical contacts were fabricated by EBL, electron-beam evaporation of a Cr (5 nm)/Au (50 nm) metal double layer and lift-off ( Fig. 2c,f ). To minimize the ionic cross-conductance we carried out atomic layer deposition (ALD) of 5 nm Al 2 O 3 , which was expected to isolate the electrodes from the electrolyte solution 16 . Finally, nanopore drilling was performed in a transmission electron microscope (TEM) working in scanning mode 25 , as shown in Fig. 2d,h (for more details see ‘Device fabrication’ section of the Methods ). The resulting structure is a GNR defined on the SiN x membrane with a nanopore located in its centre. Figure 1: Schematics and characterization of the GNR transistor–nanopore measuring set-up. a , Schematic of the set-up (side view). A single DNA molecule is translocating through a nanopore fabricated in a SiN x membrane. b , Artistic representation of the device. c , Photograph of the fluidic cell. d , I – V G characteristics of a liquid-gated GNR with a nanopore in 10 mM KCl. Gating is performed by changing the transmembrane voltage while V sd = 5 mV. e , I – V characteristic of a 10 nm nanopore in 10 mM KCl buffer after connecting the GNR. Dots are experimental points, and the continuous line is the fit from which the value of the conductance is extrapolated. f , I – V characteristic of a GNR in 10 mM KCl (same device as in e ). Dots are experimental points, and the continuous line is the fit from which the value of the resistance is extrapolated. R wet means in buffer conditions as opposed to dry conditions. Full size image Figure 2: Fabrication of a solid-state nanopore with a GNR transistor. a – d , Schematics of device fabrication steps: fabrication of SiN x membrane ( a ); transfer of CVD graphene monolayer ( b ); graphene nanoribbon pattering and electrode fabrication ( c ); pore drilling ( d ). e , Optical micrograph of a SiN x membrane with a transferred CVD graphene monolayer on top. The dashed line highlights the transferred CVD graphene monolayer. Image dimensions, 250 µm × 250 µm. f , Optical micrograph of Cr/Au electrodes contacting four GNRs on the SiN x membrane. From four GNRs we select one for drilling. Image dimensions, 120 µm × 120 µm. g , TEM micrographs of a GNR before (left) and after (right) drilling. h , TEM image of a nanopore (same device as in Fig. 1e ). Full size image To perform device characterization and experiments, we placed our chips in a custom-made microfluidic chamber ( Fig. 1c ) in order to carry out simultaneous measurements of the current flowing through the GNR and the ionic current flowing through the nanopore (for more details see ‘Experimental set-up’ section of the Methods ). We performed our<|im_end|> <|im_start|>assistant If we wanted to count the number of people in a crowd, we could make on the fly estimates, very likely to be imprecise, or we could ask each person to pass through a turnstile. The latter resembles the model that EPFL researchers have used for creating a "DNA reader" that is able to detect the passage of individual DNA molecules through a tiny hole: a nanopore with integrated graphene transistor. The DNA molecules are diluted in a solution containing ions and are driven by an electric field through a membrane with a nanopore. When the molecule goes through the orifice, it provokes a slight perturbation to the field, detectable not only by the modulations in ionic current but also by concomitant modulation in the graphene transistor current. Based on this information, it is possible to determine whether a DNA molecule has passed through the membrane or not. This system is based on a method that has been known for over a dozen years. The original technique was not as reliable since it presented a number of shortcomings such as clogging pores and lack of precision, among others. "We thought that we would be able to solve these problems by creating a membrane as thin as possible while maintaining the orifice's strength", said Aleksandra Radenovic from the Laboratory of Nanoscale Biology at EPFL. Together with Floriano Traversi, postdoctoral student, and colleagues from the Laboratory of Nanoscale Electronics and Structures, she came across the material that turned out to be both the strongest and most resilient: graphene, which consists of a single layer of carbon molecules. The strips of graphene or nanoribbons used in the experiment were produced at EPFL, thanks to the work carried out at the Center for Micro Nanotechnology (CMI) and the Center for Electron Microscopy (CIME). "Through an amazing coincidence, continued the researcher, the graphene layer's thickness measures 0.335 nm, which exactly fits the gap existing between two DNA bases, whereas in the materials used so far there was a 15 nm thickness." As a result, while previously it was not possible to individually analyze the passage of DNA bases through these "long" tunnels – at a molecular scale –, the new method is likely to provide a much higher precision. Eventually, it could be used for DNA sequencing. However they are not there yet. In only 5 milliseconds, up to 50'000 DNA bases can pass through the pores. The electric output signal is not clear enough for "reading" the live sequence of the DNA strand passage. "However, the possibility of detecting the passage of DNA with graphene nanoribbons is a breakthrough as well as a significant opportunity", said Aleksandra Radenovic. She noted that, for example, the device is also able to detect the passage of other kinds of proteins and provide information on their size and/or shape. This crucial step towards new methods of molecular analysis has received an ERC grant and is featured in an article published in Nature Nanotechnology. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 22925, 21395, 76307, 4692, 649, 1180, 439, 3254, 1474, 55269, 26148, 323, 1436, 13893, 387, 1511, 311, 19019, 8668, 15922, 35715, 13, 4452, 11, 76307, 4692, 527, 11383, 70554, 304, 1672, 15853, 79348, 430, 527, 439, 12314, 439, 220, 868, 23963, 11, 902, 3727, 433, 5107, 369, 279, 7766, 311, 1373, 3927, 23963, 13, 12441, 1994, 374, 1193, 220, 15, 13, 16596, 26807, 12314, 320, 26378, 12031, 311, 279, 27032, 1990, 1403, 23963, 304, 264, 15922, 8957, 8, 323, 1436, 9093, 3493, 264, 14791, 39654, 369, 62119, 8522, 13, 5810, 11, 584, 1501, 430, 264, 6573, 21395, 76307, 461, 649, 387, 18751, 449, 264, 66192, 20622, 269, 36180, 99041, 311, 1893, 264, 12271, 369, 15922, 1380, 2588, 13, 1666, 15922, 35715, 3351, 1555, 279, 97551, 11, 279, 3756, 649, 25291, 6767, 21701, 304, 220, 21427, 1510, 323, 4442, 304, 2254, 22465, 304, 279, 99041, 11, 902, 649, 2225, 387, 1511, 311, 11388, 279, 35715, 13, 1226, 21635, 279, 26670, 1990, 1521, 1403, 17738, 323, 1005, 279, 220, 21427, 1510, 22323, 439, 264, 1972, 7394, 2585, 315, 279, 66192, 6108, 60199, 3756, 13, 4802, 22925, 21395, 76307, 4692, 220, 16, 649, 387, 1511, 311, 5647, 220, 17, 1174, 220, 18, 1174, 220, 19, 1174, 220, 20, 1174, 220, 21, 1174, 220, 22, 1174, 220, 23, 323, 37735, 220, 24, 1174, 220, 605, 15922, 35715, 555, 31259, 279, 35715, 1555, 279, 97551, 1234, 459, 9435, 4754, 323, 16967, 279, 220, 21427, 1510, 12579, 1555, 279, 97551, 13, 10541, 279, 1404, 315, 279, 97551, 649, 387, 33519, 220, 806, 323, 279, 7766, 649, 387, 18751, 449, 1023, 3254, 1474, 55269, 12823, 220, 24, 1174, 220, 605, 1174, 220, 717, 323, 18468, 24717, 220, 1032, 1174, 220, 975, 1174, 220, 868, 1174, 220, 845, 1174, 814, 617, 3686, 311, 6493, 62119, 828, 13, 3861, 2944, 369, 420, 374, 430, 279, 76307, 4692, 527, 11383, 70554, 304, 12095, 45, 865, 477, 12095, 46, 220, 17, 79348, 11, 902, 617, 26839, 288, 430, 527, 3544, 7863, 311, 279, 1404, 315, 264, 15922, 2385, 13, 12441, 1994, 220, 1114, 76307, 4692, 617, 6051, 1027, 1511, 439, 459, 10778, 311, 8776, 6573, 21395, 76307, 4692, 220, 972, 1174, 220, 777, 1174, 220, 508, 662, 763, 1521, 7766, 11, 66192, 14385, 439, 279, 39654, 3769, 11, 902, 6276, 11, 304, 17966, 11, 3254, 31113, 11175, 304, 279, 220, 21427, 1510, 4245, 311, 1202, 3254, 12, 22612, 26839, 13, 4452, 11, 279, 12309, 3544, 15696, 315, 279, 66192, 6324, 304, 420, 11223, 17484, 3152, 433, 4250, 387, 1511, 439, 264, 60199, 72048, 11, 323, 279, 54180, 389, 220, 21427, 1510, 22323, 864, 7548, 12842, 2635, 287, 13, 362, 58535, 5603, 374, 311, 32172, 279, 5410, 11, 12309, 12314, 12095, 45, 865, 39654, 449, 264, 60199, 72048, 13, 362, 8205, 315, 60199, 80390, 617, 1027, 63234, 11223, 369, 420, 7580, 11, 2737, 46258, 11716, 77, 6427, 80390, 220, 1691, 1174, 66192, 20622, 540, 2690, 220, 1313, 323, 66192, 20622, 269, 581, 47620, 320, 26228, 43427, 8, 220, 1419, 662, 578, 18468, 315, 3254, 1380, 2588, 4455, 706, 1101, 1027, 21091, 9526, 750, 1701, 46258, 20622, 540, 2690, 323, 20314, 11716, 77, 6427, 22323, 220, 1187, 662, 10541, 11716, 77, 6427, 18468, 1436, 304, 17966, 387, 1511, 311, 11322, 3254, 2385, 11175, 11, 279, 17632, 315, 279, 4642, 11716, 77, 6427, 3158, 449, 279, 76307, 461, 8625, 264, 5199, 4360, 13, 39578, 11, 51692, 20622, 363, 556, 2115, 23937, 1380, 380, 1105, 617, 8767, 1027, 11093, 449, 264, 6573, 21395, 76307, 461, 311, 11388, 15922, 1380, 2588, 220, 845, 662, 33242, 454, 461, 449, 264, 480, 27416, 3756, 2057, 13354, 349, 1057, 7766, 320, 23966, 13, 220, 16, 883, 584, 6137, 555, 6968, 264, 220, 508, 5392, 76, 7716, 875, 12095, 45, 865, 39654, 320, 12264, 120, 220, 508, 64012, 76, 25800, 220, 508, 64012, 76, 304, 1404, 705, 8272, 555, 279, 8481, 315, 264, 11742, 68857, 414, 65374, 320, 34, 12757, 7435, 62376, 66192, 1647, 337, 1155, 320, 23966, 13, 220, 17, 65, 23379, 7609, 12441, 1994, 20622, 269, 581, 47620, 1051, 4613, 1701, 17130, 15502, 309, 46282, 5814, 320, 8428, 43, 8, 323, 24463, 56563, 28772, 1880, 28075, 320, 4403, 36, 570, 9479, 11, 20314, 19015, 1051, 70554, 555, 469, 9574, 11, 17130, 15502, 309, 3721, 96649, 315, 264, 4656, 320, 20, 26807, 5738, 66432, 320, 1135, 26807, 8, 9501, 2033, 6324, 323, 12157, 12744, 320, 23966, 13, 220, 17, 66, 17514, 7609, 2057, 30437, 279, 220, 21427, 5425, 15204, 1076, 685, 584, 11953, 704, 25524, 6324, 65374, 320, 984, 35, 8, 315, 220, 20, 26807, 1708, 220, 17, 507, 220, 18, 1174, 902, 574, 3685, 311, 43223, 279, 80390, 505, 279, 73396, 668, 6425, 220, 845, 662, 17830, 11, 76307, 461, 39662, 574, 10887, 304, 264, 18874, 17130, 73757, 320, 21695, 8, 3318, 304, 36201, 3941, 220, 914, 1174, 439, 6982, 304, 23966, 13, 220, 17, 67, 20393, 320, 2000, 810, 3649, 1518, 3451, 7130, 59251, 529, 3857, 315, 279, 19331, 7609, 578, 13239, 6070, 374, 264, 480, 27416, 4613, 389, 279, 12095, 45, 865, 39654, 449, 264, 76307, 461, 7559, 304, 1202, 12541, 13, 19575, 220, 16, 25, 328, 2464, 29470, 323, 60993, 315, 279, 480, 27416, 99041, 4235, 19285, 454, 461, 30090, 743, 5352, 13, 264, 1174, 328, 82149, 315, 279, 743, 5352, 320, 3002, 1684, 570, 362, 3254, 15922, 43030, 374, 1380, 1092, 1113, 1555, 264, 76307, 461, 70554, 304, 264, 12095, 45, 865, 39654, 13, 293, 1174, 5277, 4633, 13340, 315, 279, 3756, 13, 272, 1174, 33255, 315, 279, 15962, 292, 2849, 13, 294, 1174, 358, 1389, 650, 480, 17910, 315, 264, 14812, 2427, 660, 480, 27416, 449, 264, 76307, 461, 304, 220, 605, 84317, 735, 5176, 13, 480, 1113, 374, 10887, 555, 10223, 279, 1380, 10759, 88554, 22465, 1418, 650, 21231, 284, 220, 20, 296, 53, 13, 384, 1174, 358, 1389, 650, 29683, 315, 264, 220, 605, 26807, 76307, 461, 304, 220, 605, 84317, 735, 5176, 4240, 1306, 21583, 279, 480, 27416, 13, 423, 2469, 527, 22772, 3585, 11, 323, 279, 19815, 1584, 374, 279, 5052, 505, 902, 279, 907, 315, 279, 6929, 685, 374, 71462, 660, 13, 282, 1174, 358, 1389, 650, 29683, 315, 264, 480, 27416, 304, 220, 605, 84317, 735, 5176, 320, 25030, 3756, 439, 304, 384, 7609, 423, 2469, 527, 22772, 3585, 11, 323, 279, 19815, 1584, 374, 279, 5052, 505, 902, 279, 907, 315, 279, 13957, 374, 71462, 660, 13, 432, 14739, 3445, 304, 4240, 4787, 439, 16475, 311, 9235, 4787, 13, 8797, 1404, 2217, 19575, 220, 17, 25, 37407, 367, 315, 264, 6573, 21395, 76307, 461, 449, 264, 480, 27416, 99041, 13, 264, 1389, 294, 1174, 328, 2464, 29470, 315, 3756, 59251, 7504, 25, 59251, 315, 12095, 45, 865, 39654, 320, 264, 7048, 8481, 315, 356, 12757, 66192, 1647, 337, 1155, 320, 293, 7048, 66192, 20622, 269, 36180, 281, 31436, 323, 72048, 59251, 320, 272, 7048, 97551, 39662, 320, 294, 7609, 384, 1174, 75939, 8162, 4539, 315, 264, 12095, 45, 865, 39654, 449, 264, 23217, 356, 12757, 66192, 1647, 337, 1155, 389, 1948, 13, 578, 67822, 1584, 22020, 279, 23217, 356, 12757, 66192, 1647, 337, 1155, 13, 4758, 15696, 11, 220, 5154, 64012, 76, 25800, 220, 5154, 64012, 76, 13, 282, 1174, 75939, 8162, 4539, 315, 4656, 10576, 84, 80390, 47208, 3116, 480, 27416, 82, 389, 279, 12095, 45, 865, 39654, 13, 5659, 3116, 480, 27416, 82, 584, 3373, 832, 369, 39662, 13, 4758, 15696, 11, 220, 4364, 64012, 76, 25800, 220, 4364, 64012, 76, 13, 342, 1174, 76770, 8162, 87286, 315, 264, 480, 27416, 1603, 320, 2414, 8, 323, 1306, 320, 1315, 8, 39662, 13, 305, 1174, 76770, 2217, 315, 264, 76307, 461, 320, 25030, 3756, 439, 304, 23966, 13, 220, 16, 68, 7609, 8797, 1404, 2217, 2057, 2804, 3756, 60993, 323, 21896, 11, 584, 9277, 1057, 24512, 304, 264, 2587, 27975, 8162, 67125, 292, 25199, 320, 23966, 13, 220, 16, 66, 883, 304, 2015, 311, 6920, 704, 58632, 22323, 315, 279, 1510, 36612, 1555, 279, 480, 27416, 323, 279, 220, 21427, 1510, 36612, 1555, 279, 76307, 461, 320, 2000, 810, 3649, 1518, 3451, 82430, 743, 5352, 529, 3857, 315, 279, 19331, 7609, 1226, 10887, 1057, 128257, 198, 128256, 78191, 198, 2746, 584, 4934, 311, 1797, 279, 1396, 315, 1274, 304, 264, 13734, 11, 584, 1436, 1304, 389, 279, 11722, 17989, 11, 1633, 4461, 311, 387, 737, 10872, 1082, 11, 477, 584, 1436, 2610, 1855, 1732, 311, 1522, 1555, 264, 2543, 47604, 13, 578, 15629, 53291, 279, 1646, 430, 19613, 6254, 12074, 617, 1511, 369, 6968, 264, 330, 56420, 6742, 1, 430, 374, 3025, 311, 11388, 279, 21765, 315, 3927, 15922, 35715, 1555, 264, 13987, 14512, 25, 264, 76307, 461, 449, 18751, 66192, 99041, 13, 578, 15922, 35715, 527, 80703, 304, 264, 6425, 8649, 65125, 323, 527, 16625, 555, 459, 9249, 2115, 1555, 264, 39654, 449, 264, 76307, 461, 13, 3277, 279, 43030, 5900, 1555, 279, 477, 22660, 11, 433, 2605, 8099, 264, 8275, 18713, 65916, 311, 279, 2115, 11, 11388, 481, 539, 1193, 555, 279, 1491, 7607, 304, 220, 21427, 1510, 719, 1101, 555, 390, 884, 52044, 67547, 304, 279, 66192, 99041, 1510, 13, 20817, 389, 420, 2038, 11, 433, 374, 3284, 311, 8417, 3508, 264, 15922, 43030, 706, 5946, 1555, 279, 39654, 477, 539, 13, 1115, 1887, 374, 3196, 389, 264, 1749, 430, 706, 1027, 3967, 369, 927, 264, 21030, 1667, 13, 578, 4113, 15105, 574, 539, 439, 15062, 2533, 433, 10666, 264, 1396, 315, 73021, 1778, 439, 272, 26330, 72028, 323, 6996, 315, 16437, 11, 4315, 3885, 13, 330, 1687, 3463, 430, 584, 1053, 387, 3025, 311, 11886, 1521, 5435, 555, 6968, 264, 39654, 439, 15792, 439, 3284, 1418, 20958, 279, 477, 22660, 596, 8333, 498, 1071, 90678, 24155, 21254, 268, 41145, 505, 279, 32184, 315, 33242, 437, 2296, 40023, 520, 19613, 6254, 13, 32255, 449, 8956, 13389, 1183, 22292, 72, 11, 1772, 38083, 278, 5575, 11, 323, 18105, 505, 279, 32184, 315, 33242, 437, 2296, 38784, 323, 71150, 11, 1364, 3782, 4028, 279, 3769, 430, 6656, 704, 311, 387, 2225, 279, 31005, 323, 1455, 59780, 25, 66192, 11, 902, 17610, 315, 264, 3254, 6324, 315, 12782, 35715, 13, 578, 31022, 315, 66192, 477, 20622, 269, 581, 47620, 1511, 304, 279, 9526, 1051, 9124, 520, 19613, 6254, 11, 9523, 311, 279, 990, 11953, 704, 520, 279, 5955, 369, 18654, 33242, 52536, 320, 34, 9972, 8, 323, 279, 5955, 369, 77976, 18654, 51856, 320, 34, 5778, 570, 330, 24798, 459, 8056, 50278, 11, 8738, 279, 32185, 11, 279, 66192, 6324, 596, 26839, 11193, 220, 15, 13, 16596, 26807, 11, 902, 7041, 18809, 279, 13225, 6484, 1990, 1403, 15922, 23963, 11, 20444, 304, 279, 7384, 1511, 779, 3117, 1070, 574, 264, 220, 868, 26807, 26839, 1210, 1666, 264, 1121, 11, 1418, 8767, 433, 574, 539, 3284, 311, 32399, 24564, 279, 21765, 315, 15922, 23963, 1555, 1521, 330, 4930, 1, 53827, 1389, 520, 264, 31206, 5569, 1389, 11, 279, 502, 1749, 374, 4461, 311, 3493, 264, 1790, 5190, 16437, 13, 38274, 11, 433, 1436, 387, 1511, 369, 15922, 62119, 13, 4452, 814, 527, 539, 1070, 3686, 13, 763, 1193, 220, 20, 31604, 11, 709, 311, 220, 1135, 6, 931, 15922, 23963, 649, 1522, 1555, 279, 72028, 13, 578, 9249, 2612, 8450, 374, 539, 2867, 3403, 369, 330, 6285, 1, 279, 3974, 8668, 315, 279, 15922, 42589, 21765, 13, 330, 11458, 11, 279, 13336, 315, 54626, 279, 21765, 315, 15922, 449, 66192, 20622, 269, 581, 47620, 374, 264, 42445, 439, 1664, 439, 264, 5199, 6776, 498, 1071, 90678, 24155, 21254, 268, 41145, 13, 3005, 10555, 430, 11, 369, 3187, 11, 279, 3756, 374, 1101, 3025, 311, 11388, 279, 21765, 315, 1023, 13124, 315, 28896, 323, 3493, 2038, 389, 872, 1404, 323, 5255, 6211, 13, 1115, 16996, 3094, 7119, 502, 5528, 315, 31206, 6492, 706, 4036, 459, 57152, 13500, 323, 374, 15109, 304, 459, 4652, 4756, 304, 22037, 33242, 52536, 13, 220, 128257, 198 ]

1,999

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Lions ( Panthera leo ) feed on diverse prey species, a range that is broadened by their cooperative hunting. Although humans are not typical prey, habitual man-eating by lions is well documented. Fathoming the motivations of the Tsavo and Mfuwe man-eaters (killed in 1898 in Kenya and 1991 in Zambia, respectively) may be elusive, but we can clarify aspects of their behaviour using dental microwear texture analysis. Specifically, we analysed the surface textures of lion teeth to assess whether these notorious man-eating lions scavenged carcasses during their depredations. Compared to wild-caught lions elsewhere in Africa and other large feliforms, including cheetahs and hyenas, dental microwear textures of the man-eaters do not suggest extreme durophagy (e.g. bone processing) shortly before death. Dental injuries to two of the three man-eaters examined may have induced shifts in feeding onto softer foods. Further, prompt carcass reclamation by humans likely limited the man-eaters’ access to bones. Man-eating was likely a viable alternative to hunting and/or scavenging ungulates due to dental disease and/or limited prey availability. Introduction Lions ( Panthera leo ) once inhabited much of Africa, southeastern Europe, and southwestern Asia 1 . Currently, lions ( Panthera leo ) occupy savannas and deserts in sub-Saharan Africa (excluding rainforests and the Sahara), with an isolated population located in the Gir Forest of India. They are highly social, and males and females each live in persistent bonded groups 2 . Lion behaviours, diets, and social groupings all vary enormously in response to spatial or temporal shifts in prey availability and habitat structure 3 . Smaller groups and females prey mainly on zebra and wildebeest whereas larger groups and males feed differentially on buffalo 4 , 5 . Lions are known to consume a diverse suite of prey with preferences for gemsbok, buffalo, wildebeest, giraffe, zebra, Thomson’s gazelle, warthog, kongoni, and topi 4 , 6 . Further, habitat and droughts can affect lion preferences and prey vulnerability to predation, with lions increasing the proportion of elephant calves consumed during droughts 7 . Their current range collapse, to 20% of historic values, is driven not by limited adaptability but rather by habitat loss and fragmentation, prey depletion, and direct persecution 8 . Man-eating, or consumption of humans as women and children are often victims, has occasionally been a dietary strategy of lions and other pantherines 9 , 10 . Two notorious lions (popularized in the 1996 film The Ghost and the Darkness ) terrorized people near Tsavo by repeatedly killing and consuming railway workers in 1898, and one from Mfuwe, Zambia consumed six people as recently as 1991 11 . Colonel J. H. Patterson, who eventually killed the Tsavo man-eaters in December 1898, estimated that they had killed and eaten 135 people 12 . However, stable isotope analysis of their hair and bone collagen suggests that they had consumed ~35 people, representing roughly 30% of the first man-eater’s diet (FMNH 23970) and ~13% of the second man-eater’s diet (FMNH 23969) 13 . The reasons for the lions’ differential reliance on humans, and for man-eating by lions in general, remain unclear. Many hypotheses have been proposed regarding the motivations of the man-eating lions, including an extended drought, a 1898 rinderpest outbreak that ravaged prey populations, various cultural causes, and/or dental disease 11 , 14 , 15 . Evidence of dental disease is quite clear in two of the three man-eating lions. One lion (the first Tsavo man-eater), with a broken canine, developed a periapical abscess and lost three lower right incisors 15 (see Fig. 1 ). The pronounced toothwear and extensive cranial remodeling suggests that the lion had broken his canine several years earlier 15 . The second Tsavo man-eater had minor injuries including a fractured upper left carnassial and subsequent pulp exposure, although these types of injuries are fairly common and were unaccompanied by disease 16 . Similarly, the man-eater from Mfuwe had fractured its right mandibular ramus. These injuries may have been decisive factors influencing their consumption of humans. While it is difficult to assess the motivations of the man-eating lions, we can clarify aspects of their behaviour prior to their death. Most notably, we can assess if their circumstances caused them to rely more heavily on scavenging carcasses shortly before they were killed, as suggested by contemporary reports of the sounds of bone-crunching on the edge of camp 12 . Dental microwear texture analysis (DMTA) can clarify the textural properties of consumed food, including durophagy in carnivorans, and clearly distinguishes feliforms that eat primarily flesh (the cheetah, Acinonyx jubatus ), from generalists ( P. leo ), and various hyenas which are known to fully consume carcasses, including bone 17 , 18 . Figure 1 Images of injuries to Tsavo’s 1st man-eater ( a ), FMNH 23970 and the Mfuwe man-eater ( b ), FMNH 163109. Image ( a ), Field Museum of Natural History image Z-94320_11c by John Weinstein documents a broken lower right canine (which had a periapical abscess) and loss of the lower three right incisors - presumably from the kick of a struggling prey - and subsequent over-eruption of the upper right incisors and rotation of the upper right canine both labially and mesially in the absence of the interlocking lower canine. In ( b ), multiple oval-shaped intraosseous lesions are visible on the right mandible, superficial to an occluded mandibular canal and associated with a chronically draining fistula 15 . Again, these injuries are consistent with blunt trauma from a powerful ungulate kick. Full size image In contrast to two-dimensional dental microwear, which relies on human identification and counting of microscopic wear features such as pits and scratches, 3D DMTA quantifies surfaces using scale-sensitive fractal analysis 19 , 20 , 21 , 22 . Complexity ( Asfc ) distinguishes taxa that consume brittle foods from taxa that consume softer ones 19 , 20 , 21 , 22 , 23 . Anisotropy ( epLsar ), the degree to which features share similar orientations, instead indicates tough food consumption when values are high 19", "role": "user" }, { "content": "An analysis of the microscopic wear on the teeth of the legendary \"man-eating lions of Tsavo\" reveals that it wasn't desperation that drove them to terrorize a railroad camp in Kenya more than a century ago. \"Our results suggest that preying on people was not the lions' last resort, rather, it was simply the easiest solution to a problem that they confronted,\" said Larisa DeSantis, assistant professor of earth and environmental studies at Vanderbilt University. The study, which she performed with Bruce Patterson, MacArthur Curator of Mammals at The Field Museum of Natural History in Chicago, is described in a paper titled \"Dietary behavior of man-eating lions as revealed by dental microwear textures\" published online Apr. 19 by the journal Scientific Reports. \"It's hard to fathom the motivations of animals that lived over a hundred years ago, but scientific specimens allow us to do just that,\" said Patterson, who has studied the Tsavo lions extensively. \"Since The Field Museum preserves these lions' remains, we can study them using techniques that would have been unimaginable a hundred years ago.\" In order to shed light on the lion's motivations, DeSantis employed state-of-the-art dental microwear analysis on the teeth of three man-eating lions from the Field Museum's collection: the two Tsavo lions and a lion from Mfuwe, Zambia which consumed at least six people in 1991. The analysis can provide valuable information about the nature of animal's diet in the days and weeks before its death. DeSantis and Patterson undertook the study to investigate the theory that prey shortages may have driven the lions to man-eating. At the time, the Tsavo region was in the midst of a two-year drought and a rinderpest epidemic that had ravaged the local wildlife. If the lions were desperate for food and scavenging carcasses, the man-eating lions should have dental microwear similar to hyenas, which routinely chew and digest the bones of their prey. The skull of one of the Tsavo man-eaters shows evidence of dental disease. Credit: Bruce Patterson and JP Brown, The Field Museum \"Despite contemporary reports of the sound of the lion's crunching on the bones of their victims at the edge of the camp, the Tsavo lion's teeth do not show wear patterns consistent with eating bones,\" said DeSantis. \"In fact, the wear patterns on their teeth are strikingly similar to those of zoo lions that are typically provisioned with soft foods like beef and horsemeat.\" The study provides new support for the proposition that dental disease and injury may play a determining role in turning individual lions into habitual man eaters. The Tsavo lion which did the most man-eating, as established through chemical analysis of the lions' bones and fur in a previous study, had severe dental disease. It had a root-tip abscess in one of its canines—a painful infection at the root of the tooth that would have made normal hunting impossible. \"Lions normally use their jaws to grab prey like zebras and buffalos and suffocate them,\" Patterson explained. \"This lion would have been challenged to subdue and kill large struggling prey; humans are so much easier to catch.\" Lt. Colonel John Patterson in 1898 with one of the Tsavo man-eaters that he shot. Credit: The Field Museum The diseased lion's partner, on the other hand, had less pronounced injuries to its teeth and jaw—injuries that are fairly common in lions which are not man eaters. According to the same chemical analysis, it consumed a lot more zebras and buffalos, and far fewer people, than its hunting companion. The fact that the Mfuwe lion also had severe structural damage to its jaw provides additional support for the role of dental problems in triggering man-eating behavior, as do a number of reports of man-eating incidents by tigers and leopards in colonial India that cite similar infirmities, the researchers pointed out. The man-eating Tsavo lions are currently on display at The Field Museum in Chicago. Credit: John Weinstein, The Field Museum \"Our data suggests that these man-eating lions didn't completely consume the carcasses of their human or animal prey,\" said DeSantis. \"Instead, people appear to have supplemented their already diverse diet. Anthropological evidence suggests that humans have been a regular item on the menu of not only lions, but also leopards and the other great cats. Today, lions seldom hunt people but as human populations continue to grow and the numbers of prey species decline, man-eating may increasingly become a viable option for many lions.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Lions ( Panthera leo ) feed on diverse prey species, a range that is broadened by their cooperative hunting. Although humans are not typical prey, habitual man-eating by lions is well documented. Fathoming the motivations of the Tsavo and Mfuwe man-eaters (killed in 1898 in Kenya and 1991 in Zambia, respectively) may be elusive, but we can clarify aspects of their behaviour using dental microwear texture analysis. Specifically, we analysed the surface textures of lion teeth to assess whether these notorious man-eating lions scavenged carcasses during their depredations. Compared to wild-caught lions elsewhere in Africa and other large feliforms, including cheetahs and hyenas, dental microwear textures of the man-eaters do not suggest extreme durophagy (e.g. bone processing) shortly before death. Dental injuries to two of the three man-eaters examined may have induced shifts in feeding onto softer foods. Further, prompt carcass reclamation by humans likely limited the man-eaters’ access to bones. Man-eating was likely a viable alternative to hunting and/or scavenging ungulates due to dental disease and/or limited prey availability. Introduction Lions ( Panthera leo ) once inhabited much of Africa, southeastern Europe, and southwestern Asia 1 . Currently, lions ( Panthera leo ) occupy savannas and deserts in sub-Saharan Africa (excluding rainforests and the Sahara), with an isolated population located in the Gir Forest of India. They are highly social, and males and females each live in persistent bonded groups 2 . Lion behaviours, diets, and social groupings all vary enormously in response to spatial or temporal shifts in prey availability and habitat structure 3 . Smaller groups and females prey mainly on zebra and wildebeest whereas larger groups and males feed differentially on buffalo 4 , 5 . Lions are known to consume a diverse suite of prey with preferences for gemsbok, buffalo, wildebeest, giraffe, zebra, Thomson’s gazelle, warthog, kongoni, and topi 4 , 6 . Further, habitat and droughts can affect lion preferences and prey vulnerability to predation, with lions increasing the proportion of elephant calves consumed during droughts 7 . Their current range collapse, to 20% of historic values, is driven not by limited adaptability but rather by habitat loss and fragmentation, prey depletion, and direct persecution 8 . Man-eating, or consumption of humans as women and children are often victims, has occasionally been a dietary strategy of lions and other pantherines 9 , 10 . Two notorious lions (popularized in the 1996 film The Ghost and the Darkness ) terrorized people near Tsavo by repeatedly killing and consuming railway workers in 1898, and one from Mfuwe, Zambia consumed six people as recently as 1991 11 . Colonel J. H. Patterson, who eventually killed the Tsavo man-eaters in December 1898, estimated that they had killed and eaten 135 people 12 . However, stable isotope analysis of their hair and bone collagen suggests that they had consumed ~35 people, representing roughly 30% of the first man-eater’s diet (FMNH 23970) and ~13% of the second man-eater’s diet (FMNH 23969) 13 . The reasons for the lions’ differential reliance on humans, and for man-eating by lions in general, remain unclear. Many hypotheses have been proposed regarding the motivations of the man-eating lions, including an extended drought, a 1898 rinderpest outbreak that ravaged prey populations, various cultural causes, and/or dental disease 11 , 14 , 15 . Evidence of dental disease is quite clear in two of the three man-eating lions. One lion (the first Tsavo man-eater), with a broken canine, developed a periapical abscess and lost three lower right incisors 15 (see Fig. 1 ). The pronounced toothwear and extensive cranial remodeling suggests that the lion had broken his canine several years earlier 15 . The second Tsavo man-eater had minor injuries including a fractured upper left carnassial and subsequent pulp exposure, although these types of injuries are fairly common and were unaccompanied by disease 16 . Similarly, the man-eater from Mfuwe had fractured its right mandibular ramus. These injuries may have been decisive factors influencing their consumption of humans. While it is difficult to assess the motivations of the man-eating lions, we can clarify aspects of their behaviour prior to their death. Most notably, we can assess if their circumstances caused them to rely more heavily on scavenging carcasses shortly before they were killed, as suggested by contemporary reports of the sounds of bone-crunching on the edge of camp 12 . Dental microwear texture analysis (DMTA) can clarify the textural properties of consumed food, including durophagy in carnivorans, and clearly distinguishes feliforms that eat primarily flesh (the cheetah, Acinonyx jubatus ), from generalists ( P. leo ), and various hyenas which are known to fully consume carcasses, including bone 17 , 18 . Figure 1 Images of injuries to Tsavo’s 1st man-eater ( a ), FMNH 23970 and the Mfuwe man-eater ( b ), FMNH 163109. Image ( a ), Field Museum of Natural History image Z-94320_11c by John Weinstein documents a broken lower right canine (which had a periapical abscess) and loss of the lower three right incisors - presumably from the kick of a struggling prey - and subsequent over-eruption of the upper right incisors and rotation of the upper right canine both labially and mesially in the absence of the interlocking lower canine. In ( b ), multiple oval-shaped intraosseous lesions are visible on the right mandible, superficial to an occluded mandibular canal and associated with a chronically draining fistula 15 . Again, these injuries are consistent with blunt trauma from a powerful ungulate kick. Full size image In contrast to two-dimensional dental microwear, which relies on human identification and counting of microscopic wear features such as pits and scratches, 3D DMTA quantifies surfaces using scale-sensitive fractal analysis 19 , 20 , 21 , 22 . Complexity ( Asfc ) distinguishes taxa that consume brittle foods from taxa that consume softer ones 19 , 20 , 21 , 22 , 23 . Anisotropy ( epLsar ), the degree to which features share similar orientations, instead indicates tough food consumption when values are high 19<|im_end|> <|im_start|>assistant An analysis of the microscopic wear on the teeth of the legendary "man-eating lions of Tsavo" reveals that it wasn't desperation that drove them to terrorize a railroad camp in Kenya more than a century ago. "Our results suggest that preying on people was not the lions' last resort, rather, it was simply the easiest solution to a problem that they confronted," said Larisa DeSantis, assistant professor of earth and environmental studies at Vanderbilt University. The study, which she performed with Bruce Patterson, MacArthur Curator of Mammals at The Field Museum of Natural History in Chicago, is described in a paper titled "Dietary behavior of man-eating lions as revealed by dental microwear textures" published online Apr. 19 by the journal Scientific Reports. "It's hard to fathom the motivations of animals that lived over a hundred years ago, but scientific specimens allow us to do just that," said Patterson, who has studied the Tsavo lions extensively. "Since The Field Museum preserves these lions' remains, we can study them using techniques that would have been unimaginable a hundred years ago." In order to shed light on the lion's motivations, DeSantis employed state-of-the-art dental microwear analysis on the teeth of three man-eating lions from the Field Museum's collection: the two Tsavo lions and a lion from Mfuwe, Zambia which consumed at least six people in 1991. The analysis can provide valuable information about the nature of animal's diet in the days and weeks before its death. DeSantis and Patterson undertook the study to investigate the theory that prey shortages may have driven the lions to man-eating. At the time, the Tsavo region was in the midst of a two-year drought and a rinderpest epidemic that had ravaged the local wildlife. If the lions were desperate for food and scavenging carcasses, the man-eating lions should have dental microwear similar to hyenas, which routinely chew and digest the bones of their prey. The skull of one of the Tsavo man-eaters shows evidence of dental disease. Credit: Bruce Patterson and JP Brown, The Field Museum "Despite contemporary reports of the sound of the lion's crunching on the bones of their victims at the edge of the camp, the Tsavo lion's teeth do not show wear patterns consistent with eating bones," said DeSantis. "In fact, the wear patterns on their teeth are strikingly similar to those of zoo lions that are typically provisioned with soft foods like beef and horsemeat." The study provides new support for the proposition that dental disease and injury may play a determining role in turning individual lions into habitual man eaters. The Tsavo lion which did the most man-eating, as established through chemical analysis of the lions' bones and fur in a previous study, had severe dental disease. It had a root-tip abscess in one of its canines—a painful infection at the root of the tooth that would have made normal hunting impossible. "Lions normally use their jaws to grab prey like zebras and buffalos and suffocate them," Patterson explained. "This lion would have been challenged to subdue and kill large struggling prey; humans are so much easier to catch." Lt. Colonel John Patterson in 1898 with one of the Tsavo man-eaters that he shot. Credit: The Field Museum The diseased lion's partner, on the other hand, had less pronounced injuries to its teeth and jaw—injuries that are fairly common in lions which are not man eaters. According to the same chemical analysis, it consumed a lot more zebras and buffalos, and far fewer people, than its hunting companion. The fact that the Mfuwe lion also had severe structural damage to its jaw provides additional support for the role of dental problems in triggering man-eating behavior, as do a number of reports of man-eating incidents by tigers and leopards in colonial India that cite similar infirmities, the researchers pointed out. The man-eating Tsavo lions are currently on display at The Field Museum in Chicago. Credit: John Weinstein, The Field Museum "Our data suggests that these man-eating lions didn't completely consume the carcasses of their human or animal prey," said DeSantis. "Instead, people appear to have supplemented their already diverse diet. Anthropological evidence suggests that humans have been a regular item on the menu of not only lions, but also leopards and the other great cats. Today, lions seldom hunt people but as human populations continue to grow and the numbers of prey species decline, man-eating may increasingly become a viable option for many lions." <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 33865, 320, 59612, 64, 89601, 883, 5510, 389, 17226, 37693, 9606, 11, 264, 2134, 430, 374, 7353, 6901, 555, 872, 48566, 23330, 13, 10541, 12966, 527, 539, 14595, 37693, 11, 84820, 893, 5773, 1113, 555, 69132, 374, 1664, 27470, 13, 435, 589, 18238, 279, 65931, 315, 279, 26132, 28316, 323, 386, 33721, 906, 893, 5773, 11796, 320, 74, 4473, 304, 220, 9378, 23, 304, 37766, 323, 220, 2550, 16, 304, 95104, 11, 15947, 8, 1253, 387, 66684, 11, 719, 584, 649, 38263, 13878, 315, 872, 17432, 1701, 29106, 19748, 654, 686, 10651, 6492, 13, 45863, 11, 584, 67458, 279, 7479, 30953, 315, 40132, 18311, 311, 8720, 3508, 1521, 44081, 893, 5773, 1113, 69132, 83750, 833, 291, 75566, 52090, 2391, 872, 2219, 1171, 811, 13, 59813, 311, 8545, 51877, 3948, 69132, 18403, 304, 10384, 323, 1023, 3544, 18515, 7398, 82, 11, 2737, 3091, 295, 1494, 82, 323, 6409, 28043, 11, 29106, 19748, 654, 686, 30953, 315, 279, 893, 5773, 11796, 656, 539, 4284, 14560, 92196, 764, 82770, 320, 68, 1326, 13, 17685, 8863, 8, 20193, 1603, 4648, 13, 48804, 15319, 311, 1403, 315, 279, 2380, 893, 5773, 11796, 25078, 1253, 617, 36572, 29735, 304, 26040, 8800, 64230, 15657, 13, 15903, 11, 10137, 75566, 395, 312, 34084, 555, 12966, 4461, 7347, 279, 893, 5773, 11796, 529, 2680, 311, 25896, 13, 2418, 5773, 1113, 574, 4461, 264, 31528, 10778, 311, 23330, 323, 5255, 83750, 833, 287, 51590, 24031, 4245, 311, 29106, 8624, 323, 5255, 7347, 37693, 18539, 13, 29438, 33865, 320, 59612, 64, 89601, 883, 3131, 70598, 1790, 315, 10384, 11, 83209, 4606, 11, 323, 99911, 13936, 220, 16, 662, 25122, 11, 69132, 320, 59612, 64, 89601, 883, 48678, 11427, 1036, 300, 323, 951, 15916, 304, 1207, 97519, 10384, 320, 80095, 11422, 1348, 37379, 323, 279, 89078, 705, 449, 459, 25181, 7187, 7559, 304, 279, 48035, 20585, 315, 6890, 13, 2435, 527, 7701, 3674, 11, 323, 25000, 323, 28585, 1855, 3974, 304, 26048, 70241, 5315, 220, 17, 662, 33199, 71177, 11, 41943, 11, 323, 3674, 1912, 826, 682, 13592, 84563, 304, 2077, 311, 29079, 477, 37015, 29735, 304, 37693, 18539, 323, 39646, 6070, 220, 18, 662, 4487, 14283, 5315, 323, 28585, 37693, 14918, 389, 1167, 51313, 323, 31331, 451, 1395, 478, 20444, 8294, 5315, 323, 25000, 5510, 2204, 34575, 389, 82455, 220, 19, 1174, 220, 20, 662, 33865, 527, 3967, 311, 25024, 264, 17226, 16578, 315, 37693, 449, 19882, 369, 43258, 65, 564, 11, 82455, 11, 31331, 451, 1395, 478, 11, 41389, 38880, 11, 1167, 51313, 11, 65332, 753, 56086, 6853, 11, 4208, 339, 540, 11, 597, 647, 21446, 11, 323, 1948, 72, 220, 19, 1174, 220, 21, 662, 15903, 11, 39646, 323, 37846, 82, 649, 7958, 40132, 19882, 323, 37693, 34104, 311, 4255, 367, 11, 449, 69132, 7859, 279, 21801, 315, 46840, 97310, 27073, 2391, 37846, 82, 220, 22, 662, 11205, 1510, 2134, 18678, 11, 311, 220, 508, 4, 315, 18526, 2819, 11, 374, 16625, 539, 555, 7347, 10737, 2968, 719, 4856, 555, 39646, 4814, 323, 88452, 11, 37693, 92948, 11, 323, 2167, 56529, 220, 23, 662, 2418, 5773, 1113, 11, 477, 15652, 315, 12966, 439, 3278, 323, 2911, 527, 3629, 12697, 11, 706, 23781, 1027, 264, 34625, 8446, 315, 69132, 323, 1023, 7363, 700, 1572, 220, 24, 1174, 220, 605, 662, 9220, 44081, 69132, 320, 44348, 1534, 304, 279, 220, 2550, 21, 4632, 578, 26099, 323, 279, 54796, 883, 8818, 1534, 1274, 3221, 26132, 28316, 555, 19352, 13419, 323, 35208, 40106, 7487, 304, 220, 9378, 23, 11, 323, 832, 505, 386, 33721, 906, 11, 95104, 27073, 4848, 1274, 439, 6051, 439, 220, 2550, 16, 220, 806, 662, 52798, 622, 13, 473, 13, 58734, 11, 889, 9778, 7577, 279, 26132, 28316, 893, 5773, 11796, 304, 6790, 220, 9378, 23, 11, 13240, 430, 814, 1047, 7577, 323, 35661, 220, 8878, 1274, 220, 717, 662, 4452, 11, 15528, 374, 51782, 6492, 315, 872, 7013, 323, 17685, 71313, 13533, 430, 814, 1047, 27073, 4056, 1758, 1274, 11, 14393, 17715, 220, 966, 4, 315, 279, 1176, 893, 5773, 977, 753, 10173, 320, 26691, 52371, 220, 14815, 2031, 8, 323, 4056, 1032, 4, 315, 279, 2132, 893, 5773, 977, 753, 10173, 320, 26691, 52371, 220, 14815, 3076, 8, 220, 1032, 662, 578, 8125, 369, 279, 69132, 529, 41264, 54180, 389, 12966, 11, 323, 369, 893, 5773, 1113, 555, 69132, 304, 4689, 11, 7293, 25420, 13, 9176, 74513, 617, 1027, 11223, 9002, 279, 65931, 315, 279, 893, 5773, 1113, 69132, 11, 2737, 459, 11838, 37846, 11, 264, 220, 9378, 23, 436, 5863, 30223, 31188, 430, 43643, 3359, 37693, 22673, 11, 5370, 13042, 11384, 11, 323, 5255, 29106, 8624, 220, 806, 1174, 220, 975, 1174, 220, 868, 662, 44796, 315, 29106, 8624, 374, 5115, 2867, 304, 1403, 315, 279, 2380, 893, 5773, 1113, 69132, 13, 3861, 40132, 320, 1820, 1176, 26132, 28316, 893, 5773, 977, 705, 449, 264, 11102, 76082, 11, 8040, 264, 62257, 391, 950, 3731, 1140, 323, 5675, 2380, 4827, 1314, 3709, 42314, 220, 868, 320, 4151, 23966, 13, 220, 16, 7609, 578, 38617, 26588, 23581, 323, 16781, 70637, 532, 70430, 13533, 430, 279, 40132, 1047, 11102, 813, 76082, 3892, 1667, 6931, 220, 868, 662, 578, 2132, 26132, 28316, 893, 5773, 977, 1047, 9099, 15319, 2737, 264, 80208, 8582, 2163, 39438, 395, 532, 323, 17876, 64188, 14675, 11, 8051, 1521, 4595, 315, 15319, 527, 14470, 4279, 323, 1051, 653, 73087, 22840, 555, 8624, 220, 845, 662, 35339, 11, 279, 893, 5773, 977, 505, 386, 33721, 906, 1047, 80208, 1202, 1314, 11837, 581, 1299, 18302, 355, 13, 4314, 15319, 1253, 617, 1027, 51391, 9547, 66700, 872, 15652, 315, 12966, 13, 6104, 433, 374, 5107, 311, 8720, 279, 65931, 315, 279, 893, 5773, 1113, 69132, 11, 584, 649, 38263, 13878, 315, 872, 17432, 4972, 311, 872, 4648, 13, 7648, 35146, 11, 584, 649, 8720, 422, 872, 13463, 9057, 1124, 311, 17631, 810, 17345, 389, 83750, 833, 287, 75566, 52090, 20193, 1603, 814, 1051, 7577, 11, 439, 12090, 555, 19225, 6821, 315, 279, 10578, 315, 17685, 48689, 3265, 287, 389, 279, 6964, 315, 3190, 220, 717, 662, 48804, 19748, 654, 686, 10651, 6492, 320, 8561, 15559, 8, 649, 38263, 279, 1495, 4269, 6012, 315, 27073, 3691, 11, 2737, 92196, 764, 82770, 304, 39438, 50775, 598, 11, 323, 9539, 19512, 21168, 18515, 7398, 82, 430, 8343, 15871, 26000, 320, 1820, 3091, 295, 1494, 11, 6515, 258, 3633, 87, 97443, 1015, 7026, 505, 4689, 1705, 320, 393, 13, 89601, 7026, 323, 5370, 6409, 28043, 902, 527, 3967, 311, 7373, 25024, 75566, 52090, 11, 2737, 17685, 220, 1114, 1174, 220, 972, 662, 19575, 220, 16, 12041, 315, 15319, 311, 26132, 28316, 753, 220, 16, 267, 893, 5773, 977, 320, 264, 7026, 24342, 52371, 220, 14815, 2031, 323, 279, 386, 33721, 906, 893, 5773, 977, 320, 293, 7026, 24342, 52371, 220, 9892, 7743, 13, 4758, 320, 264, 7026, 8771, 16730, 315, 18955, 11346, 2217, 1901, 12, 26576, 508, 62, 806, 66, 555, 3842, 56682, 9477, 264, 11102, 4827, 1314, 76082, 320, 8370, 1047, 264, 62257, 391, 950, 3731, 1140, 8, 323, 4814, 315, 279, 4827, 2380, 1314, 3709, 42314, 482, 36548, 505, 279, 10536, 315, 264, 20558, 37693, 482, 323, 17876, 927, 12, 112644, 562, 315, 279, 8582, 1314, 3709, 42314, 323, 12984, 315, 279, 8582, 1314, 76082, 2225, 10278, 34575, 323, 11083, 34575, 304, 279, 19821, 315, 279, 958, 90582, 4827, 76082, 13, 763, 320, 293, 7026, 5361, 61137, 35831, 50938, 437, 325, 788, 63324, 527, 9621, 389, 279, 1314, 11837, 1260, 11, 59915, 311, 459, 18274, 10391, 11837, 581, 1299, 40021, 323, 5938, 449, 264, 27076, 2740, 74109, 40902, 5724, 220, 868, 662, 14077, 11, 1521, 15319, 527, 13263, 449, 49770, 30988, 505, 264, 8147, 51590, 6468, 10536, 13, 8797, 1404, 2217, 763, 13168, 311, 1403, 33520, 29106, 19748, 654, 686, 11, 902, 34744, 389, 3823, 22654, 323, 26060, 315, 90090, 10051, 4519, 1778, 439, 63008, 323, 66839, 11, 220, 18, 35, 423, 8673, 32, 10484, 9803, 27529, 1701, 5569, 57767, 27700, 278, 6492, 220, 777, 1174, 220, 508, 1174, 220, 1691, 1174, 220, 1313, 662, 71718, 320, 1666, 8480, 883, 19512, 21168, 77314, 430, 25024, 95749, 15657, 505, 77314, 430, 25024, 64230, 6305, 220, 777, 1174, 220, 508, 1174, 220, 1691, 1174, 220, 1313, 1174, 220, 1419, 662, 1556, 285, 354, 18237, 320, 4248, 43, 99182, 7026, 279, 8547, 311, 902, 4519, 4430, 4528, 89935, 11, 4619, 15151, 11292, 3691, 15652, 994, 2819, 527, 1579, 220, 777, 128257, 198, 128256, 78191, 198, 2127, 6492, 315, 279, 90090, 10051, 389, 279, 18311, 315, 279, 28812, 330, 1543, 5773, 1113, 69132, 315, 26132, 28316, 1, 21667, 430, 433, 5828, 956, 74424, 430, 23980, 1124, 311, 8818, 553, 264, 51576, 3190, 304, 37766, 810, 1109, 264, 9478, 4227, 13, 330, 8140, 3135, 4284, 430, 864, 7169, 389, 1274, 574, 539, 279, 69132, 6, 1566, 22541, 11, 4856, 11, 433, 574, 5042, 279, 30689, 6425, 311, 264, 3575, 430, 814, 41782, 1359, 1071, 32404, 10994, 1611, 50, 38966, 11, 18328, 14561, 315, 9578, 323, 12434, 7978, 520, 84126, 3907, 13, 578, 4007, 11, 902, 1364, 10887, 449, 24785, 58734, 11, 7553, 60762, 13182, 859, 315, 386, 8836, 1147, 520, 578, 8771, 16730, 315, 18955, 11346, 304, 10780, 11, 374, 7633, 304, 264, 5684, 25891, 330, 35, 3978, 661, 7865, 315, 893, 5773, 1113, 69132, 439, 10675, 555, 29106, 19748, 654, 686, 30953, 1, 4756, 2930, 5186, 13, 220, 777, 555, 279, 8486, 38130, 29140, 13, 330, 2181, 596, 2653, 311, 282, 73555, 279, 65931, 315, 10099, 430, 12439, 927, 264, 7895, 1667, 4227, 11, 719, 12624, 57749, 2187, 603, 311, 656, 1120, 430, 1359, 1071, 58734, 11, 889, 706, 20041, 279, 26132, 28316, 69132, 42817, 13, 330, 12834, 578, 8771, 16730, 75998, 1521, 69132, 6, 8625, 11, 584, 649, 4007, 1124, 1701, 12823, 430, 1053, 617, 1027, 87212, 481, 264, 7895, 1667, 4227, 1210, 763, 2015, 311, 25351, 3177, 389, 279, 40132, 596, 65931, 11, 1611, 50, 38966, 20011, 1614, 8838, 10826, 38921, 29106, 19748, 654, 686, 6492, 389, 279, 18311, 315, 2380, 893, 5773, 1113, 69132, 505, 279, 8771, 16730, 596, 4526, 25, 279, 1403, 26132, 28316, 69132, 323, 264, 40132, 505, 386, 33721, 906, 11, 95104, 902, 27073, 520, 3325, 4848, 1274, 304, 220, 2550, 16, 13, 578, 6492, 649, 3493, 15525, 2038, 922, 279, 7138, 315, 10065, 596, 10173, 304, 279, 2919, 323, 5672, 1603, 1202, 4648, 13, 1611, 50, 38966, 323, 58734, 19165, 1982, 279, 4007, 311, 19874, 279, 10334, 430, 37693, 67276, 1253, 617, 16625, 279, 69132, 311, 893, 5773, 1113, 13, 2468, 279, 892, 11, 279, 26132, 28316, 5654, 574, 304, 279, 35446, 315, 264, 1403, 4771, 37846, 323, 264, 436, 5863, 30223, 42620, 430, 1047, 43643, 3359, 279, 2254, 30405, 13, 1442, 279, 69132, 1051, 28495, 369, 3691, 323, 83750, 833, 287, 75566, 52090, 11, 279, 893, 5773, 1113, 69132, 1288, 617, 29106, 19748, 654, 686, 4528, 311, 6409, 28043, 11, 902, 40076, 37433, 323, 21552, 279, 25896, 315, 872, 37693, 13, 578, 35113, 315, 832, 315, 279, 26132, 28316, 893, 5773, 11796, 5039, 6029, 315, 29106, 8624, 13, 16666, 25, 24785, 58734, 323, 49880, 10690, 11, 578, 8771, 16730, 330, 20397, 19225, 6821, 315, 279, 5222, 315, 279, 40132, 596, 42834, 287, 389, 279, 25896, 315, 872, 12697, 520, 279, 6964, 315, 279, 3190, 11, 279, 26132, 28316, 40132, 596, 18311, 656, 539, 1501, 10051, 12912, 13263, 449, 12459, 25896, 1359, 1071, 1611, 50, 38966, 13, 330, 644, 2144, 11, 279, 10051, 12912, 389, 872, 18311, 527, 21933, 398, 4528, 311, 1884, 315, 42014, 69132, 430, 527, 11383, 17575, 291, 449, 8579, 15657, 1093, 25309, 323, 15580, 2727, 266, 1210, 578, 4007, 5825, 502, 1862, 369, 279, 41180, 430, 29106, 8624, 323, 11134, 1253, 1514, 264, 26679, 3560, 304, 13353, 3927, 69132, 1139, 84820, 893, 8343, 388, 13, 578, 26132, 28316, 40132, 902, 1550, 279, 1455, 893, 5773, 1113, 11, 439, 9749, 1555, 11742, 6492, 315, 279, 69132, 6, 25896, 323, 18742, 304, 264, 3766, 4007, 11, 1047, 15748, 29106, 8624, 13, 1102, 1047, 264, 3789, 84329, 3731, 1140, 304, 832, 315, 1202, 649, 1572, 29096, 26175, 19405, 520, 279, 3789, 315, 279, 26588, 430, 1053, 617, 1903, 4725, 23330, 12266, 13, 330, 43, 919, 14614, 1005, 872, 82356, 311, 11894, 37693, 1093, 14017, 71861, 323, 11783, 278, 437, 323, 8657, 82615, 1124, 1359, 58734, 11497, 13, 330, 2028, 40132, 1053, 617, 1027, 29991, 311, 1207, 24567, 323, 5622, 3544, 20558, 37693, 26, 12966, 527, 779, 1790, 8831, 311, 2339, 1210, 42970, 13, 52798, 3842, 58734, 304, 220, 9378, 23, 449, 832, 315, 279, 26132, 28316, 893, 5773, 11796, 430, 568, 6689, 13, 16666, 25, 578, 8771, 16730, 578, 6759, 1503, 40132, 596, 8427, 11, 389, 279, 1023, 1450, 11, 1047, 2753, 38617, 15319, 311, 1202, 18311, 323, 16942, 49525, 90927, 430, 527, 14470, 4279, 304, 69132, 902, 527, 539, 893, 8343, 388, 13, 10771, 311, 279, 1890, 11742, 6492, 11, 433, 27073, 264, 2763, 810, 14017, 71861, 323, 11783, 278, 437, 11, 323, 3117, 17162, 1274, 11, 1109, 1202, 23330, 22489, 13, 578, 2144, 430, 279, 386, 33721, 906, 40132, 1101, 1047, 15748, 24693, 5674, 311, 1202, 16942, 5825, 5217, 1862, 369, 279, 3560, 315, 29106, 5435, 304, 52605, 893, 5773, 1113, 7865, 11, 439, 656, 264, 1396, 315, 6821, 315, 893, 5773, 1113, 24455, 555, 259, 33214, 323, 514, 454, 2402, 304, 37683, 6890, 430, 39396, 4528, 4225, 2923, 1385, 11, 279, 12074, 14618, 704, 13, 578, 893, 5773, 1113, 26132, 28316, 69132, 527, 5131, 389, 3113, 520, 578, 8771, 16730, 304, 10780, 13, 16666, 25, 3842, 56682, 11, 578, 8771, 16730, 330, 8140, 828, 13533, 430, 1521, 893, 5773, 1113, 69132, 3287, 956, 6724, 25024, 279, 75566, 52090, 315, 872, 3823, 477, 10065, 37693, 1359, 1071, 1611, 50, 38966, 13, 330, 31887, 11, 1274, 5101, 311, 617, 89804, 872, 2736, 17226, 10173, 13, 70384, 5848, 6029, 13533, 430, 12966, 617, 1027, 264, 5912, 1537, 389, 279, 5130, 315, 539, 1193, 69132, 11, 719, 1101, 514, 454, 2402, 323, 279, 1023, 2294, 19987, 13, 11450, 11, 69132, 56452, 19614, 1274, 719, 439, 3823, 22673, 3136, 311, 3139, 323, 279, 5219, 315, 37693, 9606, 18174, 11, 893, 5773, 1113, 1253, 15098, 3719, 264, 31528, 3072, 369, 1690, 69132, 1210, 220, 128257, 198 ]

2,380

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Graphene nanoscrolls are Archimedean-type spirals formed by rolling single-layer graphene sheets. Their unique structure makes them conceptually interesting and understanding their formation gives important information on the manipulation and characteristics of various carbon nanostructures. Here we report a 100% efficient process to transform nitrogen-doped reduced graphene oxide sheets into homogeneous nanoscrolls by decoration with magnetic γ-Fe 2 O 3 nanoparticles. Through a large number of control experiments, magnetic characterization of the decorated nanoparticles, and ab initio calculations, we conclude that the rolling is initiated by the strong adsorption of maghemite nanoparticles at nitrogen defects in the graphene lattice and their mutual magnetic interaction. The nanoscroll formation is fully reversible and upon removal of the maghemite nanoparticles, the nanoscrolls return to open sheets. Besides supplying information on the rolling mechanism of graphene nanoscrolls, our results also provide important information on the stabilization of iron oxide nanoparticles. Introduction Graphene-based materials have emerged as a key material in nanotechnology and continuously find new areas of applications 1 , 2 , 3 , 4 , 5 . Reduced graphene oxide (rGOx) nanoscrolls are new members in the graphene family, formed by rolling single graphene sheets from one side or from a corner to form Archimedean-type spirals, more commonly known as Swiss rolls. Owing to their unique structure, graphene nanoscrolls are predicted to retain the excellent high conductance of single graphene sheets 6 . This is in contrast to single-walled carbon nanotubes where structural constraints on the electron wavefunctions make them either metallic or semiconducting, depending on their diameter and chirality 7 . Concurrent with unique electronic properties, the appropriate layer spacing of nanoscrolls might allow for energy storage applications 8 , 9 . Despite fascinating properties and a handful of theoretical studies of graphene nanoscrolls 10 , 11 , 12 , 13 , 14 , only few experimental studies 15 , 16 , 17 , 18 are reported for rGOx nanoscrolls. Viculis et al . 17 showed that exfoliation of graphite by alkali metals followed by very strong sonication led to the formation of nanoscrolls, whereas Wang et al . 18 showed that the aggregation of Ag particles on graphene sheets together with high-power sonication initiated the rolling of the rGOx nanoscrolls. However, in none of these studies a thorough explanation is given on how and why the graphene sheets form rolled structures, and with few exceptions 15 the efficiency is low. Here we describe a simple and efficient solution-based process, complemented by a detailed analysis of the rolling mechanism. We show that symmetric nitrogen-doped (13%) rGOx(N-rGOx) nanoscrolls are formed by decorating N-rGOx with magnetic iron oxide particles in the form of maghemite γ-Fe 2 O 3 . In contrast, we show that a similar decoration by less magnetic hematite (α-Fe 2 O 3 ) or non-magnetic palladium oxide particles never leads to any rolling. Similarly, control experiments with low-level or non-N-rGOx decorated by maghemite particles show no rolling, indicating that the nitrogen defects are largely involved in the rolling mechanism. Different to earlier reports 18 and to theoretical predictions 14 , we show that the rolling process is fully reversible and that the N-rGOx can be fully transformed back to open graphene sheets by the removal of iron oxide particles through acid washing. We conclude that the rolling is initiated by the strong adsorption of maghemite nanoparticles at nitrogen defects in the graphene lattice and their mutual magnetic interaction. Our experimental observations are supported by ab initio density functional theory calculations. Results Physical properties of the nanoscrolls The basis of our study relies on attempts to decorate N-rGOx sheets by hematite and tungsten oxide nanoparticles to obtain materials appropriate for water oxidation. In the context of this work, we have come across a very peculiar effect. When the N-rGOx sheets unintentionally were decorated by maghemite nanoparticles, a metastable form of hematite that stabilizes under slightly different conditions, the micrographs of transmission electron microscopy (TEM) consistently revealed the presence of almost 100% of N-rGOx nanoscrolls instead of the commonly open N-rGOx sheets obtained by hematite decoration. Both hematite and maghemite have technologically interesting properties: hematite is used as catalyst for water oxidation 19 , 20 or as paint pigment, whereas maghemite is used as a contrast media in magnetic resonance or as magnetic recording media 21 . Despite many similarities, the two materials also display significant differences. Hematite crystallizes in a rhombohedral structure, whereas maghemite forms a cubic structure 21 , 22 . The difference in crystal structure rationalizes the magnetic properties of maghemite and hematite, where maghemite is ferrimagnetic and displays a much stronger magnetic moment (~540 mT) than the weakly ferromagnetic hematite (~1 mT). However, nanoparticles of both maghemite and hematite exhibit superparamagnetic behaviour, as each nanoparticle forms single magnetic domains 23 , 24 . We show in our study that the magnetically interacting maghemite particles and their strong adsorption on the N-rGOx sheets seem to be the main reasons for the formation of the N-rGOx nanoscrolls. The rolling mechanism of N-rGOx nanoscrolls is revealed by conducting a large number of control experiments to tune and test the synthesis conditions. The conditions leading to the highest ratio of, and most symmetric, nanoscrolls were achieved by adding iron(III) chloride, tungsten hexacarbonyl, and polyvinylpyrrolidone (PVP) and hydrazine into a N-rGOx methanol dispersion, followed by heating under reflux for 24 h (see Methods ). The scheme for the optimal conditions leading to nearly 100% (the only exception was some few very large graphene sheets, >5 μm) of N-rGOx nanoscrolls is shown in Fig. 1 (route a), together with the conditions used when hematite is formed and the decorated N-rGOx remain as open flat sheets ( Fig. 1 , route b). The formation of maghemite and hematite can be controlled by slight changes in the solution. When using a pure methanol solution, formation of maghemite particles is observed, whereas replacing a part of the methanol by water leads to the formation of hematite. Figure 1: Schematic process for the adsorption of iron oxide nanoparticles. (route", "role": "user" }, { "content": "Researchers at Umea University, together with researchers at Uppsala University and Stockholm University, show in a new study how nitrogen doped graphene can be rolled into perfect Archimedean nano scrolls by adhering magnetic iron oxide nanoparticles on the surface of the graphene sheets. The new material may have very good properties for application as electrodes in for example Li-ion batteries. Graphene is one of the most interesting materials for future applications in everything from high performance electronics, optical components to flexible and strong materials. Ordinary graphene consists of carbon sheets that are single or few atomic layers thick. In the study the researchers have modified the graphene by replacing some of the carbon atoms by nitrogen atoms. By this method they obtain anchoring sites for the iron oxide nanoparticles that are decorated onto the graphene sheets in a solution process. In the decoration process one can control the type of iron oxide nanoparticles that are formed on the graphene surface, so that they either form so called hematite (the reddish form of iron oxide that often is found in nature) or maghemite, a less stable and more magnetic form of iron oxide. \"Interestingly we observed that when the graphene is decorated by maghemite, the graphene sheets spontaneously start to roll into perfect Archimedean nano scrolls, while when decorated by the less magnetic hematite nanoparticles the graphene remain as open sheets, says Thomas Wågberg, Senior lecturer at the Department of Physics at Umeå University. Snapshot of a partially re-opened nanoscroll. The atomic layer thick graphene resembles a thin foil with some few wrinkles. The nanoscrolls can be visualized as traditional \"Swiss rolls\" where the sponge-cake represents the graphene, and the creamy filling is the iron oxide nanoparticles. The graphene nanoscrolls are however around one million times thinner. The results that now have been published in Nature Communications are conceptually interesting for several reasons. It shows that the magnetic interaction between the iron oxide nanoparticles is one of the main effects behind the scroll formation. It also shows that the nitrogen defects in the graphene lattice are necessary for both stabilizing a sufficiently high number of maghemite nanoparticles, and also responsible for \"buckling\" the graphene sheets and thereby lowering the formation energy of the nanoscrolls. The process is extraordinary efficient. Almost 100 percent of the graphene sheets are scrolled. After the decoration with maghemite particles the research team could not find any open graphene sheets. Moreover, they showed that by removing the iron oxide nanoparticles by acid treatment the nanoscrolls again open up and go back to single graphene sheets. \"Besides adding valuable fundamental understanding in the physics and chemistry of graphene, nitrogen-doping and nanoparticles we have reasons to believe that the iron oxide decorated nitrogen doped graphene nanoscrolls have very good properties for application as electrodes in for example Li-ion batteries, one of the most important batteries in daily life electronics, \" says Thomas Wågberg. The study has been conducted within the \"The artificial leaf\" project which is funded by Knut and Alice Wallenberg foundation to physicist, chemists, and plant science researchers at Umeå University. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Graphene nanoscrolls are Archimedean-type spirals formed by rolling single-layer graphene sheets. Their unique structure makes them conceptually interesting and understanding their formation gives important information on the manipulation and characteristics of various carbon nanostructures. Here we report a 100% efficient process to transform nitrogen-doped reduced graphene oxide sheets into homogeneous nanoscrolls by decoration with magnetic γ-Fe 2 O 3 nanoparticles. Through a large number of control experiments, magnetic characterization of the decorated nanoparticles, and ab initio calculations, we conclude that the rolling is initiated by the strong adsorption of maghemite nanoparticles at nitrogen defects in the graphene lattice and their mutual magnetic interaction. The nanoscroll formation is fully reversible and upon removal of the maghemite nanoparticles, the nanoscrolls return to open sheets. Besides supplying information on the rolling mechanism of graphene nanoscrolls, our results also provide important information on the stabilization of iron oxide nanoparticles. Introduction Graphene-based materials have emerged as a key material in nanotechnology and continuously find new areas of applications 1 , 2 , 3 , 4 , 5 . Reduced graphene oxide (rGOx) nanoscrolls are new members in the graphene family, formed by rolling single graphene sheets from one side or from a corner to form Archimedean-type spirals, more commonly known as Swiss rolls. Owing to their unique structure, graphene nanoscrolls are predicted to retain the excellent high conductance of single graphene sheets 6 . This is in contrast to single-walled carbon nanotubes where structural constraints on the electron wavefunctions make them either metallic or semiconducting, depending on their diameter and chirality 7 . Concurrent with unique electronic properties, the appropriate layer spacing of nanoscrolls might allow for energy storage applications 8 , 9 . Despite fascinating properties and a handful of theoretical studies of graphene nanoscrolls 10 , 11 , 12 , 13 , 14 , only few experimental studies 15 , 16 , 17 , 18 are reported for rGOx nanoscrolls. Viculis et al . 17 showed that exfoliation of graphite by alkali metals followed by very strong sonication led to the formation of nanoscrolls, whereas Wang et al . 18 showed that the aggregation of Ag particles on graphene sheets together with high-power sonication initiated the rolling of the rGOx nanoscrolls. However, in none of these studies a thorough explanation is given on how and why the graphene sheets form rolled structures, and with few exceptions 15 the efficiency is low. Here we describe a simple and efficient solution-based process, complemented by a detailed analysis of the rolling mechanism. We show that symmetric nitrogen-doped (13%) rGOx(N-rGOx) nanoscrolls are formed by decorating N-rGOx with magnetic iron oxide particles in the form of maghemite γ-Fe 2 O 3 . In contrast, we show that a similar decoration by less magnetic hematite (α-Fe 2 O 3 ) or non-magnetic palladium oxide particles never leads to any rolling. Similarly, control experiments with low-level or non-N-rGOx decorated by maghemite particles show no rolling, indicating that the nitrogen defects are largely involved in the rolling mechanism. Different to earlier reports 18 and to theoretical predictions 14 , we show that the rolling process is fully reversible and that the N-rGOx can be fully transformed back to open graphene sheets by the removal of iron oxide particles through acid washing. We conclude that the rolling is initiated by the strong adsorption of maghemite nanoparticles at nitrogen defects in the graphene lattice and their mutual magnetic interaction. Our experimental observations are supported by ab initio density functional theory calculations. Results Physical properties of the nanoscrolls The basis of our study relies on attempts to decorate N-rGOx sheets by hematite and tungsten oxide nanoparticles to obtain materials appropriate for water oxidation. In the context of this work, we have come across a very peculiar effect. When the N-rGOx sheets unintentionally were decorated by maghemite nanoparticles, a metastable form of hematite that stabilizes under slightly different conditions, the micrographs of transmission electron microscopy (TEM) consistently revealed the presence of almost 100% of N-rGOx nanoscrolls instead of the commonly open N-rGOx sheets obtained by hematite decoration. Both hematite and maghemite have technologically interesting properties: hematite is used as catalyst for water oxidation 19 , 20 or as paint pigment, whereas maghemite is used as a contrast media in magnetic resonance or as magnetic recording media 21 . Despite many similarities, the two materials also display significant differences. Hematite crystallizes in a rhombohedral structure, whereas maghemite forms a cubic structure 21 , 22 . The difference in crystal structure rationalizes the magnetic properties of maghemite and hematite, where maghemite is ferrimagnetic and displays a much stronger magnetic moment (~540 mT) than the weakly ferromagnetic hematite (~1 mT). However, nanoparticles of both maghemite and hematite exhibit superparamagnetic behaviour, as each nanoparticle forms single magnetic domains 23 , 24 . We show in our study that the magnetically interacting maghemite particles and their strong adsorption on the N-rGOx sheets seem to be the main reasons for the formation of the N-rGOx nanoscrolls. The rolling mechanism of N-rGOx nanoscrolls is revealed by conducting a large number of control experiments to tune and test the synthesis conditions. The conditions leading to the highest ratio of, and most symmetric, nanoscrolls were achieved by adding iron(III) chloride, tungsten hexacarbonyl, and polyvinylpyrrolidone (PVP) and hydrazine into a N-rGOx methanol dispersion, followed by heating under reflux for 24 h (see Methods ). The scheme for the optimal conditions leading to nearly 100% (the only exception was some few very large graphene sheets, >5 μm) of N-rGOx nanoscrolls is shown in Fig. 1 (route a), together with the conditions used when hematite is formed and the decorated N-rGOx remain as open flat sheets ( Fig. 1 , route b). The formation of maghemite and hematite can be controlled by slight changes in the solution. When using a pure methanol solution, formation of maghemite particles is observed, whereas replacing a part of the methanol by water leads to the formation of hematite. Figure 1: Schematic process for the adsorption of iron oxide nanoparticles. (route<|im_end|> <|im_start|>assistant Researchers at Umea University, together with researchers at Uppsala University and Stockholm University, show in a new study how nitrogen doped graphene can be rolled into perfect Archimedean nano scrolls by adhering magnetic iron oxide nanoparticles on the surface of the graphene sheets. The new material may have very good properties for application as electrodes in for example Li-ion batteries. Graphene is one of the most interesting materials for future applications in everything from high performance electronics, optical components to flexible and strong materials. Ordinary graphene consists of carbon sheets that are single or few atomic layers thick. In the study the researchers have modified the graphene by replacing some of the carbon atoms by nitrogen atoms. By this method they obtain anchoring sites for the iron oxide nanoparticles that are decorated onto the graphene sheets in a solution process. In the decoration process one can control the type of iron oxide nanoparticles that are formed on the graphene surface, so that they either form so called hematite (the reddish form of iron oxide that often is found in nature) or maghemite, a less stable and more magnetic form of iron oxide. "Interestingly we observed that when the graphene is decorated by maghemite, the graphene sheets spontaneously start to roll into perfect Archimedean nano scrolls, while when decorated by the less magnetic hematite nanoparticles the graphene remain as open sheets, says Thomas Wågberg, Senior lecturer at the Department of Physics at Umeå University. Snapshot of a partially re-opened nanoscroll. The atomic layer thick graphene resembles a thin foil with some few wrinkles. The nanoscrolls can be visualized as traditional "Swiss rolls" where the sponge-cake represents the graphene, and the creamy filling is the iron oxide nanoparticles. The graphene nanoscrolls are however around one million times thinner. The results that now have been published in Nature Communications are conceptually interesting for several reasons. It shows that the magnetic interaction between the iron oxide nanoparticles is one of the main effects behind the scroll formation. It also shows that the nitrogen defects in the graphene lattice are necessary for both stabilizing a sufficiently high number of maghemite nanoparticles, and also responsible for "buckling" the graphene sheets and thereby lowering the formation energy of the nanoscrolls. The process is extraordinary efficient. Almost 100 percent of the graphene sheets are scrolled. After the decoration with maghemite particles the research team could not find any open graphene sheets. Moreover, they showed that by removing the iron oxide nanoparticles by acid treatment the nanoscrolls again open up and go back to single graphene sheets. "Besides adding valuable fundamental understanding in the physics and chemistry of graphene, nitrogen-doping and nanoparticles we have reasons to believe that the iron oxide decorated nitrogen doped graphene nanoscrolls have very good properties for application as electrodes in for example Li-ion batteries, one of the most important batteries in daily life electronics, " says Thomas Wågberg. The study has been conducted within the "The artificial leaf" project which is funded by Knut and Alice Wallenberg foundation to physicist, chemists, and plant science researchers at Umeå University. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 12441, 1994, 20622, 437, 15598, 82, 527, 9683, 76585, 5420, 10827, 18823, 1147, 14454, 555, 20700, 3254, 48435, 66192, 25112, 13, 11205, 5016, 6070, 3727, 1124, 7434, 1870, 7185, 323, 8830, 872, 18488, 6835, 3062, 2038, 389, 279, 34786, 323, 17910, 315, 5370, 12782, 51593, 47194, 13, 5810, 584, 1934, 264, 220, 1041, 4, 11297, 1920, 311, 5276, 47503, 1773, 16771, 11293, 66192, 51180, 25112, 1139, 87282, 20622, 437, 15598, 82, 555, 20841, 449, 24924, 63127, 12, 6251, 220, 17, 507, 220, 18, 94753, 13, 17331, 264, 3544, 1396, 315, 2585, 21896, 11, 24924, 60993, 315, 279, 37109, 94753, 11, 323, 671, 3003, 822, 29217, 11, 584, 32194, 430, 279, 20700, 374, 33230, 555, 279, 3831, 14058, 66181, 315, 4983, 30132, 635, 94753, 520, 47503, 42655, 304, 279, 66192, 55372, 323, 872, 27848, 24924, 16628, 13, 578, 20622, 437, 15598, 18488, 374, 7373, 81193, 323, 5304, 17065, 315, 279, 4983, 30132, 635, 94753, 11, 279, 20622, 437, 15598, 82, 471, 311, 1825, 25112, 13, 31909, 44413, 2038, 389, 279, 20700, 17383, 315, 66192, 20622, 437, 15598, 82, 11, 1057, 3135, 1101, 3493, 3062, 2038, 389, 279, 83938, 315, 11245, 51180, 94753, 13, 29438, 12441, 1994, 6108, 7384, 617, 22763, 439, 264, 1401, 3769, 304, 20622, 52536, 323, 31978, 1505, 502, 5789, 315, 8522, 220, 16, 1174, 220, 17, 1174, 220, 18, 1174, 220, 19, 1174, 220, 20, 662, 80569, 66192, 51180, 320, 81, 15881, 87, 8, 20622, 437, 15598, 82, 527, 502, 3697, 304, 279, 66192, 3070, 11, 14454, 555, 20700, 3254, 66192, 25112, 505, 832, 3185, 477, 505, 264, 9309, 311, 1376, 9683, 76585, 5420, 10827, 18823, 1147, 11, 810, 17037, 3967, 439, 30791, 28473, 13, 507, 24510, 311, 872, 5016, 6070, 11, 66192, 20622, 437, 15598, 82, 527, 19698, 311, 14389, 279, 9250, 1579, 6929, 685, 315, 3254, 66192, 25112, 220, 21, 662, 1115, 374, 304, 13168, 311, 3254, 2695, 4841, 12782, 20622, 354, 51725, 1405, 24693, 17413, 389, 279, 17130, 12330, 22124, 1304, 1124, 3060, 46258, 477, 5347, 1965, 1076, 287, 11, 11911, 389, 872, 23899, 323, 71546, 2786, 220, 22, 662, 43804, 449, 5016, 14683, 6012, 11, 279, 8475, 6324, 27032, 315, 20622, 437, 15598, 82, 2643, 2187, 369, 4907, 5942, 8522, 220, 23, 1174, 220, 24, 662, 18185, 27387, 6012, 323, 264, 23810, 315, 32887, 7978, 315, 66192, 20622, 437, 15598, 82, 220, 605, 1174, 220, 806, 1174, 220, 717, 1174, 220, 1032, 1174, 220, 975, 1174, 1193, 2478, 22772, 7978, 220, 868, 1174, 220, 845, 1174, 220, 1114, 1174, 220, 972, 527, 5068, 369, 436, 15881, 87, 20622, 437, 15598, 82, 13, 44847, 65130, 1880, 453, 662, 220, 1114, 8710, 430, 506, 8566, 7246, 315, 95273, 555, 58998, 8115, 37182, 8272, 555, 1633, 3831, 4538, 20901, 6197, 311, 279, 18488, 315, 20622, 437, 15598, 82, 11, 20444, 29346, 1880, 453, 662, 220, 972, 8710, 430, 279, 52729, 315, 4701, 19252, 389, 66192, 25112, 3871, 449, 1579, 27624, 4538, 20901, 33230, 279, 20700, 315, 279, 436, 15881, 87, 20622, 437, 15598, 82, 13, 4452, 11, 304, 7000, 315, 1521, 7978, 264, 17879, 16540, 374, 2728, 389, 1268, 323, 3249, 279, 66192, 25112, 1376, 23255, 14726, 11, 323, 449, 2478, 20157, 220, 868, 279, 15374, 374, 3428, 13, 5810, 584, 7664, 264, 4382, 323, 11297, 6425, 6108, 1920, 11, 23606, 291, 555, 264, 11944, 6492, 315, 279, 20700, 17383, 13, 1226, 1501, 430, 55443, 47503, 1773, 16771, 320, 1032, 11587, 436, 15881, 87, 8368, 3880, 15881, 87, 8, 20622, 437, 15598, 82, 527, 14454, 555, 49682, 452, 3880, 15881, 87, 449, 24924, 11245, 51180, 19252, 304, 279, 1376, 315, 4983, 30132, 635, 63127, 12, 6251, 220, 17, 507, 220, 18, 662, 763, 13168, 11, 584, 1501, 430, 264, 4528, 20841, 555, 2753, 24924, 96849, 635, 320, 19481, 12, 6251, 220, 17, 507, 220, 18, 883, 477, 2536, 1474, 39100, 67597, 13786, 51180, 19252, 2646, 11767, 311, 904, 20700, 13, 35339, 11, 2585, 21896, 449, 3428, 11852, 477, 2536, 11500, 3880, 15881, 87, 37109, 555, 4983, 30132, 635, 19252, 1501, 912, 20700, 11, 19392, 430, 279, 47503, 42655, 527, 14090, 6532, 304, 279, 20700, 17383, 13, 34496, 311, 6931, 6821, 220, 972, 323, 311, 32887, 20492, 220, 975, 1174, 584, 1501, 430, 279, 20700, 1920, 374, 7373, 81193, 323, 430, 279, 452, 3880, 15881, 87, 649, 387, 7373, 24411, 1203, 311, 1825, 66192, 25112, 555, 279, 17065, 315, 11245, 51180, 19252, 1555, 13935, 28786, 13, 1226, 32194, 430, 279, 20700, 374, 33230, 555, 279, 3831, 14058, 66181, 315, 4983, 30132, 635, 94753, 520, 47503, 42655, 304, 279, 66192, 55372, 323, 872, 27848, 24924, 16628, 13, 5751, 22772, 24654, 527, 7396, 555, 671, 3003, 822, 17915, 16003, 10334, 29217, 13, 18591, 28479, 6012, 315, 279, 20622, 437, 15598, 82, 578, 8197, 315, 1057, 4007, 34744, 389, 13865, 311, 57681, 452, 3880, 15881, 87, 25112, 555, 96849, 635, 323, 85307, 16172, 51180, 94753, 311, 6994, 7384, 8475, 369, 3090, 71162, 13, 763, 279, 2317, 315, 420, 990, 11, 584, 617, 2586, 4028, 264, 1633, 44797, 2515, 13, 3277, 279, 452, 3880, 15881, 87, 25112, 70576, 750, 1051, 37109, 555, 4983, 30132, 635, 94753, 11, 264, 68370, 481, 1376, 315, 96849, 635, 430, 27276, 4861, 1234, 10284, 2204, 4787, 11, 279, 8162, 87286, 315, 18874, 17130, 92914, 320, 21695, 8, 21356, 10675, 279, 9546, 315, 4661, 220, 1041, 4, 315, 452, 3880, 15881, 87, 20622, 437, 15598, 82, 4619, 315, 279, 17037, 1825, 452, 3880, 15881, 87, 25112, 12457, 555, 96849, 635, 20841, 13, 11995, 96849, 635, 323, 4983, 30132, 635, 617, 2869, 30450, 7185, 6012, 25, 96849, 635, 374, 1511, 439, 51483, 369, 3090, 71162, 220, 777, 1174, 220, 508, 477, 439, 6308, 77678, 11, 20444, 4983, 30132, 635, 374, 1511, 439, 264, 13168, 3772, 304, 24924, 58081, 477, 439, 24924, 14975, 3772, 220, 1691, 662, 18185, 1690, 43874, 11, 279, 1403, 7384, 1101, 3113, 5199, 12062, 13, 33924, 266, 635, 64568, 4861, 304, 264, 22408, 81487, 71, 36620, 6070, 11, 20444, 4983, 30132, 635, 7739, 264, 41999, 6070, 220, 1691, 1174, 220, 1313, 662, 578, 6811, 304, 26110, 6070, 25442, 4861, 279, 24924, 6012, 315, 4983, 30132, 635, 323, 96849, 635, 11, 1405, 4983, 30132, 635, 374, 58139, 318, 39100, 323, 19207, 264, 1790, 16643, 24924, 4545, 31857, 17048, 296, 51, 8, 1109, 279, 7621, 398, 18728, 442, 39100, 96849, 635, 31857, 16, 296, 51, 570, 4452, 11, 94753, 315, 2225, 4983, 30132, 635, 323, 96849, 635, 31324, 2307, 913, 39100, 17432, 11, 439, 1855, 76307, 7203, 7739, 3254, 24924, 31576, 220, 1419, 1174, 220, 1187, 662, 1226, 1501, 304, 1057, 4007, 430, 279, 33297, 2740, 45830, 4983, 30132, 635, 19252, 323, 872, 3831, 14058, 66181, 389, 279, 452, 3880, 15881, 87, 25112, 2873, 311, 387, 279, 1925, 8125, 369, 279, 18488, 315, 279, 452, 3880, 15881, 87, 20622, 437, 15598, 82, 13, 578, 20700, 17383, 315, 452, 3880, 15881, 87, 20622, 437, 15598, 82, 374, 10675, 555, 31474, 264, 3544, 1396, 315, 2585, 21896, 311, 26306, 323, 1296, 279, 39975, 4787, 13, 578, 4787, 6522, 311, 279, 8592, 11595, 315, 11, 323, 1455, 55443, 11, 20622, 437, 15598, 82, 1051, 17427, 555, 7999, 11245, 7, 23440, 8, 82882, 11, 85307, 16172, 12651, 582, 76370, 3633, 75, 11, 323, 10062, 9799, 4010, 3368, 81, 1098, 307, 606, 320, 47, 13683, 8, 323, 6409, 67, 8875, 483, 1139, 264, 452, 3880, 15881, 87, 21747, 39710, 86712, 11, 8272, 555, 24494, 1234, 93262, 369, 220, 1187, 305, 320, 4151, 19331, 7609, 578, 13155, 369, 279, 23669, 4787, 6522, 311, 7154, 220, 1041, 4, 320, 1820, 1193, 4788, 574, 1063, 2478, 1633, 3544, 66192, 25112, 11, 871, 20, 33983, 76, 8, 315, 452, 3880, 15881, 87, 20622, 437, 15598, 82, 374, 6982, 304, 23966, 13, 220, 16, 320, 9143, 264, 705, 3871, 449, 279, 4787, 1511, 994, 96849, 635, 374, 14454, 323, 279, 37109, 452, 3880, 15881, 87, 7293, 439, 1825, 10269, 25112, 320, 23966, 13, 220, 16, 1174, 6149, 293, 570, 578, 18488, 315, 4983, 30132, 635, 323, 96849, 635, 649, 387, 14400, 555, 8275, 4442, 304, 279, 6425, 13, 3277, 1701, 264, 10748, 21747, 39710, 6425, 11, 18488, 315, 4983, 30132, 635, 19252, 374, 13468, 11, 20444, 25935, 264, 961, 315, 279, 21747, 39710, 555, 3090, 11767, 311, 279, 18488, 315, 96849, 635, 13, 19575, 220, 16, 25, 328, 82149, 1920, 369, 279, 14058, 66181, 315, 11245, 51180, 94753, 13, 320, 9143, 128257, 198, 128256, 78191, 198, 60210, 520, 549, 2727, 64, 3907, 11, 3871, 449, 12074, 520, 549, 60643, 6181, 3907, 323, 53182, 3907, 11, 1501, 304, 264, 502, 4007, 1268, 47503, 294, 16771, 66192, 649, 387, 23255, 1139, 4832, 9683, 76585, 5420, 51593, 79664, 555, 36051, 287, 24924, 11245, 51180, 94753, 389, 279, 7479, 315, 279, 66192, 25112, 13, 578, 502, 3769, 1253, 617, 1633, 1695, 6012, 369, 3851, 439, 80390, 304, 369, 3187, 14851, 80846, 27360, 13, 12441, 1994, 374, 832, 315, 279, 1455, 7185, 7384, 369, 3938, 8522, 304, 4395, 505, 1579, 5178, 31591, 11, 29393, 6956, 311, 19303, 323, 3831, 7384, 13, 99011, 66192, 17610, 315, 12782, 25112, 430, 527, 3254, 477, 2478, 25524, 13931, 12314, 13, 763, 279, 4007, 279, 12074, 617, 11041, 279, 66192, 555, 25935, 1063, 315, 279, 12782, 33299, 555, 47503, 33299, 13, 3296, 420, 1749, 814, 6994, 34330, 5620, 6732, 369, 279, 11245, 51180, 94753, 430, 527, 37109, 8800, 279, 66192, 25112, 304, 264, 6425, 1920, 13, 763, 279, 20841, 1920, 832, 649, 2585, 279, 955, 315, 11245, 51180, 94753, 430, 527, 14454, 389, 279, 66192, 7479, 11, 779, 430, 814, 3060, 1376, 779, 2663, 96849, 635, 320, 1820, 63244, 819, 1376, 315, 11245, 51180, 430, 3629, 374, 1766, 304, 7138, 8, 477, 4983, 30132, 635, 11, 264, 2753, 15528, 323, 810, 24924, 1376, 315, 11245, 51180, 13, 330, 82990, 584, 13468, 430, 994, 279, 66192, 374, 37109, 555, 4983, 30132, 635, 11, 279, 66192, 25112, 88558, 1212, 311, 6638, 1139, 4832, 9683, 76585, 5420, 51593, 79664, 11, 1418, 994, 37109, 555, 279, 2753, 24924, 96849, 635, 94753, 279, 66192, 7293, 439, 1825, 25112, 11, 2795, 11355, 468, 3870, 70, 7881, 11, 19903, 72235, 520, 279, 6011, 315, 28415, 520, 549, 2727, 3870, 3907, 13, 69797, 315, 264, 26310, 312, 26770, 291, 20622, 437, 15598, 13, 578, 25524, 6324, 12314, 66192, 53291, 264, 15792, 47499, 449, 1063, 2478, 74207, 13, 578, 20622, 437, 15598, 82, 649, 387, 9302, 1534, 439, 8776, 330, 13521, 1056, 28473, 1, 1405, 279, 69448, 1824, 731, 11105, 279, 66192, 11, 323, 279, 47985, 21973, 374, 279, 11245, 51180, 94753, 13, 578, 66192, 20622, 437, 15598, 82, 527, 4869, 2212, 832, 3610, 3115, 65355, 13, 578, 3135, 430, 1457, 617, 1027, 4756, 304, 22037, 26545, 527, 7434, 1870, 7185, 369, 3892, 8125, 13, 1102, 5039, 430, 279, 24924, 16628, 1990, 279, 11245, 51180, 94753, 374, 832, 315, 279, 1925, 6372, 4920, 279, 9236, 18488, 13, 1102, 1101, 5039, 430, 279, 47503, 42655, 304, 279, 66192, 55372, 527, 5995, 369, 2225, 27276, 4954, 264, 40044, 1579, 1396, 315, 4983, 30132, 635, 94753, 11, 323, 1101, 8647, 369, 330, 65, 1983, 2785, 1, 279, 66192, 25112, 323, 28592, 46301, 279, 18488, 4907, 315, 279, 20622, 437, 15598, 82, 13, 578, 1920, 374, 24674, 11297, 13, 35403, 220, 1041, 3346, 315, 279, 66192, 25112, 527, 96719, 13, 4740, 279, 20841, 449, 4983, 30132, 635, 19252, 279, 3495, 2128, 1436, 539, 1505, 904, 1825, 66192, 25112, 13, 23674, 11, 814, 8710, 430, 555, 18054, 279, 11245, 51180, 94753, 555, 13935, 6514, 279, 20622, 437, 15598, 82, 1578, 1825, 709, 323, 733, 1203, 311, 3254, 66192, 25112, 13, 330, 52555, 7999, 15525, 16188, 8830, 304, 279, 22027, 323, 30903, 315, 66192, 11, 47503, 1773, 34807, 323, 94753, 584, 617, 8125, 311, 4510, 430, 279, 11245, 51180, 37109, 47503, 294, 16771, 66192, 20622, 437, 15598, 82, 617, 1633, 1695, 6012, 369, 3851, 439, 80390, 304, 369, 3187, 14851, 80846, 27360, 11, 832, 315, 279, 1455, 3062, 27360, 304, 7446, 2324, 31591, 11, 330, 2795, 11355, 468, 3870, 70, 7881, 13, 578, 4007, 706, 1027, 13375, 2949, 279, 330, 791, 21075, 16312, 1, 2447, 902, 374, 24853, 555, 13934, 332, 323, 30505, 9935, 56936, 16665, 311, 83323, 11, 8590, 1705, 11, 323, 6136, 8198, 12074, 520, 549, 2727, 3870, 3907, 13, 220, 128257, 198 ]

2,056

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Photothermal heating represents a major constraint that limits the performance of many nanoscale optoelectronic and optomechanical devices including nanolasers, quantum optomechanical resonators, and integrated photonic circuits. Here, we demonstrate the direct laser refrigeration of a semiconductor optomechanical resonator >20 K below room temperature based on the emission of upconverted, anti-Stokes photoluminescence of trivalent ytterbium ions doped within a yttrium-lithium-fluoride (YLF) host crystal. Optically-refrigerating the lattice of a dielectric resonator has the potential to impact several fields including scanning probe microscopy, the sensing of weak forces, the measurement of atomic masses, and the development of radiation-balanced solid-state lasers. In addition, optically refrigerated resonators may be used in the future as a promising starting point to perform motional cooling for exploration of quantum effects at mesoscopic length scales, temperature control within integrated photonic devices, and solid-state laser refrigeration of quantum materials. Introduction Photothermal heating is a perennial challenge in the development of advanced optical devices at nanometer length scales given that a material’s optical index of refraction, bandgap, and Young’s modulus all vary with temperature. For instance, reducing the mechanical motion of an optomechanical resonator to its quantum ground state requires that the temperature ( T ) must be much less than h ν / k B , where ν is the mode frequency, h and k B are Planck and Boltzmann constants, respectively 1 . Critically, incident laser irradiances must be kept low enough to avoid photothermal heating of the resonator above cryogenic temperatures 1 , 2 , 3 , 4 , 5 . Here, we demonstrate an approach for the photothermal cooling of nanoscale optoelectronic devices through the emission of anti-Stokes photoluminescence. In particular, we used a micrometer-scale grain of 10% Yb 3+ -doped YLiF 4 (Yb:YLF) located at the end of a semiconductor optomechanical resonator (CdS) to cool the resonator >20 K below room temperature following excitation with a continuous wave laser source with wavelength λ 0 = 1020 nm. The idea of refrigerating metallic sodium vapors using anti-Stokes luminescence was first proposed by Pringsheim in 1929 6 . Following the development of the laser, Doppler cooling of metallic vapors led to the first observation of Bose–Einstein condensates in 1995 7 . The first experimental report of solid-state laser cooling came in 1995 using Yb 3+ -doped ZBLANP glass (Yb:ZBLANP) 8 . Since then, two decades of research in the area of solid-state laser refrigeration has culminated in the development of a solid-state optical cryo-cooler with bulk Yb:YLF single crystals grown using the Czochralski method 9 , which has cooled crystals to 91 K from room temperature. The primary advantage of using crystalline materials for solid-state laser cooling is the existence of well-defined crystal-field levels, which minimizes inhomogenous broadening of rare-earth (RE) absorption spectra. Recently, this has enabled the first experimental demonstrations of cold Brownian motion 10 since Einstein’s seminal paper 11 on Brownian motion in 1905. The increased optical entropy of the blue-shifted photons makes this cooling cycle consistent with the second law of thermodynamics 12 . Recently, laser refrigeration of a macroscopic Czochralski grown Yb:YLF crystal was used to cool a semiconductor FTIR detector (HgCdTe) to 135 K 13 . In contrast, in this work the temperature of a nanoscale semiconductor optomechanical resonator (CdSNR) is reduced using laser refrigeration of a hydrothermally synthesized Yb:YLF microcrystal attached to it. The cooling of a load using a microscopic cooler enables local cooling. In addition, it also offers a route towards rapidly achieving a thermal steady (μs to ms scale) temperature state within nanoscale devices. The device is suspended in vacuum from a silicon wafer to reduce the potential for photothermal heating of the adjacent silicon substrate. Van der Waals bonding is used to attach a low-cost, hydrothermal ceramic Yb:YLF microcrystal 10 to the end of the resonator cavity. RE (Yb 3+ ) point-defects within the YLF emit anti-Stokes photoluminescence, which cools both the YLF microcrystal, and also the underlying semiconductor optomechanical resonator. The YLF serves both as a local thermometer (discussed in more detail below) and also as a heat sink, which extracts thermal energy from the cantilever, increasing its Young’s modulus, and thereby blue-shifting the cantilever’s optomechanical eigenfrequency. The transmitted laser causes minimal heating of the cantilever, supporting the YLF crystal owing to its small thickness (150 nm) and extremely low absorption coefficient of CdS at 1020 nm 14 . The temperature of the source and the cantilever system are measured using two independent non-contact temperature measurement methods—differential luminescence thermometry 15 and optomechanical thermometry 16 , respectively, which agree well with each other. The results below suggest several potential applications for using solid-state laser refrigeration to rapidly cool a wide range of materials used in scanning probe microscopy 17 , 18 , 19 , cavity optomechanics 2 , 5 , 20 , 21 , integrated photonics 22 , 23 , 24 , the sensing of small masses and weak forces 25 , 26 , 27 , 28 , quantum information science 29 , and radiation-balanced lasers 30 . Results Optomechanical thermometry A CdSNR was placed at the end of a clean silicon substrate, and a hydrothermally grown 10% Yb:YLF crystal was placed at the free end of the CdSNR cantilever. CdS was chosen because of its wide bandgap and low-cost, though in principle any material with low near-infrared (NIR) absorption can be used. A bright-field optical image of a representative sample is shown in Fig. 1b . The silicon substrate was loaded inside a cryostat chamber such that the free end of the cantilever was suspended over the axial hole in the cryostat, and the system was pumped to ~10 −4 Torr. As shown in Fig. 1a , a 1020-nm laser was focused onto the Yb:YLF crystal at the end of the cantilever. The time-dependent intensity of the forward-scattered 1020 nm laser was measured by focusing it onto an avalanche photodiode (APD). To measure the cantilever’s eigenfrequencies the voltage vs. time signal was Fourier-transformed to obtain its thermomechanical noise spectrum 31 , 32 . A representative power", "role": "user" }, { "content": "To the general public, lasers heat objects. And generally, that would be correct. But lasers also show promise to do quite the opposite—to cool materials. Lasers that can cool materials could revolutionize fields ranging from bio-imaging to quantum communication. In 2015, University of Washington researchers announced that they can use a laser to cool water and other liquids below room temperature. Now that same team has used a similar approach to refrigerate something quite different: A solid semiconductor. As the team shows in a paper published June 23 in Nature Communications, they could use an infrared laser to cool the solid semiconductor by at least 20 degrees C, or 36 F, below room temperature. The device is a cantilever—similar to a diving board. Like a diving board after a swimmer jumps off into the water, the cantilever can vibrate at a specific frequency. But this cantilever doesn't need a diver to vibrate. It can oscillate in response to thermal energy, or heat energy, at room temperature. Devices like these could make ideal optomechanical sensors, where their vibrations can be detected by a laser. But that laser also heats the cantilever, which dampens its performance. \"Historically, the laser heating of nanoscale devices was a major problem that was swept under the rug,\" said senior author Peter Pauzauskie, a UW professor of materials science and engineering and a senior scientist at the Pacific Northwest National Laboratory. \"We are using infrared light to cool the resonator, which reduces interference or 'noise' in the system. This method of solid-state refrigeration could significantly improve the sensitivity of optomechanical resonators, broaden their applications in consumer electronics, lasers and scientific instruments, and pave the way for new applications, such as photonic circuits.\" The team is the first to demonstrate \"solid-state laser refrigeration of nanoscale sensors,\" added Pauzauskie, who is also a faculty member at the UW Molecular Engineering & Sciences Institute and the UW Institute for Nano-engineered Systems. The results have wide potential applications due to both the improved performance of the resonator and the method used to cool it. The vibrations of semiconductor resonators have made them useful as mechanical sensors to detect acceleration, mass, temperature and other properties in a variety of electronics—such as accelerometers to detect the direction a smartphone is facing. Reduced interference could improve performance of these sensors. In addition, using a laser to cool the resonator is a much more targeted approach to improve sensor performance compared to trying to cool an entire sensor. In their experimental setup, a tiny ribbon, or nanoribbon, of cadmium sulfide extended from a block of silicon—and would naturally undergo thermal oscillation at room temperature. An image of the team's experimental setup, taken using a bright-field microscope. The silicon platform, labeled \"Si,\" is shown in white at the bottom of the image. The nanoribbon of cadmium sulfide is labeled \"CdSNR.\" At its tip is the ceramic crystal, labeled \"Yb:YLF.\" Scale bar is 20 micrometers. Credit: Pant et al. 2020, Nature Communications At the end of this diving board, the team placed a tiny ceramic crystal containing a specific type of impurity, ytterbium ions. When the team focused an infrared laser beam at the crystal, the impurities absorbed a small amount of energy from the crystal, causing it to glow in light that is shorter in wavelength than the laser color that excited it. This \"blueshift glow\" effect cooled the ceramic crystal and the semiconductor nanoribbon it was attached to. \"These crystals were carefully synthesized with a specific concentration of ytterbium to maximize the cooling efficiency,\" said co-author Xiaojing Xia, a UW doctoral student in molecular engineering. The researchers used two methods to measure how much the laser cooled the semiconductor. First, they observed changes to the oscillation frequency of the nanoribbon. \"The nanoribbon becomes more stiff and brittle after cooling—more resistant to bending and compression. As a result, it oscillates at a higher frequency, which verified that the laser had cooled the resonator,\" said Pauzauskie. The team also observed that the light emitted by the crystal shifted on average to longer wavelengths as they increased laser power, which also indicated cooling. Using these two methods, the researchers calculated that the resonator's temperature had dropped by as much as 20 degrees C below room temperature. The refrigeration effect took less than 1 millisecond and lasted as long as the excitation laser was on. \"In the coming years, I will eagerly look to see our laser cooling technology adapted by scientists from various fields to enhance the performance of quantum sensors,\" said lead author Anupum Pant, a UW doctoral student in materials science and engineering. Researchers say the method has other potential applications. It could form the heart of highly precise scientific instruments, using changes in oscillations of the resonator to accurately measure an object's mass, such as a single virus particle. Lasers that cool solid components could also be used to develop cooling systems that keep key components in electronic systems from overheating. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Photothermal heating represents a major constraint that limits the performance of many nanoscale optoelectronic and optomechanical devices including nanolasers, quantum optomechanical resonators, and integrated photonic circuits. Here, we demonstrate the direct laser refrigeration of a semiconductor optomechanical resonator >20 K below room temperature based on the emission of upconverted, anti-Stokes photoluminescence of trivalent ytterbium ions doped within a yttrium-lithium-fluoride (YLF) host crystal. Optically-refrigerating the lattice of a dielectric resonator has the potential to impact several fields including scanning probe microscopy, the sensing of weak forces, the measurement of atomic masses, and the development of radiation-balanced solid-state lasers. In addition, optically refrigerated resonators may be used in the future as a promising starting point to perform motional cooling for exploration of quantum effects at mesoscopic length scales, temperature control within integrated photonic devices, and solid-state laser refrigeration of quantum materials. Introduction Photothermal heating is a perennial challenge in the development of advanced optical devices at nanometer length scales given that a material’s optical index of refraction, bandgap, and Young’s modulus all vary with temperature. For instance, reducing the mechanical motion of an optomechanical resonator to its quantum ground state requires that the temperature ( T ) must be much less than h ν / k B , where ν is the mode frequency, h and k B are Planck and Boltzmann constants, respectively 1 . Critically, incident laser irradiances must be kept low enough to avoid photothermal heating of the resonator above cryogenic temperatures 1 , 2 , 3 , 4 , 5 . Here, we demonstrate an approach for the photothermal cooling of nanoscale optoelectronic devices through the emission of anti-Stokes photoluminescence. In particular, we used a micrometer-scale grain of 10% Yb 3+ -doped YLiF 4 (Yb:YLF) located at the end of a semiconductor optomechanical resonator (CdS) to cool the resonator >20 K below room temperature following excitation with a continuous wave laser source with wavelength λ 0 = 1020 nm. The idea of refrigerating metallic sodium vapors using anti-Stokes luminescence was first proposed by Pringsheim in 1929 6 . Following the development of the laser, Doppler cooling of metallic vapors led to the first observation of Bose–Einstein condensates in 1995 7 . The first experimental report of solid-state laser cooling came in 1995 using Yb 3+ -doped ZBLANP glass (Yb:ZBLANP) 8 . Since then, two decades of research in the area of solid-state laser refrigeration has culminated in the development of a solid-state optical cryo-cooler with bulk Yb:YLF single crystals grown using the Czochralski method 9 , which has cooled crystals to 91 K from room temperature. The primary advantage of using crystalline materials for solid-state laser cooling is the existence of well-defined crystal-field levels, which minimizes inhomogenous broadening of rare-earth (RE) absorption spectra. Recently, this has enabled the first experimental demonstrations of cold Brownian motion 10 since Einstein’s seminal paper 11 on Brownian motion in 1905. The increased optical entropy of the blue-shifted photons makes this cooling cycle consistent with the second law of thermodynamics 12 . Recently, laser refrigeration of a macroscopic Czochralski grown Yb:YLF crystal was used to cool a semiconductor FTIR detector (HgCdTe) to 135 K 13 . In contrast, in this work the temperature of a nanoscale semiconductor optomechanical resonator (CdSNR) is reduced using laser refrigeration of a hydrothermally synthesized Yb:YLF microcrystal attached to it. The cooling of a load using a microscopic cooler enables local cooling. In addition, it also offers a route towards rapidly achieving a thermal steady (μs to ms scale) temperature state within nanoscale devices. The device is suspended in vacuum from a silicon wafer to reduce the potential for photothermal heating of the adjacent silicon substrate. Van der Waals bonding is used to attach a low-cost, hydrothermal ceramic Yb:YLF microcrystal 10 to the end of the resonator cavity. RE (Yb 3+ ) point-defects within the YLF emit anti-Stokes photoluminescence, which cools both the YLF microcrystal, and also the underlying semiconductor optomechanical resonator. The YLF serves both as a local thermometer (discussed in more detail below) and also as a heat sink, which extracts thermal energy from the cantilever, increasing its Young’s modulus, and thereby blue-shifting the cantilever’s optomechanical eigenfrequency. The transmitted laser causes minimal heating of the cantilever, supporting the YLF crystal owing to its small thickness (150 nm) and extremely low absorption coefficient of CdS at 1020 nm 14 . The temperature of the source and the cantilever system are measured using two independent non-contact temperature measurement methods—differential luminescence thermometry 15 and optomechanical thermometry 16 , respectively, which agree well with each other. The results below suggest several potential applications for using solid-state laser refrigeration to rapidly cool a wide range of materials used in scanning probe microscopy 17 , 18 , 19 , cavity optomechanics 2 , 5 , 20 , 21 , integrated photonics 22 , 23 , 24 , the sensing of small masses and weak forces 25 , 26 , 27 , 28 , quantum information science 29 , and radiation-balanced lasers 30 . Results Optomechanical thermometry A CdSNR was placed at the end of a clean silicon substrate, and a hydrothermally grown 10% Yb:YLF crystal was placed at the free end of the CdSNR cantilever. CdS was chosen because of its wide bandgap and low-cost, though in principle any material with low near-infrared (NIR) absorption can be used. A bright-field optical image of a representative sample is shown in Fig. 1b . The silicon substrate was loaded inside a cryostat chamber such that the free end of the cantilever was suspended over the axial hole in the cryostat, and the system was pumped to ~10 −4 Torr. As shown in Fig. 1a , a 1020-nm laser was focused onto the Yb:YLF crystal at the end of the cantilever. The time-dependent intensity of the forward-scattered 1020 nm laser was measured by focusing it onto an avalanche photodiode (APD). To measure the cantilever’s eigenfrequencies the voltage vs. time signal was Fourier-transformed to obtain its thermomechanical noise spectrum 31 , 32 . A representative power<|im_end|> <|im_start|>assistant To the general public, lasers heat objects. And generally, that would be correct. But lasers also show promise to do quite the opposite—to cool materials. Lasers that can cool materials could revolutionize fields ranging from bio-imaging to quantum communication. In 2015, University of Washington researchers announced that they can use a laser to cool water and other liquids below room temperature. Now that same team has used a similar approach to refrigerate something quite different: A solid semiconductor. As the team shows in a paper published June 23 in Nature Communications, they could use an infrared laser to cool the solid semiconductor by at least 20 degrees C, or 36 F, below room temperature. The device is a cantilever—similar to a diving board. Like a diving board after a swimmer jumps off into the water, the cantilever can vibrate at a specific frequency. But this cantilever doesn't need a diver to vibrate. It can oscillate in response to thermal energy, or heat energy, at room temperature. Devices like these could make ideal optomechanical sensors, where their vibrations can be detected by a laser. But that laser also heats the cantilever, which dampens its performance. "Historically, the laser heating of nanoscale devices was a major problem that was swept under the rug," said senior author Peter Pauzauskie, a UW professor of materials science and engineering and a senior scientist at the Pacific Northwest National Laboratory. "We are using infrared light to cool the resonator, which reduces interference or 'noise' in the system. This method of solid-state refrigeration could significantly improve the sensitivity of optomechanical resonators, broaden their applications in consumer electronics, lasers and scientific instruments, and pave the way for new applications, such as photonic circuits." The team is the first to demonstrate "solid-state laser refrigeration of nanoscale sensors," added Pauzauskie, who is also a faculty member at the UW Molecular Engineering & Sciences Institute and the UW Institute for Nano-engineered Systems. The results have wide potential applications due to both the improved performance of the resonator and the method used to cool it. The vibrations of semiconductor resonators have made them useful as mechanical sensors to detect acceleration, mass, temperature and other properties in a variety of electronics—such as accelerometers to detect the direction a smartphone is facing. Reduced interference could improve performance of these sensors. In addition, using a laser to cool the resonator is a much more targeted approach to improve sensor performance compared to trying to cool an entire sensor. In their experimental setup, a tiny ribbon, or nanoribbon, of cadmium sulfide extended from a block of silicon—and would naturally undergo thermal oscillation at room temperature. An image of the team's experimental setup, taken using a bright-field microscope. The silicon platform, labeled "Si," is shown in white at the bottom of the image. The nanoribbon of cadmium sulfide is labeled "CdSNR." At its tip is the ceramic crystal, labeled "Yb:YLF." Scale bar is 20 micrometers. Credit: Pant et al. 2020, Nature Communications At the end of this diving board, the team placed a tiny ceramic crystal containing a specific type of impurity, ytterbium ions. When the team focused an infrared laser beam at the crystal, the impurities absorbed a small amount of energy from the crystal, causing it to glow in light that is shorter in wavelength than the laser color that excited it. This "blueshift glow" effect cooled the ceramic crystal and the semiconductor nanoribbon it was attached to. "These crystals were carefully synthesized with a specific concentration of ytterbium to maximize the cooling efficiency," said co-author Xiaojing Xia, a UW doctoral student in molecular engineering. The researchers used two methods to measure how much the laser cooled the semiconductor. First, they observed changes to the oscillation frequency of the nanoribbon. "The nanoribbon becomes more stiff and brittle after cooling—more resistant to bending and compression. As a result, it oscillates at a higher frequency, which verified that the laser had cooled the resonator," said Pauzauskie. The team also observed that the light emitted by the crystal shifted on average to longer wavelengths as they increased laser power, which also indicated cooling. Using these two methods, the researchers calculated that the resonator's temperature had dropped by as much as 20 degrees C below room temperature. The refrigeration effect took less than 1 millisecond and lasted as long as the excitation laser was on. "In the coming years, I will eagerly look to see our laser cooling technology adapted by scientists from various fields to enhance the performance of quantum sensors," said lead author Anupum Pant, a UW doctoral student in materials science and engineering. Researchers say the method has other potential applications. It could form the heart of highly precise scientific instruments, using changes in oscillations of the resonator to accurately measure an object's mass, such as a single virus particle. Lasers that cool solid components could also be used to develop cooling systems that keep key components in electronic systems from overheating. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 18235, 91096, 24494, 11105, 264, 3682, 22295, 430, 13693, 279, 5178, 315, 1690, 20622, 437, 2296, 3469, 4748, 772, 8535, 323, 3469, 638, 5776, 950, 7766, 2737, 20622, 19736, 388, 11, 31228, 3469, 638, 5776, 950, 29280, 3046, 11, 323, 18751, 4604, 14338, 46121, 13, 5810, 11, 584, 20461, 279, 2167, 21120, 30477, 367, 315, 264, 87836, 3469, 638, 5776, 950, 29280, 859, 871, 508, 735, 3770, 3130, 9499, 3196, 389, 279, 41353, 315, 709, 77304, 11, 7294, 40720, 8099, 4604, 1152, 1572, 36634, 315, 490, 12031, 69853, 466, 65, 2411, 65125, 294, 16771, 2949, 264, 69853, 376, 2411, 2922, 411, 2411, 12556, 84, 269, 579, 320, 56, 23433, 8, 3552, 26110, 13, 16963, 2740, 44107, 65044, 1113, 279, 55372, 315, 264, 2815, 47262, 29280, 859, 706, 279, 4754, 311, 5536, 3892, 5151, 2737, 36201, 22477, 92914, 11, 279, 60199, 315, 7621, 8603, 11, 279, 19179, 315, 25524, 32738, 11, 323, 279, 4500, 315, 25407, 84225, 4979, 6573, 21395, 72475, 13, 763, 5369, 11, 3469, 2740, 30477, 660, 29280, 3046, 1253, 387, 1511, 304, 279, 3938, 439, 264, 26455, 6041, 1486, 311, 2804, 3937, 4001, 28015, 369, 27501, 315, 31228, 6372, 520, 11083, 84667, 3160, 29505, 11, 9499, 2585, 2949, 18751, 4604, 14338, 7766, 11, 323, 6573, 21395, 21120, 30477, 367, 315, 31228, 7384, 13, 29438, 18235, 91096, 24494, 374, 264, 74718, 8815, 304, 279, 4500, 315, 11084, 29393, 7766, 520, 20622, 21037, 3160, 29505, 2728, 430, 264, 3769, 753, 29393, 1963, 315, 2098, 16597, 11, 7200, 42510, 11, 323, 13566, 753, 75124, 682, 13592, 449, 9499, 13, 1789, 2937, 11, 18189, 279, 22936, 11633, 315, 459, 3469, 638, 5776, 950, 29280, 859, 311, 1202, 31228, 5015, 1614, 7612, 430, 279, 9499, 320, 350, 883, 2011, 387, 1790, 2753, 1109, 305, 99786, 611, 597, 426, 1174, 1405, 99786, 374, 279, 3941, 11900, 11, 305, 323, 597, 426, 527, 9878, 377, 323, 47047, 89, 18022, 18508, 11, 15947, 220, 16, 662, 34307, 2740, 11, 10672, 21120, 37819, 10272, 1634, 2011, 387, 8774, 3428, 3403, 311, 5766, 4604, 91096, 24494, 315, 279, 29280, 859, 3485, 16106, 29569, 20472, 220, 16, 1174, 220, 17, 1174, 220, 18, 1174, 220, 19, 1174, 220, 20, 662, 5810, 11, 584, 20461, 459, 5603, 369, 279, 4604, 91096, 28015, 315, 20622, 437, 2296, 3469, 4748, 772, 8535, 7766, 1555, 279, 41353, 315, 7294, 40720, 8099, 4604, 1152, 1572, 36634, 13, 763, 4040, 11, 584, 1511, 264, 19748, 88371, 13230, 24875, 315, 220, 605, 4, 816, 65, 220, 18, 10, 482, 67, 16771, 816, 46521, 37, 220, 19, 320, 56, 65, 25, 56, 23433, 8, 7559, 520, 279, 842, 315, 264, 87836, 3469, 638, 5776, 950, 29280, 859, 320, 91300, 50, 8, 311, 7155, 279, 29280, 859, 871, 508, 735, 3770, 3130, 9499, 2768, 3521, 7709, 449, 264, 19815, 12330, 21120, 2592, 449, 46406, 49438, 220, 15, 284, 220, 4278, 15, 26807, 13, 578, 4623, 315, 30477, 1113, 46258, 39695, 68857, 1105, 1701, 7294, 40720, 8099, 41263, 1572, 36634, 574, 1176, 11223, 555, 2394, 826, 21215, 304, 220, 5926, 24, 220, 21, 662, 23548, 279, 4500, 315, 279, 21120, 11, 97674, 13206, 28015, 315, 46258, 68857, 1105, 6197, 311, 279, 1176, 22695, 315, 94558, 4235, 36, 37494, 9955, 729, 988, 304, 220, 2550, 20, 220, 22, 662, 578, 1176, 22772, 1934, 315, 6573, 21395, 21120, 28015, 3782, 304, 220, 2550, 20, 1701, 816, 65, 220, 18, 10, 482, 67, 16771, 1901, 9574, 1111, 47, 9168, 320, 56, 65, 25, 57, 9574, 1111, 47, 8, 220, 23, 662, 8876, 1243, 11, 1403, 11026, 315, 3495, 304, 279, 3158, 315, 6573, 21395, 21120, 30477, 367, 706, 11957, 52299, 304, 279, 4500, 315, 264, 6573, 21395, 29393, 16106, 78, 23283, 22847, 449, 20155, 816, 65, 25, 56, 23433, 3254, 48473, 15042, 1701, 279, 123203, 5059, 81, 1147, 6780, 1749, 220, 24, 1174, 902, 706, 65410, 48473, 311, 220, 5925, 735, 505, 3130, 9499, 13, 578, 6156, 9610, 315, 1701, 64568, 483, 7384, 369, 6573, 21395, 21120, 28015, 374, 279, 14209, 315, 1664, 39817, 26110, 19677, 5990, 11, 902, 21877, 4861, 304, 35940, 53595, 7353, 6147, 315, 9024, 86187, 320, 793, 8, 44225, 63697, 13, 42096, 11, 420, 706, 9147, 279, 1176, 22772, 44895, 315, 9439, 10690, 1122, 11633, 220, 605, 2533, 55152, 753, 90773, 5684, 220, 806, 389, 10690, 1122, 11633, 304, 220, 7028, 20, 13, 578, 7319, 29393, 48602, 315, 279, 6437, 91043, 291, 89235, 3727, 420, 28015, 11008, 13263, 449, 279, 2132, 2383, 315, 30945, 80011, 220, 717, 662, 42096, 11, 21120, 30477, 367, 315, 264, 18563, 58510, 123203, 5059, 81, 1147, 6780, 15042, 816, 65, 25, 56, 23433, 26110, 574, 1511, 311, 7155, 264, 87836, 24182, 2871, 32314, 320, 39, 70, 91300, 6777, 8, 311, 220, 8878, 735, 220, 1032, 662, 763, 13168, 11, 304, 420, 990, 279, 9499, 315, 264, 20622, 437, 2296, 87836, 3469, 638, 5776, 950, 29280, 859, 320, 91300, 19503, 49, 8, 374, 11293, 1701, 21120, 30477, 367, 315, 264, 17055, 700, 76, 750, 92106, 816, 65, 25, 56, 23433, 8162, 5192, 14272, 12673, 311, 433, 13, 578, 28015, 315, 264, 2865, 1701, 264, 90090, 36921, 20682, 2254, 28015, 13, 763, 5369, 11, 433, 1101, 6209, 264, 6149, 7119, 19019, 32145, 264, 29487, 24981, 320, 44223, 82, 311, 10030, 5569, 8, 9499, 1614, 2949, 20622, 437, 2296, 7766, 13, 578, 3756, 374, 22340, 304, 29302, 505, 264, 51692, 10667, 809, 311, 8108, 279, 4754, 369, 4604, 91096, 24494, 315, 279, 24894, 51692, 54057, 13, 13000, 2761, 29614, 1147, 64186, 374, 1511, 311, 15866, 264, 3428, 41238, 11, 17055, 69218, 43124, 816, 65, 25, 56, 23433, 8162, 5192, 14272, 220, 605, 311, 279, 842, 315, 279, 29280, 859, 56429, 13, 3680, 320, 56, 65, 220, 18, 10, 883, 1486, 29899, 115192, 2949, 279, 816, 23433, 17105, 7294, 40720, 8099, 4604, 1152, 1572, 36634, 11, 902, 1080, 3145, 2225, 279, 816, 23433, 8162, 5192, 14272, 11, 323, 1101, 279, 16940, 87836, 3469, 638, 5776, 950, 29280, 859, 13, 578, 816, 23433, 17482, 2225, 439, 264, 2254, 93297, 320, 17242, 59942, 304, 810, 7872, 3770, 8, 323, 1101, 439, 264, 8798, 19868, 11, 902, 49062, 29487, 4907, 505, 279, 16869, 458, 424, 11, 7859, 1202, 13566, 753, 75124, 11, 323, 28592, 6437, 7666, 18148, 279, 16869, 458, 424, 753, 3469, 638, 5776, 950, 29824, 47621, 13, 578, 34699, 21120, 11384, 17832, 24494, 315, 279, 16869, 458, 424, 11, 12899, 279, 816, 23433, 26110, 56612, 311, 1202, 2678, 26839, 320, 3965, 26807, 8, 323, 9193, 3428, 44225, 36706, 315, 85090, 50, 520, 220, 4278, 15, 26807, 220, 975, 662, 578, 9499, 315, 279, 2592, 323, 279, 16869, 458, 424, 1887, 527, 17303, 1701, 1403, 9678, 2536, 54096, 9499, 19179, 5528, 2345, 67, 69757, 41263, 1572, 36634, 30945, 7133, 220, 868, 323, 3469, 638, 5776, 950, 30945, 7133, 220, 845, 1174, 15947, 11, 902, 7655, 1664, 449, 1855, 1023, 13, 578, 3135, 3770, 4284, 3892, 4754, 8522, 369, 1701, 6573, 21395, 21120, 30477, 367, 311, 19019, 7155, 264, 7029, 2134, 315, 7384, 1511, 304, 36201, 22477, 92914, 220, 1114, 1174, 220, 972, 1174, 220, 777, 1174, 56429, 3469, 638, 5776, 1233, 220, 17, 1174, 220, 20, 1174, 220, 508, 1174, 220, 1691, 1174, 18751, 69010, 1233, 220, 1313, 1174, 220, 1419, 1174, 220, 1187, 1174, 279, 60199, 315, 2678, 32738, 323, 7621, 8603, 220, 914, 1174, 220, 1627, 1174, 220, 1544, 1174, 220, 1591, 1174, 31228, 2038, 8198, 220, 1682, 1174, 323, 25407, 84225, 4979, 72475, 220, 966, 662, 18591, 16963, 638, 5776, 950, 30945, 7133, 362, 85090, 19503, 49, 574, 9277, 520, 279, 842, 315, 264, 4335, 51692, 54057, 11, 323, 264, 17055, 700, 76, 750, 15042, 220, 605, 4, 816, 65, 25, 56, 23433, 26110, 574, 9277, 520, 279, 1949, 842, 315, 279, 85090, 19503, 49, 16869, 458, 424, 13, 85090, 50, 574, 12146, 1606, 315, 1202, 7029, 7200, 42510, 323, 3428, 41238, 11, 3582, 304, 17966, 904, 3769, 449, 3428, 3221, 3502, 82482, 320, 45, 2871, 8, 44225, 649, 387, 1511, 13, 362, 10107, 19677, 29393, 2217, 315, 264, 18740, 6205, 374, 6982, 304, 23966, 13, 220, 16, 65, 662, 578, 51692, 54057, 574, 6799, 4871, 264, 16106, 109524, 25199, 1778, 430, 279, 1949, 842, 315, 279, 16869, 458, 424, 574, 22340, 927, 279, 98280, 14512, 304, 279, 16106, 109524, 11, 323, 279, 1887, 574, 62454, 311, 4056, 605, 25173, 19, 8611, 81, 13, 1666, 6982, 304, 23966, 13, 220, 16, 64, 1174, 264, 220, 4278, 15, 5392, 76, 21120, 574, 10968, 8800, 279, 816, 65, 25, 56, 23433, 26110, 520, 279, 842, 315, 279, 16869, 458, 424, 13, 578, 892, 43918, 21261, 315, 279, 4741, 31419, 22688, 220, 4278, 15, 26807, 21120, 574, 17303, 555, 21760, 433, 8800, 459, 96694, 4604, 31559, 536, 320, 2599, 35, 570, 2057, 6767, 279, 16869, 458, 424, 753, 29824, 69, 72831, 279, 22465, 6296, 13, 892, 8450, 574, 90054, 33952, 291, 311, 6994, 1202, 30945, 638, 5776, 950, 12248, 20326, 220, 2148, 1174, 220, 843, 662, 362, 18740, 2410, 128257, 198, 128256, 78191, 198, 1271, 279, 4689, 586, 11, 72475, 8798, 6302, 13, 1628, 8965, 11, 430, 1053, 387, 4495, 13, 2030, 72475, 1101, 1501, 11471, 311, 656, 5115, 279, 14329, 50617, 7155, 7384, 13, 16132, 388, 430, 649, 7155, 7384, 1436, 14110, 553, 5151, 24950, 505, 17332, 38025, 4210, 311, 31228, 10758, 13, 763, 220, 679, 20, 11, 3907, 315, 6652, 12074, 7376, 430, 814, 649, 1005, 264, 21120, 311, 7155, 3090, 323, 1023, 67849, 3770, 3130, 9499, 13, 4800, 430, 1890, 2128, 706, 1511, 264, 4528, 5603, 311, 30477, 349, 2555, 5115, 2204, 25, 362, 6573, 87836, 13, 1666, 279, 2128, 5039, 304, 264, 5684, 4756, 5651, 220, 1419, 304, 22037, 26545, 11, 814, 1436, 1005, 459, 59141, 21120, 311, 7155, 279, 6573, 87836, 555, 520, 3325, 220, 508, 12628, 356, 11, 477, 220, 1927, 435, 11, 3770, 3130, 9499, 13, 578, 3756, 374, 264, 16869, 458, 424, 2345, 65387, 311, 264, 43515, 4580, 13, 9086, 264, 43515, 4580, 1306, 264, 16587, 1195, 35308, 1022, 1139, 279, 3090, 11, 279, 16869, 458, 424, 649, 348, 44192, 520, 264, 3230, 11900, 13, 2030, 420, 16869, 458, 424, 3250, 956, 1205, 264, 37441, 311, 348, 44192, 13, 1102, 649, 43524, 349, 304, 2077, 311, 29487, 4907, 11, 477, 8798, 4907, 11, 520, 3130, 9499, 13, 41477, 1093, 1521, 1436, 1304, 10728, 3469, 638, 5776, 950, 26148, 11, 1405, 872, 78352, 649, 387, 16914, 555, 264, 21120, 13, 2030, 430, 21120, 1101, 77662, 279, 16869, 458, 424, 11, 902, 41369, 729, 1202, 5178, 13, 330, 50083, 2740, 11, 279, 21120, 24494, 315, 20622, 437, 2296, 7766, 574, 264, 3682, 3575, 430, 574, 41323, 1234, 279, 29742, 1359, 1071, 10195, 3229, 11291, 393, 2933, 4458, 355, 31422, 11, 264, 66716, 14561, 315, 7384, 8198, 323, 15009, 323, 264, 10195, 28568, 520, 279, 16867, 40505, 5165, 32184, 13, 330, 1687, 527, 1701, 59141, 3177, 311, 7155, 279, 29280, 859, 11, 902, 26338, 32317, 477, 364, 53318, 6, 304, 279, 1887, 13, 1115, 1749, 315, 6573, 21395, 30477, 367, 1436, 12207, 7417, 279, 27541, 315, 3469, 638, 5776, 950, 29280, 3046, 11, 84713, 872, 8522, 304, 11761, 31591, 11, 72475, 323, 12624, 24198, 11, 323, 94123, 279, 1648, 369, 502, 8522, 11, 1778, 439, 4604, 14338, 46121, 1210, 578, 2128, 374, 279, 1176, 311, 20461, 330, 32127, 21395, 21120, 30477, 367, 315, 20622, 437, 2296, 26148, 1359, 3779, 393, 2933, 4458, 355, 31422, 11, 889, 374, 1101, 264, 22291, 4562, 520, 279, 66716, 60825, 17005, 612, 23199, 10181, 323, 279, 66716, 10181, 369, 64051, 50725, 12616, 15264, 13, 578, 3135, 617, 7029, 4754, 8522, 4245, 311, 2225, 279, 13241, 5178, 315, 279, 29280, 859, 323, 279, 1749, 1511, 311, 7155, 433, 13, 578, 78352, 315, 87836, 29280, 3046, 617, 1903, 1124, 5505, 439, 22936, 26148, 311, 11388, 31903, 11, 3148, 11, 9499, 323, 1023, 6012, 304, 264, 8205, 315, 31591, 2345, 21470, 439, 14511, 33504, 311, 11388, 279, 5216, 264, 22234, 374, 13176, 13, 80569, 32317, 1436, 7417, 5178, 315, 1521, 26148, 13, 763, 5369, 11, 1701, 264, 21120, 311, 7155, 279, 29280, 859, 374, 264, 1790, 810, 17550, 5603, 311, 7417, 12271, 5178, 7863, 311, 4560, 311, 7155, 459, 4553, 12271, 13, 763, 872, 22772, 6642, 11, 264, 13987, 45667, 11, 477, 20622, 269, 36180, 11, 315, 19973, 51318, 40769, 579, 11838, 505, 264, 2565, 315, 51692, 17223, 1053, 18182, 37771, 29487, 43524, 367, 520, 3130, 9499, 13, 1556, 2217, 315, 279, 2128, 596, 22772, 6642, 11, 4529, 1701, 264, 10107, 19677, 73757, 13, 578, 51692, 5452, 11, 30929, 330, 22771, 1359, 374, 6982, 304, 4251, 520, 279, 5740, 315, 279, 2217, 13, 578, 20622, 269, 36180, 315, 19973, 51318, 40769, 579, 374, 30929, 330, 91300, 19503, 49, 1210, 2468, 1202, 11813, 374, 279, 43124, 26110, 11, 30929, 330, 56, 65, 25, 56, 23433, 1210, 25635, 3703, 374, 220, 508, 19748, 442, 2481, 13, 16666, 25, 54222, 1880, 453, 13, 220, 2366, 15, 11, 22037, 26545, 2468, 279, 842, 315, 420, 43515, 4580, 11, 279, 2128, 9277, 264, 13987, 43124, 26110, 8649, 264, 3230, 955, 315, 3242, 5631, 11, 69853, 466, 65, 2411, 65125, 13, 3277, 279, 2128, 10968, 459, 59141, 21120, 24310, 520, 279, 26110, 11, 279, 3242, 38333, 42101, 264, 2678, 3392, 315, 4907, 505, 279, 26110, 11, 14718, 433, 311, 37066, 304, 3177, 430, 374, 24210, 304, 46406, 1109, 279, 21120, 1933, 430, 12304, 433, 13, 1115, 330, 2067, 1157, 48933, 37066, 1, 2515, 65410, 279, 43124, 26110, 323, 279, 87836, 20622, 269, 36180, 433, 574, 12673, 311, 13, 330, 9673, 48473, 1051, 15884, 92106, 449, 264, 3230, 20545, 315, 69853, 466, 65, 2411, 311, 35608, 279, 28015, 15374, 1359, 1071, 1080, 43802, 41235, 21963, 287, 41235, 11, 264, 66716, 74657, 5575, 304, 31206, 15009, 13, 578, 12074, 1511, 1403, 5528, 311, 6767, 1268, 1790, 279, 21120, 65410, 279, 87836, 13, 5629, 11, 814, 13468, 4442, 311, 279, 43524, 367, 11900, 315, 279, 20622, 269, 36180, 13, 330, 791, 20622, 269, 36180, 9221, 810, 31161, 323, 95749, 1306, 28015, 2345, 6518, 31785, 311, 58218, 323, 26168, 13, 1666, 264, 1121, 11, 433, 43524, 988, 520, 264, 5190, 11900, 11, 902, 24884, 430, 279, 21120, 1047, 65410, 279, 29280, 859, 1359, 1071, 393, 2933, 4458, 355, 31422, 13, 578, 2128, 1101, 13468, 430, 279, 3177, 48042, 555, 279, 26110, 30073, 389, 5578, 311, 5129, 93959, 439, 814, 7319, 21120, 2410, 11, 902, 1101, 16717, 28015, 13, 12362, 1521, 1403, 5528, 11, 279, 12074, 16997, 430, 279, 29280, 859, 596, 9499, 1047, 12504, 555, 439, 1790, 439, 220, 508, 12628, 356, 3770, 3130, 9499, 13, 578, 30477, 367, 2515, 3952, 2753, 1109, 220, 16, 2606, 46966, 323, 36513, 439, 1317, 439, 279, 3521, 7709, 21120, 574, 389, 13, 330, 644, 279, 5108, 1667, 11, 358, 690, 63473, 1427, 311, 1518, 1057, 21120, 28015, 5557, 30464, 555, 14248, 505, 5370, 5151, 311, 18885, 279, 5178, 315, 31228, 26148, 1359, 1071, 3063, 3229, 1556, 455, 372, 54222, 11, 264, 66716, 74657, 5575, 304, 7384, 8198, 323, 15009, 13, 59250, 2019, 279, 1749, 706, 1023, 4754, 8522, 13, 1102, 1436, 1376, 279, 4851, 315, 7701, 24473, 12624, 24198, 11, 1701, 4442, 304, 43524, 811, 315, 279, 29280, 859, 311, 30357, 6767, 459, 1665, 596, 3148, 11, 1778, 439, 264, 3254, 17188, 19320, 13, 16132, 388, 430, 7155, 6573, 6956, 1436, 1101, 387, 1511, 311, 2274, 28015, 6067, 430, 2567, 1401, 6956, 304, 14683, 6067, 505, 72389, 1113, 13, 220, 128257, 198 ]

2,581

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Two-dimensional (2D) materials such as graphene and transition-metal dichalcogenides reveal the electronic phases that emerge when a bulk crystal is reduced to a monolayer 1 , 2 , 3 , 4 . Transition-metal oxide perovskites host a variety of correlated electronic phases 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , so similar behaviour in monolayer materials based on transition-metal oxide perovskites would open the door to a rich spectrum of exotic 2D correlated phases that have not yet been explored. Here we report the fabrication of freestanding perovskite films with high crystalline quality almost down to a single unit cell. Using a recently developed method based on water-soluble Sr 3 Al 2 O 6 as the sacrificial buffer layer 13 , 14 we synthesize freestanding SrTiO 3 and BiFeO 3 ultrathin films by reactive molecular beam epitaxy and transfer them to diverse substrates, in particular crystalline silicon wafers and holey carbon films. We find that freestanding BiFeO 3 films exhibit unexpected and giant tetragonality and polarization when approaching the 2D limit. Our results demonstrate the absence of a critical thickness for stabilizing the crystalline order in the freestanding ultrathin oxide films. The ability to synthesize and transfer crystalline freestanding perovskite films without any thickness limitation onto any desired substrate creates opportunities for research into 2D correlated phases and interfacial phenomena that have not previously been technically possible. Main Two-dimensional (2D) materials have recently generated substantial interest owing to their remarkable electronic properties and potential for electronic applications 1 , 2 , 3 , 4 . In conventional 2D materials, such as graphene and transition-metal dichalcogenides, these properties are largely controlled by the weakly interacting electrons of the s and p orbitals 1 , 4 . By contrast, the strongly interacting electrons of the d orbital in transition-metal oxide perovskites give rise to a rich spectrum of exotic phases, including high-temperature superconductivity 5 , 6 , colossal magnetoresistance 7 , 8 , Mott metal–insulator transitions 9 , 10 and multiferroicity 11 , 12 . Like conventional 2D materials, 2D transition-metal oxide perovskites are expected to exhibit new fundamental properties and to enable the development of multifunctional electronic devices. This prospect is, however, hindered by the technical challenges of exfoliating three-dimensional oxide crystals or lifting strongly bonded ultrathin-oxide films from the substrate. Many techniques have been used to synthesize freestanding films, involving selective etching of the buffer layer using acid 15 , 16 , dissolving the NaCl substrate using water 17 and melting the film–substrate interface using laser 18 and ion implantations 19 . These techniques are difficult to generalize to a wide range of perovskite oxides. Recently, Lu et al. developed a method of synthesizing high-quality freestanding perovskite oxides using water-soluble Sr 3 Al 2 O 6 (SAO) as a sacrificial buffer layer 13 , 14 , providing a step towards the search for similarly exotic 2D correlated phases in perovskite oxides. In this work we show that high-quality freestanding perovskite oxides such as SrTiO 3 (STO) and BiFeO 3 (BFO) films as thin as a single unit cell can be synthesized and transferred onto any desired substrates, for example, silicon wafer and holey carbon. Surprisingly, freestanding BFO films exhibit a rhombohedral-like (R-like) to tetragonal-like (T-like) phase transition and show both a large c / a ratio and giant polarization when approaching the ultimate 2D limit. Epitaxial SAO and the subsequent perovskite oxide films were grown by reactive molecular beam epitaxy instead of the pulsed laser deposition used in earlier works 13 , 14 . The growth condition of the SAO sacrificial buffer layers was carefully optimized to show clear fourfold reconstructed electron diffraction patterns that exhibit four intensity oscillation periods during the growth of the one-unit-cell SAO, as described in Methods and Extended Data Fig. 1 . A series of freestanding STO and BFO films of various thicknesses were grown and transferred. All samples exhibit atomic flat surfaces, possessing clear atomic steps and terraces (see Extended Data Fig. 1 ). Freestanding films several millimetres square were released by dissolving the SAO buffer layer in deionized water with mechanical support from a polydimethylsiloxane (PDMS) tape or silicone-coated polyethylene terephthalate (PET), and then transferred onto the desired substrate for scanning transmission electron microscopy (STEM) imaging: silicon wafer for cross-sectional imaging and holey carbon TEM grids for plan-view imaging (Fig. 1 ). Fig. 1: Growth and transfer of ultrathin freestanding SrTiO 3 films. a , Schematic of a film with an SAO buffer layer. b , The sacrificial SAO layer is dissolved in water to release the top oxide films with the mechanical support of PDMS. c , New heterostructures and interfaces are formed when the freestanding film is transferred onto the desired substrate. d , e , Atomically resolved cross-sectional ( d ) and low-magnification plan-view ( e ) HAADF images of a two-unit-cell freestanding STO film transferred to a silicon wafer and a holey carbon TEM grid, respectively. f , g , Atomically resolved cross-sectional ( f ) and low-magnification plan-view ( g ) HAADF images of a representative four-unit-cell freestanding STO film, showing the excellent flexibility of ultrathin freestanding films. Full size image We first demonstrate that ultrathin single-crystalline freestanding STO films as thin as one unit cell can be fabricated and transferred. As shown in Fig. 1d, e and 2 , freestanding STO films of various thicknesses were synthesized by oxide molecular beam epitaxy and characterized by TEM using selected-area electron diffraction (SAED) and plan-view and cross-sectional high-angle annular dark-field (HAADF) imaging with atomic resolution. The SAED diffraction spots observed are sharp, narrow and round, indicating that all films, including the one-unit-cell-thick film, are of single-crystalline form. Atomically resolved cross-sectional and plan-view HAADF images show high crystalline quality in four-, three- and two-unit-cell-thick freestanding STO films, well below the previously reported five-unit-cell critical thickness below which the crystalline lattice will collapse 14 . We note that with decrease in thickness the freestanding STO films become extremely sensitive to electron beams,", "role": "user" }, { "content": "A team of researchers from Nanjing University in China, the University of Nebraska and the University of California in the U.S. has found a way to produce free-standing films of perovskite oxide. In their paper published in the journal Nature, the group describes the process they developed and how well it worked when tested. Yorick Birkhölzer and Gertjan Koster from the University of Twente have published a News and Views piece on the work done by the team in the same journal issue. Birkhölzer and Koster point out that many new materials are made by going to extremes—making them really big or really small. Making them small has led to many recent discoveries, they note, including a technique to make graphene. One area of research has focused on ways to produce transition-metal oxides in a thinner format. It has been slow going, however, due to their crystalline nature. Unlike some materials, transition-metal oxides do not naturally form into layers with a top layer that can be peeled off. Instead, they form in strongly bonded 3-D structures. Because of this, some in the field have worried that it might never be possible to produce them in desired forms. But now, the researchers with this new effort have found a way to produce two transition-metal oxides (perovskite oxides strontium titanate and bismuth ferrite) in a thin-film format. The process developed by the researchers involved using molecular beam epitaxy to apply a buffer layer onto a substrate followed by a layer of perovskite. Once the sandwich of materials was made, the researchers used water to dissolve the buffer layer, allowing the perovskite to be removed and placed onto other substrates. The researchers report that their process worked so well they were able to extract films of perovskite near the theoretical limit—one square unit cell (with approximately 0.4-nanometer sides). “Through our successful fabrication of ultrathin perovskite oxides down to the monolayer limit, we’ve created a new class of two-dimensional materials,” says Xiaoqing Pan, professor of materials science & engineering and Henry Samueli Endowed Chair in Engineering at UCI. “Since these crystals have strongly correlated effects, we anticipate they will exhibit qualities similar to graphene that will be foundational to next-generation energy and information technologies.” Credit: Xiaoqing Pan / UCI Birkhölzer and Koster point out that the work done by the combined Chinese and American team demonstrated that it is possible to produce at least some transition-metal oxides in a thin film format. Their research also allayed fears that such a film would collapse, making it unusable. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Two-dimensional (2D) materials such as graphene and transition-metal dichalcogenides reveal the electronic phases that emerge when a bulk crystal is reduced to a monolayer 1 , 2 , 3 , 4 . Transition-metal oxide perovskites host a variety of correlated electronic phases 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , so similar behaviour in monolayer materials based on transition-metal oxide perovskites would open the door to a rich spectrum of exotic 2D correlated phases that have not yet been explored. Here we report the fabrication of freestanding perovskite films with high crystalline quality almost down to a single unit cell. Using a recently developed method based on water-soluble Sr 3 Al 2 O 6 as the sacrificial buffer layer 13 , 14 we synthesize freestanding SrTiO 3 and BiFeO 3 ultrathin films by reactive molecular beam epitaxy and transfer them to diverse substrates, in particular crystalline silicon wafers and holey carbon films. We find that freestanding BiFeO 3 films exhibit unexpected and giant tetragonality and polarization when approaching the 2D limit. Our results demonstrate the absence of a critical thickness for stabilizing the crystalline order in the freestanding ultrathin oxide films. The ability to synthesize and transfer crystalline freestanding perovskite films without any thickness limitation onto any desired substrate creates opportunities for research into 2D correlated phases and interfacial phenomena that have not previously been technically possible. Main Two-dimensional (2D) materials have recently generated substantial interest owing to their remarkable electronic properties and potential for electronic applications 1 , 2 , 3 , 4 . In conventional 2D materials, such as graphene and transition-metal dichalcogenides, these properties are largely controlled by the weakly interacting electrons of the s and p orbitals 1 , 4 . By contrast, the strongly interacting electrons of the d orbital in transition-metal oxide perovskites give rise to a rich spectrum of exotic phases, including high-temperature superconductivity 5 , 6 , colossal magnetoresistance 7 , 8 , Mott metal–insulator transitions 9 , 10 and multiferroicity 11 , 12 . Like conventional 2D materials, 2D transition-metal oxide perovskites are expected to exhibit new fundamental properties and to enable the development of multifunctional electronic devices. This prospect is, however, hindered by the technical challenges of exfoliating three-dimensional oxide crystals or lifting strongly bonded ultrathin-oxide films from the substrate. Many techniques have been used to synthesize freestanding films, involving selective etching of the buffer layer using acid 15 , 16 , dissolving the NaCl substrate using water 17 and melting the film–substrate interface using laser 18 and ion implantations 19 . These techniques are difficult to generalize to a wide range of perovskite oxides. Recently, Lu et al. developed a method of synthesizing high-quality freestanding perovskite oxides using water-soluble Sr 3 Al 2 O 6 (SAO) as a sacrificial buffer layer 13 , 14 , providing a step towards the search for similarly exotic 2D correlated phases in perovskite oxides. In this work we show that high-quality freestanding perovskite oxides such as SrTiO 3 (STO) and BiFeO 3 (BFO) films as thin as a single unit cell can be synthesized and transferred onto any desired substrates, for example, silicon wafer and holey carbon. Surprisingly, freestanding BFO films exhibit a rhombohedral-like (R-like) to tetragonal-like (T-like) phase transition and show both a large c / a ratio and giant polarization when approaching the ultimate 2D limit. Epitaxial SAO and the subsequent perovskite oxide films were grown by reactive molecular beam epitaxy instead of the pulsed laser deposition used in earlier works 13 , 14 . The growth condition of the SAO sacrificial buffer layers was carefully optimized to show clear fourfold reconstructed electron diffraction patterns that exhibit four intensity oscillation periods during the growth of the one-unit-cell SAO, as described in Methods and Extended Data Fig. 1 . A series of freestanding STO and BFO films of various thicknesses were grown and transferred. All samples exhibit atomic flat surfaces, possessing clear atomic steps and terraces (see Extended Data Fig. 1 ). Freestanding films several millimetres square were released by dissolving the SAO buffer layer in deionized water with mechanical support from a polydimethylsiloxane (PDMS) tape or silicone-coated polyethylene terephthalate (PET), and then transferred onto the desired substrate for scanning transmission electron microscopy (STEM) imaging: silicon wafer for cross-sectional imaging and holey carbon TEM grids for plan-view imaging (Fig. 1 ). Fig. 1: Growth and transfer of ultrathin freestanding SrTiO 3 films. a , Schematic of a film with an SAO buffer layer. b , The sacrificial SAO layer is dissolved in water to release the top oxide films with the mechanical support of PDMS. c , New heterostructures and interfaces are formed when the freestanding film is transferred onto the desired substrate. d , e , Atomically resolved cross-sectional ( d ) and low-magnification plan-view ( e ) HAADF images of a two-unit-cell freestanding STO film transferred to a silicon wafer and a holey carbon TEM grid, respectively. f , g , Atomically resolved cross-sectional ( f ) and low-magnification plan-view ( g ) HAADF images of a representative four-unit-cell freestanding STO film, showing the excellent flexibility of ultrathin freestanding films. Full size image We first demonstrate that ultrathin single-crystalline freestanding STO films as thin as one unit cell can be fabricated and transferred. As shown in Fig. 1d, e and 2 , freestanding STO films of various thicknesses were synthesized by oxide molecular beam epitaxy and characterized by TEM using selected-area electron diffraction (SAED) and plan-view and cross-sectional high-angle annular dark-field (HAADF) imaging with atomic resolution. The SAED diffraction spots observed are sharp, narrow and round, indicating that all films, including the one-unit-cell-thick film, are of single-crystalline form. Atomically resolved cross-sectional and plan-view HAADF images show high crystalline quality in four-, three- and two-unit-cell-thick freestanding STO films, well below the previously reported five-unit-cell critical thickness below which the crystalline lattice will collapse 14 . We note that with decrease in thickness the freestanding STO films become extremely sensitive to electron beams,<|im_end|> <|im_start|>assistant A team of researchers from Nanjing University in China, the University of Nebraska and the University of California in the U.S. has found a way to produce free-standing films of perovskite oxide. In their paper published in the journal Nature, the group describes the process they developed and how well it worked when tested. Yorick Birkhölzer and Gertjan Koster from the University of Twente have published a News and Views piece on the work done by the team in the same journal issue. Birkhölzer and Koster point out that many new materials are made by going to extremes—making them really big or really small. Making them small has led to many recent discoveries, they note, including a technique to make graphene. One area of research has focused on ways to produce transition-metal oxides in a thinner format. It has been slow going, however, due to their crystalline nature. Unlike some materials, transition-metal oxides do not naturally form into layers with a top layer that can be peeled off. Instead, they form in strongly bonded 3-D structures. Because of this, some in the field have worried that it might never be possible to produce them in desired forms. But now, the researchers with this new effort have found a way to produce two transition-metal oxides (perovskite oxides strontium titanate and bismuth ferrite) in a thin-film format. The process developed by the researchers involved using molecular beam epitaxy to apply a buffer layer onto a substrate followed by a layer of perovskite. Once the sandwich of materials was made, the researchers used water to dissolve the buffer layer, allowing the perovskite to be removed and placed onto other substrates. The researchers report that their process worked so well they were able to extract films of perovskite near the theoretical limit—one square unit cell (with approximately 0.4-nanometer sides). “Through our successful fabrication of ultrathin perovskite oxides down to the monolayer limit, we’ve created a new class of two-dimensional materials,” says Xiaoqing Pan, professor of materials science & engineering and Henry Samueli Endowed Chair in Engineering at UCI. “Since these crystals have strongly correlated effects, we anticipate they will exhibit qualities similar to graphene that will be foundational to next-generation energy and information technologies.” Credit: Xiaoqing Pan / UCI Birkhölzer and Koster point out that the work done by the combined Chinese and American team demonstrated that it is possible to produce at least some transition-metal oxides in a thin film format. Their research also allayed fears that such a film would collapse, making it unusable. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 9220, 33520, 320, 17, 35, 8, 7384, 1778, 439, 66192, 323, 9320, 89932, 29953, 17356, 11968, 3422, 16805, 279, 14683, 35530, 430, 34044, 994, 264, 20155, 26110, 374, 11293, 311, 264, 1647, 337, 1155, 220, 16, 1174, 220, 17, 1174, 220, 18, 1174, 220, 19, 662, 38821, 89932, 51180, 824, 869, 4991, 3695, 3552, 264, 8205, 315, 49393, 14683, 35530, 220, 20, 1174, 220, 21, 1174, 220, 22, 1174, 220, 23, 1174, 220, 24, 1174, 220, 605, 1174, 220, 806, 1174, 220, 717, 1174, 779, 4528, 17432, 304, 1647, 337, 1155, 7384, 3196, 389, 9320, 89932, 51180, 824, 869, 4991, 3695, 1053, 1825, 279, 6134, 311, 264, 9257, 20326, 315, 39418, 220, 17, 35, 49393, 35530, 430, 617, 539, 3686, 1027, 36131, 13, 5810, 584, 1934, 279, 59251, 315, 3541, 478, 26673, 824, 869, 4991, 635, 12631, 449, 1579, 64568, 483, 4367, 4661, 1523, 311, 264, 3254, 5089, 2849, 13, 12362, 264, 6051, 8040, 1749, 3196, 389, 3090, 1355, 337, 41572, 34688, 220, 18, 1708, 220, 17, 507, 220, 21, 439, 279, 17475, 16895, 4240, 6324, 220, 1032, 1174, 220, 975, 584, 6925, 27985, 3541, 478, 26673, 34688, 46451, 46, 220, 18, 323, 12371, 6251, 46, 220, 18, 37232, 589, 258, 12631, 555, 56563, 31206, 24310, 67422, 14092, 323, 8481, 1124, 311, 17226, 16146, 988, 11, 304, 4040, 64568, 483, 51692, 289, 2642, 388, 323, 14512, 88, 12782, 12631, 13, 1226, 1505, 430, 3541, 478, 26673, 12371, 6251, 46, 220, 18, 12631, 31324, 16907, 323, 14880, 28953, 56250, 2786, 323, 83245, 994, 31047, 279, 220, 17, 35, 4017, 13, 5751, 3135, 20461, 279, 19821, 315, 264, 9200, 26839, 369, 27276, 4954, 279, 64568, 483, 2015, 304, 279, 3541, 478, 26673, 37232, 589, 258, 51180, 12631, 13, 578, 5845, 311, 6925, 27985, 323, 8481, 64568, 483, 3541, 478, 26673, 824, 869, 4991, 635, 12631, 2085, 904, 26839, 20893, 8800, 904, 12974, 54057, 11705, 10708, 369, 3495, 1139, 220, 17, 35, 49393, 35530, 323, 958, 22974, 532, 44247, 430, 617, 539, 8767, 1027, 32654, 3284, 13, 4802, 9220, 33520, 320, 17, 35, 8, 7384, 617, 6051, 8066, 12190, 2802, 56612, 311, 872, 23649, 14683, 6012, 323, 4754, 369, 14683, 8522, 220, 16, 1174, 220, 17, 1174, 220, 18, 1174, 220, 19, 662, 763, 21349, 220, 17, 35, 7384, 11, 1778, 439, 66192, 323, 9320, 89932, 29953, 17356, 11968, 3422, 11, 1521, 6012, 527, 14090, 14400, 555, 279, 7621, 398, 45830, 57678, 315, 279, 274, 323, 281, 27605, 1147, 220, 16, 1174, 220, 19, 662, 3296, 13168, 11, 279, 16917, 45830, 57678, 315, 279, 294, 65691, 304, 9320, 89932, 51180, 824, 869, 4991, 3695, 3041, 10205, 311, 264, 9257, 20326, 315, 39418, 35530, 11, 2737, 1579, 12, 35658, 2307, 77752, 1968, 220, 20, 1174, 220, 21, 1174, 97937, 33297, 4692, 4011, 220, 22, 1174, 220, 23, 1174, 386, 1751, 9501, 4235, 1354, 10733, 34692, 220, 24, 1174, 220, 605, 323, 2814, 11691, 299, 62791, 220, 806, 1174, 220, 717, 662, 9086, 21349, 220, 17, 35, 7384, 11, 220, 17, 35, 9320, 89932, 51180, 824, 869, 4991, 3695, 527, 3685, 311, 31324, 502, 16188, 6012, 323, 311, 7431, 279, 4500, 315, 62387, 600, 278, 14683, 7766, 13, 1115, 22199, 374, 11, 4869, 11, 57780, 291, 555, 279, 11156, 11774, 315, 506, 8566, 23747, 2380, 33520, 51180, 48473, 477, 33510, 16917, 70241, 37232, 589, 258, 12, 55189, 12631, 505, 279, 54057, 13, 9176, 12823, 617, 1027, 1511, 311, 6925, 27985, 3541, 478, 26673, 12631, 11, 16239, 44010, 1880, 28075, 315, 279, 4240, 6324, 1701, 13935, 220, 868, 1174, 220, 845, 1174, 14091, 20222, 279, 13106, 5176, 54057, 1701, 3090, 220, 1114, 323, 50684, 279, 4632, 4235, 29714, 349, 3834, 1701, 21120, 220, 972, 323, 28772, 46460, 811, 220, 777, 662, 4314, 12823, 527, 5107, 311, 93640, 311, 264, 7029, 2134, 315, 824, 869, 4991, 635, 19488, 3422, 13, 42096, 11, 18866, 1880, 453, 13, 8040, 264, 1749, 315, 52389, 4954, 1579, 22867, 3541, 478, 26673, 824, 869, 4991, 635, 19488, 3422, 1701, 3090, 1355, 337, 41572, 34688, 220, 18, 1708, 220, 17, 507, 220, 21, 320, 7934, 46, 8, 439, 264, 17475, 16895, 4240, 6324, 220, 1032, 1174, 220, 975, 1174, 8405, 264, 3094, 7119, 279, 2778, 369, 30293, 39418, 220, 17, 35, 49393, 35530, 304, 824, 869, 4991, 635, 19488, 3422, 13, 763, 420, 990, 584, 1501, 430, 1579, 22867, 3541, 478, 26673, 824, 869, 4991, 635, 19488, 3422, 1778, 439, 34688, 46451, 46, 220, 18, 320, 790, 46, 8, 323, 12371, 6251, 46, 220, 18, 320, 33, 3873, 8, 12631, 439, 15792, 439, 264, 3254, 5089, 2849, 649, 387, 92106, 323, 23217, 8800, 904, 12974, 16146, 988, 11, 369, 3187, 11, 51692, 10667, 809, 323, 14512, 88, 12782, 13, 8242, 49264, 11, 3541, 478, 26673, 426, 3873, 12631, 31324, 264, 22408, 81487, 71, 36620, 12970, 320, 49, 12970, 8, 311, 28953, 4193, 25180, 12970, 320, 51, 12970, 8, 10474, 9320, 323, 1501, 2225, 264, 3544, 272, 611, 264, 11595, 323, 14880, 83245, 994, 31047, 279, 17139, 220, 17, 35, 4017, 13, 11266, 275, 710, 532, 16998, 46, 323, 279, 17876, 824, 869, 4991, 635, 51180, 12631, 1051, 15042, 555, 56563, 31206, 24310, 67422, 14092, 4619, 315, 279, 7893, 32424, 21120, 65374, 1511, 304, 6931, 4375, 220, 1032, 1174, 220, 975, 662, 578, 6650, 3044, 315, 279, 16998, 46, 17475, 16895, 4240, 13931, 574, 15884, 34440, 311, 1501, 2867, 3116, 20557, 83104, 17130, 3722, 16597, 12912, 430, 31324, 3116, 21261, 43524, 367, 18852, 2391, 279, 6650, 315, 279, 832, 61675, 33001, 16998, 46, 11, 439, 7633, 304, 19331, 323, 41665, 2956, 23966, 13, 220, 16, 662, 362, 4101, 315, 3541, 478, 26673, 4015, 46, 323, 426, 3873, 12631, 315, 5370, 26839, 288, 1051, 15042, 323, 23217, 13, 2052, 10688, 31324, 25524, 10269, 27529, 11, 60662, 2867, 25524, 7504, 323, 7317, 2492, 320, 4151, 41665, 2956, 23966, 13, 220, 16, 7609, 7730, 478, 26673, 12631, 3892, 2606, 86366, 417, 9518, 1051, 6004, 555, 14091, 20222, 279, 16998, 46, 4240, 6324, 304, 409, 290, 1534, 3090, 449, 22936, 1862, 505, 264, 10062, 13223, 42972, 35904, 5241, 2194, 320, 23891, 4931, 8, 17401, 477, 54025, 23283, 660, 10062, 88640, 259, 486, 764, 31392, 349, 320, 80504, 705, 323, 1243, 23217, 8800, 279, 12974, 54057, 369, 36201, 18874, 17130, 92914, 320, 15642, 8, 32758, 25, 51692, 10667, 809, 369, 5425, 97319, 32758, 323, 14512, 88, 12782, 76770, 57449, 369, 3197, 23318, 32758, 320, 30035, 13, 220, 16, 7609, 23966, 13, 220, 16, 25, 34871, 323, 8481, 315, 37232, 589, 258, 3541, 478, 26673, 34688, 46451, 46, 220, 18, 12631, 13, 264, 1174, 328, 82149, 315, 264, 4632, 449, 459, 16998, 46, 4240, 6324, 13, 293, 1174, 578, 17475, 16895, 16998, 46, 6324, 374, 56767, 304, 3090, 311, 4984, 279, 1948, 51180, 12631, 449, 279, 22936, 1862, 315, 27572, 4931, 13, 272, 1174, 1561, 30548, 78, 47194, 323, 25066, 527, 14454, 994, 279, 3541, 478, 26673, 4632, 374, 23217, 8800, 279, 12974, 54057, 13, 294, 1174, 384, 1174, 40616, 2740, 20250, 5425, 97319, 320, 294, 883, 323, 3428, 1474, 3326, 2461, 3197, 23318, 320, 384, 883, 42416, 92363, 5448, 315, 264, 1403, 61675, 33001, 3541, 478, 26673, 4015, 46, 4632, 23217, 311, 264, 51692, 10667, 809, 323, 264, 14512, 88, 12782, 76770, 5950, 11, 15947, 13, 282, 1174, 342, 1174, 40616, 2740, 20250, 5425, 97319, 320, 282, 883, 323, 3428, 1474, 3326, 2461, 3197, 23318, 320, 342, 883, 42416, 92363, 5448, 315, 264, 18740, 3116, 61675, 33001, 3541, 478, 26673, 4015, 46, 4632, 11, 9204, 279, 9250, 25152, 315, 37232, 589, 258, 3541, 478, 26673, 12631, 13, 8797, 1404, 2217, 1226, 1176, 20461, 430, 37232, 589, 258, 3254, 48689, 599, 543, 483, 3541, 478, 26673, 4015, 46, 12631, 439, 15792, 439, 832, 5089, 2849, 649, 387, 70554, 323, 23217, 13, 1666, 6982, 304, 23966, 13, 220, 16, 67, 11, 384, 323, 220, 17, 1174, 3541, 478, 26673, 4015, 46, 12631, 315, 5370, 26839, 288, 1051, 92106, 555, 51180, 31206, 24310, 67422, 14092, 323, 32971, 555, 76770, 1701, 4183, 30122, 17130, 3722, 16597, 320, 7934, 1507, 8, 323, 3197, 23318, 323, 5425, 97319, 1579, 35481, 3008, 1299, 6453, 19677, 320, 17455, 92363, 8, 32758, 449, 25524, 11175, 13, 578, 16998, 1507, 3722, 16597, 19300, 13468, 527, 17676, 11, 15376, 323, 4883, 11, 19392, 430, 682, 12631, 11, 2737, 279, 832, 61675, 33001, 7716, 875, 4632, 11, 527, 315, 3254, 48689, 599, 543, 483, 1376, 13, 40616, 2740, 20250, 5425, 97319, 323, 3197, 23318, 42416, 92363, 5448, 1501, 1579, 64568, 483, 4367, 304, 3116, 37619, 2380, 12, 323, 1403, 61675, 33001, 7716, 875, 3541, 478, 26673, 4015, 46, 12631, 11, 1664, 3770, 279, 8767, 5068, 4330, 61675, 33001, 9200, 26839, 3770, 902, 279, 64568, 483, 55372, 690, 18678, 220, 975, 662, 1226, 5296, 430, 449, 18979, 304, 26839, 279, 3541, 478, 26673, 4015, 46, 12631, 3719, 9193, 16614, 311, 17130, 51045, 11, 128257, 198, 128256, 78191, 198, 32, 2128, 315, 12074, 505, 33242, 99268, 3907, 304, 5734, 11, 279, 3907, 315, 38379, 323, 279, 3907, 315, 7188, 304, 279, 549, 815, 13, 706, 1766, 264, 1648, 311, 8356, 1949, 56703, 12631, 315, 824, 869, 4991, 635, 51180, 13, 763, 872, 5684, 4756, 304, 279, 8486, 22037, 11, 279, 1912, 16964, 279, 1920, 814, 8040, 323, 1268, 1664, 433, 6575, 994, 12793, 13, 816, 269, 875, 426, 14468, 71, 50902, 7215, 323, 480, 531, 23685, 735, 11975, 505, 279, 3907, 315, 12015, 6960, 617, 4756, 264, 5513, 323, 25987, 6710, 389, 279, 990, 2884, 555, 279, 2128, 304, 279, 1890, 8486, 4360, 13, 426, 14468, 71, 50902, 7215, 323, 735, 11975, 1486, 704, 430, 1690, 502, 7384, 527, 1903, 555, 2133, 311, 69971, 2345, 28936, 1124, 2216, 2466, 477, 2216, 2678, 13, 25274, 1124, 2678, 706, 6197, 311, 1690, 3293, 54098, 11, 814, 5296, 11, 2737, 264, 15105, 311, 1304, 66192, 13, 3861, 3158, 315, 3495, 706, 10968, 389, 5627, 311, 8356, 9320, 89932, 19488, 3422, 304, 264, 65355, 3645, 13, 1102, 706, 1027, 6435, 2133, 11, 4869, 11, 4245, 311, 872, 64568, 483, 7138, 13, 27140, 1063, 7384, 11, 9320, 89932, 19488, 3422, 656, 539, 18182, 1376, 1139, 13931, 449, 264, 1948, 6324, 430, 649, 387, 83612, 1022, 13, 12361, 11, 814, 1376, 304, 16917, 70241, 220, 18, 9607, 14726, 13, 9393, 315, 420, 11, 1063, 304, 279, 2115, 617, 18290, 430, 433, 2643, 2646, 387, 3284, 311, 8356, 1124, 304, 12974, 7739, 13, 2030, 1457, 11, 279, 12074, 449, 420, 502, 5149, 617, 1766, 264, 1648, 311, 8356, 1403, 9320, 89932, 19488, 3422, 320, 716, 869, 4991, 635, 19488, 3422, 610, 546, 2411, 86612, 349, 323, 293, 2191, 952, 58139, 635, 8, 304, 264, 15792, 2269, 9672, 3645, 13, 578, 1920, 8040, 555, 279, 12074, 6532, 1701, 31206, 24310, 67422, 14092, 311, 3881, 264, 4240, 6324, 8800, 264, 54057, 8272, 555, 264, 6324, 315, 824, 869, 4991, 635, 13, 9843, 279, 28974, 315, 7384, 574, 1903, 11, 279, 12074, 1511, 3090, 311, 73739, 279, 4240, 6324, 11, 10923, 279, 824, 869, 4991, 635, 311, 387, 7108, 323, 9277, 8800, 1023, 16146, 988, 13, 578, 12074, 1934, 430, 872, 1920, 6575, 779, 1664, 814, 1051, 3025, 311, 8819, 12631, 315, 824, 869, 4991, 635, 3221, 279, 32887, 4017, 87671, 9518, 5089, 2849, 320, 4291, 13489, 220, 15, 13, 19, 5392, 276, 21037, 11314, 570, 1054, 24798, 1057, 6992, 59251, 315, 37232, 589, 258, 824, 869, 4991, 635, 19488, 3422, 1523, 311, 279, 1647, 337, 1155, 4017, 11, 584, 4070, 3549, 264, 502, 538, 315, 1403, 33520, 7384, 2476, 2795, 66690, 90684, 11233, 11, 14561, 315, 7384, 8198, 612, 15009, 323, 18063, 33007, 72, 4060, 13111, 16478, 304, 17005, 520, 549, 11487, 13, 1054, 12834, 1521, 48473, 617, 16917, 49393, 6372, 11, 584, 48248, 814, 690, 31324, 29600, 4528, 311, 66192, 430, 690, 387, 89328, 311, 1828, 43927, 4907, 323, 2038, 14645, 2029, 16666, 25, 66690, 90684, 11233, 611, 549, 11487, 426, 14468, 71, 50902, 7215, 323, 735, 11975, 1486, 704, 430, 279, 990, 2884, 555, 279, 11093, 8620, 323, 3778, 2128, 21091, 430, 433, 374, 3284, 311, 8356, 520, 3325, 1063, 9320, 89932, 19488, 3422, 304, 264, 15792, 4632, 3645, 13, 11205, 3495, 1101, 682, 43995, 24087, 430, 1778, 264, 4632, 1053, 18678, 11, 3339, 433, 16236, 481, 13, 220, 128257, 198 ]

2,055

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Feathers are remarkable evolutionary innovations that are associated with complex adaptations of the skin in modern birds. Fossilised feathers in non-avian dinosaurs and basal birds provide insights into feather evolution, but how associated integumentary adaptations evolved is unclear. Here we report the discovery of fossil skin, preserved with remarkable nanoscale fidelity, in three non-avian maniraptoran dinosaurs and a basal bird from the Cretaceous Jehol biota (China). The skin comprises patches of desquamating epidermal corneocytes that preserve a cytoskeletal array of helically coiled α-keratin tonofibrils. This structure confirms that basal birds and non-avian dinosaurs shed small epidermal flakes as in modern mammals and birds, but structural differences imply that these Cretaceous taxa had lower body heat production than modern birds. Feathered epidermis acquired many, but not all, anatomically modern attributes close to the base of the Maniraptora by the Middle Jurassic. Introduction The integument of vertebrates is a complex multilayered organ with essential functions in homoeostasis, resisting mechanical stress and preventing pathogenic attack 1 . Its evolution is characterised by recurrent anatomical innovation of novel tissue structures (e.g., scales, feathers and hair) that, in amniotes, are linked to major evolutionary radiations 2 . Feathers are associated with structural, biochemical and functional modifications of the skin 2 , including a lipid-rich corneous layer characterised by continuous shedding 3 . Evo-devo studies 4 and fossilised feathers 5 , 6 , 7 have illuminated aspects of early feather evolution, but how the skin of basal birds and feathered non-avian dinosaurs evolved in tandem with feathers has received little attention. Like mammal hair, the skin of birds is thinner than in most reptiles and is shed in millimetre- scale flakes (comprising shed corneocytes, i.e., terminally differentiated keratinocytes), not as large patches or a whole skin moult 2 . Desquamation of small patches of corneocytes, however, also occurs in crocodilians and chelonians and is considered primitive to synchronised cyclical skin shedding in squamates 8 . Crocodilians and birds, the groups that phylogenetically bracket non-avian dinosaurs, both possess the basal condition; parsimony suggests that this skin shedding mechanism was shared with non-avian dinosaurs. During dinosaur evolution, the increase in metabolic rate towards a true endothermic physiology (as in modern birds) was associated with profound changes in integument structure 9 relating to a subcutaneous hydraulic skeletal system, an intricate dermo-subcutaneous muscle system, and a lipid-rich corneous layer characterised by continuous shedding 3 . The pattern and timing of acquisition of these ultrastructural skin characters, however, is poorly resolved and there is no a priori reason to assume that the ultrastructure of the skin of feathered non-avian dinosaurs and early birds would have resembled that of their modern counterparts. Dinosaur skin is usually preserved as an external mould 10 and rarely as organic remains 11 , 12 or in authigenic minerals 13 , 14 , 15 . Although mineralised fossil skin can retain (sub-)cellular anatomical features 16 , 17 , dinosaur skin is rarely investigated at the ultrastructural level 14 . Critically, despite reports of preserved epidermis in a non-feathered dinosaur 10 there is no known evidence of the epidermis 18 in basal birds or of preserved skin in feathered non-avian dinosaurs. The coevolutionary history of skin and feathers is therefore largely unknown. Here we report the discovery of fossilised skin in the feathered non-avian maniraptoran dinosaurs Beipiaosaurus, Sinornithosaurus and Microraptor , and the bird Confuciusornis from the Early Cretaceous Jehol biota (NE China; Supplementary Fig. 1 ). The ultrastructure of the preserved tissues reveals that feathered skin had evolved many, but not all, modern attributes by the origin of the Maniraptora in the Middle Jurassic. Results and discussion Fossil soft tissue structure Small patches of tissue (0.01–0.4 mm 2 ; Fig. 1a–d and Supplementary Figs. 2 – 6 ) are closely associated with fossil feathers (i.e., usually within 500 µm of carbonaceous feather residues, Supplementary Fig. 2e, g, j, k, o, s, t ). The patches are definitively of fossil tissue, and do not reflect surface contamination with modern material during sample preparation, as they are preserved in calcium phosphate (see 'Taphonomy', below); further, several samples show margins that are overlapped, in part, by the surrounding matrix. The tissues have not, therefore, simply adhered to the sample surface as a result of contamination from airborne particles in the laboratory. Fig. 1 Phosphatised soft tissues in non-avian maniraptoran dinosaurs and a basal bird. a – h Backscatter electron images of tissue in Confuciusornis (IVPP V 13171; a , e , f ), Beipiaosaurus (IVPP V STM31-1; b , g ), Sinornithosaurus (IVPP V 12811; c , h ) and Microraptor (IVPP V 17972A; d ). a – d Small irregularly shaped patches of tissue. e Detail of tissue surface showing polygonal texture. f Focused ion beam-milled vertical section through the soft tissue showing internal fibrous layer separating two structureless layers. g , h Fractured oblique section through the soft tissues, showing the layers visible in f Full size image The tissue patches are typically 3–6 µm thick and planar (Fig. 1a–e ). Transverse sections and fractured surfaces show an inner fibrous layer (1.0–1.2 µm thick) between two thinner structureless layers (0.2–0.5 µm thick) (Fig. 1f–h ). The external surface of the structureless layer is smooth and can show a subtle polygonal texture defined by polygons 10–15 µm wide (Fig. 1e, h ). The fibrous layer also shows polygons (Figs. 1f, h and 2a–e , and Supplementary Fig. 6 ) that contain arrays of densely packed fibres 0.1–0.5 µm wide (Fig. 2f–i and Supplementary Fig. 5f ). Well-preserved fibres show helicoidal twisting (Fig. 2h, i ). Fibres in marginal parts of each polygon are 0.1–0.3 µm wide and oriented parallel to the tissue surface; those in the interior of each polygon are 0.3–0.5 µm wide and are usually perpendicular to the tissue surface (Fig. 2b, h and Supplementary Fig. S6d ). In the marginal 1–2 µm of each polygon, the fibres are usually orthogonal to the lateral polygon margin and terminate at, or bridge the junction between, adjacent polygons", "role": "user" }, { "content": "Palaeontologists from University College Cork (UCC) in Ireland have discovered 125 million-year-old dandruff preserved amongst the plumage of feathered dinosaurs and early birds, revealing the first evidence of how dinosaurs shed their skin. UCC's Dr Maria McNamara and her team studied the fossil cells, and dandruff from modern birds, with powerful electron microscopes for the study, published today in the journal Nature Communications. \"The fossil cells are preserved with incredible detail – right down to the level of nanoscale keratin fibrils. What's remarkable is that the fossil dandruff is almost identical to that in modern birds – even the spiral twisting of individual fibres is still visible,\" said Dr Maria McNamara. Just like human dandruff, the fossil dandruff is made of tough cells called corneocytes, which in life are dry and full of the protein keratin. The study suggests that this modern skin feature evolved sometime in the late Middle Jurassic, around the same time as a host of other skin features evolved. \"There was a burst of evolution of feathered dinosaurs and birds at this time, and it's exciting to see evidence that the skin of early birds and dinosaurs was evolving rapidly in response to bearing feathers,\" Dr McNamara added. Dr McNamara led the study, in collaboration with her postdoctoral researcher Dr Chris Rogers; Dr Andre Toulouse and Tara Foley, also from UCC; Dr Paddy Orr from UCD, Ireland; and an international team of palaeontologists from the UK and China. The dandruff is the first evidence of how dinosaurs shed their skin. The feathered dinosaurs studied - Microraptor, Beipiaosaurus and Sinornithosaurus – clearly shed their skin in flakes, like the early bird Confuciusornis studied by the team and also modern birds and mammals, and not as a single piece or several large pieces, as in many modern reptiles. Co-author Professor Mike Benton, from the University of Bristol's School of Earth Sciences, said: \"It's unusual to be able to study the skin of a dinosaur, and the fact this is dandruff proves the dinosaur was not shedding its whole skin like a modern lizard or snake but losing skin fragments from between its feathers.\" Modern birds have very fatty corneocytes with loosely packed keratin, which allows them to cool down quickly when they are flying for extended periods. The corneocytes in the fossil dinosaurs and birds, however, were packed with keratin, suggesting that the fossils didn't get as warm as modern birds, presumably because they couldn't fly at all or for as long periods. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Feathers are remarkable evolutionary innovations that are associated with complex adaptations of the skin in modern birds. Fossilised feathers in non-avian dinosaurs and basal birds provide insights into feather evolution, but how associated integumentary adaptations evolved is unclear. Here we report the discovery of fossil skin, preserved with remarkable nanoscale fidelity, in three non-avian maniraptoran dinosaurs and a basal bird from the Cretaceous Jehol biota (China). The skin comprises patches of desquamating epidermal corneocytes that preserve a cytoskeletal array of helically coiled α-keratin tonofibrils. This structure confirms that basal birds and non-avian dinosaurs shed small epidermal flakes as in modern mammals and birds, but structural differences imply that these Cretaceous taxa had lower body heat production than modern birds. Feathered epidermis acquired many, but not all, anatomically modern attributes close to the base of the Maniraptora by the Middle Jurassic. Introduction The integument of vertebrates is a complex multilayered organ with essential functions in homoeostasis, resisting mechanical stress and preventing pathogenic attack 1 . Its evolution is characterised by recurrent anatomical innovation of novel tissue structures (e.g., scales, feathers and hair) that, in amniotes, are linked to major evolutionary radiations 2 . Feathers are associated with structural, biochemical and functional modifications of the skin 2 , including a lipid-rich corneous layer characterised by continuous shedding 3 . Evo-devo studies 4 and fossilised feathers 5 , 6 , 7 have illuminated aspects of early feather evolution, but how the skin of basal birds and feathered non-avian dinosaurs evolved in tandem with feathers has received little attention. Like mammal hair, the skin of birds is thinner than in most reptiles and is shed in millimetre- scale flakes (comprising shed corneocytes, i.e., terminally differentiated keratinocytes), not as large patches or a whole skin moult 2 . Desquamation of small patches of corneocytes, however, also occurs in crocodilians and chelonians and is considered primitive to synchronised cyclical skin shedding in squamates 8 . Crocodilians and birds, the groups that phylogenetically bracket non-avian dinosaurs, both possess the basal condition; parsimony suggests that this skin shedding mechanism was shared with non-avian dinosaurs. During dinosaur evolution, the increase in metabolic rate towards a true endothermic physiology (as in modern birds) was associated with profound changes in integument structure 9 relating to a subcutaneous hydraulic skeletal system, an intricate dermo-subcutaneous muscle system, and a lipid-rich corneous layer characterised by continuous shedding 3 . The pattern and timing of acquisition of these ultrastructural skin characters, however, is poorly resolved and there is no a priori reason to assume that the ultrastructure of the skin of feathered non-avian dinosaurs and early birds would have resembled that of their modern counterparts. Dinosaur skin is usually preserved as an external mould 10 and rarely as organic remains 11 , 12 or in authigenic minerals 13 , 14 , 15 . Although mineralised fossil skin can retain (sub-)cellular anatomical features 16 , 17 , dinosaur skin is rarely investigated at the ultrastructural level 14 . Critically, despite reports of preserved epidermis in a non-feathered dinosaur 10 there is no known evidence of the epidermis 18 in basal birds or of preserved skin in feathered non-avian dinosaurs. The coevolutionary history of skin and feathers is therefore largely unknown. Here we report the discovery of fossilised skin in the feathered non-avian maniraptoran dinosaurs Beipiaosaurus, Sinornithosaurus and Microraptor , and the bird Confuciusornis from the Early Cretaceous Jehol biota (NE China; Supplementary Fig. 1 ). The ultrastructure of the preserved tissues reveals that feathered skin had evolved many, but not all, modern attributes by the origin of the Maniraptora in the Middle Jurassic. Results and discussion Fossil soft tissue structure Small patches of tissue (0.01–0.4 mm 2 ; Fig. 1a–d and Supplementary Figs. 2 – 6 ) are closely associated with fossil feathers (i.e., usually within 500 µm of carbonaceous feather residues, Supplementary Fig. 2e, g, j, k, o, s, t ). The patches are definitively of fossil tissue, and do not reflect surface contamination with modern material during sample preparation, as they are preserved in calcium phosphate (see 'Taphonomy', below); further, several samples show margins that are overlapped, in part, by the surrounding matrix. The tissues have not, therefore, simply adhered to the sample surface as a result of contamination from airborne particles in the laboratory. Fig. 1 Phosphatised soft tissues in non-avian maniraptoran dinosaurs and a basal bird. a – h Backscatter electron images of tissue in Confuciusornis (IVPP V 13171; a , e , f ), Beipiaosaurus (IVPP V STM31-1; b , g ), Sinornithosaurus (IVPP V 12811; c , h ) and Microraptor (IVPP V 17972A; d ). a – d Small irregularly shaped patches of tissue. e Detail of tissue surface showing polygonal texture. f Focused ion beam-milled vertical section through the soft tissue showing internal fibrous layer separating two structureless layers. g , h Fractured oblique section through the soft tissues, showing the layers visible in f Full size image The tissue patches are typically 3–6 µm thick and planar (Fig. 1a–e ). Transverse sections and fractured surfaces show an inner fibrous layer (1.0–1.2 µm thick) between two thinner structureless layers (0.2–0.5 µm thick) (Fig. 1f–h ). The external surface of the structureless layer is smooth and can show a subtle polygonal texture defined by polygons 10–15 µm wide (Fig. 1e, h ). The fibrous layer also shows polygons (Figs. 1f, h and 2a–e , and Supplementary Fig. 6 ) that contain arrays of densely packed fibres 0.1–0.5 µm wide (Fig. 2f–i and Supplementary Fig. 5f ). Well-preserved fibres show helicoidal twisting (Fig. 2h, i ). Fibres in marginal parts of each polygon are 0.1–0.3 µm wide and oriented parallel to the tissue surface; those in the interior of each polygon are 0.3–0.5 µm wide and are usually perpendicular to the tissue surface (Fig. 2b, h and Supplementary Fig. S6d ). In the marginal 1–2 µm of each polygon, the fibres are usually orthogonal to the lateral polygon margin and terminate at, or bridge the junction between, adjacent polygons<|im_end|> <|im_start|>assistant Palaeontologists from University College Cork (UCC) in Ireland have discovered 125 million-year-old dandruff preserved amongst the plumage of feathered dinosaurs and early birds, revealing the first evidence of how dinosaurs shed their skin. UCC's Dr Maria McNamara and her team studied the fossil cells, and dandruff from modern birds, with powerful electron microscopes for the study, published today in the journal Nature Communications. "The fossil cells are preserved with incredible detail – right down to the level of nanoscale keratin fibrils. What's remarkable is that the fossil dandruff is almost identical to that in modern birds – even the spiral twisting of individual fibres is still visible," said Dr Maria McNamara. Just like human dandruff, the fossil dandruff is made of tough cells called corneocytes, which in life are dry and full of the protein keratin. The study suggests that this modern skin feature evolved sometime in the late Middle Jurassic, around the same time as a host of other skin features evolved. "There was a burst of evolution of feathered dinosaurs and birds at this time, and it's exciting to see evidence that the skin of early birds and dinosaurs was evolving rapidly in response to bearing feathers," Dr McNamara added. Dr McNamara led the study, in collaboration with her postdoctoral researcher Dr Chris Rogers; Dr Andre Toulouse and Tara Foley, also from UCC; Dr Paddy Orr from UCD, Ireland; and an international team of palaeontologists from the UK and China. The dandruff is the first evidence of how dinosaurs shed their skin. The feathered dinosaurs studied - Microraptor, Beipiaosaurus and Sinornithosaurus – clearly shed their skin in flakes, like the early bird Confuciusornis studied by the team and also modern birds and mammals, and not as a single piece or several large pieces, as in many modern reptiles. Co-author Professor Mike Benton, from the University of Bristol's School of Earth Sciences, said: "It's unusual to be able to study the skin of a dinosaur, and the fact this is dandruff proves the dinosaur was not shedding its whole skin like a modern lizard or snake but losing skin fragments from between its feathers." Modern birds have very fatty corneocytes with loosely packed keratin, which allows them to cool down quickly when they are flying for extended periods. The corneocytes in the fossil dinosaurs and birds, however, were packed with keratin, suggesting that the fossils didn't get as warm as modern birds, presumably because they couldn't fly at all or for as long periods. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 3926, 19568, 527, 23649, 41993, 46045, 430, 527, 5938, 449, 6485, 77765, 315, 279, 6930, 304, 6617, 20229, 13, 435, 85061, 4147, 56994, 304, 2536, 12, 60278, 65375, 323, 80710, 20229, 3493, 26793, 1139, 50876, 15740, 11, 719, 1268, 5938, 5503, 1143, 661, 77765, 28995, 374, 25420, 13, 5810, 584, 1934, 279, 18841, 315, 31376, 6930, 11, 34683, 449, 23649, 20622, 437, 2296, 83604, 11, 304, 2380, 2536, 12, 60278, 893, 404, 33757, 276, 65375, 323, 264, 80710, 12224, 505, 279, 356, 2171, 77140, 63033, 337, 6160, 6217, 320, 23078, 570, 578, 6930, 41095, 29760, 315, 951, 87801, 1113, 4248, 1814, 14991, 1867, 818, 57878, 430, 21813, 264, 9693, 43681, 86255, 1358, 315, 11591, 2740, 1080, 2230, 19581, 12, 7197, 15111, 8941, 1073, 10892, 8839, 13, 1115, 6070, 43496, 430, 80710, 20229, 323, 2536, 12, 60278, 65375, 25351, 2678, 4248, 1814, 14991, 82723, 439, 304, 6617, 56669, 323, 20229, 11, 719, 24693, 12062, 34608, 430, 1521, 356, 2171, 77140, 77314, 1047, 4827, 2547, 8798, 5788, 1109, 6617, 20229, 13, 79976, 291, 4248, 1814, 34965, 19426, 1690, 11, 719, 539, 682, 11, 75893, 2740, 6617, 8365, 3345, 311, 279, 2385, 315, 279, 2418, 404, 2756, 6347, 555, 279, 12877, 84474, 13, 29438, 578, 5503, 1143, 315, 67861, 99868, 374, 264, 6485, 2814, 321, 1155, 291, 2942, 449, 7718, 5865, 304, 5105, 4748, 537, 10949, 11, 70441, 22936, 8631, 323, 27252, 1853, 29569, 3440, 220, 16, 662, 11699, 15740, 374, 3752, 4147, 555, 65174, 75893, 950, 19297, 315, 11775, 20438, 14726, 320, 68, 1326, 2637, 29505, 11, 56994, 323, 7013, 8, 430, 11, 304, 1097, 7907, 6429, 11, 527, 10815, 311, 3682, 41993, 12164, 811, 220, 17, 662, 3926, 19568, 527, 5938, 449, 24693, 11, 93532, 323, 16003, 29882, 315, 279, 6930, 220, 17, 1174, 2737, 264, 68700, 41947, 1867, 818, 788, 6324, 3752, 4147, 555, 19815, 80417, 220, 18, 662, 98970, 6953, 3415, 7978, 220, 19, 323, 31376, 4147, 56994, 220, 20, 1174, 220, 21, 1174, 220, 22, 617, 75648, 13878, 315, 4216, 50876, 15740, 11, 719, 1268, 279, 6930, 315, 80710, 20229, 323, 50876, 291, 2536, 12, 60278, 65375, 28995, 304, 67042, 449, 56994, 706, 4036, 2697, 6666, 13, 9086, 36041, 278, 7013, 11, 279, 6930, 315, 20229, 374, 65355, 1109, 304, 1455, 64873, 3742, 323, 374, 25351, 304, 2606, 318, 47987, 12, 5569, 82723, 320, 884, 34754, 25351, 1867, 818, 57878, 11, 602, 1770, 2637, 10415, 750, 89142, 34801, 15111, 57878, 705, 539, 439, 3544, 29760, 477, 264, 4459, 6930, 54409, 4937, 220, 17, 662, 3959, 447, 27279, 315, 2678, 29760, 315, 1867, 818, 57878, 11, 4869, 11, 1101, 13980, 304, 14425, 20720, 26707, 323, 523, 65467, 5493, 323, 374, 6646, 28694, 311, 14453, 4147, 44448, 32348, 6930, 80417, 304, 8330, 309, 988, 220, 23, 662, 25611, 20720, 26707, 323, 20229, 11, 279, 5315, 430, 37555, 86945, 37774, 32742, 2536, 12, 60278, 65375, 11, 2225, 15575, 279, 80710, 3044, 26, 10364, 65556, 13533, 430, 420, 6930, 80417, 17383, 574, 6222, 449, 2536, 12, 60278, 65375, 13, 12220, 63989, 15740, 11, 279, 5376, 304, 41861, 4478, 7119, 264, 837, 842, 1605, 21914, 78152, 320, 300, 304, 6617, 20229, 8, 574, 5938, 449, 28254, 4442, 304, 5503, 1143, 6070, 220, 24, 23343, 311, 264, 1207, 10453, 18133, 44175, 69397, 1887, 11, 459, 57216, 2761, 6489, 18451, 10453, 18133, 16124, 1887, 11, 323, 264, 68700, 41947, 1867, 818, 788, 6324, 3752, 4147, 555, 19815, 80417, 220, 18, 662, 578, 5497, 323, 18912, 315, 24279, 315, 1521, 24955, 96797, 6930, 5885, 11, 4869, 11, 374, 31555, 20250, 323, 1070, 374, 912, 264, 4972, 72, 2944, 311, 9855, 430, 279, 24955, 7993, 315, 279, 6930, 315, 50876, 291, 2536, 12, 60278, 65375, 323, 4216, 20229, 1053, 617, 96858, 430, 315, 872, 6617, 38495, 13, 423, 89247, 6930, 374, 6118, 34683, 439, 459, 9434, 51370, 220, 605, 323, 19029, 439, 17808, 8625, 220, 806, 1174, 220, 717, 477, 304, 4259, 6569, 292, 34072, 220, 1032, 1174, 220, 975, 1174, 220, 868, 662, 10541, 25107, 4147, 31376, 6930, 649, 14389, 320, 2008, 63096, 5997, 1299, 75893, 950, 4519, 220, 845, 1174, 220, 1114, 1174, 63989, 6930, 374, 19029, 27313, 520, 279, 24955, 96797, 2237, 220, 975, 662, 34307, 2740, 11, 8994, 6821, 315, 34683, 4248, 1814, 34965, 304, 264, 2536, 34303, 1894, 291, 63989, 220, 605, 1070, 374, 912, 3967, 6029, 315, 279, 4248, 1814, 34965, 220, 972, 304, 80710, 20229, 477, 315, 34683, 6930, 304, 50876, 291, 2536, 12, 60278, 65375, 13, 578, 1080, 5230, 3294, 661, 3925, 315, 6930, 323, 56994, 374, 9093, 14090, 9987, 13, 5810, 584, 1934, 279, 18841, 315, 31376, 4147, 6930, 304, 279, 50876, 291, 2536, 12, 60278, 893, 404, 33757, 276, 65375, 2893, 575, 689, 437, 43613, 11, 18098, 1540, 411, 437, 43613, 323, 28095, 7787, 33757, 1174, 323, 279, 12224, 15323, 1791, 9334, 1540, 285, 505, 279, 23591, 356, 2171, 77140, 63033, 337, 6160, 6217, 320, 4031, 5734, 26, 99371, 23966, 13, 220, 16, 7609, 578, 24955, 7993, 315, 279, 34683, 39881, 21667, 430, 50876, 291, 6930, 1047, 28995, 1690, 11, 719, 539, 682, 11, 6617, 8365, 555, 279, 6371, 315, 279, 2418, 404, 2756, 6347, 304, 279, 12877, 84474, 13, 18591, 323, 10430, 435, 85061, 8579, 20438, 6070, 15344, 29760, 315, 20438, 320, 15, 13, 1721, 4235, 15, 13, 19, 9653, 220, 17, 2652, 23966, 13, 220, 16, 64, 4235, 67, 323, 99371, 435, 14801, 13, 220, 17, 1389, 220, 21, 883, 527, 15499, 5938, 449, 31376, 56994, 320, 72, 1770, 2637, 6118, 2949, 220, 2636, 64012, 76, 315, 12782, 77140, 50876, 71783, 11, 99371, 23966, 13, 220, 17, 68, 11, 342, 11, 503, 11, 597, 11, 297, 11, 274, 11, 259, 7609, 578, 29760, 527, 31388, 3210, 315, 31376, 20438, 11, 323, 656, 539, 8881, 7479, 47810, 449, 6617, 3769, 2391, 6205, 18459, 11, 439, 814, 527, 34683, 304, 35719, 79106, 320, 4151, 364, 51, 1366, 17404, 518, 3770, 1237, 4726, 11, 3892, 10688, 1501, 37682, 430, 527, 29204, 5795, 11, 304, 961, 11, 555, 279, 14932, 6303, 13, 578, 39881, 617, 539, 11, 9093, 11, 5042, 36051, 291, 311, 279, 6205, 7479, 439, 264, 1121, 315, 47810, 505, 70863, 19252, 304, 279, 27692, 13, 23966, 13, 220, 16, 2405, 24527, 3689, 291, 8579, 39881, 304, 2536, 12, 60278, 893, 404, 33757, 276, 65375, 323, 264, 80710, 12224, 13, 264, 1389, 305, 6984, 71350, 17130, 5448, 315, 20438, 304, 15323, 1791, 9334, 1540, 285, 320, 3166, 4505, 650, 220, 9263, 6028, 26, 264, 1174, 384, 1174, 282, 7026, 2893, 575, 689, 437, 43613, 320, 3166, 4505, 650, 48273, 2148, 12, 16, 26, 293, 1174, 342, 7026, 18098, 1540, 411, 437, 43613, 320, 3166, 4505, 650, 220, 4386, 806, 26, 272, 1174, 305, 883, 323, 28095, 7787, 33757, 320, 3166, 4505, 650, 220, 11128, 5332, 32, 26, 294, 7609, 264, 1389, 294, 15344, 42408, 398, 27367, 29760, 315, 20438, 13, 384, 26855, 315, 20438, 7479, 9204, 30472, 278, 10651, 13, 282, 435, 21012, 28772, 24310, 1474, 4473, 12414, 3857, 1555, 279, 8579, 20438, 9204, 5419, 16178, 27620, 6324, 50545, 1403, 6070, 1752, 13931, 13, 342, 1174, 305, 2939, 533, 3149, 1536, 37526, 3857, 1555, 279, 8579, 39881, 11, 9204, 279, 13931, 9621, 304, 282, 8797, 1404, 2217, 578, 20438, 29760, 527, 11383, 220, 18, 4235, 21, 64012, 76, 12314, 323, 3197, 277, 320, 30035, 13, 220, 16, 64, 4235, 68, 7609, 4149, 4550, 14491, 323, 80208, 27529, 1501, 459, 9358, 16178, 27620, 6324, 320, 16, 13, 15, 4235, 16, 13, 17, 64012, 76, 12314, 8, 1990, 1403, 65355, 6070, 1752, 13931, 320, 15, 13, 17, 4235, 15, 13, 20, 64012, 76, 12314, 8, 320, 30035, 13, 220, 16, 69, 4235, 71, 7609, 578, 9434, 7479, 315, 279, 6070, 1752, 6324, 374, 11113, 323, 649, 1501, 264, 27545, 30472, 278, 10651, 4613, 555, 69259, 220, 605, 4235, 868, 64012, 76, 7029, 320, 30035, 13, 220, 16, 68, 11, 305, 7609, 578, 16178, 27620, 6324, 1101, 5039, 69259, 320, 37, 14801, 13, 220, 16, 69, 11, 305, 323, 220, 17, 64, 4235, 68, 1174, 323, 99371, 23966, 13, 220, 21, 883, 430, 6782, 18893, 315, 97617, 19937, 16178, 417, 220, 15, 13, 16, 4235, 15, 13, 20, 64012, 76, 7029, 320, 30035, 13, 220, 17, 69, 4235, 72, 323, 99371, 23966, 13, 220, 20, 69, 7609, 8489, 2320, 52202, 16178, 417, 1501, 11591, 292, 71916, 80654, 320, 30035, 13, 220, 17, 71, 11, 602, 7609, 43564, 417, 304, 32873, 5596, 315, 1855, 30472, 527, 220, 15, 13, 16, 4235, 15, 13, 18, 64012, 76, 7029, 323, 42208, 15638, 311, 279, 20438, 7479, 26, 1884, 304, 279, 15135, 315, 1855, 30472, 527, 220, 15, 13, 18, 4235, 15, 13, 20, 64012, 76, 7029, 323, 527, 6118, 77933, 311, 279, 20438, 7479, 320, 30035, 13, 220, 17, 65, 11, 305, 323, 99371, 23966, 13, 328, 21, 67, 7609, 763, 279, 32873, 220, 16, 4235, 17, 64012, 76, 315, 1855, 30472, 11, 279, 16178, 417, 527, 6118, 95680, 311, 279, 45569, 30472, 4850, 323, 30754, 520, 11, 477, 14497, 279, 49341, 1990, 11, 24894, 69259, 128257, 198, 128256, 78191, 198, 20577, 6043, 546, 22012, 505, 3907, 9304, 53036, 320, 52, 3791, 8, 304, 14990, 617, 11352, 220, 6549, 3610, 4771, 6418, 294, 74976, 1386, 34683, 24059, 279, 42272, 425, 315, 50876, 291, 65375, 323, 4216, 20229, 11, 31720, 279, 1176, 6029, 315, 1268, 65375, 25351, 872, 6930, 13, 549, 3791, 596, 2999, 23880, 55751, 309, 5169, 323, 1077, 2128, 20041, 279, 31376, 7917, 11, 323, 294, 74976, 1386, 505, 6617, 20229, 11, 449, 8147, 17130, 8162, 82025, 369, 279, 4007, 11, 4756, 3432, 304, 279, 8486, 22037, 26545, 13, 330, 791, 31376, 7917, 527, 34683, 449, 15400, 7872, 1389, 1314, 1523, 311, 279, 2237, 315, 20622, 437, 2296, 34801, 15111, 95235, 8839, 13, 3639, 596, 23649, 374, 430, 279, 31376, 294, 74976, 1386, 374, 4661, 20086, 311, 430, 304, 6617, 20229, 1389, 1524, 279, 42197, 80654, 315, 3927, 16178, 417, 374, 2103, 9621, 1359, 1071, 2999, 23880, 55751, 309, 5169, 13, 4702, 1093, 3823, 294, 74976, 1386, 11, 279, 31376, 294, 74976, 1386, 374, 1903, 315, 11292, 7917, 2663, 1867, 818, 57878, 11, 902, 304, 2324, 527, 9235, 323, 2539, 315, 279, 13128, 34801, 15111, 13, 578, 4007, 13533, 430, 420, 6617, 6930, 4668, 28995, 36113, 304, 279, 3389, 12877, 84474, 11, 2212, 279, 1890, 892, 439, 264, 3552, 315, 1023, 6930, 4519, 28995, 13, 330, 3947, 574, 264, 21165, 315, 15740, 315, 50876, 291, 65375, 323, 20229, 520, 420, 892, 11, 323, 433, 596, 13548, 311, 1518, 6029, 430, 279, 6930, 315, 4216, 20229, 323, 65375, 574, 42028, 19019, 304, 2077, 311, 18534, 56994, 1359, 2999, 55751, 309, 5169, 3779, 13, 2999, 55751, 309, 5169, 6197, 279, 4007, 11, 304, 20632, 449, 1077, 1772, 38083, 278, 32185, 2999, 11517, 34467, 26, 2999, 27525, 350, 67730, 323, 70797, 80906, 11, 1101, 505, 549, 3791, 26, 2999, 393, 23290, 87119, 505, 549, 6620, 11, 14990, 26, 323, 459, 6625, 2128, 315, 11091, 6043, 546, 22012, 505, 279, 6560, 323, 5734, 13, 578, 294, 74976, 1386, 374, 279, 1176, 6029, 315, 1268, 65375, 25351, 872, 6930, 13, 578, 50876, 291, 65375, 20041, 482, 28095, 7787, 33757, 11, 2893, 575, 689, 437, 43613, 323, 18098, 1540, 411, 437, 43613, 1389, 9539, 25351, 872, 6930, 304, 82723, 11, 1093, 279, 4216, 12224, 15323, 1791, 9334, 1540, 285, 20041, 555, 279, 2128, 323, 1101, 6617, 20229, 323, 56669, 11, 323, 539, 439, 264, 3254, 6710, 477, 3892, 3544, 9863, 11, 439, 304, 1690, 6617, 64873, 3742, 13, 3623, 43802, 17054, 11519, 93783, 11, 505, 279, 3907, 315, 45039, 596, 6150, 315, 9420, 23199, 11, 1071, 25, 330, 2181, 596, 19018, 311, 387, 3025, 311, 4007, 279, 6930, 315, 264, 63989, 11, 323, 279, 2144, 420, 374, 294, 74976, 1386, 36862, 279, 63989, 574, 539, 80417, 1202, 4459, 6930, 1093, 264, 6617, 95911, 477, 26332, 719, 13490, 6930, 35603, 505, 1990, 1202, 56994, 1210, 18766, 20229, 617, 1633, 40085, 1867, 818, 57878, 449, 63557, 19937, 34801, 15111, 11, 902, 6276, 1124, 311, 7155, 1523, 6288, 994, 814, 527, 16706, 369, 11838, 18852, 13, 578, 1867, 818, 57878, 304, 279, 31376, 65375, 323, 20229, 11, 4869, 11, 1051, 19937, 449, 34801, 15111, 11, 23377, 430, 279, 81473, 3287, 956, 636, 439, 8369, 439, 6617, 20229, 11, 36548, 1606, 814, 7846, 956, 11722, 520, 682, 477, 369, 439, 1317, 18852, 13, 220, 128257, 198 ]

2,078

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Late Pliocene and Early Pleistocene epochs 3.6 to 0.8 million years ago 1 had climates resembling those forecasted under future warming 2 . Palaeoclimatic records show strong polar amplification with mean annual temperatures of 11–19 °C above contemporary values 3 , 4 . The biological communities inhabiting the Arctic during this time remain poorly known because fossils are rare 5 . Here we report an ancient environmental DNA 6 (eDNA) record describing the rich plant and animal assemblages of the Kap København Formation in North Greenland, dated to around two million years ago. The record shows an open boreal forest ecosystem with mixed vegetation of poplar, birch and thuja trees, as well as a variety of Arctic and boreal shrubs and herbs, many of which had not previously been detected at the site from macrofossil and pollen records. The DNA record confirms the presence of hare and mitochondrial DNA from animals including mastodons, reindeer, rodents and geese, all ancestral to their present-day and late Pleistocene relatives. The presence of marine species including horseshoe crab and green algae support a warmer climate than today. The reconstructed ecosystem has no modern analogue. The survival of such ancient eDNA probably relates to its binding to mineral surfaces. Our findings open new areas of genetic research, demonstrating that it is possible to track the ecology and evolution of biological communities from two million years ago using ancient eDNA. Main The Kap København Formation is located in Peary Land, North Greenland (82° 24′ N 22° 12′ W) in what is now a polar desert. The upper depositional sequence contains well-preserved terrestrial animal and plant remains washed into an estuary during a warmer Early Pleistocene interglacial cycle 7 (Fig. 1 ). Nearly 40 years of palaeoenvironmental and climate research at the site provide a unique perspective into a period when the site was situated at the boreal Arctic ecotone with reconstructed summer and winter average minimum temperatures of 10 °C and −17 °C respectively—more than 10 °C warmer than the present 7 , 8 , 9 , 10 , 11 . These conditions must have driven substantial ablation of the Greenland Ice Sheet, possibly producing one of the last ice-free intervals 7 in the last 2.4 million years (Myr). Although the Kap København Formation is known to yield well-preserved macrofossils from a coniferous boreal forest and a rich insect fauna, few traces of vertebrates have been found. To date, these comprise remains from lagomorph genera, their coprolites and Aphodius beetles, which live in and on mammalian dung 10 , 11 . However, the approximately 3.4 Myr old Fyles Leaf bed and Beaver Pond on Ellesmere Island in Arctic Canada preserve fossils of mammals that potentially could have colonized Greenland, such as the extinct bear ( Protarctos abstrusus ), extinct beavers ( Dipoides sp.), the small canine Eucyon and Arctic giant camelines 4 , 12 , 13 (similar to Paracamelus ). Whether the Nares Strait was a sufficient barrier to isolate northern Greenland from colonization by this fauna remains an open question. Fig. 1: Geographical location and depositional sequence. a . Location of Kap København Formation in North Greenland at the entrance to the Independence Fjord (82° 24′ N 22° 12′ W) and locations of other Arctic Plio-Pleistocene fossil-bearing sites (red dots). b , Spatial distribution of the erosional remnants of the 100-m thick succession of shallow marine near-shore sediments between Mudderbugt and the low mountains towards the north (a + b refers to location 74a and 74b). c , Glacial–interglacial division of the depositional succession of clay Member A and units B1, B2 and B3 constituting sandy Member B. Sampling intervals for all sites are projected onto the sedimentary succession of locality 50. Sedimentological log modified after ref. 7 . Circled numbers on the map mark sample sites for environmental DNA analyses, absolute burial dating and palaeomagnetism. Numbered sites refer to previous publications 7 , 10 , 11 , 14 , 61 . Full size image The Kap København Formation is formally subdivided into two members 7 (Fig. 1 ). The lower Member A consists of up to 50 m of laminated mud with an Arctic ostracod, foraminifera and mollusc fauna deposited in an offshore glaciomarine environment 14 . The overlying Member B consists of 40–50 m of sandy (units B1 and B3) and silty (unit B2) deposits (Extended Data Fig. 1 ), including thin organic-rich beds with an interglacial macrofossil fauna that were deposited closer to the shore in a shallow marine or estuarine environment represented by upper and lower shoreface sedimentary facies 7 . The specific depositional environments are also reflected in the mineralogy of the units, where the proximal B3 locality has the lowest clay and highest quartz contents (Sample compositions in Supplementary Tables 4.2.1 and 4.2.2 and unit averages in Supplementary Tables 4.2.3 and 4.2.4 ). The architecture of the basin infill suggests that Member B units thicken towards the present coast—that is, distal to the sediment source in the low mountains in the north (Fig. 1 ). Abundant organic detritus horizons are recorded in units B1 and B3, which also contain beds rich in Arctic and boreal plant and invertebrate macrofossils, as well as terrestrial mosses 10 , 15 . Therefore, the taphonomy of the DNA most probably reflects the biological communities eroded from a range of habitats, fluvially transported to the foreshore and concentrated as organic detritus mixed into sandy near-shore sediments within units B1 and B3. Conversely, the deeper water facies from Member A and unit B2 have a stronger marine signal. This scenario is supported by the similarities in the mineralogic composition between Kap København Formation sediments and Kim Fjelde sediments (Supplementary Tables 4.2.1 and 4.2.5 ). Geological age A series of complementary studies has successively narrowed the depositional age bracket of the Kap København Formation from 4.0–0.7 Myr to a 20,000-year-long age bracket around 2.4 Myr (see Supplementary Information, sections 1 – 3 ). This was achieved by a combination of palaeomagnetism, biostratigraphy and allostratigraphy 7", "role": "user" }, { "content": "Scientists discovered the oldest known DNA and used it to reveal what life was like 2 million years ago in the northern tip of Greenland. Today, it's a barren Arctic desert, but back then it was a lush landscape of trees and vegetation with an array of animals, even the now extinct mastodon. \"The study opens the door into a past that has basically been lost,\" said lead author Kurt Kjær, a geologist and glacier expert at the University of Copenhagen. With animal fossils hard to come by, the researchers extracted environmental DNA, also known as eDNA, from soil samples. This is the genetic material that organisms shed into their surroundings—for example, through hair, waste, spit or decomposing carcasses. Studying really old DNA can be a challenge because the genetic material breaks down over time, leaving scientists with only tiny fragments. But with the latest technology, researchers were able to get genetic information out of the small, damaged bits of DNA, explained senior author Eske Willerslev, a geneticist at the University of Cambridge. In their study, published Wednesday in the journal Nature, they compared the DNA to that of different species, looking for matches. The samples came from a sediment deposit called the Kap København formation in Peary Land. Today, the area is a polar desert, Kjær said. This illustration provided by researchers depicts Kap Kobenhavn, Greenland, two million years ago, when the temperature was significantly warmer than northernmost Greenland today. Scientists have analyzed 2-million-year-old DNA extracted from dirt samples in the area, revealing an ancient ecosystem unlike anything seen on Earth today, including traces of mastodons and horseshoe crabs roaming the Arctic. Credit: Beth Zaiken via AP But millions of years ago, this region was undergoing a period of intense climate change that sent temperatures up, Willerslev said. Sediment likely built up for tens of thousands of years at the site before the climate cooled and cemented the finds into permafrost. The cold environment would help preserve the delicate bits of DNA—until scientists came along and drilled the samples out, beginning in 2006. During the region's warm period, when average temperatures were 20 to 34 degrees Fahrenheit (11 to 19 degrees Celsius) higher than today, the area was filled with an unusual array of plant and animal life, the researchers reported. The DNA fragments suggest a mix of Arctic plants, like birch trees and willow shrubs, with ones that usually prefer warmer climates, like firs and cedars. The DNA also showed traces of animals including geese, hares, reindeer and lemmings. Previously, a dung beetle and some hare remains had been the only signs of animal life at the site, Willerslev said. Professors Eske Willerslev and Kurt H. Kjaer expose fresh layers for sampling of sediments at Kap Kobenhavn, Greenland. Scientists have analyzed 2-million-year-old DNA extracted from dirt samples in the area, revealing an ancient ecosystem unlike anything seen on Earth today, including traces of mastodons and horseshoe crabs roaming the Arctic. Credit: Svend Funder via AP One big surprise was finding DNA from the mastodon, an extinct species that looks like a mix between an elephant and a mammoth, Kjær said. Many mastodon fossils have previously been found from temperate forests in North America. That's an ocean away from Greenland, and much farther south, Willerslev said. \"I wouldn't have, in a million years, expected to find mastodons in northern Greenland,\" said Love Dalen, a researcher in evolutionary genomics at Stockholm University who was not involved in the study. Because the sediment built up in the mouth of a fjord, researchers were also able to get clues about marine life from this time period. The DNA suggests horseshoe crabs and green algae lived in the area—meaning the nearby waters were likely much warmer back then, Kjær said. By pulling dozens of species out of just a few sediment samples, the study highlights some of eDNA's advantages, said Benjamin Vernot, an ancient DNA researcher at Germany's Max Planck Institute for Evolutionary Anthropology who was not involved in the study. This 2006 photo provided by researchers shows a close-up of organic material in coastal deposits at Kap Kobenhavn, Greenland. The organic layers show traces of the rich plant flora and insect fauna that lived two million years ago. Scientists have analyzed 2-million-year-old DNA extracted from dirt samples in the area, revealing an ancient ecosystem unlike anything seen on Earth today, including traces of mastodons and horseshoe crabs roaming the Arctic. Credit: Svend Funder via AP \"You really get a broader picture of the ecosystem at a particular time,\" Vernot said. \"You don't have to go and find this piece of wood to study this plant, and this bone to study this mammoth.\" Based on the data available, it's hard to say for sure whether these species truly lived side by side, or if the DNA was mixed together from different parts of the landscape, said Laura Epp, an eDNA expert at Germany's University of Konstanz who was not involved in the study. This 2006 photo provided by researchers shows geological formations at Kap Kobenhavn, Greenland. At the bottom of the section, the deep marine deposits are overlain by the coastal deposits of fine sandy material. The two people at the top are sampling for environmental DNA. Scientists have analyzed 2-million-year-old DNA extracted from dirt samples in the area, revealing an ancient ecosystem unlike anything seen on Earth today, including traces of mastodons and horseshoe crabs roaming the Arctic. Credit: Svend Funder via AP But Epp said this kind of DNA research is valuable to show \"hidden diversity\" in ancient landscapes. Willerslev believes that because these plants and animals survived during a time of dramatic climate change, their DNA could offer a \"genetic roadmap\" to help us adapt to current warming. Stockholm University's Dalen expects ancient DNA research to keep pushing deeper into the past. He worked on the study that previously held the \"oldest DNA\" record, from a mammoth tooth around a million years old. This 2006 photo provided by researchers shows the landscape at Kap Kobenhavn, Greenland. The many hills have been formed by rivers running towards the coast. Scientists have analyzed 2-million-year-old DNA extracted from dirt samples in the area, revealing an ancient ecosystem unlike anything seen on Earth today, including traces of mastodons and horseshoe crabs roaming the Arctic. Credit: Kurt H. Kjaer via AP \"I wouldn't be surprised if you can go at least one or perhaps a few million years further back, assuming you can find the right samples,\" Dalen said. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Late Pliocene and Early Pleistocene epochs 3.6 to 0.8 million years ago 1 had climates resembling those forecasted under future warming 2 . Palaeoclimatic records show strong polar amplification with mean annual temperatures of 11–19 °C above contemporary values 3 , 4 . The biological communities inhabiting the Arctic during this time remain poorly known because fossils are rare 5 . Here we report an ancient environmental DNA 6 (eDNA) record describing the rich plant and animal assemblages of the Kap København Formation in North Greenland, dated to around two million years ago. The record shows an open boreal forest ecosystem with mixed vegetation of poplar, birch and thuja trees, as well as a variety of Arctic and boreal shrubs and herbs, many of which had not previously been detected at the site from macrofossil and pollen records. The DNA record confirms the presence of hare and mitochondrial DNA from animals including mastodons, reindeer, rodents and geese, all ancestral to their present-day and late Pleistocene relatives. The presence of marine species including horseshoe crab and green algae support a warmer climate than today. The reconstructed ecosystem has no modern analogue. The survival of such ancient eDNA probably relates to its binding to mineral surfaces. Our findings open new areas of genetic research, demonstrating that it is possible to track the ecology and evolution of biological communities from two million years ago using ancient eDNA. Main The Kap København Formation is located in Peary Land, North Greenland (82° 24′ N 22° 12′ W) in what is now a polar desert. The upper depositional sequence contains well-preserved terrestrial animal and plant remains washed into an estuary during a warmer Early Pleistocene interglacial cycle 7 (Fig. 1 ). Nearly 40 years of palaeoenvironmental and climate research at the site provide a unique perspective into a period when the site was situated at the boreal Arctic ecotone with reconstructed summer and winter average minimum temperatures of 10 °C and −17 °C respectively—more than 10 °C warmer than the present 7 , 8 , 9 , 10 , 11 . These conditions must have driven substantial ablation of the Greenland Ice Sheet, possibly producing one of the last ice-free intervals 7 in the last 2.4 million years (Myr). Although the Kap København Formation is known to yield well-preserved macrofossils from a coniferous boreal forest and a rich insect fauna, few traces of vertebrates have been found. To date, these comprise remains from lagomorph genera, their coprolites and Aphodius beetles, which live in and on mammalian dung 10 , 11 . However, the approximately 3.4 Myr old Fyles Leaf bed and Beaver Pond on Ellesmere Island in Arctic Canada preserve fossils of mammals that potentially could have colonized Greenland, such as the extinct bear ( Protarctos abstrusus ), extinct beavers ( Dipoides sp.), the small canine Eucyon and Arctic giant camelines 4 , 12 , 13 (similar to Paracamelus ). Whether the Nares Strait was a sufficient barrier to isolate northern Greenland from colonization by this fauna remains an open question. Fig. 1: Geographical location and depositional sequence. a . Location of Kap København Formation in North Greenland at the entrance to the Independence Fjord (82° 24′ N 22° 12′ W) and locations of other Arctic Plio-Pleistocene fossil-bearing sites (red dots). b , Spatial distribution of the erosional remnants of the 100-m thick succession of shallow marine near-shore sediments between Mudderbugt and the low mountains towards the north (a + b refers to location 74a and 74b). c , Glacial–interglacial division of the depositional succession of clay Member A and units B1, B2 and B3 constituting sandy Member B. Sampling intervals for all sites are projected onto the sedimentary succession of locality 50. Sedimentological log modified after ref. 7 . Circled numbers on the map mark sample sites for environmental DNA analyses, absolute burial dating and palaeomagnetism. Numbered sites refer to previous publications 7 , 10 , 11 , 14 , 61 . Full size image The Kap København Formation is formally subdivided into two members 7 (Fig. 1 ). The lower Member A consists of up to 50 m of laminated mud with an Arctic ostracod, foraminifera and mollusc fauna deposited in an offshore glaciomarine environment 14 . The overlying Member B consists of 40–50 m of sandy (units B1 and B3) and silty (unit B2) deposits (Extended Data Fig. 1 ), including thin organic-rich beds with an interglacial macrofossil fauna that were deposited closer to the shore in a shallow marine or estuarine environment represented by upper and lower shoreface sedimentary facies 7 . The specific depositional environments are also reflected in the mineralogy of the units, where the proximal B3 locality has the lowest clay and highest quartz contents (Sample compositions in Supplementary Tables 4.2.1 and 4.2.2 and unit averages in Supplementary Tables 4.2.3 and 4.2.4 ). The architecture of the basin infill suggests that Member B units thicken towards the present coast—that is, distal to the sediment source in the low mountains in the north (Fig. 1 ). Abundant organic detritus horizons are recorded in units B1 and B3, which also contain beds rich in Arctic and boreal plant and invertebrate macrofossils, as well as terrestrial mosses 10 , 15 . Therefore, the taphonomy of the DNA most probably reflects the biological communities eroded from a range of habitats, fluvially transported to the foreshore and concentrated as organic detritus mixed into sandy near-shore sediments within units B1 and B3. Conversely, the deeper water facies from Member A and unit B2 have a stronger marine signal. This scenario is supported by the similarities in the mineralogic composition between Kap København Formation sediments and Kim Fjelde sediments (Supplementary Tables 4.2.1 and 4.2.5 ). Geological age A series of complementary studies has successively narrowed the depositional age bracket of the Kap København Formation from 4.0–0.7 Myr to a 20,000-year-long age bracket around 2.4 Myr (see Supplementary Information, sections 1 – 3 ). This was achieved by a combination of palaeomagnetism, biostratigraphy and allostratigraphy 7<|im_end|> <|im_start|>assistant Scientists discovered the oldest known DNA and used it to reveal what life was like 2 million years ago in the northern tip of Greenland. Today, it's a barren Arctic desert, but back then it was a lush landscape of trees and vegetation with an array of animals, even the now extinct mastodon. "The study opens the door into a past that has basically been lost," said lead author Kurt Kjær, a geologist and glacier expert at the University of Copenhagen. With animal fossils hard to come by, the researchers extracted environmental DNA, also known as eDNA, from soil samples. This is the genetic material that organisms shed into their surroundings—for example, through hair, waste, spit or decomposing carcasses. Studying really old DNA can be a challenge because the genetic material breaks down over time, leaving scientists with only tiny fragments. But with the latest technology, researchers were able to get genetic information out of the small, damaged bits of DNA, explained senior author Eske Willerslev, a geneticist at the University of Cambridge. In their study, published Wednesday in the journal Nature, they compared the DNA to that of different species, looking for matches. The samples came from a sediment deposit called the Kap København formation in Peary Land. Today, the area is a polar desert, Kjær said. This illustration provided by researchers depicts Kap Kobenhavn, Greenland, two million years ago, when the temperature was significantly warmer than northernmost Greenland today. Scientists have analyzed 2-million-year-old DNA extracted from dirt samples in the area, revealing an ancient ecosystem unlike anything seen on Earth today, including traces of mastodons and horseshoe crabs roaming the Arctic. Credit: Beth Zaiken via AP But millions of years ago, this region was undergoing a period of intense climate change that sent temperatures up, Willerslev said. Sediment likely built up for tens of thousands of years at the site before the climate cooled and cemented the finds into permafrost. The cold environment would help preserve the delicate bits of DNA—until scientists came along and drilled the samples out, beginning in 2006. During the region's warm period, when average temperatures were 20 to 34 degrees Fahrenheit (11 to 19 degrees Celsius) higher than today, the area was filled with an unusual array of plant and animal life, the researchers reported. The DNA fragments suggest a mix of Arctic plants, like birch trees and willow shrubs, with ones that usually prefer warmer climates, like firs and cedars. The DNA also showed traces of animals including geese, hares, reindeer and lemmings. Previously, a dung beetle and some hare remains had been the only signs of animal life at the site, Willerslev said. Professors Eske Willerslev and Kurt H. Kjaer expose fresh layers for sampling of sediments at Kap Kobenhavn, Greenland. Scientists have analyzed 2-million-year-old DNA extracted from dirt samples in the area, revealing an ancient ecosystem unlike anything seen on Earth today, including traces of mastodons and horseshoe crabs roaming the Arctic. Credit: Svend Funder via AP One big surprise was finding DNA from the mastodon, an extinct species that looks like a mix between an elephant and a mammoth, Kjær said. Many mastodon fossils have previously been found from temperate forests in North America. That's an ocean away from Greenland, and much farther south, Willerslev said. "I wouldn't have, in a million years, expected to find mastodons in northern Greenland," said Love Dalen, a researcher in evolutionary genomics at Stockholm University who was not involved in the study. Because the sediment built up in the mouth of a fjord, researchers were also able to get clues about marine life from this time period. The DNA suggests horseshoe crabs and green algae lived in the area—meaning the nearby waters were likely much warmer back then, Kjær said. By pulling dozens of species out of just a few sediment samples, the study highlights some of eDNA's advantages, said Benjamin Vernot, an ancient DNA researcher at Germany's Max Planck Institute for Evolutionary Anthropology who was not involved in the study. This 2006 photo provided by researchers shows a close-up of organic material in coastal deposits at Kap Kobenhavn, Greenland. The organic layers show traces of the rich plant flora and insect fauna that lived two million years ago. Scientists have analyzed 2-million-year-old DNA extracted from dirt samples in the area, revealing an ancient ecosystem unlike anything seen on Earth today, including traces of mastodons and horseshoe crabs roaming the Arctic. Credit: Svend Funder via AP "You really get a broader picture of the ecosystem at a particular time," Vernot said. "You don't have to go and find this piece of wood to study this plant, and this bone to study this mammoth." Based on the data available, it's hard to say for sure whether these species truly lived side by side, or if the DNA was mixed together from different parts of the landscape, said Laura Epp, an eDNA expert at Germany's University of Konstanz who was not involved in the study. This 2006 photo provided by researchers shows geological formations at Kap Kobenhavn, Greenland. At the bottom of the section, the deep marine deposits are overlain by the coastal deposits of fine sandy material. The two people at the top are sampling for environmental DNA. Scientists have analyzed 2-million-year-old DNA extracted from dirt samples in the area, revealing an ancient ecosystem unlike anything seen on Earth today, including traces of mastodons and horseshoe crabs roaming the Arctic. Credit: Svend Funder via AP But Epp said this kind of DNA research is valuable to show "hidden diversity" in ancient landscapes. Willerslev believes that because these plants and animals survived during a time of dramatic climate change, their DNA could offer a "genetic roadmap" to help us adapt to current warming. Stockholm University's Dalen expects ancient DNA research to keep pushing deeper into the past. He worked on the study that previously held the "oldest DNA" record, from a mammoth tooth around a million years old. This 2006 photo provided by researchers shows the landscape at Kap Kobenhavn, Greenland. The many hills have been formed by rivers running towards the coast. Scientists have analyzed 2-million-year-old DNA extracted from dirt samples in the area, revealing an ancient ecosystem unlike anything seen on Earth today, including traces of mastodons and horseshoe crabs roaming the Arctic. Credit: Kurt H. Kjaer via AP "I wouldn't be surprised if you can go at least one or perhaps a few million years further back, assuming you can find the right samples," Dalen said. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 36931, 393, 747, 78782, 323, 23591, 33540, 380, 78782, 40446, 220, 18, 13, 21, 311, 220, 15, 13, 23, 3610, 1667, 4227, 220, 16, 1047, 92399, 71707, 1884, 18057, 291, 1234, 3938, 24808, 220, 17, 662, 11165, 6043, 511, 4763, 780, 7576, 1501, 3831, 25685, 23201, 2461, 449, 3152, 9974, 20472, 315, 220, 806, 4235, 777, 37386, 34, 3485, 19225, 2819, 220, 18, 1174, 220, 19, 662, 578, 24156, 10977, 26318, 5977, 279, 37518, 2391, 420, 892, 7293, 31555, 3967, 1606, 81473, 527, 9024, 220, 20, 662, 5810, 584, 1934, 459, 14154, 12434, 15922, 220, 21, 320, 68, 56420, 8, 3335, 23524, 279, 9257, 6136, 323, 10065, 439, 28111, 1154, 315, 279, 32765, 735, 6282, 42077, 72466, 304, 4892, 73778, 11, 30105, 311, 2212, 1403, 3610, 1667, 4227, 13, 578, 3335, 5039, 459, 1825, 39786, 278, 13952, 26031, 449, 9709, 54832, 315, 2477, 14115, 11, 15606, 331, 323, 78474, 5697, 12690, 11, 439, 1664, 439, 264, 8205, 315, 37518, 323, 39786, 278, 14362, 16115, 323, 42393, 11, 1690, 315, 902, 1047, 539, 8767, 1027, 16914, 520, 279, 2816, 505, 18563, 69, 85061, 323, 79784, 7576, 13, 578, 15922, 3335, 43496, 279, 9546, 315, 96018, 323, 72061, 15922, 505, 10099, 2737, 19218, 347, 2439, 11, 15601, 97362, 11, 94209, 323, 3980, 2423, 11, 682, 78771, 311, 872, 3118, 11477, 323, 3389, 33540, 380, 78782, 29658, 13, 578, 9546, 315, 29691, 9606, 2737, 60475, 4385, 4748, 60512, 323, 6307, 68951, 1862, 264, 46039, 10182, 1109, 3432, 13, 578, 83104, 26031, 706, 912, 6617, 91343, 13, 578, 20237, 315, 1778, 14154, 384, 56420, 4762, 36716, 311, 1202, 11212, 311, 25107, 27529, 13, 5751, 14955, 1825, 502, 5789, 315, 19465, 3495, 11, 45296, 430, 433, 374, 3284, 311, 3839, 279, 72546, 323, 15740, 315, 24156, 10977, 505, 1403, 3610, 1667, 4227, 1701, 14154, 384, 56420, 13, 4802, 578, 32765, 735, 6282, 42077, 72466, 374, 7559, 304, 5250, 661, 11680, 11, 4892, 73778, 320, 6086, 11877, 220, 1187, 39615, 452, 220, 1313, 11877, 220, 717, 39615, 468, 8, 304, 1148, 374, 1457, 264, 25685, 24521, 13, 578, 8582, 26364, 3079, 8668, 5727, 1664, 2320, 52202, 80492, 10065, 323, 6136, 8625, 38593, 1139, 459, 1826, 3620, 2391, 264, 46039, 23591, 33540, 380, 78782, 958, 6200, 33211, 11008, 220, 22, 320, 30035, 13, 220, 16, 7609, 49669, 220, 1272, 1667, 315, 11091, 6043, 16355, 3182, 278, 323, 10182, 3495, 520, 279, 2816, 3493, 264, 5016, 13356, 1139, 264, 4261, 994, 279, 2816, 574, 31183, 520, 279, 39786, 278, 37518, 12208, 354, 606, 449, 83104, 7474, 323, 12688, 5578, 8187, 20472, 315, 220, 605, 37386, 34, 323, 25173, 1114, 37386, 34, 15947, 2345, 6518, 1109, 220, 605, 37386, 34, 46039, 1109, 279, 3118, 220, 22, 1174, 220, 23, 1174, 220, 24, 1174, 220, 605, 1174, 220, 806, 662, 4314, 4787, 2011, 617, 16625, 12190, 671, 2354, 315, 279, 73778, 20534, 28841, 11, 11000, 17843, 832, 315, 279, 1566, 10054, 12862, 28090, 220, 22, 304, 279, 1566, 220, 17, 13, 19, 3610, 1667, 320, 5159, 81, 570, 10541, 279, 32765, 735, 6282, 42077, 72466, 374, 3967, 311, 7692, 1664, 2320, 52202, 18563, 69, 3746, 8839, 505, 264, 390, 11691, 788, 39786, 278, 13952, 323, 264, 9257, 27080, 100014, 11, 2478, 35483, 315, 67861, 99868, 617, 1027, 1766, 13, 2057, 2457, 11, 1521, 54350, 8625, 505, 22171, 316, 16751, 84535, 11, 872, 6293, 1098, 3695, 323, 98408, 347, 9334, 49112, 645, 11, 902, 3974, 304, 323, 389, 36041, 10700, 86636, 220, 605, 1174, 220, 806, 662, 4452, 11, 279, 13489, 220, 18, 13, 19, 3092, 81, 2362, 435, 2552, 27967, 4950, 323, 92534, 71965, 389, 4072, 645, 61031, 10951, 304, 37518, 7008, 21813, 81473, 315, 56669, 430, 13893, 1436, 617, 15235, 1534, 73778, 11, 1778, 439, 279, 69918, 11984, 320, 11970, 277, 302, 437, 671, 496, 355, 355, 7026, 69918, 387, 22292, 320, 56147, 590, 288, 993, 25390, 279, 2678, 76082, 469, 1791, 26039, 323, 37518, 14880, 6730, 11243, 220, 19, 1174, 220, 717, 1174, 220, 1032, 320, 65387, 311, 4366, 582, 36662, 355, 7609, 13440, 279, 452, 5518, 83163, 574, 264, 14343, 22881, 311, 43223, 18671, 73778, 505, 96553, 555, 420, 100014, 8625, 459, 1825, 3488, 13, 23966, 13, 220, 16, 25, 4323, 32277, 3813, 323, 26364, 3079, 8668, 13, 264, 662, 10067, 315, 32765, 735, 6282, 42077, 72466, 304, 4892, 73778, 520, 279, 20396, 311, 279, 44177, 435, 73, 541, 320, 6086, 11877, 220, 1187, 39615, 452, 220, 1313, 11877, 220, 717, 39615, 468, 8, 323, 10687, 315, 1023, 37518, 393, 26205, 9483, 273, 380, 78782, 31376, 92253, 6732, 320, 1171, 32094, 570, 293, 1174, 75797, 8141, 315, 279, 43219, 4001, 73440, 315, 279, 220, 1041, 1474, 12314, 50787, 315, 26682, 29691, 3221, 7666, 461, 11163, 12843, 1990, 386, 57229, 2365, 83, 323, 279, 3428, 24405, 7119, 279, 10411, 320, 64, 489, 293, 19813, 311, 3813, 220, 5728, 64, 323, 220, 5728, 65, 570, 272, 1174, 8444, 33211, 4235, 2295, 6200, 33211, 13096, 315, 279, 26364, 3079, 50787, 315, 37148, 12308, 362, 323, 8316, 426, 16, 11, 426, 17, 323, 426, 18, 9129, 10831, 68539, 12308, 426, 13, 96409, 28090, 369, 682, 6732, 527, 28448, 8800, 279, 59132, 661, 50787, 315, 69187, 220, 1135, 13, 36378, 3904, 5848, 1515, 11041, 1306, 2098, 13, 220, 22, 662, 16741, 839, 5219, 389, 279, 2472, 1906, 6205, 6732, 369, 12434, 15922, 29060, 11, 10973, 55763, 5029, 323, 11091, 6043, 316, 64333, 2191, 13, 5742, 291, 6732, 8464, 311, 3766, 29085, 220, 22, 1174, 220, 605, 1174, 220, 806, 1174, 220, 975, 1174, 220, 5547, 662, 8797, 1404, 2217, 578, 32765, 735, 6282, 42077, 72466, 374, 37402, 67609, 4591, 1139, 1403, 3697, 220, 22, 320, 30035, 13, 220, 16, 7609, 578, 4827, 12308, 362, 17610, 315, 709, 311, 220, 1135, 296, 315, 79533, 660, 27275, 449, 459, 37518, 67094, 582, 347, 11, 369, 8778, 333, 2473, 323, 55509, 26089, 100014, 54568, 304, 459, 39500, 2840, 25471, 316, 75314, 4676, 220, 975, 662, 578, 927, 6852, 12308, 426, 17610, 315, 220, 1272, 4235, 1135, 296, 315, 68539, 320, 26726, 426, 16, 323, 426, 18, 8, 323, 5554, 1919, 320, 3928, 426, 17, 8, 34751, 320, 54290, 2956, 23966, 13, 220, 16, 7026, 2737, 15792, 17808, 41947, 28036, 449, 459, 958, 6200, 33211, 18563, 69, 85061, 100014, 430, 1051, 54568, 12401, 311, 279, 31284, 304, 264, 26682, 29691, 477, 1826, 19253, 483, 4676, 15609, 555, 8582, 323, 4827, 31284, 1594, 59132, 661, 3547, 552, 220, 22, 662, 578, 3230, 26364, 3079, 22484, 527, 1101, 27000, 304, 279, 25107, 16035, 315, 279, 8316, 11, 1405, 279, 22267, 2931, 426, 18, 69187, 706, 279, 15821, 37148, 323, 8592, 52255, 8970, 320, 18031, 62644, 304, 99371, 43252, 220, 19, 13, 17, 13, 16, 323, 220, 19, 13, 17, 13, 17, 323, 5089, 49920, 304, 99371, 43252, 220, 19, 13, 17, 13, 18, 323, 220, 19, 13, 17, 13, 19, 7609, 578, 18112, 315, 279, 58309, 4225, 484, 13533, 430, 12308, 426, 8316, 270, 9890, 7119, 279, 3118, 13962, 41128, 374, 11, 1612, 278, 311, 279, 59132, 2592, 304, 279, 3428, 24405, 304, 279, 10411, 320, 30035, 13, 220, 16, 7609, 3765, 1263, 519, 17808, 3474, 1018, 355, 4917, 64947, 527, 12715, 304, 8316, 426, 16, 323, 426, 18, 11, 902, 1101, 6782, 28036, 9257, 304, 37518, 323, 39786, 278, 6136, 323, 304, 65932, 65216, 18563, 69, 3746, 8839, 11, 439, 1664, 439, 80492, 78343, 288, 220, 605, 1174, 220, 868, 662, 15636, 11, 279, 259, 1366, 17404, 315, 279, 15922, 1455, 4762, 27053, 279, 24156, 10977, 2781, 6879, 505, 264, 2134, 315, 71699, 11, 1344, 12328, 34575, 40460, 311, 279, 12018, 2548, 461, 323, 38626, 439, 17808, 3474, 1018, 355, 9709, 1139, 68539, 3221, 7666, 461, 11163, 12843, 2949, 8316, 426, 16, 323, 426, 18, 13, 82671, 11, 279, 19662, 3090, 3547, 552, 505, 12308, 362, 323, 5089, 426, 17, 617, 264, 16643, 29691, 8450, 13, 1115, 15398, 374, 7396, 555, 279, 43874, 304, 279, 25107, 540, 292, 18528, 1990, 32765, 735, 6282, 42077, 72466, 11163, 12843, 323, 13818, 435, 73, 301, 451, 11163, 12843, 320, 10254, 67082, 43252, 220, 19, 13, 17, 13, 16, 323, 220, 19, 13, 17, 13, 20, 7609, 80850, 4325, 362, 4101, 315, 58535, 7978, 706, 2450, 3210, 74035, 279, 26364, 3079, 4325, 32742, 315, 279, 32765, 735, 6282, 42077, 72466, 505, 220, 19, 13, 15, 4235, 15, 13, 22, 3092, 81, 311, 264, 220, 508, 11, 931, 4771, 24725, 4325, 32742, 2212, 220, 17, 13, 19, 3092, 81, 320, 4151, 99371, 8245, 11, 14491, 220, 16, 1389, 220, 18, 7609, 1115, 574, 17427, 555, 264, 10824, 315, 11091, 6043, 316, 64333, 2191, 11, 17332, 496, 266, 93170, 323, 63747, 496, 266, 93170, 220, 22, 128257, 198, 128256, 78191, 198, 72326, 11352, 279, 24417, 3967, 15922, 323, 1511, 433, 311, 16805, 1148, 2324, 574, 1093, 220, 17, 3610, 1667, 4227, 304, 279, 18671, 11813, 315, 73778, 13, 11450, 11, 433, 596, 264, 95088, 37518, 24521, 11, 719, 1203, 1243, 433, 574, 264, 58367, 18921, 315, 12690, 323, 54832, 449, 459, 1358, 315, 10099, 11, 1524, 279, 1457, 69918, 19218, 77152, 13, 330, 791, 4007, 16264, 279, 6134, 1139, 264, 3347, 430, 706, 13524, 1027, 5675, 1359, 1071, 3063, 3229, 44023, 735, 73, 34571, 11, 264, 3980, 16549, 323, 94867, 6335, 520, 279, 3907, 315, 64161, 13, 3161, 10065, 81473, 2653, 311, 2586, 555, 11, 279, 12074, 28532, 12434, 15922, 11, 1101, 3967, 439, 384, 56420, 11, 505, 17614, 10688, 13, 1115, 374, 279, 19465, 3769, 430, 44304, 25351, 1139, 872, 40190, 72318, 3187, 11, 1555, 7013, 11, 12571, 11, 57087, 477, 29602, 8478, 75566, 52090, 13, 7814, 7169, 2216, 2362, 15922, 649, 387, 264, 8815, 1606, 279, 19465, 3769, 18808, 1523, 927, 892, 11, 9564, 14248, 449, 1193, 13987, 35603, 13, 2030, 449, 279, 5652, 5557, 11, 12074, 1051, 3025, 311, 636, 19465, 2038, 704, 315, 279, 2678, 11, 20727, 9660, 315, 15922, 11, 11497, 10195, 3229, 9419, 441, 4946, 388, 3532, 11, 264, 19465, 380, 520, 279, 3907, 315, 24562, 13, 763, 872, 4007, 11, 4756, 8079, 304, 279, 8486, 22037, 11, 814, 7863, 279, 15922, 311, 430, 315, 2204, 9606, 11, 3411, 369, 9248, 13, 578, 10688, 3782, 505, 264, 59132, 16946, 2663, 279, 32765, 735, 6282, 42077, 18488, 304, 5250, 661, 11680, 13, 11450, 11, 279, 3158, 374, 264, 25685, 24521, 11, 735, 73, 34571, 1071, 13, 1115, 40134, 3984, 555, 12074, 62991, 32765, 60248, 40967, 31697, 11, 73778, 11, 1403, 3610, 1667, 4227, 11, 994, 279, 9499, 574, 12207, 46039, 1109, 18671, 3646, 73778, 3432, 13, 57116, 617, 30239, 220, 17, 46149, 4771, 6418, 15922, 28532, 505, 26351, 10688, 304, 279, 3158, 11, 31720, 459, 14154, 26031, 20426, 4205, 3970, 389, 9420, 3432, 11, 2737, 35483, 315, 19218, 347, 2439, 323, 60475, 4385, 4748, 1589, 3518, 69353, 279, 37518, 13, 16666, 25, 29103, 65808, 37533, 4669, 10314, 2030, 11990, 315, 1667, 4227, 11, 420, 5654, 574, 47397, 264, 4261, 315, 19428, 10182, 2349, 430, 3288, 20472, 709, 11, 4946, 388, 3532, 1071, 13, 36378, 3904, 4461, 5918, 709, 369, 22781, 315, 9214, 315, 1667, 520, 279, 2816, 1603, 279, 10182, 65410, 323, 24532, 291, 279, 14035, 1139, 824, 99161, 42602, 13, 578, 9439, 4676, 1053, 1520, 21813, 279, 36301, 9660, 315, 15922, 2345, 39830, 14248, 3782, 3235, 323, 68865, 279, 10688, 704, 11, 7314, 304, 220, 1049, 21, 13, 12220, 279, 5654, 596, 8369, 4261, 11, 994, 5578, 20472, 1051, 220, 508, 311, 220, 1958, 12628, 69823, 320, 806, 311, 220, 777, 12628, 62447, 8, 5190, 1109, 3432, 11, 279, 3158, 574, 10409, 449, 459, 19018, 1358, 315, 6136, 323, 10065, 2324, 11, 279, 12074, 5068, 13, 578, 15922, 35603, 4284, 264, 6651, 315, 37518, 11012, 11, 1093, 15606, 331, 12690, 323, 690, 363, 14362, 16115, 11, 449, 6305, 430, 6118, 10932, 46039, 92399, 11, 1093, 282, 17260, 323, 272, 291, 1590, 13, 578, 15922, 1101, 8710, 35483, 315, 10099, 2737, 3980, 2423, 11, 305, 5518, 11, 15601, 97362, 323, 514, 3906, 826, 13, 59787, 11, 264, 86636, 98486, 323, 1063, 96018, 8625, 1047, 1027, 279, 1193, 12195, 315, 10065, 2324, 520, 279, 2816, 11, 4946, 388, 3532, 1071, 13, 8626, 434, 1105, 9419, 441, 4946, 388, 3532, 323, 44023, 473, 13, 735, 5697, 261, 29241, 7878, 13931, 369, 25936, 315, 11163, 12843, 520, 32765, 60248, 40967, 31697, 11, 73778, 13, 57116, 617, 30239, 220, 17, 46149, 4771, 6418, 15922, 28532, 505, 26351, 10688, 304, 279, 3158, 11, 31720, 459, 14154, 26031, 20426, 4205, 3970, 389, 9420, 3432, 11, 2737, 35483, 315, 19218, 347, 2439, 323, 60475, 4385, 4748, 1589, 3518, 69353, 279, 37518, 13, 16666, 25, 64705, 408, 435, 8154, 4669, 10314, 3861, 2466, 13051, 574, 9455, 15922, 505, 279, 19218, 77152, 11, 459, 69918, 9606, 430, 5992, 1093, 264, 6651, 1990, 459, 46840, 323, 264, 33820, 68504, 11, 735, 73, 34571, 1071, 13, 9176, 19218, 77152, 81473, 617, 8767, 1027, 1766, 505, 6940, 349, 36658, 304, 4892, 5270, 13, 3011, 596, 459, 18435, 3201, 505, 73778, 11, 323, 1790, 43726, 10007, 11, 4946, 388, 3532, 1071, 13, 330, 40, 8434, 956, 617, 11, 304, 264, 3610, 1667, 11, 3685, 311, 1505, 19218, 347, 2439, 304, 18671, 73778, 1359, 1071, 10919, 29210, 268, 11, 264, 32185, 304, 41993, 4173, 24203, 520, 53182, 3907, 889, 574, 539, 6532, 304, 279, 4007, 13, 9393, 279, 59132, 5918, 709, 304, 279, 11013, 315, 264, 76471, 541, 11, 12074, 1051, 1101, 3025, 311, 636, 43775, 922, 29691, 2324, 505, 420, 892, 4261, 13, 578, 15922, 13533, 60475, 4385, 4748, 1589, 3518, 323, 6307, 68951, 12439, 304, 279, 3158, 2345, 57865, 279, 14373, 21160, 1051, 4461, 1790, 46039, 1203, 1243, 11, 735, 73, 34571, 1071, 13, 3296, 23062, 22700, 315, 9606, 704, 315, 1120, 264, 2478, 59132, 10688, 11, 279, 4007, 22020, 1063, 315, 384, 56420, 596, 22934, 11, 1071, 30411, 49845, 354, 11, 459, 14154, 15922, 32185, 520, 10057, 596, 7639, 9878, 377, 10181, 369, 38321, 661, 70384, 2508, 889, 574, 539, 6532, 304, 279, 4007, 13, 1115, 220, 1049, 21, 6685, 3984, 555, 12074, 5039, 264, 3345, 5352, 315, 17808, 3769, 304, 35335, 34751, 520, 32765, 60248, 40967, 31697, 11, 73778, 13, 578, 17808, 13931, 1501, 35483, 315, 279, 9257, 6136, 82088, 323, 27080, 100014, 430, 12439, 1403, 3610, 1667, 4227, 13, 57116, 617, 30239, 220, 17, 46149, 4771, 6418, 15922, 28532, 505, 26351, 10688, 304, 279, 3158, 11, 31720, 459, 14154, 26031, 20426, 4205, 3970, 389, 9420, 3432, 11, 2737, 35483, 315, 19218, 347, 2439, 323, 60475, 4385, 4748, 1589, 3518, 69353, 279, 37518, 13, 16666, 25, 64705, 408, 435, 8154, 4669, 10314, 330, 2675, 2216, 636, 264, 27927, 6945, 315, 279, 26031, 520, 264, 4040, 892, 1359, 49845, 354, 1071, 13, 330, 2675, 1541, 956, 617, 311, 733, 323, 1505, 420, 6710, 315, 7732, 311, 4007, 420, 6136, 11, 323, 420, 17685, 311, 4007, 420, 33820, 68504, 1210, 20817, 389, 279, 828, 2561, 11, 433, 596, 2653, 311, 2019, 369, 2771, 3508, 1521, 9606, 9615, 12439, 3185, 555, 3185, 11, 477, 422, 279, 15922, 574, 9709, 3871, 505, 2204, 5596, 315, 279, 18921, 11, 1071, 30928, 469, 604, 11, 459, 384, 56420, 6335, 520, 10057, 596, 3907, 315, 24277, 267, 12341, 889, 574, 539, 6532, 304, 279, 4007, 13, 1115, 220, 1049, 21, 6685, 3984, 555, 12074, 5039, 86278, 62264, 520, 32765, 60248, 40967, 31697, 11, 73778, 13, 2468, 279, 5740, 315, 279, 3857, 11, 279, 5655, 29691, 34751, 527, 29204, 467, 555, 279, 35335, 34751, 315, 7060, 68539, 3769, 13, 578, 1403, 1274, 520, 279, 1948, 527, 25936, 369, 12434, 15922, 13, 57116, 617, 30239, 220, 17, 46149, 4771, 6418, 15922, 28532, 505, 26351, 10688, 304, 279, 3158, 11, 31720, 459, 14154, 26031, 20426, 4205, 3970, 389, 9420, 3432, 11, 2737, 35483, 315, 19218, 347, 2439, 323, 60475, 4385, 4748, 1589, 3518, 69353, 279, 37518, 13, 16666, 25, 64705, 408, 435, 8154, 4669, 10314, 2030, 469, 604, 1071, 420, 3169, 315, 15922, 3495, 374, 15525, 311, 1501, 330, 6397, 20057, 1, 304, 14154, 55890, 13, 4946, 388, 3532, 13919, 430, 1606, 1521, 11012, 323, 10099, 26968, 2391, 264, 892, 315, 22520, 10182, 2349, 11, 872, 15922, 1436, 3085, 264, 330, 4469, 5411, 69917, 1, 311, 1520, 603, 10737, 311, 1510, 24808, 13, 53182, 3907, 596, 29210, 268, 25283, 14154, 15922, 3495, 311, 2567, 17919, 19662, 1139, 279, 3347, 13, 1283, 6575, 389, 279, 4007, 430, 8767, 5762, 279, 330, 337, 5086, 15922, 1, 3335, 11, 505, 264, 33820, 68504, 26588, 2212, 264, 3610, 1667, 2362, 13, 1115, 220, 1049, 21, 6685, 3984, 555, 12074, 5039, 279, 18921, 520, 32765, 60248, 40967, 31697, 11, 73778, 13, 578, 1690, 35231, 617, 1027, 14454, 555, 36617, 4401, 7119, 279, 13962, 13, 57116, 617, 30239, 220, 17, 46149, 4771, 6418, 15922, 28532, 505, 26351, 10688, 304, 279, 3158, 11, 31720, 459, 14154, 26031, 20426, 4205, 3970, 389, 9420, 3432, 11, 2737, 35483, 315, 19218, 347, 2439, 323, 60475, 4385, 4748, 1589, 3518, 69353, 279, 37518, 13, 16666, 25, 44023, 473, 13, 735, 5697, 261, 4669, 10314, 330, 40, 8434, 956, 387, 14792, 422, 499, 649, 733, 520, 3325, 832, 477, 8530, 264, 2478, 3610, 1667, 4726, 1203, 11, 26619, 499, 649, 1505, 279, 1314, 10688, 1359, 29210, 268, 1071, 13, 220, 128257, 198 ]

2,876

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Interest in circulating RNAs for monitoring and diagnosing human health has grown significantly. There are few datasets describing baseline expression levels for total cell-free circulating RNA from healthy control subjects. In this study, total extracellular RNA (exRNA) was isolated and sequenced from 183 plasma samples, 204 urine samples and 46 saliva samples from 55 male college athletes ages 18–25 years. Many participants provided more than one sample, allowing us to investigate variability in an individual’s exRNA expression levels over time. Here we provide a systematic analysis of small exRNAs present in each biofluid, as well as an analysis of exogenous RNAs. The small RNA profile of each biofluid is distinct. We find that a large number of RNA fragments in plasma (63%) and urine (54%) have sequences that are assigned to YRNA and tRNA fragments respectively. Surprisingly, while many miRNAs can be detected, there are few miRNAs that are consistently detected in all samples from a single biofluid, and profiles of miRNA are different for each biofluid. Not unexpectedly, saliva samples have high levels of exogenous sequence that can be traced to bacteria. These data significantly contribute to the current number of sequenced exRNA samples from normal healthy individuals. Introduction The field of circulating extracellular molecules is rapidly growing, fueled by the potential for development of new diagnostic and therapeutic tools. As the field is still largely in an exploratory and descriptive phase, there are no standardized methods for sample collection, isolation, or analysis. It is currently unclear what the expectations for a good quality sample should be, and each biofluid under various disease and injury conditions will likely have diverse contents and different criteria for quality. Large datasets examining different biofluids, isolation methods, detection platforms and analysis tools are important to further our understanding of the extent and types of extracellular material present in biofluids. These data will help inform us about how best to develop additional tools to enrich and capture specific types of information. Circulating extracellular molecular material includes RNAs, DNA, lipids, and proteins (reviewed in refs 1 , 2 , 3 , 4 ). Carrying these materials to their targets, cells/tissues/organs, and protecting them from degradation, are a variety of extracellular vesicles, lipoproteins, and other RNA-binding proteins 5 , 6 , 7 . A growing number of isolation methods for profiling circulating extracellular molecules have been, and are being, developed. There is still considerable work necessary to identify the most efficient inclusive or selective protocols, depending on the downstream question. There is also a need for rigorous characterization of the biological functions of circulating extracellular RNAs. There are few large datasets describing the extracellular contents in biofluid samples from normal controls 8 , 9 , 10 , 11 , 12 , 13 . Here we describe the largest dataset to date, focusing on total cell-free RNA (extracellular RNA), using next generation sequencing to profile the small RNA (16–32 nts) payload of human biofluids. Extracellular RNA was isolated and the small RNA content sequenced for 183 plasma samples, 204 urine samples and 46 saliva samples from 55 male college athletes ages 18–25 years. We examined the total RNA in an attempt not to exclude any information in our profile, as extracellular RNAs are packaged not only into extracellular vesicles, but are also associated with lipoproteins 5 and AGO2 6 , 7 . We profiled the RNA contents from these samples and examined the prevalence of different RNA biotypes. YRNA and tRNA fragments have previously been identified as abundant RNA species in extracellular vesicles and in biofluids 14 , 15 , 16 , 17 , 18 , 19 , 20 . We also found significant expression of YRNA and tRNA fragments in plasma and urine, respectively. The reasons for such high levels of these small RNA fragments and their functions, are not yet known. YRNA fragments do not appear to be a part of the same regulatory pathway as miRNA or generated by Dicer 21 . They may play a role in apoptosis 18 , 22 , the degradation of misprocessed RNAs 23 , and/or DNA replication 24 . tRNA fragments (TRFs) can be created in response to stress (reviewed in ref. 25 ). tRNA fragments have also been found to have a unique role in displacing RNA binding proteins that can protect mRNAs from degradation 26 . It should be noted, that tRNAs also have many different modifications along them, which may interfere with their full representation by conventional sequencing approaches 27 , 28 . miRNAs make up a large portion of the reads generated for each sample. miRNAs typically function in post-transcriptional gene regulation. Their role in extracellular vesicles appears to be less well understood and is potentially more diverse - as a means to rapidly remove miRNA, and as a way to alter local tissue microenvironment and regulate surrounding cells (reviewed in refs 3 and 29 ). We also detect piRNAs that repress transposable elements in the germline (reviewed in ref. 30 ). It is unknown what role piRNA play in circulating biofluids from normal healthy individuals. We also detect other small RNA species 31 that are expressed at low levels in biofluids. Throughout the analysis, it is important to bear in mind that sequencing data provides information on the proportion of RNA biotypes relative to one another in each sample, but not absolute concentrations of RNAs. Therefore, many of the analyses are presented as RPM or percentages of total input reads or reads mapping to the human genome. Results Summary of the input read alignments Total cell-free RNA was isolated from plasma, urine, and saliva; sequencing libraries were created using the Illumina TruSeq small RNA preparation kit. We sequenced the small RNA contents from 183 plasma samples, 204 urine samples and 46 saliva samples taken from male college athletes age 18–25. In our comparison of small RNAs in biofluids, we excluded plasma samples with <5% miRNA mapped reads and urine and saliva samples with <0.5% miRNA mapped reads (calculated from the total number", "role": "user" }, { "content": "Following a three-year study of the Arizona State University football program, researchers at the Translational Genomics Research Institute (TGen) have created the largest dataset to date of extracellular small RNAs, which are potential biomarkers for diagnosing medical conditions, including concussions. Details of the dataset were published today in Scientific Reports, an online open-access journal of the Nature Publishing Group. The study amassed a collection of biomarkers from the ASU student-athletes' biofluids: blood, urine and saliva. A portion of that information will be used with data from helmet sensors that recorded the number, intensity and direction of head impacts during games and practices from the 2013-16 football teams. TGen researchers are using that combined data to potentially develop new diagnostic and therapeutic tools. \"Large datasets—examining different biofluids, isolation methods, detection platforms and analysis tools—are important to further our understanding of the extent and types of extracellular materials present when someone is injured or develops disease,\" said Dr. Kendall Van Keuren-Jensen, TGen Associate Professor of Neurogenomics and Co-Director of TGen's Center for Noninvasive Diagnostics, and one of the study's senior authors. \"Concussion safety, protocol and diagnostics are key components of Sun Devil Athletics' student-athlete welfare program,\" said Ray Anderson, ASU Vice President for University Athletics. \"Our partnership with TGen and the research conducted with these biomarkers will ideally provide doctors, trainers and administrators with a mechanism to proactively safeguard the health of our student-athletes. We are proud and excited to be a part of this groundbreaking study that will significantly expand research in this important area of scientific discovery.\" Because the data is being published in an open access journal, they are available to aid other researchers studying how to develop tests for the detection and extent of injuries involving everything from automobile accidents to battlefield explosions. Sensors in the ASU student-athlete football helmets were wirelessly connected to a field-level computer as part of the Sideline Response System—a head impact monitoring and research tool developed and deployed by Riddell, a leading provider of helmets to the NFL and major college football teams. \"Riddell is pleased to be engaged with TGen on its important research as it has great potential to help the scientific community worldwide in the development of new breakthroughs, particularly in the area of brain health,\" said Dan Arment, President and Chief Executive Officer of Riddell, the industry leader in football helmet technology and innovation. TGen researchers used advanced genomic sequencing to identify the biomarkers of extracellular RNA (exRNA), strands of genetic material that are released from cells, and which can be detected in biofluids. TGen sequenced, or spelled out, the chemical letters that make up these biomarkers from among 183 blood samples, 204 urine samples and 46 saliva samples derived from among 55 consenting student-athletes, ages 18-25. \"The small RNA profile of each biofluid is distinct,\" the study said. \"These data significantly contribute to the current number of sequenced exRNA samples from young healthy individuals.\" By identifying biofluids associated with healthy individuals, researchers hope to use these as standards for assessing disease and injury: \"Establishing a baseline for individuals when they are healthy may provide the most meaningful comparisons when exploring early indicators of disease, severity or outcome,\" the study said. \"These data will help inform us about how best to develop additional tools to enrich and capture specific types of information,\" according to the paper, titled: \"Total Extracellular Small RNA Profiles from Plasma, Saliva, and Urine of Healthy Subjects.\" \"We have tried to provide the most comprehensive profile of the small RNA species detected in our samples,\" said Dr. Matt Huentelman, TGen Professor of Neurogenomics, and one of the study's lead authors. \"This information may prove to be essential as the field moves toward using RNA expression changes for the detection of health, disease and injury.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Interest in circulating RNAs for monitoring and diagnosing human health has grown significantly. There are few datasets describing baseline expression levels for total cell-free circulating RNA from healthy control subjects. In this study, total extracellular RNA (exRNA) was isolated and sequenced from 183 plasma samples, 204 urine samples and 46 saliva samples from 55 male college athletes ages 18–25 years. Many participants provided more than one sample, allowing us to investigate variability in an individual’s exRNA expression levels over time. Here we provide a systematic analysis of small exRNAs present in each biofluid, as well as an analysis of exogenous RNAs. The small RNA profile of each biofluid is distinct. We find that a large number of RNA fragments in plasma (63%) and urine (54%) have sequences that are assigned to YRNA and tRNA fragments respectively. Surprisingly, while many miRNAs can be detected, there are few miRNAs that are consistently detected in all samples from a single biofluid, and profiles of miRNA are different for each biofluid. Not unexpectedly, saliva samples have high levels of exogenous sequence that can be traced to bacteria. These data significantly contribute to the current number of sequenced exRNA samples from normal healthy individuals. Introduction The field of circulating extracellular molecules is rapidly growing, fueled by the potential for development of new diagnostic and therapeutic tools. As the field is still largely in an exploratory and descriptive phase, there are no standardized methods for sample collection, isolation, or analysis. It is currently unclear what the expectations for a good quality sample should be, and each biofluid under various disease and injury conditions will likely have diverse contents and different criteria for quality. Large datasets examining different biofluids, isolation methods, detection platforms and analysis tools are important to further our understanding of the extent and types of extracellular material present in biofluids. These data will help inform us about how best to develop additional tools to enrich and capture specific types of information. Circulating extracellular molecular material includes RNAs, DNA, lipids, and proteins (reviewed in refs 1 , 2 , 3 , 4 ). Carrying these materials to their targets, cells/tissues/organs, and protecting them from degradation, are a variety of extracellular vesicles, lipoproteins, and other RNA-binding proteins 5 , 6 , 7 . A growing number of isolation methods for profiling circulating extracellular molecules have been, and are being, developed. There is still considerable work necessary to identify the most efficient inclusive or selective protocols, depending on the downstream question. There is also a need for rigorous characterization of the biological functions of circulating extracellular RNAs. There are few large datasets describing the extracellular contents in biofluid samples from normal controls 8 , 9 , 10 , 11 , 12 , 13 . Here we describe the largest dataset to date, focusing on total cell-free RNA (extracellular RNA), using next generation sequencing to profile the small RNA (16–32 nts) payload of human biofluids. Extracellular RNA was isolated and the small RNA content sequenced for 183 plasma samples, 204 urine samples and 46 saliva samples from 55 male college athletes ages 18–25 years. We examined the total RNA in an attempt not to exclude any information in our profile, as extracellular RNAs are packaged not only into extracellular vesicles, but are also associated with lipoproteins 5 and AGO2 6 , 7 . We profiled the RNA contents from these samples and examined the prevalence of different RNA biotypes. YRNA and tRNA fragments have previously been identified as abundant RNA species in extracellular vesicles and in biofluids 14 , 15 , 16 , 17 , 18 , 19 , 20 . We also found significant expression of YRNA and tRNA fragments in plasma and urine, respectively. The reasons for such high levels of these small RNA fragments and their functions, are not yet known. YRNA fragments do not appear to be a part of the same regulatory pathway as miRNA or generated by Dicer 21 . They may play a role in apoptosis 18 , 22 , the degradation of misprocessed RNAs 23 , and/or DNA replication 24 . tRNA fragments (TRFs) can be created in response to stress (reviewed in ref. 25 ). tRNA fragments have also been found to have a unique role in displacing RNA binding proteins that can protect mRNAs from degradation 26 . It should be noted, that tRNAs also have many different modifications along them, which may interfere with their full representation by conventional sequencing approaches 27 , 28 . miRNAs make up a large portion of the reads generated for each sample. miRNAs typically function in post-transcriptional gene regulation. Their role in extracellular vesicles appears to be less well understood and is potentially more diverse - as a means to rapidly remove miRNA, and as a way to alter local tissue microenvironment and regulate surrounding cells (reviewed in refs 3 and 29 ). We also detect piRNAs that repress transposable elements in the germline (reviewed in ref. 30 ). It is unknown what role piRNA play in circulating biofluids from normal healthy individuals. We also detect other small RNA species 31 that are expressed at low levels in biofluids. Throughout the analysis, it is important to bear in mind that sequencing data provides information on the proportion of RNA biotypes relative to one another in each sample, but not absolute concentrations of RNAs. Therefore, many of the analyses are presented as RPM or percentages of total input reads or reads mapping to the human genome. Results Summary of the input read alignments Total cell-free RNA was isolated from plasma, urine, and saliva; sequencing libraries were created using the Illumina TruSeq small RNA preparation kit. We sequenced the small RNA contents from 183 plasma samples, 204 urine samples and 46 saliva samples taken from male college athletes age 18–25. In our comparison of small RNAs in biofluids, we excluded plasma samples with <5% miRNA mapped reads and urine and saliva samples with <0.5% miRNA mapped reads (calculated from the total number<|im_end|> <|im_start|>assistant Following a three-year study of the Arizona State University football program, researchers at the Translational Genomics Research Institute (TGen) have created the largest dataset to date of extracellular small RNAs, which are potential biomarkers for diagnosing medical conditions, including concussions. Details of the dataset were published today in Scientific Reports, an online open-access journal of the Nature Publishing Group. The study amassed a collection of biomarkers from the ASU student-athletes' biofluids: blood, urine and saliva. A portion of that information will be used with data from helmet sensors that recorded the number, intensity and direction of head impacts during games and practices from the 2013-16 football teams. TGen researchers are using that combined data to potentially develop new diagnostic and therapeutic tools. "Large datasets—examining different biofluids, isolation methods, detection platforms and analysis tools—are important to further our understanding of the extent and types of extracellular materials present when someone is injured or develops disease," said Dr. Kendall Van Keuren-Jensen, TGen Associate Professor of Neurogenomics and Co-Director of TGen's Center for Noninvasive Diagnostics, and one of the study's senior authors. "Concussion safety, protocol and diagnostics are key components of Sun Devil Athletics' student-athlete welfare program," said Ray Anderson, ASU Vice President for University Athletics. "Our partnership with TGen and the research conducted with these biomarkers will ideally provide doctors, trainers and administrators with a mechanism to proactively safeguard the health of our student-athletes. We are proud and excited to be a part of this groundbreaking study that will significantly expand research in this important area of scientific discovery." Because the data is being published in an open access journal, they are available to aid other researchers studying how to develop tests for the detection and extent of injuries involving everything from automobile accidents to battlefield explosions. Sensors in the ASU student-athlete football helmets were wirelessly connected to a field-level computer as part of the Sideline Response System—a head impact monitoring and research tool developed and deployed by Riddell, a leading provider of helmets to the NFL and major college football teams. "Riddell is pleased to be engaged with TGen on its important research as it has great potential to help the scientific community worldwide in the development of new breakthroughs, particularly in the area of brain health," said Dan Arment, President and Chief Executive Officer of Riddell, the industry leader in football helmet technology and innovation. TGen researchers used advanced genomic sequencing to identify the biomarkers of extracellular RNA (exRNA), strands of genetic material that are released from cells, and which can be detected in biofluids. TGen sequenced, or spelled out, the chemical letters that make up these biomarkers from among 183 blood samples, 204 urine samples and 46 saliva samples derived from among 55 consenting student-athletes, ages 18-25. "The small RNA profile of each biofluid is distinct," the study said. "These data significantly contribute to the current number of sequenced exRNA samples from young healthy individuals." By identifying biofluids associated with healthy individuals, researchers hope to use these as standards for assessing disease and injury: "Establishing a baseline for individuals when they are healthy may provide the most meaningful comparisons when exploring early indicators of disease, severity or outcome," the study said. "These data will help inform us about how best to develop additional tools to enrich and capture specific types of information," according to the paper, titled: "Total Extracellular Small RNA Profiles from Plasma, Saliva, and Urine of Healthy Subjects." "We have tried to provide the most comprehensive profile of the small RNA species detected in our samples," said Dr. Matt Huentelman, TGen Professor of Neurogenomics, and one of the study's lead authors. "This information may prove to be essential as the field moves toward using RNA expression changes for the detection of health, disease and injury." <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 25074, 304, 54828, 46916, 2170, 369, 16967, 323, 13493, 14759, 3823, 2890, 706, 15042, 12207, 13, 2684, 527, 2478, 30525, 23524, 26954, 7645, 5990, 369, 2860, 2849, 12862, 54828, 41214, 505, 9498, 2585, 15223, 13, 763, 420, 4007, 11, 2860, 11741, 65441, 41214, 320, 327, 31820, 8, 574, 25181, 323, 11506, 5886, 505, 220, 10750, 32426, 10688, 11, 220, 7854, 40335, 10688, 323, 220, 2790, 85657, 10688, 505, 220, 2131, 8762, 7926, 23579, 17051, 220, 972, 4235, 914, 1667, 13, 9176, 13324, 3984, 810, 1109, 832, 6205, 11, 10923, 603, 311, 19874, 54709, 304, 459, 3927, 753, 506, 31820, 7645, 5990, 927, 892, 13, 5810, 584, 3493, 264, 37538, 6492, 315, 2678, 506, 51295, 2170, 3118, 304, 1855, 17332, 67125, 11, 439, 1664, 439, 459, 6492, 315, 506, 53595, 46916, 2170, 13, 578, 2678, 41214, 5643, 315, 1855, 17332, 67125, 374, 12742, 13, 1226, 1505, 430, 264, 3544, 1396, 315, 41214, 35603, 304, 32426, 320, 5495, 11587, 323, 40335, 320, 4370, 11587, 617, 24630, 430, 527, 12893, 311, 816, 31820, 323, 259, 31820, 35603, 15947, 13, 8242, 49264, 11, 1418, 1690, 9686, 51295, 2170, 649, 387, 16914, 11, 1070, 527, 2478, 9686, 51295, 2170, 430, 527, 21356, 16914, 304, 682, 10688, 505, 264, 3254, 17332, 67125, 11, 323, 21542, 315, 9686, 31820, 527, 2204, 369, 1855, 17332, 67125, 13, 2876, 51709, 11, 85657, 10688, 617, 1579, 5990, 315, 506, 53595, 8668, 430, 649, 387, 51400, 311, 24032, 13, 4314, 828, 12207, 17210, 311, 279, 1510, 1396, 315, 11506, 5886, 506, 31820, 10688, 505, 4725, 9498, 7931, 13, 29438, 578, 2115, 315, 54828, 11741, 65441, 35715, 374, 19019, 7982, 11, 59461, 555, 279, 4754, 369, 4500, 315, 502, 15439, 323, 37471, 7526, 13, 1666, 279, 2115, 374, 2103, 14090, 304, 459, 48539, 5382, 323, 53944, 10474, 11, 1070, 527, 912, 51114, 5528, 369, 6205, 4526, 11, 31398, 11, 477, 6492, 13, 1102, 374, 5131, 25420, 1148, 279, 17078, 369, 264, 1695, 4367, 6205, 1288, 387, 11, 323, 1855, 17332, 67125, 1234, 5370, 8624, 323, 11134, 4787, 690, 4461, 617, 17226, 8970, 323, 2204, 13186, 369, 4367, 13, 20902, 30525, 38936, 2204, 17332, 67125, 82, 11, 31398, 5528, 11, 18468, 15771, 323, 6492, 7526, 527, 3062, 311, 4726, 1057, 8830, 315, 279, 13112, 323, 4595, 315, 11741, 65441, 3769, 3118, 304, 17332, 67125, 82, 13, 4314, 828, 690, 1520, 6179, 603, 922, 1268, 1888, 311, 2274, 5217, 7526, 311, 31518, 323, 12602, 3230, 4595, 315, 2038, 13, 16741, 15853, 11741, 65441, 31206, 3769, 5764, 46916, 2170, 11, 15922, 11, 19588, 3447, 11, 323, 28896, 320, 19981, 291, 304, 44243, 220, 16, 1174, 220, 17, 1174, 220, 18, 1174, 220, 19, 7609, 3341, 28609, 1521, 7384, 311, 872, 11811, 11, 7917, 5640, 18934, 42461, 598, 11, 323, 22973, 1124, 505, 53568, 11, 527, 264, 8205, 315, 11741, 65441, 65635, 4440, 11, 19588, 454, 5646, 1354, 11, 323, 1023, 41214, 65500, 28896, 220, 20, 1174, 220, 21, 1174, 220, 22, 662, 362, 7982, 1396, 315, 31398, 5528, 369, 56186, 54828, 11741, 65441, 35715, 617, 1027, 11, 323, 527, 1694, 11, 8040, 13, 2684, 374, 2103, 24779, 990, 5995, 311, 10765, 279, 1455, 11297, 29408, 477, 44010, 32885, 11, 11911, 389, 279, 52452, 3488, 13, 2684, 374, 1101, 264, 1205, 369, 47999, 60993, 315, 279, 24156, 5865, 315, 54828, 11741, 65441, 46916, 2170, 13, 2684, 527, 2478, 3544, 30525, 23524, 279, 11741, 65441, 8970, 304, 17332, 67125, 10688, 505, 4725, 11835, 220, 23, 1174, 220, 24, 1174, 220, 605, 1174, 220, 806, 1174, 220, 717, 1174, 220, 1032, 662, 5810, 584, 7664, 279, 7928, 10550, 311, 2457, 11, 21760, 389, 2860, 2849, 12862, 41214, 320, 39749, 65441, 41214, 705, 1701, 1828, 9659, 62119, 311, 5643, 279, 2678, 41214, 320, 845, 4235, 843, 308, 2641, 8, 7885, 315, 3823, 17332, 67125, 82, 13, 72334, 65441, 41214, 574, 25181, 323, 279, 2678, 41214, 2262, 11506, 5886, 369, 220, 10750, 32426, 10688, 11, 220, 7854, 40335, 10688, 323, 220, 2790, 85657, 10688, 505, 220, 2131, 8762, 7926, 23579, 17051, 220, 972, 4235, 914, 1667, 13, 1226, 25078, 279, 2860, 41214, 304, 459, 4879, 539, 311, 22429, 904, 2038, 304, 1057, 5643, 11, 439, 11741, 65441, 46916, 2170, 527, 47237, 539, 1193, 1139, 11741, 65441, 65635, 4440, 11, 719, 527, 1101, 5938, 449, 19588, 454, 5646, 1354, 220, 20, 323, 15432, 46, 17, 220, 21, 1174, 220, 22, 662, 1226, 5643, 67, 279, 41214, 8970, 505, 1521, 10688, 323, 25078, 279, 38009, 315, 2204, 41214, 6160, 22583, 13, 816, 31820, 323, 259, 31820, 35603, 617, 8767, 1027, 11054, 439, 44611, 41214, 9606, 304, 11741, 65441, 65635, 4440, 323, 304, 17332, 67125, 82, 220, 975, 1174, 220, 868, 1174, 220, 845, 1174, 220, 1114, 1174, 220, 972, 1174, 220, 777, 1174, 220, 508, 662, 1226, 1101, 1766, 5199, 7645, 315, 816, 31820, 323, 259, 31820, 35603, 304, 32426, 323, 40335, 11, 15947, 13, 578, 8125, 369, 1778, 1579, 5990, 315, 1521, 2678, 41214, 35603, 323, 872, 5865, 11, 527, 539, 3686, 3967, 13, 816, 31820, 35603, 656, 539, 5101, 311, 387, 264, 961, 315, 279, 1890, 23331, 38970, 439, 9686, 31820, 477, 8066, 555, 423, 13296, 220, 1691, 662, 2435, 1253, 1514, 264, 3560, 304, 95874, 220, 972, 1174, 220, 1313, 1174, 279, 53568, 315, 5906, 35122, 46916, 2170, 220, 1419, 1174, 323, 5255, 15922, 48891, 220, 1187, 662, 259, 31820, 35603, 320, 2434, 49400, 8, 649, 387, 3549, 304, 2077, 311, 8631, 320, 19981, 291, 304, 2098, 13, 220, 914, 7609, 259, 31820, 35603, 617, 1101, 1027, 1766, 311, 617, 264, 5016, 3560, 304, 13770, 4628, 41214, 11212, 28896, 430, 649, 6144, 296, 51295, 2170, 505, 53568, 220, 1627, 662, 1102, 1288, 387, 10555, 11, 430, 259, 51295, 2170, 1101, 617, 1690, 2204, 29882, 3235, 1124, 11, 902, 1253, 40978, 449, 872, 2539, 13340, 555, 21349, 62119, 20414, 220, 1544, 1174, 220, 1591, 662, 9686, 51295, 2170, 1304, 709, 264, 3544, 13651, 315, 279, 16181, 8066, 369, 1855, 6205, 13, 9686, 51295, 2170, 11383, 734, 304, 1772, 39160, 1479, 278, 15207, 19812, 13, 11205, 3560, 304, 11741, 65441, 65635, 4440, 8111, 311, 387, 2753, 1664, 16365, 323, 374, 13893, 810, 17226, 482, 439, 264, 3445, 311, 19019, 4148, 9686, 31820, 11, 323, 439, 264, 1648, 311, 11857, 2254, 20438, 8162, 24175, 323, 37377, 14932, 7917, 320, 19981, 291, 304, 44243, 220, 18, 323, 220, 1682, 7609, 1226, 1101, 11388, 9115, 51295, 2170, 430, 312, 1911, 1380, 17877, 5540, 304, 279, 17684, 1029, 483, 320, 19981, 291, 304, 2098, 13, 220, 966, 7609, 1102, 374, 9987, 1148, 3560, 9115, 31820, 1514, 304, 54828, 17332, 67125, 82, 505, 4725, 9498, 7931, 13, 1226, 1101, 11388, 1023, 2678, 41214, 9606, 220, 2148, 430, 527, 13605, 520, 3428, 5990, 304, 17332, 67125, 82, 13, 46982, 279, 6492, 11, 433, 374, 3062, 311, 11984, 304, 4059, 430, 62119, 828, 5825, 2038, 389, 279, 21801, 315, 41214, 6160, 22583, 8844, 311, 832, 2500, 304, 1855, 6205, 11, 719, 539, 10973, 32466, 315, 46916, 2170, 13, 15636, 11, 1690, 315, 279, 29060, 527, 10666, 439, 54874, 477, 54208, 315, 2860, 1988, 16181, 477, 16181, 13021, 311, 279, 3823, 33869, 13, 18591, 22241, 315, 279, 1988, 1373, 93916, 10884, 2849, 12862, 41214, 574, 25181, 505, 32426, 11, 40335, 11, 323, 85657, 26, 62119, 20797, 1051, 3549, 1701, 279, 61720, 2259, 102287, 20794, 2678, 41214, 18459, 16530, 13, 1226, 11506, 5886, 279, 2678, 41214, 8970, 505, 220, 10750, 32426, 10688, 11, 220, 7854, 40335, 10688, 323, 220, 2790, 85657, 10688, 4529, 505, 8762, 7926, 23579, 4325, 220, 972, 4235, 914, 13, 763, 1057, 12593, 315, 2678, 46916, 2170, 304, 17332, 67125, 82, 11, 584, 28544, 32426, 10688, 449, 366, 20, 4, 9686, 31820, 24784, 16181, 323, 40335, 323, 85657, 10688, 449, 366, 15, 13, 20, 4, 9686, 31820, 24784, 16181, 320, 5531, 50904, 505, 279, 2860, 1396, 128257, 198, 128256, 78191, 198, 28055, 264, 2380, 4771, 4007, 315, 279, 17368, 3314, 3907, 9141, 2068, 11, 12074, 520, 279, 4149, 75, 1697, 9500, 24203, 8483, 10181, 320, 51, 10172, 8, 617, 3549, 279, 7928, 10550, 311, 2457, 315, 11741, 65441, 2678, 46916, 2170, 11, 902, 527, 4754, 39538, 91141, 369, 13493, 14759, 6593, 4787, 11, 2737, 3613, 39833, 13, 12589, 315, 279, 10550, 1051, 4756, 3432, 304, 38130, 29140, 11, 459, 2930, 1825, 43256, 8486, 315, 279, 22037, 37933, 5856, 13, 578, 4007, 93250, 264, 4526, 315, 39538, 91141, 505, 279, 5871, 52, 5575, 12, 589, 14203, 6, 17332, 67125, 82, 25, 6680, 11, 40335, 323, 85657, 13, 362, 13651, 315, 430, 2038, 690, 387, 1511, 449, 828, 505, 32635, 26148, 430, 12715, 279, 1396, 11, 21261, 323, 5216, 315, 2010, 25949, 2391, 3953, 323, 12659, 505, 279, 220, 679, 18, 12, 845, 9141, 7411, 13, 350, 10172, 12074, 527, 1701, 430, 11093, 828, 311, 13893, 2274, 502, 15439, 323, 37471, 7526, 13, 330, 35353, 30525, 2345, 42716, 5859, 2204, 17332, 67125, 82, 11, 31398, 5528, 11, 18468, 15771, 323, 6492, 7526, 83872, 3062, 311, 4726, 1057, 8830, 315, 279, 13112, 323, 4595, 315, 11741, 65441, 7384, 3118, 994, 4423, 374, 15902, 477, 39671, 8624, 1359, 1071, 2999, 13, 74176, 13000, 6706, 21904, 12278, 35117, 11, 350, 10172, 33468, 17054, 315, 32359, 4469, 24203, 323, 3623, 9607, 66576, 315, 350, 10172, 596, 5955, 369, 11842, 258, 78134, 7923, 15920, 11, 323, 832, 315, 279, 4007, 596, 10195, 12283, 13, 330, 1128, 66, 17861, 7296, 11, 11766, 323, 50518, 527, 1401, 6956, 315, 8219, 40301, 70831, 6, 5575, 12, 91044, 23460, 2068, 1359, 1071, 13558, 21293, 11, 5871, 52, 23270, 4900, 369, 3907, 70831, 13, 330, 8140, 15664, 449, 350, 10172, 323, 279, 3495, 13375, 449, 1521, 39538, 91141, 690, 50663, 3493, 16410, 11, 51191, 323, 38212, 449, 264, 17383, 311, 463, 64119, 49071, 279, 2890, 315, 1057, 5575, 12, 589, 14203, 13, 1226, 527, 12691, 323, 12304, 311, 387, 264, 961, 315, 420, 64955, 4007, 430, 690, 12207, 9407, 3495, 304, 420, 3062, 3158, 315, 12624, 18841, 1210, 9393, 279, 828, 374, 1694, 4756, 304, 459, 1825, 2680, 8486, 11, 814, 527, 2561, 311, 12576, 1023, 12074, 21630, 1268, 311, 2274, 7177, 369, 279, 18468, 323, 13112, 315, 15319, 16239, 4395, 505, 35528, 33788, 311, 38486, 56506, 13, 95520, 304, 279, 5871, 52, 5575, 12, 91044, 9141, 65720, 1051, 9244, 16117, 8599, 311, 264, 2115, 11852, 6500, 439, 961, 315, 279, 34989, 4939, 6075, 744, 29096, 2010, 5536, 16967, 323, 3495, 5507, 8040, 323, 27167, 555, 432, 1810, 616, 11, 264, 6522, 9287, 315, 65720, 311, 279, 12873, 323, 3682, 7926, 9141, 7411, 13, 330, 49, 1810, 616, 374, 18949, 311, 387, 17045, 449, 350, 10172, 389, 1202, 3062, 3495, 439, 433, 706, 2294, 4754, 311, 1520, 279, 12624, 4029, 15603, 304, 279, 4500, 315, 502, 42445, 82, 11, 8104, 304, 279, 3158, 315, 8271, 2890, 1359, 1071, 11824, 1676, 479, 11, 4900, 323, 14681, 18362, 20148, 315, 432, 1810, 616, 11, 279, 5064, 7808, 304, 9141, 32635, 5557, 323, 19297, 13, 350, 10172, 12074, 1511, 11084, 81064, 62119, 311, 10765, 279, 39538, 91141, 315, 11741, 65441, 41214, 320, 327, 31820, 705, 69864, 315, 19465, 3769, 430, 527, 6004, 505, 7917, 11, 323, 902, 649, 387, 16914, 304, 17332, 67125, 82, 13, 350, 10172, 11506, 5886, 11, 477, 68918, 704, 11, 279, 11742, 12197, 430, 1304, 709, 1521, 39538, 91141, 505, 4315, 220, 10750, 6680, 10688, 11, 220, 7854, 40335, 10688, 323, 220, 2790, 85657, 10688, 14592, 505, 4315, 220, 2131, 93501, 5575, 12, 589, 14203, 11, 17051, 220, 972, 12, 914, 13, 330, 791, 2678, 41214, 5643, 315, 1855, 17332, 67125, 374, 12742, 1359, 279, 4007, 1071, 13, 330, 9673, 828, 12207, 17210, 311, 279, 1510, 1396, 315, 11506, 5886, 506, 31820, 10688, 505, 3995, 9498, 7931, 1210, 3296, 25607, 17332, 67125, 82, 5938, 449, 9498, 7931, 11, 12074, 3987, 311, 1005, 1521, 439, 10886, 369, 47614, 8624, 323, 11134, 25, 330, 69320, 287, 264, 26954, 369, 7931, 994, 814, 527, 9498, 1253, 3493, 279, 1455, 23222, 36595, 994, 24919, 4216, 34824, 315, 8624, 11, 31020, 477, 15632, 1359, 279, 4007, 1071, 13, 330, 9673, 828, 690, 1520, 6179, 603, 922, 1268, 1888, 311, 2274, 5217, 7526, 311, 31518, 323, 12602, 3230, 4595, 315, 2038, 1359, 4184, 311, 279, 5684, 11, 25891, 25, 330, 7749, 72334, 65441, 15344, 41214, 72827, 505, 65632, 11, 8375, 10126, 11, 323, 17229, 483, 315, 44454, 65818, 1210, 330, 1687, 617, 6818, 311, 3493, 279, 1455, 16195, 5643, 315, 279, 2678, 41214, 9606, 16914, 304, 1057, 10688, 1359, 1071, 2999, 13, 13678, 473, 11942, 64641, 11, 350, 10172, 17054, 315, 32359, 4469, 24203, 11, 323, 832, 315, 279, 4007, 596, 3063, 12283, 13, 330, 2028, 2038, 1253, 12391, 311, 387, 7718, 439, 279, 2115, 11031, 9017, 1701, 41214, 7645, 4442, 369, 279, 18468, 315, 2890, 11, 8624, 323, 11134, 1210, 220, 128257, 198 ]

2,144

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract The glycans displayed on mammalian cells can differ markedly from those on microbes. Such differences could, in principle, be 'read' by carbohydrate-binding proteins, or lectins. We used glycan microarrays to show that human intelectin-1 (hIntL-1) does not bind known human glycan epitopes but does interact with multiple glycan epitopes found exclusively on microbes: β-linked D -galactofuranose (β-Gal f ), D -phosphoglycerol–modified glycans, heptoses, D - glycero- D - talo -oct-2-ulosonic acid (KO) and 3-deoxy- D- manno -oct-2-ulosonic acid (KDO). The 1.6-Å-resolution crystal structure of hIntL-1 complexed with β-Gal f revealed that hIntL-1 uses a bound calcium ion to coordinate terminal exocyclic 1,2-diols. N -acetylneuraminic acid (Neu5Ac), a sialic acid widespread in human glycans, has an exocyclic 1,2-diol but does not bind hIntL-1, probably owing to unfavorable steric and electronic effects. hIntL-1 marks only Streptococcus pneumoniae serotypes that display surface glycans with terminal 1,2-diol groups. This ligand selectivity suggests that hIntL-1 functions in microbial surveillance. Main Organisms that serve as hosts for microbes must distinguish microbial cells from those of their own 1 , 2 . A mechanism of differentiation is especially important at sites in which host tissues contact the environment, such as the lung, intestine and skin 3 , 4 . Differences in cellular surface glycosylation can serve as markers of a cell's identity—its developmental state, its tissue type or its being self or nonself 5 . Cell-surface glycans can be distinguished by carbohydrate-binding proteins, or lectins 6 , which are typically categorized on the basis of their monosaccharide selectivity 7 . These lectins can be exploited for host defense, as in the case of innate immune lectins, such as mannose-binding lectin 8 . In serum, mannose-binding lectin is precomplexed with mannose-binding lectin–associated serine proteases, and interaction of this complex with a cell surface results in activation of the lectin pathway of complement and ultimately leads to pathogen opsonization and clearance 9 , 10 . Other humoral lectins implicated in immunity include ficolins, collectins, galectins and HIP/PAP 1 , 11 , 12 , 13 . One group of lectins whose specificity has been unclear is the intelectins (IntLs). The first IntL protein was reported in Xenopus laevis oocytes 14 . Homologs have since been identified in many other chordates, including other amphibians, fishes and many mammals. IntLs belong to a family of lectins termed X-type lectins 15 and have been shown to exist as homo-oligomers of 35-kDa monomers. They are reported to function as calcium ion–dependent lectins; however, they do not contain the calcium-dependent C-type-lectin sequence motif 16 present in many human lectins. IntLs instead contain a fibrinogen-like domain (FBD, residues 37–82 in hIntL-1 (ref. 17 )) and have been proposed to be most similar to ficolins, a class of FBD-containing innate immune lectins 11 . Several observations have implicated IntLs in innate immunity. Mammalian IntLs are predominantly produced by lung and intestinal goblet cells, and intestinal Paneth cells 17 , 18 , 19 . In sheep and mice, IntL expression increases upon infection with intestinal parasitic nematodes 20 , 21 . In humans, the mucus induced by allergic reactions is enriched in IntLs 22 , 23 . Moreover, hIntL-1 has been reported to be the intestinal lactoferrin receptor 24 and to function as a tumor marker 25 . It also has been suggested to be involved in metabolic disorders including diabetes, in which it is known as omentin 26 . Given these diverse potential functions, we set out to examine the ligand specificity of hIntL-1. hIntL-1 has been reported to bind furanose residues (five-membered-ring saccharide isomers), including ribofuranose (Rib f ) and a β-Gal f –containing disaccharide 17 , 27 . The monosaccharide Gal f is present in the cell-surface glycans produced by a number of microbes, but the biosynthetic enzymes that mediate Gal f incorporation are absent in humans 28 , 29 , 30 . The presence of Gal f in microbial but not human glycans is an example of phylogenetic glycan differences 31 . This is just one example, and collectively the surface glycans of microbes are generated from more than 700 unique building blocks, whereas fewer than 35 carbohydrate residues are needed to assemble mammalian glycans 32 , 33 . In principle, targeting of monosaccharide residues unique to microbes could be used by the innate immune system to differentiate mammalian cells from microbes. We reasoned that clues to hIntL-1 function would emerge from determining the glycans to which hIntL-1 binds and the molecular basis for its recognition selectivity. Here, we use glycan microarrays to demonstrate that hIntL-1 preferentially binds microbial over human glycans. Given the diversity of microbial glycans, a lectin that binds a single microbial saccharide epitope (for example, galactofuranose) would be expected to have specialized functions. It is therefore striking that hIntL-1 does not engage a single monosaccharide or even related saccharides but instead interacts with multiple structurally divergent microbial monosaccharide residues. We have used X-ray crystallography to reveal the molecular mechanism by which hIntL-1 recognizes its targets: hIntL-1 binds its carbohydrate ligands through calcium ion–dependent coordination of a conserved exocyclic, terminal 1,2-diol. The functional-group selectivity observed in the glycan arrays is manifested in the context of cells because hIntL-1 targets S. pneumoniae serotypes that display its glycan ligands. Results hIntL-1 binds β-Gal f Native hIntL-1 has been shown to exist as a disulfide-linked trimer 17 , 27 . Therefore, we first developed a robust expression system that yields the protein as a disulfide-linked trimer that can be purified with an immobilized–β-Gal f column ( Supplementary Fig. 1a,b ). Because lectin-carbohydrate interactions often depend on multivalent binding 34 , 35 we postulated that hIntL-1 trimers might bind avidly to multivalent carbohydrate displays. Hence, we evaluated hIntL-1 carbohydrate binding specificity by using immobilized biotinylated carbohydrates (β- D -Gal f , β- D -galactopyranose (β-Gal p ) and β- D -ribofuranose (β-Rib f )) in an enzyme-linked immunosorbent-like assay (ELISA) ( Fig. 1a and Supplementary Fig. 1c,d ). We chose the monosaccharide epitopes that we tested on the basis of a previous study in", "role": "user" }, { "content": "The newfound ability of a protein of the intestines and lungs to distinguish between human cells and the cells of bacterial invaders could underpin new strategies to fight infections. Writing this week (July 6, 2015) in the journal Nature Structural and Molecular Biology, a team led by University of Wisconsin-Madison Professor Laura Kiessling describes the knack of a human protein known as intelectin to distinguish between our cells and those of the disease-causing microbes that invade our bodies. \"This has the potential to change the game in terms of how we combat microbes,\" says Kiessling. The discovery by Kiessling and several collaborating groups also helps illuminate a previously unrecognized line of defense against microbial invaders. In addition to Kiessling's lab, groups in the labs of UW-Madison bacteriology Professor Katrina Forest, Scripps Research Institute cell and molecular biology Professor James Paulson, and Emory University biochemistry Professor Richard Cummings contributed to the study. Intelectin is not new to science, Kiessling notes, but its ability to selectively identify many different kinds of pathogens and distinguish those cells from human cells was unknown. \"The protein is upregulated with infection,\" explains Kiessling, \"and while no one has yet shown that it is an antimicrobial protein, there are multiple lines of evidence that suggest it is.\" TheWisconsin group established that intelectin has all the properties needed to function in the immune system's surveillance complex. That makes sense, Kiessling explains, as the protein is found mostly in the cells in the intestine and respiratory system, the places most likely to be entry points for microbial pathogens. Intelectin performs its surveillance role through its ability to selectively recognize the carbohydrate molecules that reside on the surface of cells. Both mammalian cells and microbial cells have carbohydrates known as glycans on their cell surfaces. However, the chemical structures of the glycan molecules vary, and the molecules that decorate the surface of human cells are markedly different from those on microbial cells. By exposing human intelectin to arrays of both human and microbial glycanS, Kiessling and her colleagues found that intelectin could recognize different kinds of microbes as well as distinguish between microbial and mammalian glycans. The role of intelectin in immune response, Kiessling believes, is likely ancient. The same kinds of proteins are found in many different kinds of animals, including sheep, mice frogs, eels, fish and even sea squirts, suggesting it has been conserved through evolutionary history. The glycans to which intelectin attaches, however, can be vastly different. In humans, for example, less than 35 chemical building blocks are used to make the cell surface molecules. In bacteria, nature deploys more than 700 chemical building blocks to make glycans. This immense increase in diversity can make accurate detection difficult. \"Human intelectin just recognizes a small portion of the glycan, a shared feature like a handle,\" explains Kiessling. \"Then it can recognize when the handles appear, even when different types of bacteria make different glycans.\" The larger insight from the study could aid in the design of the next generation of antibiotics, which are urgently needed as many pathogens have become resistant to the antibiotics now most commonly used to treat infection. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract The glycans displayed on mammalian cells can differ markedly from those on microbes. Such differences could, in principle, be 'read' by carbohydrate-binding proteins, or lectins. We used glycan microarrays to show that human intelectin-1 (hIntL-1) does not bind known human glycan epitopes but does interact with multiple glycan epitopes found exclusively on microbes: β-linked D -galactofuranose (β-Gal f ), D -phosphoglycerol–modified glycans, heptoses, D - glycero- D - talo -oct-2-ulosonic acid (KO) and 3-deoxy- D- manno -oct-2-ulosonic acid (KDO). The 1.6-Å-resolution crystal structure of hIntL-1 complexed with β-Gal f revealed that hIntL-1 uses a bound calcium ion to coordinate terminal exocyclic 1,2-diols. N -acetylneuraminic acid (Neu5Ac), a sialic acid widespread in human glycans, has an exocyclic 1,2-diol but does not bind hIntL-1, probably owing to unfavorable steric and electronic effects. hIntL-1 marks only Streptococcus pneumoniae serotypes that display surface glycans with terminal 1,2-diol groups. This ligand selectivity suggests that hIntL-1 functions in microbial surveillance. Main Organisms that serve as hosts for microbes must distinguish microbial cells from those of their own 1 , 2 . A mechanism of differentiation is especially important at sites in which host tissues contact the environment, such as the lung, intestine and skin 3 , 4 . Differences in cellular surface glycosylation can serve as markers of a cell's identity—its developmental state, its tissue type or its being self or nonself 5 . Cell-surface glycans can be distinguished by carbohydrate-binding proteins, or lectins 6 , which are typically categorized on the basis of their monosaccharide selectivity 7 . These lectins can be exploited for host defense, as in the case of innate immune lectins, such as mannose-binding lectin 8 . In serum, mannose-binding lectin is precomplexed with mannose-binding lectin–associated serine proteases, and interaction of this complex with a cell surface results in activation of the lectin pathway of complement and ultimately leads to pathogen opsonization and clearance 9 , 10 . Other humoral lectins implicated in immunity include ficolins, collectins, galectins and HIP/PAP 1 , 11 , 12 , 13 . One group of lectins whose specificity has been unclear is the intelectins (IntLs). The first IntL protein was reported in Xenopus laevis oocytes 14 . Homologs have since been identified in many other chordates, including other amphibians, fishes and many mammals. IntLs belong to a family of lectins termed X-type lectins 15 and have been shown to exist as homo-oligomers of 35-kDa monomers. They are reported to function as calcium ion–dependent lectins; however, they do not contain the calcium-dependent C-type-lectin sequence motif 16 present in many human lectins. IntLs instead contain a fibrinogen-like domain (FBD, residues 37–82 in hIntL-1 (ref. 17 )) and have been proposed to be most similar to ficolins, a class of FBD-containing innate immune lectins 11 . Several observations have implicated IntLs in innate immunity. Mammalian IntLs are predominantly produced by lung and intestinal goblet cells, and intestinal Paneth cells 17 , 18 , 19 . In sheep and mice, IntL expression increases upon infection with intestinal parasitic nematodes 20 , 21 . In humans, the mucus induced by allergic reactions is enriched in IntLs 22 , 23 . Moreover, hIntL-1 has been reported to be the intestinal lactoferrin receptor 24 and to function as a tumor marker 25 . It also has been suggested to be involved in metabolic disorders including diabetes, in which it is known as omentin 26 . Given these diverse potential functions, we set out to examine the ligand specificity of hIntL-1. hIntL-1 has been reported to bind furanose residues (five-membered-ring saccharide isomers), including ribofuranose (Rib f ) and a β-Gal f –containing disaccharide 17 , 27 . The monosaccharide Gal f is present in the cell-surface glycans produced by a number of microbes, but the biosynthetic enzymes that mediate Gal f incorporation are absent in humans 28 , 29 , 30 . The presence of Gal f in microbial but not human glycans is an example of phylogenetic glycan differences 31 . This is just one example, and collectively the surface glycans of microbes are generated from more than 700 unique building blocks, whereas fewer than 35 carbohydrate residues are needed to assemble mammalian glycans 32 , 33 . In principle, targeting of monosaccharide residues unique to microbes could be used by the innate immune system to differentiate mammalian cells from microbes. We reasoned that clues to hIntL-1 function would emerge from determining the glycans to which hIntL-1 binds and the molecular basis for its recognition selectivity. Here, we use glycan microarrays to demonstrate that hIntL-1 preferentially binds microbial over human glycans. Given the diversity of microbial glycans, a lectin that binds a single microbial saccharide epitope (for example, galactofuranose) would be expected to have specialized functions. It is therefore striking that hIntL-1 does not engage a single monosaccharide or even related saccharides but instead interacts with multiple structurally divergent microbial monosaccharide residues. We have used X-ray crystallography to reveal the molecular mechanism by which hIntL-1 recognizes its targets: hIntL-1 binds its carbohydrate ligands through calcium ion–dependent coordination of a conserved exocyclic, terminal 1,2-diol. The functional-group selectivity observed in the glycan arrays is manifested in the context of cells because hIntL-1 targets S. pneumoniae serotypes that display its glycan ligands. Results hIntL-1 binds β-Gal f Native hIntL-1 has been shown to exist as a disulfide-linked trimer 17 , 27 . Therefore, we first developed a robust expression system that yields the protein as a disulfide-linked trimer that can be purified with an immobilized–β-Gal f column ( Supplementary Fig. 1a,b ). Because lectin-carbohydrate interactions often depend on multivalent binding 34 , 35 we postulated that hIntL-1 trimers might bind avidly to multivalent carbohydrate displays. Hence, we evaluated hIntL-1 carbohydrate binding specificity by using immobilized biotinylated carbohydrates (β- D -Gal f , β- D -galactopyranose (β-Gal p ) and β- D -ribofuranose (β-Rib f )) in an enzyme-linked immunosorbent-like assay (ELISA) ( Fig. 1a and Supplementary Fig. 1c,d ). We chose the monosaccharide epitopes that we tested on the basis of a previous study in<|im_end|> <|im_start|>assistant The newfound ability of a protein of the intestines and lungs to distinguish between human cells and the cells of bacterial invaders could underpin new strategies to fight infections. Writing this week (July 6, 2015) in the journal Nature Structural and Molecular Biology, a team led by University of Wisconsin-Madison Professor Laura Kiessling describes the knack of a human protein known as intelectin to distinguish between our cells and those of the disease-causing microbes that invade our bodies. "This has the potential to change the game in terms of how we combat microbes," says Kiessling. The discovery by Kiessling and several collaborating groups also helps illuminate a previously unrecognized line of defense against microbial invaders. In addition to Kiessling's lab, groups in the labs of UW-Madison bacteriology Professor Katrina Forest, Scripps Research Institute cell and molecular biology Professor James Paulson, and Emory University biochemistry Professor Richard Cummings contributed to the study. Intelectin is not new to science, Kiessling notes, but its ability to selectively identify many different kinds of pathogens and distinguish those cells from human cells was unknown. "The protein is upregulated with infection," explains Kiessling, "and while no one has yet shown that it is an antimicrobial protein, there are multiple lines of evidence that suggest it is." TheWisconsin group established that intelectin has all the properties needed to function in the immune system's surveillance complex. That makes sense, Kiessling explains, as the protein is found mostly in the cells in the intestine and respiratory system, the places most likely to be entry points for microbial pathogens. Intelectin performs its surveillance role through its ability to selectively recognize the carbohydrate molecules that reside on the surface of cells. Both mammalian cells and microbial cells have carbohydrates known as glycans on their cell surfaces. However, the chemical structures of the glycan molecules vary, and the molecules that decorate the surface of human cells are markedly different from those on microbial cells. By exposing human intelectin to arrays of both human and microbial glycanS, Kiessling and her colleagues found that intelectin could recognize different kinds of microbes as well as distinguish between microbial and mammalian glycans. The role of intelectin in immune response, Kiessling believes, is likely ancient. The same kinds of proteins are found in many different kinds of animals, including sheep, mice frogs, eels, fish and even sea squirts, suggesting it has been conserved through evolutionary history. The glycans to which intelectin attaches, however, can be vastly different. In humans, for example, less than 35 chemical building blocks are used to make the cell surface molecules. In bacteria, nature deploys more than 700 chemical building blocks to make glycans. This immense increase in diversity can make accurate detection difficult. "Human intelectin just recognizes a small portion of the glycan, a shared feature like a handle," explains Kiessling. "Then it can recognize when the handles appear, even when different types of bacteria make different glycans." The larger insight from the study could aid in the design of the next generation of antibiotics, which are urgently needed as many pathogens have become resistant to the antibiotics now most commonly used to treat infection. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 578, 72157, 598, 12882, 389, 36041, 10700, 7917, 649, 1782, 88101, 505, 1884, 389, 80727, 13, 15483, 12062, 1436, 11, 304, 17966, 11, 387, 364, 888, 6, 555, 67732, 65500, 28896, 11, 477, 16920, 1354, 13, 1226, 1511, 37807, 4919, 8162, 67993, 311, 1501, 430, 3823, 528, 19493, 258, 12, 16, 320, 71, 1090, 43, 12, 16, 8, 1587, 539, 10950, 3967, 3823, 37807, 4919, 67422, 19031, 719, 1587, 16681, 449, 5361, 37807, 4919, 67422, 19031, 1766, 24121, 389, 80727, 25, 34318, 55514, 423, 482, 16876, 533, 1073, 27105, 974, 320, 52355, 12279, 278, 282, 7026, 423, 482, 764, 24527, 540, 68590, 337, 4235, 28261, 72157, 598, 11, 568, 418, 20274, 11, 423, 482, 72157, 2382, 12, 423, 482, 8374, 78, 482, 42792, 12, 17, 12, 29752, 14338, 13935, 320, 56047, 8, 323, 220, 18, 6953, 61263, 12, 423, 12, 893, 2201, 482, 42792, 12, 17, 12, 29752, 14338, 13935, 320, 42, 5989, 570, 578, 220, 16, 13, 21, 12, 106453, 64036, 26110, 6070, 315, 305, 1090, 43, 12, 16, 6485, 291, 449, 34318, 12279, 278, 282, 10675, 430, 305, 1090, 43, 12, 16, 5829, 264, 6965, 35719, 28772, 311, 16580, 15372, 506, 511, 66404, 220, 16, 11, 17, 51389, 3145, 13, 452, 482, 582, 87348, 818, 324, 8778, 292, 13935, 320, 8989, 84, 20, 11916, 705, 264, 274, 532, 292, 13935, 24716, 304, 3823, 72157, 598, 11, 706, 459, 506, 511, 66404, 220, 16, 11, 17, 1773, 25947, 719, 1587, 539, 10950, 305, 1090, 43, 12, 16, 11, 4762, 56612, 311, 93071, 357, 11893, 323, 14683, 6372, 13, 305, 1090, 43, 12, 16, 15785, 1193, 36772, 418, 511, 92411, 69329, 68, 1446, 22583, 430, 3113, 7479, 72157, 598, 449, 15372, 220, 16, 11, 17, 1773, 25947, 5315, 13, 1115, 29413, 438, 3373, 1968, 13533, 430, 305, 1090, 43, 12, 16, 5865, 304, 75418, 22156, 13, 4802, 10995, 13978, 430, 8854, 439, 18939, 369, 80727, 2011, 33137, 75418, 7917, 505, 1884, 315, 872, 1866, 220, 16, 1174, 220, 17, 662, 362, 17383, 315, 60038, 374, 5423, 3062, 520, 6732, 304, 902, 3552, 39881, 3729, 279, 4676, 11, 1778, 439, 279, 21271, 11, 92234, 323, 6930, 220, 18, 1174, 220, 19, 662, 86897, 304, 35693, 7479, 37807, 9594, 79933, 649, 8854, 439, 24915, 315, 264, 2849, 596, 9764, 2345, 1220, 48006, 1614, 11, 1202, 20438, 955, 477, 1202, 1694, 659, 477, 2536, 726, 220, 20, 662, 14299, 1355, 10730, 72157, 598, 649, 387, 39575, 555, 67732, 65500, 28896, 11, 477, 16920, 1354, 220, 21, 1174, 902, 527, 11383, 71974, 389, 279, 8197, 315, 872, 1647, 437, 582, 1799, 579, 3373, 1968, 220, 22, 662, 4314, 16920, 1354, 649, 387, 51763, 369, 3552, 9232, 11, 439, 304, 279, 1162, 315, 65070, 22852, 16920, 1354, 11, 1778, 439, 38908, 974, 65500, 16920, 258, 220, 23, 662, 763, 41529, 11, 38908, 974, 65500, 16920, 258, 374, 864, 24126, 291, 449, 38908, 974, 65500, 16920, 258, 4235, 50187, 1446, 483, 5541, 2315, 11, 323, 16628, 315, 420, 6485, 449, 264, 2849, 7479, 3135, 304, 15449, 315, 279, 16920, 258, 38970, 315, 23606, 323, 13967, 11767, 311, 1853, 11968, 1200, 942, 2065, 323, 36654, 220, 24, 1174, 220, 605, 662, 7089, 2854, 10020, 16920, 1354, 69702, 304, 40368, 2997, 282, 27561, 1354, 11, 6667, 1354, 11, 13819, 772, 1354, 323, 81396, 16744, 2599, 220, 16, 1174, 220, 806, 1174, 220, 717, 1174, 220, 1032, 662, 3861, 1912, 315, 16920, 1354, 6832, 76041, 706, 1027, 25420, 374, 279, 528, 19493, 1354, 320, 1090, 43, 82, 570, 578, 1176, 1357, 43, 13128, 574, 5068, 304, 49329, 46970, 1208, 68, 2749, 297, 57878, 220, 975, 662, 13525, 1640, 82, 617, 2533, 1027, 11054, 304, 1690, 1023, 44321, 988, 11, 2737, 1023, 89022, 5493, 11, 95461, 323, 1690, 56669, 13, 1357, 43, 82, 9352, 311, 264, 3070, 315, 16920, 1354, 61937, 1630, 10827, 16920, 1354, 220, 868, 323, 617, 1027, 6982, 311, 3073, 439, 55513, 12, 337, 343, 69638, 315, 220, 1758, 12934, 31516, 1647, 69638, 13, 2435, 527, 5068, 311, 734, 439, 35719, 28772, 4235, 38655, 16920, 1354, 26, 4869, 11, 814, 656, 539, 6782, 279, 35719, 43918, 356, 10827, 12, 772, 258, 8668, 60612, 220, 845, 3118, 304, 1690, 3823, 16920, 1354, 13, 1357, 43, 82, 4619, 6782, 264, 95235, 258, 11968, 12970, 8106, 320, 37, 9740, 11, 71783, 220, 1806, 4235, 6086, 304, 305, 1090, 43, 12, 16, 320, 1116, 13, 220, 1114, 12254, 323, 617, 1027, 11223, 311, 387, 1455, 4528, 311, 282, 27561, 1354, 11, 264, 538, 315, 435, 9740, 93871, 65070, 22852, 16920, 1354, 220, 806, 662, 26778, 24654, 617, 69702, 1357, 43, 82, 304, 65070, 40368, 13, 386, 8836, 10700, 1357, 43, 82, 527, 47904, 9124, 555, 21271, 323, 63900, 75517, 1169, 7917, 11, 323, 63900, 11233, 774, 7917, 220, 1114, 1174, 220, 972, 1174, 220, 777, 662, 763, 33012, 323, 24548, 11, 1357, 43, 7645, 12992, 5304, 19405, 449, 63900, 33403, 49086, 24566, 266, 2601, 220, 508, 1174, 220, 1691, 662, 763, 12966, 11, 279, 296, 38601, 36572, 555, 57596, 25481, 374, 69671, 304, 1357, 43, 82, 220, 1313, 1174, 220, 1419, 662, 23674, 11, 305, 1090, 43, 12, 16, 706, 1027, 5068, 311, 387, 279, 63900, 51644, 1073, 618, 258, 35268, 220, 1187, 323, 311, 734, 439, 264, 36254, 11381, 220, 914, 662, 1102, 1101, 706, 1027, 12090, 311, 387, 6532, 304, 41861, 24673, 2737, 20335, 11, 304, 902, 433, 374, 3967, 439, 297, 479, 258, 220, 1627, 662, 16644, 1521, 17226, 4754, 5865, 11, 584, 743, 704, 311, 21635, 279, 29413, 438, 76041, 315, 305, 1090, 43, 12, 16, 13, 305, 1090, 43, 12, 16, 706, 1027, 5068, 311, 10950, 18742, 276, 974, 71783, 320, 53770, 44650, 291, 77029, 11347, 1799, 579, 374, 69638, 705, 2737, 20735, 1073, 27105, 974, 320, 99984, 282, 883, 323, 264, 34318, 12279, 278, 282, 1389, 778, 2101, 834, 582, 1799, 579, 220, 1114, 1174, 220, 1544, 662, 578, 1647, 437, 582, 1799, 579, 10845, 282, 374, 3118, 304, 279, 2849, 1355, 10730, 72157, 598, 9124, 555, 264, 1396, 315, 80727, 11, 719, 279, 49554, 1910, 18015, 56067, 430, 1812, 6629, 10845, 282, 88465, 527, 28310, 304, 12966, 220, 1591, 1174, 220, 1682, 1174, 220, 966, 662, 578, 9546, 315, 10845, 282, 304, 75418, 719, 539, 3823, 72157, 598, 374, 459, 3187, 315, 37555, 86945, 5411, 37807, 4919, 12062, 220, 2148, 662, 1115, 374, 1120, 832, 3187, 11, 323, 45925, 279, 7479, 72157, 598, 315, 80727, 527, 8066, 505, 810, 1109, 220, 7007, 5016, 4857, 10215, 11, 20444, 17162, 1109, 220, 1758, 67732, 71783, 527, 4460, 311, 42840, 36041, 10700, 72157, 598, 220, 843, 1174, 220, 1644, 662, 763, 17966, 11, 25103, 315, 1647, 437, 582, 1799, 579, 71783, 5016, 311, 80727, 1436, 387, 1511, 555, 279, 65070, 22852, 1887, 311, 54263, 36041, 10700, 7917, 505, 80727, 13, 1226, 93469, 430, 43775, 311, 305, 1090, 43, 12, 16, 734, 1053, 34044, 505, 26679, 279, 72157, 598, 311, 902, 305, 1090, 43, 12, 16, 58585, 323, 279, 31206, 8197, 369, 1202, 18324, 3373, 1968, 13, 5810, 11, 584, 1005, 37807, 4919, 8162, 67993, 311, 20461, 430, 305, 1090, 43, 12, 16, 10932, 31668, 58585, 75418, 927, 3823, 72157, 598, 13, 16644, 279, 20057, 315, 75418, 72157, 598, 11, 264, 16920, 258, 430, 58585, 264, 3254, 75418, 11347, 1799, 579, 67422, 2862, 320, 2000, 3187, 11, 15730, 533, 1073, 27105, 974, 8, 1053, 387, 3685, 311, 617, 28175, 5865, 13, 1102, 374, 9093, 21933, 430, 305, 1090, 43, 12, 16, 1587, 539, 16988, 264, 3254, 1647, 437, 582, 1799, 579, 477, 1524, 5552, 11347, 1799, 3422, 719, 4619, 84261, 449, 5361, 2080, 43024, 37441, 16149, 75418, 1647, 437, 582, 1799, 579, 71783, 13, 1226, 617, 1511, 1630, 30630, 26110, 848, 1976, 88, 311, 16805, 279, 31206, 17383, 555, 902, 305, 1090, 43, 12, 16, 45799, 1202, 11811, 25, 305, 1090, 43, 12, 16, 58585, 1202, 67732, 29413, 2914, 1555, 35719, 28772, 4235, 38655, 38793, 315, 264, 1615, 2841, 506, 511, 66404, 11, 15372, 220, 16, 11, 17, 1773, 25947, 13, 578, 16003, 4449, 3373, 1968, 13468, 304, 279, 37807, 4919, 18893, 374, 79754, 304, 279, 2317, 315, 7917, 1606, 305, 1090, 43, 12, 16, 11811, 328, 13, 69329, 68, 1446, 22583, 430, 3113, 1202, 37807, 4919, 29413, 2914, 13, 18591, 305, 1090, 43, 12, 16, 58585, 34318, 12279, 278, 282, 17118, 305, 1090, 43, 12, 16, 706, 1027, 6982, 311, 3073, 439, 264, 834, 14643, 579, 55514, 490, 3212, 220, 1114, 1174, 220, 1544, 662, 15636, 11, 584, 1176, 8040, 264, 22514, 7645, 1887, 430, 36508, 279, 13128, 439, 264, 834, 14643, 579, 55514, 490, 3212, 430, 649, 387, 92600, 449, 459, 77441, 1534, 4235, 52355, 12279, 278, 282, 3330, 320, 99371, 23966, 13, 220, 16, 64, 8568, 7609, 9393, 16920, 258, 24948, 34658, 349, 22639, 3629, 6904, 389, 2814, 12031, 11212, 220, 1958, 1174, 220, 1758, 584, 1772, 7913, 430, 305, 1090, 43, 12, 16, 11259, 388, 2643, 10950, 56653, 398, 311, 2814, 12031, 67732, 19207, 13, 32140, 11, 584, 26126, 305, 1090, 43, 12, 16, 67732, 11212, 76041, 555, 1701, 77441, 1534, 6160, 354, 258, 4010, 660, 62345, 320, 52355, 12, 423, 482, 53619, 282, 1174, 34318, 12, 423, 482, 16876, 533, 1289, 6713, 974, 320, 52355, 12279, 278, 281, 883, 323, 34318, 12, 423, 482, 462, 754, 69, 27105, 974, 320, 52355, 11151, 581, 282, 12254, 304, 459, 49242, 55514, 33119, 437, 30986, 306, 12970, 65033, 320, 2818, 35301, 8, 320, 23966, 13, 220, 16, 64, 323, 99371, 23966, 13, 220, 16, 66, 12260, 7609, 1226, 14896, 279, 1647, 437, 582, 1799, 579, 67422, 19031, 430, 584, 12793, 389, 279, 8197, 315, 264, 3766, 4007, 304, 128257, 198, 128256, 78191, 198, 791, 94621, 5845, 315, 264, 13128, 315, 279, 39408, 1572, 323, 45274, 311, 33137, 1990, 3823, 7917, 323, 279, 7917, 315, 45964, 91321, 1436, 1234, 13576, 502, 15174, 311, 4465, 30020, 13, 24838, 420, 2046, 320, 29527, 220, 21, 11, 220, 679, 20, 8, 304, 279, 8486, 22037, 73800, 323, 60825, 40023, 11, 264, 2128, 6197, 555, 3907, 315, 21073, 5364, 329, 3416, 17054, 30928, 30558, 434, 2785, 16964, 279, 94350, 315, 264, 3823, 13128, 3967, 439, 528, 19493, 258, 311, 33137, 1990, 1057, 7917, 323, 1884, 315, 279, 8624, 51877, 985, 80727, 430, 75272, 1057, 13162, 13, 330, 2028, 706, 279, 4754, 311, 2349, 279, 1847, 304, 3878, 315, 1268, 584, 12896, 80727, 1359, 2795, 30558, 434, 2785, 13, 578, 18841, 555, 30558, 434, 2785, 323, 3892, 73301, 5315, 1101, 8779, 88682, 264, 8767, 97239, 1584, 315, 9232, 2403, 75418, 91321, 13, 763, 5369, 311, 30558, 434, 2785, 596, 10278, 11, 5315, 304, 279, 51048, 315, 66716, 5364, 329, 3416, 17854, 31226, 17054, 69756, 20585, 11, 76780, 60643, 8483, 10181, 2849, 323, 31206, 34458, 17054, 7957, 7043, 942, 11, 323, 5867, 683, 3907, 17332, 52755, 17054, 12131, 88471, 20162, 311, 279, 4007, 13, 1357, 19493, 258, 374, 539, 502, 311, 8198, 11, 30558, 434, 2785, 8554, 11, 719, 1202, 5845, 311, 82775, 10765, 1690, 2204, 13124, 315, 78284, 323, 33137, 1884, 7917, 505, 3823, 7917, 574, 9987, 13, 330, 791, 13128, 374, 709, 81722, 449, 19405, 1359, 15100, 30558, 434, 2785, 11, 330, 438, 1418, 912, 832, 706, 3686, 6982, 430, 433, 374, 459, 79312, 83059, 13128, 11, 1070, 527, 5361, 5238, 315, 6029, 430, 4284, 433, 374, 1210, 578, 79848, 19396, 1912, 9749, 430, 528, 19493, 258, 706, 682, 279, 6012, 4460, 311, 734, 304, 279, 22852, 1887, 596, 22156, 6485, 13, 3011, 3727, 5647, 11, 30558, 434, 2785, 15100, 11, 439, 279, 13128, 374, 1766, 10213, 304, 279, 7917, 304, 279, 92234, 323, 42631, 1887, 11, 279, 7634, 1455, 4461, 311, 387, 4441, 3585, 369, 75418, 78284, 13, 1357, 19493, 258, 27772, 1202, 22156, 3560, 1555, 1202, 5845, 311, 82775, 15641, 279, 67732, 35715, 430, 48383, 389, 279, 7479, 315, 7917, 13, 11995, 36041, 10700, 7917, 323, 75418, 7917, 617, 62345, 3967, 439, 72157, 598, 389, 872, 2849, 27529, 13, 4452, 11, 279, 11742, 14726, 315, 279, 37807, 4919, 35715, 13592, 11, 323, 279, 35715, 430, 57681, 279, 7479, 315, 3823, 7917, 527, 88101, 2204, 505, 1884, 389, 75418, 7917, 13, 3296, 47066, 3823, 528, 19493, 258, 311, 18893, 315, 2225, 3823, 323, 75418, 37807, 4919, 50, 11, 30558, 434, 2785, 323, 1077, 18105, 1766, 430, 528, 19493, 258, 1436, 15641, 2204, 13124, 315, 80727, 439, 1664, 439, 33137, 1990, 75418, 323, 36041, 10700, 72157, 598, 13, 578, 3560, 315, 528, 19493, 258, 304, 22852, 2077, 11, 30558, 434, 2785, 13919, 11, 374, 4461, 14154, 13, 578, 1890, 13124, 315, 28896, 527, 1766, 304, 1690, 2204, 13124, 315, 10099, 11, 2737, 33012, 11, 24548, 90546, 11, 384, 2053, 11, 7795, 323, 1524, 9581, 8330, 20242, 11, 23377, 433, 706, 1027, 1615, 2841, 1555, 41993, 3925, 13, 578, 72157, 598, 311, 902, 528, 19493, 258, 85603, 11, 4869, 11, 649, 387, 53108, 2204, 13, 763, 12966, 11, 369, 3187, 11, 2753, 1109, 220, 1758, 11742, 4857, 10215, 527, 1511, 311, 1304, 279, 2849, 7479, 35715, 13, 763, 24032, 11, 7138, 2219, 34398, 810, 1109, 220, 7007, 11742, 4857, 10215, 311, 1304, 72157, 598, 13, 1115, 38883, 5376, 304, 20057, 649, 1304, 13687, 18468, 5107, 13, 330, 35075, 528, 19493, 258, 1120, 45799, 264, 2678, 13651, 315, 279, 37807, 4919, 11, 264, 6222, 4668, 1093, 264, 3790, 1359, 15100, 30558, 434, 2785, 13, 330, 12487, 433, 649, 15641, 994, 279, 13777, 5101, 11, 1524, 994, 2204, 4595, 315, 24032, 1304, 2204, 72157, 598, 1210, 578, 8294, 20616, 505, 279, 4007, 1436, 12576, 304, 279, 2955, 315, 279, 1828, 9659, 315, 46850, 11, 902, 527, 77720, 4460, 439, 1690, 78284, 617, 3719, 31785, 311, 279, 46850, 1457, 1455, 17037, 1511, 311, 4322, 19405, 13, 220, 128257, 198 ]

2,298

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Although normally dormant, hair follicle stem cells (HFSCs) quickly become activated to divide during a new hair cycle. The quiescence of HFSCs is known to be regulated by a number of intrinsic and extrinsic mechanisms. Here we provide several lines of evidence to demonstrate that HFSCs utilize glycolytic metabolism and produce significantly more lactate than other cells in the epidermis. Furthermore, lactate generation appears to be critical for the activation of HFSCs as deletion of lactate dehydrogenase (Ldha) prevented their activation. Conversely, genetically promoting lactate production in HFSCs through mitochondrial pyruvate carrier 1 (Mpc1) deletion accelerated their activation and the hair cycle. Finally, we identify small molecules that increase lactate production by stimulating Myc levels or inhibiting Mpc1 carrier activity and can topically induce the hair cycle. These data suggest that HFSCs maintain a metabolic state that allows them to remain dormant and yet quickly respond to appropriate proliferative stimuli. Main The hair follicle is able to undergo cyclical rounds of rest (telogen), regeneration (anagen) and degeneration (catagen). The ability of the hair follicle to maintain this cycle depends on the presence of the hair follicle stem cells, which reside in the bulge ( Fig. 1 ). At the start of anagen, bulge stem cells are activated by signals received from the dermal papilla, which at that stage abuts the bulge area 1 , 2 . These stem cells exit the bulge and proliferate downwards, creating a trail that becomes the outer root sheath. Bulge stem cells are capable of giving rise to all the different cell types of the hair follicle. The ability of HFSCs to maintain quiescence and yet become proliferative for a couple days before returning to quiescence is unique in this tissue, and the precise mechanism by which these cells are endowed with this ability is not fully understood. While significant effort has produced a wealth of knowledge on both the transcriptional and epigenetic mechanisms by which HFSCs are maintained and give rise to various lineages 3 , 4 , little is known about metabolic pathways in the hair follicle or adult stem cells in vivo . Figure 1: Lactate dehydrogenase activity is enriched in HFSCs. ( a ) IHC staining for Ldha expression across the hair cycle shows Ldha protein confined to the HFSC niche, the bulge, indicated by the bracket. IHC staining for Sox9 on serial sections demarcates the HFSC population. Scale bars, 20 μm. ( b ) Immunoblotting on FACS-isolated HFSC populations (α6low/Cd34 + and α6hi/Cd34 + ) versus total epidermis (Epi) shows differential expression of Ldha in the stem cell niche. Sox9 is a marker of HFSCs, and β-actin is a loading control. ( c ) Colorimetric assay for Ldh enzyme activity in the epidermis shows highest activity in the bulge (brackets) and subcuticular muscle layer (bracket). This activity is enriched in the bulge across different stages of the hair cycle. Activity is indicated by purple colour; pink is a nuclear counterstain. Note also that developing hair shafts in pigmented mice show strong deposits of melanin as observed here; hair shafts never displayed any purple stain indicative of Ldh activity. Scale bars, 50 μm. ( d ) Ldh activity in sorted cell populations, measured using a plate-reader-based assay, also shows the highest Ldh activity in two separate HFSC populations (α6hi/Cd34 + and α6low/Cd34 + ) compared with epidermal cells (Epi) and fibroblasts (FBs). Each bar represents the average signal for each cell type where n = 9 mice pooled from 3 independent experiments. Shown as mean ± s.e.m. Paired t -test was performed, P < 0.05 shown for each cell type versus epidermal cells. ( e ) HFSCs and epidermal cells were isolated during telogen (day 50) by FACS, and metabolites were extracted and analysed by LC–MS. Heatmaps show relative levels of glycolytic and TCA cycle metabolites from cells isolated from different mice in independent experiments with cells from three animals in each. G6P-F6P, glucose-6-phosphate and fructose-6-phosphate; FBP, fructose-bisphosphate; DHAP, dihydroxyacetone phosphate; 3PG, 3-phosphoglycerate; and αKG, alpha-ketoglutarate. Asterisks indicate significant difference in metabolite levels between epidermal cells and HFSCs. For ( e ) paired t -test was performed; ∗ P < 0.05; ∗ ∗ P < 0.01; ∗ ∗ ∗ P < 0.001; NS, P > 0.05; n = 9 mice pooled from 3 independent experiments. Unprocessed original scans of blots are shown in Supplementary Fig. 6 . Full size image Considering the fact that there are essentially no published data on metabolic states of any cell in the hair follicle, a detailed study of metabolism was necessary to understand the nature of HFSCs and their progeny. Several previous studies employed genetic disruption of the mitochondrial electron transport chain in the epidermis by deletion under the control of a pan-epidermal keratin promoter and found that mitochondrial function was essential for maintenance of the follicle 5 , 6 , 7 , 8 . However, these studies did not explore the metabolic requirements for specific cell types within the tissue, nor did they explore a role for glycolytic metabolism. In this study, we present methods to study the metabolism of HFSCs in vivo , and provide evidence that these cells take advantage of a distinct mode of metabolism not found in their progeny. In the process, we also define small molecules that can take advantage of the unique metabolism of HFSCs to ignite the hair cycle in otherwise quiescent follicles. RESULTS Numerous studies have uncovered unique gene expression signatures in HFSCs versus other follicle cells or cells of the interfollicular epidermis 9 , 10 , 11 , 12 . Many of these signatures are regulated by transcription factors that were later shown to play important roles in HFSC homeostasis 13 . Lactate dehydrogenase is most commonly encoded by the Ldha and Ldhb genes in mammals, the protein products of which form homo- or hetero-tetramers to catalyse the NADH-dependent reduction of pyruvate to lactate and NAD + -dependent oxidation of lactate to pyruvate 14 . By immunostaining, Ldha appeared to be enriched in quiescent", "role": "user" }, { "content": "UCLA researchers have discovered a new way to activate the stem cells in the hair follicle to make hair grow. The research, led by scientists Heather Christofk and William Lowry, may lead to new drugs that could promote hair growth for people with baldness or alopecia, which is hair loss associated with such factors as hormonal imbalance, stress, aging or chemotherapy treatment. The research was published in the journal Nature Cell Biology. Hair follicle stem cells are long-lived cells in the hair follicle; they are present in the skin and produce hair throughout a person's lifetime. They are \"quiescent,\" meaning they are normally inactive, but they quickly activate during a new hair cycle, which is when new hair growth occurs. The quiescence of hair follicle stem cells is regulated by many factors. In certain cases they fail to activate, which is what causes hair loss. In this study, Christofk and Lowry, of Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, found that hair follicle stem cell metabolism is different from other cells of the skin. Cellular metabolism involves the breakdown of the nutrients needed for cells to divide, make energy and respond to their environment. The process of metabolism uses enzymes that alter these nutrients to produce \"metabolites.\" As hair follicle stem cells consume the nutrient glucose—a form of sugar—from the bloodstream, they process the glucose to eventually produce a metabolite called pyruvate. The cells then can either send pyruvate to their mitochondria—the part of the cell that creates energy—or can convert pyruvate into another metabolite called lactate. \"Our observations about hair follicle stem cell metabolism prompted us to examine whether genetically diminishing the entry of pyruvate into the mitochondria would force hair follicle stem cells to make more lactate, and if that would activate the cells and grow hair more quickly,\" said Christofk, an associate professor of biological chemistry and molecular and medical pharmacology. The research team first blocked the production of lactate genetically in mice and showed that this prevented hair follicle stem cell activation. Conversely, in collaboration with the Rutter lab at University of Utah, they increased lactate production genetically in the mice and this accelerated hair follicle stem cell activation, increasing the hair cycle. \"Before this, no one knew that increasing or decreasing the lactate would have an effect on hair follicle stem cells,\" said Lowry, a professor of molecular, cell and developmental biology. \"Once we saw how altering lactate production in the mice influenced hair growth, it led us to look for potential drugs that could be applied to the skin and have the same effect.\" The team identified two drugs that, when applied to the skin of mice, influenced hair follicle stem cells in distinct ways to promote lactate production. The first drug, called RCGD423, activates a cellular signaling pathway called JAK-Stat, which transmits information from outside the cell to the nucleus of the cell. The research showed that JAK-Stat activation leads to the increased production of lactate and this in turn drives hair follicle stem cell activation and quicker hair growth. The other drug, called UK5099, blocks pyruvate from entering the mitochondria, which forces the production of lactate in the hair follicle stem cells and accelerates hair growth in mice. \"Through this study, we gained a lot of interesting insight into new ways to activate stem cells,\" said Aimee Flores, a predoctoral trainee in Lowry's lab and first author of the study. \"The idea of using drugs to stimulate hair growth through hair follicle stem cells is very promising given how many millions of people, both men and women, deal with hair loss. I think we've only just begun to understand the critical role metabolism plays in hair growth and stem cells in general; I'm looking forward to the potential application of these new findings for hair loss and beyond.\" The use of RCGD423 to promote hair growth is covered by a provisional patent application filed by the UCLA Technology Development Group on behalf of UC Regents. The use of UK5099 to promote hair growth is covered by a separate provisional patent filed by the UCLA Technology Development Group on behalf of UC Regents, with Lowry and Christofk as inventors. The experimental drugs described above were used in preclinical tests only and have not been tested in humans or approved by the Food and Drug Administration as safe and effective for use in humans. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Although normally dormant, hair follicle stem cells (HFSCs) quickly become activated to divide during a new hair cycle. The quiescence of HFSCs is known to be regulated by a number of intrinsic and extrinsic mechanisms. Here we provide several lines of evidence to demonstrate that HFSCs utilize glycolytic metabolism and produce significantly more lactate than other cells in the epidermis. Furthermore, lactate generation appears to be critical for the activation of HFSCs as deletion of lactate dehydrogenase (Ldha) prevented their activation. Conversely, genetically promoting lactate production in HFSCs through mitochondrial pyruvate carrier 1 (Mpc1) deletion accelerated their activation and the hair cycle. Finally, we identify small molecules that increase lactate production by stimulating Myc levels or inhibiting Mpc1 carrier activity and can topically induce the hair cycle. These data suggest that HFSCs maintain a metabolic state that allows them to remain dormant and yet quickly respond to appropriate proliferative stimuli. Main The hair follicle is able to undergo cyclical rounds of rest (telogen), regeneration (anagen) and degeneration (catagen). The ability of the hair follicle to maintain this cycle depends on the presence of the hair follicle stem cells, which reside in the bulge ( Fig. 1 ). At the start of anagen, bulge stem cells are activated by signals received from the dermal papilla, which at that stage abuts the bulge area 1 , 2 . These stem cells exit the bulge and proliferate downwards, creating a trail that becomes the outer root sheath. Bulge stem cells are capable of giving rise to all the different cell types of the hair follicle. The ability of HFSCs to maintain quiescence and yet become proliferative for a couple days before returning to quiescence is unique in this tissue, and the precise mechanism by which these cells are endowed with this ability is not fully understood. While significant effort has produced a wealth of knowledge on both the transcriptional and epigenetic mechanisms by which HFSCs are maintained and give rise to various lineages 3 , 4 , little is known about metabolic pathways in the hair follicle or adult stem cells in vivo . Figure 1: Lactate dehydrogenase activity is enriched in HFSCs. ( a ) IHC staining for Ldha expression across the hair cycle shows Ldha protein confined to the HFSC niche, the bulge, indicated by the bracket. IHC staining for Sox9 on serial sections demarcates the HFSC population. Scale bars, 20 μm. ( b ) Immunoblotting on FACS-isolated HFSC populations (α6low/Cd34 + and α6hi/Cd34 + ) versus total epidermis (Epi) shows differential expression of Ldha in the stem cell niche. Sox9 is a marker of HFSCs, and β-actin is a loading control. ( c ) Colorimetric assay for Ldh enzyme activity in the epidermis shows highest activity in the bulge (brackets) and subcuticular muscle layer (bracket). This activity is enriched in the bulge across different stages of the hair cycle. Activity is indicated by purple colour; pink is a nuclear counterstain. Note also that developing hair shafts in pigmented mice show strong deposits of melanin as observed here; hair shafts never displayed any purple stain indicative of Ldh activity. Scale bars, 50 μm. ( d ) Ldh activity in sorted cell populations, measured using a plate-reader-based assay, also shows the highest Ldh activity in two separate HFSC populations (α6hi/Cd34 + and α6low/Cd34 + ) compared with epidermal cells (Epi) and fibroblasts (FBs). Each bar represents the average signal for each cell type where n = 9 mice pooled from 3 independent experiments. Shown as mean ± s.e.m. Paired t -test was performed, P < 0.05 shown for each cell type versus epidermal cells. ( e ) HFSCs and epidermal cells were isolated during telogen (day 50) by FACS, and metabolites were extracted and analysed by LC–MS. Heatmaps show relative levels of glycolytic and TCA cycle metabolites from cells isolated from different mice in independent experiments with cells from three animals in each. G6P-F6P, glucose-6-phosphate and fructose-6-phosphate; FBP, fructose-bisphosphate; DHAP, dihydroxyacetone phosphate; 3PG, 3-phosphoglycerate; and αKG, alpha-ketoglutarate. Asterisks indicate significant difference in metabolite levels between epidermal cells and HFSCs. For ( e ) paired t -test was performed; ∗ P < 0.05; ∗ ∗ P < 0.01; ∗ ∗ ∗ P < 0.001; NS, P > 0.05; n = 9 mice pooled from 3 independent experiments. Unprocessed original scans of blots are shown in Supplementary Fig. 6 . Full size image Considering the fact that there are essentially no published data on metabolic states of any cell in the hair follicle, a detailed study of metabolism was necessary to understand the nature of HFSCs and their progeny. Several previous studies employed genetic disruption of the mitochondrial electron transport chain in the epidermis by deletion under the control of a pan-epidermal keratin promoter and found that mitochondrial function was essential for maintenance of the follicle 5 , 6 , 7 , 8 . However, these studies did not explore the metabolic requirements for specific cell types within the tissue, nor did they explore a role for glycolytic metabolism. In this study, we present methods to study the metabolism of HFSCs in vivo , and provide evidence that these cells take advantage of a distinct mode of metabolism not found in their progeny. In the process, we also define small molecules that can take advantage of the unique metabolism of HFSCs to ignite the hair cycle in otherwise quiescent follicles. RESULTS Numerous studies have uncovered unique gene expression signatures in HFSCs versus other follicle cells or cells of the interfollicular epidermis 9 , 10 , 11 , 12 . Many of these signatures are regulated by transcription factors that were later shown to play important roles in HFSC homeostasis 13 . Lactate dehydrogenase is most commonly encoded by the Ldha and Ldhb genes in mammals, the protein products of which form homo- or hetero-tetramers to catalyse the NADH-dependent reduction of pyruvate to lactate and NAD + -dependent oxidation of lactate to pyruvate 14 . By immunostaining, Ldha appeared to be enriched in quiescent<|im_end|> <|im_start|>assistant UCLA researchers have discovered a new way to activate the stem cells in the hair follicle to make hair grow. The research, led by scientists Heather Christofk and William Lowry, may lead to new drugs that could promote hair growth for people with baldness or alopecia, which is hair loss associated with such factors as hormonal imbalance, stress, aging or chemotherapy treatment. The research was published in the journal Nature Cell Biology. Hair follicle stem cells are long-lived cells in the hair follicle; they are present in the skin and produce hair throughout a person's lifetime. They are "quiescent," meaning they are normally inactive, but they quickly activate during a new hair cycle, which is when new hair growth occurs. The quiescence of hair follicle stem cells is regulated by many factors. In certain cases they fail to activate, which is what causes hair loss. In this study, Christofk and Lowry, of Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, found that hair follicle stem cell metabolism is different from other cells of the skin. Cellular metabolism involves the breakdown of the nutrients needed for cells to divide, make energy and respond to their environment. The process of metabolism uses enzymes that alter these nutrients to produce "metabolites." As hair follicle stem cells consume the nutrient glucose—a form of sugar—from the bloodstream, they process the glucose to eventually produce a metabolite called pyruvate. The cells then can either send pyruvate to their mitochondria—the part of the cell that creates energy—or can convert pyruvate into another metabolite called lactate. "Our observations about hair follicle stem cell metabolism prompted us to examine whether genetically diminishing the entry of pyruvate into the mitochondria would force hair follicle stem cells to make more lactate, and if that would activate the cells and grow hair more quickly," said Christofk, an associate professor of biological chemistry and molecular and medical pharmacology. The research team first blocked the production of lactate genetically in mice and showed that this prevented hair follicle stem cell activation. Conversely, in collaboration with the Rutter lab at University of Utah, they increased lactate production genetically in the mice and this accelerated hair follicle stem cell activation, increasing the hair cycle. "Before this, no one knew that increasing or decreasing the lactate would have an effect on hair follicle stem cells," said Lowry, a professor of molecular, cell and developmental biology. "Once we saw how altering lactate production in the mice influenced hair growth, it led us to look for potential drugs that could be applied to the skin and have the same effect." The team identified two drugs that, when applied to the skin of mice, influenced hair follicle stem cells in distinct ways to promote lactate production. The first drug, called RCGD423, activates a cellular signaling pathway called JAK-Stat, which transmits information from outside the cell to the nucleus of the cell. The research showed that JAK-Stat activation leads to the increased production of lactate and this in turn drives hair follicle stem cell activation and quicker hair growth. The other drug, called UK5099, blocks pyruvate from entering the mitochondria, which forces the production of lactate in the hair follicle stem cells and accelerates hair growth in mice. "Through this study, we gained a lot of interesting insight into new ways to activate stem cells," said Aimee Flores, a predoctoral trainee in Lowry's lab and first author of the study. "The idea of using drugs to stimulate hair growth through hair follicle stem cells is very promising given how many millions of people, both men and women, deal with hair loss. I think we've only just begun to understand the critical role metabolism plays in hair growth and stem cells in general; I'm looking forward to the potential application of these new findings for hair loss and beyond." The use of RCGD423 to promote hair growth is covered by a provisional patent application filed by the UCLA Technology Development Group on behalf of UC Regents. The use of UK5099 to promote hair growth is covered by a separate provisional patent filed by the UCLA Technology Development Group on behalf of UC Regents, with Lowry and Christofk as inventors. The experimental drugs described above were used in preclinical tests only and have not been tested in humans or approved by the Food and Drug Administration as safe and effective for use in humans. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 10541, 14614, 89460, 11, 7013, 82714, 273, 19646, 7917, 320, 50816, 3624, 82, 8, 6288, 3719, 22756, 311, 22497, 2391, 264, 502, 7013, 11008, 13, 578, 934, 552, 36634, 315, 51658, 3624, 82, 374, 3967, 311, 387, 35319, 555, 264, 1396, 315, 47701, 323, 11741, 28692, 24717, 13, 5810, 584, 3493, 3892, 5238, 315, 6029, 311, 20461, 430, 51658, 3624, 82, 29166, 37807, 2119, 70504, 39097, 323, 8356, 12207, 810, 51644, 349, 1109, 1023, 7917, 304, 279, 4248, 1814, 34965, 13, 24296, 11, 51644, 349, 9659, 8111, 311, 387, 9200, 369, 279, 15449, 315, 51658, 3624, 82, 439, 37166, 315, 51644, 349, 409, 67229, 4469, 521, 320, 43, 67, 4317, 8, 32098, 872, 15449, 13, 82671, 11, 52033, 22923, 51644, 349, 5788, 304, 51658, 3624, 82, 1555, 72061, 4611, 2739, 85, 349, 19115, 220, 16, 320, 44, 4080, 16, 8, 37166, 49858, 872, 15449, 323, 279, 7013, 11008, 13, 17830, 11, 584, 10765, 2678, 35715, 430, 5376, 51644, 349, 5788, 555, 65792, 3092, 66, 5990, 477, 20747, 5977, 386, 4080, 16, 19115, 5820, 323, 649, 1948, 2740, 49853, 279, 7013, 11008, 13, 4314, 828, 4284, 430, 51658, 3624, 82, 10519, 264, 41861, 1614, 430, 6276, 1124, 311, 7293, 89460, 323, 3686, 6288, 6013, 311, 8475, 43036, 1413, 56688, 13, 4802, 578, 7013, 82714, 273, 374, 3025, 311, 37771, 44448, 32348, 20101, 315, 2800, 320, 23774, 11968, 705, 60517, 320, 276, 8703, 8, 323, 5367, 17699, 320, 4719, 8703, 570, 578, 5845, 315, 279, 7013, 82714, 273, 311, 10519, 420, 11008, 14117, 389, 279, 9546, 315, 279, 7013, 82714, 273, 19646, 7917, 11, 902, 48383, 304, 279, 7173, 713, 320, 23966, 13, 220, 16, 7609, 2468, 279, 1212, 315, 459, 8703, 11, 7173, 713, 19646, 7917, 527, 22756, 555, 17738, 4036, 505, 279, 2761, 14991, 26365, 6374, 11, 902, 520, 430, 6566, 671, 6256, 279, 7173, 713, 3158, 220, 16, 1174, 220, 17, 662, 4314, 19646, 7917, 4974, 279, 7173, 713, 323, 43036, 349, 92370, 11, 6968, 264, 9025, 430, 9221, 279, 16335, 3789, 1364, 589, 13, 13805, 713, 19646, 7917, 527, 13171, 315, 7231, 10205, 311, 682, 279, 2204, 2849, 4595, 315, 279, 7013, 82714, 273, 13, 578, 5845, 315, 51658, 3624, 82, 311, 10519, 934, 552, 36634, 323, 3686, 3719, 43036, 1413, 369, 264, 5743, 2919, 1603, 13758, 311, 934, 552, 36634, 374, 5016, 304, 420, 20438, 11, 323, 279, 24473, 17383, 555, 902, 1521, 7917, 527, 98728, 449, 420, 5845, 374, 539, 7373, 16365, 13, 6104, 5199, 5149, 706, 9124, 264, 12205, 315, 6677, 389, 2225, 279, 46940, 278, 323, 4248, 6569, 5411, 24717, 555, 902, 51658, 3624, 82, 527, 18908, 323, 3041, 10205, 311, 5370, 1584, 1154, 220, 18, 1174, 220, 19, 1174, 2697, 374, 3967, 922, 41861, 44014, 304, 279, 7013, 82714, 273, 477, 6822, 19646, 7917, 304, 41294, 662, 19575, 220, 16, 25, 445, 533, 349, 409, 67229, 4469, 521, 5820, 374, 69671, 304, 51658, 3624, 82, 13, 320, 264, 883, 358, 23263, 88896, 369, 445, 67, 4317, 7645, 4028, 279, 7013, 11008, 5039, 445, 67, 4317, 13128, 45408, 311, 279, 51658, 3624, 35149, 11, 279, 7173, 713, 11, 16717, 555, 279, 32742, 13, 358, 23263, 88896, 369, 39645, 24, 389, 6275, 14491, 2486, 8362, 988, 279, 51658, 3624, 7187, 13, 25635, 16283, 11, 220, 508, 33983, 76, 13, 320, 293, 883, 67335, 677, 9363, 1303, 389, 435, 63787, 31530, 81619, 51658, 3624, 22673, 320, 19481, 21, 10516, 11547, 67, 1958, 489, 323, 19581, 21, 6151, 11547, 67, 1958, 489, 883, 19579, 2860, 4248, 1814, 34965, 320, 36, 2554, 8, 5039, 41264, 7645, 315, 445, 67, 4317, 304, 279, 19646, 2849, 35149, 13, 39645, 24, 374, 264, 11381, 315, 51658, 3624, 82, 11, 323, 34318, 12, 533, 258, 374, 264, 8441, 2585, 13, 320, 272, 883, 3562, 318, 16743, 65033, 369, 445, 31721, 49242, 5820, 304, 279, 4248, 1814, 34965, 5039, 8592, 5820, 304, 279, 7173, 713, 320, 1347, 18889, 8, 323, 1207, 10453, 24553, 16124, 6324, 320, 1347, 5827, 570, 1115, 5820, 374, 69671, 304, 279, 7173, 713, 4028, 2204, 18094, 315, 279, 7013, 11008, 13, 15330, 374, 16717, 555, 25977, 12745, 26, 18718, 374, 264, 11499, 5663, 267, 467, 13, 7181, 1101, 430, 11469, 7013, 31468, 82, 304, 24623, 28078, 24548, 1501, 3831, 34751, 315, 68012, 258, 439, 13468, 1618, 26, 7013, 31468, 82, 2646, 12882, 904, 25977, 53064, 64005, 315, 445, 31721, 5820, 13, 25635, 16283, 11, 220, 1135, 33983, 76, 13, 320, 294, 883, 445, 31721, 5820, 304, 10839, 2849, 22673, 11, 17303, 1701, 264, 12235, 91579, 6108, 65033, 11, 1101, 5039, 279, 8592, 445, 31721, 5820, 304, 1403, 8821, 51658, 3624, 22673, 320, 19481, 21, 6151, 11547, 67, 1958, 489, 323, 19581, 21, 10516, 11547, 67, 1958, 489, 883, 7863, 449, 4248, 1814, 14991, 7917, 320, 36, 2554, 8, 323, 16178, 299, 2067, 12019, 320, 16606, 82, 570, 9062, 3703, 11105, 279, 5578, 8450, 369, 1855, 2849, 955, 1405, 308, 284, 220, 24, 24548, 76476, 505, 220, 18, 9678, 21896, 13, 1443, 785, 439, 3152, 20903, 274, 1770, 749, 13, 16056, 2757, 259, 482, 1985, 574, 10887, 11, 393, 366, 220, 15, 13, 2304, 6982, 369, 1855, 2849, 955, 19579, 4248, 1814, 14991, 7917, 13, 320, 384, 883, 51658, 3624, 82, 323, 4248, 1814, 14991, 7917, 1051, 25181, 2391, 19227, 11968, 320, 1316, 220, 1135, 8, 555, 435, 63787, 11, 323, 28168, 3695, 1051, 28532, 323, 67458, 555, 31971, 4235, 4931, 13, 27162, 18106, 1501, 8844, 5990, 315, 37807, 2119, 70504, 323, 350, 5158, 11008, 28168, 3695, 505, 7917, 25181, 505, 2204, 24548, 304, 9678, 21896, 449, 7917, 505, 2380, 10099, 304, 1855, 13, 480, 21, 47, 7424, 21, 47, 11, 34323, 12, 21, 63837, 93473, 323, 1448, 87873, 12, 21, 63837, 93473, 26, 435, 27187, 11, 1448, 87873, 1481, 285, 764, 93473, 26, 33887, 2599, 11, 1891, 67229, 4223, 68323, 606, 79106, 26, 220, 18, 11637, 11, 220, 18, 63837, 24527, 540, 68590, 349, 26, 323, 19581, 44016, 11, 8451, 12934, 295, 98347, 41297, 349, 13, 68598, 93934, 13519, 5199, 6811, 304, 28168, 635, 5990, 1990, 4248, 1814, 14991, 7917, 323, 51658, 3624, 82, 13, 1789, 320, 384, 883, 35526, 259, 482, 1985, 574, 10887, 26, 12264, 245, 393, 366, 220, 15, 13, 2304, 26, 12264, 245, 12264, 245, 393, 366, 220, 15, 13, 1721, 26, 12264, 245, 12264, 245, 12264, 245, 393, 366, 220, 15, 13, 4119, 26, 3119, 11, 393, 871, 220, 15, 13, 2304, 26, 308, 284, 220, 24, 24548, 76476, 505, 220, 18, 9678, 21896, 13, 1252, 35122, 4113, 43739, 315, 1529, 2469, 527, 6982, 304, 99371, 23966, 13, 220, 21, 662, 8797, 1404, 2217, 56877, 279, 2144, 430, 1070, 527, 16168, 912, 4756, 828, 389, 41861, 5415, 315, 904, 2849, 304, 279, 7013, 82714, 273, 11, 264, 11944, 4007, 315, 39097, 574, 5995, 311, 3619, 279, 7138, 315, 51658, 3624, 82, 323, 872, 84360, 88, 13, 26778, 3766, 7978, 20011, 19465, 44219, 315, 279, 72061, 17130, 7710, 8957, 304, 279, 4248, 1814, 34965, 555, 37166, 1234, 279, 2585, 315, 264, 7363, 12, 752, 1814, 14991, 34801, 15111, 66642, 323, 1766, 430, 72061, 734, 574, 7718, 369, 13709, 315, 279, 82714, 273, 220, 20, 1174, 220, 21, 1174, 220, 22, 1174, 220, 23, 662, 4452, 11, 1521, 7978, 1550, 539, 13488, 279, 41861, 8670, 369, 3230, 2849, 4595, 2949, 279, 20438, 11, 6463, 1550, 814, 13488, 264, 3560, 369, 37807, 2119, 70504, 39097, 13, 763, 420, 4007, 11, 584, 3118, 5528, 311, 4007, 279, 39097, 315, 51658, 3624, 82, 304, 41294, 1174, 323, 3493, 6029, 430, 1521, 7917, 1935, 9610, 315, 264, 12742, 3941, 315, 39097, 539, 1766, 304, 872, 84360, 88, 13, 763, 279, 1920, 11, 584, 1101, 7124, 2678, 35715, 430, 649, 1935, 9610, 315, 279, 5016, 39097, 315, 51658, 3624, 82, 311, 90536, 279, 7013, 11008, 304, 6062, 934, 552, 1189, 82714, 645, 13, 54128, 86915, 7978, 617, 43522, 5016, 15207, 7645, 33728, 304, 51658, 3624, 82, 19579, 1023, 82714, 273, 7917, 477, 7917, 315, 279, 958, 8566, 416, 1299, 4248, 1814, 34965, 220, 24, 1174, 220, 605, 1174, 220, 806, 1174, 220, 717, 662, 9176, 315, 1521, 33728, 527, 35319, 555, 46940, 9547, 430, 1051, 3010, 6982, 311, 1514, 3062, 13073, 304, 51658, 3624, 2162, 537, 10949, 220, 1032, 662, 445, 533, 349, 409, 67229, 4469, 521, 374, 1455, 17037, 21136, 555, 279, 445, 67, 4317, 323, 445, 31721, 65, 21389, 304, 56669, 11, 279, 13128, 3956, 315, 902, 1376, 55513, 12, 477, 30548, 78, 2442, 295, 2453, 388, 311, 34454, 88, 325, 279, 452, 1846, 39, 43918, 14278, 315, 4611, 2739, 85, 349, 311, 51644, 349, 323, 452, 1846, 489, 482, 38655, 71162, 315, 51644, 349, 311, 4611, 2739, 85, 349, 220, 975, 662, 3296, 33119, 537, 2101, 11, 445, 67, 4317, 9922, 311, 387, 69671, 304, 934, 552, 1189, 128257, 198, 128256, 78191, 198, 52, 42235, 12074, 617, 11352, 264, 502, 1648, 311, 20891, 279, 19646, 7917, 304, 279, 7013, 82714, 273, 311, 1304, 7013, 3139, 13, 578, 3495, 11, 6197, 555, 14248, 47363, 3771, 1073, 74, 323, 12656, 12310, 894, 11, 1253, 3063, 311, 502, 11217, 430, 1436, 12192, 7013, 6650, 369, 1274, 449, 48653, 2136, 477, 54266, 81060, 11, 902, 374, 7013, 4814, 5938, 449, 1778, 9547, 439, 74218, 68331, 11, 8631, 11, 30084, 477, 62730, 6514, 13, 578, 3495, 574, 4756, 304, 279, 8486, 22037, 14299, 40023, 13, 26781, 82714, 273, 19646, 7917, 527, 1317, 62954, 7917, 304, 279, 7013, 82714, 273, 26, 814, 527, 3118, 304, 279, 6930, 323, 8356, 7013, 6957, 264, 1732, 596, 19569, 13, 2435, 527, 330, 447, 552, 1189, 1359, 7438, 814, 527, 14614, 32899, 11, 719, 814, 6288, 20891, 2391, 264, 502, 7013, 11008, 11, 902, 374, 994, 502, 7013, 6650, 13980, 13, 578, 934, 552, 36634, 315, 7013, 82714, 273, 19646, 7917, 374, 35319, 555, 1690, 9547, 13, 763, 3738, 5157, 814, 3775, 311, 20891, 11, 902, 374, 1148, 11384, 7013, 4814, 13, 763, 420, 4007, 11, 3771, 1073, 74, 323, 12310, 894, 11, 315, 34362, 323, 3279, 96960, 16273, 5955, 315, 3263, 75989, 19152, 323, 81948, 14299, 8483, 520, 50751, 11, 1766, 430, 7013, 82714, 273, 19646, 2849, 39097, 374, 2204, 505, 1023, 7917, 315, 279, 6930, 13, 88207, 39097, 18065, 279, 31085, 315, 279, 37493, 4460, 369, 7917, 311, 22497, 11, 1304, 4907, 323, 6013, 311, 872, 4676, 13, 578, 1920, 315, 39097, 5829, 56067, 430, 11857, 1521, 37493, 311, 8356, 330, 4150, 53904, 3695, 1210, 1666, 7013, 82714, 273, 19646, 7917, 25024, 279, 50123, 34323, 29096, 1376, 315, 13465, 88958, 279, 100216, 11, 814, 1920, 279, 34323, 311, 9778, 8356, 264, 28168, 635, 2663, 4611, 2739, 85, 349, 13, 578, 7917, 1243, 649, 3060, 3708, 4611, 2739, 85, 349, 311, 872, 55042, 4298, 22416, 961, 315, 279, 2849, 430, 11705, 4907, 51749, 649, 5625, 4611, 2739, 85, 349, 1139, 2500, 28168, 635, 2663, 51644, 349, 13, 330, 8140, 24654, 922, 7013, 82714, 273, 19646, 2849, 39097, 29746, 603, 311, 21635, 3508, 52033, 84153, 279, 4441, 315, 4611, 2739, 85, 349, 1139, 279, 55042, 4298, 1053, 5457, 7013, 82714, 273, 19646, 7917, 311, 1304, 810, 51644, 349, 11, 323, 422, 430, 1053, 20891, 279, 7917, 323, 3139, 7013, 810, 6288, 1359, 1071, 3771, 1073, 74, 11, 459, 22712, 14561, 315, 24156, 30903, 323, 31206, 323, 6593, 36449, 2508, 13, 578, 3495, 2128, 1176, 19857, 279, 5788, 315, 51644, 349, 52033, 304, 24548, 323, 8710, 430, 420, 32098, 7013, 82714, 273, 19646, 2849, 15449, 13, 82671, 11, 304, 20632, 449, 279, 432, 6339, 10278, 520, 3907, 315, 23195, 11, 814, 7319, 51644, 349, 5788, 52033, 304, 279, 24548, 323, 420, 49858, 7013, 82714, 273, 19646, 2849, 15449, 11, 7859, 279, 7013, 11008, 13, 330, 10438, 420, 11, 912, 832, 7020, 430, 7859, 477, 44649, 279, 51644, 349, 1053, 617, 459, 2515, 389, 7013, 82714, 273, 19646, 7917, 1359, 1071, 12310, 894, 11, 264, 14561, 315, 31206, 11, 2849, 323, 48006, 34458, 13, 330, 12805, 584, 5602, 1268, 60923, 51644, 349, 5788, 304, 279, 24548, 28160, 7013, 6650, 11, 433, 6197, 603, 311, 1427, 369, 4754, 11217, 430, 1436, 387, 9435, 311, 279, 6930, 323, 617, 279, 1890, 2515, 1210, 578, 2128, 11054, 1403, 11217, 430, 11, 994, 9435, 311, 279, 6930, 315, 24548, 11, 28160, 7013, 82714, 273, 19646, 7917, 304, 12742, 5627, 311, 12192, 51644, 349, 5788, 13, 578, 1176, 5623, 11, 2663, 432, 8974, 35, 19711, 11, 75042, 264, 35693, 43080, 38970, 2663, 622, 12173, 12, 16257, 11, 902, 1380, 45803, 2038, 505, 4994, 279, 2849, 311, 279, 62607, 315, 279, 2849, 13, 578, 3495, 8710, 430, 622, 12173, 12, 16257, 15449, 11767, 311, 279, 7319, 5788, 315, 51644, 349, 323, 420, 304, 2543, 20722, 7013, 82714, 273, 19646, 2849, 15449, 323, 39392, 7013, 6650, 13, 578, 1023, 5623, 11, 2663, 6560, 12448, 24, 11, 10215, 4611, 2739, 85, 349, 505, 16661, 279, 55042, 4298, 11, 902, 8603, 279, 5788, 315, 51644, 349, 304, 279, 7013, 82714, 273, 19646, 7917, 323, 14511, 988, 7013, 6650, 304, 24548, 13, 330, 24798, 420, 4007, 11, 584, 18661, 264, 2763, 315, 7185, 20616, 1139, 502, 5627, 311, 20891, 19646, 7917, 1359, 1071, 362, 547, 68, 74052, 11, 264, 864, 38083, 278, 5542, 2176, 304, 12310, 894, 596, 10278, 323, 1176, 3229, 315, 279, 4007, 13, 330, 791, 4623, 315, 1701, 11217, 311, 51077, 7013, 6650, 1555, 7013, 82714, 273, 19646, 7917, 374, 1633, 26455, 2728, 1268, 1690, 11990, 315, 1274, 11, 2225, 3026, 323, 3278, 11, 3568, 449, 7013, 4814, 13, 358, 1781, 584, 3077, 1193, 1120, 22088, 311, 3619, 279, 9200, 3560, 39097, 11335, 304, 7013, 6650, 323, 19646, 7917, 304, 4689, 26, 358, 2846, 3411, 4741, 311, 279, 4754, 3851, 315, 1521, 502, 14955, 369, 7013, 4814, 323, 7953, 1210, 578, 1005, 315, 432, 8974, 35, 19711, 311, 12192, 7013, 6650, 374, 9960, 555, 264, 78090, 25589, 3851, 13019, 555, 279, 50751, 12053, 11050, 5856, 389, 17981, 315, 31613, 78777, 13, 578, 1005, 315, 6560, 12448, 24, 311, 12192, 7013, 6650, 374, 9960, 555, 264, 8821, 78090, 25589, 13019, 555, 279, 50751, 12053, 11050, 5856, 389, 17981, 315, 31613, 78777, 11, 449, 12310, 894, 323, 3771, 1073, 74, 439, 17459, 1105, 13, 578, 22772, 11217, 7633, 3485, 1051, 1511, 304, 864, 91899, 7177, 1193, 323, 617, 539, 1027, 12793, 304, 12966, 477, 12054, 555, 279, 12369, 323, 26166, 17128, 439, 6220, 323, 7524, 369, 1005, 304, 12966, 13, 220, 128257, 198 ]

2,408

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract We study experimentally a fine structure of the optical Laue diffraction from two-dimensional periodic photonic lattices. The periodic photonic lattices with the C 4 v square symmetry, orthogonal C 2 v symmetry and hexagonal C 6 v symmetry are composed of submicron dielectric elements fabricated by the direct laser writing technique. We observe surprisingly strong optical diffraction from a finite number of elements that provides an excellent tool to determine not only the symmetry but also exact number of particles in the finite-length structure and the sample shape. Using different samples with orthogonal C 2 v symmetry and varying the lattice spacing, we observe experimentally a transition between the regime of multi-order diffraction, being typical for photonic crystals to the regime where only the zero-order diffraction can be observed, being is a clear fingerprint of dielectric metasurfaces characterized by effective parameters. Introduction Diffraction of waves of different nature (e.g., X-rays, electrons, neutrons, photons, etc) is a common phenomenon underlying many experimental tools employed for the study of crystalline structures and the analysis of physical properties of ordered bulk materials 1 . Nowadays, diffraction of electrons is widely used to detect the number of stacking sheets of planar two-dimensional (2D) materials such as graphene 2 , carbon nanofilms 3 , transition metal dichalcogenides 4 , etc. For the three-dimensional (3D) photonic crystals, when the period of the spatial modulation of dielectric permittivity becomes comparable with the wavelength of light, the Bragg diffraction gives rise to the appearance of the bandgaps in the energy spectrum 5 , 6 , 7 . An instructive example is the analysis of optical Bragg diffraction from different opal-based photonic structures, including thin opal films 8 , 9 , 10 , bulk samples of synthetic opals 11 , 12 , 13 and opal-based colloidal structures 14 , 15 . Opals are built up of quasi-spherical particles of amorphous silica a -SiO 2 , each of them having a rather hard shell and porous core 16 . Opals possess bandgaps in the visible range due to the typical size of the constitutive particles a -SiO 2 of some hundreds of nanometers. This provides a unique way for the direct observation of angle-resolved diffraction patterns in the visible spectral range. Thin photonic films composed of several layers have been studied by spectroscopic techniques. In particular, the results of optical studies of opal films composed of 6 layers are given in ref. 10 . Also, diffraction patterns from woodpile films consisting of 20 layers were studied depending on the internal refractive index contrast Δ n in ref. 17 . A detailed picture of a transformation of the optical diffraction patterns during the transition from thin opals films to 3D opal-based photonic crystals was studied in refs 7 and 10 . In spite of a large amount of experimental studies of periodic structures 18 , 19 , 20 , 21 , diffraction of light from two-dimensional planar photonic structures composed of just a single layer (the so-called metasurface) and several elements in the plane was not studied experimentally in detail, to the best of our knowledge. We emphasize that diffraction is a unique tool for the studies of optical properties of true two-dimensional structures because other methods, such as reflection and transmission spectroscopy, produce a very weak response from a single sub-micron layer. In contrast, here we demonstrate that the 2D structures composed of a finite number of sub-micron dielectric scatterers give rise to surprisingly strong intensity of optical diffraction that can be visible by a naked eye on a screen placed just behind the metasurface sample. With the intention to further deepen our understanding of light scattering in periodic media, a number of challenging problems can be formulated: What are novel effects in optical diffraction from finite-size 2D photonic structures, beyond the well-known results of X-rays, neutrons and photons diffraction from thin films and 3D structures? Can one obtain from the light scattering direct information about the number and spatial distribution of sub-micron particles? And finally the most intriguing question: is it possible to observe in optical diffraction a transition between 2D photonic films and metasurfaces? The study of metasurfaces has attracted much attention in recent years 22 , 23 due to their many useful functionalities and potentially important applications, ranging from simple elements of flat optics for unusual beam steering 24 , 25 , high efficiency of planar sensing devices 26 and other types of light control 27 , 28 in both linear and nonlinear regimes 29 . We notice that a transition in light scattering regimes from photonic crystals to all-dielectric metamaterials and a corresponding phase diagram were studied in ref. 30 . In this study, we use a direct laser writing (DLW) 31 , 32 , 33 technique to fabricate true 2D photonic structures or metasurfaces as periodic arrays of submicron dielectric particles or their inverted counterparts with the square C 4 v , orthogonal C 2 v and hexagonal C 6 v lattice symmetry. We study experimentally optical diffraction from fabricated direct and inverted finite-size 2D structures and observe directly (on a screen placed after the sample) a variety of diffraction patterns of exceeding beauty. The fine structure of the patterns allows detecting exact number of scatterers in any direction. Using a set of anisotropic samples with orthogonal C 2 v lattice symmetry, we demonstrate both experimentally and theoretically a transition from multi-order diffraction regime which is characteristic for photonic crystals to the regime where only the zero-order diffraction was observed being a fingerprint of metasurfaces characterized by effective parameters. Results Sample fabrication The problem of fabrication of 2D photonic structures of almost arbitrary shape can be solved with the recently developed DLW method. This technology is based on the nonlinear two-photon polymerization of a photosensitive material in the focus of a femtosecond laser beam. A high resolution of the technique is due to the intensity-threshold character of the polymerization process which occurs in a region with sizes significantly smaller than the size of the", "role": "user" }, { "content": "Scientists from Russia and Australia have proposed a simple new way of counting microscopic particles in optical materials by means of a laser. A light beam passing through such a material splits and forms a characteristic pattern consisting of numerous bright spots on a projection screen. The researchers found that the number of these spots corresponds exactly to the number of scattering microscopic particles in the optical material. Therefore, the structure and shape of any optical material can be determined without resorting to the use of expensive electron or atomic-force microscopy. According to the researchers, the new method will help design optical devices much faster. The work was published in Scientific Reports. The production of optical circuits requires devices that can amplify optical signals, bring them into focus, rotate and change their type of motion. Ordinary lenses cannot cope with these tasks at nanoscale, so scientists are working with artificial optical materials—photonic crystals and metamaterials, which can control the propagation of light in extraordinary ways. However, fabricating optical materials with desired properties is a laborious process that needs improvement. The scientists from ITMO University, Ioffe Institute, and Australian National University have suggested analyzing the structure of photonic crystals using optical diffraction—that is, by looking at the light pattern generated when the sample is exposed to a laser beam. The study has shown that the number of spots in the pattern is equal to the number of scattering microscopic particles in the sample structure. Previously, such small particles could only be seen and counted with powerful and expensive electron or atomic-force microscopes. \"The light senses heterogeneity,\" says Mikhail Rybin, first author of the paper, senior researcher at the Department of Nanophotonics and Metamaterials at ITMO University. \"Depending on the shape and relative position of the scatterers, the light wave continues to propagate differently behind the sample. In other words, the structure of the sample affects the diffraction pattern, which will be projected on the screen. We found out that it is possible to determine the precise number of scatterers in the material. This helps understand not only the type of the sample lattice (square, triangular), but also to establish its structure (20 to 20 particles, or 30 to 15) just by counting light spots on the screen.\" Experimentally obtained and simulated diffraction patterns for a sample. Credit: ITMO University The new method is a much more affordable alternative to expensive electron or atomic-force microscopy and in this case, does not spoil the sample. \"Even a schoolboy can buy a laser pointer, adapt a small lens to focus the light better, fix the sample and shine a laser beam on it,\" notes Mikhail Rybin. \"In addition, our method makes it possible to study optical materials without changing their structure in contrast to electron microscopy, where the sample surface has to be covered by a conductive metal layer, which impairs optical properties of the sample.\" The new method has already enabled scientists to investigate the transition between two main classes of optical materials: photonic crystals and metasurfaces. In the study, they have determined the lattice parameters, which define whether the light perceives the material as a two-dimensional photonic crystal or a metasurface. In both classes, the scattering particles (rings, balls, cylinders of 200 to 300 nanometers) are arranged in a flat lattice. However, with a two-dimensional photonic crystal, the light perceives the sample as a set of separate particles and generates a complex pattern on the screen behind the sample. Metasurfaces appear homogenous via the technique—the screen shows a single bright spot, indicating that the scattering particles are located close enough to each other that the light does not register separate particles and passes through the sample without splitting. In order for the light beam to pass through a metasurface, the distance between the particles has to be smaller than the wavelength of light. For some structures, it is necessary to produce a lattice in which the distance between particles is two to three times smaller than the light wavelength. Often, however, meta-properties can manifest themselves at larger distances between the particles. It is important to find the maximum allowable distance, since reducing the structure by one single nanometer makes the technology more expensive. For the light with a wavelength of 530 nanometers (green color), the distance of 500 nanometers between the scattering particles is already enough. \"A green light beam perceives the structure with a period of 500 nanometers as a homogenous material. Therefore, it is not always necessary to fabricate a lattice with a period smaller than the wavelength, because producing larger structures is much easier from technological standpoint. For one wavelength, the material will act as a photonic crystal and as a metasurface for another. That is why designing such structures, we can evaluate maximum lattice period with laser,\" concludes Mikhail Rybin. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract We study experimentally a fine structure of the optical Laue diffraction from two-dimensional periodic photonic lattices. The periodic photonic lattices with the C 4 v square symmetry, orthogonal C 2 v symmetry and hexagonal C 6 v symmetry are composed of submicron dielectric elements fabricated by the direct laser writing technique. We observe surprisingly strong optical diffraction from a finite number of elements that provides an excellent tool to determine not only the symmetry but also exact number of particles in the finite-length structure and the sample shape. Using different samples with orthogonal C 2 v symmetry and varying the lattice spacing, we observe experimentally a transition between the regime of multi-order diffraction, being typical for photonic crystals to the regime where only the zero-order diffraction can be observed, being is a clear fingerprint of dielectric metasurfaces characterized by effective parameters. Introduction Diffraction of waves of different nature (e.g., X-rays, electrons, neutrons, photons, etc) is a common phenomenon underlying many experimental tools employed for the study of crystalline structures and the analysis of physical properties of ordered bulk materials 1 . Nowadays, diffraction of electrons is widely used to detect the number of stacking sheets of planar two-dimensional (2D) materials such as graphene 2 , carbon nanofilms 3 , transition metal dichalcogenides 4 , etc. For the three-dimensional (3D) photonic crystals, when the period of the spatial modulation of dielectric permittivity becomes comparable with the wavelength of light, the Bragg diffraction gives rise to the appearance of the bandgaps in the energy spectrum 5 , 6 , 7 . An instructive example is the analysis of optical Bragg diffraction from different opal-based photonic structures, including thin opal films 8 , 9 , 10 , bulk samples of synthetic opals 11 , 12 , 13 and opal-based colloidal structures 14 , 15 . Opals are built up of quasi-spherical particles of amorphous silica a -SiO 2 , each of them having a rather hard shell and porous core 16 . Opals possess bandgaps in the visible range due to the typical size of the constitutive particles a -SiO 2 of some hundreds of nanometers. This provides a unique way for the direct observation of angle-resolved diffraction patterns in the visible spectral range. Thin photonic films composed of several layers have been studied by spectroscopic techniques. In particular, the results of optical studies of opal films composed of 6 layers are given in ref. 10 . Also, diffraction patterns from woodpile films consisting of 20 layers were studied depending on the internal refractive index contrast Δ n in ref. 17 . A detailed picture of a transformation of the optical diffraction patterns during the transition from thin opals films to 3D opal-based photonic crystals was studied in refs 7 and 10 . In spite of a large amount of experimental studies of periodic structures 18 , 19 , 20 , 21 , diffraction of light from two-dimensional planar photonic structures composed of just a single layer (the so-called metasurface) and several elements in the plane was not studied experimentally in detail, to the best of our knowledge. We emphasize that diffraction is a unique tool for the studies of optical properties of true two-dimensional structures because other methods, such as reflection and transmission spectroscopy, produce a very weak response from a single sub-micron layer. In contrast, here we demonstrate that the 2D structures composed of a finite number of sub-micron dielectric scatterers give rise to surprisingly strong intensity of optical diffraction that can be visible by a naked eye on a screen placed just behind the metasurface sample. With the intention to further deepen our understanding of light scattering in periodic media, a number of challenging problems can be formulated: What are novel effects in optical diffraction from finite-size 2D photonic structures, beyond the well-known results of X-rays, neutrons and photons diffraction from thin films and 3D structures? Can one obtain from the light scattering direct information about the number and spatial distribution of sub-micron particles? And finally the most intriguing question: is it possible to observe in optical diffraction a transition between 2D photonic films and metasurfaces? The study of metasurfaces has attracted much attention in recent years 22 , 23 due to their many useful functionalities and potentially important applications, ranging from simple elements of flat optics for unusual beam steering 24 , 25 , high efficiency of planar sensing devices 26 and other types of light control 27 , 28 in both linear and nonlinear regimes 29 . We notice that a transition in light scattering regimes from photonic crystals to all-dielectric metamaterials and a corresponding phase diagram were studied in ref. 30 . In this study, we use a direct laser writing (DLW) 31 , 32 , 33 technique to fabricate true 2D photonic structures or metasurfaces as periodic arrays of submicron dielectric particles or their inverted counterparts with the square C 4 v , orthogonal C 2 v and hexagonal C 6 v lattice symmetry. We study experimentally optical diffraction from fabricated direct and inverted finite-size 2D structures and observe directly (on a screen placed after the sample) a variety of diffraction patterns of exceeding beauty. The fine structure of the patterns allows detecting exact number of scatterers in any direction. Using a set of anisotropic samples with orthogonal C 2 v lattice symmetry, we demonstrate both experimentally and theoretically a transition from multi-order diffraction regime which is characteristic for photonic crystals to the regime where only the zero-order diffraction was observed being a fingerprint of metasurfaces characterized by effective parameters. Results Sample fabrication The problem of fabrication of 2D photonic structures of almost arbitrary shape can be solved with the recently developed DLW method. This technology is based on the nonlinear two-photon polymerization of a photosensitive material in the focus of a femtosecond laser beam. A high resolution of the technique is due to the intensity-threshold character of the polymerization process which occurs in a region with sizes significantly smaller than the size of the<|im_end|> <|im_start|>assistant Scientists from Russia and Australia have proposed a simple new way of counting microscopic particles in optical materials by means of a laser. A light beam passing through such a material splits and forms a characteristic pattern consisting of numerous bright spots on a projection screen. The researchers found that the number of these spots corresponds exactly to the number of scattering microscopic particles in the optical material. Therefore, the structure and shape of any optical material can be determined without resorting to the use of expensive electron or atomic-force microscopy. According to the researchers, the new method will help design optical devices much faster. The work was published in Scientific Reports. The production of optical circuits requires devices that can amplify optical signals, bring them into focus, rotate and change their type of motion. Ordinary lenses cannot cope with these tasks at nanoscale, so scientists are working with artificial optical materials—photonic crystals and metamaterials, which can control the propagation of light in extraordinary ways. However, fabricating optical materials with desired properties is a laborious process that needs improvement. The scientists from ITMO University, Ioffe Institute, and Australian National University have suggested analyzing the structure of photonic crystals using optical diffraction—that is, by looking at the light pattern generated when the sample is exposed to a laser beam. The study has shown that the number of spots in the pattern is equal to the number of scattering microscopic particles in the sample structure. Previously, such small particles could only be seen and counted with powerful and expensive electron or atomic-force microscopes. "The light senses heterogeneity," says Mikhail Rybin, first author of the paper, senior researcher at the Department of Nanophotonics and Metamaterials at ITMO University. "Depending on the shape and relative position of the scatterers, the light wave continues to propagate differently behind the sample. In other words, the structure of the sample affects the diffraction pattern, which will be projected on the screen. We found out that it is possible to determine the precise number of scatterers in the material. This helps understand not only the type of the sample lattice (square, triangular), but also to establish its structure (20 to 20 particles, or 30 to 15) just by counting light spots on the screen." Experimentally obtained and simulated diffraction patterns for a sample. Credit: ITMO University The new method is a much more affordable alternative to expensive electron or atomic-force microscopy and in this case, does not spoil the sample. "Even a schoolboy can buy a laser pointer, adapt a small lens to focus the light better, fix the sample and shine a laser beam on it," notes Mikhail Rybin. "In addition, our method makes it possible to study optical materials without changing their structure in contrast to electron microscopy, where the sample surface has to be covered by a conductive metal layer, which impairs optical properties of the sample." The new method has already enabled scientists to investigate the transition between two main classes of optical materials: photonic crystals and metasurfaces. In the study, they have determined the lattice parameters, which define whether the light perceives the material as a two-dimensional photonic crystal or a metasurface. In both classes, the scattering particles (rings, balls, cylinders of 200 to 300 nanometers) are arranged in a flat lattice. However, with a two-dimensional photonic crystal, the light perceives the sample as a set of separate particles and generates a complex pattern on the screen behind the sample. Metasurfaces appear homogenous via the technique—the screen shows a single bright spot, indicating that the scattering particles are located close enough to each other that the light does not register separate particles and passes through the sample without splitting. In order for the light beam to pass through a metasurface, the distance between the particles has to be smaller than the wavelength of light. For some structures, it is necessary to produce a lattice in which the distance between particles is two to three times smaller than the light wavelength. Often, however, meta-properties can manifest themselves at larger distances between the particles. It is important to find the maximum allowable distance, since reducing the structure by one single nanometer makes the technology more expensive. For the light with a wavelength of 530 nanometers (green color), the distance of 500 nanometers between the scattering particles is already enough. "A green light beam perceives the structure with a period of 500 nanometers as a homogenous material. Therefore, it is not always necessary to fabricate a lattice with a period smaller than the wavelength, because producing larger structures is much easier from technological standpoint. For one wavelength, the material will act as a photonic crystal and as a metasurface for another. That is why designing such structures, we can evaluate maximum lattice period with laser," concludes Mikhail Rybin. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 1226, 4007, 9526, 750, 264, 7060, 6070, 315, 279, 29393, 5034, 361, 3722, 16597, 505, 1403, 33520, 39445, 4604, 14338, 326, 1617, 1238, 13, 578, 39445, 4604, 14338, 326, 1617, 1238, 449, 279, 356, 220, 19, 348, 9518, 46220, 11, 95680, 356, 220, 17, 348, 46220, 323, 12651, 24346, 356, 220, 21, 348, 46220, 527, 24306, 315, 1207, 21914, 2298, 2815, 47262, 5540, 70554, 555, 279, 2167, 21120, 4477, 15105, 13, 1226, 23846, 29392, 3831, 29393, 3722, 16597, 505, 264, 35326, 1396, 315, 5540, 430, 5825, 459, 9250, 5507, 311, 8417, 539, 1193, 279, 46220, 719, 1101, 4839, 1396, 315, 19252, 304, 279, 35326, 30425, 6070, 323, 279, 6205, 6211, 13, 12362, 2204, 10688, 449, 95680, 356, 220, 17, 348, 46220, 323, 29865, 279, 55372, 27032, 11, 584, 23846, 9526, 750, 264, 9320, 1990, 279, 17942, 315, 7447, 24747, 3722, 16597, 11, 1694, 14595, 369, 4604, 14338, 48473, 311, 279, 17942, 1405, 1193, 279, 7315, 24747, 3722, 16597, 649, 387, 13468, 11, 1694, 374, 264, 2867, 43697, 315, 2815, 47262, 2322, 300, 324, 7760, 32971, 555, 7524, 5137, 13, 29438, 29469, 16597, 315, 17301, 315, 2204, 7138, 320, 68, 1326, 2637, 1630, 82817, 11, 57678, 11, 26878, 26692, 11, 89235, 11, 5099, 8, 374, 264, 4279, 25885, 16940, 1690, 22772, 7526, 20011, 369, 279, 4007, 315, 64568, 483, 14726, 323, 279, 6492, 315, 7106, 6012, 315, 11713, 20155, 7384, 220, 16, 662, 87581, 11, 3722, 16597, 315, 57678, 374, 13882, 1511, 311, 11388, 279, 1396, 315, 75172, 25112, 315, 3197, 277, 1403, 33520, 320, 17, 35, 8, 7384, 1778, 439, 66192, 220, 17, 1174, 12782, 20622, 47899, 1026, 220, 18, 1174, 9320, 9501, 29953, 17356, 11968, 3422, 220, 19, 1174, 5099, 13, 1789, 279, 2380, 33520, 320, 18, 35, 8, 4604, 14338, 48473, 11, 994, 279, 4261, 315, 279, 29079, 67547, 315, 2815, 47262, 14175, 1468, 1968, 9221, 30139, 449, 279, 46406, 315, 3177, 11, 279, 3320, 16094, 3722, 16597, 6835, 10205, 311, 279, 11341, 315, 279, 7200, 70, 2690, 304, 279, 4907, 20326, 220, 20, 1174, 220, 21, 1174, 220, 22, 662, 1556, 21745, 535, 3187, 374, 279, 6492, 315, 29393, 3320, 16094, 3722, 16597, 505, 2204, 1200, 278, 6108, 4604, 14338, 14726, 11, 2737, 15792, 1200, 278, 12631, 220, 23, 1174, 220, 24, 1174, 220, 605, 1174, 20155, 10688, 315, 28367, 1200, 1147, 220, 806, 1174, 220, 717, 1174, 220, 1032, 323, 1200, 278, 6108, 82048, 26966, 14726, 220, 975, 1174, 220, 868, 662, 10901, 1147, 527, 5918, 709, 315, 48844, 1355, 45845, 19252, 315, 1097, 16751, 788, 77889, 264, 482, 22771, 46, 220, 17, 1174, 1855, 315, 1124, 3515, 264, 4856, 2653, 12811, 323, 94761, 6332, 220, 845, 662, 10901, 1147, 15575, 7200, 70, 2690, 304, 279, 9621, 2134, 4245, 311, 279, 14595, 1404, 315, 279, 9129, 6844, 19252, 264, 482, 22771, 46, 220, 17, 315, 1063, 11758, 315, 20622, 33504, 13, 1115, 5825, 264, 5016, 1648, 369, 279, 2167, 22695, 315, 9392, 11849, 8905, 3722, 16597, 12912, 304, 279, 9621, 57077, 2134, 13, 70722, 4604, 14338, 12631, 24306, 315, 3892, 13931, 617, 1027, 20041, 555, 66425, 58510, 12823, 13, 763, 4040, 11, 279, 3135, 315, 29393, 7978, 315, 1200, 278, 12631, 24306, 315, 220, 21, 13931, 527, 2728, 304, 2098, 13, 220, 605, 662, 7429, 11, 3722, 16597, 12912, 505, 7732, 12470, 12631, 31706, 315, 220, 508, 13931, 1051, 20041, 11911, 389, 279, 5419, 19914, 3104, 1963, 13168, 82263, 308, 304, 2098, 13, 220, 1114, 662, 362, 11944, 6945, 315, 264, 18475, 315, 279, 29393, 3722, 16597, 12912, 2391, 279, 9320, 505, 15792, 1200, 1147, 12631, 311, 220, 18, 35, 1200, 278, 6108, 4604, 14338, 48473, 574, 20041, 304, 44243, 220, 22, 323, 220, 605, 662, 763, 34781, 315, 264, 3544, 3392, 315, 22772, 7978, 315, 39445, 14726, 220, 972, 1174, 220, 777, 1174, 220, 508, 1174, 220, 1691, 1174, 3722, 16597, 315, 3177, 505, 1403, 33520, 3197, 277, 4604, 14338, 14726, 24306, 315, 1120, 264, 3254, 6324, 320, 1820, 779, 19434, 2322, 300, 10730, 8, 323, 3892, 5540, 304, 279, 11277, 574, 539, 20041, 9526, 750, 304, 7872, 11, 311, 279, 1888, 315, 1057, 6677, 13, 1226, 47032, 430, 3722, 16597, 374, 264, 5016, 5507, 369, 279, 7978, 315, 29393, 6012, 315, 837, 1403, 33520, 14726, 1606, 1023, 5528, 11, 1778, 439, 22599, 323, 18874, 66425, 51856, 11, 8356, 264, 1633, 7621, 2077, 505, 264, 3254, 1207, 1474, 292, 2298, 6324, 13, 763, 13168, 11, 1618, 584, 20461, 430, 279, 220, 17, 35, 14726, 24306, 315, 264, 35326, 1396, 315, 1207, 1474, 292, 2298, 2815, 47262, 45577, 388, 3041, 10205, 311, 29392, 3831, 21261, 315, 29393, 3722, 16597, 430, 649, 387, 9621, 555, 264, 19557, 8071, 389, 264, 4264, 9277, 1120, 4920, 279, 2322, 300, 10730, 6205, 13, 3161, 279, 14944, 311, 4726, 92792, 1057, 8830, 315, 3177, 72916, 304, 39445, 3772, 11, 264, 1396, 315, 17436, 5435, 649, 387, 60394, 25, 3639, 527, 11775, 6372, 304, 29393, 3722, 16597, 505, 35326, 7321, 220, 17, 35, 4604, 14338, 14726, 11, 7953, 279, 1664, 22015, 3135, 315, 1630, 82817, 11, 26878, 26692, 323, 89235, 3722, 16597, 505, 15792, 12631, 323, 220, 18, 35, 14726, 30, 3053, 832, 6994, 505, 279, 3177, 72916, 2167, 2038, 922, 279, 1396, 323, 29079, 8141, 315, 1207, 1474, 292, 2298, 19252, 30, 1628, 5616, 279, 1455, 41765, 3488, 25, 374, 433, 3284, 311, 23846, 304, 29393, 3722, 16597, 264, 9320, 1990, 220, 17, 35, 4604, 14338, 12631, 323, 2322, 300, 324, 7760, 30, 578, 4007, 315, 2322, 300, 324, 7760, 706, 29123, 1790, 6666, 304, 3293, 1667, 220, 1313, 1174, 220, 1419, 4245, 311, 872, 1690, 5505, 93180, 323, 13893, 3062, 8522, 11, 24950, 505, 4382, 5540, 315, 10269, 70985, 369, 19018, 24310, 33277, 220, 1187, 1174, 220, 914, 1174, 1579, 15374, 315, 3197, 277, 60199, 7766, 220, 1627, 323, 1023, 4595, 315, 3177, 2585, 220, 1544, 1174, 220, 1591, 304, 2225, 13790, 323, 75098, 61911, 220, 1682, 662, 1226, 5406, 430, 264, 9320, 304, 3177, 72916, 61911, 505, 4604, 14338, 48473, 311, 682, 1773, 648, 47262, 88848, 2229, 82, 323, 264, 12435, 10474, 13861, 1051, 20041, 304, 2098, 13, 220, 966, 662, 763, 420, 4007, 11, 584, 1005, 264, 2167, 21120, 4477, 320, 16931, 54, 8, 220, 2148, 1174, 220, 843, 1174, 220, 1644, 15105, 311, 13354, 349, 837, 220, 17, 35, 4604, 14338, 14726, 477, 2322, 300, 324, 7760, 439, 39445, 18893, 315, 1207, 21914, 2298, 2815, 47262, 19252, 477, 872, 47801, 38495, 449, 279, 9518, 356, 220, 19, 348, 1174, 95680, 356, 220, 17, 348, 323, 12651, 24346, 356, 220, 21, 348, 55372, 46220, 13, 1226, 4007, 9526, 750, 29393, 3722, 16597, 505, 70554, 2167, 323, 47801, 35326, 7321, 220, 17, 35, 14726, 323, 23846, 6089, 320, 263, 264, 4264, 9277, 1306, 279, 6205, 8, 264, 8205, 315, 3722, 16597, 12912, 315, 49005, 13444, 13, 578, 7060, 6070, 315, 279, 12912, 6276, 54626, 4839, 1396, 315, 45577, 388, 304, 904, 5216, 13, 12362, 264, 743, 315, 459, 285, 79432, 10688, 449, 95680, 356, 220, 17, 348, 55372, 46220, 11, 584, 20461, 2225, 9526, 750, 323, 63234, 264, 9320, 505, 7447, 24747, 3722, 16597, 17942, 902, 374, 29683, 369, 4604, 14338, 48473, 311, 279, 17942, 1405, 1193, 279, 7315, 24747, 3722, 16597, 574, 13468, 1694, 264, 43697, 315, 2322, 300, 324, 7760, 32971, 555, 7524, 5137, 13, 18591, 19690, 59251, 578, 3575, 315, 59251, 315, 220, 17, 35, 4604, 14338, 14726, 315, 4661, 25142, 6211, 649, 387, 29056, 449, 279, 6051, 8040, 34075, 54, 1749, 13, 1115, 5557, 374, 3196, 389, 279, 75098, 1403, 63837, 26934, 47393, 2065, 315, 264, 7397, 19245, 3769, 304, 279, 5357, 315, 264, 5103, 83, 974, 1321, 21120, 24310, 13, 362, 1579, 11175, 315, 279, 15105, 374, 4245, 311, 279, 21261, 7716, 7308, 3752, 315, 279, 47393, 2065, 1920, 902, 13980, 304, 264, 5654, 449, 12562, 12207, 9333, 1109, 279, 1404, 315, 279, 128257, 198, 128256, 78191, 198, 72326, 505, 8524, 323, 8494, 617, 11223, 264, 4382, 502, 1648, 315, 26060, 90090, 19252, 304, 29393, 7384, 555, 3445, 315, 264, 21120, 13, 362, 3177, 24310, 12579, 1555, 1778, 264, 3769, 41567, 323, 7739, 264, 29683, 5497, 31706, 315, 12387, 10107, 19300, 389, 264, 22343, 4264, 13, 578, 12074, 1766, 430, 279, 1396, 315, 1521, 19300, 34310, 7041, 311, 279, 1396, 315, 72916, 90090, 19252, 304, 279, 29393, 3769, 13, 15636, 11, 279, 6070, 323, 6211, 315, 904, 29393, 3769, 649, 387, 11075, 2085, 22541, 287, 311, 279, 1005, 315, 11646, 17130, 477, 25524, 81149, 92914, 13, 10771, 311, 279, 12074, 11, 279, 502, 1749, 690, 1520, 2955, 29393, 7766, 1790, 10819, 13, 578, 990, 574, 4756, 304, 38130, 29140, 13, 578, 5788, 315, 29393, 46121, 7612, 7766, 430, 649, 97168, 29393, 17738, 11, 4546, 1124, 1139, 5357, 11, 17348, 323, 2349, 872, 955, 315, 11633, 13, 99011, 36057, 4250, 37586, 449, 1521, 9256, 520, 20622, 437, 2296, 11, 779, 14248, 527, 3318, 449, 21075, 29393, 7384, 2345, 52399, 14338, 48473, 323, 88848, 2229, 82, 11, 902, 649, 2585, 279, 54743, 315, 3177, 304, 24674, 5627, 13, 4452, 11, 13354, 1113, 29393, 7384, 449, 12974, 6012, 374, 264, 9511, 1245, 1920, 430, 3966, 16048, 13, 578, 14248, 505, 8871, 10754, 3907, 11, 358, 1885, 68, 10181, 11, 323, 13673, 5165, 3907, 617, 12090, 42118, 279, 6070, 315, 4604, 14338, 48473, 1701, 29393, 3722, 16597, 41128, 374, 11, 555, 3411, 520, 279, 3177, 5497, 8066, 994, 279, 6205, 374, 15246, 311, 264, 21120, 24310, 13, 578, 4007, 706, 6982, 430, 279, 1396, 315, 19300, 304, 279, 5497, 374, 6273, 311, 279, 1396, 315, 72916, 90090, 19252, 304, 279, 6205, 6070, 13, 59787, 11, 1778, 2678, 19252, 1436, 1193, 387, 3970, 323, 31094, 449, 8147, 323, 11646, 17130, 477, 25524, 81149, 8162, 82025, 13, 330, 791, 3177, 38207, 30548, 76730, 1359, 2795, 92551, 26775, 7006, 11, 1176, 3229, 315, 279, 5684, 11, 10195, 32185, 520, 279, 6011, 315, 33242, 5237, 26934, 1233, 323, 6344, 309, 2229, 82, 520, 8871, 10754, 3907, 13, 330, 80245, 389, 279, 6211, 323, 8844, 2361, 315, 279, 45577, 388, 11, 279, 3177, 12330, 9731, 311, 58514, 22009, 4920, 279, 6205, 13, 763, 1023, 4339, 11, 279, 6070, 315, 279, 6205, 22223, 279, 3722, 16597, 5497, 11, 902, 690, 387, 28448, 389, 279, 4264, 13, 1226, 1766, 704, 430, 433, 374, 3284, 311, 8417, 279, 24473, 1396, 315, 45577, 388, 304, 279, 3769, 13, 1115, 8779, 3619, 539, 1193, 279, 955, 315, 279, 6205, 55372, 320, 38576, 11, 66594, 705, 719, 1101, 311, 5813, 1202, 6070, 320, 508, 311, 220, 508, 19252, 11, 477, 220, 966, 311, 220, 868, 8, 1120, 555, 26060, 3177, 19300, 389, 279, 4264, 1210, 47893, 750, 12457, 323, 46836, 3722, 16597, 12912, 369, 264, 6205, 13, 16666, 25, 8871, 10754, 3907, 578, 502, 1749, 374, 264, 1790, 810, 17049, 10778, 311, 11646, 17130, 477, 25524, 81149, 92914, 323, 304, 420, 1162, 11, 1587, 539, 65893, 279, 6205, 13, 330, 13461, 264, 2978, 17627, 649, 3780, 264, 21120, 7597, 11, 10737, 264, 2678, 18848, 311, 5357, 279, 3177, 2731, 11, 5155, 279, 6205, 323, 33505, 264, 21120, 24310, 389, 433, 1359, 8554, 92551, 26775, 7006, 13, 330, 644, 5369, 11, 1057, 1749, 3727, 433, 3284, 311, 4007, 29393, 7384, 2085, 10223, 872, 6070, 304, 13168, 311, 17130, 92914, 11, 1405, 279, 6205, 7479, 706, 311, 387, 9960, 555, 264, 6929, 535, 9501, 6324, 11, 902, 3242, 4825, 29393, 6012, 315, 279, 6205, 1210, 578, 502, 1749, 706, 2736, 9147, 14248, 311, 19874, 279, 9320, 1990, 1403, 1925, 6989, 315, 29393, 7384, 25, 4604, 14338, 48473, 323, 2322, 300, 324, 7760, 13, 763, 279, 4007, 11, 814, 617, 11075, 279, 55372, 5137, 11, 902, 7124, 3508, 279, 3177, 62822, 1924, 279, 3769, 439, 264, 1403, 33520, 4604, 14338, 26110, 477, 264, 2322, 300, 10730, 13, 763, 2225, 6989, 11, 279, 72916, 19252, 320, 81, 826, 11, 20953, 11, 75421, 315, 220, 1049, 311, 220, 3101, 20622, 33504, 8, 527, 28902, 304, 264, 10269, 55372, 13, 4452, 11, 449, 264, 1403, 33520, 4604, 14338, 26110, 11, 279, 3177, 62822, 1924, 279, 6205, 439, 264, 743, 315, 8821, 19252, 323, 27983, 264, 6485, 5497, 389, 279, 4264, 4920, 279, 6205, 13, 6344, 300, 324, 7760, 5101, 5105, 53595, 4669, 279, 15105, 22416, 4264, 5039, 264, 3254, 10107, 7858, 11, 19392, 430, 279, 72916, 19252, 527, 7559, 3345, 3403, 311, 1855, 1023, 430, 279, 3177, 1587, 539, 4254, 8821, 19252, 323, 16609, 1555, 279, 6205, 2085, 45473, 13, 763, 2015, 369, 279, 3177, 24310, 311, 1522, 1555, 264, 2322, 300, 10730, 11, 279, 6138, 1990, 279, 19252, 706, 311, 387, 9333, 1109, 279, 46406, 315, 3177, 13, 1789, 1063, 14726, 11, 433, 374, 5995, 311, 8356, 264, 55372, 304, 902, 279, 6138, 1990, 19252, 374, 1403, 311, 2380, 3115, 9333, 1109, 279, 3177, 46406, 13, 36016, 11, 4869, 11, 8999, 68179, 649, 14794, 5694, 520, 8294, 27650, 1990, 279, 19252, 13, 1102, 374, 3062, 311, 1505, 279, 7340, 85852, 6138, 11, 2533, 18189, 279, 6070, 555, 832, 3254, 20622, 21037, 3727, 279, 5557, 810, 11646, 13, 1789, 279, 3177, 449, 264, 46406, 315, 220, 17252, 20622, 33504, 320, 13553, 1933, 705, 279, 6138, 315, 220, 2636, 20622, 33504, 1990, 279, 72916, 19252, 374, 2736, 3403, 13, 330, 32, 6307, 3177, 24310, 62822, 1924, 279, 6070, 449, 264, 4261, 315, 220, 2636, 20622, 33504, 439, 264, 5105, 53595, 3769, 13, 15636, 11, 433, 374, 539, 2744, 5995, 311, 13354, 349, 264, 55372, 449, 264, 4261, 9333, 1109, 279, 46406, 11, 1606, 17843, 8294, 14726, 374, 1790, 8831, 505, 30116, 51882, 13, 1789, 832, 46406, 11, 279, 3769, 690, 1180, 439, 264, 4604, 14338, 26110, 323, 439, 264, 2322, 300, 10730, 369, 2500, 13, 3011, 374, 3249, 30829, 1778, 14726, 11, 584, 649, 15806, 7340, 55372, 4261, 449, 21120, 1359, 45537, 92551, 26775, 7006, 13, 220, 128257, 198 ]

2,317

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Because parental care is expected to depend on the fitness returns generated by each unit of investment, it should be sensitive to both offspring condition and parental ability to invest. The Trivers-Willard Hypothesis (TWH) predicts that parents who are in good condition will bias investment towards sons, while parents who are in poor condition will bias investment towards daughters because high-quality sons are expected to out-reproduce high quality daughters, while low-quality daughters are expected to out-reproduce low quality sons. We report results from an online experiment testing the Trivers-Willard effect by measuring implicit and explicit psychological preferences and behaviorally implied preferences for sons or daughters both as a function of their social and economic status and in the aftermath of a priming task designed to make participants feel wealthy or poor. We find only limited support for predictions derived from the TWH and instead find that women have strong preferences for girls and men have preferences for boys. Introduction Our current understanding of how resources are allocated to maximize the reproductive success of sons and daughters is based on Fisher’s principle of equal investment in the sexes 1 . Carl Duesing was the first to demonstrate that many sexually reproducing species produce an equal number of males and females because the total reproductive value of males and females is necessarily equal 2 . However, because sex allocation depends on the fitness returns to parental effort, selection will favor equal investment in sons and daughters only when the cost of producing each sex is identical. This argument is one of the best understood and most celebrated theories in evolutionary biology 3 because it provides a framework for understanding the observed variance in sex ratios across species. In humans, although parental expenditure in each sex is expected to be equal, excess male mortality throughout the period of parental investment decreases the average costs of producing sons 1 . This is why most human populations are male- biased at birth 4 , 5 but nearly equal among individuals who are sexually mature. Although population-wide sex ratios are expected to be highly constrained due to frequency-dependent selection, evolution can favor deviations from Fisherian sex ratios if producing one sex has a greater payoff than the other in terms of the production of grand-offspring. Trivers and Willard, for example, hypothesized that natural selection should favor a parent’s ability to adjust offspring sex ratios according to their ability to invest 6 . The Trivers-Willard Hypothesis (TWH) relies on 3 critical assumptions: (1) that parental condition is correlated with offspring condition, (2) that offspring condition is correlated with condition in adulthood and (3) that condition differentially affects the mating success of each sex (e.g., males in good condition out-reproducing females in good condition and females in poor condition out-reproducing males in poor condition). Because these conditions are seen to hold for many species of mammals, Trivers and Willard argued that mothers in good condition should invest more in producing males while mothers who are in poor condition should invest more in producing females. In the years since it was proposed, the TWH has been subject to hundreds of tests, with mixed results and ongoing debates about such issues as the appropriateness of the species or population being studied, the timing of when such biases are expected to occur, and the validity of various measures of parental investment, parental condition, and offspring condition 7 . In its original formulation, the TWH focused exclusively on maternal condition and sex ratios at birth in mammals. However, because most investment in human offspring occurs postnatally and comes from both parents, many of the most convincing studies of TW effects in human populations have also analyzed care by fathers and have included measures of sex-biased investment after birth 8 . For example, Cronk collected data on sex biases in parental investment among the Mukogodo of Kenya, who are at the bottom of a regional hierarchy whereby men often either do not marry or have delayed marriage, and, as a result, have lower mean reproductive success than the women. He found that, on average, Mukogodo parents wean daughters later, spend more time nursing and holding daughters, remain physically closer to daughters, and are more likely to take their daughters than their sons for medical care, all of which results in better growth performance for Mukogodo girls, than boys, and a female bias in the sex ratio of children aged 0 through 4 years 9 , 10 , 11 . Meanwhile, a study of parents in the United States, using self-reports and diary data, found no evidence that parents’ socioeconomic status is associated with biased investment in either sex 12 . These contradictory results point to another potential pitfall that many studies purporting to test the TWH encounter by failing to sufficiently distinguish between physiological, psychological and behavioral outcomes. There is an abundance of evidence that there are often large discrepancies between stated offspring sex preferences and parents’ actual behavior toward offspring 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 and it is often the case that studies using behavioral measures are more likely to provide support 16 , 17 , 18 . Therefore it is crucial that researchers distinguish between physiological outcomes (e.g., factors that hinder the implantation of embryos), preferences implied by behavior (e.g., time spent nursing) and those assessed psychologically (e.g., self-reports or implicit preferences) that depend on whether the offspring is male or female. Other studies have further complicated attempts to reach a scientific consensus by showing that offspring condition, regardless of sex, and overall family income, can affect investment decisions. Increasing a family’s resources, for example, has been shown to result in a shift from concerns with efficiency to concerns with equity 19 and some studies have shown that poor households reduce investment in children who are at high risk but then increase investment in those children once the families obtain", "role": "user" }, { "content": "Finnish and American researchers in evolutionary biology conducted an online experiment and survey revealing that women prefer and are more likely to invest in their daughters and men in their sons. The study was designed to test the impact of parental resources on offspring sex preferences. Specifically, the authors sought to test the Trivers–Willard hypothesis that predicts that parents in good conditions will bias investment toward sons, while parents in poor conditions will bias investment toward daughters. \"However, our study failed to show that the parents' preferences for the offspring's gender are affected by their status, wealth, education or childhood environment. Instead, parental preferences were best predicted by their sex. Women from all socioeconomic backgrounds expressed implicit and explicit preferences for daughters: they chose to donate more to charities supporting girls and preferred to adopt girls. In contrast, men expressed consistent, albeit weaker, preferences for sons,\" explains lead author, Postdoctoral Researcher Robert Lynch from the University of Turku, Finland. The researchers tested the Trivers–Willard effect with an online experiment by measuring implicit and explicit psychological preferences and behaviourally implied preferences for sons or daughters both as a function of their social and economic status and in the aftermath of a priming task designed to make participants feel wealthy or poor. The results of the research help to make sense of the often contradictory findings on offspring sex preferences. The effects of parental condition and status, competing genetic interests between males and females, economic constraints on families, and the effects of cultural practices all conspire to complicate the evolutionary outcomes of parental investment strategies. \"Frequently, the impact of one factor, for example, the genetic sexual conflict between males and females, can mask the impact of another, such as the Trivers–Willard Hypothesis. This can make it difficult to parse their effects and make clear predictions about 'optimal' parental investment strategies from an evolutionary perspective. We hope that our study can shed new light on these strategies and provide a better understanding of evolutionary biology in humans,\" states Lynch. In addition to Postdoctoral Researcher Robert Lynch from the University of Turku, the study included researchers from Rutgers University and Arizona State University in the United States. The article was published in the journal Scientific Reports. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Because parental care is expected to depend on the fitness returns generated by each unit of investment, it should be sensitive to both offspring condition and parental ability to invest. The Trivers-Willard Hypothesis (TWH) predicts that parents who are in good condition will bias investment towards sons, while parents who are in poor condition will bias investment towards daughters because high-quality sons are expected to out-reproduce high quality daughters, while low-quality daughters are expected to out-reproduce low quality sons. We report results from an online experiment testing the Trivers-Willard effect by measuring implicit and explicit psychological preferences and behaviorally implied preferences for sons or daughters both as a function of their social and economic status and in the aftermath of a priming task designed to make participants feel wealthy or poor. We find only limited support for predictions derived from the TWH and instead find that women have strong preferences for girls and men have preferences for boys. Introduction Our current understanding of how resources are allocated to maximize the reproductive success of sons and daughters is based on Fisher’s principle of equal investment in the sexes 1 . Carl Duesing was the first to demonstrate that many sexually reproducing species produce an equal number of males and females because the total reproductive value of males and females is necessarily equal 2 . However, because sex allocation depends on the fitness returns to parental effort, selection will favor equal investment in sons and daughters only when the cost of producing each sex is identical. This argument is one of the best understood and most celebrated theories in evolutionary biology 3 because it provides a framework for understanding the observed variance in sex ratios across species. In humans, although parental expenditure in each sex is expected to be equal, excess male mortality throughout the period of parental investment decreases the average costs of producing sons 1 . This is why most human populations are male- biased at birth 4 , 5 but nearly equal among individuals who are sexually mature. Although population-wide sex ratios are expected to be highly constrained due to frequency-dependent selection, evolution can favor deviations from Fisherian sex ratios if producing one sex has a greater payoff than the other in terms of the production of grand-offspring. Trivers and Willard, for example, hypothesized that natural selection should favor a parent’s ability to adjust offspring sex ratios according to their ability to invest 6 . The Trivers-Willard Hypothesis (TWH) relies on 3 critical assumptions: (1) that parental condition is correlated with offspring condition, (2) that offspring condition is correlated with condition in adulthood and (3) that condition differentially affects the mating success of each sex (e.g., males in good condition out-reproducing females in good condition and females in poor condition out-reproducing males in poor condition). Because these conditions are seen to hold for many species of mammals, Trivers and Willard argued that mothers in good condition should invest more in producing males while mothers who are in poor condition should invest more in producing females. In the years since it was proposed, the TWH has been subject to hundreds of tests, with mixed results and ongoing debates about such issues as the appropriateness of the species or population being studied, the timing of when such biases are expected to occur, and the validity of various measures of parental investment, parental condition, and offspring condition 7 . In its original formulation, the TWH focused exclusively on maternal condition and sex ratios at birth in mammals. However, because most investment in human offspring occurs postnatally and comes from both parents, many of the most convincing studies of TW effects in human populations have also analyzed care by fathers and have included measures of sex-biased investment after birth 8 . For example, Cronk collected data on sex biases in parental investment among the Mukogodo of Kenya, who are at the bottom of a regional hierarchy whereby men often either do not marry or have delayed marriage, and, as a result, have lower mean reproductive success than the women. He found that, on average, Mukogodo parents wean daughters later, spend more time nursing and holding daughters, remain physically closer to daughters, and are more likely to take their daughters than their sons for medical care, all of which results in better growth performance for Mukogodo girls, than boys, and a female bias in the sex ratio of children aged 0 through 4 years 9 , 10 , 11 . Meanwhile, a study of parents in the United States, using self-reports and diary data, found no evidence that parents’ socioeconomic status is associated with biased investment in either sex 12 . These contradictory results point to another potential pitfall that many studies purporting to test the TWH encounter by failing to sufficiently distinguish between physiological, psychological and behavioral outcomes. There is an abundance of evidence that there are often large discrepancies between stated offspring sex preferences and parents’ actual behavior toward offspring 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 and it is often the case that studies using behavioral measures are more likely to provide support 16 , 17 , 18 . Therefore it is crucial that researchers distinguish between physiological outcomes (e.g., factors that hinder the implantation of embryos), preferences implied by behavior (e.g., time spent nursing) and those assessed psychologically (e.g., self-reports or implicit preferences) that depend on whether the offspring is male or female. Other studies have further complicated attempts to reach a scientific consensus by showing that offspring condition, regardless of sex, and overall family income, can affect investment decisions. Increasing a family’s resources, for example, has been shown to result in a shift from concerns with efficiency to concerns with equity 19 and some studies have shown that poor households reduce investment in children who are at high risk but then increase investment in those children once the families obtain<|im_end|> <|im_start|>assistant Finnish and American researchers in evolutionary biology conducted an online experiment and survey revealing that women prefer and are more likely to invest in their daughters and men in their sons. The study was designed to test the impact of parental resources on offspring sex preferences. Specifically, the authors sought to test the Trivers–Willard hypothesis that predicts that parents in good conditions will bias investment toward sons, while parents in poor conditions will bias investment toward daughters. "However, our study failed to show that the parents' preferences for the offspring's gender are affected by their status, wealth, education or childhood environment. Instead, parental preferences were best predicted by their sex. Women from all socioeconomic backgrounds expressed implicit and explicit preferences for daughters: they chose to donate more to charities supporting girls and preferred to adopt girls. In contrast, men expressed consistent, albeit weaker, preferences for sons," explains lead author, Postdoctoral Researcher Robert Lynch from the University of Turku, Finland. The researchers tested the Trivers–Willard effect with an online experiment by measuring implicit and explicit psychological preferences and behaviourally implied preferences for sons or daughters both as a function of their social and economic status and in the aftermath of a priming task designed to make participants feel wealthy or poor. The results of the research help to make sense of the often contradictory findings on offspring sex preferences. The effects of parental condition and status, competing genetic interests between males and females, economic constraints on families, and the effects of cultural practices all conspire to complicate the evolutionary outcomes of parental investment strategies. "Frequently, the impact of one factor, for example, the genetic sexual conflict between males and females, can mask the impact of another, such as the Trivers–Willard Hypothesis. This can make it difficult to parse their effects and make clear predictions about 'optimal' parental investment strategies from an evolutionary perspective. We hope that our study can shed new light on these strategies and provide a better understanding of evolutionary biology in humans," states Lynch. In addition to Postdoctoral Researcher Robert Lynch from the University of Turku, the study included researchers from Rutgers University and Arizona State University in the United States. The article was published in the journal Scientific Reports. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 9393, 46679, 2512, 374, 3685, 311, 6904, 389, 279, 17479, 4780, 8066, 555, 1855, 5089, 315, 9341, 11, 433, 1288, 387, 16614, 311, 2225, 46471, 3044, 323, 46679, 5845, 311, 2793, 13, 578, 1183, 1986, 12, 10149, 569, 39515, 78, 13491, 320, 51, 20484, 8, 56978, 430, 6699, 889, 527, 304, 1695, 3044, 690, 15837, 9341, 7119, 26419, 11, 1418, 6699, 889, 527, 304, 8009, 3044, 690, 15837, 9341, 7119, 30968, 1606, 1579, 22867, 26419, 527, 3685, 311, 704, 5621, 98374, 1579, 4367, 30968, 11, 1418, 3428, 22867, 30968, 527, 3685, 311, 704, 5621, 98374, 3428, 4367, 26419, 13, 1226, 1934, 3135, 505, 459, 2930, 9526, 7649, 279, 1183, 1986, 12, 10149, 569, 2515, 555, 30090, 18479, 323, 11720, 24064, 19882, 323, 7865, 750, 6259, 19882, 369, 26419, 477, 30968, 2225, 439, 264, 734, 315, 872, 3674, 323, 7100, 2704, 323, 304, 279, 40696, 315, 264, 9036, 287, 3465, 6319, 311, 1304, 13324, 2733, 28994, 477, 8009, 13, 1226, 1505, 1193, 7347, 1862, 369, 20492, 14592, 505, 279, 350, 20484, 323, 4619, 1505, 430, 3278, 617, 3831, 19882, 369, 7724, 323, 3026, 617, 19882, 369, 13305, 13, 29438, 5751, 1510, 8830, 315, 1268, 5070, 527, 20816, 311, 35608, 279, 42889, 2450, 315, 26419, 323, 30968, 374, 3196, 389, 36604, 753, 17966, 315, 6273, 9341, 304, 279, 76032, 220, 16, 662, 22770, 423, 1157, 287, 574, 279, 1176, 311, 20461, 430, 1690, 27681, 14843, 6253, 9606, 8356, 459, 6273, 1396, 315, 25000, 323, 28585, 1606, 279, 2860, 42889, 907, 315, 25000, 323, 28585, 374, 14647, 6273, 220, 17, 662, 4452, 11, 1606, 1877, 24691, 14117, 389, 279, 17479, 4780, 311, 46679, 5149, 11, 6727, 690, 4799, 6273, 9341, 304, 26419, 323, 30968, 1193, 994, 279, 2853, 315, 17843, 1855, 1877, 374, 20086, 13, 1115, 5811, 374, 832, 315, 279, 1888, 16365, 323, 1455, 28284, 26018, 304, 41993, 34458, 220, 18, 1606, 433, 5825, 264, 12914, 369, 8830, 279, 13468, 33373, 304, 1877, 42338, 4028, 9606, 13, 763, 12966, 11, 8051, 46679, 45426, 304, 1855, 1877, 374, 3685, 311, 387, 6273, 11, 13937, 8762, 29528, 6957, 279, 4261, 315, 46679, 9341, 43154, 279, 5578, 7194, 315, 17843, 26419, 220, 16, 662, 1115, 374, 3249, 1455, 3823, 22673, 527, 8762, 12, 48761, 520, 7342, 220, 19, 1174, 220, 20, 719, 7154, 6273, 4315, 7931, 889, 527, 27681, 15196, 13, 10541, 7187, 25480, 1877, 42338, 527, 3685, 311, 387, 7701, 54852, 4245, 311, 11900, 43918, 6727, 11, 15740, 649, 4799, 86365, 505, 36604, 1122, 1877, 42338, 422, 17843, 832, 1877, 706, 264, 7191, 85365, 1109, 279, 1023, 304, 3878, 315, 279, 5788, 315, 6800, 12744, 30323, 13, 1183, 1986, 323, 4946, 569, 11, 369, 3187, 11, 22601, 83979, 430, 5933, 6727, 1288, 4799, 264, 2748, 753, 5845, 311, 7652, 46471, 1877, 42338, 4184, 311, 872, 5845, 311, 2793, 220, 21, 662, 578, 1183, 1986, 12, 10149, 569, 39515, 78, 13491, 320, 51, 20484, 8, 34744, 389, 220, 18, 9200, 32946, 25, 320, 16, 8, 430, 46679, 3044, 374, 49393, 449, 46471, 3044, 11, 320, 17, 8, 430, 46471, 3044, 374, 49393, 449, 3044, 304, 64033, 323, 320, 18, 8, 430, 3044, 2204, 34575, 22223, 279, 73219, 2450, 315, 1855, 1877, 320, 68, 1326, 2637, 25000, 304, 1695, 3044, 704, 5621, 8723, 6253, 28585, 304, 1695, 3044, 323, 28585, 304, 8009, 3044, 704, 5621, 8723, 6253, 25000, 304, 8009, 3044, 570, 9393, 1521, 4787, 527, 3970, 311, 3412, 369, 1690, 9606, 315, 56669, 11, 1183, 1986, 323, 4946, 569, 18784, 430, 27698, 304, 1695, 3044, 1288, 2793, 810, 304, 17843, 25000, 1418, 27698, 889, 527, 304, 8009, 3044, 1288, 2793, 810, 304, 17843, 28585, 13, 763, 279, 1667, 2533, 433, 574, 11223, 11, 279, 350, 20484, 706, 1027, 3917, 311, 11758, 315, 7177, 11, 449, 9709, 3135, 323, 14529, 37635, 922, 1778, 4819, 439, 279, 7333, 13827, 434, 315, 279, 9606, 477, 7187, 1694, 20041, 11, 279, 18912, 315, 994, 1778, 50183, 527, 3685, 311, 12446, 11, 323, 279, 32939, 315, 5370, 11193, 315, 46679, 9341, 11, 46679, 3044, 11, 323, 46471, 3044, 220, 22, 662, 763, 1202, 4113, 55986, 11, 279, 350, 20484, 10968, 24121, 389, 50150, 3044, 323, 1877, 42338, 520, 7342, 304, 56669, 13, 4452, 11, 1606, 1455, 9341, 304, 3823, 46471, 13980, 1772, 34397, 750, 323, 4131, 505, 2225, 6699, 11, 1690, 315, 279, 1455, 40661, 7978, 315, 36655, 6372, 304, 3823, 22673, 617, 1101, 30239, 2512, 555, 40317, 323, 617, 5343, 11193, 315, 1877, 1481, 72, 1503, 9341, 1306, 7342, 220, 23, 662, 1789, 3187, 11, 56917, 74, 14890, 828, 389, 1877, 50183, 304, 46679, 9341, 4315, 279, 70319, 540, 6132, 315, 37766, 11, 889, 527, 520, 279, 5740, 315, 264, 15481, 30022, 49001, 3026, 3629, 3060, 656, 539, 32918, 477, 617, 23540, 11103, 11, 323, 11, 439, 264, 1121, 11, 617, 4827, 3152, 42889, 2450, 1109, 279, 3278, 13, 1283, 1766, 430, 11, 389, 5578, 11, 70319, 540, 6132, 6699, 584, 276, 30968, 3010, 11, 8493, 810, 892, 28456, 323, 10168, 30968, 11, 7293, 22655, 12401, 311, 30968, 11, 323, 527, 810, 4461, 311, 1935, 872, 30968, 1109, 872, 26419, 369, 6593, 2512, 11, 682, 315, 902, 3135, 304, 2731, 6650, 5178, 369, 70319, 540, 6132, 7724, 11, 1109, 13305, 11, 323, 264, 8954, 15837, 304, 279, 1877, 11595, 315, 2911, 20330, 220, 15, 1555, 220, 19, 1667, 220, 24, 1174, 220, 605, 1174, 220, 806, 662, 26982, 11, 264, 4007, 315, 6699, 304, 279, 3723, 4273, 11, 1701, 659, 5621, 3476, 323, 47242, 828, 11, 1766, 912, 6029, 430, 6699, 529, 80431, 2704, 374, 5938, 449, 48761, 9341, 304, 3060, 1877, 220, 717, 662, 4314, 71240, 3135, 1486, 311, 2500, 4754, 20428, 13772, 430, 1690, 7978, 4087, 403, 287, 311, 1296, 279, 350, 20484, 13123, 555, 22109, 311, 40044, 33137, 1990, 53194, 11, 24064, 323, 36695, 20124, 13, 2684, 374, 459, 37492, 315, 6029, 430, 1070, 527, 3629, 3544, 91367, 1990, 11224, 46471, 1877, 19882, 323, 6699, 529, 5150, 7865, 9017, 46471, 220, 18, 1174, 220, 19, 1174, 220, 20, 1174, 220, 21, 1174, 220, 22, 1174, 220, 23, 1174, 220, 24, 1174, 220, 605, 1174, 220, 806, 1174, 220, 717, 1174, 220, 1032, 1174, 220, 975, 1174, 220, 868, 323, 433, 374, 3629, 279, 1162, 430, 7978, 1701, 36695, 11193, 527, 810, 4461, 311, 3493, 1862, 220, 845, 1174, 220, 1114, 1174, 220, 972, 662, 15636, 433, 374, 16996, 430, 12074, 33137, 1990, 53194, 20124, 320, 68, 1326, 2637, 9547, 430, 57780, 279, 46460, 367, 315, 89873, 705, 19882, 6259, 555, 7865, 320, 68, 1326, 2637, 892, 7543, 28456, 8, 323, 1884, 32448, 96655, 320, 68, 1326, 2637, 659, 5621, 3476, 477, 18479, 19882, 8, 430, 6904, 389, 3508, 279, 46471, 374, 8762, 477, 8954, 13, 7089, 7978, 617, 4726, 17395, 13865, 311, 5662, 264, 12624, 24811, 555, 9204, 430, 46471, 3044, 11, 15851, 315, 1877, 11, 323, 8244, 3070, 8070, 11, 649, 7958, 9341, 11429, 13, 74540, 264, 3070, 753, 5070, 11, 369, 3187, 11, 706, 1027, 6982, 311, 1121, 304, 264, 6541, 505, 10742, 449, 15374, 311, 10742, 449, 25452, 220, 777, 323, 1063, 7978, 617, 6982, 430, 8009, 29939, 8108, 9341, 304, 2911, 889, 527, 520, 1579, 5326, 719, 1243, 5376, 9341, 304, 1884, 2911, 3131, 279, 8689, 6994, 128257, 198, 128256, 78191, 198, 37, 6258, 819, 323, 3778, 12074, 304, 41993, 34458, 13375, 459, 2930, 9526, 323, 10795, 31720, 430, 3278, 10932, 323, 527, 810, 4461, 311, 2793, 304, 872, 30968, 323, 3026, 304, 872, 26419, 13, 578, 4007, 574, 6319, 311, 1296, 279, 5536, 315, 46679, 5070, 389, 46471, 1877, 19882, 13, 45863, 11, 279, 12283, 16495, 311, 1296, 279, 1183, 1986, 4235, 10149, 569, 31178, 430, 56978, 430, 6699, 304, 1695, 4787, 690, 15837, 9341, 9017, 26419, 11, 1418, 6699, 304, 8009, 4787, 690, 15837, 9341, 9017, 30968, 13, 330, 11458, 11, 1057, 4007, 4745, 311, 1501, 430, 279, 6699, 6, 19882, 369, 279, 46471, 596, 10026, 527, 11754, 555, 872, 2704, 11, 12205, 11, 6873, 477, 20587, 4676, 13, 12361, 11, 46679, 19882, 1051, 1888, 19698, 555, 872, 1877, 13, 11215, 505, 682, 80431, 36576, 13605, 18479, 323, 11720, 19882, 369, 30968, 25, 814, 14896, 311, 33009, 810, 311, 51371, 12899, 7724, 323, 15236, 311, 11142, 7724, 13, 763, 13168, 11, 3026, 13605, 13263, 11, 43169, 43383, 11, 19882, 369, 26419, 1359, 15100, 3063, 3229, 11, 3962, 38083, 278, 8483, 261, 8563, 38206, 505, 279, 3907, 315, 8877, 12407, 11, 37355, 13, 578, 12074, 12793, 279, 1183, 1986, 4235, 10149, 569, 2515, 449, 459, 2930, 9526, 555, 30090, 18479, 323, 11720, 24064, 19882, 323, 17432, 750, 6259, 19882, 369, 26419, 477, 30968, 2225, 439, 264, 734, 315, 872, 3674, 323, 7100, 2704, 323, 304, 279, 40696, 315, 264, 9036, 287, 3465, 6319, 311, 1304, 13324, 2733, 28994, 477, 8009, 13, 578, 3135, 315, 279, 3495, 1520, 311, 1304, 5647, 315, 279, 3629, 71240, 14955, 389, 46471, 1877, 19882, 13, 578, 6372, 315, 46679, 3044, 323, 2704, 11, 27260, 19465, 12034, 1990, 25000, 323, 28585, 11, 7100, 17413, 389, 8689, 11, 323, 279, 6372, 315, 13042, 12659, 682, 1615, 23772, 311, 1391, 49895, 279, 41993, 20124, 315, 46679, 9341, 15174, 13, 330, 37, 70941, 11, 279, 5536, 315, 832, 8331, 11, 369, 3187, 11, 279, 19465, 7392, 12324, 1990, 25000, 323, 28585, 11, 649, 7056, 279, 5536, 315, 2500, 11, 1778, 439, 279, 1183, 1986, 4235, 10149, 569, 39515, 78, 13491, 13, 1115, 649, 1304, 433, 5107, 311, 4820, 872, 6372, 323, 1304, 2867, 20492, 922, 364, 2985, 2931, 6, 46679, 9341, 15174, 505, 459, 41993, 13356, 13, 1226, 3987, 430, 1057, 4007, 649, 25351, 502, 3177, 389, 1521, 15174, 323, 3493, 264, 2731, 8830, 315, 41993, 34458, 304, 12966, 1359, 5415, 38206, 13, 763, 5369, 311, 3962, 38083, 278, 8483, 261, 8563, 38206, 505, 279, 3907, 315, 8877, 12407, 11, 279, 4007, 5343, 12074, 505, 72091, 3907, 323, 17368, 3314, 3907, 304, 279, 3723, 4273, 13, 578, 4652, 574, 4756, 304, 279, 8486, 38130, 29140, 13, 220, 128257, 198 ]

1,683

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Medical imaging has enormous potential for early disease prediction, but is impeded by the difficulty and expense of acquiring data sets before symptom onset. UK Biobank aims to address this problem directly by acquiring high-quality, consistently acquired imaging data from 100,000 predominantly healthy participants, with health outcomes being tracked over the coming decades. The brain imaging includes structural, diffusion and functional modalities. Along with body and cardiac imaging, genetics, lifestyle measures, biological phenotyping and health records, this imaging is expected to enable discovery of imaging markers of a broad range of diseases at their earliest stages, as well as provide unique insight into disease mechanisms. We describe UK Biobank brain imaging and present results derived from the first 5,000 participants' data release. Although this covers just 5% of the ultimate cohort, it has already yielded a rich range of associations between brain imaging and other measures collected by UK Biobank. Main The primary clinical role of brain imaging to date has been in diagnosis and monitoring of disease progression, rather than providing predictive markers for preventative stratification or early therapeutic intervention. The predominant strategy for finding image-based markers of neurological and psychiatric disease has been to identify patients early in the diagnostic process to maximize statistical power in a small cohort (tens to hundreds of subjects). A key factor motivating the use of small, clinically defined cohorts is the expense, time and specialized hardware associated with imaging. This approach has been effective in providing markers of disease progression, but identifying imaging markers of early disease requires measurements at the pre-symptomatic stage. Image-based measures of brain structure and function may evolve in a complex way throughout aging and the progression of neuropathology. Thus, markers with utility in monitoring disease progression post-diagnostically may not manifest pre-symptomatically, and conversely the most sensitive early predictors of disease may have plateaued by the time existing diagnoses become accurate. Nevertheless, when known risk factors have enabled risk-stratified cohorts, imaging has been able to predict disease before symptom presentation. For example, magnetic resonance imaging (MRI) has demonstrated altered brain activity that is associated with the APOE genotype decades in advance of symptoms associated with Alzheimer's disease 1 , and conversion from mild cognitive impairment to Alzheimer's has been predicted 2 . These studies suggest that the primary obstacle to identifying early imaging markers is obtaining data in pre-symptomatic cohorts drawn from the general population. Alternatively, pre-symptomatic cohorts can be assembled using a prospective approach, in which a large number of healthy participants are intensively phenotyped (including imaging) and subsequently monitored for long-term health outcomes. Although this approach is expensive, it is also efficient, as it captures early biomarkers and risk factors for a broad range of diseases. It further becomes possible to discover unexpected interactions between risk factors (such as lifestyle and genetics). To date, the largest brain imaging studies have gathered data on a few thousand subjects. Although this approach has identified associations between imaging and highly prevalent diseases, existing cohorts are still too small to produce sufficient incidence of many diseases if participants are recruited without identifying risk factors. UK Biobank is a prospective epidemiological resource gathering extensive questionnaires, physical and cognitive measures, and biological samples (including genotyping) in a cohort of 500,000 participants 3 . Participants consent to allow access to their full health records from the UK National Health Service, enabling researchers to relate phenotypic measures to long-term health outcomes. This is particularly powerful as a result of the combination of the number of subjects and the breadth of linked data. Participants were 40–69 years of age at baseline recruitment; this aims to balance the goals of characterizing subjects before disease onset against the delay before health outcomes accumulate. The cohort is particularly appropriate for the study of age-associated pathology. All data from UK Biobank are available to researchers world-wide on application, with no preferential access for the scientists leading the study. An imaging extension to the existing UK Biobank study was funded in 2016 to scan 100,000 subjects from the existing cohort, aiming to complete by 2022. Imaging includes MRI of the brain, heart and body, low-dose X-ray bone and joint scans, and ultrasound of the carotid arteries. Identification of disease risk factors should increase over time with emerging clinical outcomes. For example, in the imaged cohort, 1,800 participants are expected to develop Alzheimer's disease by 2022, rising to 6,000 by 2027 (diabetes: 8,000 rising to 14,000; stroke: 1,800 to 4,000; Parkinson's: 1,200 to 2,800) 4 . Here we present example analytic approaches and studies that will be enabled by UK Biobank. The identification of new imaging biomarkers of disease risk could support diagnosis, development of therapeutics and assessment of interventions. The multi-modal, multi-organ imaging enables the study of interactions between organ systems, for example, between cardiovascular health and dementia. The breadth of imaging makes this data set valuable for multi-systemic syndromes such as frailty, accelerated aging characterized by general loss of reserves and poor tolerance to stressors, which indicates increased risk for a range of conditions including dementia 5 . This kind of resource can also evince hypotheses regarding causal mechanisms of disease that could be tested in follow-up interventional studies. Examples include modifiable risk factors, such as the association of obesity with later life cognitive dysfunction 6 , and the ability to study complex interactions of risk factors with lifestyle, environment and genetics. Finally, UK Biobank will enable validation and extension of associations identified by smaller-scale studies, including the testing of hypotheses that combine results from multiple previous studies. Results Design rationale and initial imaging phase The imaging study was designed to achieve the target of 100,000 subjects, each scanned once, over 5–6 years at three dedicated, identical centers operating 7 days per week, each scanning 18 subjects per day (ref. 7 ). This requirement places tight timing constraints, corresponding to one subject imaged every 36 min (Online Methods ). The first imaging center was built to establish feasibility and scanned 10,000 subjects over a 2-year ramp-up period. Two", "role": "user" }, { "content": "Exciting early results from analysing the brain imaging data, alongside thousands of measures of lifestyle, physical fitness, cognitive health and physical measures such as body-mass-index (BMI) and bone density have been published in Nature Neuroscience. The high quality of the imaging data and very large number of subjects allowed researchers to identify more than 30,000 significant associations between the many different brain imaging measures and the non-imaging measures. The findings have now been made available for use by researchers worldwide. Results included: Strong associations between people's cognitive processing speed and markers of the integrity of the brain's \"wiring\" and the size of brain structures. These effects increased in strength as people aged.A negative correlation between brain activity during a simple shape-matching task and intelligence, an effect that didn't relate to participants' age. This might be because the people who scored more highly on the cognitive tests needed to use less of their brain to carry out the task.A pattern of strong associations between higher blood pressure, greater alcohol consumption, and several measures that could reflect injury to connections in the brain.A separate pattern of correlations, linking intake of alcohol and tobacco and changes in red blood cells and cardiac fitness, to brain imaging signals associated with increased iron deposits in the brain.Researchers also unearthed some more complicated patterns of correlation. For example, one pattern links brain imaging to intelligence, level of education, and a set of lifestyle factors that at first appear unrelated – including amount of time spent outdoors. It is plausible that, taken together, these factors create a profile of socio-economic-status and its relation to the brain.However, because UK Biobank is an \"observational\" study that characterizes a cross-section of individuals, it's not always straightforward to establish which factors cause which, but such results should help scientists to define much more precise questions to address in the future search for ways of preventing or treating brain disease. UK Biobank will be the world's largest health imaging study. The imaging is funded by the Medical Research Council, Wellcome Trust, and the British Heart Foundation. It was launched in April 2016 after a number of years of planning and consultation with a large number of health and scanning experts. With the ambitious goal of imaging 100,000 existing UK Biobank participants, it is creating the biggest collection of scans of internal organs, to transform the way scientists study a wide range of diseases, including dementia, arthritis, cancer, heart attacks and stroke. Today's paper describes the brain imaging part of UK Biobank, led by Professsors Steve Smith and Karla Miller from the University of Oxford, and Professor Paul Matthews from Imperial College London. Professor Miller said: \"We are using cutting-edge MRI scans and Big Data analysis methods to get the most comprehensive window into the brain that current imaging technology allows.\" \"These results are just a first glimpse into this massive, rich dataset will that emerge in the coming years. It is an unparalleled resource that will transform our understanding of many common diseases.\" Professor Matthews, Edmond and Lily Safra Chair and Head of Brain Sciences at Imperial, added: \"These results are exciting, but merely provide a first hint of what can be discovered with the UK Biobank. This project also is a landmark because of the way it has been done: 500,000 volunteers across the U.K. are donating their time to be part of it and more than 125 scientists from across the world contributed to the design of the imaging enhancement alone. Imperial College scientists played a major role in its inception and leadership as part of a team recruited by the U.K. biobank from a number of UK universities. This is a wonderful example of \"open science\". The paper reports first results from this remarkable data resource, which includes six different kinds of brain imaging done in the 30 minutes that each volunteer is in the brain scanner. Professor Smith explained: \"We have 'structural imaging' - that tells us about brain anatomy – the shapes and sizes of the different parts of the brain. Another kind – 'functional MRI' - tells us about complex patterns of brain activity. Yet another kind – 'diffusion MRI' - tells us about the brain's wiring diagram. The rich and diverse information contained in these scans will reveal how the working of the brain can change with aging and disease; different diseases will best be understood through different combinations of information across these different images.\" UK Biobank has already scanned 10,000 participants, including images of the heart, body, bone and blood vessels in addition to brain scans. This will be by far the largest brain imaging study ever conducted; within another 5 years UK Biobank will have completed the scanning of 100,000 participants. One reason for needing such large numbers of participants is to have enough subjects to allow discovery of early, possibly subtle, markers of future disease risk, both for a range of common diseases and for rare neurological disorders like motor neuron disease. An important objective of the UK Biobank is to provide a resource for discovery of new insights into diseases like Alzheimer's, which demands scanning healthy subjects years or decades before they develop symptoms. From the UK Biobank data, scientists anywhere can aim to learn much more about brain diseases - and their relationship to a broad range of other diseases or disease risks - to guide the development of earlier targeted treatment (or changes in lifestyle) that could in the future prevent major diseases from ever happening. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Medical imaging has enormous potential for early disease prediction, but is impeded by the difficulty and expense of acquiring data sets before symptom onset. UK Biobank aims to address this problem directly by acquiring high-quality, consistently acquired imaging data from 100,000 predominantly healthy participants, with health outcomes being tracked over the coming decades. The brain imaging includes structural, diffusion and functional modalities. Along with body and cardiac imaging, genetics, lifestyle measures, biological phenotyping and health records, this imaging is expected to enable discovery of imaging markers of a broad range of diseases at their earliest stages, as well as provide unique insight into disease mechanisms. We describe UK Biobank brain imaging and present results derived from the first 5,000 participants' data release. Although this covers just 5% of the ultimate cohort, it has already yielded a rich range of associations between brain imaging and other measures collected by UK Biobank. Main The primary clinical role of brain imaging to date has been in diagnosis and monitoring of disease progression, rather than providing predictive markers for preventative stratification or early therapeutic intervention. The predominant strategy for finding image-based markers of neurological and psychiatric disease has been to identify patients early in the diagnostic process to maximize statistical power in a small cohort (tens to hundreds of subjects). A key factor motivating the use of small, clinically defined cohorts is the expense, time and specialized hardware associated with imaging. This approach has been effective in providing markers of disease progression, but identifying imaging markers of early disease requires measurements at the pre-symptomatic stage. Image-based measures of brain structure and function may evolve in a complex way throughout aging and the progression of neuropathology. Thus, markers with utility in monitoring disease progression post-diagnostically may not manifest pre-symptomatically, and conversely the most sensitive early predictors of disease may have plateaued by the time existing diagnoses become accurate. Nevertheless, when known risk factors have enabled risk-stratified cohorts, imaging has been able to predict disease before symptom presentation. For example, magnetic resonance imaging (MRI) has demonstrated altered brain activity that is associated with the APOE genotype decades in advance of symptoms associated with Alzheimer's disease 1 , and conversion from mild cognitive impairment to Alzheimer's has been predicted 2 . These studies suggest that the primary obstacle to identifying early imaging markers is obtaining data in pre-symptomatic cohorts drawn from the general population. Alternatively, pre-symptomatic cohorts can be assembled using a prospective approach, in which a large number of healthy participants are intensively phenotyped (including imaging) and subsequently monitored for long-term health outcomes. Although this approach is expensive, it is also efficient, as it captures early biomarkers and risk factors for a broad range of diseases. It further becomes possible to discover unexpected interactions between risk factors (such as lifestyle and genetics). To date, the largest brain imaging studies have gathered data on a few thousand subjects. Although this approach has identified associations between imaging and highly prevalent diseases, existing cohorts are still too small to produce sufficient incidence of many diseases if participants are recruited without identifying risk factors. UK Biobank is a prospective epidemiological resource gathering extensive questionnaires, physical and cognitive measures, and biological samples (including genotyping) in a cohort of 500,000 participants 3 . Participants consent to allow access to their full health records from the UK National Health Service, enabling researchers to relate phenotypic measures to long-term health outcomes. This is particularly powerful as a result of the combination of the number of subjects and the breadth of linked data. Participants were 40–69 years of age at baseline recruitment; this aims to balance the goals of characterizing subjects before disease onset against the delay before health outcomes accumulate. The cohort is particularly appropriate for the study of age-associated pathology. All data from UK Biobank are available to researchers world-wide on application, with no preferential access for the scientists leading the study. An imaging extension to the existing UK Biobank study was funded in 2016 to scan 100,000 subjects from the existing cohort, aiming to complete by 2022. Imaging includes MRI of the brain, heart and body, low-dose X-ray bone and joint scans, and ultrasound of the carotid arteries. Identification of disease risk factors should increase over time with emerging clinical outcomes. For example, in the imaged cohort, 1,800 participants are expected to develop Alzheimer's disease by 2022, rising to 6,000 by 2027 (diabetes: 8,000 rising to 14,000; stroke: 1,800 to 4,000; Parkinson's: 1,200 to 2,800) 4 . Here we present example analytic approaches and studies that will be enabled by UK Biobank. The identification of new imaging biomarkers of disease risk could support diagnosis, development of therapeutics and assessment of interventions. The multi-modal, multi-organ imaging enables the study of interactions between organ systems, for example, between cardiovascular health and dementia. The breadth of imaging makes this data set valuable for multi-systemic syndromes such as frailty, accelerated aging characterized by general loss of reserves and poor tolerance to stressors, which indicates increased risk for a range of conditions including dementia 5 . This kind of resource can also evince hypotheses regarding causal mechanisms of disease that could be tested in follow-up interventional studies. Examples include modifiable risk factors, such as the association of obesity with later life cognitive dysfunction 6 , and the ability to study complex interactions of risk factors with lifestyle, environment and genetics. Finally, UK Biobank will enable validation and extension of associations identified by smaller-scale studies, including the testing of hypotheses that combine results from multiple previous studies. Results Design rationale and initial imaging phase The imaging study was designed to achieve the target of 100,000 subjects, each scanned once, over 5–6 years at three dedicated, identical centers operating 7 days per week, each scanning 18 subjects per day (ref. 7 ). This requirement places tight timing constraints, corresponding to one subject imaged every 36 min (Online Methods ). The first imaging center was built to establish feasibility and scanned 10,000 subjects over a 2-year ramp-up period. Two<|im_end|> <|im_start|>assistant Exciting early results from analysing the brain imaging data, alongside thousands of measures of lifestyle, physical fitness, cognitive health and physical measures such as body-mass-index (BMI) and bone density have been published in Nature Neuroscience. The high quality of the imaging data and very large number of subjects allowed researchers to identify more than 30,000 significant associations between the many different brain imaging measures and the non-imaging measures. The findings have now been made available for use by researchers worldwide. Results included: Strong associations between people's cognitive processing speed and markers of the integrity of the brain's "wiring" and the size of brain structures. These effects increased in strength as people aged.A negative correlation between brain activity during a simple shape-matching task and intelligence, an effect that didn't relate to participants' age. This might be because the people who scored more highly on the cognitive tests needed to use less of their brain to carry out the task.A pattern of strong associations between higher blood pressure, greater alcohol consumption, and several measures that could reflect injury to connections in the brain.A separate pattern of correlations, linking intake of alcohol and tobacco and changes in red blood cells and cardiac fitness, to brain imaging signals associated with increased iron deposits in the brain.Researchers also unearthed some more complicated patterns of correlation. For example, one pattern links brain imaging to intelligence, level of education, and a set of lifestyle factors that at first appear unrelated – including amount of time spent outdoors. It is plausible that, taken together, these factors create a profile of socio-economic-status and its relation to the brain.However, because UK Biobank is an "observational" study that characterizes a cross-section of individuals, it's not always straightforward to establish which factors cause which, but such results should help scientists to define much more precise questions to address in the future search for ways of preventing or treating brain disease. UK Biobank will be the world's largest health imaging study. The imaging is funded by the Medical Research Council, Wellcome Trust, and the British Heart Foundation. It was launched in April 2016 after a number of years of planning and consultation with a large number of health and scanning experts. With the ambitious goal of imaging 100,000 existing UK Biobank participants, it is creating the biggest collection of scans of internal organs, to transform the way scientists study a wide range of diseases, including dementia, arthritis, cancer, heart attacks and stroke. Today's paper describes the brain imaging part of UK Biobank, led by Professsors Steve Smith and Karla Miller from the University of Oxford, and Professor Paul Matthews from Imperial College London. Professor Miller said: "We are using cutting-edge MRI scans and Big Data analysis methods to get the most comprehensive window into the brain that current imaging technology allows." "These results are just a first glimpse into this massive, rich dataset will that emerge in the coming years. It is an unparalleled resource that will transform our understanding of many common diseases." Professor Matthews, Edmond and Lily Safra Chair and Head of Brain Sciences at Imperial, added: "These results are exciting, but merely provide a first hint of what can be discovered with the UK Biobank. This project also is a landmark because of the way it has been done: 500,000 volunteers across the U.K. are donating their time to be part of it and more than 125 scientists from across the world contributed to the design of the imaging enhancement alone. Imperial College scientists played a major role in its inception and leadership as part of a team recruited by the U.K. biobank from a number of UK universities. This is a wonderful example of "open science". The paper reports first results from this remarkable data resource, which includes six different kinds of brain imaging done in the 30 minutes that each volunteer is in the brain scanner. Professor Smith explained: "We have 'structural imaging' - that tells us about brain anatomy – the shapes and sizes of the different parts of the brain. Another kind – 'functional MRI' - tells us about complex patterns of brain activity. Yet another kind – 'diffusion MRI' - tells us about the brain's wiring diagram. The rich and diverse information contained in these scans will reveal how the working of the brain can change with aging and disease; different diseases will best be understood through different combinations of information across these different images." UK Biobank has already scanned 10,000 participants, including images of the heart, body, bone and blood vessels in addition to brain scans. This will be by far the largest brain imaging study ever conducted; within another 5 years UK Biobank will have completed the scanning of 100,000 participants. One reason for needing such large numbers of participants is to have enough subjects to allow discovery of early, possibly subtle, markers of future disease risk, both for a range of common diseases and for rare neurological disorders like motor neuron disease. An important objective of the UK Biobank is to provide a resource for discovery of new insights into diseases like Alzheimer's, which demands scanning healthy subjects years or decades before they develop symptoms. From the UK Biobank data, scientists anywhere can aim to learn much more about brain diseases - and their relationship to a broad range of other diseases or disease risks - to guide the development of earlier targeted treatment (or changes in lifestyle) that could in the future prevent major diseases from ever happening. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 13235, 32758, 706, 23205, 4754, 369, 4216, 8624, 20212, 11, 719, 374, 3242, 31035, 555, 279, 17250, 323, 20900, 315, 42990, 828, 7437, 1603, 49648, 42080, 13, 6560, 12371, 677, 1201, 22262, 311, 2686, 420, 3575, 6089, 555, 42990, 1579, 22867, 11, 21356, 19426, 32758, 828, 505, 220, 1041, 11, 931, 47904, 9498, 13324, 11, 449, 2890, 20124, 1694, 34156, 927, 279, 5108, 11026, 13, 578, 8271, 32758, 5764, 24693, 11, 58430, 323, 16003, 13531, 1385, 13, 32944, 449, 2547, 323, 47345, 32758, 11, 56104, 11, 19433, 11193, 11, 24156, 14345, 67247, 323, 2890, 7576, 11, 420, 32758, 374, 3685, 311, 7431, 18841, 315, 32758, 24915, 315, 264, 7353, 2134, 315, 19338, 520, 872, 30758, 18094, 11, 439, 1664, 439, 3493, 5016, 20616, 1139, 8624, 24717, 13, 1226, 7664, 6560, 12371, 677, 1201, 8271, 32758, 323, 3118, 3135, 14592, 505, 279, 1176, 220, 20, 11, 931, 13324, 6, 828, 4984, 13, 10541, 420, 14861, 1120, 220, 20, 4, 315, 279, 17139, 41944, 11, 433, 706, 2736, 58487, 264, 9257, 2134, 315, 30257, 1990, 8271, 32758, 323, 1023, 11193, 14890, 555, 6560, 12371, 677, 1201, 13, 4802, 578, 6156, 14830, 3560, 315, 8271, 32758, 311, 2457, 706, 1027, 304, 23842, 323, 16967, 315, 8624, 33824, 11, 4856, 1109, 8405, 60336, 24915, 369, 97420, 44397, 2461, 477, 4216, 37471, 21623, 13, 578, 96531, 8446, 369, 9455, 2217, 6108, 24915, 315, 64908, 323, 47657, 8624, 706, 1027, 311, 10765, 6978, 4216, 304, 279, 15439, 1920, 311, 35608, 29564, 2410, 304, 264, 2678, 41944, 320, 83, 729, 311, 11758, 315, 15223, 570, 362, 1401, 8331, 89689, 279, 1005, 315, 2678, 11, 70432, 4613, 90388, 374, 279, 20900, 11, 892, 323, 28175, 12035, 5938, 449, 32758, 13, 1115, 5603, 706, 1027, 7524, 304, 8405, 24915, 315, 8624, 33824, 11, 719, 25607, 32758, 24915, 315, 4216, 8624, 7612, 22323, 520, 279, 864, 1355, 1631, 418, 13795, 6566, 13, 4758, 6108, 11193, 315, 8271, 6070, 323, 734, 1253, 38680, 304, 264, 6485, 1648, 6957, 30084, 323, 279, 33824, 315, 98666, 589, 2508, 13, 14636, 11, 24915, 449, 15919, 304, 16967, 8624, 33824, 1772, 51389, 8372, 2740, 1253, 539, 14794, 864, 1355, 1631, 80797, 7167, 11, 323, 7669, 989, 279, 1455, 16614, 4216, 95222, 315, 8624, 1253, 617, 65388, 291, 555, 279, 892, 6484, 85488, 3719, 13687, 13, 35053, 11, 994, 3967, 5326, 9547, 617, 9147, 5326, 42728, 266, 1908, 90388, 11, 32758, 706, 1027, 3025, 311, 7168, 8624, 1603, 49648, 15864, 13, 1789, 3187, 11, 24924, 58081, 32758, 320, 79770, 8, 706, 21091, 29852, 8271, 5820, 430, 374, 5938, 449, 279, 362, 2089, 36, 80285, 11026, 304, 12178, 315, 13803, 5938, 449, 44531, 596, 8624, 220, 16, 1174, 323, 14747, 505, 23900, 25702, 53317, 311, 44531, 596, 706, 1027, 19698, 220, 17, 662, 4314, 7978, 4284, 430, 279, 6156, 33287, 311, 25607, 4216, 32758, 24915, 374, 19546, 828, 304, 864, 1355, 1631, 418, 13795, 90388, 15107, 505, 279, 4689, 7187, 13, 39578, 11, 864, 1355, 1631, 418, 13795, 90388, 649, 387, 35105, 1701, 264, 33547, 5603, 11, 304, 902, 264, 3544, 1396, 315, 9498, 13324, 527, 25228, 3210, 14345, 354, 33601, 320, 16564, 32758, 8, 323, 28520, 41223, 369, 1317, 9860, 2890, 20124, 13, 10541, 420, 5603, 374, 11646, 11, 433, 374, 1101, 11297, 11, 439, 433, 41255, 4216, 39538, 91141, 323, 5326, 9547, 369, 264, 7353, 2134, 315, 19338, 13, 1102, 4726, 9221, 3284, 311, 7142, 16907, 22639, 1990, 5326, 9547, 320, 21470, 439, 19433, 323, 56104, 570, 2057, 2457, 11, 279, 7928, 8271, 32758, 7978, 617, 20802, 828, 389, 264, 2478, 16579, 15223, 13, 10541, 420, 5603, 706, 11054, 30257, 1990, 32758, 323, 7701, 46941, 19338, 11, 6484, 90388, 527, 2103, 2288, 2678, 311, 8356, 14343, 39775, 315, 1690, 19338, 422, 13324, 527, 45425, 2085, 25607, 5326, 9547, 13, 6560, 12371, 677, 1201, 374, 264, 33547, 62057, 5848, 5211, 23738, 16781, 3488, 69663, 11, 7106, 323, 25702, 11193, 11, 323, 24156, 10688, 320, 16564, 4173, 67247, 8, 304, 264, 41944, 315, 220, 2636, 11, 931, 13324, 220, 18, 662, 52878, 14771, 311, 2187, 2680, 311, 872, 2539, 2890, 7576, 505, 279, 6560, 5165, 6401, 5475, 11, 28462, 12074, 311, 29243, 14345, 37941, 292, 11193, 311, 1317, 9860, 2890, 20124, 13, 1115, 374, 8104, 8147, 439, 264, 1121, 315, 279, 10824, 315, 279, 1396, 315, 15223, 323, 279, 58321, 315, 10815, 828, 13, 52878, 1051, 220, 1272, 4235, 3076, 1667, 315, 4325, 520, 26954, 34102, 26, 420, 22262, 311, 8335, 279, 9021, 315, 3752, 4954, 15223, 1603, 8624, 42080, 2403, 279, 7781, 1603, 2890, 20124, 47376, 13, 578, 41944, 374, 8104, 8475, 369, 279, 4007, 315, 4325, 75968, 77041, 13, 2052, 828, 505, 6560, 12371, 677, 1201, 527, 2561, 311, 12074, 1917, 25480, 389, 3851, 11, 449, 912, 10932, 2335, 2680, 369, 279, 14248, 6522, 279, 4007, 13, 1556, 32758, 9070, 311, 279, 6484, 6560, 12371, 677, 1201, 4007, 574, 24853, 304, 220, 679, 21, 311, 8737, 220, 1041, 11, 931, 15223, 505, 279, 6484, 41944, 11, 38178, 311, 4686, 555, 220, 2366, 17, 13, 65606, 5764, 52460, 315, 279, 8271, 11, 4851, 323, 2547, 11, 3428, 1773, 974, 1630, 30630, 17685, 323, 10496, 43739, 11, 323, 63859, 315, 279, 1841, 354, 307, 85648, 13, 59776, 315, 8624, 5326, 9547, 1288, 5376, 927, 892, 449, 24084, 14830, 20124, 13, 1789, 3187, 11, 304, 279, 737, 3359, 41944, 11, 220, 16, 11, 4728, 13324, 527, 3685, 311, 2274, 44531, 596, 8624, 555, 220, 2366, 17, 11, 16448, 311, 220, 21, 11, 931, 555, 220, 2366, 22, 320, 8747, 16629, 25, 220, 23, 11, 931, 16448, 311, 220, 975, 11, 931, 26, 12943, 25, 220, 16, 11, 4728, 311, 220, 19, 11, 931, 26, 62145, 596, 25, 220, 16, 11, 1049, 311, 220, 17, 11, 4728, 8, 220, 19, 662, 5810, 584, 3118, 3187, 79136, 20414, 323, 7978, 430, 690, 387, 9147, 555, 6560, 12371, 677, 1201, 13, 578, 22654, 315, 502, 32758, 39538, 91141, 315, 8624, 5326, 1436, 1862, 23842, 11, 4500, 315, 9139, 88886, 323, 15813, 315, 39455, 13, 578, 7447, 26177, 11, 7447, 12, 8629, 32758, 20682, 279, 4007, 315, 22639, 1990, 2942, 6067, 11, 369, 3187, 11, 1990, 41713, 2890, 323, 52857, 13, 578, 58321, 315, 32758, 3727, 420, 828, 743, 15525, 369, 7447, 37748, 292, 22013, 442, 288, 1778, 439, 91223, 1919, 11, 49858, 30084, 32971, 555, 4689, 4814, 315, 30600, 323, 8009, 25065, 311, 8631, 1105, 11, 902, 15151, 7319, 5326, 369, 264, 2134, 315, 4787, 2737, 52857, 220, 20, 662, 1115, 3169, 315, 5211, 649, 1101, 3721, 1736, 74513, 9002, 59557, 24717, 315, 8624, 430, 1436, 387, 12793, 304, 1833, 5352, 958, 44322, 7978, 13, 26379, 2997, 1491, 23444, 5326, 9547, 11, 1778, 439, 279, 15360, 315, 33048, 449, 3010, 2324, 25702, 32403, 220, 21, 1174, 323, 279, 5845, 311, 4007, 6485, 22639, 315, 5326, 9547, 449, 19433, 11, 4676, 323, 56104, 13, 17830, 11, 6560, 12371, 677, 1201, 690, 7431, 10741, 323, 9070, 315, 30257, 11054, 555, 9333, 13230, 7978, 11, 2737, 279, 7649, 315, 74513, 430, 16343, 3135, 505, 5361, 3766, 7978, 13, 18591, 7127, 57916, 323, 2926, 32758, 10474, 578, 32758, 4007, 574, 6319, 311, 11322, 279, 2218, 315, 220, 1041, 11, 931, 15223, 11, 1855, 48548, 3131, 11, 927, 220, 20, 4235, 21, 1667, 520, 2380, 12514, 11, 20086, 19169, 10565, 220, 22, 2919, 824, 2046, 11, 1855, 36201, 220, 972, 15223, 824, 1938, 320, 1116, 13, 220, 22, 7609, 1115, 16686, 7634, 10508, 18912, 17413, 11, 12435, 311, 832, 3917, 737, 3359, 1475, 220, 1927, 1332, 320, 20171, 19331, 7609, 578, 1176, 32758, 4219, 574, 5918, 311, 5813, 69543, 323, 48548, 220, 605, 11, 931, 15223, 927, 264, 220, 17, 4771, 23091, 5352, 4261, 13, 9220, 128257, 198, 128256, 78191, 198, 42821, 5977, 4216, 3135, 505, 22209, 287, 279, 8271, 32758, 828, 11, 16662, 9214, 315, 11193, 315, 19433, 11, 7106, 17479, 11, 25702, 2890, 323, 7106, 11193, 1778, 439, 2547, 1474, 395, 22214, 320, 96626, 8, 323, 17685, 17915, 617, 1027, 4756, 304, 22037, 85879, 13, 578, 1579, 4367, 315, 279, 32758, 828, 323, 1633, 3544, 1396, 315, 15223, 5535, 12074, 311, 10765, 810, 1109, 220, 966, 11, 931, 5199, 30257, 1990, 279, 1690, 2204, 8271, 32758, 11193, 323, 279, 2536, 38025, 4210, 11193, 13, 578, 14955, 617, 1457, 1027, 1903, 2561, 369, 1005, 555, 12074, 15603, 13, 18591, 5343, 25, 27191, 30257, 1990, 1274, 596, 25702, 8863, 4732, 323, 24915, 315, 279, 17025, 315, 279, 8271, 596, 330, 86, 6322, 1, 323, 279, 1404, 315, 8271, 14726, 13, 4314, 6372, 7319, 304, 8333, 439, 1274, 20330, 885, 8389, 26670, 1990, 8271, 5820, 2391, 264, 4382, 6211, 1474, 33024, 3465, 323, 11478, 11, 459, 2515, 430, 3287, 956, 29243, 311, 13324, 6, 4325, 13, 1115, 2643, 387, 1606, 279, 1274, 889, 16957, 810, 7701, 389, 279, 25702, 7177, 4460, 311, 1005, 2753, 315, 872, 8271, 311, 6920, 704, 279, 3465, 885, 5497, 315, 3831, 30257, 1990, 5190, 6680, 7410, 11, 7191, 13200, 15652, 11, 323, 3892, 11193, 430, 1436, 8881, 11134, 311, 13537, 304, 279, 8271, 885, 8821, 5497, 315, 69916, 11, 31799, 23730, 315, 13200, 323, 27531, 323, 4442, 304, 2579, 6680, 7917, 323, 47345, 17479, 11, 311, 8271, 32758, 17738, 5938, 449, 7319, 11245, 34751, 304, 279, 8271, 8542, 2974, 388, 1101, 79675, 291, 1063, 810, 17395, 12912, 315, 26670, 13, 1789, 3187, 11, 832, 5497, 7902, 8271, 32758, 311, 11478, 11, 2237, 315, 6873, 11, 323, 264, 743, 315, 19433, 9547, 430, 520, 1176, 5101, 46305, 1389, 2737, 3392, 315, 892, 7543, 34632, 13, 1102, 374, 50434, 430, 11, 4529, 3871, 11, 1521, 9547, 1893, 264, 5643, 315, 41589, 77249, 36098, 323, 1202, 12976, 311, 279, 8271, 67103, 2099, 11, 1606, 6560, 12371, 677, 1201, 374, 459, 330, 23604, 1697, 1, 4007, 430, 3752, 4861, 264, 5425, 22327, 315, 7931, 11, 433, 596, 539, 2744, 31439, 311, 5813, 902, 9547, 5353, 902, 11, 719, 1778, 3135, 1288, 1520, 14248, 311, 7124, 1790, 810, 24473, 4860, 311, 2686, 304, 279, 3938, 2778, 369, 5627, 315, 27252, 477, 27723, 8271, 8624, 13, 6560, 12371, 677, 1201, 690, 387, 279, 1917, 596, 7928, 2890, 32758, 4007, 13, 578, 32758, 374, 24853, 555, 279, 13235, 8483, 9251, 11, 8489, 2063, 17236, 11, 323, 279, 8013, 18449, 5114, 13, 1102, 574, 11887, 304, 5936, 220, 679, 21, 1306, 264, 1396, 315, 1667, 315, 9293, 323, 29173, 449, 264, 3544, 1396, 315, 2890, 323, 36201, 11909, 13, 3161, 279, 32855, 5915, 315, 32758, 220, 1041, 11, 931, 6484, 6560, 12371, 677, 1201, 13324, 11, 433, 374, 6968, 279, 8706, 4526, 315, 43739, 315, 5419, 36853, 11, 311, 5276, 279, 1648, 14248, 4007, 264, 7029, 2134, 315, 19338, 11, 2737, 52857, 11, 55652, 11, 9572, 11, 4851, 8951, 323, 12943, 13, 11450, 596, 5684, 16964, 279, 8271, 32758, 961, 315, 6560, 12371, 677, 1201, 11, 6197, 555, 8626, 434, 82, 1105, 14129, 9259, 323, 13528, 4355, 17472, 505, 279, 3907, 315, 26275, 11, 323, 17054, 7043, 51784, 505, 31013, 9304, 7295, 13, 17054, 17472, 1071, 25, 330, 1687, 527, 1701, 14713, 48448, 52460, 43739, 323, 6295, 2956, 6492, 5528, 311, 636, 279, 1455, 16195, 3321, 1139, 279, 8271, 430, 1510, 32758, 5557, 6276, 1210, 330, 9673, 3135, 527, 1120, 264, 1176, 40942, 1139, 420, 11191, 11, 9257, 10550, 690, 430, 34044, 304, 279, 5108, 1667, 13, 1102, 374, 459, 71257, 5211, 430, 690, 5276, 1057, 8830, 315, 1690, 4279, 19338, 1210, 17054, 51784, 11, 3279, 12669, 323, 48390, 12867, 969, 16478, 323, 11452, 315, 31417, 23199, 520, 31013, 11, 3779, 25, 330, 9673, 3135, 527, 13548, 11, 719, 16632, 3493, 264, 1176, 13310, 315, 1148, 649, 387, 11352, 449, 279, 6560, 12371, 677, 1201, 13, 1115, 2447, 1101, 374, 264, 38350, 1606, 315, 279, 1648, 433, 706, 1027, 2884, 25, 220, 2636, 11, 931, 23872, 4028, 279, 549, 11606, 13, 527, 61959, 872, 892, 311, 387, 961, 315, 433, 323, 810, 1109, 220, 6549, 14248, 505, 4028, 279, 1917, 20162, 311, 279, 2955, 315, 279, 32758, 27886, 7636, 13, 31013, 9304, 14248, 6476, 264, 3682, 3560, 304, 1202, 54529, 323, 11692, 439, 961, 315, 264, 2128, 45425, 555, 279, 549, 11606, 13, 6160, 677, 1201, 505, 264, 1396, 315, 6560, 23978, 13, 1115, 374, 264, 11364, 3187, 315, 330, 2569, 8198, 3343, 578, 5684, 6821, 1176, 3135, 505, 420, 23649, 828, 5211, 11, 902, 5764, 4848, 2204, 13124, 315, 8271, 32758, 2884, 304, 279, 220, 966, 4520, 430, 1855, 26202, 374, 304, 279, 8271, 21438, 13, 17054, 9259, 11497, 25, 330, 1687, 617, 364, 96797, 32758, 6, 482, 430, 10975, 603, 922, 8271, 62690, 1389, 279, 21483, 323, 12562, 315, 279, 2204, 5596, 315, 279, 8271, 13, 13596, 3169, 1389, 364, 50328, 52460, 6, 482, 10975, 603, 922, 6485, 12912, 315, 8271, 5820, 13, 14968, 2500, 3169, 1389, 364, 13798, 7713, 52460, 6, 482, 10975, 603, 922, 279, 8271, 596, 19358, 13861, 13, 578, 9257, 323, 17226, 2038, 13282, 304, 1521, 43739, 690, 16805, 1268, 279, 3318, 315, 279, 8271, 649, 2349, 449, 30084, 323, 8624, 26, 2204, 19338, 690, 1888, 387, 16365, 1555, 2204, 28559, 315, 2038, 4028, 1521, 2204, 5448, 1210, 6560, 12371, 677, 1201, 706, 2736, 48548, 220, 605, 11, 931, 13324, 11, 2737, 5448, 315, 279, 4851, 11, 2547, 11, 17685, 323, 6680, 31080, 304, 5369, 311, 8271, 43739, 13, 1115, 690, 387, 555, 3117, 279, 7928, 8271, 32758, 4007, 3596, 13375, 26, 2949, 2500, 220, 20, 1667, 6560, 12371, 677, 1201, 690, 617, 8308, 279, 36201, 315, 220, 1041, 11, 931, 13324, 13, 3861, 2944, 369, 33921, 1778, 3544, 5219, 315, 13324, 374, 311, 617, 3403, 15223, 311, 2187, 18841, 315, 4216, 11, 11000, 27545, 11, 24915, 315, 3938, 8624, 5326, 11, 2225, 369, 264, 2134, 315, 4279, 19338, 323, 369, 9024, 64908, 24673, 1093, 9048, 49384, 8624, 13, 1556, 3062, 16945, 315, 279, 6560, 12371, 677, 1201, 374, 311, 3493, 264, 5211, 369, 18841, 315, 502, 26793, 1139, 19338, 1093, 44531, 596, 11, 902, 18651, 36201, 9498, 15223, 1667, 477, 11026, 1603, 814, 2274, 13803, 13, 5659, 279, 6560, 12371, 677, 1201, 828, 11, 14248, 12660, 649, 9395, 311, 4048, 1790, 810, 922, 8271, 19338, 482, 323, 872, 5133, 311, 264, 7353, 2134, 315, 1023, 19338, 477, 8624, 15635, 482, 311, 8641, 279, 4500, 315, 6931, 17550, 6514, 320, 269, 4442, 304, 19433, 8, 430, 1436, 304, 279, 3938, 5471, 3682, 19338, 505, 3596, 12765, 13, 220, 128257, 198 ]

2,410

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Photosynthetic reaction centres harvest the energy content of sunlight by transporting electrons across an energy-transducing biological membrane. Here we use time-resolved serial femtosecond crystallography 1 using an X-ray free-electron laser 2 to observe light-induced structural changes in the photosynthetic reaction centre of Blastochloris viridis on a timescale of picoseconds. Structural perturbations first occur at the special pair of chlorophyll molecules of the photosynthetic reaction centre that are photo-oxidized by light. Electron transfer to the menaquinone acceptor on the opposite side of the membrane induces a movement of this cofactor together with lower amplitude protein rearrangements. These observations reveal how proteins use conformational dynamics to stabilize the charge-separation steps of electron-transfer reactions. Main Our biosphere depends on the electron-transfer reactions of photosynthesis as a primary source of energy. Photosystems and photosynthetic reaction centres form a family of integral membrane protein complexes found in plants, algae, cyanobacteria and photosynthetic bacteria that convert the energy of a captured photon into a charge-separated state. The photosynthetic reaction centre of the purple non-sulfur bacterium B. viridis ( Bv RC) contains three transmembrane subunits called H, L and M and a periplasmic subunit C. These subunits support four bacteriochlorophyll (BCh) molecules, two bacteriopheophytin (BPh) molecules, a tightly bound menaquinone (Q A ), a mobile ubiquinone (Q B ), a single non-haem iron and four haem cofactors (Fig. 1 ). Electron-transfer reactions originate at a special pair (SP) of strongly interacting bacteriochlorophylls that, in B. viridis , have an absorption maximum at 960 nm. Photo-oxidation of the SP liberates an electron that is transferred to the active branch BPh L within a few picoseconds, is transferred to the tightly bound menaquinone (Q A ) in less than a nanosecond and is transferred to the mobile ubiquinone (Q B ) in microseconds. SP + is reduced by subunit C, and a second photo-oxidation event transfers a second electron to Q B − , which is protonated from the cytoplasm and released into the membrane as ubiquinol (H 2 Q). Other proteins participate in a cyclic flow that returns electrons to subunit C and the net effect is that two protons are transported across an energy-transducing membrane for every photon absorbed. Fig. 1: Electron-transfer steps of the photosynthetic reaction centre of B. viridis . Cartoon representation of the H, L, M and C subunits. Cofactors are shown in black including the SP molecule, two monomeric BCh molecules, two BPh molecules, a tightly bound Q A molecule, a mobile Q B molecule, a non-haem iron (Fe 2+ ) and four haems. The approximate boundaries of the membrane are suggested in blue. The electron-transfer pathway: SP → BPh L → Q A is referred to as the A-branch. Approximate timescales for the first two electron-transfer events, from SP to BPh L and from BPh L to Q A , are shown. Full size image Electrons may tunnel between cofactors when they are separated by approximately 10 Å or less 3 . The primary electron-transfer step 4 from SP to BPh L occurs in 2.8 ± 0.2 ps across a distance of 10 Å by means of a two-step hopping mechanism via the monomeric BCh L molecule 5 and is more rapid than conventional Marcus theory. By contrast, the 9 Å electron-transfer step from BPh L to Q A has a single exponential decay time 6 of 230 ± 30 ps, which is consistent with conventional Marcus theory. Coherent nuclear motions 7 and protein structural changes 8 have been suggested to influence the initial charge-transfer reactions of photosynthesis, yet the specific nature of these putative protein motions is unknown. Flash-freeze crystallographic trapping studies 9 , time-resolved Laue diffraction 10 and time-resolved serial femtosecond crystallography 11 , 12 , 13 , 14 (TR-SFX) have revealed structural changes in bacterial photosynthetic reaction centres 9 , 10 and cyanobacterial photosystem II (PSII) 11 , 12 , 13 , 14 that occur on the late microsecond-to-millisecond timescale, yet, to our knowledge, no time-resolved crystallographic studies on the timescale of the primary charge-separation reactions of photosynthesis have been reported. Here we apply time-resolved serial femtosecond crystallography 1 using an X-ray free electron laser (XFEL) to investigate the ultrafast structural response of Bv RC to light. We photo-excited the special pair with 150-fs pulses centred at 960 nm (Extended Data Fig. 1 ). X-ray pulses with a duration of 40 fs were generated at the Linac Coherent Light Source (LCLS) 2 and were used to record diffraction patterns from tens of thousands of microcrystals for the time points ∆ t = 1 ps, 5 ps (two repeats), 20 ps, 300 ps (two repeats) and 8 μs after photoexcitation (Extended Data Table 1 ). Time point ∆ t = 1 ps populates the photo-excited charge transfer state of the SP in which charge rearrangements have occurred within the bacteriochlorophyll dimer but are before the primary electron-transfer step; ∆ t = 5 ps and 20 ps are after the initial charge-transfer step and SP is oxidized and BPh L is reduced; ∆ t = 300 ps is longer than the time constant for electron transfer to Q A and menaquinone is reduced; and ∆ t = 8 μs corresponds to a meta-stable charge-separated state. Extended Data Figure 2 presents overviews of the F o (light) − F o (dark) isomorphous difference Fourier electron density maps (‘light’ corresponds to data collected from photo-activated microcrystals whereas ‘dark’ corresponds to data collected from microcrystals that were not photo-activated) for all time points. Difference electron density features are visible above 4.0 σ (where σ is the root mean square electron density of the map) near SP for all time points and strong features associated with Q A are visible for ∆ t ≥ 300 ps (Extended Data Table 2 ). In contrast to ultrafast TR-SFX studies of bacteriorhodopsin 15 , photoactive yellow protein 16 , rsEGFP 17 and bacterial phytochromes 18 in which ultrafast structural changes are driven by the movements of atoms owing to a photo-isomerization event, TR-SFX measurements of Bv RC", "role": "user" }, { "content": "Photosynthesis is the primary source of energy for almost all life-on-earth. A new study, published in Nature, provide new insight into how evolution has optimized the light-driven movements of electrons in photosynthesis to achieve almost perfect overall efficiency. Almost all life on earth has the energy-transducing reactions of photosynthesis as their primary source of energy. These light-driven reactions occur in plants, algae and photosynthetic bacteria. An X-ray structure of a protein provides scientists with a lot of information as to how they perform their biological task in a living cell. X-ray films show structural changes within a protein In this work scientists used a method called time-resolved X-ray crystallography to make a movie of structural changes within the protein responsible for the light-driven chemical reactions of photosynthesis. To achieve this scientists at the University of Gothenburg used a world-leading X-ray source in California (an X-ray free electron laser) to examine if structural rearrangements within photosynthetic proteins occur on the time-it-takes light to cross a hair of your head. Remarkably, these measurements showed that the protein changes structure on this time-scale. Subtle movements in the protein were seen Scientists at the University of Gothenburg observed that these movements were very subtle, with both the electron donor (a chemical group which absorbs light and releases an electron) and the electron acceptor (a chemical group which is located 2 nm away and which receives this electron) moving less than 0.03 nm (1 nm = 10-9 m or a millionth of a millimeter) in 300 ps (1 ps = 10-12 sec is called a picosecond and is a millionth of a millionth of a second). The protein as a whole also changed structure very slightly in order to prevent the electron returning to where it began, which would otherwise make the reaction useless. These results are fundamental to how evolution has optimized energy transducing proteins over billions of years to allow them to perform redox reactions without energy being lost in the process. \"Time-resolved crystallography studies of a photosynthetic protein from bacteria reveal how light-induced electron movements are stabilized by protein structural changes occurring on a time-scale of picoseconds,\" says Richard Neutze, professor at the University of Gothenburg. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Photosynthetic reaction centres harvest the energy content of sunlight by transporting electrons across an energy-transducing biological membrane. Here we use time-resolved serial femtosecond crystallography 1 using an X-ray free-electron laser 2 to observe light-induced structural changes in the photosynthetic reaction centre of Blastochloris viridis on a timescale of picoseconds. Structural perturbations first occur at the special pair of chlorophyll molecules of the photosynthetic reaction centre that are photo-oxidized by light. Electron transfer to the menaquinone acceptor on the opposite side of the membrane induces a movement of this cofactor together with lower amplitude protein rearrangements. These observations reveal how proteins use conformational dynamics to stabilize the charge-separation steps of electron-transfer reactions. Main Our biosphere depends on the electron-transfer reactions of photosynthesis as a primary source of energy. Photosystems and photosynthetic reaction centres form a family of integral membrane protein complexes found in plants, algae, cyanobacteria and photosynthetic bacteria that convert the energy of a captured photon into a charge-separated state. The photosynthetic reaction centre of the purple non-sulfur bacterium B. viridis ( Bv RC) contains three transmembrane subunits called H, L and M and a periplasmic subunit C. These subunits support four bacteriochlorophyll (BCh) molecules, two bacteriopheophytin (BPh) molecules, a tightly bound menaquinone (Q A ), a mobile ubiquinone (Q B ), a single non-haem iron and four haem cofactors (Fig. 1 ). Electron-transfer reactions originate at a special pair (SP) of strongly interacting bacteriochlorophylls that, in B. viridis , have an absorption maximum at 960 nm. Photo-oxidation of the SP liberates an electron that is transferred to the active branch BPh L within a few picoseconds, is transferred to the tightly bound menaquinone (Q A ) in less than a nanosecond and is transferred to the mobile ubiquinone (Q B ) in microseconds. SP + is reduced by subunit C, and a second photo-oxidation event transfers a second electron to Q B − , which is protonated from the cytoplasm and released into the membrane as ubiquinol (H 2 Q). Other proteins participate in a cyclic flow that returns electrons to subunit C and the net effect is that two protons are transported across an energy-transducing membrane for every photon absorbed. Fig. 1: Electron-transfer steps of the photosynthetic reaction centre of B. viridis . Cartoon representation of the H, L, M and C subunits. Cofactors are shown in black including the SP molecule, two monomeric BCh molecules, two BPh molecules, a tightly bound Q A molecule, a mobile Q B molecule, a non-haem iron (Fe 2+ ) and four haems. The approximate boundaries of the membrane are suggested in blue. The electron-transfer pathway: SP → BPh L → Q A is referred to as the A-branch. Approximate timescales for the first two electron-transfer events, from SP to BPh L and from BPh L to Q A , are shown. Full size image Electrons may tunnel between cofactors when they are separated by approximately 10 Å or less 3 . The primary electron-transfer step 4 from SP to BPh L occurs in 2.8 ± 0.2 ps across a distance of 10 Å by means of a two-step hopping mechanism via the monomeric BCh L molecule 5 and is more rapid than conventional Marcus theory. By contrast, the 9 Å electron-transfer step from BPh L to Q A has a single exponential decay time 6 of 230 ± 30 ps, which is consistent with conventional Marcus theory. Coherent nuclear motions 7 and protein structural changes 8 have been suggested to influence the initial charge-transfer reactions of photosynthesis, yet the specific nature of these putative protein motions is unknown. Flash-freeze crystallographic trapping studies 9 , time-resolved Laue diffraction 10 and time-resolved serial femtosecond crystallography 11 , 12 , 13 , 14 (TR-SFX) have revealed structural changes in bacterial photosynthetic reaction centres 9 , 10 and cyanobacterial photosystem II (PSII) 11 , 12 , 13 , 14 that occur on the late microsecond-to-millisecond timescale, yet, to our knowledge, no time-resolved crystallographic studies on the timescale of the primary charge-separation reactions of photosynthesis have been reported. Here we apply time-resolved serial femtosecond crystallography 1 using an X-ray free electron laser (XFEL) to investigate the ultrafast structural response of Bv RC to light. We photo-excited the special pair with 150-fs pulses centred at 960 nm (Extended Data Fig. 1 ). X-ray pulses with a duration of 40 fs were generated at the Linac Coherent Light Source (LCLS) 2 and were used to record diffraction patterns from tens of thousands of microcrystals for the time points ∆ t = 1 ps, 5 ps (two repeats), 20 ps, 300 ps (two repeats) and 8 μs after photoexcitation (Extended Data Table 1 ). Time point ∆ t = 1 ps populates the photo-excited charge transfer state of the SP in which charge rearrangements have occurred within the bacteriochlorophyll dimer but are before the primary electron-transfer step; ∆ t = 5 ps and 20 ps are after the initial charge-transfer step and SP is oxidized and BPh L is reduced; ∆ t = 300 ps is longer than the time constant for electron transfer to Q A and menaquinone is reduced; and ∆ t = 8 μs corresponds to a meta-stable charge-separated state. Extended Data Figure 2 presents overviews of the F o (light) − F o (dark) isomorphous difference Fourier electron density maps (‘light’ corresponds to data collected from photo-activated microcrystals whereas ‘dark’ corresponds to data collected from microcrystals that were not photo-activated) for all time points. Difference electron density features are visible above 4.0 σ (where σ is the root mean square electron density of the map) near SP for all time points and strong features associated with Q A are visible for ∆ t ≥ 300 ps (Extended Data Table 2 ). In contrast to ultrafast TR-SFX studies of bacteriorhodopsin 15 , photoactive yellow protein 16 , rsEGFP 17 and bacterial phytochromes 18 in which ultrafast structural changes are driven by the movements of atoms owing to a photo-isomerization event, TR-SFX measurements of Bv RC<|im_end|> <|im_start|>assistant Photosynthesis is the primary source of energy for almost all life-on-earth. A new study, published in Nature, provide new insight into how evolution has optimized the light-driven movements of electrons in photosynthesis to achieve almost perfect overall efficiency. Almost all life on earth has the energy-transducing reactions of photosynthesis as their primary source of energy. These light-driven reactions occur in plants, algae and photosynthetic bacteria. An X-ray structure of a protein provides scientists with a lot of information as to how they perform their biological task in a living cell. X-ray films show structural changes within a protein In this work scientists used a method called time-resolved X-ray crystallography to make a movie of structural changes within the protein responsible for the light-driven chemical reactions of photosynthesis. To achieve this scientists at the University of Gothenburg used a world-leading X-ray source in California (an X-ray free electron laser) to examine if structural rearrangements within photosynthetic proteins occur on the time-it-takes light to cross a hair of your head. Remarkably, these measurements showed that the protein changes structure on this time-scale. Subtle movements in the protein were seen Scientists at the University of Gothenburg observed that these movements were very subtle, with both the electron donor (a chemical group which absorbs light and releases an electron) and the electron acceptor (a chemical group which is located 2 nm away and which receives this electron) moving less than 0.03 nm (1 nm = 10-9 m or a millionth of a millimeter) in 300 ps (1 ps = 10-12 sec is called a picosecond and is a millionth of a millionth of a second). The protein as a whole also changed structure very slightly in order to prevent the electron returning to where it began, which would otherwise make the reaction useless. These results are fundamental to how evolution has optimized energy transducing proteins over billions of years to allow them to perform redox reactions without energy being lost in the process. "Time-resolved crystallography studies of a photosynthetic protein from bacteria reveal how light-induced electron movements are stabilized by protein structural changes occurring on a time-scale of picoseconds," says Richard Neutze, professor at the University of Gothenburg. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 16912, 1910, 18015, 13010, 36282, 24322, 279, 4907, 2262, 315, 40120, 555, 67757, 57678, 4028, 459, 4907, 39160, 1072, 6253, 24156, 39654, 13, 5810, 584, 1005, 892, 11849, 8905, 6275, 5103, 83, 974, 1321, 26110, 848, 1976, 88, 220, 16, 1701, 459, 1630, 30630, 1949, 37081, 2298, 21120, 220, 17, 311, 23846, 3177, 38973, 24693, 4442, 304, 279, 7397, 1910, 18015, 13010, 12541, 315, 58436, 5059, 9761, 285, 9043, 85342, 389, 264, 3115, 2296, 315, 10532, 76989, 13, 73800, 18713, 9225, 811, 1176, 12446, 520, 279, 3361, 6857, 315, 37833, 5237, 25734, 35715, 315, 279, 7397, 1910, 18015, 13010, 12541, 430, 527, 6685, 12, 85078, 1534, 555, 3177, 13, 77976, 8481, 311, 279, 3026, 64, 36444, 606, 4287, 269, 389, 279, 14329, 3185, 315, 279, 39654, 90974, 264, 7351, 315, 420, 69903, 5739, 3871, 449, 4827, 45209, 13128, 56427, 526, 3808, 13, 4314, 24654, 16805, 1268, 28896, 1005, 390, 1659, 278, 30295, 311, 70236, 279, 6900, 7962, 36235, 7504, 315, 17130, 93791, 25481, 13, 4802, 5751, 49554, 8182, 14117, 389, 279, 17130, 93791, 25481, 315, 7397, 74767, 439, 264, 6156, 2592, 315, 4907, 13, 16912, 95890, 323, 7397, 1910, 18015, 13010, 36282, 1376, 264, 3070, 315, 26154, 39654, 13128, 69125, 1766, 304, 11012, 11, 68951, 11, 58988, 677, 78852, 323, 7397, 1910, 18015, 24032, 430, 5625, 279, 4907, 315, 264, 17439, 69010, 1139, 264, 6900, 73792, 1614, 13, 578, 7397, 1910, 18015, 13010, 12541, 315, 279, 25977, 2536, 1355, 14643, 324, 17854, 2411, 426, 13, 9043, 85342, 320, 426, 85, 22322, 8, 5727, 2380, 1380, 10759, 88554, 1207, 26726, 2663, 473, 11, 445, 323, 386, 323, 264, 824, 10567, 10753, 292, 1207, 3928, 356, 13, 4314, 1207, 26726, 1862, 3116, 17854, 822, 72967, 5237, 25734, 320, 33, 1163, 8, 35715, 11, 1403, 17854, 72, 81509, 5237, 16820, 258, 320, 33, 3438, 8, 35715, 11, 264, 40069, 6965, 3026, 64, 36444, 606, 320, 48, 362, 7026, 264, 6505, 53336, 258, 606, 320, 48, 426, 7026, 264, 3254, 2536, 2902, 64, 336, 11245, 323, 3116, 6520, 336, 69903, 21846, 320, 30035, 13, 220, 16, 7609, 77976, 93791, 25481, 82316, 520, 264, 3361, 6857, 320, 4695, 8, 315, 16917, 45830, 17854, 822, 72967, 5237, 25734, 82, 430, 11, 304, 426, 13, 9043, 85342, 1174, 617, 459, 44225, 7340, 520, 220, 16415, 26807, 13, 11064, 12, 85078, 367, 315, 279, 9440, 34929, 988, 459, 17130, 430, 374, 23217, 311, 279, 4642, 9046, 426, 3438, 445, 2949, 264, 2478, 10532, 76989, 11, 374, 23217, 311, 279, 40069, 6965, 3026, 64, 36444, 606, 320, 48, 362, 883, 304, 2753, 1109, 264, 20622, 974, 1321, 323, 374, 23217, 311, 279, 6505, 53336, 258, 606, 320, 48, 426, 883, 304, 85862, 13, 9440, 489, 374, 11293, 555, 1207, 3928, 356, 11, 323, 264, 2132, 6685, 12, 85078, 367, 1567, 31711, 264, 2132, 17130, 311, 1229, 426, 25173, 1174, 902, 374, 82586, 660, 505, 279, 9693, 99705, 10753, 323, 6004, 1139, 279, 39654, 439, 53336, 258, 337, 320, 39, 220, 17, 1229, 570, 7089, 28896, 16136, 304, 264, 77102, 6530, 430, 4780, 57678, 311, 1207, 3928, 356, 323, 279, 4272, 2515, 374, 430, 1403, 463, 35511, 527, 40460, 4028, 459, 4907, 39160, 1072, 6253, 39654, 369, 1475, 69010, 42101, 13, 23966, 13, 220, 16, 25, 77976, 93791, 7504, 315, 279, 7397, 1910, 18015, 13010, 12541, 315, 426, 13, 9043, 85342, 662, 69530, 13340, 315, 279, 473, 11, 445, 11, 386, 323, 356, 1207, 26726, 13, 356, 1073, 21846, 527, 6982, 304, 3776, 2737, 279, 9440, 43030, 11, 1403, 1647, 316, 11893, 426, 1163, 35715, 11, 1403, 426, 3438, 35715, 11, 264, 40069, 6965, 1229, 362, 43030, 11, 264, 6505, 1229, 426, 43030, 11, 264, 2536, 2902, 64, 336, 11245, 320, 6251, 220, 17, 10, 883, 323, 3116, 6520, 12116, 13, 578, 45968, 23546, 315, 279, 39654, 527, 12090, 304, 6437, 13, 578, 17130, 93791, 38970, 25, 9440, 11651, 426, 3438, 445, 11651, 1229, 362, 374, 14183, 311, 439, 279, 362, 12, 18424, 13, 44919, 3509, 3115, 31296, 369, 279, 1176, 1403, 17130, 93791, 4455, 11, 505, 9440, 311, 426, 3438, 445, 323, 505, 426, 3438, 445, 311, 1229, 362, 1174, 527, 6982, 13, 8797, 1404, 2217, 10085, 26692, 1253, 26711, 1990, 69903, 21846, 994, 814, 527, 19180, 555, 13489, 220, 605, 80352, 477, 2753, 220, 18, 662, 578, 6156, 17130, 93791, 3094, 220, 19, 505, 9440, 311, 426, 3438, 445, 13980, 304, 220, 17, 13, 23, 20903, 220, 15, 13, 17, 4831, 4028, 264, 6138, 315, 220, 605, 80352, 555, 3445, 315, 264, 1403, 30308, 93338, 17383, 4669, 279, 1647, 316, 11893, 426, 1163, 445, 43030, 220, 20, 323, 374, 810, 11295, 1109, 21349, 36783, 10334, 13, 3296, 13168, 11, 279, 220, 24, 80352, 17130, 93791, 3094, 505, 426, 3438, 445, 311, 1229, 362, 706, 264, 3254, 59855, 31815, 892, 220, 21, 315, 220, 9870, 20903, 220, 966, 4831, 11, 902, 374, 13263, 449, 21349, 36783, 10334, 13, 3623, 38638, 11499, 54245, 220, 22, 323, 13128, 24693, 4442, 220, 23, 617, 1027, 12090, 311, 10383, 279, 2926, 6900, 93791, 25481, 315, 7397, 74767, 11, 3686, 279, 3230, 7138, 315, 1521, 2231, 1413, 13128, 54245, 374, 9987, 13, 17710, 12862, 3059, 26110, 848, 79173, 93669, 7978, 220, 24, 1174, 892, 11849, 8905, 5034, 361, 3722, 16597, 220, 605, 323, 892, 11849, 8905, 6275, 5103, 83, 974, 1321, 26110, 848, 1976, 88, 220, 806, 1174, 220, 717, 1174, 220, 1032, 1174, 220, 975, 320, 2434, 6354, 16786, 8, 617, 10675, 24693, 4442, 304, 45964, 7397, 1910, 18015, 13010, 36282, 220, 24, 1174, 220, 605, 323, 58988, 677, 71034, 7397, 615, 8105, 320, 5119, 5660, 8, 220, 806, 1174, 220, 717, 1174, 220, 1032, 1174, 220, 975, 430, 12446, 389, 279, 3389, 8162, 5686, 4791, 1474, 66458, 3115, 2296, 11, 3686, 11, 311, 1057, 6677, 11, 912, 892, 11849, 8905, 26110, 848, 79173, 7978, 389, 279, 3115, 2296, 315, 279, 6156, 6900, 7962, 36235, 25481, 315, 7397, 74767, 617, 1027, 5068, 13, 5810, 584, 3881, 892, 11849, 8905, 6275, 5103, 83, 974, 1321, 26110, 848, 1976, 88, 220, 16, 1701, 459, 1630, 30630, 1949, 17130, 21120, 320, 67238, 2818, 8, 311, 19874, 279, 24955, 9533, 24693, 2077, 315, 426, 85, 22322, 311, 3177, 13, 1226, 6685, 98033, 1639, 279, 3361, 6857, 449, 220, 3965, 2269, 82, 66557, 2960, 1171, 520, 220, 16415, 26807, 320, 54290, 2956, 23966, 13, 220, 16, 7609, 1630, 30630, 66557, 449, 264, 8250, 315, 220, 1272, 8789, 1051, 8066, 520, 279, 8732, 582, 3623, 38638, 8828, 8922, 320, 43, 88816, 8, 220, 17, 323, 1051, 1511, 311, 3335, 3722, 16597, 12912, 505, 22781, 315, 9214, 315, 8162, 5192, 92475, 369, 279, 892, 3585, 12264, 228, 259, 284, 220, 16, 4831, 11, 220, 20, 4831, 320, 20375, 44694, 705, 220, 508, 4831, 11, 220, 3101, 4831, 320, 20375, 44694, 8, 323, 220, 23, 33983, 82, 1306, 6685, 40541, 7709, 320, 54290, 2956, 6771, 220, 16, 7609, 4212, 1486, 12264, 228, 259, 284, 220, 16, 4831, 2477, 24031, 279, 6685, 98033, 1639, 6900, 8481, 1614, 315, 279, 9440, 304, 902, 6900, 56427, 526, 3808, 617, 10222, 2949, 279, 17854, 822, 72967, 5237, 25734, 294, 3212, 719, 527, 1603, 279, 6156, 17130, 93791, 3094, 26, 12264, 228, 259, 284, 220, 20, 4831, 323, 220, 508, 4831, 527, 1306, 279, 2926, 6900, 93791, 3094, 323, 9440, 374, 36172, 1534, 323, 426, 3438, 445, 374, 11293, 26, 12264, 228, 259, 284, 220, 3101, 4831, 374, 5129, 1109, 279, 892, 6926, 369, 17130, 8481, 311, 1229, 362, 323, 3026, 64, 36444, 606, 374, 11293, 26, 323, 12264, 228, 259, 284, 220, 23, 33983, 82, 34310, 311, 264, 8999, 5594, 481, 6900, 73792, 1614, 13, 41665, 2956, 19575, 220, 17, 18911, 927, 5182, 315, 279, 435, 297, 320, 4238, 8, 25173, 435, 297, 320, 23449, 8, 374, 316, 16751, 788, 6811, 90054, 17130, 17915, 14370, 320, 14336, 4238, 529, 34310, 311, 828, 14890, 505, 6685, 12, 31262, 8162, 5192, 92475, 20444, 3451, 23449, 529, 34310, 311, 828, 14890, 505, 8162, 5192, 92475, 430, 1051, 539, 6685, 12, 31262, 8, 369, 682, 892, 3585, 13, 56180, 17130, 17915, 4519, 527, 9621, 3485, 220, 19, 13, 15, 48823, 320, 2940, 48823, 374, 279, 3789, 3152, 9518, 17130, 17915, 315, 279, 2472, 8, 3221, 9440, 369, 682, 892, 3585, 323, 3831, 4519, 5938, 449, 1229, 362, 527, 9621, 369, 12264, 228, 259, 63247, 220, 3101, 4831, 320, 54290, 2956, 6771, 220, 17, 7609, 763, 13168, 311, 24955, 9533, 5091, 6354, 16786, 7978, 315, 17854, 2521, 100830, 3806, 258, 220, 868, 1174, 6685, 3104, 14071, 13128, 220, 845, 1174, 10242, 9560, 11960, 220, 1114, 323, 45964, 37555, 998, 41484, 288, 220, 972, 304, 902, 24955, 9533, 24693, 4442, 527, 16625, 555, 279, 19567, 315, 33299, 56612, 311, 264, 6685, 31530, 26429, 2065, 1567, 11, 5091, 6354, 16786, 22323, 315, 426, 85, 22322, 128257, 198, 128256, 78191, 198, 32872, 74767, 374, 279, 6156, 2592, 315, 4907, 369, 4661, 682, 2324, 10539, 86187, 13, 362, 502, 4007, 11, 4756, 304, 22037, 11, 3493, 502, 20616, 1139, 1268, 15740, 706, 34440, 279, 3177, 32505, 19567, 315, 57678, 304, 7397, 74767, 311, 11322, 4661, 4832, 8244, 15374, 13, 35403, 682, 2324, 389, 9578, 706, 279, 4907, 39160, 1072, 6253, 25481, 315, 7397, 74767, 439, 872, 6156, 2592, 315, 4907, 13, 4314, 3177, 32505, 25481, 12446, 304, 11012, 11, 68951, 323, 7397, 1910, 18015, 24032, 13, 1556, 1630, 30630, 6070, 315, 264, 13128, 5825, 14248, 449, 264, 2763, 315, 2038, 439, 311, 1268, 814, 2804, 872, 24156, 3465, 304, 264, 5496, 2849, 13, 1630, 30630, 12631, 1501, 24693, 4442, 2949, 264, 13128, 763, 420, 990, 14248, 1511, 264, 1749, 2663, 892, 11849, 8905, 1630, 30630, 26110, 848, 1976, 88, 311, 1304, 264, 5818, 315, 24693, 4442, 2949, 279, 13128, 8647, 369, 279, 3177, 32505, 11742, 25481, 315, 7397, 74767, 13, 2057, 11322, 420, 14248, 520, 279, 3907, 315, 6122, 3473, 10481, 1511, 264, 1917, 69475, 1630, 30630, 2592, 304, 7188, 320, 276, 1630, 30630, 1949, 17130, 21120, 8, 311, 21635, 422, 24693, 56427, 526, 3808, 2949, 7397, 1910, 18015, 28896, 12446, 389, 279, 892, 38611, 2442, 2094, 3177, 311, 5425, 264, 7013, 315, 701, 2010, 13, 83833, 2915, 11, 1521, 22323, 8710, 430, 279, 13128, 4442, 6070, 389, 420, 892, 13230, 13, 3804, 11489, 19567, 304, 279, 13128, 1051, 3970, 57116, 520, 279, 3907, 315, 6122, 3473, 10481, 13468, 430, 1521, 19567, 1051, 1633, 27545, 11, 449, 2225, 279, 17130, 35558, 320, 64, 11742, 1912, 902, 91111, 3177, 323, 19786, 459, 17130, 8, 323, 279, 17130, 4287, 269, 320, 64, 11742, 1912, 902, 374, 7559, 220, 17, 26807, 3201, 323, 902, 21879, 420, 17130, 8, 7366, 2753, 1109, 220, 15, 13, 2839, 26807, 320, 16, 26807, 284, 220, 605, 12, 24, 296, 477, 264, 3610, 339, 315, 264, 2606, 26402, 8, 304, 220, 3101, 4831, 320, 16, 4831, 284, 220, 605, 12, 717, 5819, 374, 2663, 264, 10532, 974, 1321, 323, 374, 264, 3610, 339, 315, 264, 3610, 339, 315, 264, 2132, 570, 578, 13128, 439, 264, 4459, 1101, 5614, 6070, 1633, 10284, 304, 2015, 311, 5471, 279, 17130, 13758, 311, 1405, 433, 6137, 11, 902, 1053, 6062, 1304, 279, 13010, 29948, 13, 4314, 3135, 527, 16188, 311, 1268, 15740, 706, 34440, 4907, 1380, 1072, 6253, 28896, 927, 33151, 315, 1667, 311, 2187, 1124, 311, 2804, 2579, 5241, 25481, 2085, 4907, 1694, 5675, 304, 279, 1920, 13, 330, 1489, 11849, 8905, 26110, 848, 1976, 88, 7978, 315, 264, 7397, 1910, 18015, 13128, 505, 24032, 16805, 1268, 3177, 38973, 17130, 19567, 527, 93163, 555, 13128, 24693, 4442, 31965, 389, 264, 892, 13230, 315, 10532, 76989, 1359, 2795, 12131, 4275, 332, 3059, 11, 14561, 520, 279, 3907, 315, 6122, 3473, 10481, 13, 220, 128257, 198 ]

1,963

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Freehand and bipolar experimental knapping of quartzite from Olduvai Gorge in Tanzania is used to conduct spatial analysis of artefact distributions using GIS techniques, and to investigate the orientation of refit lines using circular histograms. The aim of our study is to discern patterns that can be applied to the archaeological record in two domains, namely the identification of knapping episodes and the utility of refitting line orientations in addressing post-depositional disturbance. Our spatial analysis shows that distinctive clustering patterns can be discerned according to knapping stance, handedness and flaking technique. The circular dispersion of refit lines in the horizontal distribution of bipolar assemblages is strongly patterned, indicating that anisotropy of conjoining sets is inherent to pristine hammer-and-anvil knapping episodes. Working on a manuscript? Avoid the common mistakes Introduction The study of spatial distributions in experimental lithic scatters covers a range of topics, including knapper handedness (Bargalló et al. 2017 ), knapper stance (Newcomer and de Sieveking, 1980 ; Barton and Bergman 1982 ; Schick 1984 ; Fischer 1990 ; Kvamme 1997 ), reduction strategy and raw material (Kvamme 1997 ), hammer type (Newcomer and de Sieveking, 1980 ; Kvamme 1997 ) and post-depositional processes (Bowers et al. 1983 ; Gifford-González et al. 1985 ; Schick 1984 ; Nielsen 1991 ; Texier et al. 1998 ; Lenoble et al. 2008 ; Bertran et al. 2015 ; Driscoll et al. 2016 ). These studies have produced relevant observations on the spatial distribution of experimental scatters, but quantitative results based on systematic GIS analyses are yet to be done. Such lack of quantification in experimental assemblages applies both to density patterns and the refitting of the lithic sets produced. Analysis of orientation patterns in archaeology is traditionally linked to the study of post-depositional processes (e.g. Isaac 1967 ; Schick 1984 ; Kreutzer 1988 ; Pope 2002 ; Lenoble and Bertran 2004 ; Boschian and Saccà, 2010 ; Benito-Calvo and de la Torre 2011 ; Benito-Calvo et al. 2009 , 2011 ; Sánchez-Romero et al. 2016 ; de la Torre and Wehr 2018 ; McPherron 2018 ), and refitting is widely recognised as a powerful tool to disentangle site formation (e.g. Cahen 1980 ; Villa 1982 , 2004 ; Hofman 1986 ; Bordes 2003 ; Deschamps and Zilhão, 2018 ). Nonetheless, most studies concerned with taphonomic processes have addressed the vertical dimension of conjoining sets and their stratigraphic implications, while the horizontal dimension has received less attention in archaeological (e.g. Austin et al. 1999 ; Pope 2002 ; Ashton et al. 2005 ; Sisk and Shea 2008 ; Santamaría et al. 2010 ; de la Torre et al. 2014 ; Deschamps and Zilhão, 2018 ) and experimental (e.g. Schick 1984 ) assemblages. This paper aims to contribute to the literature by exploring spatial dynamics of experimental knapping episodes and conclusions that can be drawn from the orientation patterns of refits. The baseline distribution for artefact and refit orientations is often assumed to be random, with the assumption that any variation is the product of natural processes. While that is certainly the case for the orientation of the long axes of items (Toots 1965 ; Nagle 1967 ; Wendt 1995 ), and it is not realistic to envisage undisturbed assemblages where artefact and bone axes are preferentially oriented (de la Torre and Benito-Calvo 2013 ), there is no evidence to suggest this random patterning is inherent to other variables such as refit lines. To address these issues, our work includes the study of refit orientation patterns and the spatial analysis of four knapping experiments on quartzite from Olduvai Gorge in Tanzania. The goal of these experiments was to recreate core-and-flake assemblages through freehand and bipolar knapping techniques. Our analysis involves refitting of all experimental sequences, digital mapping of the artefact distribution, spatial analysis of artefact clusters and analysis of the refit orientation patterns. Through this, the study aims to elucidate clustering patterns of experimental lithic scatters, and reflect on the validity of orientation data of refit sets for spatial analysis in Palaeolithic assemblages. Materials and methods This paper involves the study of four knapping experiments (named Exp. 18, Exp. 40, Exp. 54 and Exp. 56) with quartzite (sensu Hay 1976 ) sourced from the Naibor Soit hills at Olduvai Gorge, Tanzania, from a repository within the Lithics Laboratory at the Institute of Archaeology, University College London. The aim of these four experiments was to produce as many flakes from individual block blanks using simple freehand and bipolar knapping techniques. Knapping All experiments were performed by one of us (TP), a right-handed knapper with 9 years of knapping experience, over a 2 × 2 m square cloth laid on top of a tile floor in an enclosed outdoor space. Two of the experiments (Exp. 18 and 40) were conducted using freehand knapping, in which the core was held in the left hand and struck with the hammerstone in the right hand. Exp. 18 was performed standing with feet 80 cm apart, and in Exp. 40 the knapper was kneeling (Fig. 1 ). Both cores were rotated and flipped whenever angles on a plane became too obtuse, but platforms were not prepared. Knapping continued until the core lost suitable flaking angles. Obtained flakes were dropped from the height of the hand. Exhausted cores were placed on the floor below their knapping position. Fig. 1 Experimental refit sets studied in this paper. a , b Exp. 18, freehand standing. c , d Exp. 40, freehand kneeling. e – h Exp. 54 ( e , f ) and Exp. 56 ( g , h ), bipolar kneeling Full size image The other two experiments (Exp. 54 and 56) involved bipolar knapping (Fig. 1 ). The cores were placed on top of the anvil and stabilised with the left hand, while the right hand struck with the hammerstone at a 90° angle to the platform. Both experiments were performed kneeling to reach the anvil, and once exhausted, cores were left in their flaking position on the anvil. Mapping", "role": "user" }, { "content": "Alfonso Benito Calvo, a geologist at the Centro Nacional de Investigación sobre la Evolución Humana (CENIEH) has participated in a paper published recently in the journal Archaeological and Anthropological Sciences, which reproduced the knapping process observed at Olduvai (Tanzania), using one of the most abundant raw materials at those sites, quartzite rocks. This was experimental work on which members from the CENIEH, University College London, Max Planck Institute and from the Universidad Autónoma de Barcelona have collaborated, based on studying the spatial patterns of the refits, that is to say, the assembly or matching of the lithic material to reconstruct the original geometry prior to knapping. First, the quartzite rocks were knapped, and then the position and orientation of each resulting fragment were plotted exhaustively, yielding detailed maps showing the distribution of the materials. \"Starting from these maps, we have carried out a spatial analysis of the layout of the fragments and their refits, using GIS applications, designed for specialist analysis of spatial databases,\" explains Benito. The results obtained have shown very different spatial patterns characteristic of each knapping technique: bipolar or freehand. Comparison of these theoretical experimental patterns with the distribution found in the sites will allow the amount of post-depositional disturbance suffered by the sites to be quantified, and thus further investigation of the processes which have affected them. Credit: CENIEH ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Freehand and bipolar experimental knapping of quartzite from Olduvai Gorge in Tanzania is used to conduct spatial analysis of artefact distributions using GIS techniques, and to investigate the orientation of refit lines using circular histograms. The aim of our study is to discern patterns that can be applied to the archaeological record in two domains, namely the identification of knapping episodes and the utility of refitting line orientations in addressing post-depositional disturbance. Our spatial analysis shows that distinctive clustering patterns can be discerned according to knapping stance, handedness and flaking technique. The circular dispersion of refit lines in the horizontal distribution of bipolar assemblages is strongly patterned, indicating that anisotropy of conjoining sets is inherent to pristine hammer-and-anvil knapping episodes. Working on a manuscript? Avoid the common mistakes Introduction The study of spatial distributions in experimental lithic scatters covers a range of topics, including knapper handedness (Bargalló et al. 2017 ), knapper stance (Newcomer and de Sieveking, 1980 ; Barton and Bergman 1982 ; Schick 1984 ; Fischer 1990 ; Kvamme 1997 ), reduction strategy and raw material (Kvamme 1997 ), hammer type (Newcomer and de Sieveking, 1980 ; Kvamme 1997 ) and post-depositional processes (Bowers et al. 1983 ; Gifford-González et al. 1985 ; Schick 1984 ; Nielsen 1991 ; Texier et al. 1998 ; Lenoble et al. 2008 ; Bertran et al. 2015 ; Driscoll et al. 2016 ). These studies have produced relevant observations on the spatial distribution of experimental scatters, but quantitative results based on systematic GIS analyses are yet to be done. Such lack of quantification in experimental assemblages applies both to density patterns and the refitting of the lithic sets produced. Analysis of orientation patterns in archaeology is traditionally linked to the study of post-depositional processes (e.g. Isaac 1967 ; Schick 1984 ; Kreutzer 1988 ; Pope 2002 ; Lenoble and Bertran 2004 ; Boschian and Saccà, 2010 ; Benito-Calvo and de la Torre 2011 ; Benito-Calvo et al. 2009 , 2011 ; Sánchez-Romero et al. 2016 ; de la Torre and Wehr 2018 ; McPherron 2018 ), and refitting is widely recognised as a powerful tool to disentangle site formation (e.g. Cahen 1980 ; Villa 1982 , 2004 ; Hofman 1986 ; Bordes 2003 ; Deschamps and Zilhão, 2018 ). Nonetheless, most studies concerned with taphonomic processes have addressed the vertical dimension of conjoining sets and their stratigraphic implications, while the horizontal dimension has received less attention in archaeological (e.g. Austin et al. 1999 ; Pope 2002 ; Ashton et al. 2005 ; Sisk and Shea 2008 ; Santamaría et al. 2010 ; de la Torre et al. 2014 ; Deschamps and Zilhão, 2018 ) and experimental (e.g. Schick 1984 ) assemblages. This paper aims to contribute to the literature by exploring spatial dynamics of experimental knapping episodes and conclusions that can be drawn from the orientation patterns of refits. The baseline distribution for artefact and refit orientations is often assumed to be random, with the assumption that any variation is the product of natural processes. While that is certainly the case for the orientation of the long axes of items (Toots 1965 ; Nagle 1967 ; Wendt 1995 ), and it is not realistic to envisage undisturbed assemblages where artefact and bone axes are preferentially oriented (de la Torre and Benito-Calvo 2013 ), there is no evidence to suggest this random patterning is inherent to other variables such as refit lines. To address these issues, our work includes the study of refit orientation patterns and the spatial analysis of four knapping experiments on quartzite from Olduvai Gorge in Tanzania. The goal of these experiments was to recreate core-and-flake assemblages through freehand and bipolar knapping techniques. Our analysis involves refitting of all experimental sequences, digital mapping of the artefact distribution, spatial analysis of artefact clusters and analysis of the refit orientation patterns. Through this, the study aims to elucidate clustering patterns of experimental lithic scatters, and reflect on the validity of orientation data of refit sets for spatial analysis in Palaeolithic assemblages. Materials and methods This paper involves the study of four knapping experiments (named Exp. 18, Exp. 40, Exp. 54 and Exp. 56) with quartzite (sensu Hay 1976 ) sourced from the Naibor Soit hills at Olduvai Gorge, Tanzania, from a repository within the Lithics Laboratory at the Institute of Archaeology, University College London. The aim of these four experiments was to produce as many flakes from individual block blanks using simple freehand and bipolar knapping techniques. Knapping All experiments were performed by one of us (TP), a right-handed knapper with 9 years of knapping experience, over a 2 × 2 m square cloth laid on top of a tile floor in an enclosed outdoor space. Two of the experiments (Exp. 18 and 40) were conducted using freehand knapping, in which the core was held in the left hand and struck with the hammerstone in the right hand. Exp. 18 was performed standing with feet 80 cm apart, and in Exp. 40 the knapper was kneeling (Fig. 1 ). Both cores were rotated and flipped whenever angles on a plane became too obtuse, but platforms were not prepared. Knapping continued until the core lost suitable flaking angles. Obtained flakes were dropped from the height of the hand. Exhausted cores were placed on the floor below their knapping position. Fig. 1 Experimental refit sets studied in this paper. a , b Exp. 18, freehand standing. c , d Exp. 40, freehand kneeling. e – h Exp. 54 ( e , f ) and Exp. 56 ( g , h ), bipolar kneeling Full size image The other two experiments (Exp. 54 and 56) involved bipolar knapping (Fig. 1 ). The cores were placed on top of the anvil and stabilised with the left hand, while the right hand struck with the hammerstone at a 90° angle to the platform. Both experiments were performed kneeling to reach the anvil, and once exhausted, cores were left in their flaking position on the anvil. Mapping<|im_end|> <|im_start|>assistant Alfonso Benito Calvo, a geologist at the Centro Nacional de Investigación sobre la Evolución Humana (CENIEH) has participated in a paper published recently in the journal Archaeological and Anthropological Sciences, which reproduced the knapping process observed at Olduvai (Tanzania), using one of the most abundant raw materials at those sites, quartzite rocks. This was experimental work on which members from the CENIEH, University College London, Max Planck Institute and from the Universidad Autónoma de Barcelona have collaborated, based on studying the spatial patterns of the refits, that is to say, the assembly or matching of the lithic material to reconstruct the original geometry prior to knapping. First, the quartzite rocks were knapped, and then the position and orientation of each resulting fragment were plotted exhaustively, yielding detailed maps showing the distribution of the materials. "Starting from these maps, we have carried out a spatial analysis of the layout of the fragments and their refits, using GIS applications, designed for specialist analysis of spatial databases," explains Benito. The results obtained have shown very different spatial patterns characteristic of each knapping technique: bipolar or freehand. Comparison of these theoretical experimental patterns with the distribution found in the sites will allow the amount of post-depositional disturbance suffered by the sites to be quantified, and thus further investigation of the processes which have affected them. Credit: CENIEH <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 3658, 10888, 323, 65919, 22772, 1168, 3713, 315, 52255, 635, 505, 10846, 12328, 2192, 480, 6809, 304, 69894, 374, 1511, 311, 6929, 29079, 6492, 315, 52448, 34210, 43785, 1701, 83471, 12823, 11, 323, 311, 19874, 279, 17140, 315, 2098, 275, 5238, 1701, 28029, 86745, 13, 578, 9395, 315, 1057, 4007, 374, 311, 42645, 12912, 430, 649, 387, 9435, 311, 279, 69637, 3335, 304, 1403, 31576, 11, 32125, 279, 22654, 315, 1168, 3713, 18243, 323, 279, 15919, 315, 2098, 15154, 1584, 89935, 304, 28118, 1772, 6953, 981, 3079, 65858, 13, 5751, 29079, 6492, 5039, 430, 35947, 59454, 12912, 649, 387, 42645, 291, 4184, 311, 1168, 3713, 30031, 11, 23415, 2136, 323, 1344, 1802, 15105, 13, 578, 28029, 86712, 315, 2098, 275, 5238, 304, 279, 16600, 8141, 315, 65919, 439, 28111, 1154, 374, 16917, 5497, 291, 11, 19392, 430, 459, 285, 354, 18237, 315, 390, 66305, 7437, 374, 38088, 311, 66085, 24354, 9976, 19415, 46352, 1168, 3713, 18243, 13, 22938, 389, 264, 47913, 30, 35106, 279, 4279, 21294, 29438, 578, 4007, 315, 29079, 43785, 304, 22772, 46282, 292, 1156, 10385, 14861, 264, 2134, 315, 13650, 11, 2737, 1168, 3183, 23415, 2136, 320, 33, 867, 543, 1832, 1880, 453, 13, 220, 679, 22, 7026, 1168, 3183, 30031, 320, 3648, 884, 261, 323, 409, 8663, 588, 10789, 11, 220, 3753, 15, 2652, 70317, 323, 31782, 1543, 220, 3753, 17, 2652, 5124, 875, 220, 3753, 19, 2652, 63016, 220, 2550, 15, 2652, 89421, 309, 2727, 220, 2550, 22, 7026, 14278, 8446, 323, 7257, 3769, 320, 42, 85, 309, 2727, 220, 2550, 22, 7026, 24354, 955, 320, 3648, 884, 261, 323, 409, 8663, 588, 10789, 11, 220, 3753, 15, 2652, 89421, 309, 2727, 220, 2550, 22, 883, 323, 1772, 6953, 981, 3079, 11618, 320, 33, 16345, 1880, 453, 13, 220, 3753, 18, 2652, 480, 3168, 541, 12279, 28143, 97465, 1880, 453, 13, 220, 3753, 20, 2652, 5124, 875, 220, 3753, 19, 2652, 64551, 220, 2550, 16, 2652, 32568, 1291, 1880, 453, 13, 220, 2550, 23, 2652, 25234, 51093, 1880, 453, 13, 220, 1049, 23, 2652, 9084, 44469, 1880, 453, 13, 220, 679, 20, 2652, 2999, 3510, 980, 1880, 453, 13, 220, 679, 21, 7609, 4314, 7978, 617, 9124, 9959, 24654, 389, 279, 29079, 8141, 315, 22772, 1156, 10385, 11, 719, 47616, 3135, 3196, 389, 37538, 83471, 29060, 527, 3686, 311, 387, 2884, 13, 15483, 6996, 315, 10484, 2461, 304, 22772, 439, 28111, 1154, 17208, 2225, 311, 17915, 12912, 323, 279, 2098, 15154, 315, 279, 46282, 292, 7437, 9124, 13, 18825, 315, 17140, 12912, 304, 39211, 2508, 374, 36342, 10815, 311, 279, 4007, 315, 1772, 6953, 981, 3079, 11618, 320, 68, 1326, 13, 42608, 220, 5162, 22, 2652, 5124, 875, 220, 3753, 19, 2652, 30718, 60622, 220, 3753, 23, 2652, 30460, 220, 1049, 17, 2652, 25234, 51093, 323, 9084, 44469, 220, 1049, 19, 2652, 72325, 1122, 323, 328, 4575, 6496, 11, 220, 679, 15, 2652, 7505, 6491, 76450, 3415, 323, 409, 1208, 8611, 265, 220, 679, 16, 2652, 7505, 6491, 76450, 3415, 1880, 453, 13, 220, 1049, 24, 1174, 220, 679, 16, 2652, 328, 99634, 11151, 316, 2382, 1880, 453, 13, 220, 679, 21, 2652, 409, 1208, 8611, 265, 323, 1226, 4171, 220, 679, 23, 2652, 4584, 3438, 618, 263, 220, 679, 23, 7026, 323, 2098, 15154, 374, 13882, 39764, 439, 264, 8147, 5507, 311, 834, 306, 4134, 2816, 18488, 320, 68, 1326, 13, 96110, 268, 220, 3753, 15, 2652, 37912, 220, 3753, 17, 1174, 220, 1049, 19, 2652, 72812, 1543, 220, 3753, 21, 2652, 426, 81492, 220, 1049, 18, 2652, 3959, 331, 14989, 323, 1901, 321, 71, 3496, 11, 220, 679, 23, 7609, 56733, 11, 1455, 7978, 11920, 449, 259, 1366, 48228, 11618, 617, 20669, 279, 12414, 13167, 315, 390, 66305, 7437, 323, 872, 44397, 54967, 292, 25127, 11, 1418, 279, 16600, 13167, 706, 4036, 2753, 6666, 304, 69637, 320, 68, 1326, 13, 19816, 1880, 453, 13, 220, 2550, 24, 2652, 30460, 220, 1049, 17, 2652, 87718, 1880, 453, 13, 220, 1049, 20, 2652, 328, 3267, 323, 86068, 220, 1049, 23, 2652, 23746, 15924, 7583, 1880, 453, 13, 220, 679, 15, 2652, 409, 1208, 8611, 265, 1880, 453, 13, 220, 679, 19, 2652, 3959, 331, 14989, 323, 1901, 321, 71, 3496, 11, 220, 679, 23, 883, 323, 22772, 320, 68, 1326, 13, 5124, 875, 220, 3753, 19, 883, 439, 28111, 1154, 13, 1115, 5684, 22262, 311, 17210, 311, 279, 17649, 555, 24919, 29079, 30295, 315, 22772, 1168, 3713, 18243, 323, 31342, 430, 649, 387, 15107, 505, 279, 17140, 12912, 315, 2098, 1220, 13, 578, 26954, 8141, 369, 52448, 34210, 323, 2098, 275, 89935, 374, 3629, 19655, 311, 387, 4288, 11, 449, 279, 25329, 430, 904, 23851, 374, 279, 2027, 315, 5933, 11618, 13, 6104, 430, 374, 7995, 279, 1162, 369, 279, 17140, 315, 279, 1317, 25776, 315, 3673, 320, 1271, 2469, 220, 5162, 20, 2652, 30162, 273, 220, 5162, 22, 2652, 42368, 83, 220, 2550, 20, 7026, 323, 433, 374, 539, 26569, 311, 85775, 425, 2073, 380, 75325, 439, 28111, 1154, 1405, 52448, 34210, 323, 17685, 25776, 527, 10932, 31668, 42208, 320, 451, 1208, 8611, 265, 323, 7505, 6491, 76450, 3415, 220, 679, 18, 7026, 1070, 374, 912, 6029, 311, 4284, 420, 4288, 93093, 1251, 374, 38088, 311, 1023, 7482, 1778, 439, 2098, 275, 5238, 13, 2057, 2686, 1521, 4819, 11, 1057, 990, 5764, 279, 4007, 315, 2098, 275, 17140, 12912, 323, 279, 29079, 6492, 315, 3116, 1168, 3713, 21896, 389, 52255, 635, 505, 10846, 12328, 2192, 480, 6809, 304, 69894, 13, 578, 5915, 315, 1521, 21896, 574, 311, 53875, 6332, 9976, 12556, 731, 439, 28111, 1154, 1555, 1949, 10888, 323, 65919, 1168, 3713, 12823, 13, 5751, 6492, 18065, 2098, 15154, 315, 682, 22772, 24630, 11, 7528, 13021, 315, 279, 52448, 34210, 8141, 11, 29079, 6492, 315, 52448, 34210, 28066, 323, 6492, 315, 279, 2098, 275, 17140, 12912, 13, 17331, 420, 11, 279, 4007, 22262, 311, 97298, 349, 59454, 12912, 315, 22772, 46282, 292, 1156, 10385, 11, 323, 8881, 389, 279, 32939, 315, 17140, 828, 315, 2098, 275, 7437, 369, 29079, 6492, 304, 11165, 6043, 66470, 439, 28111, 1154, 13, 32009, 323, 5528, 1115, 5684, 18065, 279, 4007, 315, 3116, 1168, 3713, 21896, 320, 31345, 7943, 13, 220, 972, 11, 7943, 13, 220, 1272, 11, 7943, 13, 220, 4370, 323, 7943, 13, 220, 3487, 8, 449, 52255, 635, 320, 82, 729, 84, 18276, 220, 4468, 21, 883, 42211, 505, 279, 13106, 581, 269, 2100, 275, 35231, 520, 10846, 12328, 2192, 480, 6809, 11, 69894, 11, 505, 264, 12827, 2949, 279, 41678, 1233, 32184, 520, 279, 10181, 315, 66102, 2508, 11, 3907, 9304, 7295, 13, 578, 9395, 315, 1521, 3116, 21896, 574, 311, 8356, 439, 1690, 82723, 505, 3927, 2565, 79640, 1701, 4382, 1949, 10888, 323, 65919, 1168, 3713, 12823, 13, 13934, 3713, 2052, 21896, 1051, 10887, 555, 832, 315, 603, 320, 4334, 705, 264, 1314, 37240, 1168, 3183, 449, 220, 24, 1667, 315, 1168, 3713, 3217, 11, 927, 264, 220, 17, 25800, 220, 17, 296, 9518, 28392, 17551, 389, 1948, 315, 264, 10228, 6558, 304, 459, 44910, 16166, 3634, 13, 9220, 315, 279, 21896, 320, 8193, 13, 220, 972, 323, 220, 1272, 8, 1051, 13375, 1701, 1949, 10888, 1168, 3713, 11, 304, 902, 279, 6332, 574, 5762, 304, 279, 2163, 1450, 323, 17948, 449, 279, 24354, 11046, 304, 279, 1314, 1450, 13, 7943, 13, 220, 972, 574, 10887, 11509, 449, 7693, 220, 1490, 10166, 10980, 11, 323, 304, 7943, 13, 220, 1272, 279, 1168, 3183, 574, 100115, 320, 30035, 13, 220, 16, 7609, 11995, 36804, 1051, 46720, 323, 47180, 15716, 27030, 389, 264, 11277, 6244, 2288, 4615, 817, 11, 719, 15771, 1051, 539, 10235, 13, 13934, 3713, 8738, 3156, 279, 6332, 5675, 14791, 1344, 1802, 27030, 13, 57747, 2692, 82723, 1051, 12504, 505, 279, 2673, 315, 279, 1450, 13, 89334, 291, 36804, 1051, 9277, 389, 279, 6558, 3770, 872, 1168, 3713, 2361, 13, 23966, 13, 220, 16, 57708, 2098, 275, 7437, 20041, 304, 420, 5684, 13, 264, 1174, 293, 7943, 13, 220, 972, 11, 1949, 10888, 11509, 13, 272, 1174, 294, 7943, 13, 220, 1272, 11, 1949, 10888, 100115, 13, 384, 1389, 305, 7943, 13, 220, 4370, 320, 384, 1174, 282, 883, 323, 7943, 13, 220, 3487, 320, 342, 1174, 305, 7026, 65919, 100115, 8797, 1404, 2217, 578, 1023, 1403, 21896, 320, 8193, 13, 220, 4370, 323, 220, 3487, 8, 6532, 65919, 1168, 3713, 320, 30035, 13, 220, 16, 7609, 578, 36804, 1051, 9277, 389, 1948, 315, 279, 459, 46352, 323, 27276, 4147, 449, 279, 2163, 1450, 11, 1418, 279, 1314, 1450, 17948, 449, 279, 24354, 11046, 520, 264, 220, 1954, 11877, 9392, 311, 279, 5452, 13, 11995, 21896, 1051, 10887, 100115, 311, 5662, 279, 459, 46352, 11, 323, 3131, 39019, 11, 36804, 1051, 2163, 304, 872, 1344, 1802, 2361, 389, 279, 459, 46352, 13, 39546, 128257, 198, 128256, 78191, 198, 2149, 22188, 708, 7505, 6491, 3400, 3415, 11, 264, 3980, 16549, 520, 279, 57674, 45689, 409, 33180, 5840, 15482, 1208, 10641, 78176, 20449, 3444, 320, 34, 965, 5484, 39, 8, 706, 31408, 304, 264, 5684, 4756, 6051, 304, 279, 8486, 66102, 5848, 323, 70384, 5848, 23199, 11, 902, 55717, 279, 1168, 3713, 1920, 13468, 520, 10846, 12328, 2192, 320, 51, 12341, 9345, 705, 1701, 832, 315, 279, 1455, 44611, 7257, 7384, 520, 1884, 6732, 11, 52255, 635, 23902, 13, 1115, 574, 22772, 990, 389, 902, 3697, 505, 279, 356, 965, 5484, 39, 11, 3907, 9304, 7295, 11, 7639, 9878, 377, 10181, 323, 505, 279, 67613, 9648, 3244, 7942, 409, 28035, 617, 78174, 11, 3196, 389, 21630, 279, 29079, 12912, 315, 279, 2098, 1220, 11, 430, 374, 311, 2019, 11, 279, 14956, 477, 12864, 315, 279, 46282, 292, 3769, 311, 44928, 279, 4113, 17484, 4972, 311, 1168, 3713, 13, 5629, 11, 279, 52255, 635, 23902, 1051, 1168, 5795, 11, 323, 1243, 279, 2361, 323, 17140, 315, 1855, 13239, 12569, 1051, 68683, 17960, 3210, 11, 78504, 11944, 14370, 9204, 279, 8141, 315, 279, 7384, 13, 330, 25639, 505, 1521, 14370, 11, 584, 617, 11953, 704, 264, 29079, 6492, 315, 279, 6932, 315, 279, 35603, 323, 872, 2098, 1220, 11, 1701, 83471, 8522, 11, 6319, 369, 24687, 6492, 315, 29079, 32906, 1359, 15100, 7505, 6491, 13, 578, 3135, 12457, 617, 6982, 1633, 2204, 29079, 12912, 29683, 315, 1855, 1168, 3713, 15105, 25, 65919, 477, 1949, 10888, 13, 43551, 315, 1521, 32887, 22772, 12912, 449, 279, 8141, 1766, 304, 279, 6732, 690, 2187, 279, 3392, 315, 1772, 6953, 981, 3079, 65858, 16654, 555, 279, 6732, 311, 387, 10484, 1908, 11, 323, 8617, 4726, 8990, 315, 279, 11618, 902, 617, 11754, 1124, 13, 16666, 25, 356, 965, 5484, 39, 220, 128257, 198 ]

1,786

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Digital image sensors in hemispherical geometries offer unique imaging advantages over their planar counterparts, such as wide field of view and low aberrations. Deforming miniature semiconductor-based sensors with high-spatial resolution into such format is challenging. Here we report a simple origami approach for fabricating single-crystalline silicon-based focal plane arrays and artificial compound eyes that have hemisphere-like structures. Convex isogonal polyhedral concepts allow certain combinations of polygons to fold into spherical formats. Using each polygon block as a sensor pixel, the silicon-based devices are shaped into maps of truncated icosahedron and fabricated on flexible sheets and further folded either into a concave or convex hemisphere. These two electronic eye prototypes represent simple and low-cost methods as well as flexible optimization parameters in terms of pixel density and design. Results demonstrated in this work combined with miniature size and simplicity of the design establish practical technology for integration with conventional electronic devices. Introduction Biological eyes are highly sophisticated and remarkably designed vision organs that have inspired biomimicry for several centuries. From lobster eye-inspired radiant heaters to moth eye-inspired anti-reflective coatings, human challenges have been solved by nature’s advice in a wide variety of applications 1 , 2 . Also, the camera, which is undoubtedly the most revolutionary invention of mankind inspired by the eye, has immensely comforted, amused, and protected human lives. Today, technological advances have improved the quality of cameras with superior resolution, long focal lengths, and smart functionalities that are implemented in almost every consumer electronics system. In addition to these evolutions, reshaping conventional planar sensor systems into hemispherical formats would empower visual recordings with features that are beyond what state-of-the-art cameras can see, such as infinite depth of field, wider view angle, and lower aberrations 3 . Studying various eye systems in biology, most eyes have photoreceptors that capture and transduce photons into electrochemical signals laid either in concave or convex curvature. The concave array is mostly found in mammals as a camera or pin-hole type while the convex array is found in insects as a compound type. The camera or pin-hole eye has an outstanding quality of vision as it focuses light into an array of photoreceptors laid in a hemispherical concave structure (i.e., retina), allowing for clear identification of objects. The retina adopts the curvilinear shape that approximates the focal plane of the lens such that human eyes have large view fields and supreme focusing capabilities 4 . The compound eye has a wider-angle field of view via hundreds to thousands of ommatidia that are densely arrayed in a hemispherical convex structure for the sensitive detection of moving objects 5 . As such, biomimicry using semiconductor sensor systems structured in hemispherical formats would extend the capabilities of camera systems by utilizing the marvelous features of biological eyes. Although numerous types of artificial eyes have been presented in the past, the inspired systems lacked the essential photo-detecting unit 6 , 7 , 8 , 9 . To take advantage of mimicking biological eyes in electronic imaging systems, photodetectors must essentially be represented in either hemispherical concave or convex formats rather than in the planar format typically found in conventional camera systems. Fabricating devices on non-planar surfaces, however, can be a major challenge because conventional fabrication techniques were developed for planar wafers or plate materials in the semiconductor industry. The simplest approach to deforming sensors was to mount optoelectronic components on a flexible printed-circuit board (FPCB), but this could only achieve hemicylindrical photodetector array designs 10 . Specialized techniques to apply stress on and bend ordinary planar silicon wafer-based CMOS image sensors have been introduced as well, which have been successful in inducing minor curvatures 11 , 12 . The available techniques for direct fabrication on non-planar surfaces, such as soft lithography, mechanical molding, and lens-assisted lithography, are consequently complicated and expensive, and have very specific requirements. Encouraged by the promising prosperity in non-planar devices, novel strategies have been investigated to circumvent the limits set by non-planar surfaces while utilizing mature semiconductor fabrication techniques for economic consideration. For instance, transfer printing of ultrathin semiconductor nanomembranes onto rubber- or plastic-like substrates transformed the shape of high-performance electronics and optoelectronics into flexible and stretchable formats 13 , 14 , 15 , 16 , 17 , 18 . These unusual semiconductor devices on complex curvilinear surfaces are versatile in various areas due to their new degree of design freedom and biomimicry merits, including the hemispherical photodetector array 19 , 20 , 21 , 22 , 23 . Successful integration of stretchable photodetectors with camera systems has demonstrated concave and convex curvilinear photodetector arrays for the hemispherical electronic eye camera that mimicked the human eye 21 and compound electronic eye camera that mimicked the arthropod eye 22 . In both designs, a large array of thin silicon photodiodes separated by serpentine traces of metal for electrical interconnects were originally fabricated on a planar host substrate and transfer-printed onto rubber substrates. Upon hydraulic actuation, the array on rubber deformed and stretched into either a concave or convex structure, where the geometry of the serpentine wire tortuosity deterministically transformed the layout without electrical or mechanical failure. Both concave and convex camera systems that used silicon optoelectronics were groundbreaking toward camera evolution, but the requirement of hydraulic actuators may be bulky in many miniaturized camera systems for consumer devices. Also, the large separation distance between photodetector pixels reserved for electrical traces that are in the micrometer range may pose limitations in resolution optimization. An approach that is both compatible with commercially available imaging systems and has flexible optimization parameters is desirable for such hemispherical photodetector arrays to become more practical. Here, we present a unique origami-inspired approach, combined with semiconductor nanomembrane-based flexible electronics technology, to build dense, scalable, and compact hemispherical photodetector arrays. Originated as an art of paper folding, origami and kirigami were recently utilized to assemble three-dimensional structures with micro/nanomembrane materials to allow an increasingly wide range of applications 24 , 25 , 26 , 27 , 28 . Precut membranes have been", "role": "user" }, { "content": "These days, we increasingly rely on our cell phone cameras to capture virtually every aspect of our lives. Far too often, however, we end up with photos that are a sub-par reproduction of reality. And while operator error sometimes comes into play, most likely, the camera's digital image sensor is the real culprit. A flat silicon surface, it just can't process images captured by a curved camera lens as well as the similarly curved image sensors—otherwise known as the retinas—in human eyes. In a breakthrough that could, for example, lead to cameras with beyond-the-state-of-the-art features such as infinite depth of field, wider view angle, low aberrations, and vastly increased pixel density, flexible optoelectronics pioneer Zhenqiang (Jack) Ma has devised a method for making curved digital image sensors in shapes that mimic an insect's compound eye (convex) and a mammal's \"pin-hole\" eye (concave). The Lynn H. Matthias and Vilas Distinguished Achievement Professor of electrical and computer engineering at the University of Wisconsin-Madison, Ma, his students and collaborators described the technique in the Nov. 24, 2017, issue of the journal Nature Communications. Curved image sensors do exist. Yet even though they outperform their flat counterparts, they haven't made it into the mainstream—in part, because of the challenges inherent in a manufacturing method that involves pressing a flat, rigid piece of silicon into a hemispherical shape without wrinkling it, breaking it or otherwise degrading its quality. A concave version of the digital image sensor bends inward for creating a hemispherical focal plane array. Credit: Yei Hwan Jung and Kan Zhang Ma's technique was inspired by traditional Japanese origami, or the art of paper-folding. To create the curved photodetector, he and his students formed pixels by mapping repeating geometric shapes—somewhat like a soccer ball—onto a thin, flat flexible sheet of silicon called a nanomembrane, which sits on a flexible substrate. Then, they used a laser to cut away some of those pixels so that the remaining silicon formed perfect seams, with no gaps, when they placed it atop a dome shape (for a the convex detector) or into a bowl shape (for a concave detector). \"We can first divide it into a hexagon and pentagon structure—and each of those can be further divided,\" says Ma. \"You can forever divide them, in theory, so that means the pixels can be really, really dense, and there are no empty areas. This is really scalable, and we can bend it into whatever shape we want.\" A convex version of the digital image sensor bends like a soccer ball for mimicking an insect’s compound eye. Credit: Yei Hwan Jung and Kan Zhang That pixel density is a boon for photographers, as a camera's ability to take high-resolution photos is determined, in megapixels, by the amount of information its sensor can capture. Currently, the researchers' prototype is approximately 7 millimeters, or roughly a quarter-inch, in diameter. That's still a bit bulky for your cell phone, but Ma says he can make the sensor even smaller. \"This membrane is a very big advance in imaging,\" he says. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Digital image sensors in hemispherical geometries offer unique imaging advantages over their planar counterparts, such as wide field of view and low aberrations. Deforming miniature semiconductor-based sensors with high-spatial resolution into such format is challenging. Here we report a simple origami approach for fabricating single-crystalline silicon-based focal plane arrays and artificial compound eyes that have hemisphere-like structures. Convex isogonal polyhedral concepts allow certain combinations of polygons to fold into spherical formats. Using each polygon block as a sensor pixel, the silicon-based devices are shaped into maps of truncated icosahedron and fabricated on flexible sheets and further folded either into a concave or convex hemisphere. These two electronic eye prototypes represent simple and low-cost methods as well as flexible optimization parameters in terms of pixel density and design. Results demonstrated in this work combined with miniature size and simplicity of the design establish practical technology for integration with conventional electronic devices. Introduction Biological eyes are highly sophisticated and remarkably designed vision organs that have inspired biomimicry for several centuries. From lobster eye-inspired radiant heaters to moth eye-inspired anti-reflective coatings, human challenges have been solved by nature’s advice in a wide variety of applications 1 , 2 . Also, the camera, which is undoubtedly the most revolutionary invention of mankind inspired by the eye, has immensely comforted, amused, and protected human lives. Today, technological advances have improved the quality of cameras with superior resolution, long focal lengths, and smart functionalities that are implemented in almost every consumer electronics system. In addition to these evolutions, reshaping conventional planar sensor systems into hemispherical formats would empower visual recordings with features that are beyond what state-of-the-art cameras can see, such as infinite depth of field, wider view angle, and lower aberrations 3 . Studying various eye systems in biology, most eyes have photoreceptors that capture and transduce photons into electrochemical signals laid either in concave or convex curvature. The concave array is mostly found in mammals as a camera or pin-hole type while the convex array is found in insects as a compound type. The camera or pin-hole eye has an outstanding quality of vision as it focuses light into an array of photoreceptors laid in a hemispherical concave structure (i.e., retina), allowing for clear identification of objects. The retina adopts the curvilinear shape that approximates the focal plane of the lens such that human eyes have large view fields and supreme focusing capabilities 4 . The compound eye has a wider-angle field of view via hundreds to thousands of ommatidia that are densely arrayed in a hemispherical convex structure for the sensitive detection of moving objects 5 . As such, biomimicry using semiconductor sensor systems structured in hemispherical formats would extend the capabilities of camera systems by utilizing the marvelous features of biological eyes. Although numerous types of artificial eyes have been presented in the past, the inspired systems lacked the essential photo-detecting unit 6 , 7 , 8 , 9 . To take advantage of mimicking biological eyes in electronic imaging systems, photodetectors must essentially be represented in either hemispherical concave or convex formats rather than in the planar format typically found in conventional camera systems. Fabricating devices on non-planar surfaces, however, can be a major challenge because conventional fabrication techniques were developed for planar wafers or plate materials in the semiconductor industry. The simplest approach to deforming sensors was to mount optoelectronic components on a flexible printed-circuit board (FPCB), but this could only achieve hemicylindrical photodetector array designs 10 . Specialized techniques to apply stress on and bend ordinary planar silicon wafer-based CMOS image sensors have been introduced as well, which have been successful in inducing minor curvatures 11 , 12 . The available techniques for direct fabrication on non-planar surfaces, such as soft lithography, mechanical molding, and lens-assisted lithography, are consequently complicated and expensive, and have very specific requirements. Encouraged by the promising prosperity in non-planar devices, novel strategies have been investigated to circumvent the limits set by non-planar surfaces while utilizing mature semiconductor fabrication techniques for economic consideration. For instance, transfer printing of ultrathin semiconductor nanomembranes onto rubber- or plastic-like substrates transformed the shape of high-performance electronics and optoelectronics into flexible and stretchable formats 13 , 14 , 15 , 16 , 17 , 18 . These unusual semiconductor devices on complex curvilinear surfaces are versatile in various areas due to their new degree of design freedom and biomimicry merits, including the hemispherical photodetector array 19 , 20 , 21 , 22 , 23 . Successful integration of stretchable photodetectors with camera systems has demonstrated concave and convex curvilinear photodetector arrays for the hemispherical electronic eye camera that mimicked the human eye 21 and compound electronic eye camera that mimicked the arthropod eye 22 . In both designs, a large array of thin silicon photodiodes separated by serpentine traces of metal for electrical interconnects were originally fabricated on a planar host substrate and transfer-printed onto rubber substrates. Upon hydraulic actuation, the array on rubber deformed and stretched into either a concave or convex structure, where the geometry of the serpentine wire tortuosity deterministically transformed the layout without electrical or mechanical failure. Both concave and convex camera systems that used silicon optoelectronics were groundbreaking toward camera evolution, but the requirement of hydraulic actuators may be bulky in many miniaturized camera systems for consumer devices. Also, the large separation distance between photodetector pixels reserved for electrical traces that are in the micrometer range may pose limitations in resolution optimization. An approach that is both compatible with commercially available imaging systems and has flexible optimization parameters is desirable for such hemispherical photodetector arrays to become more practical. Here, we present a unique origami-inspired approach, combined with semiconductor nanomembrane-based flexible electronics technology, to build dense, scalable, and compact hemispherical photodetector arrays. Originated as an art of paper folding, origami and kirigami were recently utilized to assemble three-dimensional structures with micro/nanomembrane materials to allow an increasingly wide range of applications 24 , 25 , 26 , 27 , 28 . Precut membranes have been<|im_end|> <|im_start|>assistant These days, we increasingly rely on our cell phone cameras to capture virtually every aspect of our lives. Far too often, however, we end up with photos that are a sub-par reproduction of reality. And while operator error sometimes comes into play, most likely, the camera's digital image sensor is the real culprit. A flat silicon surface, it just can't process images captured by a curved camera lens as well as the similarly curved image sensors—otherwise known as the retinas—in human eyes. In a breakthrough that could, for example, lead to cameras with beyond-the-state-of-the-art features such as infinite depth of field, wider view angle, low aberrations, and vastly increased pixel density, flexible optoelectronics pioneer Zhenqiang (Jack) Ma has devised a method for making curved digital image sensors in shapes that mimic an insect's compound eye (convex) and a mammal's "pin-hole" eye (concave). The Lynn H. Matthias and Vilas Distinguished Achievement Professor of electrical and computer engineering at the University of Wisconsin-Madison, Ma, his students and collaborators described the technique in the Nov. 24, 2017, issue of the journal Nature Communications. Curved image sensors do exist. Yet even though they outperform their flat counterparts, they haven't made it into the mainstream—in part, because of the challenges inherent in a manufacturing method that involves pressing a flat, rigid piece of silicon into a hemispherical shape without wrinkling it, breaking it or otherwise degrading its quality. A concave version of the digital image sensor bends inward for creating a hemispherical focal plane array. Credit: Yei Hwan Jung and Kan Zhang Ma's technique was inspired by traditional Japanese origami, or the art of paper-folding. To create the curved photodetector, he and his students formed pixels by mapping repeating geometric shapes—somewhat like a soccer ball—onto a thin, flat flexible sheet of silicon called a nanomembrane, which sits on a flexible substrate. Then, they used a laser to cut away some of those pixels so that the remaining silicon formed perfect seams, with no gaps, when they placed it atop a dome shape (for a the convex detector) or into a bowl shape (for a concave detector). "We can first divide it into a hexagon and pentagon structure—and each of those can be further divided," says Ma. "You can forever divide them, in theory, so that means the pixels can be really, really dense, and there are no empty areas. This is really scalable, and we can bend it into whatever shape we want." A convex version of the digital image sensor bends like a soccer ball for mimicking an insect’s compound eye. Credit: Yei Hwan Jung and Kan Zhang That pixel density is a boon for photographers, as a camera's ability to take high-resolution photos is determined, in megapixels, by the amount of information its sensor can capture. Currently, the researchers' prototype is approximately 7 millimeters, or roughly a quarter-inch, in diameter. That's still a bit bulky for your cell phone, but Ma says he can make the sensor even smaller. "This membrane is a very big advance in imaging," he says. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 14434, 2217, 26148, 304, 17728, 285, 45845, 69086, 4108, 3085, 5016, 32758, 22934, 927, 872, 3197, 277, 38495, 11, 1778, 439, 7029, 2115, 315, 1684, 323, 3428, 82102, 811, 13, 1611, 55857, 57863, 87836, 6108, 26148, 449, 1579, 1355, 33514, 11175, 1139, 1778, 3645, 374, 17436, 13, 5810, 584, 1934, 264, 4382, 2780, 10830, 5603, 369, 13354, 1113, 3254, 48689, 599, 543, 483, 51692, 6108, 42199, 11277, 18893, 323, 21075, 24549, 6548, 430, 617, 69766, 12970, 14726, 13, 30088, 327, 374, 67071, 10062, 71, 36620, 19476, 2187, 3738, 28559, 315, 69259, 311, 11816, 1139, 65251, 20447, 13, 12362, 1855, 30472, 2565, 439, 264, 12271, 13252, 11, 279, 51692, 6108, 7766, 527, 27367, 1139, 14370, 315, 60856, 220, 17038, 1494, 291, 2298, 323, 70554, 389, 19303, 25112, 323, 4726, 48135, 3060, 1139, 264, 3613, 525, 477, 67030, 69766, 13, 4314, 1403, 14683, 8071, 47728, 4097, 4382, 323, 3428, 41238, 5528, 439, 1664, 439, 19303, 26329, 5137, 304, 3878, 315, 13252, 17915, 323, 2955, 13, 18591, 21091, 304, 420, 990, 11093, 449, 57863, 1404, 323, 40075, 315, 279, 2955, 5813, 15325, 5557, 369, 18052, 449, 21349, 14683, 7766, 13, 29438, 63711, 6548, 527, 7701, 27877, 323, 49723, 6319, 11376, 36853, 430, 617, 14948, 39538, 318, 292, 894, 369, 3892, 24552, 13, 5659, 80815, 8071, 53161, 77443, 82467, 311, 98178, 8071, 53161, 7294, 12, 36013, 535, 92025, 11, 3823, 11774, 617, 1027, 29056, 555, 7138, 753, 9650, 304, 264, 7029, 8205, 315, 8522, 220, 16, 1174, 220, 17, 662, 7429, 11, 279, 6382, 11, 902, 374, 38048, 279, 1455, 30191, 28229, 315, 43384, 14948, 555, 279, 8071, 11, 706, 63689, 6981, 291, 11, 86324, 11, 323, 2682, 3823, 6439, 13, 11450, 11, 30116, 31003, 617, 13241, 279, 4367, 315, 18632, 449, 16757, 11175, 11, 1317, 42199, 29416, 11, 323, 7941, 93180, 430, 527, 11798, 304, 4661, 1475, 11761, 31591, 1887, 13, 763, 5369, 311, 1521, 3721, 20813, 11, 64793, 14550, 21349, 3197, 277, 12271, 6067, 1139, 17728, 285, 45845, 20447, 1053, 26285, 9302, 38140, 449, 4519, 430, 527, 7953, 1148, 1614, 8838, 10826, 38921, 18632, 649, 1518, 11, 1778, 439, 24746, 8149, 315, 2115, 11, 22622, 1684, 9392, 11, 323, 4827, 82102, 811, 220, 18, 662, 7814, 7169, 5370, 8071, 6067, 304, 34458, 11, 1455, 6548, 617, 4604, 461, 58650, 430, 12602, 323, 1380, 13677, 89235, 1139, 25396, 32056, 17738, 17551, 3060, 304, 3613, 525, 477, 67030, 83233, 13, 578, 3613, 525, 1358, 374, 10213, 1766, 304, 56669, 439, 264, 6382, 477, 9160, 87693, 955, 1418, 279, 67030, 1358, 374, 1766, 304, 41911, 439, 264, 24549, 955, 13, 578, 6382, 477, 9160, 87693, 8071, 706, 459, 19310, 4367, 315, 11376, 439, 433, 24400, 3177, 1139, 459, 1358, 315, 4604, 461, 58650, 17551, 304, 264, 17728, 285, 45845, 3613, 525, 6070, 320, 72, 1770, 2637, 84827, 705, 10923, 369, 2867, 22654, 315, 6302, 13, 578, 84827, 87057, 279, 2917, 85, 72033, 6211, 430, 10049, 48571, 279, 42199, 11277, 315, 279, 18848, 1778, 430, 3823, 6548, 617, 3544, 1684, 5151, 323, 44222, 21760, 17357, 220, 19, 662, 578, 24549, 8071, 706, 264, 22622, 35481, 2115, 315, 1684, 4669, 11758, 311, 9214, 315, 297, 3906, 266, 87800, 430, 527, 97617, 1358, 291, 304, 264, 17728, 285, 45845, 67030, 6070, 369, 279, 16614, 18468, 315, 7366, 6302, 220, 20, 662, 1666, 1778, 11, 39538, 318, 292, 894, 1701, 87836, 12271, 6067, 34030, 304, 17728, 285, 45845, 20447, 1053, 13334, 279, 17357, 315, 6382, 6067, 555, 35988, 279, 81292, 4519, 315, 24156, 6548, 13, 10541, 12387, 4595, 315, 21075, 6548, 617, 1027, 10666, 304, 279, 3347, 11, 279, 14948, 6067, 49101, 279, 7718, 6685, 1773, 13478, 287, 5089, 220, 21, 1174, 220, 22, 1174, 220, 23, 1174, 220, 24, 662, 2057, 1935, 9610, 315, 28003, 16671, 24156, 6548, 304, 14683, 32758, 6067, 11, 4604, 347, 295, 10829, 2011, 16168, 387, 15609, 304, 3060, 17728, 285, 45845, 3613, 525, 477, 67030, 20447, 4856, 1109, 304, 279, 3197, 277, 3645, 11383, 1766, 304, 21349, 6382, 6067, 13, 37407, 1113, 7766, 389, 2536, 74081, 277, 27529, 11, 4869, 11, 649, 387, 264, 3682, 8815, 1606, 21349, 59251, 12823, 1051, 8040, 369, 3197, 277, 289, 2642, 388, 477, 12235, 7384, 304, 279, 87836, 5064, 13, 578, 45648, 5603, 311, 409, 55857, 26148, 574, 311, 6606, 3469, 4748, 772, 8535, 6956, 389, 264, 19303, 17124, 1824, 38368, 4580, 320, 37, 4977, 33, 705, 719, 420, 1436, 1193, 11322, 17728, 2912, 75, 63506, 4604, 347, 295, 1279, 1358, 14769, 220, 605, 662, 9984, 1534, 12823, 311, 3881, 8631, 389, 323, 37920, 19664, 3197, 277, 51692, 10667, 809, 6108, 18582, 3204, 2217, 26148, 617, 1027, 11784, 439, 1664, 11, 902, 617, 1027, 6992, 304, 96811, 9099, 2917, 85, 2859, 220, 806, 1174, 220, 717, 662, 578, 2561, 12823, 369, 2167, 59251, 389, 2536, 74081, 277, 27529, 11, 1778, 439, 8579, 46282, 5814, 11, 22936, 66157, 11, 323, 18848, 35915, 13539, 46282, 5814, 11, 527, 52394, 17395, 323, 11646, 11, 323, 617, 1633, 3230, 8670, 13, 10984, 414, 3359, 555, 279, 26455, 44202, 304, 2536, 74081, 277, 7766, 11, 11775, 15174, 617, 1027, 27313, 311, 10408, 688, 279, 13693, 743, 555, 2536, 74081, 277, 27529, 1418, 35988, 15196, 87836, 59251, 12823, 369, 7100, 18361, 13, 1789, 2937, 11, 8481, 18991, 315, 37232, 589, 258, 87836, 20622, 316, 60163, 14997, 8800, 23506, 12, 477, 12466, 12970, 16146, 988, 24411, 279, 6211, 315, 1579, 58574, 31591, 323, 3469, 4748, 772, 28429, 1139, 19303, 323, 14841, 481, 20447, 220, 1032, 1174, 220, 975, 1174, 220, 868, 1174, 220, 845, 1174, 220, 1114, 1174, 220, 972, 662, 4314, 19018, 87836, 7766, 389, 6485, 2917, 85, 72033, 27529, 527, 33045, 304, 5370, 5789, 4245, 311, 872, 502, 8547, 315, 2955, 11542, 323, 39538, 318, 292, 894, 50932, 11, 2737, 279, 17728, 285, 45845, 4604, 347, 295, 1279, 1358, 220, 777, 1174, 220, 508, 1174, 220, 1691, 1174, 220, 1313, 1174, 220, 1419, 662, 46626, 18052, 315, 14841, 481, 4604, 347, 295, 10829, 449, 6382, 6067, 706, 21091, 3613, 525, 323, 67030, 2917, 85, 72033, 4604, 347, 295, 1279, 18893, 369, 279, 17728, 285, 45845, 14683, 8071, 6382, 430, 28003, 19011, 279, 3823, 8071, 220, 1691, 323, 24549, 14683, 8071, 6382, 430, 28003, 19011, 279, 802, 98643, 347, 8071, 220, 1313, 662, 763, 2225, 14769, 11, 264, 3544, 1358, 315, 15792, 51692, 4604, 31559, 2601, 19180, 555, 1446, 79, 27970, 35483, 315, 9501, 369, 20314, 958, 6595, 82, 1051, 13517, 70554, 389, 264, 3197, 277, 3552, 54057, 323, 8481, 43245, 291, 8800, 23506, 16146, 988, 13, 30538, 44175, 1180, 4090, 11, 279, 1358, 389, 23506, 409, 10365, 323, 41398, 1139, 3060, 264, 3613, 525, 477, 67030, 6070, 11, 1405, 279, 17484, 315, 279, 1446, 79, 27970, 9244, 16831, 84, 22828, 6449, 38210, 24411, 279, 6932, 2085, 20314, 477, 22936, 8060, 13, 11995, 3613, 525, 323, 67030, 6382, 6067, 430, 1511, 51692, 3469, 4748, 772, 28429, 1051, 64955, 9017, 6382, 15740, 11, 719, 279, 16686, 315, 44175, 81553, 3046, 1253, 387, 78921, 304, 1690, 13726, 2693, 1534, 6382, 6067, 369, 11761, 7766, 13, 7429, 11, 279, 3544, 25768, 6138, 1990, 4604, 347, 295, 1279, 16128, 4694, 369, 20314, 35483, 430, 527, 304, 279, 19748, 88371, 2134, 1253, 17477, 9669, 304, 11175, 26329, 13, 1556, 5603, 430, 374, 2225, 18641, 449, 54453, 2561, 32758, 6067, 323, 706, 19303, 26329, 5137, 374, 35946, 369, 1778, 17728, 285, 45845, 4604, 347, 295, 1279, 18893, 311, 3719, 810, 15325, 13, 5810, 11, 584, 3118, 264, 5016, 2780, 10830, 53161, 5603, 11, 11093, 449, 87836, 20622, 316, 60163, 2194, 6108, 19303, 31591, 5557, 11, 311, 1977, 29050, 11, 69311, 11, 323, 17251, 17728, 285, 45845, 4604, 347, 295, 1279, 18893, 13, 17554, 660, 439, 459, 1989, 315, 5684, 45842, 11, 2780, 10830, 323, 73730, 343, 10830, 1051, 6051, 34716, 311, 42840, 2380, 33520, 14726, 449, 8162, 9809, 276, 316, 60163, 2194, 7384, 311, 2187, 459, 15098, 7029, 2134, 315, 8522, 220, 1187, 1174, 220, 914, 1174, 220, 1627, 1174, 220, 1544, 1174, 220, 1591, 662, 42770, 332, 79348, 617, 1027, 128257, 198, 128256, 78191, 198, 9673, 2919, 11, 584, 15098, 17631, 389, 1057, 2849, 4641, 18632, 311, 12602, 21907, 1475, 13189, 315, 1057, 6439, 13, 13759, 2288, 3629, 11, 4869, 11, 584, 842, 709, 449, 7397, 430, 527, 264, 1207, 58098, 39656, 315, 8903, 13, 1628, 1418, 5793, 1493, 7170, 4131, 1139, 1514, 11, 1455, 4461, 11, 279, 6382, 596, 7528, 2217, 12271, 374, 279, 1972, 75283, 13, 362, 10269, 51692, 7479, 11, 433, 1120, 649, 956, 1920, 5448, 17439, 555, 264, 50264, 6382, 18848, 439, 1664, 439, 279, 30293, 50264, 2217, 26148, 2345, 61036, 3967, 439, 279, 2160, 20718, 49525, 3823, 6548, 13, 763, 264, 42445, 430, 1436, 11, 369, 3187, 11, 3063, 311, 18632, 449, 7953, 10826, 21395, 8838, 10826, 38921, 4519, 1778, 439, 24746, 8149, 315, 2115, 11, 22622, 1684, 9392, 11, 3428, 82102, 811, 11, 323, 53108, 7319, 13252, 17915, 11, 19303, 3469, 4748, 772, 28429, 54047, 1901, 12301, 80, 28323, 320, 33731, 8, 11583, 706, 69120, 264, 1749, 369, 3339, 50264, 7528, 2217, 26148, 304, 21483, 430, 56459, 459, 27080, 596, 24549, 8071, 320, 12296, 327, 8, 323, 264, 36041, 278, 596, 330, 13576, 87693, 1, 8071, 320, 41546, 525, 570, 578, 45638, 473, 13, 90587, 323, 64749, 300, 423, 80382, 66695, 17054, 315, 20314, 323, 6500, 15009, 520, 279, 3907, 315, 21073, 5364, 329, 3416, 11, 11583, 11, 813, 4236, 323, 79119, 7633, 279, 15105, 304, 279, 4723, 13, 220, 1187, 11, 220, 679, 22, 11, 4360, 315, 279, 8486, 22037, 26545, 13, 13182, 2111, 2217, 26148, 656, 3073, 13, 14968, 1524, 3582, 814, 704, 29588, 872, 10269, 38495, 11, 814, 9167, 956, 1903, 433, 1139, 279, 21391, 49525, 961, 11, 1606, 315, 279, 11774, 38088, 304, 264, 15266, 1749, 430, 18065, 26422, 264, 10269, 11, 33956, 6710, 315, 51692, 1139, 264, 17728, 285, 45845, 6211, 2085, 58370, 2785, 433, 11, 15061, 433, 477, 6062, 409, 33359, 1202, 4367, 13, 362, 3613, 525, 2373, 315, 279, 7528, 2217, 12271, 93897, 63018, 369, 6968, 264, 17728, 285, 45845, 42199, 11277, 1358, 13, 16666, 25, 816, 20568, 473, 16965, 50432, 323, 31663, 37120, 11583, 596, 15105, 574, 14948, 555, 8776, 11002, 2780, 10830, 11, 477, 279, 1989, 315, 5684, 2269, 15345, 13, 2057, 1893, 279, 50264, 4604, 347, 295, 1279, 11, 568, 323, 813, 4236, 14454, 16128, 555, 13021, 40916, 53584, 21483, 2345, 57839, 81575, 1093, 264, 22963, 5041, 2345, 10138, 264, 15792, 11, 10269, 19303, 11071, 315, 51692, 2663, 264, 20622, 316, 60163, 2194, 11, 902, 23874, 389, 264, 19303, 54057, 13, 5112, 11, 814, 1511, 264, 21120, 311, 4018, 3201, 1063, 315, 1884, 16128, 779, 430, 279, 9861, 51692, 14454, 4832, 74788, 11, 449, 912, 33251, 11, 994, 814, 9277, 433, 47088, 264, 58438, 6211, 320, 2000, 264, 279, 67030, 32314, 8, 477, 1139, 264, 19763, 6211, 320, 2000, 264, 3613, 525, 32314, 570, 330, 1687, 649, 1176, 22497, 433, 1139, 264, 12651, 6241, 323, 20801, 6241, 6070, 17223, 1855, 315, 1884, 649, 387, 4726, 18255, 1359, 2795, 11583, 13, 330, 2675, 649, 16058, 22497, 1124, 11, 304, 10334, 11, 779, 430, 3445, 279, 16128, 649, 387, 2216, 11, 2216, 29050, 11, 323, 1070, 527, 912, 4384, 5789, 13, 1115, 374, 2216, 69311, 11, 323, 584, 649, 37920, 433, 1139, 8996, 6211, 584, 1390, 1210, 362, 67030, 2373, 315, 279, 7528, 2217, 12271, 93897, 1093, 264, 22963, 5041, 369, 28003, 16671, 459, 27080, 753, 24549, 8071, 13, 16666, 25, 816, 20568, 473, 16965, 50432, 323, 31663, 37120, 3011, 13252, 17915, 374, 264, 87101, 369, 48277, 11, 439, 264, 6382, 596, 5845, 311, 1935, 1579, 64036, 7397, 374, 11075, 11, 304, 19262, 391, 10486, 11, 555, 279, 3392, 315, 2038, 1202, 12271, 649, 12602, 13, 25122, 11, 279, 12074, 6, 25018, 374, 13489, 220, 22, 2606, 55336, 11, 477, 17715, 264, 8502, 25224, 11, 304, 23899, 13, 3011, 596, 2103, 264, 2766, 78921, 369, 701, 2849, 4641, 11, 719, 11583, 2795, 568, 649, 1304, 279, 12271, 1524, 9333, 13, 330, 2028, 39654, 374, 264, 1633, 2466, 12178, 304, 32758, 1359, 568, 2795, 13, 220, 128257, 198 ]

2,027

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract We sought to determine predictive factors for selective laser trabeculoplasty (SLT) outcome. 252 eyes from 198 adult patients with open-angle glaucoma who underwent SLT between July 2016 and February 2018 with a minimum 6 month follow up were reviewed. We defined success as ≥20% IOP reduction or ≥1 medication reduction without an IOP lowering procedure. We also evaluated the relationship of these factors to postoperative IOP elevation >5 mmHg (IOP spikes). Our primary outcome measure was association between age, type and severity of glaucoma, pigmentation of the trabecular meshwork (PTM), total energy delivered, and baseline intraocular pressure (IOP) with success. At 2 and 6 months, 33.6% (76/226) and 38.5% (97/252) of eyes met success criteria respectively. Baseline IOP > 18 mmHg was significantly associated with success both at 2 and 6 months, reducing IOP by 5.4 ± 5.3 mmHg (23.7% reduction), whereas those with lower baseline remained at −0.7 ± 4.6 mmHg (4.9% increase) at 6 months ( P < 0.001). No other baseline characteristics significantly predicted success or IOP spikes. Patients with higher baseline IOPs had greater success rates and mean IOP reduction at both 2 and 6 months following SLT. Age, type and severity of glaucoma, PTM, or total energy delivery had no association with procedural success or IOP spikes. Patients with higher baseline IOP may experience greater lowering of IOP after SLT. However, SLT may be equally successful for patients with a variety of other characteristics. Introduction Second in frequency only to cataracts, glaucoma causes more cases of blindness worldwide than any other ocular disease and currently affects over 70 million people, 10% of whom eventually lose their sight due to optic nerve damage 1 . Since it is estimated to continue increasing in incidence, refining treatment approaches become more crucial every year to preserve sight 2 . Selective laser trabeculoplasty (SLT) reduces intraocular pressure (IOP) by improving aqueous outflow likely by biological rather than anatomic changes in the trabecular meshwork (TM) with proven efficacy ranging from 15–66% and a better safety profile than its predecessor, Argon Laser Trabeculoplasty (ALT) 1 , 3 . Originally indicated only for primary open-angle glaucoma (POAG), it has been shown to be efficacious for many other types of open-angle glaucoma 4 . Building on the principles of ALT, it uses frequency-doubled short pulse (Q-switched) Nd:YAG laser and selectively targets pigmented cells of the TM without damaging the overall anatomical structure of the meshwork 3 . The larger spot size of 400 μm for SLT compared to 50 μm for ALT allows for broader coverage of the angle and eliminates the need for as fine a focus while still providing the “champagne bubble” feedback that is generally recommended every two or three burns for appropriate energy delivery 5 , 6 , 7 . Although efficacy and safety of SLT have been well documented, predictive factors for outcome of SLT tend to vary in the literature and large-scale investigations on this topic are limited. SLT has reportedly worked best for patients with ocular hypertension, POAG, pseudoexfoliation, or pigmentary glaucoma 7 . Pigmentation of TM (PTM) has not been associated with efficacy of the procedure 8 , but with higher risk of IOP spikes 9 . 360° treatment have been reported to be more effective than 180° treatment in one setting 10 , although many surgeons opt to treat 180° at a time in hopes of decreasing risk of IOP spikes. With the growing interest in using SLT as first-line treatment and well known issues with medication compliance, determining which patients would have the best response to this therapy is increasingly important 11 , 12 , 13 . In this study, we attempted to determine possible predictive factors for both successful outcomes and common complications, including postoperative IOP spike following SLT treatment. Patients and Methods We first obtained University of Missouri Institutional Review Board (IRB) approval who granted us a waiver of informed consent due to the retrospective nature of the study with deidentified data. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. We performed a retrospective chart review of 252 eyes of 198 adult open-angle glaucoma patients who underwent SLT at University of Missouri between July 2016 and February 2018 in accordance with the guidelines and regulations of our IRB approval. All patients completed minimum 6 months follow up visit after SLT. We collected pre-op and post-op data at 2 and 6 month follow-up. Our primary outcome measure was correlation between patient age, type and severity of glaucoma, PTM, or total energy delivery with procedural success. Success was defined as ≥20% IOP reduction or any reduction of medication without increasing IOP, and failure was not meeting these criteria or requiring an additional IOP-lowering surgery before the time point considered. Our secondary outcome measure was association of baseline characteristics to IOP reduction, medication reduction, and postoperative IOP spike (defined as elevation of IOP > 5 mmHg from baseline 1 hour after the procedure). Laser procedure and protocols All SLT was performed with the 532 nm frequency doubled Q-switched Nd:YAG laser using 3 ns pulse and spot size of 400 micrometer. Power varied from 0.6 to 1.4 mJ and was titrated until microbubbles were visualized then reduced by 0.1 mJ. The settings for the SLT laser and therefore total energy varied depending on TM pigmentation. At 1 hour post procedure, a Goldmann applanation tonometer was used to check IOP by the treating physician or skilled ophthalmic technician. A drop of Timolol or Brimonidine was given to the operative eye prior to procedure, and no steroid was used postoperatively. No additional ocular hypotensive drops were given after the procedure unless the patient experienced an IOP spike. IOP was checked similarly at 2 weeks, 2 months, and 6 months post-procedure. Full slit lamp examination with gonioscopy and visual acuity testing were done at 2 weeks, 2 months,", "role": "user" }, { "content": "More than 70 million people worldwide suffer from glaucoma, a condition that causes a build-up of fluid and pressure inside the eye and can eventually lead to blindness. Treatment options have traditionally included eye drops to reduce the fluid the eye produces or surgery to unclog the eye's drainage. But a new study from the University of Missouri School of Medicine and MU Health Care provides insight into which patients might benefit most from a noninvasive treatment called selective laser trabeculoplasty (SLT), which relieves pressure by using a laser to alter the eye tissue, resulting in better fluid drainage. \"There's been a lack of evidence about how well SLT works, how safe it is and the ideal candidate,\" said senior author Jella An, MD, an assistant professor of ophthalmology and a fellowship-trained glaucoma specialist at MU Health Care's Mason Eye Institute. \"Because so little is known about SLT, there is a lot of apprehension among specialists about using it as a first-line treatment for glaucoma. Our research findings have helped me redefine the ideal patient for this procedure.\" An's research team reviewed 252 SLT procedures on 198 adult patients with open-angle glaucoma to determine what percentage of these surgeries achieved a 20% or greater reduction in intraocular pressure (IOP). Two months after surgery, 33.6% of patients met success criteria. At the six-month mark, 38.5% achieved the threshold. The researchers discovered patients with a higher baseline IOP had larger reductions in pressure. \"We discovered significant improvement in patients with more severe cases, which convinced me that patients with the highest pressure will benefit the most from this laser therapy,\" An said. Age, type and severity of glaucoma did not significantly predict a successful outcome. In addition, less than 5% of patients studied experienced the most common adverse event of an IOP spike after the procedure. \"This study really increased my comfort level to offer SLT as a primary therapy,\" An said. \"Prior to this research, I would prescribe these patients multiple medications, creating the possibility of side effects and poor adherence, which could lead to disease progression. Now I offer this laser first if they are a good candidate because of its safety profile. If it doesn't work, we can always move forward with other options.\" In addition to An, the study's lead author was MU School of Medicine ophthalmology resident Matthew Hirabayashi, MD. Vikram Ponnusamy, MD, a recent graduate of MU School of Medicine, also contributed to the findings. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract We sought to determine predictive factors for selective laser trabeculoplasty (SLT) outcome. 252 eyes from 198 adult patients with open-angle glaucoma who underwent SLT between July 2016 and February 2018 with a minimum 6 month follow up were reviewed. We defined success as ≥20% IOP reduction or ≥1 medication reduction without an IOP lowering procedure. We also evaluated the relationship of these factors to postoperative IOP elevation >5 mmHg (IOP spikes). Our primary outcome measure was association between age, type and severity of glaucoma, pigmentation of the trabecular meshwork (PTM), total energy delivered, and baseline intraocular pressure (IOP) with success. At 2 and 6 months, 33.6% (76/226) and 38.5% (97/252) of eyes met success criteria respectively. Baseline IOP > 18 mmHg was significantly associated with success both at 2 and 6 months, reducing IOP by 5.4 ± 5.3 mmHg (23.7% reduction), whereas those with lower baseline remained at −0.7 ± 4.6 mmHg (4.9% increase) at 6 months ( P < 0.001). No other baseline characteristics significantly predicted success or IOP spikes. Patients with higher baseline IOPs had greater success rates and mean IOP reduction at both 2 and 6 months following SLT. Age, type and severity of glaucoma, PTM, or total energy delivery had no association with procedural success or IOP spikes. Patients with higher baseline IOP may experience greater lowering of IOP after SLT. However, SLT may be equally successful for patients with a variety of other characteristics. Introduction Second in frequency only to cataracts, glaucoma causes more cases of blindness worldwide than any other ocular disease and currently affects over 70 million people, 10% of whom eventually lose their sight due to optic nerve damage 1 . Since it is estimated to continue increasing in incidence, refining treatment approaches become more crucial every year to preserve sight 2 . Selective laser trabeculoplasty (SLT) reduces intraocular pressure (IOP) by improving aqueous outflow likely by biological rather than anatomic changes in the trabecular meshwork (TM) with proven efficacy ranging from 15–66% and a better safety profile than its predecessor, Argon Laser Trabeculoplasty (ALT) 1 , 3 . Originally indicated only for primary open-angle glaucoma (POAG), it has been shown to be efficacious for many other types of open-angle glaucoma 4 . Building on the principles of ALT, it uses frequency-doubled short pulse (Q-switched) Nd:YAG laser and selectively targets pigmented cells of the TM without damaging the overall anatomical structure of the meshwork 3 . The larger spot size of 400 μm for SLT compared to 50 μm for ALT allows for broader coverage of the angle and eliminates the need for as fine a focus while still providing the “champagne bubble” feedback that is generally recommended every two or three burns for appropriate energy delivery 5 , 6 , 7 . Although efficacy and safety of SLT have been well documented, predictive factors for outcome of SLT tend to vary in the literature and large-scale investigations on this topic are limited. SLT has reportedly worked best for patients with ocular hypertension, POAG, pseudoexfoliation, or pigmentary glaucoma 7 . Pigmentation of TM (PTM) has not been associated with efficacy of the procedure 8 , but with higher risk of IOP spikes 9 . 360° treatment have been reported to be more effective than 180° treatment in one setting 10 , although many surgeons opt to treat 180° at a time in hopes of decreasing risk of IOP spikes. With the growing interest in using SLT as first-line treatment and well known issues with medication compliance, determining which patients would have the best response to this therapy is increasingly important 11 , 12 , 13 . In this study, we attempted to determine possible predictive factors for both successful outcomes and common complications, including postoperative IOP spike following SLT treatment. Patients and Methods We first obtained University of Missouri Institutional Review Board (IRB) approval who granted us a waiver of informed consent due to the retrospective nature of the study with deidentified data. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. We performed a retrospective chart review of 252 eyes of 198 adult open-angle glaucoma patients who underwent SLT at University of Missouri between July 2016 and February 2018 in accordance with the guidelines and regulations of our IRB approval. All patients completed minimum 6 months follow up visit after SLT. We collected pre-op and post-op data at 2 and 6 month follow-up. Our primary outcome measure was correlation between patient age, type and severity of glaucoma, PTM, or total energy delivery with procedural success. Success was defined as ≥20% IOP reduction or any reduction of medication without increasing IOP, and failure was not meeting these criteria or requiring an additional IOP-lowering surgery before the time point considered. Our secondary outcome measure was association of baseline characteristics to IOP reduction, medication reduction, and postoperative IOP spike (defined as elevation of IOP > 5 mmHg from baseline 1 hour after the procedure). Laser procedure and protocols All SLT was performed with the 532 nm frequency doubled Q-switched Nd:YAG laser using 3 ns pulse and spot size of 400 micrometer. Power varied from 0.6 to 1.4 mJ and was titrated until microbubbles were visualized then reduced by 0.1 mJ. The settings for the SLT laser and therefore total energy varied depending on TM pigmentation. At 1 hour post procedure, a Goldmann applanation tonometer was used to check IOP by the treating physician or skilled ophthalmic technician. A drop of Timolol or Brimonidine was given to the operative eye prior to procedure, and no steroid was used postoperatively. No additional ocular hypotensive drops were given after the procedure unless the patient experienced an IOP spike. IOP was checked similarly at 2 weeks, 2 months, and 6 months post-procedure. Full slit lamp examination with gonioscopy and visual acuity testing were done at 2 weeks, 2 months,<|im_end|> <|im_start|>assistant More than 70 million people worldwide suffer from glaucoma, a condition that causes a build-up of fluid and pressure inside the eye and can eventually lead to blindness. Treatment options have traditionally included eye drops to reduce the fluid the eye produces or surgery to unclog the eye's drainage. But a new study from the University of Missouri School of Medicine and MU Health Care provides insight into which patients might benefit most from a noninvasive treatment called selective laser trabeculoplasty (SLT), which relieves pressure by using a laser to alter the eye tissue, resulting in better fluid drainage. "There's been a lack of evidence about how well SLT works, how safe it is and the ideal candidate," said senior author Jella An, MD, an assistant professor of ophthalmology and a fellowship-trained glaucoma specialist at MU Health Care's Mason Eye Institute. "Because so little is known about SLT, there is a lot of apprehension among specialists about using it as a first-line treatment for glaucoma. Our research findings have helped me redefine the ideal patient for this procedure." An's research team reviewed 252 SLT procedures on 198 adult patients with open-angle glaucoma to determine what percentage of these surgeries achieved a 20% or greater reduction in intraocular pressure (IOP). Two months after surgery, 33.6% of patients met success criteria. At the six-month mark, 38.5% achieved the threshold. The researchers discovered patients with a higher baseline IOP had larger reductions in pressure. "We discovered significant improvement in patients with more severe cases, which convinced me that patients with the highest pressure will benefit the most from this laser therapy," An said. Age, type and severity of glaucoma did not significantly predict a successful outcome. In addition, less than 5% of patients studied experienced the most common adverse event of an IOP spike after the procedure. "This study really increased my comfort level to offer SLT as a primary therapy," An said. "Prior to this research, I would prescribe these patients multiple medications, creating the possibility of side effects and poor adherence, which could lead to disease progression. Now I offer this laser first if they are a good candidate because of its safety profile. If it doesn't work, we can always move forward with other options." In addition to An, the study's lead author was MU School of Medicine ophthalmology resident Matthew Hirabayashi, MD. Vikram Ponnusamy, MD, a recent graduate of MU School of Medicine, also contributed to the findings. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 1226, 16495, 311, 8417, 60336, 9547, 369, 44010, 21120, 18062, 762, 360, 92335, 88, 320, 8143, 51, 8, 15632, 13, 220, 12326, 6548, 505, 220, 3753, 6822, 6978, 449, 1825, 35481, 2840, 2933, 82945, 889, 55093, 17216, 51, 1990, 5887, 220, 679, 21, 323, 7552, 220, 679, 23, 449, 264, 8187, 220, 21, 2305, 1833, 709, 1051, 22690, 13, 1226, 4613, 2450, 439, 63247, 508, 4, 358, 3143, 14278, 477, 63247, 16, 24099, 14278, 2085, 459, 358, 3143, 46301, 10537, 13, 1226, 1101, 26126, 279, 5133, 315, 1521, 9547, 311, 1772, 43719, 358, 3143, 27255, 871, 20, 9653, 39, 70, 320, 40, 3143, 51760, 570, 5751, 6156, 15632, 6767, 574, 15360, 1990, 4325, 11, 955, 323, 31020, 315, 2840, 2933, 82945, 11, 24623, 32199, 315, 279, 18062, 762, 1299, 11546, 1816, 320, 2898, 44, 705, 2860, 4907, 12886, 11, 323, 26954, 50938, 68797, 7410, 320, 40, 3143, 8, 449, 2450, 13, 2468, 220, 17, 323, 220, 21, 4038, 11, 220, 1644, 13, 21, 4, 320, 4767, 14, 14057, 8, 323, 220, 1987, 13, 20, 4, 320, 3534, 14, 12326, 8, 315, 6548, 2322, 2450, 13186, 15947, 13, 15004, 4939, 358, 3143, 871, 220, 972, 9653, 39, 70, 574, 12207, 5938, 449, 2450, 2225, 520, 220, 17, 323, 220, 21, 4038, 11, 18189, 358, 3143, 555, 220, 20, 13, 19, 20903, 220, 20, 13, 18, 9653, 39, 70, 320, 1419, 13, 22, 4, 14278, 705, 20444, 1884, 449, 4827, 26954, 14958, 520, 25173, 15, 13, 22, 20903, 220, 19, 13, 21, 9653, 39, 70, 320, 19, 13, 24, 4, 5376, 8, 520, 220, 21, 4038, 320, 393, 366, 220, 15, 13, 4119, 570, 2360, 1023, 26954, 17910, 12207, 19698, 2450, 477, 358, 3143, 51760, 13, 44430, 449, 5190, 26954, 358, 3143, 82, 1047, 7191, 2450, 7969, 323, 3152, 358, 3143, 14278, 520, 2225, 220, 17, 323, 220, 21, 4038, 2768, 17216, 51, 13, 13381, 11, 955, 323, 31020, 315, 2840, 2933, 82945, 11, 19932, 44, 11, 477, 2860, 4907, 9889, 1047, 912, 15360, 449, 62781, 2450, 477, 358, 3143, 51760, 13, 44430, 449, 5190, 26954, 358, 3143, 1253, 3217, 7191, 46301, 315, 358, 3143, 1306, 17216, 51, 13, 4452, 11, 17216, 51, 1253, 387, 18813, 6992, 369, 6978, 449, 264, 8205, 315, 1023, 17910, 13, 29438, 10657, 304, 11900, 1193, 311, 272, 6526, 11613, 11, 2840, 2933, 82945, 11384, 810, 5157, 315, 85515, 15603, 1109, 904, 1023, 18274, 1299, 8624, 323, 5131, 22223, 927, 220, 2031, 3610, 1274, 11, 220, 605, 4, 315, 8884, 9778, 9229, 872, 14254, 4245, 311, 81209, 32015, 5674, 220, 16, 662, 8876, 433, 374, 13240, 311, 3136, 7859, 304, 39775, 11, 74285, 6514, 20414, 3719, 810, 16996, 1475, 1060, 311, 21813, 14254, 220, 17, 662, 8593, 535, 21120, 18062, 762, 360, 92335, 88, 320, 8143, 51, 8, 26338, 50938, 68797, 7410, 320, 40, 3143, 8, 555, 18899, 66300, 788, 704, 5072, 4461, 555, 24156, 4856, 1109, 459, 6756, 4442, 304, 279, 18062, 762, 1299, 11546, 1816, 320, 22809, 8, 449, 17033, 41265, 24950, 505, 220, 868, 4235, 2287, 4, 323, 264, 2731, 7296, 5643, 1109, 1202, 40274, 11, 7793, 263, 40708, 127889, 762, 360, 92335, 88, 320, 36930, 8, 220, 16, 1174, 220, 18, 662, 25842, 16717, 1193, 369, 6156, 1825, 35481, 2840, 2933, 82945, 320, 2089, 1929, 705, 433, 706, 1027, 6982, 311, 387, 31914, 19995, 369, 1690, 1023, 4595, 315, 1825, 35481, 2840, 2933, 82945, 220, 19, 662, 17283, 389, 279, 16565, 315, 50512, 11, 433, 5829, 11900, 1773, 5599, 839, 2875, 28334, 320, 48, 48296, 291, 8, 88468, 25, 56, 1929, 21120, 323, 82775, 11811, 24623, 28078, 7917, 315, 279, 24929, 2085, 34446, 279, 8244, 75893, 950, 6070, 315, 279, 11546, 1816, 220, 18, 662, 578, 8294, 7858, 1404, 315, 220, 3443, 33983, 76, 369, 17216, 51, 7863, 311, 220, 1135, 33983, 76, 369, 50512, 6276, 369, 27927, 10401, 315, 279, 9392, 323, 60944, 279, 1205, 369, 439, 7060, 264, 5357, 1418, 2103, 8405, 279, 1054, 331, 1141, 24812, 24529, 863, 11302, 430, 374, 8965, 11349, 1475, 1403, 477, 2380, 44154, 369, 8475, 4907, 9889, 220, 20, 1174, 220, 21, 1174, 220, 22, 662, 10541, 41265, 323, 7296, 315, 17216, 51, 617, 1027, 1664, 27470, 11, 60336, 9547, 369, 15632, 315, 17216, 51, 8541, 311, 13592, 304, 279, 17649, 323, 3544, 13230, 26969, 389, 420, 8712, 527, 7347, 13, 17216, 51, 706, 18307, 6575, 1888, 369, 6978, 449, 18274, 1299, 63308, 11, 13228, 1929, 11, 35850, 327, 8566, 7246, 11, 477, 77678, 661, 2840, 2933, 82945, 220, 22, 662, 49654, 32199, 315, 24929, 320, 2898, 44, 8, 706, 539, 1027, 5938, 449, 41265, 315, 279, 10537, 220, 23, 1174, 719, 449, 5190, 5326, 315, 358, 3143, 51760, 220, 24, 662, 220, 6843, 11877, 6514, 617, 1027, 5068, 311, 387, 810, 7524, 1109, 220, 5245, 11877, 6514, 304, 832, 6376, 220, 605, 1174, 8051, 1690, 74272, 3469, 311, 4322, 220, 5245, 11877, 520, 264, 892, 304, 16388, 315, 44649, 5326, 315, 358, 3143, 51760, 13, 3161, 279, 7982, 2802, 304, 1701, 17216, 51, 439, 1176, 8614, 6514, 323, 1664, 3967, 4819, 449, 24099, 8907, 11, 26679, 902, 6978, 1053, 617, 279, 1888, 2077, 311, 420, 15419, 374, 15098, 3062, 220, 806, 1174, 220, 717, 1174, 220, 1032, 662, 763, 420, 4007, 11, 584, 17644, 311, 8417, 3284, 60336, 9547, 369, 2225, 6992, 20124, 323, 4279, 36505, 11, 2737, 1772, 43719, 358, 3143, 37393, 2768, 17216, 51, 6514, 13, 44430, 323, 19331, 1226, 1176, 12457, 3907, 315, 25378, 98984, 10506, 8925, 320, 2871, 33, 8, 14765, 889, 11938, 603, 264, 54205, 315, 16369, 14771, 4245, 311, 279, 79929, 7138, 315, 279, 4007, 449, 409, 43360, 828, 13, 2052, 16346, 10887, 304, 7978, 16239, 3823, 13324, 1051, 304, 18859, 449, 279, 31308, 10886, 315, 279, 33232, 323, 5426, 3495, 13093, 323, 449, 279, 220, 5162, 19, 42021, 315, 77434, 323, 1202, 3010, 41693, 477, 30139, 31308, 10886, 13, 1226, 10887, 264, 79929, 9676, 3477, 315, 220, 12326, 6548, 315, 220, 3753, 6822, 1825, 35481, 2840, 2933, 82945, 6978, 889, 55093, 17216, 51, 520, 3907, 315, 25378, 1990, 5887, 220, 679, 21, 323, 7552, 220, 679, 23, 304, 18859, 449, 279, 17959, 323, 14640, 315, 1057, 16646, 33, 14765, 13, 2052, 6978, 8308, 8187, 220, 21, 4038, 1833, 709, 4034, 1306, 17216, 51, 13, 1226, 14890, 864, 30592, 323, 1772, 30592, 828, 520, 220, 17, 323, 220, 21, 2305, 1833, 5352, 13, 5751, 6156, 15632, 6767, 574, 26670, 1990, 8893, 4325, 11, 955, 323, 31020, 315, 2840, 2933, 82945, 11, 19932, 44, 11, 477, 2860, 4907, 9889, 449, 62781, 2450, 13, 13346, 574, 4613, 439, 63247, 508, 4, 358, 3143, 14278, 477, 904, 14278, 315, 24099, 2085, 7859, 358, 3143, 11, 323, 8060, 574, 539, 6574, 1521, 13186, 477, 23537, 459, 5217, 358, 3143, 2922, 90714, 15173, 1603, 279, 892, 1486, 6646, 13, 5751, 14580, 15632, 6767, 574, 15360, 315, 26954, 17910, 311, 358, 3143, 14278, 11, 24099, 14278, 11, 323, 1772, 43719, 358, 3143, 37393, 320, 9910, 439, 27255, 315, 358, 3143, 871, 220, 20, 9653, 39, 70, 505, 26954, 220, 16, 6596, 1306, 279, 10537, 570, 40708, 10537, 323, 32885, 2052, 17216, 51, 574, 10887, 449, 279, 220, 20711, 26807, 11900, 35717, 1229, 48296, 291, 88468, 25, 56, 1929, 21120, 1701, 220, 18, 12548, 28334, 323, 7858, 1404, 315, 220, 3443, 19748, 88371, 13, 7572, 28830, 505, 220, 15, 13, 21, 311, 220, 16, 13, 19, 296, 41, 323, 574, 8305, 55373, 3156, 8162, 65, 35395, 1051, 9302, 1534, 1243, 11293, 555, 220, 15, 13, 16, 296, 41, 13, 578, 5110, 369, 279, 17216, 51, 21120, 323, 9093, 2860, 4907, 28830, 11911, 389, 24929, 24623, 32199, 13, 2468, 220, 16, 6596, 1772, 10537, 11, 264, 7573, 18022, 1469, 36990, 8941, 21037, 574, 1511, 311, 1817, 358, 3143, 555, 279, 27723, 28378, 477, 26611, 297, 81937, 292, 54611, 13, 362, 6068, 315, 9538, 337, 337, 477, 3320, 26490, 91073, 574, 2728, 311, 279, 64885, 8071, 4972, 311, 10537, 11, 323, 912, 77848, 574, 1511, 1772, 3376, 8046, 13, 2360, 5217, 18274, 1299, 9950, 354, 4114, 21701, 1051, 2728, 1306, 279, 10537, 7389, 279, 8893, 10534, 459, 358, 3143, 37393, 13, 358, 3143, 574, 10273, 30293, 520, 220, 17, 5672, 11, 220, 17, 4038, 11, 323, 220, 21, 4038, 1772, 10039, 13498, 13, 8797, 79130, 29062, 24481, 449, 64592, 3614, 8728, 323, 9302, 1645, 35594, 7649, 1051, 2884, 520, 220, 17, 5672, 11, 220, 17, 4038, 11, 128257, 198, 128256, 78191, 198, 7816, 1109, 220, 2031, 3610, 1274, 15603, 7831, 505, 2840, 2933, 82945, 11, 264, 3044, 430, 11384, 264, 1977, 5352, 315, 15962, 323, 7410, 4871, 279, 8071, 323, 649, 9778, 3063, 311, 85515, 13, 31969, 2671, 617, 36342, 5343, 8071, 21701, 311, 8108, 279, 15962, 279, 8071, 19159, 477, 15173, 311, 21482, 848, 279, 8071, 596, 58592, 13, 2030, 264, 502, 4007, 505, 279, 3907, 315, 25378, 6150, 315, 19152, 323, 60886, 6401, 10852, 5825, 20616, 1139, 902, 6978, 2643, 8935, 1455, 505, 264, 2536, 258, 78134, 6514, 2663, 44010, 21120, 18062, 762, 360, 92335, 88, 320, 8143, 51, 705, 902, 1375, 39235, 7410, 555, 1701, 264, 21120, 311, 11857, 279, 8071, 20438, 11, 13239, 304, 2731, 15962, 58592, 13, 330, 3947, 596, 1027, 264, 6996, 315, 6029, 922, 1268, 1664, 17216, 51, 4375, 11, 1268, 6220, 433, 374, 323, 279, 10728, 9322, 1359, 1071, 10195, 3229, 622, 6985, 1556, 11, 14306, 11, 459, 18328, 14561, 315, 297, 81937, 2508, 323, 264, 63349, 70024, 2840, 2933, 82945, 24687, 520, 60886, 6401, 10852, 596, 29927, 28929, 10181, 13, 330, 18433, 779, 2697, 374, 3967, 922, 17216, 51, 11, 1070, 374, 264, 2763, 315, 47291, 2711, 4315, 35416, 922, 1701, 433, 439, 264, 1176, 8614, 6514, 369, 2840, 2933, 82945, 13, 5751, 3495, 14955, 617, 9087, 757, 84375, 279, 10728, 8893, 369, 420, 10537, 1210, 1556, 596, 3495, 2128, 22690, 220, 12326, 17216, 51, 16346, 389, 220, 3753, 6822, 6978, 449, 1825, 35481, 2840, 2933, 82945, 311, 8417, 1148, 11668, 315, 1521, 68823, 17427, 264, 220, 508, 4, 477, 7191, 14278, 304, 50938, 68797, 7410, 320, 40, 3143, 570, 9220, 4038, 1306, 15173, 11, 220, 1644, 13, 21, 4, 315, 6978, 2322, 2450, 13186, 13, 2468, 279, 4848, 23086, 1906, 11, 220, 1987, 13, 20, 4, 17427, 279, 12447, 13, 578, 12074, 11352, 6978, 449, 264, 5190, 26954, 358, 3143, 1047, 8294, 47311, 304, 7410, 13, 330, 1687, 11352, 5199, 16048, 304, 6978, 449, 810, 15748, 5157, 11, 902, 22954, 757, 430, 6978, 449, 279, 8592, 7410, 690, 8935, 279, 1455, 505, 420, 21120, 15419, 1359, 1556, 1071, 13, 13381, 11, 955, 323, 31020, 315, 2840, 2933, 82945, 1550, 539, 12207, 7168, 264, 6992, 15632, 13, 763, 5369, 11, 2753, 1109, 220, 20, 4, 315, 6978, 20041, 10534, 279, 1455, 4279, 31959, 1567, 315, 459, 358, 3143, 37393, 1306, 279, 10537, 13, 330, 2028, 4007, 2216, 7319, 856, 6981, 2237, 311, 3085, 17216, 51, 439, 264, 6156, 15419, 1359, 1556, 1071, 13, 330, 50571, 311, 420, 3495, 11, 358, 1053, 72333, 1521, 6978, 5361, 31010, 11, 6968, 279, 13336, 315, 3185, 6372, 323, 8009, 71628, 11, 902, 1436, 3063, 311, 8624, 33824, 13, 4800, 358, 3085, 420, 21120, 1176, 422, 814, 527, 264, 1695, 9322, 1606, 315, 1202, 7296, 5643, 13, 1442, 433, 3250, 956, 990, 11, 584, 649, 2744, 3351, 4741, 449, 1023, 2671, 1210, 763, 5369, 311, 1556, 11, 279, 4007, 596, 3063, 3229, 574, 60886, 6150, 315, 19152, 297, 81937, 2508, 19504, 19475, 80735, 98286, 31478, 11, 14306, 13, 29476, 2453, 393, 27476, 355, 27322, 11, 14306, 11, 264, 3293, 19560, 315, 60886, 6150, 315, 19152, 11, 1101, 20162, 311, 279, 14955, 13, 220, 128257, 198 ]

1,956

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Aerobic methanotrophic bacteria have evolved a specialist lifestyle dependent on consumption of methane and other short-chain carbon compounds. However, their apparent substrate specialism runs contrary to the high relative abundance of these microorganisms in dynamic environments, where the availability of methane and oxygen fluctuates. In this work, we provide in situ and ex situ evidence that verrucomicrobial methanotrophs are mixotrophs. Verrucomicrobia-dominated soil communities from an acidic geothermal field in Rotokawa, New Zealand rapidly oxidised methane and hydrogen simultaneously. We isolated and characterised a verrucomicrobial strain from these soils, Methylacidiphilum sp. RTK17.1, and showed that it constitutively oxidises molecular hydrogen. Genomic analysis confirmed that this strain encoded two [NiFe]-hydrogenases (group 1d and 3b), and biochemical assays revealed that it used hydrogen as an electron donor for aerobic respiration and carbon fixation. While the strain could grow heterotrophically on methane or autotrophically on hydrogen, it grew optimally by combining these metabolic strategies. Hydrogen oxidation was particularly important for adaptation to methane and oxygen limitation. Complementary to recent findings of hydrogenotrophic growth by Methylacidiphilum fumariolicum SolV, our findings illustrate that verrucomicrobial methanotrophs have evolved to simultaneously utilise hydrogen and methane from geothermal sources to meet energy and carbon demands where nutrient flux is dynamic. This mixotrophic lifestyle is likely to have facilitated expansion of the niche space occupied by these microorganisms, allowing them to become dominant in geothermally influenced surface soils. Genes encoding putative oxygen-tolerant uptake [NiFe]-hydrogenases were identified in all publicly available methanotroph genomes, suggesting hydrogen oxidation is a general metabolic strategy in this guild. Introduction Aerobic methane-oxidising bacteria (methanotrophs) consume the potent greenhouse gas methane (CH 4 ) ( Kirschke et al., 2013 ). They serve as the primary biological sink of atmospheric methane (~30 Tg annum −1 ) ( Hanson and Hanson, 1996 ) and, together with anaerobic methane-oxidising archaea, also capture the majority of biologically and geologically produced CH 4 before it enters the atmosphere ( Oremland and Culbertson, 1992 ). Relative to their global impact as greenhouse gas mitigators, aerobic methanotrophs exhibit low phylogenetic diversity and are presently limited to 26 genera in the Alphaproteobacteria and Gammaproteobacteria ( Euzéby, 1997 ), two candidate genera in the phylum Verrucomicrobia ( Op den Camp et al., 2009 ; van Teeseling et al., 2014 ), and two representatives of candidate phylum NC10 ( Ettwig et al., 2010 ; Haroon et al., 2013 ). Reflecting their aerobic methylotrophic lifestyle, methanotrophs thrive in oxic–anoxic interfaces where CH 4 fluxes are high, including peat bogs, wetlands, rice paddies, forest soils and geothermal habitats ( Singh et al., 2010 ; Knief, 2015 ). However, they also exist within soil and marine ecosystems where CH 4 and oxygen (O 2 ) are more variable ( Knief et al., 2003 ; Tavormina et al., 2010 ; Knief, 2015 ). Based on current paradigms, aerobic methanotrophs are thought to primarily grow on one-carbon (C1) compounds in the environment ( Dedysh et al., 2005 ). All species can grow by oxidising CH 4 to methanol via particulate or soluble methane monooxygenase. They subsequently oxidise methanol to carbon dioxide (CO 2 ), yielding reducing equivalents (e.g. NADH) for respiration and biosynthesis. Proteobacterial methanotrophs generate biomass by assimilating the intermediate formaldehyde via the ribulose monophosphate or serine pathways ( Hanson and Hanson, 1996 ). In contrast, verrucomicrobial methanotrophs oxidise methanol directly to formate ( Keltjens et al., 2014 ) and generate biomass by fixing CO 2 via the Calvin–Benson–Bassham cycle ( Khadem et al., 2011 ). While these specialist C1-based metabolisms are thought to be the primary growth strategy under optimal conditions (i.e. CH 4 and O 2 replete conditions), they would presumably be less effective in dynamic environments where CH 4 and oxidant availability are likely to fluctuate. To add to this complexity, the methane monooxygenase reaction (CH 4 +O 2 +[NAD(P)H+H + ]/QH 2 →CH 3 OH+NAD(P) + /Q+H 2 O) ( Hakemian and Rosenzweig, 2007 ) is metabolically demanding, given it requires simultaneous sources of CH 4 , endogenous reductant (NAD(P)H or quinol) and exogenous O 2 to proceed. Methanotrophs therefore must carefully allocate resources to meet carbon, energy and reductant demands ( Hanson and Hanson, 1996 ). This complex balancing act provokes that, in order to be viable in environments limited for CH 4 and O 2 gases ( Knief et al., 2003 ; Tavormina et al., 2010 ), methanotrophs should be able to supplement C1 usage with other energy-yielding strategies. Recent pure culture studies have provided evidence that CH 4 -oxidising bacteria are indeed more metabolically versatile than previously thought. A minority of conventional methanotrophs can meet energy demands by oxidising the trace concentrations of CH 4 (1.8 ppmv) found in the atmosphere ( Kolb et al., 2005 ; Ho et al., 2013 ; Cai et al., 2016 ). Contrary to the long-held paradigm that methanotrophs are obligate methylotrophs, species from three alphaproteobacterial genera have been shown to grow on simple organic acids, alcohols and short-chain alkane gases ( Dedysh et al., 2005 ; Crombie and Murrell, 2014 ). Most recently, it has been shown that some methanotrophs are not exclusive heterotrophs: the verrucomicrobium Methylacidiphilum fumariolicum SolV can sustain chemolithoautotrophic growth on molecular hydrogen (H 2 ) through the activity of two [NiFe]-hydrogenases ( Mohammadi et al., 2016 ). Proteobacterial methanotrophs can also consume H 2 , though to date this process has only been reported as providing reductant to supplement methanotrophic growth ( Chen and Yoch, 1987 ; Shah et al., 1995 ; Hanczár et al., 2002 ). Our recent findings demonstrating a widespread distribution and diversity of hydrogenases in aerobic bacteria, in specific methanotrophs ( Greening et al., 2014a , 2014b , 2015 , 2016 ), led us to surmise that H 2 metabolism could serve a multifaceted role in adaptation of methanotrophic bacteria to their environment. Specifically, H 2 may serve as an important electron donor for the organism to meet carbon, energy and reductant demands in response to fluctuations in CH 4 and oxidant availability. In this work, we addressed this", "role": "user" }, { "content": "An international research team co-led by a Monash biologist has shown that methane-oxidising bacteria – key organisms responsible for greenhouse gas mitigation – are more flexible and resilient than previously thought. Soil bacteria that oxidise methane (methanotrophs) are globally important in capturing methane before it enters the atmosphere, and we now know that they can consume hydrogen gas to enhance their growth and survival. This new research, published in the prestigious International Society for Microbial Ecology Journal, has major implications for greenhouse gas mitigation. Industrial companies are using methanotrophs to convert methane gas emissions into useful products, for example liquid fuels and protein feeds. \"The findings of this research explain why methanotrophs are abundant in soil ecosystems,\" said Dr Chris Greening from the Centre for Geometric Biology at Monash University. \"Methane is a challenging energy source to assimilate. \"By being able to use hydrogen as well, methanotrophs can grow better in a range of conditions.\" Methanotrophs can survive in environments when methane or oxygen are no longer available. \"It was their very existence in such environments that led us to investigate the possibilities that these organisms might also use other energy-yielding strategies,\" Dr Greening said. Dr Greening's lab focuses on the metabolic strategies that microorganisms use to persist in unfavourable environments and he studies this in relation to the core areas of global change, disease and biodiversity. In this latest study, Dr Greening and collaborators isolated and characterised a methanotroph from a New Zealand volcanic field. The strain could grow on methane or hydrogen separately, but performed best when both gases were available. \"This study is significant because it shows that key consumers of methane emissions are also able to grow on inorganic compounds such as hydrogen,\" Dr Greening said. \"This new knowledge helps us to reduce emissions of greenhouse gases. \" Industrial processes such as petroleum production and waste treatment release large amounts of the methane, carbon dioxide and hydrogen into the atmosphere. \"By using these gas-guzzling bacteria, it's possible to convert these gases into useful liquid fuels and feeds instead,\" Dr Greening said. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Aerobic methanotrophic bacteria have evolved a specialist lifestyle dependent on consumption of methane and other short-chain carbon compounds. However, their apparent substrate specialism runs contrary to the high relative abundance of these microorganisms in dynamic environments, where the availability of methane and oxygen fluctuates. In this work, we provide in situ and ex situ evidence that verrucomicrobial methanotrophs are mixotrophs. Verrucomicrobia-dominated soil communities from an acidic geothermal field in Rotokawa, New Zealand rapidly oxidised methane and hydrogen simultaneously. We isolated and characterised a verrucomicrobial strain from these soils, Methylacidiphilum sp. RTK17.1, and showed that it constitutively oxidises molecular hydrogen. Genomic analysis confirmed that this strain encoded two [NiFe]-hydrogenases (group 1d and 3b), and biochemical assays revealed that it used hydrogen as an electron donor for aerobic respiration and carbon fixation. While the strain could grow heterotrophically on methane or autotrophically on hydrogen, it grew optimally by combining these metabolic strategies. Hydrogen oxidation was particularly important for adaptation to methane and oxygen limitation. Complementary to recent findings of hydrogenotrophic growth by Methylacidiphilum fumariolicum SolV, our findings illustrate that verrucomicrobial methanotrophs have evolved to simultaneously utilise hydrogen and methane from geothermal sources to meet energy and carbon demands where nutrient flux is dynamic. This mixotrophic lifestyle is likely to have facilitated expansion of the niche space occupied by these microorganisms, allowing them to become dominant in geothermally influenced surface soils. Genes encoding putative oxygen-tolerant uptake [NiFe]-hydrogenases were identified in all publicly available methanotroph genomes, suggesting hydrogen oxidation is a general metabolic strategy in this guild. Introduction Aerobic methane-oxidising bacteria (methanotrophs) consume the potent greenhouse gas methane (CH 4 ) ( Kirschke et al., 2013 ). They serve as the primary biological sink of atmospheric methane (~30 Tg annum −1 ) ( Hanson and Hanson, 1996 ) and, together with anaerobic methane-oxidising archaea, also capture the majority of biologically and geologically produced CH 4 before it enters the atmosphere ( Oremland and Culbertson, 1992 ). Relative to their global impact as greenhouse gas mitigators, aerobic methanotrophs exhibit low phylogenetic diversity and are presently limited to 26 genera in the Alphaproteobacteria and Gammaproteobacteria ( Euzéby, 1997 ), two candidate genera in the phylum Verrucomicrobia ( Op den Camp et al., 2009 ; van Teeseling et al., 2014 ), and two representatives of candidate phylum NC10 ( Ettwig et al., 2010 ; Haroon et al., 2013 ). Reflecting their aerobic methylotrophic lifestyle, methanotrophs thrive in oxic–anoxic interfaces where CH 4 fluxes are high, including peat bogs, wetlands, rice paddies, forest soils and geothermal habitats ( Singh et al., 2010 ; Knief, 2015 ). However, they also exist within soil and marine ecosystems where CH 4 and oxygen (O 2 ) are more variable ( Knief et al., 2003 ; Tavormina et al., 2010 ; Knief, 2015 ). Based on current paradigms, aerobic methanotrophs are thought to primarily grow on one-carbon (C1) compounds in the environment ( Dedysh et al., 2005 ). All species can grow by oxidising CH 4 to methanol via particulate or soluble methane monooxygenase. They subsequently oxidise methanol to carbon dioxide (CO 2 ), yielding reducing equivalents (e.g. NADH) for respiration and biosynthesis. Proteobacterial methanotrophs generate biomass by assimilating the intermediate formaldehyde via the ribulose monophosphate or serine pathways ( Hanson and Hanson, 1996 ). In contrast, verrucomicrobial methanotrophs oxidise methanol directly to formate ( Keltjens et al., 2014 ) and generate biomass by fixing CO 2 via the Calvin–Benson–Bassham cycle ( Khadem et al., 2011 ). While these specialist C1-based metabolisms are thought to be the primary growth strategy under optimal conditions (i.e. CH 4 and O 2 replete conditions), they would presumably be less effective in dynamic environments where CH 4 and oxidant availability are likely to fluctuate. To add to this complexity, the methane monooxygenase reaction (CH 4 +O 2 +[NAD(P)H+H + ]/QH 2 →CH 3 OH+NAD(P) + /Q+H 2 O) ( Hakemian and Rosenzweig, 2007 ) is metabolically demanding, given it requires simultaneous sources of CH 4 , endogenous reductant (NAD(P)H or quinol) and exogenous O 2 to proceed. Methanotrophs therefore must carefully allocate resources to meet carbon, energy and reductant demands ( Hanson and Hanson, 1996 ). This complex balancing act provokes that, in order to be viable in environments limited for CH 4 and O 2 gases ( Knief et al., 2003 ; Tavormina et al., 2010 ), methanotrophs should be able to supplement C1 usage with other energy-yielding strategies. Recent pure culture studies have provided evidence that CH 4 -oxidising bacteria are indeed more metabolically versatile than previously thought. A minority of conventional methanotrophs can meet energy demands by oxidising the trace concentrations of CH 4 (1.8 ppmv) found in the atmosphere ( Kolb et al., 2005 ; Ho et al., 2013 ; Cai et al., 2016 ). Contrary to the long-held paradigm that methanotrophs are obligate methylotrophs, species from three alphaproteobacterial genera have been shown to grow on simple organic acids, alcohols and short-chain alkane gases ( Dedysh et al., 2005 ; Crombie and Murrell, 2014 ). Most recently, it has been shown that some methanotrophs are not exclusive heterotrophs: the verrucomicrobium Methylacidiphilum fumariolicum SolV can sustain chemolithoautotrophic growth on molecular hydrogen (H 2 ) through the activity of two [NiFe]-hydrogenases ( Mohammadi et al., 2016 ). Proteobacterial methanotrophs can also consume H 2 , though to date this process has only been reported as providing reductant to supplement methanotrophic growth ( Chen and Yoch, 1987 ; Shah et al., 1995 ; Hanczár et al., 2002 ). Our recent findings demonstrating a widespread distribution and diversity of hydrogenases in aerobic bacteria, in specific methanotrophs ( Greening et al., 2014a , 2014b , 2015 , 2016 ), led us to surmise that H 2 metabolism could serve a multifaceted role in adaptation of methanotrophic bacteria to their environment. Specifically, H 2 may serve as an important electron donor for the organism to meet carbon, energy and reductant demands in response to fluctuations in CH 4 and oxidant availability. In this work, we addressed this<|im_end|> <|im_start|>assistant An international research team co-led by a Monash biologist has shown that methane-oxidising bacteria – key organisms responsible for greenhouse gas mitigation – are more flexible and resilient than previously thought. Soil bacteria that oxidise methane (methanotrophs) are globally important in capturing methane before it enters the atmosphere, and we now know that they can consume hydrogen gas to enhance their growth and survival. This new research, published in the prestigious International Society for Microbial Ecology Journal, has major implications for greenhouse gas mitigation. Industrial companies are using methanotrophs to convert methane gas emissions into useful products, for example liquid fuels and protein feeds. "The findings of this research explain why methanotrophs are abundant in soil ecosystems," said Dr Chris Greening from the Centre for Geometric Biology at Monash University. "Methane is a challenging energy source to assimilate. "By being able to use hydrogen as well, methanotrophs can grow better in a range of conditions." Methanotrophs can survive in environments when methane or oxygen are no longer available. "It was their very existence in such environments that led us to investigate the possibilities that these organisms might also use other energy-yielding strategies," Dr Greening said. Dr Greening's lab focuses on the metabolic strategies that microorganisms use to persist in unfavourable environments and he studies this in relation to the core areas of global change, disease and biodiversity. In this latest study, Dr Greening and collaborators isolated and characterised a methanotroph from a New Zealand volcanic field. The strain could grow on methane or hydrogen separately, but performed best when both gases were available. "This study is significant because it shows that key consumers of methane emissions are also able to grow on inorganic compounds such as hydrogen," Dr Greening said. "This new knowledge helps us to reduce emissions of greenhouse gases. " Industrial processes such as petroleum production and waste treatment release large amounts of the methane, carbon dioxide and hydrogen into the atmosphere. "By using these gas-guzzling bacteria, it's possible to convert these gases into useful liquid fuels and feeds instead," Dr Greening said. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 64150, 31906, 21747, 276, 354, 42810, 24032, 617, 28995, 264, 24687, 19433, 18222, 389, 15652, 315, 61083, 323, 1023, 2875, 66286, 12782, 32246, 13, 4452, 11, 872, 10186, 54057, 3361, 2191, 8640, 26102, 311, 279, 1579, 8844, 37492, 315, 1521, 8162, 76991, 304, 8915, 22484, 11, 1405, 279, 18539, 315, 61083, 323, 24463, 39388, 52085, 13, 763, 420, 990, 11, 584, 3493, 304, 10109, 323, 506, 10109, 6029, 430, 72567, 84, 884, 83059, 21747, 276, 354, 22761, 82, 527, 6651, 354, 22761, 82, 13, 650, 618, 84, 884, 2823, 14840, 90723, 17614, 10977, 505, 459, 84903, 3980, 91096, 2115, 304, 28460, 564, 14406, 11, 1561, 17340, 19019, 36172, 4147, 61083, 323, 35784, 25291, 13, 1226, 25181, 323, 3752, 4147, 264, 72567, 84, 884, 83059, 26800, 505, 1521, 69561, 11, 386, 42972, 58156, 15619, 321, 372, 993, 13, 10860, 42, 1114, 13, 16, 11, 323, 8710, 430, 433, 9129, 332, 3210, 36172, 5014, 31206, 35784, 13, 9500, 3151, 6492, 11007, 430, 420, 26800, 21136, 1403, 510, 57594, 6251, 11958, 67229, 4469, 2315, 320, 4166, 220, 16, 67, 323, 220, 18, 65, 705, 323, 93532, 99592, 10675, 430, 433, 1511, 35784, 439, 459, 17130, 35558, 369, 91490, 594, 29579, 323, 12782, 84862, 13, 6104, 279, 26800, 1436, 3139, 30548, 354, 22761, 2740, 389, 61083, 477, 3154, 354, 22761, 2740, 389, 35784, 11, 433, 14264, 7706, 750, 555, 35271, 1521, 41861, 15174, 13, 40602, 4469, 71162, 574, 8104, 3062, 369, 34185, 311, 61083, 323, 24463, 20893, 13, 1219, 67082, 311, 3293, 14955, 315, 35784, 354, 42810, 6650, 555, 386, 42972, 58156, 15619, 321, 372, 282, 372, 2850, 7918, 372, 11730, 53, 11, 1057, 14955, 41468, 430, 72567, 84, 884, 83059, 21747, 276, 354, 22761, 82, 617, 28995, 311, 25291, 69152, 35784, 323, 61083, 505, 3980, 91096, 8336, 311, 3449, 4907, 323, 12782, 18651, 1405, 50123, 31405, 374, 8915, 13, 1115, 6651, 354, 42810, 19433, 374, 4461, 311, 617, 72849, 14800, 315, 279, 35149, 3634, 25366, 555, 1521, 8162, 76991, 11, 10923, 1124, 311, 3719, 25462, 304, 3980, 1605, 76, 750, 28160, 7479, 69561, 13, 9500, 288, 11418, 2231, 1413, 24463, 2442, 22847, 519, 69575, 510, 57594, 6251, 11958, 67229, 4469, 2315, 1051, 11054, 304, 682, 17880, 2561, 21747, 276, 354, 22761, 85381, 11, 23377, 35784, 71162, 374, 264, 4689, 41861, 8446, 304, 420, 27509, 13, 29438, 64150, 31906, 61083, 12, 85078, 3876, 24032, 320, 69991, 276, 354, 22761, 82, 8, 25024, 279, 36875, 37647, 6962, 61083, 320, 2198, 220, 19, 883, 320, 735, 82965, 441, 1880, 453, 2637, 220, 679, 18, 7609, 2435, 8854, 439, 279, 6156, 24156, 19868, 315, 45475, 61083, 31857, 966, 350, 70, 87757, 25173, 16, 883, 320, 76313, 323, 76313, 11, 220, 2550, 21, 883, 323, 11, 3871, 449, 41390, 261, 31906, 61083, 12, 85078, 3876, 39211, 64, 11, 1101, 12602, 279, 8857, 315, 6160, 30450, 323, 3980, 30450, 9124, 6969, 220, 19, 1603, 433, 29933, 279, 16975, 320, 34543, 86794, 323, 32794, 9339, 942, 11, 220, 2550, 17, 7609, 40502, 311, 872, 3728, 5536, 439, 37647, 6962, 36090, 3046, 11, 91490, 21747, 276, 354, 22761, 82, 31324, 3428, 37555, 86945, 5411, 20057, 323, 527, 50801, 7347, 311, 220, 1627, 84535, 304, 279, 1708, 764, 391, 5646, 677, 78852, 323, 31079, 2235, 5646, 677, 78852, 320, 469, 5308, 978, 1729, 11, 220, 2550, 22, 7026, 1403, 9322, 84535, 304, 279, 1343, 28433, 650, 618, 84, 884, 2823, 14840, 320, 10901, 3453, 9702, 1880, 453, 2637, 220, 1049, 24, 2652, 5355, 2722, 288, 20659, 1880, 453, 2637, 220, 679, 19, 7026, 323, 1403, 24005, 315, 9322, 1343, 28433, 20660, 605, 320, 469, 5683, 38022, 1880, 453, 2637, 220, 679, 15, 2652, 5340, 9186, 1880, 453, 2637, 220, 679, 18, 7609, 35698, 287, 872, 91490, 79574, 354, 42810, 19433, 11, 21747, 276, 354, 22761, 82, 41972, 304, 297, 14668, 4235, 276, 82329, 25066, 1405, 6969, 220, 19, 31405, 288, 527, 1579, 11, 2737, 1069, 266, 293, 27403, 11, 14739, 8329, 11, 20228, 54269, 552, 11, 13952, 69561, 323, 3980, 91096, 71699, 320, 27992, 1880, 453, 2637, 220, 679, 15, 2652, 13934, 4843, 11, 220, 679, 20, 7609, 4452, 11, 814, 1101, 3073, 2949, 17614, 323, 29691, 61951, 1405, 6969, 220, 19, 323, 24463, 320, 46, 220, 17, 883, 527, 810, 3977, 320, 13934, 4843, 1880, 453, 2637, 220, 1049, 18, 2652, 350, 402, 494, 2259, 1880, 453, 2637, 220, 679, 15, 2652, 13934, 4843, 11, 220, 679, 20, 7609, 20817, 389, 1510, 28417, 343, 1026, 11, 91490, 21747, 276, 354, 22761, 82, 527, 3463, 311, 15871, 3139, 389, 832, 24948, 6098, 320, 34, 16, 8, 32246, 304, 279, 4676, 320, 423, 9497, 939, 1880, 453, 2637, 220, 1049, 20, 7609, 2052, 9606, 649, 3139, 555, 36172, 3876, 6969, 220, 19, 311, 21747, 39710, 4669, 2598, 6468, 477, 88045, 61083, 1647, 2689, 19472, 521, 13, 2435, 28520, 36172, 1082, 21747, 39710, 311, 12782, 40589, 320, 8445, 220, 17, 7026, 78504, 18189, 86106, 320, 68, 1326, 13, 452, 1846, 39, 8, 369, 594, 29579, 323, 49554, 74767, 13, 15542, 677, 71034, 21747, 276, 354, 22761, 82, 7068, 58758, 555, 40054, 321, 1113, 279, 29539, 16287, 86836, 4669, 279, 20735, 360, 974, 1647, 5237, 93473, 477, 1446, 483, 44014, 320, 76313, 323, 76313, 11, 220, 2550, 21, 7609, 763, 13168, 11, 72567, 84, 884, 83059, 21747, 276, 354, 22761, 82, 36172, 1082, 21747, 39710, 6089, 311, 1376, 349, 320, 735, 3903, 73, 729, 1880, 453, 2637, 220, 679, 19, 883, 323, 7068, 58758, 555, 36351, 7432, 220, 17, 4669, 279, 51983, 4235, 33, 34237, 4235, 33, 395, 5721, 11008, 320, 20774, 60472, 1880, 453, 2637, 220, 679, 16, 7609, 6104, 1521, 24687, 356, 16, 6108, 28168, 13978, 527, 3463, 311, 387, 279, 6156, 6650, 8446, 1234, 23669, 4787, 320, 72, 1770, 13, 6969, 220, 19, 323, 507, 220, 17, 312, 5282, 4787, 705, 814, 1053, 36548, 387, 2753, 7524, 304, 8915, 22484, 1405, 6969, 220, 19, 323, 36172, 519, 18539, 527, 4461, 311, 39388, 6426, 13, 2057, 923, 311, 420, 23965, 11, 279, 61083, 1647, 2689, 19472, 521, 13010, 320, 2198, 220, 19, 489, 46, 220, 17, 489, 58, 45, 1846, 5417, 8, 39, 10, 39, 489, 2331, 14, 48, 39, 220, 17, 11651, 2198, 220, 18, 29822, 72822, 1846, 5417, 8, 489, 611, 48, 10, 39, 220, 17, 507, 8, 320, 72398, 336, 1122, 323, 35120, 89, 906, 343, 11, 220, 1049, 22, 883, 374, 28168, 2740, 26192, 11, 2728, 433, 7612, 58632, 8336, 315, 6969, 220, 19, 1174, 842, 53595, 312, 1076, 519, 320, 45, 1846, 5417, 8, 39, 477, 934, 258, 337, 8, 323, 506, 53595, 507, 220, 17, 311, 10570, 13, 57175, 276, 354, 22761, 82, 9093, 2011, 15884, 22864, 5070, 311, 3449, 12782, 11, 4907, 323, 312, 1076, 519, 18651, 320, 76313, 323, 76313, 11, 220, 2550, 21, 7609, 1115, 6485, 44463, 1180, 2605, 8099, 430, 11, 304, 2015, 311, 387, 31528, 304, 22484, 7347, 369, 6969, 220, 19, 323, 507, 220, 17, 45612, 320, 13934, 4843, 1880, 453, 2637, 220, 1049, 18, 2652, 350, 402, 494, 2259, 1880, 453, 2637, 220, 679, 15, 7026, 21747, 276, 354, 22761, 82, 1288, 387, 3025, 311, 22822, 356, 16, 10648, 449, 1023, 4907, 12303, 100092, 15174, 13, 35390, 10748, 7829, 7978, 617, 3984, 6029, 430, 6969, 220, 19, 482, 85078, 3876, 24032, 527, 13118, 810, 28168, 2740, 33045, 1109, 8767, 3463, 13, 362, 23413, 315, 21349, 21747, 276, 354, 22761, 82, 649, 3449, 4907, 18651, 555, 36172, 3876, 279, 11917, 32466, 315, 6969, 220, 19, 320, 16, 13, 23, 64697, 85, 8, 1766, 304, 279, 16975, 320, 46615, 65, 1880, 453, 2637, 220, 1049, 20, 2652, 17723, 1880, 453, 2637, 220, 679, 18, 2652, 356, 2192, 1880, 453, 2637, 220, 679, 21, 7609, 35341, 661, 311, 279, 1317, 58606, 49340, 430, 21747, 276, 354, 22761, 82, 527, 12611, 349, 79574, 354, 22761, 82, 11, 9606, 505, 2380, 65695, 391, 5646, 677, 71034, 84535, 617, 1027, 6982, 311, 3139, 389, 4382, 17808, 33969, 11, 453, 40375, 3145, 323, 2875, 66286, 58998, 2194, 45612, 320, 423, 9497, 939, 1880, 453, 2637, 220, 1049, 20, 2652, 92707, 22493, 323, 386, 852, 657, 11, 220, 679, 19, 7609, 7648, 6051, 11, 433, 706, 1027, 6982, 430, 1063, 21747, 276, 354, 22761, 82, 527, 539, 14079, 30548, 354, 22761, 82, 25, 279, 72567, 84, 884, 2823, 65, 2411, 386, 42972, 58156, 15619, 321, 372, 282, 372, 2850, 7918, 372, 11730, 53, 649, 14201, 8590, 48218, 78, 2784, 354, 42810, 6650, 389, 31206, 35784, 320, 39, 220, 17, 883, 1555, 279, 5820, 315, 1403, 510, 57594, 6251, 11958, 67229, 4469, 2315, 320, 20409, 8836, 2836, 1880, 453, 2637, 220, 679, 21, 7609, 15542, 677, 71034, 21747, 276, 354, 22761, 82, 649, 1101, 25024, 473, 220, 17, 1174, 3582, 311, 2457, 420, 1920, 706, 1193, 1027, 5068, 439, 8405, 312, 1076, 519, 311, 22822, 21747, 276, 354, 42810, 6650, 320, 25507, 323, 816, 5059, 11, 220, 3753, 22, 2652, 37617, 1880, 453, 2637, 220, 2550, 20, 2652, 473, 1149, 89, 42354, 1880, 453, 2637, 220, 1049, 17, 7609, 5751, 3293, 14955, 45296, 264, 24716, 8141, 323, 20057, 315, 35784, 2315, 304, 91490, 24032, 11, 304, 3230, 21747, 276, 354, 22761, 82, 320, 7997, 287, 1880, 453, 2637, 220, 679, 19, 64, 1174, 220, 679, 19, 65, 1174, 220, 679, 20, 1174, 220, 679, 21, 7026, 6197, 603, 311, 1765, 74306, 430, 473, 220, 17, 39097, 1436, 8854, 264, 62387, 582, 25489, 3560, 304, 34185, 315, 21747, 276, 354, 42810, 24032, 311, 872, 4676, 13, 45863, 11, 473, 220, 17, 1253, 8854, 439, 459, 3062, 17130, 35558, 369, 279, 47120, 311, 3449, 12782, 11, 4907, 323, 312, 1076, 519, 18651, 304, 2077, 311, 65649, 304, 6969, 220, 19, 323, 36172, 519, 18539, 13, 763, 420, 990, 11, 584, 20669, 420, 128257, 198, 128256, 78191, 198, 2127, 6625, 3495, 2128, 1080, 35054, 555, 264, 3206, 1003, 88704, 706, 6982, 430, 61083, 12, 85078, 3876, 24032, 1389, 1401, 44304, 8647, 369, 37647, 6962, 66860, 1389, 527, 810, 19303, 323, 59780, 1109, 8767, 3463, 13, 76619, 24032, 430, 36172, 1082, 61083, 320, 69991, 276, 354, 22761, 82, 8, 527, 31550, 3062, 304, 40880, 61083, 1603, 433, 29933, 279, 16975, 11, 323, 584, 1457, 1440, 430, 814, 649, 25024, 35784, 6962, 311, 18885, 872, 6650, 323, 20237, 13, 1115, 502, 3495, 11, 4756, 304, 279, 41385, 7327, 13581, 369, 18654, 48059, 78375, 10139, 11, 706, 3682, 25127, 369, 37647, 6962, 66860, 13, 25563, 5220, 527, 1701, 21747, 276, 354, 22761, 82, 311, 5625, 61083, 6962, 20748, 1139, 5505, 3956, 11, 369, 3187, 14812, 40373, 323, 13128, 35496, 13, 330, 791, 14955, 315, 420, 3495, 10552, 3249, 21747, 276, 354, 22761, 82, 527, 44611, 304, 17614, 61951, 1359, 1071, 2999, 11517, 7997, 287, 505, 279, 14821, 369, 4323, 24264, 40023, 520, 3206, 1003, 3907, 13, 330, 44, 774, 2194, 374, 264, 17436, 4907, 2592, 311, 40054, 76457, 13, 330, 1383, 1694, 3025, 311, 1005, 35784, 439, 1664, 11, 21747, 276, 354, 22761, 82, 649, 3139, 2731, 304, 264, 2134, 315, 4787, 1210, 57175, 276, 354, 22761, 82, 649, 18167, 304, 22484, 994, 61083, 477, 24463, 527, 912, 5129, 2561, 13, 330, 2181, 574, 872, 1633, 14209, 304, 1778, 22484, 430, 6197, 603, 311, 19874, 279, 24525, 430, 1521, 44304, 2643, 1101, 1005, 1023, 4907, 12303, 100092, 15174, 1359, 2999, 7997, 287, 1071, 13, 2999, 7997, 287, 596, 10278, 24400, 389, 279, 41861, 15174, 430, 8162, 76991, 1005, 311, 23135, 304, 9662, 27089, 481, 22484, 323, 568, 7978, 420, 304, 12976, 311, 279, 6332, 5789, 315, 3728, 2349, 11, 8624, 323, 73119, 13, 763, 420, 5652, 4007, 11, 2999, 7997, 287, 323, 79119, 25181, 323, 3752, 4147, 264, 21747, 276, 354, 22761, 505, 264, 1561, 17340, 67164, 2115, 13, 578, 26800, 1436, 3139, 389, 61083, 477, 35784, 26214, 11, 719, 10887, 1888, 994, 2225, 45612, 1051, 2561, 13, 330, 2028, 4007, 374, 5199, 1606, 433, 5039, 430, 1401, 13723, 315, 61083, 20748, 527, 1101, 3025, 311, 3139, 389, 304, 61694, 32246, 1778, 439, 35784, 1359, 2999, 7997, 287, 1071, 13, 330, 2028, 502, 6677, 8779, 603, 311, 8108, 20748, 315, 37647, 45612, 13, 330, 25563, 11618, 1778, 439, 60063, 5788, 323, 12571, 6514, 4984, 3544, 15055, 315, 279, 61083, 11, 12782, 40589, 323, 35784, 1139, 279, 16975, 13, 330, 1383, 1701, 1521, 6962, 2427, 9065, 2785, 24032, 11, 433, 596, 3284, 311, 5625, 1521, 45612, 1139, 5505, 14812, 40373, 323, 35496, 4619, 1359, 2999, 7997, 287, 1071, 13, 220, 128257, 198 ]

2,090

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract We have developed a new synthesis method that includes a chemical vapor deposition process in a chamber settled in organic liquid, and applied its nonequilibrium reaction field to the development of novel carbon nanomaterials. In the synthesis at 1110–1120 K, using graphene oxide as a catalyst support, iron acetate and cobalt acetate as catalyst precursors, and 2-propanol as a carbon source as well as the organic liquid, we succeeded to create carbon nanofiber composed of novel pot-shaped units, named carbon nanopot. A carbon nanopot has a complex and regular nanostructure consisting of several parts made of different layer numbers of graphene and a deep hollow space. Dense graphene edges, hydroxylated presumably, are localized around its closed end. The typical size of a carbon nanopot was 20–40 nm in outer diameter, 5–30 nm in inner diameter, and 100–200 nm in length. A growth model of carbon nanopot and its applications are proposed. Access provided by MPDL Services gGmbH c/o Max Planck Digital Library Working on a manuscript? Avoid the common mistakes I. INTRODUCTION Carbon is capable of forming various hexagonal networks incorporating partially pentagonal or heptangular structures with sp 2 hybrids. 1 A variety of carbon nanomaterials with unique forms, including fullerenes, 2 carbon nanotubes (CNTs), 3 graphene 4 and so on, have been generated owing to this versatility. Even as for CNTs or nanofibers, bamboo-type, 5 cup-stacked-type, 6 beaded 7 and necklace-type 8 tubes, nanobells, 9 and nanocoils 10 as well as cylindrical ones have been reported. Applications of these materials have been intensively examined so as to take advantage of their structural features or physical properties. As the properties of carbon nanomaterials could be superior or peculiar depending on their structures, 1 creating novel carbon nanomaterials has been one of the significant subjects in materials research. One of the effective approaches to produce novel structures is the application of nonequilibrium conditions such as high temperature gradients or rapid cooling in the synthesis. It is known that inhibition of a reverse reaction or control of precipitation through rapid cooling is a key point in the arc discharge synthesis of fullerene 11 or chemical vapor deposition (CVD) of graphene, 12 respectively. The high growth rate of CNTs is achieved in the liquid phase deposition, and is attributed to the high gradient of temperature around catalysts immersed in an organic liquid. 13 A flaw of this technique is the difficulty in applying catalysts that are solvable to organic liquids or peeled from substrates due to violent bubbling during the deposition. To resolve the flaw, we have been developing a synthesis technique, named submarine-style substrate heating CVD, in which catalysts do not contact organic liquid despite the fact that the synthesis chamber is settled in the liquid. In the present study, we have adopted graphene oxide 14 (GO) as a catalyst support in applying this CVD method to the synthesis of carbon nanomaterials, and succeeded to synthesize nanofibers composed of novel pot-shaped carbon nanomaterials, named carbon nanopot in this study. GO is well-known as an excellent support of metal nanoparticles, and its potential applications in catalysis, light energy conversion, fuel cells, and sensors have been examined. 15 On the other hand, CNTs were produced in a conventional CVD with GO-supported Ni nanoparticles. 16 No further investigation, however, into the synthesis of carbon nanomaterials with GO-supported catalysts has been reported to the best of our knowledge. Catalyst supporting materials made of sp 2 carbon could not only disperse metal nanoparticles as well as zeolite 17 but also affect the structure of produced materials made of the same sp 2 carbon. Nanobell has been already known as a container-shaped carbon nanomaterial that is synthesized in the appearance of fiber. This material was separated into pieces through intense ultrasonication for the application as drug-delivery vehicle in a recent study. 18 The properties of carbon nanopot, such as the capacity and the controlled release of medicine, are expected to be definitely superior to those of nanobell as the aspect ratio of a nanopot is much larger than that of a nanobell. In addition, a nanopot has a complex structure in which graphene edges are distributed unevenly at its outer surface and are exposed densely around its closed end, which would enable one to develop new nanomaterials processing unavailable to conventional nanomaterials. The growth mechanism of this uniquely structured nanomaterial should be also discussed. Several formation mechanisms have been proposed for CNT. 19 Two general modes, tip-growth mode 20 and base-growth mode 21 are accepted widely in the catalyzed CVD of CNTs on substrates. Depending on the strength of the catalyst-substrate (or -support) interaction, catalyst particles separate from the substrate during the precipitation of CNT across the particle bottom in the former mode, and are anchored to the substrate surface while CNT precipitates out around the particle’s apex in the latter mode. The state of catalyst particles during the CNT growth, and the diffusion of carbon after carbon source, such as hydrocarbon, is decomposed on the surface of catalyst particles have been also debatable, whether the catalyst is in the liquid 22 , 23 or solid state 24 and whether the carbon diffusion is a volume one 24 , 25 or a surface one, 26 , 27 respectively. Several in situ atomic-scale electron microscopy studies were conducted to approach the heart of these issues. Those studies have revealed that catalyst particles exhibit successive elongation and contraction during the formation of the bamboo-type CNTs in the tip-growth mode while they remain crystalline. 28 , 29 This dynamic deformation of the catalyst particle could also take place in the formation of carbon nanopots. However, one should note that these two nanomaterials are distinct from each other in their nanostructures as described above, which suggests that some aspects of the growth mechanism of carbon nanopot could be unique. As for the carbon diffusion, both a surface one 28 and a volume one 29 , 30 have been confirmed or supported. In this paper, we report the development of the submarine-style", "role": "user" }, { "content": "A novel, pot-shaped, carbon nanomaterial developed by researchers from Kumamoto University, Japan is several times deeper than any hollow carbon nanostructure previously produced. This unique characteristic enables the material to gradually release substances contained within and is expected to be beneficial in applications such as drug delivery systems. Carbon is an element that is light, abundant, has a strong binding force, and eco-friendly. The range of carbon-based materials is expected to become more widespread in the eco-friendly society of the future. Recently, nanosized (one-billionth of a meter) carbon materials have been developed with lengths, widths, or heights below 100 nm. These materials take extreme forms such as tiny grained substances, thin sheet-like substances, and slim fibrous substances. Example of these new materials are fullerenes, which are hollow cage-like carbon molecules; carbon nanotubes, cylindrical nanostructures of carbon molecules; and graphene, one-atom thick sheets of carbon molecules. Why are these tiny substances needed? One reason is that reactions with other materials can be much larger if a substance has an increased surface area. When using nanomaterials in place of existing materials, it is possible to significantly change surface area without changing weight and volume, thereby improving both size and performance. The development of carbon nanomaterials has provided novel nanostructured materials with shapes and characteristics that surpass existing materials. Now, research from the laboratory of Kumamoto University's Associate Prof. Yokoi has resulted in the successful development of a container-type carbon nanomaterial with a much deeper orifice than that found in similar materials. To create the new material, researchers used their own, newly developed method of material synthesis. The container-shaped nanomaterial has a complex form consisting of varied layers of stacked graphene at the bottom, the body, and the neck areas of the container, and the graphene edges along the outer surface of the body were found to be very dense. Due to these innovate features, Associate Prof. Yokoi and colleagues named the material the \"carbon nanopot.\" The black arrow indicates the end of the opening of carbon nanopot. A structural schematic of the carbon nanopot showing hydroxyl groups bonded to the edges of the graphene layers near the closed end of the nanopot is also indicated (not to scale). Credit: Journal of Materials Research, 31((1): 117-126, 14-Jan-2016, doi:10.1557/jmr.2015.389.Copyright: Materials Research Society The carbon nanopot has an outer diameter of 20 ~ 40 nm, an inner diameter of 5 ~ 30 nm, and a length of 100 ~ 200 nm. During its creation, the carbon nanopot is linked to a carbon nanofiber with a length of 20 ~ 100 μm meaning that the carbon nanopot is also available as a carbon nanofiber. At the junction between nanopots, the bottom of one pot simply sits on the opening of the next without sharing a graphene sheet connection. Consequently, separating nanopots is very easy. \"From a detailed surface analysis, hydrophilic hydroxyl groups were found clustered along the outer surface of the carbon nanopot body,\" said Associate Prof. Yokoi. \"Graphene is usually hydrophobic however, if hydroxyl groups are densely packed on the outer surface of the body, that area will be hydrophilic. In other words, carbon nanopots could be a unique nanomaterial with both hydrophobic and hydrophilic characteristics. We are currently in the process of performing a more sophisticated surface analysis in order to get that assurance.\" Since this new carbon nanopot has a relatively deep orifice, one of its expected uses is to improve drug delivery systems by acting as a new foundation for medicine to be carried into and be absorbed by the body. This finding was posted as an Invited Feature Paper in the Journal of Materials Research, on January 13th, 2016. Additionally, the paper was elected as a Key Scientific Article in Advances in Engineering (AIE) on July 9th, 2016. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract We have developed a new synthesis method that includes a chemical vapor deposition process in a chamber settled in organic liquid, and applied its nonequilibrium reaction field to the development of novel carbon nanomaterials. In the synthesis at 1110–1120 K, using graphene oxide as a catalyst support, iron acetate and cobalt acetate as catalyst precursors, and 2-propanol as a carbon source as well as the organic liquid, we succeeded to create carbon nanofiber composed of novel pot-shaped units, named carbon nanopot. A carbon nanopot has a complex and regular nanostructure consisting of several parts made of different layer numbers of graphene and a deep hollow space. Dense graphene edges, hydroxylated presumably, are localized around its closed end. The typical size of a carbon nanopot was 20–40 nm in outer diameter, 5–30 nm in inner diameter, and 100–200 nm in length. A growth model of carbon nanopot and its applications are proposed. Access provided by MPDL Services gGmbH c/o Max Planck Digital Library Working on a manuscript? Avoid the common mistakes I. INTRODUCTION Carbon is capable of forming various hexagonal networks incorporating partially pentagonal or heptangular structures with sp 2 hybrids. 1 A variety of carbon nanomaterials with unique forms, including fullerenes, 2 carbon nanotubes (CNTs), 3 graphene 4 and so on, have been generated owing to this versatility. Even as for CNTs or nanofibers, bamboo-type, 5 cup-stacked-type, 6 beaded 7 and necklace-type 8 tubes, nanobells, 9 and nanocoils 10 as well as cylindrical ones have been reported. Applications of these materials have been intensively examined so as to take advantage of their structural features or physical properties. As the properties of carbon nanomaterials could be superior or peculiar depending on their structures, 1 creating novel carbon nanomaterials has been one of the significant subjects in materials research. One of the effective approaches to produce novel structures is the application of nonequilibrium conditions such as high temperature gradients or rapid cooling in the synthesis. It is known that inhibition of a reverse reaction or control of precipitation through rapid cooling is a key point in the arc discharge synthesis of fullerene 11 or chemical vapor deposition (CVD) of graphene, 12 respectively. The high growth rate of CNTs is achieved in the liquid phase deposition, and is attributed to the high gradient of temperature around catalysts immersed in an organic liquid. 13 A flaw of this technique is the difficulty in applying catalysts that are solvable to organic liquids or peeled from substrates due to violent bubbling during the deposition. To resolve the flaw, we have been developing a synthesis technique, named submarine-style substrate heating CVD, in which catalysts do not contact organic liquid despite the fact that the synthesis chamber is settled in the liquid. In the present study, we have adopted graphene oxide 14 (GO) as a catalyst support in applying this CVD method to the synthesis of carbon nanomaterials, and succeeded to synthesize nanofibers composed of novel pot-shaped carbon nanomaterials, named carbon nanopot in this study. GO is well-known as an excellent support of metal nanoparticles, and its potential applications in catalysis, light energy conversion, fuel cells, and sensors have been examined. 15 On the other hand, CNTs were produced in a conventional CVD with GO-supported Ni nanoparticles. 16 No further investigation, however, into the synthesis of carbon nanomaterials with GO-supported catalysts has been reported to the best of our knowledge. Catalyst supporting materials made of sp 2 carbon could not only disperse metal nanoparticles as well as zeolite 17 but also affect the structure of produced materials made of the same sp 2 carbon. Nanobell has been already known as a container-shaped carbon nanomaterial that is synthesized in the appearance of fiber. This material was separated into pieces through intense ultrasonication for the application as drug-delivery vehicle in a recent study. 18 The properties of carbon nanopot, such as the capacity and the controlled release of medicine, are expected to be definitely superior to those of nanobell as the aspect ratio of a nanopot is much larger than that of a nanobell. In addition, a nanopot has a complex structure in which graphene edges are distributed unevenly at its outer surface and are exposed densely around its closed end, which would enable one to develop new nanomaterials processing unavailable to conventional nanomaterials. The growth mechanism of this uniquely structured nanomaterial should be also discussed. Several formation mechanisms have been proposed for CNT. 19 Two general modes, tip-growth mode 20 and base-growth mode 21 are accepted widely in the catalyzed CVD of CNTs on substrates. Depending on the strength of the catalyst-substrate (or -support) interaction, catalyst particles separate from the substrate during the precipitation of CNT across the particle bottom in the former mode, and are anchored to the substrate surface while CNT precipitates out around the particle’s apex in the latter mode. The state of catalyst particles during the CNT growth, and the diffusion of carbon after carbon source, such as hydrocarbon, is decomposed on the surface of catalyst particles have been also debatable, whether the catalyst is in the liquid 22 , 23 or solid state 24 and whether the carbon diffusion is a volume one 24 , 25 or a surface one, 26 , 27 respectively. Several in situ atomic-scale electron microscopy studies were conducted to approach the heart of these issues. Those studies have revealed that catalyst particles exhibit successive elongation and contraction during the formation of the bamboo-type CNTs in the tip-growth mode while they remain crystalline. 28 , 29 This dynamic deformation of the catalyst particle could also take place in the formation of carbon nanopots. However, one should note that these two nanomaterials are distinct from each other in their nanostructures as described above, which suggests that some aspects of the growth mechanism of carbon nanopot could be unique. As for the carbon diffusion, both a surface one 28 and a volume one 29 , 30 have been confirmed or supported. In this paper, we report the development of the submarine-style<|im_end|> <|im_start|>assistant A novel, pot-shaped, carbon nanomaterial developed by researchers from Kumamoto University, Japan is several times deeper than any hollow carbon nanostructure previously produced. This unique characteristic enables the material to gradually release substances contained within and is expected to be beneficial in applications such as drug delivery systems. Carbon is an element that is light, abundant, has a strong binding force, and eco-friendly. The range of carbon-based materials is expected to become more widespread in the eco-friendly society of the future. Recently, nanosized (one-billionth of a meter) carbon materials have been developed with lengths, widths, or heights below 100 nm. These materials take extreme forms such as tiny grained substances, thin sheet-like substances, and slim fibrous substances. Example of these new materials are fullerenes, which are hollow cage-like carbon molecules; carbon nanotubes, cylindrical nanostructures of carbon molecules; and graphene, one-atom thick sheets of carbon molecules. Why are these tiny substances needed? One reason is that reactions with other materials can be much larger if a substance has an increased surface area. When using nanomaterials in place of existing materials, it is possible to significantly change surface area without changing weight and volume, thereby improving both size and performance. The development of carbon nanomaterials has provided novel nanostructured materials with shapes and characteristics that surpass existing materials. Now, research from the laboratory of Kumamoto University's Associate Prof. Yokoi has resulted in the successful development of a container-type carbon nanomaterial with a much deeper orifice than that found in similar materials. To create the new material, researchers used their own, newly developed method of material synthesis. The container-shaped nanomaterial has a complex form consisting of varied layers of stacked graphene at the bottom, the body, and the neck areas of the container, and the graphene edges along the outer surface of the body were found to be very dense. Due to these innovate features, Associate Prof. Yokoi and colleagues named the material the "carbon nanopot." The black arrow indicates the end of the opening of carbon nanopot. A structural schematic of the carbon nanopot showing hydroxyl groups bonded to the edges of the graphene layers near the closed end of the nanopot is also indicated (not to scale). Credit: Journal of Materials Research, 31((1): 117-126, 14-Jan-2016, doi:10.1557/jmr.2015.389.Copyright: Materials Research Society The carbon nanopot has an outer diameter of 20 ~ 40 nm, an inner diameter of 5 ~ 30 nm, and a length of 100 ~ 200 nm. During its creation, the carbon nanopot is linked to a carbon nanofiber with a length of 20 ~ 100 μm meaning that the carbon nanopot is also available as a carbon nanofiber. At the junction between nanopots, the bottom of one pot simply sits on the opening of the next without sharing a graphene sheet connection. Consequently, separating nanopots is very easy. "From a detailed surface analysis, hydrophilic hydroxyl groups were found clustered along the outer surface of the carbon nanopot body," said Associate Prof. Yokoi. "Graphene is usually hydrophobic however, if hydroxyl groups are densely packed on the outer surface of the body, that area will be hydrophilic. In other words, carbon nanopots could be a unique nanomaterial with both hydrophobic and hydrophilic characteristics. We are currently in the process of performing a more sophisticated surface analysis in order to get that assurance." Since this new carbon nanopot has a relatively deep orifice, one of its expected uses is to improve drug delivery systems by acting as a new foundation for medicine to be carried into and be absorbed by the body. This finding was posted as an Invited Feature Paper in the Journal of Materials Research, on January 13th, 2016. Additionally, the paper was elected as a Key Scientific Article in Advances in Engineering (AIE) on July 9th, 2016. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 1226, 617, 8040, 264, 502, 39975, 1749, 430, 5764, 264, 11742, 38752, 65374, 1920, 304, 264, 25199, 23183, 304, 17808, 14812, 11, 323, 9435, 1202, 7000, 447, 46780, 13010, 2115, 311, 279, 4500, 315, 11775, 12782, 20622, 316, 2229, 82, 13, 763, 279, 39975, 520, 220, 5037, 15, 4235, 7261, 15, 735, 11, 1701, 66192, 51180, 439, 264, 51483, 1862, 11, 11245, 65802, 349, 323, 34928, 3223, 65802, 349, 439, 51483, 5956, 34291, 11, 323, 220, 17, 10039, 857, 337, 439, 264, 12782, 2592, 439, 1664, 439, 279, 17808, 14812, 11, 584, 26399, 311, 1893, 12782, 20622, 1073, 8799, 24306, 315, 11775, 3419, 35831, 8316, 11, 7086, 12782, 76307, 354, 13, 362, 12782, 76307, 354, 706, 264, 6485, 323, 5912, 51593, 7993, 31706, 315, 3892, 5596, 1903, 315, 2204, 6324, 5219, 315, 66192, 323, 264, 5655, 42902, 3634, 13, 43622, 66192, 13116, 11, 17055, 87, 4010, 660, 36548, 11, 527, 44589, 2212, 1202, 8036, 842, 13, 578, 14595, 1404, 315, 264, 12782, 76307, 354, 574, 220, 508, 4235, 1272, 26807, 304, 16335, 23899, 11, 220, 20, 4235, 966, 26807, 304, 9358, 23899, 11, 323, 220, 1041, 4235, 1049, 26807, 304, 3160, 13, 362, 6650, 1646, 315, 12782, 76307, 354, 323, 1202, 8522, 527, 11223, 13, 9742, 3984, 555, 9599, 16931, 8471, 342, 38, 32198, 272, 20886, 7639, 9878, 377, 14434, 11896, 22938, 389, 264, 47913, 30, 35106, 279, 4279, 21294, 358, 13, 9403, 91199, 22208, 374, 13171, 315, 30164, 5370, 12651, 24346, 14488, 52913, 26310, 20801, 24346, 477, 568, 418, 4328, 14726, 449, 993, 220, 17, 97205, 13, 220, 16, 362, 8205, 315, 12782, 20622, 316, 2229, 82, 449, 5016, 7739, 11, 2737, 2539, 17848, 288, 11, 220, 17, 12782, 20622, 354, 51725, 320, 98354, 82, 705, 220, 18, 66192, 220, 19, 323, 779, 389, 11, 617, 1027, 8066, 56612, 311, 420, 60112, 13, 7570, 439, 369, 356, 6542, 82, 477, 20622, 1073, 581, 388, 11, 59982, 10827, 11, 220, 20, 10747, 5594, 11440, 10827, 11, 220, 21, 387, 14589, 220, 22, 323, 55547, 10827, 220, 23, 34083, 11, 20622, 677, 6572, 11, 220, 24, 323, 20622, 13441, 8839, 220, 605, 439, 1664, 439, 79610, 6305, 617, 1027, 5068, 13, 32625, 315, 1521, 7384, 617, 1027, 25228, 3210, 25078, 779, 439, 311, 1935, 9610, 315, 872, 24693, 4519, 477, 7106, 6012, 13, 1666, 279, 6012, 315, 12782, 20622, 316, 2229, 82, 1436, 387, 16757, 477, 44797, 11911, 389, 872, 14726, 11, 220, 16, 6968, 11775, 12782, 20622, 316, 2229, 82, 706, 1027, 832, 315, 279, 5199, 15223, 304, 7384, 3495, 13, 3861, 315, 279, 7524, 20414, 311, 8356, 11775, 14726, 374, 279, 3851, 315, 7000, 447, 46780, 4787, 1778, 439, 1579, 9499, 53249, 477, 11295, 28015, 304, 279, 39975, 13, 1102, 374, 3967, 430, 61478, 315, 264, 10134, 13010, 477, 2585, 315, 61050, 1555, 11295, 28015, 374, 264, 1401, 1486, 304, 279, 15952, 32643, 39975, 315, 88018, 1994, 220, 806, 477, 11742, 38752, 65374, 320, 34, 12757, 8, 315, 66192, 11, 220, 717, 15947, 13, 578, 1579, 6650, 4478, 315, 356, 6542, 82, 374, 17427, 304, 279, 14812, 10474, 65374, 11, 323, 374, 30706, 311, 279, 1579, 20779, 315, 9499, 2212, 51483, 82, 78308, 304, 459, 17808, 14812, 13, 220, 1032, 362, 26784, 315, 420, 15105, 374, 279, 17250, 304, 19486, 51483, 82, 430, 527, 2092, 24694, 311, 17808, 67849, 477, 83612, 505, 16146, 988, 4245, 311, 16806, 78869, 9894, 2391, 279, 65374, 13, 2057, 9006, 279, 26784, 11, 584, 617, 1027, 11469, 264, 39975, 15105, 11, 7086, 58629, 11549, 54057, 24494, 356, 12757, 11, 304, 902, 51483, 82, 656, 539, 3729, 17808, 14812, 8994, 279, 2144, 430, 279, 39975, 25199, 374, 23183, 304, 279, 14812, 13, 763, 279, 3118, 4007, 11, 584, 617, 18306, 66192, 51180, 220, 975, 320, 15881, 8, 439, 264, 51483, 1862, 304, 19486, 420, 356, 12757, 1749, 311, 279, 39975, 315, 12782, 20622, 316, 2229, 82, 11, 323, 26399, 311, 6925, 27985, 20622, 1073, 581, 388, 24306, 315, 11775, 3419, 35831, 12782, 20622, 316, 2229, 82, 11, 7086, 12782, 76307, 354, 304, 420, 4007, 13, 12890, 374, 1664, 22015, 439, 459, 9250, 1862, 315, 9501, 94753, 11, 323, 1202, 4754, 8522, 304, 34454, 4548, 11, 3177, 4907, 14747, 11, 10633, 7917, 11, 323, 26148, 617, 1027, 25078, 13, 220, 868, 1952, 279, 1023, 1450, 11, 356, 6542, 82, 1051, 9124, 304, 264, 21349, 356, 12757, 449, 12890, 88213, 22652, 94753, 13, 220, 845, 2360, 4726, 8990, 11, 4869, 11, 1139, 279, 39975, 315, 12782, 20622, 316, 2229, 82, 449, 12890, 88213, 51483, 82, 706, 1027, 5068, 311, 279, 1888, 315, 1057, 6677, 13, 88957, 12899, 7384, 1903, 315, 993, 220, 17, 12782, 1436, 539, 1193, 834, 82344, 9501, 94753, 439, 1664, 439, 14017, 337, 635, 220, 1114, 719, 1101, 7958, 279, 6070, 315, 9124, 7384, 1903, 315, 279, 1890, 993, 220, 17, 12782, 13, 33242, 677, 616, 706, 1027, 2736, 3967, 439, 264, 5593, 35831, 12782, 20622, 316, 2229, 430, 374, 92106, 304, 279, 11341, 315, 24722, 13, 1115, 3769, 574, 19180, 1139, 9863, 1555, 19428, 37232, 1525, 20901, 369, 279, 3851, 439, 5623, 48226, 6633, 7458, 304, 264, 3293, 4007, 13, 220, 972, 578, 6012, 315, 12782, 76307, 354, 11, 1778, 439, 279, 8824, 323, 279, 14400, 4984, 315, 16088, 11, 527, 3685, 311, 387, 8659, 16757, 311, 1884, 315, 20622, 677, 616, 439, 279, 13189, 11595, 315, 264, 76307, 354, 374, 1790, 8294, 1109, 430, 315, 264, 20622, 677, 616, 13, 763, 5369, 11, 264, 76307, 354, 706, 264, 6485, 6070, 304, 902, 66192, 13116, 527, 4332, 61437, 398, 520, 1202, 16335, 7479, 323, 527, 15246, 97617, 2212, 1202, 8036, 842, 11, 902, 1053, 7431, 832, 311, 2274, 502, 20622, 316, 2229, 82, 8863, 36087, 311, 21349, 20622, 316, 2229, 82, 13, 578, 6650, 17383, 315, 420, 42329, 34030, 20622, 316, 2229, 1288, 387, 1101, 14407, 13, 26778, 18488, 24717, 617, 1027, 11223, 369, 356, 6542, 13, 220, 777, 9220, 4689, 20362, 11, 11813, 2427, 19632, 3941, 220, 508, 323, 2385, 2427, 19632, 3941, 220, 1691, 527, 11928, 13882, 304, 279, 34454, 88, 16284, 356, 12757, 315, 356, 6542, 82, 389, 16146, 988, 13, 40730, 389, 279, 8333, 315, 279, 51483, 18451, 71015, 320, 269, 482, 24249, 8, 16628, 11, 51483, 19252, 8821, 505, 279, 54057, 2391, 279, 61050, 315, 356, 6542, 4028, 279, 19320, 5740, 304, 279, 4846, 3941, 11, 323, 527, 78219, 311, 279, 54057, 7479, 1418, 356, 6542, 36841, 82829, 704, 2212, 279, 19320, 753, 72627, 304, 279, 15629, 3941, 13, 578, 1614, 315, 51483, 19252, 2391, 279, 356, 6542, 6650, 11, 323, 279, 58430, 315, 12782, 1306, 12782, 2592, 11, 1778, 439, 17055, 74441, 11, 374, 29602, 3950, 389, 279, 7479, 315, 51483, 19252, 617, 1027, 1101, 4316, 15436, 11, 3508, 279, 51483, 374, 304, 279, 14812, 220, 1313, 1174, 220, 1419, 477, 6573, 1614, 220, 1187, 323, 3508, 279, 12782, 58430, 374, 264, 8286, 832, 220, 1187, 1174, 220, 914, 477, 264, 7479, 832, 11, 220, 1627, 1174, 220, 1544, 15947, 13, 26778, 304, 10109, 25524, 13230, 17130, 92914, 7978, 1051, 13375, 311, 5603, 279, 4851, 315, 1521, 4819, 13, 13266, 7978, 617, 10675, 430, 51483, 19252, 31324, 50024, 74595, 367, 323, 71895, 2391, 279, 18488, 315, 279, 59982, 10827, 356, 6542, 82, 304, 279, 11813, 2427, 19632, 3941, 1418, 814, 7293, 64568, 483, 13, 220, 1591, 1174, 220, 1682, 1115, 8915, 91621, 315, 279, 51483, 19320, 1436, 1101, 1935, 2035, 304, 279, 18488, 315, 12782, 76307, 2469, 13, 4452, 11, 832, 1288, 5296, 430, 1521, 1403, 20622, 316, 2229, 82, 527, 12742, 505, 1855, 1023, 304, 872, 51593, 47194, 439, 7633, 3485, 11, 902, 13533, 430, 1063, 13878, 315, 279, 6650, 17383, 315, 12782, 76307, 354, 1436, 387, 5016, 13, 1666, 369, 279, 12782, 58430, 11, 2225, 264, 7479, 832, 220, 1591, 323, 264, 8286, 832, 220, 1682, 1174, 220, 966, 617, 1027, 11007, 477, 7396, 13, 763, 420, 5684, 11, 584, 1934, 279, 4500, 315, 279, 58629, 11549, 128257, 198, 128256, 78191, 198, 32, 11775, 11, 3419, 35831, 11, 12782, 20622, 316, 2229, 8040, 555, 12074, 505, 86341, 57960, 3907, 11, 6457, 374, 3892, 3115, 19662, 1109, 904, 42902, 12782, 51593, 7993, 8767, 9124, 13, 1115, 5016, 29683, 20682, 279, 3769, 311, 27115, 4984, 33155, 13282, 2949, 323, 374, 3685, 311, 387, 24629, 304, 8522, 1778, 439, 5623, 9889, 6067, 13, 22208, 374, 459, 2449, 430, 374, 3177, 11, 44611, 11, 706, 264, 3831, 11212, 5457, 11, 323, 42688, 22658, 13, 578, 2134, 315, 12782, 6108, 7384, 374, 3685, 311, 3719, 810, 24716, 304, 279, 42688, 22658, 8396, 315, 279, 3938, 13, 42096, 11, 20622, 437, 1534, 320, 606, 70173, 339, 315, 264, 23819, 8, 12782, 7384, 617, 1027, 8040, 449, 29416, 11, 65511, 11, 477, 36394, 3770, 220, 1041, 26807, 13, 4314, 7384, 1935, 14560, 7739, 1778, 439, 13987, 1099, 2692, 33155, 11, 15792, 11071, 12970, 33155, 11, 323, 30453, 16178, 27620, 33155, 13, 13688, 315, 1521, 502, 7384, 527, 2539, 17848, 288, 11, 902, 527, 42902, 36460, 12970, 12782, 35715, 26, 12782, 20622, 354, 51725, 11, 79610, 51593, 47194, 315, 12782, 35715, 26, 323, 66192, 11, 832, 12, 22612, 12314, 25112, 315, 12782, 35715, 13, 8595, 527, 1521, 13987, 33155, 4460, 30, 3861, 2944, 374, 430, 25481, 449, 1023, 7384, 649, 387, 1790, 8294, 422, 264, 20278, 706, 459, 7319, 7479, 3158, 13, 3277, 1701, 20622, 316, 2229, 82, 304, 2035, 315, 6484, 7384, 11, 433, 374, 3284, 311, 12207, 2349, 7479, 3158, 2085, 10223, 4785, 323, 8286, 11, 28592, 18899, 2225, 1404, 323, 5178, 13, 578, 4500, 315, 12782, 20622, 316, 2229, 82, 706, 3984, 11775, 51593, 52243, 7384, 449, 21483, 323, 17910, 430, 53120, 6484, 7384, 13, 4800, 11, 3495, 505, 279, 27692, 315, 86341, 57960, 3907, 596, 33468, 8626, 13, 94636, 6870, 706, 19543, 304, 279, 6992, 4500, 315, 264, 5593, 10827, 12782, 20622, 316, 2229, 449, 264, 1790, 19662, 477, 22660, 1109, 430, 1766, 304, 4528, 7384, 13, 2057, 1893, 279, 502, 3769, 11, 12074, 1511, 872, 1866, 11, 13945, 8040, 1749, 315, 3769, 39975, 13, 578, 5593, 35831, 20622, 316, 2229, 706, 264, 6485, 1376, 31706, 315, 28830, 13931, 315, 42415, 66192, 520, 279, 5740, 11, 279, 2547, 11, 323, 279, 13272, 5789, 315, 279, 5593, 11, 323, 279, 66192, 13116, 3235, 279, 16335, 7479, 315, 279, 2547, 1051, 1766, 311, 387, 1633, 29050, 13, 24586, 311, 1521, 92064, 4519, 11, 33468, 8626, 13, 94636, 6870, 323, 18105, 7086, 279, 3769, 279, 330, 74441, 76307, 354, 1210, 578, 3776, 18404, 15151, 279, 842, 315, 279, 8736, 315, 12782, 76307, 354, 13, 362, 24693, 68144, 315, 279, 12782, 76307, 354, 9204, 17055, 87, 4010, 5315, 70241, 311, 279, 13116, 315, 279, 66192, 13931, 3221, 279, 8036, 842, 315, 279, 76307, 354, 374, 1101, 16717, 320, 1962, 311, 5569, 570, 16666, 25, 10139, 315, 32009, 8483, 11, 220, 2148, 1209, 16, 1680, 220, 8546, 12, 9390, 11, 220, 975, 67552, 12, 679, 21, 11, 36995, 25, 605, 13, 9992, 22, 4537, 21620, 13, 679, 20, 13, 20422, 732, 2220, 25, 32009, 8483, 13581, 578, 12782, 76307, 354, 706, 459, 16335, 23899, 315, 220, 508, 4056, 220, 1272, 26807, 11, 459, 9358, 23899, 315, 220, 20, 4056, 220, 966, 26807, 11, 323, 264, 3160, 315, 220, 1041, 4056, 220, 1049, 26807, 13, 12220, 1202, 9886, 11, 279, 12782, 76307, 354, 374, 10815, 311, 264, 12782, 20622, 1073, 8799, 449, 264, 3160, 315, 220, 508, 4056, 220, 1041, 33983, 76, 7438, 430, 279, 12782, 76307, 354, 374, 1101, 2561, 439, 264, 12782, 20622, 1073, 8799, 13, 2468, 279, 49341, 1990, 76307, 2469, 11, 279, 5740, 315, 832, 3419, 5042, 23874, 389, 279, 8736, 315, 279, 1828, 2085, 11821, 264, 66192, 11071, 3717, 13, 53123, 11, 50545, 76307, 2469, 374, 1633, 4228, 13, 330, 3915, 264, 11944, 7479, 6492, 11, 17055, 46185, 292, 17055, 87, 4010, 5315, 1051, 1766, 93858, 3235, 279, 16335, 7479, 315, 279, 12782, 76307, 354, 2547, 1359, 1071, 33468, 8626, 13, 94636, 6870, 13, 330, 11461, 1994, 374, 6118, 17055, 764, 31906, 4869, 11, 422, 17055, 87, 4010, 5315, 527, 97617, 19937, 389, 279, 16335, 7479, 315, 279, 2547, 11, 430, 3158, 690, 387, 17055, 46185, 292, 13, 763, 1023, 4339, 11, 12782, 76307, 2469, 1436, 387, 264, 5016, 20622, 316, 2229, 449, 2225, 17055, 764, 31906, 323, 17055, 46185, 292, 17910, 13, 1226, 527, 5131, 304, 279, 1920, 315, 16785, 264, 810, 27877, 7479, 6492, 304, 2015, 311, 636, 430, 44701, 1210, 8876, 420, 502, 12782, 76307, 354, 706, 264, 12309, 5655, 477, 22660, 11, 832, 315, 1202, 3685, 5829, 374, 311, 7417, 5623, 9889, 6067, 555, 15718, 439, 264, 502, 16665, 369, 16088, 311, 387, 11953, 1139, 323, 387, 42101, 555, 279, 2547, 13, 1115, 9455, 574, 8621, 439, 459, 19337, 1639, 20595, 18343, 304, 279, 10139, 315, 32009, 8483, 11, 389, 6186, 220, 1032, 339, 11, 220, 679, 21, 13, 23212, 11, 279, 5684, 574, 16689, 439, 264, 5422, 38130, 13659, 304, 91958, 304, 17005, 320, 32, 5484, 8, 389, 5887, 220, 24, 339, 11, 220, 679, 21, 13, 220, 128257, 198 ]

2,189

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Piezoelectric coefficients are constrained by the intrinsic crystal structure of the constituent material. Here we describe design and manufacturing routes to previously inaccessible classes of piezoelectric materials that have arbitrary piezoelectric coefficient tensors. Our scheme is based on the manipulation of electric displacement maps from families of structural cell patterns. We implement our designs by additively manufacturing free-form, perovskite-based piezoelectric nanocomposites with complex three-dimensional architectures. The resulting voltage response of the activated piezoelectric metamaterials at a given mode can be selectively suppressed, reversed or enhanced with applied stress. Additionally, these electromechanical metamaterials achieve high specific piezoelectric constants and tailorable flexibility using only a fraction of their parent materials. This strategy may be applied to create the next generation of intelligent infrastructure, able to perform a variety of structural and functional tasks, including simultaneous impact absorption and monitoring, three-dimensional pressure mapping and directionality detection. Main The direct piezoelectric constant correlates the electric displacement of a material with an applied stress 1 , 2 , 3 . Owing to their ability to convert mechanical to electrical energy and vice versa, piezoelectric materials have widespread applications in pressure sensing 4 , 5 , ultrasonic sensing 6 , 7 , actuation 8 , 9 and energy harvesting 10 , 11 . The piezoelectric charge constants of bulk piezoelectric ceramics, polymer-piezoelectric composites and their respective foams are dictated by their intrinsic crystallographic structures and compositions 12 , resulting in common coupling modes of operation 13 . Additionally, their intrinsic microstructures are strongly coupled with other physical properties, including mass densities and mechanical properties 14 . Chemical modifications such as doping 15 , 16 have been introduced to change the piezoelectric constants in certain directions by altering the crystallographic structures, but their design space is restricted by the limited set of doping agents 17 . It also comes at the cost of other coupled physical properties such as mechanical flexibility and sensitivity 18 , 19 . Casting and templating techniques have been used to produce piezoelectric foams 20 , 21 that showcase the potential for reduced mass densities and improved hydrostatic figures of merit, but their piezoelectric coefficients, described by a square foam model 22 , are largely limited by the intrinsic crystalline orientation and occupy only a narrow area within piezoelectric anisotropy space. Here we report a set of concepts in which a wealth of direct piezoelectric responses can be generated through rationally designed piezoelectric architectural units and are realized via additive manufacturing of highly sensitive piezo-active lattice materials. Our strategy begins by designing families of three-dimensional (3D) structural node units assembled from parameterized projection patterns, which allows us to generate and manipulate a set of electric displacement maps with a given pressure, thereby achieving full control of piezoelectric constant tensor signatures. These unit cells are then tessellated in three dimensions, forming metamaterial blocks that occupy a vast piezoelectric anisotropy design space, enabling arbitrary selection of the coupled operational mode. Upon polarizing the as-fabricated piezoelectric material, we have demonstrated that piezoelectric behaviour in any direction can be selectively reversed, suppressed or enhanced, achieving distinct voltage response signatures with applied stress. To implement this concept, we prepared functionalized lead zirconate titanate (PZT) nanoparticle colloids. These nanoparticles are then covalently bonded with entrapped photo-active monomers. These concentrated piezoelectric colloids are subsequently sculpted into arbitrary 3D form factors through high-resolution additive manufacturing. We found that building blocks with designed piezoelectric signatures could be assembled into intelligent infrastructures to achieve a variety of functions, including force magnitude and directionality sensing, impact absorption and self-monitoring, and location mapping, without any additional sensing component. These free-form PZT nanocomposite piezoelectric metamaterials not only achieve a high piezoelectric charge constant and voltage constant at low volume fractions but also simultaneously possess high flexibility, characteristics that have not been attainable in previous piezoelectric foams or polymers. This study paves the way for a class of rationally designed electromechanical coupling materials, thus moving structural metamaterials 23 , 24 towards smart infrastructures. Design of 3D piezoelectric responses We developed a strategy to realize the full design space of piezoelectric coefficients through the spatial arrangement of piezoelectric ligaments. Our scheme involves analysing configurations of projection patterns from a 3D node unit classified by connectivity. The evolutions of projection patterns give rise to diverse electric displacement maps (Fig. 1a–h ), from which the piezoelectric coefficient tensor space d 3 M ( M = 1–3) can be designed, going beyond the limitations of the monolithic piezoelectric ceramics, polymers and their composite feedstock whose piezoelectric coefficients are located in the {−−+} quadrants 25 , 26 , 27 , 28 and {++−} quadrants 29 , 30 . Here the dimensionless piezoelectric tensor space, \${{\\bar{\\bf d}}}_{3M}\$ , is defined by normalizing d 3 M by the length of the vector { d 31 , d 32 , d 33 }. To capture the broadest possible design space, we start with the minimum number of intersecting microstruts at a node that can be tessellated into 3D periodic lattices. All intersecting struts are represented as vectors originating from the node, that is, \${\\bf{L}}_i\$ ( i = 1– N , where N is the node unit connectivity). In building our projection patterns, we define \${\\bf{l}}^j_i\$ as the 2D projection of \${\\bf{L}}_i\$ onto three orthogonal planes through the global 1–2–3 coordinate system of the 3D piezoelectric cube (Fig. 1a , \${\\bf{L}}_i = \\frac{1}{2}\\mathop {\\sum }\\limits_j^3 {\\bf{l}}_i^j\$ , where j = 1, 2 or 3). As an example, we use piezoelectric ceramic and its composites, which have \${{\\bar{\\bf d}}}_{3M}\$ distributed in the {−−+} quadrants 25 , 26 , 27 , 28 , as the base material with which to construct the electric displacement maps. The white arrows pointing upwards or downwards against the 3-direction indicate the positive or negative electric displacement response of the strut along the 3-direction (that is, the poling direction). Fig. 1: Design of piezoelectric metamaterials for tailorable piezoelectric charge constants. Designing 3D node units by configuring the projection patterns. a – g , Node unit designs from 3-, 4-, 5- and 8-strut", "role": "user" }, { "content": "The piezoelectric materials that inhabit everything from our cell phones to musical greeting cards may be getting an upgrade thanks to work discussed in the journal Nature Materials released online Jan 21. Xiaoyu 'Rayne' Zheng, assistant professor of mechanical engineering in the College of Engineering, and a member of the Macromolecules Innovation Institute, and his team have developed methods to 3-D print piezoelectric materials that can be custom-designed to convert movement, impact and stress from any directions to electrical energy. \"Piezoelectric materials convert strain and stress into electric charges,\" Zheng explained. The piezoelectric materials come in only a few defined shapes and are made of brittle crystal and ceramic—the kind that require a clean room to manufacture. Zheng's team has developed a technique to 3-D print these materials so they are not restricted by shape or size. The material can also be activated—providing the next generation of intelligent infrastructures and smart materials for tactile sensing, impact and vibration monitoring, energy harvesting, and other applications. Unleash the freedom to design piezoelectrics Piezoelectric materials were originally discovered in the 19th century. Since then the advances in manufacturing technology has led to the requirement of clean-rooms and a complex procedure that produces films and blocks which are connected to electronics after machining. The expensive process and the inherent brittleness of the material, has limited the ability to maximize the material's potential. The printed flexible sheet of piezoelectric material. Credit: Virginia Tech Zheng's team developed a model that allows them to manipulate and design arbitrary piezoelectric constants, resulting in the material generating electric charge movement in response to incoming forces and vibrations from any direction, via a set of 3-D printable topologies. Unlike conventional piezoelectrics where electric charge movements are prescribed by the intrinsic crystals, the new method allows users to prescribe and program voltage responses to be magnified, reversed or suppressed in any direction. \"We have developed a design method and printing platform to freely design the sensitivity and operational modes of piezoelectric materials,\" Zheng said. \"By programming the 3-D active topology, you can achieve pretty much any combination of piezoelectric coefficients within a material, and use them as transducers and sensors that are not only flexible and strong, but also respond to pressure, vibrations and impacts via electric signals that tell the location, magnitude and direction of the impacts within any location of these materials.\" 3-D printing of piezoelectrics, sensors and transducers A factor in current piezoelectric fabrication is the natural crystal used. At the atomic level, the orientation of atoms are fixed. Zheng's team has produced a substitute that mimics the crystal but allows for the lattice orientation to be altered by design. \"We have synthesized a class of highly sensitive piezoelectric inks that can be sculpted into complex three-dimensional features with ultraviolet light. The inks contain highly concentrated piezoelectric nanocrystals bonded with UV-sensitive gels, which form a solution—a milky mixture like melted crystal—that we print with a high-resolution digital light 3-D printer,\" Zheng said. The team demonstrated the 3-D printed materials at a scale measuring fractions of the diameter of a human hair. \"We can tailor the architecture to make them more flexible and use them, for instance, as energy harvesting devices, wrapping them around any arbitrary curvature,\" Zheng said. \"We can make them thick, and light, stiff or energy-absorbing.\" The material has sensitivities 5-fold higher than flexible piezoelectric polymers. The stiffness and shape of the material can be tuned and produced as a thin sheet resembling a strip of gauze, or as a stiff block. \"We have a team making them into wearable devices, like rings, insoles, and fitting them into a boxing glove where we will be able to record impact forces and monitor the health of the user,\" said Zheng. \"The ability to achieve the desired mechanical, electrical and thermal properties will significantly reduce the time and effort needed to develop practical materials,\" said Shashank Priya, associate VP for research at Penn State and former professor of mechanical engineering at Virginia Tech. New applications The team has printed and demonstrated smart materials wrapped around curved surfaces, worn on hands and fingers to convert motion, and harvest the mechanical energy, but the applications go well beyond wearables and consumer electronics. Zheng sees the technology as a leap into robotics, energy harvesting, tactile sensing and intelligent infrastructure, where a structure is made entirely with piezoelectric material, sensing impacts, vibrations and motions, and allowing for those to be monitored and located. The team has printed a small smart bridge to demonstrate its applicability to sensing the locations of dropping impacts, as well as its magnitude, while robust enough to absorb the impact energy. The team also demonstrated their application of a smart transducer that converts underwater vibration signals to electric voltages. \"Traditionally, if you wanted to monitor the internal strength of a structure, you would need to have a lot of individual sensors placed all over the structure, each with a number of leads and connectors,\" said Huachen Cui, a doctoral student with Zheng and first author of the Nature Materials paper. \"Here, the structure itself is the sensor—it can monitor itself.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Piezoelectric coefficients are constrained by the intrinsic crystal structure of the constituent material. Here we describe design and manufacturing routes to previously inaccessible classes of piezoelectric materials that have arbitrary piezoelectric coefficient tensors. Our scheme is based on the manipulation of electric displacement maps from families of structural cell patterns. We implement our designs by additively manufacturing free-form, perovskite-based piezoelectric nanocomposites with complex three-dimensional architectures. The resulting voltage response of the activated piezoelectric metamaterials at a given mode can be selectively suppressed, reversed or enhanced with applied stress. Additionally, these electromechanical metamaterials achieve high specific piezoelectric constants and tailorable flexibility using only a fraction of their parent materials. This strategy may be applied to create the next generation of intelligent infrastructure, able to perform a variety of structural and functional tasks, including simultaneous impact absorption and monitoring, three-dimensional pressure mapping and directionality detection. Main The direct piezoelectric constant correlates the electric displacement of a material with an applied stress 1 , 2 , 3 . Owing to their ability to convert mechanical to electrical energy and vice versa, piezoelectric materials have widespread applications in pressure sensing 4 , 5 , ultrasonic sensing 6 , 7 , actuation 8 , 9 and energy harvesting 10 , 11 . The piezoelectric charge constants of bulk piezoelectric ceramics, polymer-piezoelectric composites and their respective foams are dictated by their intrinsic crystallographic structures and compositions 12 , resulting in common coupling modes of operation 13 . Additionally, their intrinsic microstructures are strongly coupled with other physical properties, including mass densities and mechanical properties 14 . Chemical modifications such as doping 15 , 16 have been introduced to change the piezoelectric constants in certain directions by altering the crystallographic structures, but their design space is restricted by the limited set of doping agents 17 . It also comes at the cost of other coupled physical properties such as mechanical flexibility and sensitivity 18 , 19 . Casting and templating techniques have been used to produce piezoelectric foams 20 , 21 that showcase the potential for reduced mass densities and improved hydrostatic figures of merit, but their piezoelectric coefficients, described by a square foam model 22 , are largely limited by the intrinsic crystalline orientation and occupy only a narrow area within piezoelectric anisotropy space. Here we report a set of concepts in which a wealth of direct piezoelectric responses can be generated through rationally designed piezoelectric architectural units and are realized via additive manufacturing of highly sensitive piezo-active lattice materials. Our strategy begins by designing families of three-dimensional (3D) structural node units assembled from parameterized projection patterns, which allows us to generate and manipulate a set of electric displacement maps with a given pressure, thereby achieving full control of piezoelectric constant tensor signatures. These unit cells are then tessellated in three dimensions, forming metamaterial blocks that occupy a vast piezoelectric anisotropy design space, enabling arbitrary selection of the coupled operational mode. Upon polarizing the as-fabricated piezoelectric material, we have demonstrated that piezoelectric behaviour in any direction can be selectively reversed, suppressed or enhanced, achieving distinct voltage response signatures with applied stress. To implement this concept, we prepared functionalized lead zirconate titanate (PZT) nanoparticle colloids. These nanoparticles are then covalently bonded with entrapped photo-active monomers. These concentrated piezoelectric colloids are subsequently sculpted into arbitrary 3D form factors through high-resolution additive manufacturing. We found that building blocks with designed piezoelectric signatures could be assembled into intelligent infrastructures to achieve a variety of functions, including force magnitude and directionality sensing, impact absorption and self-monitoring, and location mapping, without any additional sensing component. These free-form PZT nanocomposite piezoelectric metamaterials not only achieve a high piezoelectric charge constant and voltage constant at low volume fractions but also simultaneously possess high flexibility, characteristics that have not been attainable in previous piezoelectric foams or polymers. This study paves the way for a class of rationally designed electromechanical coupling materials, thus moving structural metamaterials 23 , 24 towards smart infrastructures. Design of 3D piezoelectric responses We developed a strategy to realize the full design space of piezoelectric coefficients through the spatial arrangement of piezoelectric ligaments. Our scheme involves analysing configurations of projection patterns from a 3D node unit classified by connectivity. The evolutions of projection patterns give rise to diverse electric displacement maps (Fig. 1a–h ), from which the piezoelectric coefficient tensor space d 3 M ( M = 1–3) can be designed, going beyond the limitations of the monolithic piezoelectric ceramics, polymers and their composite feedstock whose piezoelectric coefficients are located in the {−−+} quadrants 25 , 26 , 27 , 28 and {++−} quadrants 29 , 30 . Here the dimensionless piezoelectric tensor space, ${{\bar{\bf d}}}_{3M}$ , is defined by normalizing d 3 M by the length of the vector { d 31 , d 32 , d 33 }. To capture the broadest possible design space, we start with the minimum number of intersecting microstruts at a node that can be tessellated into 3D periodic lattices. All intersecting struts are represented as vectors originating from the node, that is, ${\bf{L}}_i$ ( i = 1– N , where N is the node unit connectivity). In building our projection patterns, we define ${\bf{l}}^j_i$ as the 2D projection of ${\bf{L}}_i$ onto three orthogonal planes through the global 1–2–3 coordinate system of the 3D piezoelectric cube (Fig. 1a , ${\bf{L}}_i = \frac{1}{2}\mathop {\sum }\limits_j^3 {\bf{l}}_i^j$ , where j = 1, 2 or 3). As an example, we use piezoelectric ceramic and its composites, which have ${{\bar{\bf d}}}_{3M}$ distributed in the {−−+} quadrants 25 , 26 , 27 , 28 , as the base material with which to construct the electric displacement maps. The white arrows pointing upwards or downwards against the 3-direction indicate the positive or negative electric displacement response of the strut along the 3-direction (that is, the poling direction). Fig. 1: Design of piezoelectric metamaterials for tailorable piezoelectric charge constants. Designing 3D node units by configuring the projection patterns. a – g , Node unit designs from 3-, 4-, 5- and 8-strut<|im_end|> <|im_start|>assistant The piezoelectric materials that inhabit everything from our cell phones to musical greeting cards may be getting an upgrade thanks to work discussed in the journal Nature Materials released online Jan 21. Xiaoyu 'Rayne' Zheng, assistant professor of mechanical engineering in the College of Engineering, and a member of the Macromolecules Innovation Institute, and his team have developed methods to 3-D print piezoelectric materials that can be custom-designed to convert movement, impact and stress from any directions to electrical energy. "Piezoelectric materials convert strain and stress into electric charges," Zheng explained. The piezoelectric materials come in only a few defined shapes and are made of brittle crystal and ceramic—the kind that require a clean room to manufacture. Zheng's team has developed a technique to 3-D print these materials so they are not restricted by shape or size. The material can also be activated—providing the next generation of intelligent infrastructures and smart materials for tactile sensing, impact and vibration monitoring, energy harvesting, and other applications. Unleash the freedom to design piezoelectrics Piezoelectric materials were originally discovered in the 19th century. Since then the advances in manufacturing technology has led to the requirement of clean-rooms and a complex procedure that produces films and blocks which are connected to electronics after machining. The expensive process and the inherent brittleness of the material, has limited the ability to maximize the material's potential. The printed flexible sheet of piezoelectric material. Credit: Virginia Tech Zheng's team developed a model that allows them to manipulate and design arbitrary piezoelectric constants, resulting in the material generating electric charge movement in response to incoming forces and vibrations from any direction, via a set of 3-D printable topologies. Unlike conventional piezoelectrics where electric charge movements are prescribed by the intrinsic crystals, the new method allows users to prescribe and program voltage responses to be magnified, reversed or suppressed in any direction. "We have developed a design method and printing platform to freely design the sensitivity and operational modes of piezoelectric materials," Zheng said. "By programming the 3-D active topology, you can achieve pretty much any combination of piezoelectric coefficients within a material, and use them as transducers and sensors that are not only flexible and strong, but also respond to pressure, vibrations and impacts via electric signals that tell the location, magnitude and direction of the impacts within any location of these materials." 3-D printing of piezoelectrics, sensors and transducers A factor in current piezoelectric fabrication is the natural crystal used. At the atomic level, the orientation of atoms are fixed. Zheng's team has produced a substitute that mimics the crystal but allows for the lattice orientation to be altered by design. "We have synthesized a class of highly sensitive piezoelectric inks that can be sculpted into complex three-dimensional features with ultraviolet light. The inks contain highly concentrated piezoelectric nanocrystals bonded with UV-sensitive gels, which form a solution—a milky mixture like melted crystal—that we print with a high-resolution digital light 3-D printer," Zheng said. The team demonstrated the 3-D printed materials at a scale measuring fractions of the diameter of a human hair. "We can tailor the architecture to make them more flexible and use them, for instance, as energy harvesting devices, wrapping them around any arbitrary curvature," Zheng said. "We can make them thick, and light, stiff or energy-absorbing." The material has sensitivities 5-fold higher than flexible piezoelectric polymers. The stiffness and shape of the material can be tuned and produced as a thin sheet resembling a strip of gauze, or as a stiff block. "We have a team making them into wearable devices, like rings, insoles, and fitting them into a boxing glove where we will be able to record impact forces and monitor the health of the user," said Zheng. "The ability to achieve the desired mechanical, electrical and thermal properties will significantly reduce the time and effort needed to develop practical materials," said Shashank Priya, associate VP for research at Penn State and former professor of mechanical engineering at Virginia Tech. New applications The team has printed and demonstrated smart materials wrapped around curved surfaces, worn on hands and fingers to convert motion, and harvest the mechanical energy, but the applications go well beyond wearables and consumer electronics. Zheng sees the technology as a leap into robotics, energy harvesting, tactile sensing and intelligent infrastructure, where a structure is made entirely with piezoelectric material, sensing impacts, vibrations and motions, and allowing for those to be monitored and located. The team has printed a small smart bridge to demonstrate its applicability to sensing the locations of dropping impacts, as well as its magnitude, while robust enough to absorb the impact energy. The team also demonstrated their application of a smart transducer that converts underwater vibration signals to electric voltages. "Traditionally, if you wanted to monitor the internal strength of a structure, you would need to have a lot of individual sensors placed all over the structure, each with a number of leads and connectors," said Huachen Cui, a doctoral student with Zheng and first author of the Nature Materials paper. "Here, the structure itself is the sensor—it can monitor itself." <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 41097, 89, 4748, 47262, 37929, 527, 54852, 555, 279, 47701, 26110, 6070, 315, 279, 75164, 3769, 13, 5810, 584, 7664, 2955, 323, 15266, 11543, 311, 8767, 82828, 6989, 315, 4447, 89, 4748, 47262, 7384, 430, 617, 25142, 4447, 89, 4748, 47262, 36706, 78187, 13, 5751, 13155, 374, 3196, 389, 279, 34786, 315, 9249, 44153, 14370, 505, 8689, 315, 24693, 2849, 12912, 13, 1226, 4305, 1057, 14769, 555, 923, 275, 3210, 15266, 1949, 8627, 11, 824, 869, 4991, 635, 6108, 4447, 89, 4748, 47262, 20622, 12255, 81239, 449, 6485, 2380, 33520, 78335, 13, 578, 13239, 22465, 2077, 315, 279, 22756, 4447, 89, 4748, 47262, 88848, 2229, 82, 520, 264, 2728, 3941, 649, 387, 82775, 56089, 11, 28537, 477, 24872, 449, 9435, 8631, 13, 23212, 11, 1521, 54707, 4842, 45983, 88848, 2229, 82, 11322, 1579, 3230, 4447, 89, 4748, 47262, 18508, 323, 9986, 25745, 25152, 1701, 1193, 264, 19983, 315, 872, 2748, 7384, 13, 1115, 8446, 1253, 387, 9435, 311, 1893, 279, 1828, 9659, 315, 25530, 14054, 11, 3025, 311, 2804, 264, 8205, 315, 24693, 323, 16003, 9256, 11, 2737, 58632, 5536, 44225, 323, 16967, 11, 2380, 33520, 7410, 13021, 323, 5216, 2786, 18468, 13, 4802, 578, 2167, 4447, 89, 4748, 47262, 6926, 97303, 279, 9249, 44153, 315, 264, 3769, 449, 459, 9435, 8631, 220, 16, 1174, 220, 17, 1174, 220, 18, 662, 507, 24510, 311, 872, 5845, 311, 5625, 22936, 311, 20314, 4907, 323, 17192, 46391, 11, 4447, 89, 4748, 47262, 7384, 617, 24716, 8522, 304, 7410, 60199, 220, 19, 1174, 220, 20, 1174, 37232, 43375, 60199, 220, 21, 1174, 220, 22, 1174, 1180, 4090, 220, 23, 1174, 220, 24, 323, 4907, 66747, 220, 605, 1174, 220, 806, 662, 578, 4447, 89, 4748, 47262, 6900, 18508, 315, 20155, 4447, 89, 4748, 47262, 96806, 11, 47393, 2320, 74466, 4748, 47262, 470, 81239, 323, 872, 20081, 12018, 4214, 527, 81498, 555, 872, 47701, 26110, 848, 79173, 14726, 323, 62644, 220, 717, 1174, 13239, 304, 4279, 59086, 20362, 315, 5784, 220, 1032, 662, 23212, 11, 872, 47701, 8162, 47194, 527, 16917, 34356, 449, 1023, 7106, 6012, 11, 2737, 3148, 90816, 323, 22936, 6012, 220, 975, 662, 36424, 29882, 1778, 439, 97928, 220, 868, 1174, 220, 845, 617, 1027, 11784, 311, 2349, 279, 4447, 89, 4748, 47262, 18508, 304, 3738, 18445, 555, 60923, 279, 26110, 848, 79173, 14726, 11, 719, 872, 2955, 3634, 374, 22486, 555, 279, 7347, 743, 315, 97928, 13307, 220, 1114, 662, 1102, 1101, 4131, 520, 279, 2853, 315, 1023, 34356, 7106, 6012, 1778, 439, 22936, 25152, 323, 27541, 220, 972, 1174, 220, 777, 662, 66848, 323, 68630, 1113, 12823, 617, 1027, 1511, 311, 8356, 4447, 89, 4748, 47262, 12018, 4214, 220, 508, 1174, 220, 1691, 430, 35883, 279, 4754, 369, 11293, 3148, 90816, 323, 13241, 17055, 2020, 12678, 315, 38559, 11, 719, 872, 4447, 89, 4748, 47262, 37929, 11, 7633, 555, 264, 9518, 32183, 1646, 220, 1313, 1174, 527, 14090, 7347, 555, 279, 47701, 64568, 483, 17140, 323, 48678, 1193, 264, 15376, 3158, 2949, 4447, 89, 4748, 47262, 459, 285, 354, 18237, 3634, 13, 5810, 584, 1934, 264, 743, 315, 19476, 304, 902, 264, 12205, 315, 2167, 4447, 89, 4748, 47262, 14847, 649, 387, 8066, 1555, 436, 30154, 6319, 4447, 89, 4748, 47262, 43563, 8316, 323, 527, 15393, 4669, 64338, 15266, 315, 7701, 16614, 4447, 13028, 32344, 55372, 7384, 13, 5751, 8446, 12302, 555, 30829, 8689, 315, 2380, 33520, 320, 18, 35, 8, 24693, 2494, 8316, 35105, 505, 5852, 1534, 22343, 12912, 11, 902, 6276, 603, 311, 7068, 323, 37735, 264, 743, 315, 9249, 44153, 14370, 449, 264, 2728, 7410, 11, 28592, 32145, 2539, 2585, 315, 4447, 89, 4748, 47262, 6926, 16000, 33728, 13, 4314, 5089, 7917, 527, 1243, 80930, 616, 660, 304, 2380, 15696, 11, 30164, 88848, 2229, 10215, 430, 48678, 264, 13057, 4447, 89, 4748, 47262, 459, 285, 354, 18237, 2955, 3634, 11, 28462, 25142, 6727, 315, 279, 34356, 25605, 3941, 13, 30538, 25685, 4954, 279, 439, 2269, 29997, 660, 4447, 89, 4748, 47262, 3769, 11, 584, 617, 21091, 430, 4447, 89, 4748, 47262, 17432, 304, 904, 5216, 649, 387, 82775, 28537, 11, 56089, 477, 24872, 11, 32145, 12742, 22465, 2077, 33728, 449, 9435, 8631, 13, 2057, 4305, 420, 7434, 11, 584, 10235, 16003, 1534, 3063, 1167, 89376, 349, 86612, 349, 320, 47, 57, 51, 8, 76307, 7203, 82048, 3447, 13, 4314, 94753, 527, 1243, 1080, 838, 4501, 70241, 449, 11751, 5795, 6685, 32344, 1647, 69638, 13, 4314, 38626, 4447, 89, 4748, 47262, 82048, 3447, 527, 28520, 27863, 291, 1139, 25142, 220, 18, 35, 1376, 9547, 1555, 1579, 64036, 64338, 15266, 13, 1226, 1766, 430, 4857, 10215, 449, 6319, 4447, 89, 4748, 47262, 33728, 1436, 387, 35105, 1139, 25530, 49276, 47194, 311, 11322, 264, 8205, 315, 5865, 11, 2737, 5457, 26703, 323, 5216, 2786, 60199, 11, 5536, 44225, 323, 659, 92734, 287, 11, 323, 3813, 13021, 11, 2085, 904, 5217, 60199, 3777, 13, 4314, 1949, 8627, 393, 57, 51, 20622, 12255, 13921, 4447, 89, 4748, 47262, 88848, 2229, 82, 539, 1193, 11322, 264, 1579, 4447, 89, 4748, 47262, 6900, 6926, 323, 22465, 6926, 520, 3428, 8286, 65995, 719, 1101, 25291, 15575, 1579, 25152, 11, 17910, 430, 617, 539, 1027, 36861, 481, 304, 3766, 4447, 89, 4748, 47262, 12018, 4214, 477, 46033, 388, 13, 1115, 4007, 281, 4798, 279, 1648, 369, 264, 538, 315, 436, 30154, 6319, 54707, 4842, 45983, 59086, 7384, 11, 8617, 7366, 24693, 88848, 2229, 82, 220, 1419, 1174, 220, 1187, 7119, 7941, 49276, 47194, 13, 7127, 315, 220, 18, 35, 4447, 89, 4748, 47262, 14847, 1226, 8040, 264, 8446, 311, 13383, 279, 2539, 2955, 3634, 315, 4447, 89, 4748, 47262, 37929, 1555, 279, 29079, 27204, 315, 4447, 89, 4748, 47262, 29413, 24469, 13, 5751, 13155, 18065, 22209, 287, 33483, 315, 22343, 12912, 505, 264, 220, 18, 35, 2494, 5089, 21771, 555, 31357, 13, 578, 3721, 20813, 315, 22343, 12912, 3041, 10205, 311, 17226, 9249, 44153, 14370, 320, 30035, 13, 220, 16, 64, 4235, 71, 7026, 505, 902, 279, 4447, 89, 4748, 47262, 36706, 16000, 3634, 294, 220, 18, 386, 320, 386, 284, 220, 16, 4235, 18, 8, 649, 387, 6319, 11, 2133, 7953, 279, 9669, 315, 279, 1647, 66470, 4447, 89, 4748, 47262, 96806, 11, 46033, 388, 323, 872, 28814, 5510, 13787, 6832, 4447, 89, 4748, 47262, 37929, 527, 7559, 304, 279, 314, 34363, 34363, 10, 92, 30236, 1821, 220, 914, 1174, 220, 1627, 1174, 220, 1544, 1174, 220, 1591, 323, 314, 1044, 34363, 92, 30236, 1821, 220, 1682, 1174, 220, 966, 662, 5810, 279, 13167, 1752, 4447, 89, 4748, 47262, 16000, 3634, 11, 1144, 2358, 36802, 2308, 36802, 13536, 294, 3500, 52635, 18, 44, 11281, 8, 1174, 374, 4613, 555, 4725, 4954, 294, 220, 18, 386, 555, 279, 3160, 315, 279, 4724, 314, 294, 220, 2148, 1174, 294, 220, 843, 1174, 294, 220, 1644, 17336, 2057, 12602, 279, 7353, 478, 3284, 2955, 3634, 11, 584, 1212, 449, 279, 8187, 1396, 315, 32896, 287, 8162, 496, 6256, 520, 264, 2494, 430, 649, 387, 80930, 616, 660, 1139, 220, 18, 35, 39445, 326, 1617, 1238, 13, 2052, 32896, 287, 610, 6256, 527, 15609, 439, 23728, 71373, 505, 279, 2494, 11, 430, 374, 11, 1144, 2358, 59, 13536, 90, 43, 3500, 62, 72, 58858, 320, 602, 284, 220, 16, 4235, 452, 1174, 1405, 452, 374, 279, 2494, 5089, 31357, 570, 763, 4857, 1057, 22343, 12912, 11, 584, 7124, 1144, 2358, 59, 13536, 95717, 3500, 61, 73, 5431, 58858, 439, 279, 220, 17, 35, 22343, 315, 1144, 2358, 59, 13536, 90, 43, 3500, 62, 72, 58858, 8800, 2380, 95680, 25761, 1555, 279, 3728, 220, 16, 4235, 17, 4235, 18, 16580, 1887, 315, 279, 220, 18, 35, 4447, 89, 4748, 47262, 24671, 320, 30035, 13, 220, 16, 64, 1174, 1144, 2358, 59, 13536, 90, 43, 3500, 62, 72, 284, 1144, 38118, 90, 16, 15523, 17, 11281, 10590, 454, 29252, 1264, 52400, 42178, 5487, 61, 18, 29252, 13536, 95717, 3500, 62, 72, 61, 73, 58858, 1174, 1405, 503, 284, 220, 16, 11, 220, 17, 477, 220, 18, 570, 1666, 459, 3187, 11, 584, 1005, 4447, 89, 4748, 47262, 43124, 323, 1202, 470, 81239, 11, 902, 617, 1144, 2358, 36802, 2308, 36802, 13536, 294, 3500, 52635, 18, 44, 11281, 8, 4332, 304, 279, 314, 34363, 34363, 10, 92, 30236, 1821, 220, 914, 1174, 220, 1627, 1174, 220, 1544, 1174, 220, 1591, 1174, 439, 279, 2385, 3769, 449, 902, 311, 9429, 279, 9249, 44153, 14370, 13, 578, 4251, 38057, 22364, 45054, 477, 92370, 2403, 279, 220, 18, 34149, 13519, 279, 6928, 477, 8389, 9249, 44153, 2077, 315, 279, 83443, 3235, 279, 220, 18, 34149, 320, 9210, 374, 11, 279, 1499, 287, 5216, 570, 23966, 13, 220, 16, 25, 7127, 315, 4447, 89, 4748, 47262, 88848, 2229, 82, 369, 9986, 25745, 4447, 89, 4748, 47262, 6900, 18508, 13, 7127, 287, 220, 18, 35, 2494, 8316, 555, 72883, 279, 22343, 12912, 13, 264, 1389, 342, 1174, 6146, 5089, 14769, 505, 220, 18, 37619, 220, 19, 37619, 220, 20, 12, 323, 220, 23, 42728, 332, 128257, 198, 128256, 78191, 198, 791, 4447, 89, 4748, 47262, 7384, 430, 33427, 4395, 505, 1057, 2849, 18084, 311, 18273, 43213, 7563, 1253, 387, 3794, 459, 14234, 9523, 311, 990, 14407, 304, 279, 8486, 22037, 32009, 6004, 2930, 4448, 220, 1691, 13, 41235, 2303, 84, 364, 30287, 818, 6, 77547, 11, 18328, 14561, 315, 22936, 15009, 304, 279, 9304, 315, 17005, 11, 323, 264, 4562, 315, 279, 7553, 442, 82206, 38710, 10181, 11, 323, 813, 2128, 617, 8040, 5528, 311, 220, 18, 9607, 1194, 4447, 89, 4748, 47262, 7384, 430, 649, 387, 2587, 69956, 311, 5625, 7351, 11, 5536, 323, 8631, 505, 904, 18445, 311, 20314, 4907, 13, 330, 72384, 89, 4748, 47262, 7384, 5625, 26800, 323, 8631, 1139, 9249, 10405, 1359, 77547, 11497, 13, 578, 4447, 89, 4748, 47262, 7384, 2586, 304, 1193, 264, 2478, 4613, 21483, 323, 527, 1903, 315, 95749, 26110, 323, 43124, 22416, 3169, 430, 1397, 264, 4335, 3130, 311, 30847, 13, 77547, 596, 2128, 706, 8040, 264, 15105, 311, 220, 18, 9607, 1194, 1521, 7384, 779, 814, 527, 539, 22486, 555, 6211, 477, 1404, 13, 578, 3769, 649, 1101, 387, 22756, 2345, 782, 1325, 287, 279, 1828, 9659, 315, 25530, 49276, 47194, 323, 7941, 7384, 369, 99683, 60199, 11, 5536, 323, 48913, 16967, 11, 4907, 66747, 11, 323, 1023, 8522, 13, 1252, 273, 1003, 279, 11542, 311, 2955, 4447, 89, 4748, 772, 6329, 41097, 89, 4748, 47262, 7384, 1051, 13517, 11352, 304, 279, 220, 777, 339, 9478, 13, 8876, 1243, 279, 31003, 304, 15266, 5557, 706, 6197, 311, 279, 16686, 315, 4335, 12, 9949, 323, 264, 6485, 10537, 430, 19159, 12631, 323, 10215, 902, 527, 8599, 311, 31591, 1306, 98423, 13, 578, 11646, 1920, 323, 279, 38088, 38430, 83, 77319, 315, 279, 3769, 11, 706, 7347, 279, 5845, 311, 35608, 279, 3769, 596, 4754, 13, 578, 17124, 19303, 11071, 315, 4447, 89, 4748, 47262, 3769, 13, 16666, 25, 13286, 17829, 77547, 596, 2128, 8040, 264, 1646, 430, 6276, 1124, 311, 37735, 323, 2955, 25142, 4447, 89, 4748, 47262, 18508, 11, 13239, 304, 279, 3769, 24038, 9249, 6900, 7351, 304, 2077, 311, 19957, 8603, 323, 78352, 505, 904, 5216, 11, 4669, 264, 743, 315, 220, 18, 9607, 43095, 1948, 9268, 13, 27140, 21349, 4447, 89, 4748, 772, 6329, 1405, 9249, 6900, 19567, 527, 32031, 555, 279, 47701, 48473, 11, 279, 502, 1749, 6276, 3932, 311, 72333, 323, 2068, 22465, 14847, 311, 387, 8622, 1908, 11, 28537, 477, 56089, 304, 904, 5216, 13, 330, 1687, 617, 8040, 264, 2955, 1749, 323, 18991, 5452, 311, 26662, 2955, 279, 27541, 323, 25605, 20362, 315, 4447, 89, 4748, 47262, 7384, 1359, 77547, 1071, 13, 330, 1383, 15840, 279, 220, 18, 9607, 4642, 45982, 11, 499, 649, 11322, 5128, 1790, 904, 10824, 315, 4447, 89, 4748, 47262, 37929, 2949, 264, 3769, 11, 323, 1005, 1124, 439, 1380, 34475, 323, 26148, 430, 527, 539, 1193, 19303, 323, 3831, 11, 719, 1101, 6013, 311, 7410, 11, 78352, 323, 25949, 4669, 9249, 17738, 430, 3371, 279, 3813, 11, 26703, 323, 5216, 315, 279, 25949, 2949, 904, 3813, 315, 1521, 7384, 1210, 220, 18, 9607, 18991, 315, 4447, 89, 4748, 772, 6329, 11, 26148, 323, 1380, 34475, 362, 8331, 304, 1510, 4447, 89, 4748, 47262, 59251, 374, 279, 5933, 26110, 1511, 13, 2468, 279, 25524, 2237, 11, 279, 17140, 315, 33299, 527, 8521, 13, 77547, 596, 2128, 706, 9124, 264, 28779, 430, 28003, 1233, 279, 26110, 719, 6276, 369, 279, 55372, 17140, 311, 387, 29852, 555, 2955, 13, 330, 1687, 617, 92106, 264, 538, 315, 7701, 16614, 4447, 89, 4748, 47262, 304, 2857, 430, 649, 387, 27863, 291, 1139, 6485, 2380, 33520, 4519, 449, 37232, 85311, 3177, 13, 578, 304, 2857, 6782, 7701, 38626, 4447, 89, 4748, 47262, 20622, 4309, 92475, 70241, 449, 30136, 57767, 342, 2053, 11, 902, 1376, 264, 6425, 29096, 7625, 8050, 21655, 1093, 50459, 26110, 41128, 584, 1194, 449, 264, 1579, 64036, 7528, 3177, 220, 18, 9607, 23185, 1359, 77547, 1071, 13, 578, 2128, 21091, 279, 220, 18, 9607, 17124, 7384, 520, 264, 5569, 30090, 65995, 315, 279, 23899, 315, 264, 3823, 7013, 13, 330, 1687, 649, 52056, 279, 18112, 311, 1304, 1124, 810, 19303, 323, 1005, 1124, 11, 369, 2937, 11, 439, 4907, 66747, 7766, 11, 42295, 1124, 2212, 904, 25142, 83233, 1359, 77547, 1071, 13, 330, 1687, 649, 1304, 1124, 12314, 11, 323, 3177, 11, 31161, 477, 4907, 97510, 269, 7278, 1210, 578, 3769, 706, 74633, 43479, 220, 20, 24325, 5190, 1109, 19303, 4447, 89, 4748, 47262, 46033, 388, 13, 578, 70334, 323, 6211, 315, 279, 3769, 649, 387, 33519, 323, 9124, 439, 264, 15792, 11071, 71707, 264, 13619, 315, 342, 2933, 3059, 11, 477, 439, 264, 31161, 2565, 13, 330, 1687, 617, 264, 2128, 3339, 1124, 1139, 78348, 7766, 11, 1093, 25562, 11, 304, 41500, 11, 323, 27442, 1124, 1139, 264, 46329, 56520, 1405, 584, 690, 387, 3025, 311, 3335, 5536, 8603, 323, 8891, 279, 2890, 315, 279, 1217, 1359, 1071, 77547, 13, 330, 791, 5845, 311, 11322, 279, 12974, 22936, 11, 20314, 323, 29487, 6012, 690, 12207, 8108, 279, 892, 323, 5149, 4460, 311, 2274, 15325, 7384, 1359, 1071, 1443, 1003, 1201, 28885, 7911, 11, 22712, 37110, 369, 3495, 520, 13813, 3314, 323, 4846, 14561, 315, 22936, 15009, 520, 13286, 17829, 13, 1561, 8522, 578, 2128, 706, 17124, 323, 21091, 7941, 7384, 20037, 2212, 50264, 27529, 11, 24634, 389, 6206, 323, 19779, 311, 5625, 11633, 11, 323, 24322, 279, 22936, 4907, 11, 719, 279, 8522, 733, 1664, 7953, 10051, 4893, 323, 11761, 31591, 13, 77547, 16008, 279, 5557, 439, 264, 32571, 1139, 74706, 11, 4907, 66747, 11, 99683, 60199, 323, 25530, 14054, 11, 1405, 264, 6070, 374, 1903, 11622, 449, 4447, 89, 4748, 47262, 3769, 11, 60199, 25949, 11, 78352, 323, 54245, 11, 323, 10923, 369, 1884, 311, 387, 41223, 323, 7559, 13, 578, 2128, 706, 17124, 264, 2678, 7941, 14497, 311, 20461, 1202, 4666, 2968, 311, 60199, 279, 10687, 315, 26156, 25949, 11, 439, 1664, 439, 1202, 26703, 11, 1418, 22514, 3403, 311, 35406, 279, 5536, 4907, 13, 578, 2128, 1101, 21091, 872, 3851, 315, 264, 7941, 1380, 30038, 430, 33822, 46474, 48913, 17738, 311, 9249, 16798, 1154, 13, 330, 43934, 17868, 11, 422, 499, 4934, 311, 8891, 279, 5419, 8333, 315, 264, 6070, 11, 499, 1053, 1205, 311, 617, 264, 2763, 315, 3927, 26148, 9277, 682, 927, 279, 6070, 11, 1855, 449, 264, 1396, 315, 11767, 323, 58170, 1359, 1071, 22546, 46799, 356, 2005, 11, 264, 74657, 5575, 449, 77547, 323, 1176, 3229, 315, 279, 22037, 32009, 5684, 13, 330, 8586, 11, 279, 6070, 5196, 374, 279, 12271, 44603, 649, 8891, 5196, 1210, 220, 128257, 198 ]

2,604

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Leads are a key feature of the Arctic ice pack during the winter owing to their substantial contribution to the surface energy balance. According to the present understanding, enhanced heat and moisture fluxes from high lead concentrations tend to produce more boundary layer clouds. However, described here in our composite analyses of diverse surface- and satellite-based observations, we find that abundant boundary layer clouds are associated with low lead flux periods, while fewer boundary layer clouds are observed for high lead flux periods. Motivated by these counterintuitive results, we conducted three-dimensional cloud-resolving simulations to investigate the underlying physics. We find that newly frozen leads with large sensible heat flux but low latent heat flux tend to dissipate low clouds. This finding indicates that the observed high lead fractions likely consist of mostly newly frozen leads that reduce any pre-existing low-level cloudiness, which in turn decreases downwelling infrared flux and accelerates the freezing of sea ice. Introduction Leads are quasi-linear openings within the interior of the polar ice pack, where the ocean is exposed directly to the atmosphere 1 . Leads range in width from several meters to tens of kilometers with narrow leads most abundant and in length from hundreds of meters to hundreds of kilometers (Supplementary Fig. 1 ). Due to the extreme air–water temperature contrast (20–40 °C), turbulent heat fluxes over leads can be two orders of magnitude larger than over the ice surface in winter 2 . While winter leads climatically cover 2–3% of the total surface area of the central Arctic and 6–9% of the Arctic peripheral seas (Supplementary Figs. 2 and 3 ), these large heat fluxes dominate the wintertime heat budget of the Arctic boundary layer 2 , 3 , 4 , 5 . Moreover, leads are also a source of moisture which can induce boundary layer clouds locally 6 . The presence of these clouds has the potential to extend the thermodynamic impact of leads over large-scale regions through their vertical and horizontal development 7 , 8 as well as the enhanced downward infrared radiative flux 9 , 10 , 11 . Boundary layer cloud cover also exerts a significant impact on the equilibrium sea ice thickness 10 , which is a key indicator of changes in Arctic heat transport 4 . Therefore, low-level clouds significantly influence how leads impact the Arctic surface energy balance. Correctly understanding the lead-modified surface energy budget is important. However, accurate determination of wintertime low-level cloud fraction over the Arctic Ocean from satellites is still a challenge owing to the presence of the underlying leads and sea ice, and the polar night. Previous observations demonstrate a replacement of thick, multi-year ice by thin, first-year ice 12 , a gradual acceleration in sea ice drift and wind stress 13 , increases in sea ice mean strain rate and the associated deformation rate 14 , and a marked widening of the marginal ice zone 15 in the Arctic. All these observational findings suggest an increasing presence of Arctic leads in the climate system, which motivates a study to understand associated changes in boundary layer clouds and thus estimate the associated large-scale heat balance in response to changes in lead fraction. As a first step in this direction, here we explore the potential influences that leads have on boundary layer clouds in the wintertime Arctic. Due to the limitation of observations in the Arctic, previous studies have mostly used model simulations to examine the clouds or convection induced by a single lead in idealized or simplified situations 8 , 11 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 . Few of those studies investigated the low-level clouds over a realistic ensemble of leads. In this study, diverse ground- and satellite-based observed records of the Arctic system near Barrow, Alaska, are combined with a three-dimensional cloud-resolving model to examine the effects of leads on boundary layer clouds. Based on the observations, we first attempt to establish a statistical relationship between the large-scale sensible heat flux due to leads and low-level cloud frequency. Furthermore, a cloud-resolving model is used to better understand the underlying physics of the observed lead-low cloud associations. We find low-level cloud occurrence frequency decreases with increasing large-scale lead flux and show that it is induced by the recently frozen leads, which constitute a majority of the satellite-detected lead fraction. Results Observed lead-low cloud associations Previous observational analysis 24 shows that low-level clouds predominate at Barrow throughout the year, especially during fall and winter. In this study, we investigate the effects of leads on low-level clouds at a local scale, offshore within 200 km of the Barrow site (as indicated by the black semicircle in Fig. 1 b, d) over the period 2008–2011 (see Methods). Profiles of the MMCR (Millimeter Wavelength Cloud Radar) derived cloud occurrence as a function of reflectivity (dBZ) for the composites of low and high large-scale lead flux are shown in Fig. 1 a, c, respectively. Based on prior research 25 , clouds are generally associated with dBZ < −10, while drizzle and light precipitation (heavy precipitation) correspond to dBZ between −10 and 10 (dBZ ≥ 10). Current understanding 16 , 20 suggests we would find more boundary layer clouds under high lead flux conditions, but we find just the opposite in our analyses. The curves in Fig. 1 c show that for the high lead flux intervals, clouds within the boundary layer (i.e., 0–1 km) with dBZ > −25 are observed to have a frequency of <10%. However, for the low lead flux periods, up to 40% of the boundary layer clouds have dBZ > −25 (Fig. 1 a). Fig. 1: MMCR derived cloud occurrence frequency and the corresponding mean lead fraction. a The vertical frequency distribution of cloud occurrence as a function of minimum reflectivity (dBZ) for the low lead flux periods. b Mean lead fraction based on AMSR-E data for four representative low lead flux periods in February 2011 (days 14, 15, 26, 27).", "role": "user" }, { "content": "The prevailing view has been that more leads are associated with more low-level clouds during winter. But University of Utah atmospheric scientists noticed something strange in their study of these leads: when lead occurrence was greater, there were fewer, not more clouds. In the wintertime Arctic, cracks in the ice called \"leads\" expose the warm ocean directly to the cold air, with some leads only a few meters wide and some kilometers wide. They play a critical role in the Arctic surface energy balance. If we want to know how much the ice is going to grow in winter, we need to understand the impacts of leads. The extreme contrast in temperature between the warm ocean and the cold air creates a flow of heat and moisture from the ocean to the atmosphere. This flow provides a lead with its own weather system which creates low-level clouds. The prevailing view has been that more leads are associated with more low-level clouds during winter. But University of Utah atmospheric scientists noticed something strange in their study of these leads: when lead occurrence was greater, there were fewer, not more clouds. In a paper published in Nature Communications, they explain why: wintertime leads rapidly freeze after opening, so most leads have newly frozen ice that shuts off the moisture supply but only some of the heat flow from the ocean, thus causing any low-level clouds to dissipate and accelerating the freezing of sea ice compared to unfrozen leads. Understanding this dynamic, the authors say, will help more accurately represent the impact of winter-time leads on low-level clouds and on the surface energy budget in the Arctic—especially as the Arctic sea ice is declining. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Leads are a key feature of the Arctic ice pack during the winter owing to their substantial contribution to the surface energy balance. According to the present understanding, enhanced heat and moisture fluxes from high lead concentrations tend to produce more boundary layer clouds. However, described here in our composite analyses of diverse surface- and satellite-based observations, we find that abundant boundary layer clouds are associated with low lead flux periods, while fewer boundary layer clouds are observed for high lead flux periods. Motivated by these counterintuitive results, we conducted three-dimensional cloud-resolving simulations to investigate the underlying physics. We find that newly frozen leads with large sensible heat flux but low latent heat flux tend to dissipate low clouds. This finding indicates that the observed high lead fractions likely consist of mostly newly frozen leads that reduce any pre-existing low-level cloudiness, which in turn decreases downwelling infrared flux and accelerates the freezing of sea ice. Introduction Leads are quasi-linear openings within the interior of the polar ice pack, where the ocean is exposed directly to the atmosphere 1 . Leads range in width from several meters to tens of kilometers with narrow leads most abundant and in length from hundreds of meters to hundreds of kilometers (Supplementary Fig. 1 ). Due to the extreme air–water temperature contrast (20–40 °C), turbulent heat fluxes over leads can be two orders of magnitude larger than over the ice surface in winter 2 . While winter leads climatically cover 2–3% of the total surface area of the central Arctic and 6–9% of the Arctic peripheral seas (Supplementary Figs. 2 and 3 ), these large heat fluxes dominate the wintertime heat budget of the Arctic boundary layer 2 , 3 , 4 , 5 . Moreover, leads are also a source of moisture which can induce boundary layer clouds locally 6 . The presence of these clouds has the potential to extend the thermodynamic impact of leads over large-scale regions through their vertical and horizontal development 7 , 8 as well as the enhanced downward infrared radiative flux 9 , 10 , 11 . Boundary layer cloud cover also exerts a significant impact on the equilibrium sea ice thickness 10 , which is a key indicator of changes in Arctic heat transport 4 . Therefore, low-level clouds significantly influence how leads impact the Arctic surface energy balance. Correctly understanding the lead-modified surface energy budget is important. However, accurate determination of wintertime low-level cloud fraction over the Arctic Ocean from satellites is still a challenge owing to the presence of the underlying leads and sea ice, and the polar night. Previous observations demonstrate a replacement of thick, multi-year ice by thin, first-year ice 12 , a gradual acceleration in sea ice drift and wind stress 13 , increases in sea ice mean strain rate and the associated deformation rate 14 , and a marked widening of the marginal ice zone 15 in the Arctic. All these observational findings suggest an increasing presence of Arctic leads in the climate system, which motivates a study to understand associated changes in boundary layer clouds and thus estimate the associated large-scale heat balance in response to changes in lead fraction. As a first step in this direction, here we explore the potential influences that leads have on boundary layer clouds in the wintertime Arctic. Due to the limitation of observations in the Arctic, previous studies have mostly used model simulations to examine the clouds or convection induced by a single lead in idealized or simplified situations 8 , 11 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 . Few of those studies investigated the low-level clouds over a realistic ensemble of leads. In this study, diverse ground- and satellite-based observed records of the Arctic system near Barrow, Alaska, are combined with a three-dimensional cloud-resolving model to examine the effects of leads on boundary layer clouds. Based on the observations, we first attempt to establish a statistical relationship between the large-scale sensible heat flux due to leads and low-level cloud frequency. Furthermore, a cloud-resolving model is used to better understand the underlying physics of the observed lead-low cloud associations. We find low-level cloud occurrence frequency decreases with increasing large-scale lead flux and show that it is induced by the recently frozen leads, which constitute a majority of the satellite-detected lead fraction. Results Observed lead-low cloud associations Previous observational analysis 24 shows that low-level clouds predominate at Barrow throughout the year, especially during fall and winter. In this study, we investigate the effects of leads on low-level clouds at a local scale, offshore within 200 km of the Barrow site (as indicated by the black semicircle in Fig. 1 b, d) over the period 2008–2011 (see Methods). Profiles of the MMCR (Millimeter Wavelength Cloud Radar) derived cloud occurrence as a function of reflectivity (dBZ) for the composites of low and high large-scale lead flux are shown in Fig. 1 a, c, respectively. Based on prior research 25 , clouds are generally associated with dBZ < −10, while drizzle and light precipitation (heavy precipitation) correspond to dBZ between −10 and 10 (dBZ ≥ 10). Current understanding 16 , 20 suggests we would find more boundary layer clouds under high lead flux conditions, but we find just the opposite in our analyses. The curves in Fig. 1 c show that for the high lead flux intervals, clouds within the boundary layer (i.e., 0–1 km) with dBZ > −25 are observed to have a frequency of <10%. However, for the low lead flux periods, up to 40% of the boundary layer clouds have dBZ > −25 (Fig. 1 a). Fig. 1: MMCR derived cloud occurrence frequency and the corresponding mean lead fraction. a The vertical frequency distribution of cloud occurrence as a function of minimum reflectivity (dBZ) for the low lead flux periods. b Mean lead fraction based on AMSR-E data for four representative low lead flux periods in February 2011 (days 14, 15, 26, 27).<|im_end|> <|im_start|>assistant The prevailing view has been that more leads are associated with more low-level clouds during winter. But University of Utah atmospheric scientists noticed something strange in their study of these leads: when lead occurrence was greater, there were fewer, not more clouds. In the wintertime Arctic, cracks in the ice called "leads" expose the warm ocean directly to the cold air, with some leads only a few meters wide and some kilometers wide. They play a critical role in the Arctic surface energy balance. If we want to know how much the ice is going to grow in winter, we need to understand the impacts of leads. The extreme contrast in temperature between the warm ocean and the cold air creates a flow of heat and moisture from the ocean to the atmosphere. This flow provides a lead with its own weather system which creates low-level clouds. The prevailing view has been that more leads are associated with more low-level clouds during winter. But University of Utah atmospheric scientists noticed something strange in their study of these leads: when lead occurrence was greater, there were fewer, not more clouds. In a paper published in Nature Communications, they explain why: wintertime leads rapidly freeze after opening, so most leads have newly frozen ice that shuts off the moisture supply but only some of the heat flow from the ocean, thus causing any low-level clouds to dissipate and accelerating the freezing of sea ice compared to unfrozen leads. Understanding this dynamic, the authors say, will help more accurately represent the impact of winter-time leads on low-level clouds and on the surface energy budget in the Arctic—especially as the Arctic sea ice is declining. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 82628, 527, 264, 1401, 4668, 315, 279, 37518, 10054, 3854, 2391, 279, 12688, 56612, 311, 872, 12190, 19035, 311, 279, 7479, 4907, 8335, 13, 10771, 311, 279, 3118, 8830, 11, 24872, 8798, 323, 32257, 31405, 288, 505, 1579, 3063, 32466, 8541, 311, 8356, 810, 19254, 6324, 30614, 13, 4452, 11, 7633, 1618, 304, 1057, 28814, 29060, 315, 17226, 7479, 12, 323, 24088, 6108, 24654, 11, 584, 1505, 430, 44611, 19254, 6324, 30614, 527, 5938, 449, 3428, 3063, 31405, 18852, 11, 1418, 17162, 19254, 6324, 30614, 527, 13468, 369, 1579, 3063, 31405, 18852, 13, 19514, 55786, 555, 1521, 5663, 396, 35251, 3135, 11, 584, 13375, 2380, 33520, 9624, 11849, 20222, 47590, 311, 19874, 279, 16940, 22027, 13, 1226, 1505, 430, 13945, 20268, 11767, 449, 3544, 38761, 8798, 31405, 719, 3428, 42767, 8798, 31405, 8541, 311, 93522, 349, 3428, 30614, 13, 1115, 9455, 15151, 430, 279, 13468, 1579, 3063, 65995, 4461, 6824, 315, 10213, 13945, 20268, 11767, 430, 8108, 904, 864, 50457, 3428, 11852, 9624, 1918, 11, 902, 304, 2543, 43154, 1523, 86, 6427, 59141, 31405, 323, 14511, 988, 279, 43318, 315, 9581, 10054, 13, 29438, 82628, 527, 48844, 62399, 49649, 2949, 279, 15135, 315, 279, 25685, 10054, 3854, 11, 1405, 279, 18435, 374, 15246, 6089, 311, 279, 16975, 220, 16, 662, 82628, 2134, 304, 2430, 505, 3892, 20645, 311, 22781, 315, 41668, 449, 15376, 11767, 1455, 44611, 323, 304, 3160, 505, 11758, 315, 20645, 311, 11758, 315, 41668, 320, 10254, 67082, 23966, 13, 220, 16, 7609, 24586, 311, 279, 14560, 3805, 4235, 13284, 9499, 13168, 320, 508, 4235, 1272, 37386, 34, 705, 83321, 8798, 31405, 288, 927, 11767, 649, 387, 1403, 10373, 315, 26703, 8294, 1109, 927, 279, 10054, 7479, 304, 12688, 220, 17, 662, 6104, 12688, 11767, 11323, 7167, 3504, 220, 17, 4235, 18, 4, 315, 279, 2860, 7479, 3158, 315, 279, 8792, 37518, 323, 220, 21, 4235, 24, 4, 315, 279, 37518, 35688, 52840, 320, 10254, 67082, 435, 14801, 13, 220, 17, 323, 220, 18, 7026, 1521, 3544, 8798, 31405, 288, 41836, 279, 289, 396, 70841, 8798, 8199, 315, 279, 37518, 19254, 6324, 220, 17, 1174, 220, 18, 1174, 220, 19, 1174, 220, 20, 662, 23674, 11, 11767, 527, 1101, 264, 2592, 315, 32257, 902, 649, 49853, 19254, 6324, 30614, 24392, 220, 21, 662, 578, 9546, 315, 1521, 30614, 706, 279, 4754, 311, 13334, 279, 30945, 61002, 5536, 315, 11767, 927, 3544, 13230, 13918, 1555, 872, 12414, 323, 16600, 4500, 220, 22, 1174, 220, 23, 439, 1664, 439, 279, 24872, 45578, 59141, 12164, 1413, 31405, 220, 24, 1174, 220, 605, 1174, 220, 806, 662, 77516, 6324, 9624, 3504, 1101, 506, 15916, 264, 5199, 5536, 389, 279, 56411, 9581, 10054, 26839, 220, 605, 1174, 902, 374, 264, 1401, 21070, 315, 4442, 304, 37518, 8798, 7710, 220, 19, 662, 15636, 11, 3428, 11852, 30614, 12207, 10383, 1268, 11767, 5536, 279, 37518, 7479, 4907, 8335, 13, 41070, 398, 8830, 279, 3063, 17515, 1908, 7479, 4907, 8199, 374, 3062, 13, 4452, 11, 13687, 26314, 315, 289, 396, 70841, 3428, 11852, 9624, 19983, 927, 279, 37518, 22302, 505, 47710, 374, 2103, 264, 8815, 56612, 311, 279, 9546, 315, 279, 16940, 11767, 323, 9581, 10054, 11, 323, 279, 25685, 3814, 13, 30013, 24654, 20461, 264, 14039, 315, 12314, 11, 7447, 4771, 10054, 555, 15792, 11, 1176, 4771, 10054, 220, 717, 1174, 264, 53722, 31903, 304, 9581, 10054, 34738, 323, 10160, 8631, 220, 1032, 1174, 12992, 304, 9581, 10054, 3152, 26800, 4478, 323, 279, 5938, 91621, 4478, 220, 975, 1174, 323, 264, 13160, 85500, 315, 279, 32873, 10054, 10353, 220, 868, 304, 279, 37518, 13, 2052, 1521, 90380, 14955, 4284, 459, 7859, 9546, 315, 37518, 11767, 304, 279, 10182, 1887, 11, 902, 12521, 988, 264, 4007, 311, 3619, 5938, 4442, 304, 19254, 6324, 30614, 323, 8617, 16430, 279, 5938, 3544, 13230, 8798, 8335, 304, 2077, 311, 4442, 304, 3063, 19983, 13, 1666, 264, 1176, 3094, 304, 420, 5216, 11, 1618, 584, 13488, 279, 4754, 34453, 430, 11767, 617, 389, 19254, 6324, 30614, 304, 279, 289, 396, 70841, 37518, 13, 24586, 311, 279, 20893, 315, 24654, 304, 279, 37518, 11, 3766, 7978, 617, 10213, 1511, 1646, 47590, 311, 21635, 279, 30614, 477, 390, 80298, 36572, 555, 264, 3254, 3063, 304, 10728, 1534, 477, 44899, 15082, 220, 23, 1174, 220, 806, 1174, 220, 845, 1174, 220, 1114, 1174, 220, 972, 1174, 220, 777, 1174, 220, 508, 1174, 220, 1691, 1174, 220, 1313, 1174, 220, 1419, 662, 44015, 315, 1884, 7978, 27313, 279, 3428, 11852, 30614, 927, 264, 26569, 40126, 315, 11767, 13, 763, 420, 4007, 11, 17226, 5015, 12, 323, 24088, 6108, 13468, 7576, 315, 279, 37518, 1887, 3221, 4821, 654, 11, 28366, 11, 527, 11093, 449, 264, 2380, 33520, 9624, 11849, 20222, 1646, 311, 21635, 279, 6372, 315, 11767, 389, 19254, 6324, 30614, 13, 20817, 389, 279, 24654, 11, 584, 1176, 4879, 311, 5813, 264, 29564, 5133, 1990, 279, 3544, 13230, 38761, 8798, 31405, 4245, 311, 11767, 323, 3428, 11852, 9624, 11900, 13, 24296, 11, 264, 9624, 11849, 20222, 1646, 374, 1511, 311, 2731, 3619, 279, 16940, 22027, 315, 279, 13468, 3063, 60369, 9624, 30257, 13, 1226, 1505, 3428, 11852, 9624, 32659, 11900, 43154, 449, 7859, 3544, 13230, 3063, 31405, 323, 1501, 430, 433, 374, 36572, 555, 279, 6051, 20268, 11767, 11, 902, 35256, 264, 8857, 315, 279, 24088, 92004, 1599, 3063, 19983, 13, 18591, 51541, 2841, 3063, 60369, 9624, 30257, 30013, 90380, 6492, 220, 1187, 5039, 430, 3428, 11852, 30614, 4255, 316, 3357, 520, 4821, 654, 6957, 279, 1060, 11, 5423, 2391, 4498, 323, 12688, 13, 763, 420, 4007, 11, 584, 19874, 279, 6372, 315, 11767, 389, 3428, 11852, 30614, 520, 264, 2254, 5569, 11, 39500, 2949, 220, 1049, 13437, 315, 279, 4821, 654, 2816, 320, 300, 16717, 555, 279, 3776, 5347, 292, 7219, 304, 23966, 13, 220, 16, 293, 11, 294, 8, 927, 279, 4261, 220, 1049, 23, 4235, 679, 16, 320, 4151, 19331, 570, 72827, 315, 279, 22403, 9150, 320, 12608, 26402, 468, 35961, 15161, 68886, 8, 14592, 9624, 32659, 439, 264, 734, 315, 8881, 1968, 320, 42055, 57, 8, 369, 279, 470, 81239, 315, 3428, 323, 1579, 3544, 13230, 3063, 31405, 527, 6982, 304, 23966, 13, 220, 16, 264, 11, 272, 11, 15947, 13, 20817, 389, 4972, 3495, 220, 914, 1174, 30614, 527, 8965, 5938, 449, 44868, 57, 366, 25173, 605, 11, 1418, 1377, 44237, 323, 3177, 61050, 320, 89945, 61050, 8, 8024, 311, 44868, 57, 1990, 25173, 605, 323, 220, 605, 320, 42055, 57, 63247, 220, 605, 570, 9303, 8830, 220, 845, 1174, 220, 508, 13533, 584, 1053, 1505, 810, 19254, 6324, 30614, 1234, 1579, 3063, 31405, 4787, 11, 719, 584, 1505, 1120, 279, 14329, 304, 1057, 29060, 13, 578, 37033, 304, 23966, 13, 220, 16, 272, 1501, 430, 369, 279, 1579, 3063, 31405, 28090, 11, 30614, 2949, 279, 19254, 6324, 320, 72, 1770, 2637, 220, 15, 4235, 16, 13437, 8, 449, 44868, 57, 871, 25173, 914, 527, 13468, 311, 617, 264, 11900, 315, 366, 605, 14697, 4452, 11, 369, 279, 3428, 3063, 31405, 18852, 11, 709, 311, 220, 1272, 4, 315, 279, 19254, 6324, 30614, 617, 44868, 57, 871, 25173, 914, 320, 30035, 13, 220, 16, 264, 570, 23966, 13, 220, 16, 25, 22403, 9150, 14592, 9624, 32659, 11900, 323, 279, 12435, 3152, 3063, 19983, 13, 264, 578, 12414, 11900, 8141, 315, 9624, 32659, 439, 264, 734, 315, 8187, 8881, 1968, 320, 42055, 57, 8, 369, 279, 3428, 3063, 31405, 18852, 13, 293, 16729, 3063, 19983, 3196, 389, 98370, 49, 13737, 828, 369, 3116, 18740, 3428, 3063, 31405, 18852, 304, 7552, 220, 679, 16, 320, 14097, 220, 975, 11, 220, 868, 11, 220, 1627, 11, 220, 1544, 570, 128257, 198, 128256, 78191, 198, 791, 61129, 1684, 706, 1027, 430, 810, 11767, 527, 5938, 449, 810, 3428, 11852, 30614, 2391, 12688, 13, 2030, 3907, 315, 23195, 45475, 14248, 14000, 2555, 15234, 304, 872, 4007, 315, 1521, 11767, 25, 994, 3063, 32659, 574, 7191, 11, 1070, 1051, 17162, 11, 539, 810, 30614, 13, 763, 279, 289, 396, 70841, 37518, 11, 45963, 304, 279, 10054, 2663, 330, 99470, 1, 29241, 279, 8369, 18435, 6089, 311, 279, 9439, 3805, 11, 449, 1063, 11767, 1193, 264, 2478, 20645, 7029, 323, 1063, 41668, 7029, 13, 2435, 1514, 264, 9200, 3560, 304, 279, 37518, 7479, 4907, 8335, 13, 1442, 584, 1390, 311, 1440, 1268, 1790, 279, 10054, 374, 2133, 311, 3139, 304, 12688, 11, 584, 1205, 311, 3619, 279, 25949, 315, 11767, 13, 578, 14560, 13168, 304, 9499, 1990, 279, 8369, 18435, 323, 279, 9439, 3805, 11705, 264, 6530, 315, 8798, 323, 32257, 505, 279, 18435, 311, 279, 16975, 13, 1115, 6530, 5825, 264, 3063, 449, 1202, 1866, 9282, 1887, 902, 11705, 3428, 11852, 30614, 13, 578, 61129, 1684, 706, 1027, 430, 810, 11767, 527, 5938, 449, 810, 3428, 11852, 30614, 2391, 12688, 13, 2030, 3907, 315, 23195, 45475, 14248, 14000, 2555, 15234, 304, 872, 4007, 315, 1521, 11767, 25, 994, 3063, 32659, 574, 7191, 11, 1070, 1051, 17162, 11, 539, 810, 30614, 13, 763, 264, 5684, 4756, 304, 22037, 26545, 11, 814, 10552, 3249, 25, 289, 396, 70841, 11767, 19019, 31030, 1306, 8736, 11, 779, 1455, 11767, 617, 13945, 20268, 10054, 430, 89678, 1022, 279, 32257, 8312, 719, 1193, 1063, 315, 279, 8798, 6530, 505, 279, 18435, 11, 8617, 14718, 904, 3428, 11852, 30614, 311, 93522, 349, 323, 69741, 279, 43318, 315, 9581, 10054, 7863, 311, 9662, 43340, 11767, 13, 46551, 420, 8915, 11, 279, 12283, 2019, 11, 690, 1520, 810, 30357, 4097, 279, 5536, 315, 12688, 7394, 11767, 389, 3428, 11852, 30614, 323, 389, 279, 7479, 4907, 8199, 304, 279, 37518, 2345, 36046, 439, 279, 37518, 9581, 10054, 374, 43848, 13, 220, 128257, 198 ]

1,622

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Although Weyl fermions have proven elusive in high-energy physics, their existence as emergent quasiparticles has been predicted in certain crystalline solids in which either inversion or time-reversal symmetry is broken 1 , 2 , 3 , 4 . Recently they have been observed in transition metal monopnictides (TMMPs) such as TaAs, a class of noncentrosymmetric materials that heretofore received only limited attention 5 , 6 , 7 . The question that arises now is whether these materials will exhibit novel, enhanced, or technologically applicable electronic properties. The TMMPs are polar metals, a rare subset of inversion-breaking crystals that would allow spontaneous polarization, were it not screened by conduction electrons 8 , 9 , 10 . Despite the absence of spontaneous polarization, polar metals can exhibit other signatures of inversion-symmetry breaking, most notably second-order nonlinear optical polarizability, χ (2) , leading to phenomena such as optical rectification and second-harmonic generation (SHG). Here we report measurements of SHG that reveal a giant, anisotropic χ (2) in the TMMPs TaAs, TaP and NbAs. With the fundamental and second-harmonic fields oriented parallel to the polar axis, the value of χ (2) is larger by almost one order of magnitude than its value in the archetypal electro-optic materials GaAs 11 and ZnTe 12 , and in fact larger than reported in any crystal to date. Main The past decade has witnessed an explosion of research investigating the role of band-structure topology, as characterized for example by the Berry curvature in momentum space, in the electronic response functions of crystalline solids 13 . While the best established example is the intrinsic anomalous Hall effect in time-reversal breaking systems 14 , several nonlocal 15 , 16 and nonlinear effects related to Berry curvature generally 17 , 18 and in Weyl semimetals (WSMs) specifically 19 , 20 have been predicted in crystals that break inversion symmetry. Of these, the most relevant to this work is a theoretical formulation 21 of SHG in terms of the shift vector, which is a quantity related to the difference in Berry connection between two bands that participate in an optical transition. Figure 1a and its caption provide a schematic and description of the optical set-up for measurement of SHG in TMMP crystals. Figure 1b, c shows results from a (112) surface of TaAs. The SH intensity from this surface is very strong, allowing for polarization rotation scans with signal-to-noise ratio above 10 6 . In contrast, SHG from a TaAs (001) surface is barely detectable (at least six orders of magnitude lower than the (112) surface). Below, we describe the use of the set-up shown in Fig. 1a to characterize the second-order optical susceptibility tensor, χ ijk , defined by the relation, P i (2 ω ) = ε 0 χ ijk (2 ω ) E j ( ω ) E k ( ω ). Figure 1: Second-harmonic generation versus angle as TaAs is effectively rotated about the axis perpendicular to the (112) surface. a , Schematic of the SHG experimental set-up. To stimulate second-harmonic light, pulses of 800 nm wavelength were focused at near-normal incidence to a 10-μm-diameter spot on the sample. Polarizers and waveplates mounted on rotating stages allowed for continuous and independent control of the polarization of the generating and second-harmonic light that reached the detector. θ 1 and θ 2 are the angles of the polarization plane after the generator and the analyser, respectively, with respect to the [1,1,−1] crystal axis. b , c , SHG intensity as a function of angle of incident polarization at 20 K. In b , c , the analyser is, respectively, parallel and perpendicular to the generator. In both plots the amplitude is normalized by the peak value in b . The solid lines are fits that include all the allowed tensor elements in 4 mm symmetry, whereas the dashed lines include only d 33 . The insets are polar plots of measured SHG intensity versus incident polarization angle. Full size image As a first step, we determined the orientation of the high-symmetry axes in the (112) surface, which are the [1,−1,0] and [1,1,−1] directions. To do so, we simultaneously rotated the linear polarization of the generating light (the generator) and the polarizer placed before the detector (the analyser), with their relative angle set at either 0° or 90°. Rotating the generator and analyser together produces scans, shown in Fig. 1b, c , which are equivalent to rotation of the sample about the surface normal. The angles at which we observe the peak and the null in Fig. 1b and the null in Fig. 1c allow us to identify the principal axes in the (112) plane of the surface. Having determined the high-symmetry directions, we characterize χ ijk by performing three of types of scans, the results of which are shown in Fig. 2 . In scans shown in Fig. 2a, b , we oriented the analyser along one of the two high-symmetry directions and rotated the plane of linear polarization of the generator through 360°. Figure 2c shows the circular dichroism of the SHG response—that is, the difference in SH generated by left and right circularly polarized light. For all three scans the SHG intensity as a function of angle is consistent with the second-order optical susceptibility tensor expected for the 4 mm point group of TaAs, as indicated by the high accuracy of the fits in Fig. 1b, c and Fig. 2a–c . Figure 2: Second-harmonic intensity with fixed analysers, circular dichroism and temperature dependence on a TaAs (112) sample. a , b , SHG as function of generator polarization with analysers fixed along 0° ( a ) and 90° ( b ), which are the [1,1,−1] and [1,−1,0] crystal axes, respectively. Solid lines are fits considering all three non-zero tensor elements. The insets are polar plots of measured SHG intensity. c , Circular dichroism (SHG intensity difference between right- and left-hand circularly polarized generation light) normalized by the peak value in Fig. 1b versus polarization angle of the", "role": "user" }, { "content": "No earlier theory had envisioned that the responses would be so large! Scientists \"poked\" three crystals with pulses of light. Unexpectedly, the crystals exhibited the largest nonlinear optical response of any known crystal. The response was a huge amount of different colored light with twice the frequency of the pulse. These crystals are members of a new class of materials known as Weyl semimetals. This work challenges our thinking on optical responses in Weyl semimetals. We expected light pulses to produce different colored light with twice the frequency but not such a huge response. The origin of this gigantic response is unknown! This study is already stimulating the development of fundamentally new theories about these responses. These materials are promising for package-penetrating sensors, night vision goggles, and other devices. Weyl fermions are novel particles that were predicted to be seen in high-energy physics experiments but have not been observed. However, scientists recently observed these particles as an emergent property of electrons in a unique set of semimetal materials. Recent studies have shown that Weyl semimetals exhibit an unexpectedly large nonlinear optical response. This response gives rise to the largest optical second harmonic generation effect of any known crystal. These observations were made in the transition metal systems: tantalum arsenide (TaAs), tantalum phosphide (TaP), and niobium arsenide (NbAs). A lthough it was clear from symmetry considerations that there would be a non-linear response in these systems, there was no theoretical prediction suggesting the large magnitude of response observed. By comparison with other well-known nonlinear crystals, the non-linear optical response in these systems is larger by factors of 10 to 100. Given the unexpected response, scientists anticipate these findings will stimulate the development of advanced ab initio methods to calculate nonlinear optical response functions in these materials. Also, Weyl semimetals are expected to have a wide range of optoelectronic applications as materials to be used for the development of terahertz generators and far-infrared radiation detectors. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Although Weyl fermions have proven elusive in high-energy physics, their existence as emergent quasiparticles has been predicted in certain crystalline solids in which either inversion or time-reversal symmetry is broken 1 , 2 , 3 , 4 . Recently they have been observed in transition metal monopnictides (TMMPs) such as TaAs, a class of noncentrosymmetric materials that heretofore received only limited attention 5 , 6 , 7 . The question that arises now is whether these materials will exhibit novel, enhanced, or technologically applicable electronic properties. The TMMPs are polar metals, a rare subset of inversion-breaking crystals that would allow spontaneous polarization, were it not screened by conduction electrons 8 , 9 , 10 . Despite the absence of spontaneous polarization, polar metals can exhibit other signatures of inversion-symmetry breaking, most notably second-order nonlinear optical polarizability, χ (2) , leading to phenomena such as optical rectification and second-harmonic generation (SHG). Here we report measurements of SHG that reveal a giant, anisotropic χ (2) in the TMMPs TaAs, TaP and NbAs. With the fundamental and second-harmonic fields oriented parallel to the polar axis, the value of χ (2) is larger by almost one order of magnitude than its value in the archetypal electro-optic materials GaAs 11 and ZnTe 12 , and in fact larger than reported in any crystal to date. Main The past decade has witnessed an explosion of research investigating the role of band-structure topology, as characterized for example by the Berry curvature in momentum space, in the electronic response functions of crystalline solids 13 . While the best established example is the intrinsic anomalous Hall effect in time-reversal breaking systems 14 , several nonlocal 15 , 16 and nonlinear effects related to Berry curvature generally 17 , 18 and in Weyl semimetals (WSMs) specifically 19 , 20 have been predicted in crystals that break inversion symmetry. Of these, the most relevant to this work is a theoretical formulation 21 of SHG in terms of the shift vector, which is a quantity related to the difference in Berry connection between two bands that participate in an optical transition. Figure 1a and its caption provide a schematic and description of the optical set-up for measurement of SHG in TMMP crystals. Figure 1b, c shows results from a (112) surface of TaAs. The SH intensity from this surface is very strong, allowing for polarization rotation scans with signal-to-noise ratio above 10 6 . In contrast, SHG from a TaAs (001) surface is barely detectable (at least six orders of magnitude lower than the (112) surface). Below, we describe the use of the set-up shown in Fig. 1a to characterize the second-order optical susceptibility tensor, χ ijk , defined by the relation, P i (2 ω ) = ε 0 χ ijk (2 ω ) E j ( ω ) E k ( ω ). Figure 1: Second-harmonic generation versus angle as TaAs is effectively rotated about the axis perpendicular to the (112) surface. a , Schematic of the SHG experimental set-up. To stimulate second-harmonic light, pulses of 800 nm wavelength were focused at near-normal incidence to a 10-μm-diameter spot on the sample. Polarizers and waveplates mounted on rotating stages allowed for continuous and independent control of the polarization of the generating and second-harmonic light that reached the detector. θ 1 and θ 2 are the angles of the polarization plane after the generator and the analyser, respectively, with respect to the [1,1,−1] crystal axis. b , c , SHG intensity as a function of angle of incident polarization at 20 K. In b , c , the analyser is, respectively, parallel and perpendicular to the generator. In both plots the amplitude is normalized by the peak value in b . The solid lines are fits that include all the allowed tensor elements in 4 mm symmetry, whereas the dashed lines include only d 33 . The insets are polar plots of measured SHG intensity versus incident polarization angle. Full size image As a first step, we determined the orientation of the high-symmetry axes in the (112) surface, which are the [1,−1,0] and [1,1,−1] directions. To do so, we simultaneously rotated the linear polarization of the generating light (the generator) and the polarizer placed before the detector (the analyser), with their relative angle set at either 0° or 90°. Rotating the generator and analyser together produces scans, shown in Fig. 1b, c , which are equivalent to rotation of the sample about the surface normal. The angles at which we observe the peak and the null in Fig. 1b and the null in Fig. 1c allow us to identify the principal axes in the (112) plane of the surface. Having determined the high-symmetry directions, we characterize χ ijk by performing three of types of scans, the results of which are shown in Fig. 2 . In scans shown in Fig. 2a, b , we oriented the analyser along one of the two high-symmetry directions and rotated the plane of linear polarization of the generator through 360°. Figure 2c shows the circular dichroism of the SHG response—that is, the difference in SH generated by left and right circularly polarized light. For all three scans the SHG intensity as a function of angle is consistent with the second-order optical susceptibility tensor expected for the 4 mm point group of TaAs, as indicated by the high accuracy of the fits in Fig. 1b, c and Fig. 2a–c . Figure 2: Second-harmonic intensity with fixed analysers, circular dichroism and temperature dependence on a TaAs (112) sample. a , b , SHG as function of generator polarization with analysers fixed along 0° ( a ) and 90° ( b ), which are the [1,1,−1] and [1,−1,0] crystal axes, respectively. Solid lines are fits considering all three non-zero tensor elements. The insets are polar plots of measured SHG intensity. c , Circular dichroism (SHG intensity difference between right- and left-hand circularly polarized generation light) normalized by the peak value in Fig. 1b versus polarization angle of the<|im_end|> <|im_start|>assistant No earlier theory had envisioned that the responses would be so large! Scientists "poked" three crystals with pulses of light. Unexpectedly, the crystals exhibited the largest nonlinear optical response of any known crystal. The response was a huge amount of different colored light with twice the frequency of the pulse. These crystals are members of a new class of materials known as Weyl semimetals. This work challenges our thinking on optical responses in Weyl semimetals. We expected light pulses to produce different colored light with twice the frequency but not such a huge response. The origin of this gigantic response is unknown! This study is already stimulating the development of fundamentally new theories about these responses. These materials are promising for package-penetrating sensors, night vision goggles, and other devices. Weyl fermions are novel particles that were predicted to be seen in high-energy physics experiments but have not been observed. However, scientists recently observed these particles as an emergent property of electrons in a unique set of semimetal materials. Recent studies have shown that Weyl semimetals exhibit an unexpectedly large nonlinear optical response. This response gives rise to the largest optical second harmonic generation effect of any known crystal. These observations were made in the transition metal systems: tantalum arsenide (TaAs), tantalum phosphide (TaP), and niobium arsenide (NbAs). A lthough it was clear from symmetry considerations that there would be a non-linear response in these systems, there was no theoretical prediction suggesting the large magnitude of response observed. By comparison with other well-known nonlinear crystals, the non-linear optical response in these systems is larger by factors of 10 to 100. Given the unexpected response, scientists anticipate these findings will stimulate the development of advanced ab initio methods to calculate nonlinear optical response functions in these materials. Also, Weyl semimetals are expected to have a wide range of optoelectronic applications as materials to be used for the development of terahertz generators and far-infrared radiation detectors. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 10541, 468, 1216, 75, 81682, 919, 617, 17033, 66684, 304, 1579, 65487, 22027, 11, 872, 14209, 439, 7425, 306, 934, 300, 575, 16641, 706, 1027, 19698, 304, 3738, 64568, 483, 82486, 304, 902, 3060, 47588, 477, 892, 5621, 3078, 278, 46220, 374, 11102, 220, 16, 1174, 220, 17, 1174, 220, 18, 1174, 220, 19, 662, 42096, 814, 617, 1027, 13468, 304, 9320, 9501, 1647, 454, 106489, 3422, 320, 22809, 5901, 82, 8, 1778, 439, 24172, 2170, 11, 264, 538, 315, 2536, 1189, 3714, 30559, 7384, 430, 1077, 295, 1073, 461, 4036, 1193, 7347, 6666, 220, 20, 1174, 220, 21, 1174, 220, 22, 662, 578, 3488, 430, 48282, 1457, 374, 3508, 1521, 7384, 690, 31324, 11775, 11, 24872, 11, 477, 2869, 30450, 8581, 14683, 6012, 13, 578, 24929, 5901, 82, 527, 25685, 37182, 11, 264, 9024, 27084, 315, 47588, 55407, 48473, 430, 1053, 2187, 54557, 83245, 11, 1051, 433, 539, 58677, 555, 390, 23985, 57678, 220, 23, 1174, 220, 24, 1174, 220, 605, 662, 18185, 279, 19821, 315, 54557, 83245, 11, 25685, 37182, 649, 31324, 1023, 33728, 315, 47588, 1355, 1631, 33342, 15061, 11, 1455, 35146, 2132, 24747, 75098, 29393, 25685, 450, 2968, 11, 100897, 320, 17, 8, 1174, 6522, 311, 44247, 1778, 439, 29393, 7763, 2461, 323, 2132, 2902, 277, 74689, 9659, 320, 8758, 38, 570, 5810, 584, 1934, 22323, 315, 6570, 38, 430, 16805, 264, 14880, 11, 459, 285, 79432, 100897, 320, 17, 8, 304, 279, 24929, 5901, 82, 24172, 2170, 11, 24172, 47, 323, 78583, 2170, 13, 3161, 279, 16188, 323, 2132, 2902, 277, 74689, 5151, 42208, 15638, 311, 279, 25685, 8183, 11, 279, 907, 315, 100897, 320, 17, 8, 374, 8294, 555, 4661, 832, 2015, 315, 26703, 1109, 1202, 907, 304, 279, 5438, 295, 1100, 278, 25396, 57212, 292, 7384, 18879, 2170, 220, 806, 323, 127265, 6777, 220, 717, 1174, 323, 304, 2144, 8294, 1109, 5068, 304, 904, 26110, 311, 2457, 13, 4802, 578, 3347, 13515, 706, 32126, 459, 25176, 315, 3495, 24834, 279, 3560, 315, 7200, 12, 7993, 45982, 11, 439, 32971, 369, 3187, 555, 279, 44685, 83233, 304, 24151, 3634, 11, 304, 279, 14683, 2077, 5865, 315, 64568, 483, 82486, 220, 1032, 662, 6104, 279, 1888, 9749, 3187, 374, 279, 47701, 37782, 30543, 11166, 2515, 304, 892, 5621, 3078, 278, 15061, 6067, 220, 975, 1174, 3892, 2536, 2497, 220, 868, 1174, 220, 845, 323, 75098, 6372, 5552, 311, 44685, 83233, 8965, 220, 1114, 1174, 220, 972, 323, 304, 468, 1216, 75, 5347, 86366, 1147, 320, 7585, 22365, 8, 11951, 220, 777, 1174, 220, 508, 617, 1027, 19698, 304, 48473, 430, 1464, 47588, 46220, 13, 5046, 1521, 11, 279, 1455, 9959, 311, 420, 990, 374, 264, 32887, 55986, 220, 1691, 315, 6570, 38, 304, 3878, 315, 279, 6541, 4724, 11, 902, 374, 264, 12472, 5552, 311, 279, 6811, 304, 44685, 3717, 1990, 1403, 21562, 430, 16136, 304, 459, 29393, 9320, 13, 19575, 220, 16, 64, 323, 1202, 17703, 3493, 264, 68144, 323, 4096, 315, 279, 29393, 743, 5352, 369, 19179, 315, 6570, 38, 304, 24929, 5901, 48473, 13, 19575, 220, 16, 65, 11, 272, 5039, 3135, 505, 264, 320, 7261, 8, 7479, 315, 24172, 2170, 13, 578, 6570, 21261, 505, 420, 7479, 374, 1633, 3831, 11, 10923, 369, 83245, 12984, 43739, 449, 8450, 4791, 29466, 1082, 11595, 3485, 220, 605, 220, 21, 662, 763, 13168, 11, 6570, 38, 505, 264, 24172, 2170, 320, 4119, 8, 7479, 374, 20025, 11388, 481, 320, 266, 3325, 4848, 10373, 315, 26703, 4827, 1109, 279, 320, 7261, 8, 7479, 570, 21883, 11, 584, 7664, 279, 1005, 315, 279, 743, 5352, 6982, 304, 23966, 13, 220, 16, 64, 311, 70755, 279, 2132, 24747, 29393, 88636, 16000, 11, 100897, 602, 42908, 1174, 4613, 555, 279, 12976, 11, 393, 602, 320, 17, 117774, 883, 284, 60247, 220, 15, 100897, 602, 42908, 320, 17, 117774, 883, 469, 503, 320, 117774, 883, 469, 597, 320, 117774, 7609, 19575, 220, 16, 25, 10657, 2902, 277, 74689, 9659, 19579, 9392, 439, 24172, 2170, 374, 13750, 46720, 922, 279, 8183, 77933, 311, 279, 320, 7261, 8, 7479, 13, 264, 1174, 328, 82149, 315, 279, 6570, 38, 22772, 743, 5352, 13, 2057, 51077, 2132, 2902, 277, 74689, 3177, 11, 66557, 315, 220, 4728, 26807, 46406, 1051, 10968, 520, 3221, 53183, 39775, 311, 264, 220, 605, 12, 44223, 76, 1773, 37144, 7858, 389, 279, 6205, 13, 56996, 12509, 323, 12330, 7426, 22563, 389, 42496, 18094, 5535, 369, 19815, 323, 9678, 2585, 315, 279, 83245, 315, 279, 24038, 323, 2132, 2902, 277, 74689, 3177, 430, 8813, 279, 32314, 13, 101174, 220, 16, 323, 101174, 220, 17, 527, 279, 27030, 315, 279, 83245, 11277, 1306, 279, 14143, 323, 279, 8678, 805, 11, 15947, 11, 449, 5201, 311, 279, 510, 16, 11, 16, 11, 34363, 16, 60, 26110, 8183, 13, 293, 1174, 272, 1174, 6570, 38, 21261, 439, 264, 734, 315, 9392, 315, 10672, 83245, 520, 220, 508, 735, 13, 763, 293, 1174, 272, 1174, 279, 8678, 805, 374, 11, 15947, 11, 15638, 323, 77933, 311, 279, 14143, 13, 763, 2225, 31794, 279, 45209, 374, 30510, 555, 279, 16557, 907, 304, 293, 662, 578, 6573, 5238, 527, 18809, 430, 2997, 682, 279, 5535, 16000, 5540, 304, 220, 19, 9653, 46220, 11, 20444, 279, 67822, 5238, 2997, 1193, 294, 220, 1644, 662, 578, 99169, 527, 25685, 31794, 315, 17303, 6570, 38, 21261, 19579, 10672, 83245, 9392, 13, 8797, 1404, 2217, 1666, 264, 1176, 3094, 11, 584, 11075, 279, 17140, 315, 279, 1579, 1355, 1631, 33342, 25776, 304, 279, 320, 7261, 8, 7479, 11, 902, 527, 279, 510, 16, 11, 34363, 16, 11, 15, 60, 323, 510, 16, 11, 16, 11, 34363, 16, 60, 18445, 13, 2057, 656, 779, 11, 584, 25291, 46720, 279, 13790, 83245, 315, 279, 24038, 3177, 320, 1820, 14143, 8, 323, 279, 25685, 3213, 9277, 1603, 279, 32314, 320, 1820, 8678, 805, 705, 449, 872, 8844, 9392, 743, 520, 3060, 220, 15, 11877, 477, 220, 1954, 11877, 13, 28460, 1113, 279, 14143, 323, 8678, 805, 3871, 19159, 43739, 11, 6982, 304, 23966, 13, 220, 16, 65, 11, 272, 1174, 902, 527, 13890, 311, 12984, 315, 279, 6205, 922, 279, 7479, 4725, 13, 578, 27030, 520, 902, 584, 23846, 279, 16557, 323, 279, 854, 304, 23966, 13, 220, 16, 65, 323, 279, 854, 304, 23966, 13, 220, 16, 66, 2187, 603, 311, 10765, 279, 12717, 25776, 304, 279, 320, 7261, 8, 11277, 315, 279, 7479, 13, 20636, 11075, 279, 1579, 1355, 1631, 33342, 18445, 11, 584, 70755, 100897, 602, 42908, 555, 16785, 2380, 315, 4595, 315, 43739, 11, 279, 3135, 315, 902, 527, 6982, 304, 23966, 13, 220, 17, 662, 763, 43739, 6982, 304, 23966, 13, 220, 17, 64, 11, 293, 1174, 584, 42208, 279, 8678, 805, 3235, 832, 315, 279, 1403, 1579, 1355, 1631, 33342, 18445, 323, 46720, 279, 11277, 315, 13790, 83245, 315, 279, 14143, 1555, 220, 6843, 11877, 13, 19575, 220, 17, 66, 5039, 279, 28029, 29953, 299, 2191, 315, 279, 6570, 38, 2077, 41128, 374, 11, 279, 6811, 304, 6570, 8066, 555, 2163, 323, 1314, 28029, 398, 25685, 1534, 3177, 13, 1789, 682, 2380, 43739, 279, 6570, 38, 21261, 439, 264, 734, 315, 9392, 374, 13263, 449, 279, 2132, 24747, 29393, 88636, 16000, 3685, 369, 279, 220, 19, 9653, 1486, 1912, 315, 24172, 2170, 11, 439, 16717, 555, 279, 1579, 13708, 315, 279, 18809, 304, 23966, 13, 220, 16, 65, 11, 272, 323, 23966, 13, 220, 17, 64, 4235, 66, 662, 19575, 220, 17, 25, 10657, 2902, 277, 74689, 21261, 449, 8521, 22209, 388, 11, 28029, 29953, 299, 2191, 323, 9499, 44393, 389, 264, 24172, 2170, 320, 7261, 8, 6205, 13, 264, 1174, 293, 1174, 6570, 38, 439, 734, 315, 14143, 83245, 449, 22209, 388, 8521, 3235, 220, 15, 11877, 320, 264, 883, 323, 220, 1954, 11877, 320, 293, 7026, 902, 527, 279, 510, 16, 11, 16, 11, 34363, 16, 60, 323, 510, 16, 11, 34363, 16, 11, 15, 60, 26110, 25776, 11, 15947, 13, 22925, 5238, 527, 18809, 13126, 682, 2380, 2536, 38029, 16000, 5540, 13, 578, 99169, 527, 25685, 31794, 315, 17303, 6570, 38, 21261, 13, 272, 1174, 46861, 29953, 299, 2191, 320, 8758, 38, 21261, 6811, 1990, 1314, 12, 323, 2163, 25417, 28029, 398, 25685, 1534, 9659, 3177, 8, 30510, 555, 279, 16557, 907, 304, 23966, 13, 220, 16, 65, 19579, 83245, 9392, 315, 279, 128257, 198, 128256, 78191, 198, 2822, 6931, 10334, 1047, 74389, 430, 279, 14847, 1053, 387, 779, 3544, 0, 57116, 330, 79, 11059, 1, 2380, 48473, 449, 66557, 315, 3177, 13, 71500, 398, 11, 279, 48473, 51713, 279, 7928, 75098, 29393, 2077, 315, 904, 3967, 26110, 13, 578, 2077, 574, 264, 6908, 3392, 315, 2204, 28296, 3177, 449, 11157, 279, 11900, 315, 279, 28334, 13, 4314, 48473, 527, 3697, 315, 264, 502, 538, 315, 7384, 3967, 439, 468, 1216, 75, 5347, 86366, 1147, 13, 1115, 990, 11774, 1057, 7422, 389, 29393, 14847, 304, 468, 1216, 75, 5347, 86366, 1147, 13, 1226, 3685, 3177, 66557, 311, 8356, 2204, 28296, 3177, 449, 11157, 279, 11900, 719, 539, 1778, 264, 6908, 2077, 13, 578, 6371, 315, 420, 58973, 2077, 374, 9987, 0, 1115, 4007, 374, 2736, 65792, 279, 4500, 315, 43593, 502, 26018, 922, 1521, 14847, 13, 4314, 7384, 527, 26455, 369, 6462, 2320, 268, 17820, 1113, 26148, 11, 3814, 11376, 95090, 11, 323, 1023, 7766, 13, 468, 1216, 75, 81682, 919, 527, 11775, 19252, 430, 1051, 19698, 311, 387, 3970, 304, 1579, 65487, 22027, 21896, 719, 617, 539, 1027, 13468, 13, 4452, 11, 14248, 6051, 13468, 1521, 19252, 439, 459, 7425, 306, 3424, 315, 57678, 304, 264, 5016, 743, 315, 5347, 318, 22029, 7384, 13, 35390, 7978, 617, 6982, 430, 468, 1216, 75, 5347, 86366, 1147, 31324, 459, 51709, 3544, 75098, 29393, 2077, 13, 1115, 2077, 6835, 10205, 311, 279, 7928, 29393, 2132, 82341, 9659, 2515, 315, 904, 3967, 26110, 13, 4314, 24654, 1051, 1903, 304, 279, 9320, 9501, 6067, 25, 95685, 372, 87364, 579, 320, 57099, 2170, 705, 95685, 372, 33088, 579, 320, 57099, 47, 705, 323, 13080, 677, 2411, 87364, 579, 320, 86107, 2170, 570, 362, 326, 4636, 433, 574, 2867, 505, 46220, 38864, 430, 1070, 1053, 387, 264, 2536, 62399, 2077, 304, 1521, 6067, 11, 1070, 574, 912, 32887, 20212, 23377, 279, 3544, 26703, 315, 2077, 13468, 13, 3296, 12593, 449, 1023, 1664, 22015, 75098, 48473, 11, 279, 2536, 62399, 29393, 2077, 304, 1521, 6067, 374, 8294, 555, 9547, 315, 220, 605, 311, 220, 1041, 13, 16644, 279, 16907, 2077, 11, 14248, 48248, 1521, 14955, 690, 51077, 279, 4500, 315, 11084, 671, 3003, 822, 5528, 311, 11294, 75098, 29393, 2077, 5865, 304, 1521, 7384, 13, 7429, 11, 468, 1216, 75, 5347, 86366, 1147, 527, 3685, 311, 617, 264, 7029, 2134, 315, 3469, 4748, 772, 8535, 8522, 439, 7384, 311, 387, 1511, 369, 279, 4500, 315, 2024, 1494, 59037, 44163, 323, 3117, 3502, 82482, 25407, 69087, 13, 220, 128257, 198 ]

1,822

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Comprehensive assessments of species’ extinction risks have documented the extinction crisis 1 and underpinned strategies for reducing those risks 2 . Global assessments reveal that, among tetrapods, 40.7% of amphibians, 25.4% of mammals and 13.6% of birds are threatened with extinction 3 . Because global assessments have been lacking, reptiles have been omitted from conservation-prioritization analyses that encompass other tetrapods 4 , 5 , 6 , 7 . Reptiles are unusually diverse in arid regions, suggesting that they may have different conservation needs 6 . Here we provide a comprehensive extinction-risk assessment of reptiles and show that at least 1,829 out of 10,196 species (21.1%) are threatened—confirming a previous extrapolation 8 and representing 15.6 billion years of phylogenetic diversity. Reptiles are threatened by the same major factors that threaten other tetrapods—agriculture, logging, urban development and invasive species—although the threat posed by climate change remains uncertain. Reptiles inhabiting forests, where these threats are strongest, are more threatened than those in arid habitats, contrary to our prediction. Birds, mammals and amphibians are unexpectedly good surrogates for the conservation of reptiles, although threatened reptiles with the smallest ranges tend to be isolated from other threatened tetrapods. Although some reptiles—including most species of crocodiles and turtles—require urgent, targeted action to prevent extinctions, efforts to protect other tetrapods, such as habitat preservation and control of trade and invasive species, will probably also benefit many reptiles. Main Although comprehensive extinction-risk assessments have been available for birds, mammals and amphibians for well over a decade 3 , reptiles have, until now, not been comprehensively assessed. Therefore, conservation science and practice has typically relied on the International Union for Conservation of Nature (IUCN) Red List categories and distributions of the other three tetrapod classes to inform policy and guide priorities for investments 2 , despite differing expectations as to how effective common strategies will be across classes 9 , 10 . With a high diversity in arid regions and some islands and archipelagos (for example, Antilles, New Caledonia and New Zealand) compared with other tetrapods, reptiles were thought to require different conservation strategies and geographical priorities 6 . In the absence of Red List assessments, researchers have resorted to indirect measures of extinction risk such as range size and human pressure 6 , 11 . Here we examine the results of a comprehensive Red List assessment of reptiles and outline their implications for the conservation needs of reptiles. Comprising the turtles (Testudines), crocodiles (Crocodylia), squamates (Squamata: lizards, snakes and amphisbaenians) and tuatara (Rhynchocephalia), reptiles are a paraphyletic class representing diverse body forms, habitat affinities and functional roles in their respective ecosystems 12 . The largely terrestrial squamates are by far the most speciose group (9,820 species in this assessment), whereas the primarily aquatic turtles and crocodiles are often larger bodied but include only 351 and 24 species, respectively. Rhynchocephalians diverged from the snake and lizard lineage in the Triassic period and include one extant species 13 . Given this diversity of reptiles, threats to their persistence are likely to be equally varied, and so these need to be specified to guide effective conservation action. Extinction risk and threats We assessed reptiles globally using the IUCN Red List criteria with input from 961 scientists (Supplementary Note 1 ) achieved primarily through 48 workshops (Supplementary Table 1 ). Across all 10,196 species assessed, 21.1% are threatened with extinction (categorized as vulnerable, endangered or critically endangered; Supplementary Table 2 ). As a group, a greater number of reptile species are threatened than birds or mammals, but fewer than amphibians. Proportionately more mammals and amphibians are threatened than reptiles (Fig. 1a ). The reptile threat prevalence falls within a previous estimate of 15–36% threatened (best estimate 19%) from a random sample of 1,500 reptile species 8 . To our knowledge, this study represents the first global test of a sampled Red List extrapolation. The proportion of turtles and crocodiles that are threatened (57.9% and 50.0%, respectively) is much higher than those of squamates (19.6%) and tuatara (0%), and comparable to the most-threatened tetrapod groups, salamanders (57.0%) and monotremes (60.0%) (Fig. 1b ). Within squamates, iguanid (73.8%) and xenosaurid (60.0%) lizards and uropeltid (61.1%) and tropidophiid (60.0%) snakes are highly threatened. Since 1500, 31 reptile species (0.3%) have been driven extinct, including 24 squamates and 7 turtles, with 2 squamate species from Christmas Island categorized as extinct in the wild (persisting only as captive populations); 40 critically endangered species are ‘possibly extinct’ (that is, species that are likely to be extinct, but that have a small chance that they may be extant; Extended Data Fig. 1 ). Additional species probably became extinct before being documented by science 14 . Fig. 1: Taxonomic patterns of extinction risk in tetrapods. a , Taxonomic patterns organized by class. The numbers above each column refer to the numbers and percentages of species threatened (that is, those categorized as critically endangered, endangered or vulnerable). b , Extinction risk by major taxonomic groups. Blue lines indicate the best estimate of the percentage of species threatened. CR, critically endangered; DD, data deficient; EN, endangered; EW, extinct in the wild; EX, extinct; LC, least concern; NT, near threatened; VU, vulnerable. Source data Full size image Limited information resulted in 1,507 species (14.8%) being categorized as data deficient, similar to the number in mammals (15.1%) and lower than for amphibians (20.4%), but much higher than for birds (0.5%). Taxonomic groups with fossorial or other secretive habits and/or restricted to poorly studied areas (such as blindsnakes (Gerrhopilidae and Typhlopidae)) had greater proportions of species categorized as data deficient (Supplementary Table 2 ). The greatest numbers of data-deficient species occur in Asia (585), South America (284) and Africa (271), with fewer data-deficient species in North and Middle America (163), Oceania (124), Australia (55), the Caribbean (34) and Europe (3). Uncertainty about the status of data-deficient species suggests that the proportion of reptiles threatened with extinction ranges from 18.0% (assuming no data-deficient species are threatened) to 32.8% (assuming all data-deficient species are threatened) with", "role": "user" }, { "content": "Reptiles are in trouble: In fact, over 21% of reptile species are threatened with extinction worldwide, according to a first-of-its-kind global assessment of more than 10,000 species. The findings show that some reptiles, including many species of crocodiles and turtles, require urgent conservation efforts to prevent their extinction. \"The results of the global reptile assessment signal the need to ramp up global efforts to conserve them,\" said study co-leader Neil Cox, of the International Union for the Conservation of Nature. \"Because reptiles are so diverse, they face a wide range of threats across a variety of habitats. \"A multifaceted action plan is necessary to protect these species, with all the evolutionary history they represent.\" The study was published Wednesday in the peer-reviewed British journal Nature. Study authors say the top threats to reptiles come from agriculture, logging, urban development and invasive species, although they acknowledge that the risk that climate change poses is uncertain. In all, of the 10,196 species assessed, they found that at least 1,829 (21%) of species were threatened with extinction (categorized as being vulnerable, endangered or critically endangered). Crocodiles and turtles are among the most at-risk species, with 57.9% and 50% of those assessed under threat, respectively. Some good news: The research revealed that efforts already underway to conserve threatened mammals, birds and amphibians are more likely than expected to also benefit many threatened reptiles. Study authors say that many of the risks that reptiles face are similar to those faced by those other animal groups and suggest that conservation efforts to protect these groups—including habitat restoration and controlling invasive species—may have also benefited reptiles. \"These study results show that reptile conservation research no longer needs to be overshadowed by that of amphibians, birds and mammals. It is concerning, though, that more than a fifth of all known reptile species are threatened,\" said Mark Auliya of the Zoological Research Museum in Bonn, Germany. In addition to turtles and crocodiles, reptiles in the study included lizards, snakes and tuatara, the only living member of a lineage that evolved in the Triassic period 200 million to 250 million years ago. \"Many reptiles, like the tuatara or pig-nosed turtle, are like living fossils, whose loss would spell the end of not just species that play unique ecosystem roles, but also many billions of years of evolutionary history, said Mike Hoffmann, of the Zoological Society of London. \"Their future survival depends on us putting nature at the heart of all we do.\" Another expert, Maureen Kearney, a program director at the National Science Foundation, said that \"the potential loss of one-fifth of all reptile species reminds us how much of Earth's biodiversity is disappearing, a crisis that is threatening all species, including humans.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Comprehensive assessments of species’ extinction risks have documented the extinction crisis 1 and underpinned strategies for reducing those risks 2 . Global assessments reveal that, among tetrapods, 40.7% of amphibians, 25.4% of mammals and 13.6% of birds are threatened with extinction 3 . Because global assessments have been lacking, reptiles have been omitted from conservation-prioritization analyses that encompass other tetrapods 4 , 5 , 6 , 7 . Reptiles are unusually diverse in arid regions, suggesting that they may have different conservation needs 6 . Here we provide a comprehensive extinction-risk assessment of reptiles and show that at least 1,829 out of 10,196 species (21.1%) are threatened—confirming a previous extrapolation 8 and representing 15.6 billion years of phylogenetic diversity. Reptiles are threatened by the same major factors that threaten other tetrapods—agriculture, logging, urban development and invasive species—although the threat posed by climate change remains uncertain. Reptiles inhabiting forests, where these threats are strongest, are more threatened than those in arid habitats, contrary to our prediction. Birds, mammals and amphibians are unexpectedly good surrogates for the conservation of reptiles, although threatened reptiles with the smallest ranges tend to be isolated from other threatened tetrapods. Although some reptiles—including most species of crocodiles and turtles—require urgent, targeted action to prevent extinctions, efforts to protect other tetrapods, such as habitat preservation and control of trade and invasive species, will probably also benefit many reptiles. Main Although comprehensive extinction-risk assessments have been available for birds, mammals and amphibians for well over a decade 3 , reptiles have, until now, not been comprehensively assessed. Therefore, conservation science and practice has typically relied on the International Union for Conservation of Nature (IUCN) Red List categories and distributions of the other three tetrapod classes to inform policy and guide priorities for investments 2 , despite differing expectations as to how effective common strategies will be across classes 9 , 10 . With a high diversity in arid regions and some islands and archipelagos (for example, Antilles, New Caledonia and New Zealand) compared with other tetrapods, reptiles were thought to require different conservation strategies and geographical priorities 6 . In the absence of Red List assessments, researchers have resorted to indirect measures of extinction risk such as range size and human pressure 6 , 11 . Here we examine the results of a comprehensive Red List assessment of reptiles and outline their implications for the conservation needs of reptiles. Comprising the turtles (Testudines), crocodiles (Crocodylia), squamates (Squamata: lizards, snakes and amphisbaenians) and tuatara (Rhynchocephalia), reptiles are a paraphyletic class representing diverse body forms, habitat affinities and functional roles in their respective ecosystems 12 . The largely terrestrial squamates are by far the most speciose group (9,820 species in this assessment), whereas the primarily aquatic turtles and crocodiles are often larger bodied but include only 351 and 24 species, respectively. Rhynchocephalians diverged from the snake and lizard lineage in the Triassic period and include one extant species 13 . Given this diversity of reptiles, threats to their persistence are likely to be equally varied, and so these need to be specified to guide effective conservation action. Extinction risk and threats We assessed reptiles globally using the IUCN Red List criteria with input from 961 scientists (Supplementary Note 1 ) achieved primarily through 48 workshops (Supplementary Table 1 ). Across all 10,196 species assessed, 21.1% are threatened with extinction (categorized as vulnerable, endangered or critically endangered; Supplementary Table 2 ). As a group, a greater number of reptile species are threatened than birds or mammals, but fewer than amphibians. Proportionately more mammals and amphibians are threatened than reptiles (Fig. 1a ). The reptile threat prevalence falls within a previous estimate of 15–36% threatened (best estimate 19%) from a random sample of 1,500 reptile species 8 . To our knowledge, this study represents the first global test of a sampled Red List extrapolation. The proportion of turtles and crocodiles that are threatened (57.9% and 50.0%, respectively) is much higher than those of squamates (19.6%) and tuatara (0%), and comparable to the most-threatened tetrapod groups, salamanders (57.0%) and monotremes (60.0%) (Fig. 1b ). Within squamates, iguanid (73.8%) and xenosaurid (60.0%) lizards and uropeltid (61.1%) and tropidophiid (60.0%) snakes are highly threatened. Since 1500, 31 reptile species (0.3%) have been driven extinct, including 24 squamates and 7 turtles, with 2 squamate species from Christmas Island categorized as extinct in the wild (persisting only as captive populations); 40 critically endangered species are ‘possibly extinct’ (that is, species that are likely to be extinct, but that have a small chance that they may be extant; Extended Data Fig. 1 ). Additional species probably became extinct before being documented by science 14 . Fig. 1: Taxonomic patterns of extinction risk in tetrapods. a , Taxonomic patterns organized by class. The numbers above each column refer to the numbers and percentages of species threatened (that is, those categorized as critically endangered, endangered or vulnerable). b , Extinction risk by major taxonomic groups. Blue lines indicate the best estimate of the percentage of species threatened. CR, critically endangered; DD, data deficient; EN, endangered; EW, extinct in the wild; EX, extinct; LC, least concern; NT, near threatened; VU, vulnerable. Source data Full size image Limited information resulted in 1,507 species (14.8%) being categorized as data deficient, similar to the number in mammals (15.1%) and lower than for amphibians (20.4%), but much higher than for birds (0.5%). Taxonomic groups with fossorial or other secretive habits and/or restricted to poorly studied areas (such as blindsnakes (Gerrhopilidae and Typhlopidae)) had greater proportions of species categorized as data deficient (Supplementary Table 2 ). The greatest numbers of data-deficient species occur in Asia (585), South America (284) and Africa (271), with fewer data-deficient species in North and Middle America (163), Oceania (124), Australia (55), the Caribbean (34) and Europe (3). Uncertainty about the status of data-deficient species suggests that the proportion of reptiles threatened with extinction ranges from 18.0% (assuming no data-deficient species are threatened) to 32.8% (assuming all data-deficient species are threatened) with<|im_end|> <|im_start|>assistant Reptiles are in trouble: In fact, over 21% of reptile species are threatened with extinction worldwide, according to a first-of-its-kind global assessment of more than 10,000 species. The findings show that some reptiles, including many species of crocodiles and turtles, require urgent conservation efforts to prevent their extinction. "The results of the global reptile assessment signal the need to ramp up global efforts to conserve them," said study co-leader Neil Cox, of the International Union for the Conservation of Nature. "Because reptiles are so diverse, they face a wide range of threats across a variety of habitats. "A multifaceted action plan is necessary to protect these species, with all the evolutionary history they represent." The study was published Wednesday in the peer-reviewed British journal Nature. Study authors say the top threats to reptiles come from agriculture, logging, urban development and invasive species, although they acknowledge that the risk that climate change poses is uncertain. In all, of the 10,196 species assessed, they found that at least 1,829 (21%) of species were threatened with extinction (categorized as being vulnerable, endangered or critically endangered). Crocodiles and turtles are among the most at-risk species, with 57.9% and 50% of those assessed under threat, respectively. Some good news: The research revealed that efforts already underway to conserve threatened mammals, birds and amphibians are more likely than expected to also benefit many threatened reptiles. Study authors say that many of the risks that reptiles face are similar to those faced by those other animal groups and suggest that conservation efforts to protect these groups—including habitat restoration and controlling invasive species—may have also benefited reptiles. "These study results show that reptile conservation research no longer needs to be overshadowed by that of amphibians, birds and mammals. It is concerning, though, that more than a fifth of all known reptile species are threatened," said Mark Auliya of the Zoological Research Museum in Bonn, Germany. In addition to turtles and crocodiles, reptiles in the study included lizards, snakes and tuatara, the only living member of a lineage that evolved in the Triassic period 200 million to 250 million years ago. "Many reptiles, like the tuatara or pig-nosed turtle, are like living fossils, whose loss would spell the end of not just species that play unique ecosystem roles, but also many billions of years of evolutionary history, said Mike Hoffmann, of the Zoological Society of London. "Their future survival depends on us putting nature at the heart of all we do." Another expert, Maureen Kearney, a program director at the National Science Foundation, said that "the potential loss of one-fifth of all reptile species reminds us how much of Earth's biodiversity is disappearing, a crisis that is threatening all species, including humans." <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 67963, 41300, 315, 9606, 529, 52609, 15635, 617, 27470, 279, 52609, 11501, 220, 16, 323, 1234, 79, 21203, 15174, 369, 18189, 1884, 15635, 220, 17, 662, 8121, 41300, 16805, 430, 11, 4315, 28953, 4714, 30797, 11, 220, 1272, 13, 22, 4, 315, 89022, 5493, 11, 220, 914, 13, 19, 4, 315, 56669, 323, 220, 1032, 13, 21, 4, 315, 20229, 527, 21699, 449, 52609, 220, 18, 662, 9393, 3728, 41300, 617, 1027, 32161, 11, 64873, 3742, 617, 1027, 40542, 505, 29711, 2320, 3334, 275, 2065, 29060, 430, 38632, 1023, 28953, 4714, 30797, 220, 19, 1174, 220, 20, 1174, 220, 21, 1174, 220, 22, 662, 1050, 418, 3742, 527, 57899, 17226, 304, 802, 307, 13918, 11, 23377, 430, 814, 1253, 617, 2204, 29711, 3966, 220, 21, 662, 5810, 584, 3493, 264, 16195, 52609, 46570, 15813, 315, 64873, 3742, 323, 1501, 430, 520, 3325, 220, 16, 11, 26218, 704, 315, 220, 605, 11, 5162, 9606, 320, 1691, 13, 16, 11587, 527, 21699, 2345, 14119, 287, 264, 3766, 71462, 367, 220, 23, 323, 14393, 220, 868, 13, 21, 7239, 1667, 315, 37555, 86945, 5411, 20057, 13, 1050, 418, 3742, 527, 21699, 555, 279, 1890, 3682, 9547, 430, 40250, 1023, 28953, 4714, 30797, 2345, 351, 2265, 10745, 11, 8558, 11, 16036, 4500, 323, 53354, 9606, 2345, 37241, 279, 6023, 37260, 555, 10182, 2349, 8625, 36218, 13, 1050, 418, 3742, 26318, 5977, 36658, 11, 1405, 1521, 18208, 527, 31005, 11, 527, 810, 21699, 1109, 1884, 304, 802, 307, 71699, 11, 26102, 311, 1057, 20212, 13, 57628, 11, 56669, 323, 89022, 5493, 527, 51709, 1695, 1765, 12184, 988, 369, 279, 29711, 315, 64873, 3742, 11, 8051, 21699, 64873, 3742, 449, 279, 25655, 21986, 8541, 311, 387, 25181, 505, 1023, 21699, 28953, 4714, 30797, 13, 10541, 1063, 64873, 3742, 76070, 1455, 9606, 315, 14425, 20720, 3742, 323, 72503, 2345, 4408, 34771, 11, 17550, 1957, 311, 5471, 1327, 74690, 11, 9045, 311, 6144, 1023, 28953, 4714, 30797, 11, 1778, 439, 39646, 46643, 323, 2585, 315, 6696, 323, 53354, 9606, 11, 690, 4762, 1101, 8935, 1690, 64873, 3742, 13, 4802, 10541, 16195, 52609, 46570, 41300, 617, 1027, 2561, 369, 20229, 11, 56669, 323, 89022, 5493, 369, 1664, 927, 264, 13515, 220, 18, 1174, 64873, 3742, 617, 11, 3156, 1457, 11, 539, 1027, 12963, 28014, 32448, 13, 15636, 11, 29711, 8198, 323, 6725, 706, 11383, 41013, 389, 279, 7327, 9323, 369, 45435, 315, 22037, 320, 40, 5576, 45, 8, 3816, 1796, 11306, 323, 43785, 315, 279, 1023, 2380, 28953, 4714, 347, 6989, 311, 6179, 4947, 323, 8641, 30601, 369, 22538, 220, 17, 1174, 8994, 61469, 17078, 439, 311, 1268, 7524, 4279, 15174, 690, 387, 4028, 6989, 220, 24, 1174, 220, 605, 662, 3161, 264, 1579, 20057, 304, 802, 307, 13918, 323, 1063, 30100, 323, 5438, 82179, 81707, 320, 2000, 3187, 11, 6898, 31355, 11, 1561, 356, 5962, 21947, 323, 1561, 17340, 8, 7863, 449, 1023, 28953, 4714, 30797, 11, 64873, 3742, 1051, 3463, 311, 1397, 2204, 29711, 15174, 323, 54001, 30601, 220, 21, 662, 763, 279, 19821, 315, 3816, 1796, 41300, 11, 12074, 617, 594, 13909, 311, 25636, 11193, 315, 52609, 5326, 1778, 439, 2134, 1404, 323, 3823, 7410, 220, 21, 1174, 220, 806, 662, 5810, 584, 21635, 279, 3135, 315, 264, 16195, 3816, 1796, 15813, 315, 64873, 3742, 323, 21782, 872, 25127, 369, 279, 29711, 3966, 315, 64873, 3742, 13, 1219, 34754, 279, 72503, 320, 2323, 664, 1572, 705, 14425, 20720, 3742, 320, 34, 28787, 1094, 24235, 705, 8330, 309, 988, 320, 50, 87801, 460, 25, 326, 35191, 11, 57196, 323, 1097, 37889, 4749, 268, 5493, 8, 323, 9964, 266, 5169, 320, 73262, 1910, 971, 59822, 19379, 705, 64873, 3742, 527, 264, 63330, 982, 29150, 538, 14393, 17226, 2547, 7739, 11, 39646, 3611, 258, 1385, 323, 16003, 13073, 304, 872, 20081, 61951, 220, 717, 662, 578, 14090, 80492, 8330, 309, 988, 527, 555, 3117, 279, 1455, 1424, 822, 325, 1912, 320, 24, 11, 18248, 9606, 304, 420, 15813, 705, 20444, 279, 15871, 72491, 72503, 323, 14425, 20720, 3742, 527, 3629, 8294, 30111, 1142, 719, 2997, 1193, 220, 18113, 323, 220, 1187, 9606, 11, 15947, 13, 18452, 1910, 971, 59822, 278, 5493, 37441, 3640, 505, 279, 26332, 323, 95911, 65009, 304, 279, 12639, 65444, 4261, 323, 2997, 832, 1327, 519, 9606, 220, 1032, 662, 16644, 420, 20057, 315, 64873, 3742, 11, 18208, 311, 872, 42056, 527, 4461, 311, 387, 18813, 28830, 11, 323, 779, 1521, 1205, 311, 387, 5300, 311, 8641, 7524, 29711, 1957, 13, 9634, 22073, 5326, 323, 18208, 1226, 32448, 64873, 3742, 31550, 1701, 279, 358, 5576, 45, 3816, 1796, 13186, 449, 1988, 505, 220, 26114, 14248, 320, 10254, 67082, 7181, 220, 16, 883, 17427, 15871, 1555, 220, 2166, 35936, 320, 10254, 67082, 6771, 220, 16, 7609, 58237, 682, 220, 605, 11, 5162, 9606, 32448, 11, 220, 1691, 13, 16, 4, 527, 21699, 449, 52609, 320, 66, 58711, 439, 20134, 11, 52356, 477, 41440, 52356, 26, 99371, 6771, 220, 17, 7609, 1666, 264, 1912, 11, 264, 7191, 1396, 315, 64873, 458, 9606, 527, 21699, 1109, 20229, 477, 56669, 11, 719, 17162, 1109, 89022, 5493, 13, 1322, 15750, 2718, 810, 56669, 323, 89022, 5493, 527, 21699, 1109, 64873, 3742, 320, 30035, 13, 220, 16, 64, 7609, 578, 64873, 458, 6023, 38009, 17503, 2949, 264, 3766, 16430, 315, 220, 868, 4235, 1927, 4, 21699, 320, 16241, 16430, 220, 777, 11587, 505, 264, 4288, 6205, 315, 220, 16, 11, 2636, 64873, 458, 9606, 220, 23, 662, 2057, 1057, 6677, 11, 420, 4007, 11105, 279, 1176, 3728, 1296, 315, 264, 49976, 3816, 1796, 71462, 367, 13, 578, 21801, 315, 72503, 323, 14425, 20720, 3742, 430, 527, 21699, 320, 3226, 13, 24, 4, 323, 220, 1135, 13, 15, 13689, 15947, 8, 374, 1790, 5190, 1109, 1884, 315, 8330, 309, 988, 320, 777, 13, 21, 11587, 323, 9964, 266, 5169, 320, 15, 34971, 323, 30139, 311, 279, 1455, 56844, 6901, 28953, 4714, 347, 5315, 11, 4371, 309, 85051, 320, 3226, 13, 15, 11587, 323, 78316, 1864, 288, 320, 1399, 13, 15, 11587, 320, 30035, 13, 220, 16, 65, 7609, 25218, 8330, 309, 988, 11, 19935, 10602, 307, 320, 5958, 13, 23, 11587, 323, 53265, 59076, 307, 320, 1399, 13, 15, 11587, 326, 35191, 323, 577, 897, 3903, 307, 320, 5547, 13, 16, 11587, 323, 21965, 307, 5237, 55583, 320, 1399, 13, 15, 11587, 57196, 527, 7701, 21699, 13, 8876, 220, 3965, 15, 11, 220, 2148, 64873, 458, 9606, 320, 15, 13, 18, 11587, 617, 1027, 16625, 69918, 11, 2737, 220, 1187, 8330, 309, 988, 323, 220, 22, 72503, 11, 449, 220, 17, 8330, 92166, 9606, 505, 10280, 10951, 71974, 439, 69918, 304, 279, 8545, 320, 40926, 287, 1193, 439, 60951, 22673, 1237, 220, 1272, 41440, 52356, 9606, 527, 3451, 54228, 69918, 529, 320, 9210, 374, 11, 9606, 430, 527, 4461, 311, 387, 69918, 11, 719, 430, 617, 264, 2678, 6140, 430, 814, 1253, 387, 1327, 519, 26, 41665, 2956, 23966, 13, 220, 16, 7609, 24086, 9606, 4762, 6244, 69918, 1603, 1694, 27470, 555, 8198, 220, 975, 662, 23966, 13, 220, 16, 25, 15545, 48228, 12912, 315, 52609, 5326, 304, 28953, 4714, 30797, 13, 264, 1174, 15545, 48228, 12912, 17057, 555, 538, 13, 578, 5219, 3485, 1855, 3330, 8464, 311, 279, 5219, 323, 54208, 315, 9606, 21699, 320, 9210, 374, 11, 1884, 71974, 439, 41440, 52356, 11, 52356, 477, 20134, 570, 293, 1174, 9634, 22073, 5326, 555, 3682, 3827, 48228, 5315, 13, 8868, 5238, 13519, 279, 1888, 16430, 315, 279, 11668, 315, 9606, 21699, 13, 12904, 11, 41440, 52356, 26, 32004, 11, 828, 87544, 26, 5301, 11, 52356, 26, 64095, 11, 69918, 304, 279, 8545, 26, 4154, 11, 69918, 26, 31971, 11, 3325, 4747, 26, 18125, 11, 3221, 21699, 26, 650, 52, 11, 20134, 13, 8922, 828, 8797, 1404, 2217, 19439, 2038, 19543, 304, 220, 16, 11, 20068, 9606, 320, 975, 13, 23, 11587, 1694, 71974, 439, 828, 87544, 11, 4528, 311, 279, 1396, 304, 56669, 320, 868, 13, 16, 11587, 323, 4827, 1109, 369, 89022, 5493, 320, 508, 13, 19, 34971, 719, 1790, 5190, 1109, 369, 20229, 320, 15, 13, 20, 53172, 15545, 48228, 5315, 449, 26495, 22676, 477, 1023, 84099, 26870, 323, 5255, 22486, 311, 31555, 20041, 5789, 320, 21470, 439, 67161, 77, 2094, 320, 38, 618, 26172, 321, 114405, 323, 14221, 764, 23085, 114405, 595, 1047, 7191, 49892, 315, 9606, 71974, 439, 828, 87544, 320, 10254, 67082, 6771, 220, 17, 7609, 578, 12474, 5219, 315, 828, 29899, 5499, 9606, 12446, 304, 13936, 320, 21535, 705, 4987, 5270, 320, 17058, 8, 323, 10384, 320, 15828, 705, 449, 17162, 828, 29899, 5499, 9606, 304, 4892, 323, 12877, 5270, 320, 9892, 705, 507, 346, 9345, 320, 8874, 705, 8494, 320, 2131, 705, 279, 35374, 320, 1958, 8, 323, 4606, 320, 18, 570, 29879, 81246, 922, 279, 2704, 315, 828, 29899, 5499, 9606, 13533, 430, 279, 21801, 315, 64873, 3742, 21699, 449, 52609, 21986, 505, 220, 972, 13, 15, 4, 320, 66463, 912, 828, 29899, 5499, 9606, 527, 21699, 8, 311, 220, 843, 13, 23, 4, 320, 66463, 682, 828, 29899, 5499, 9606, 527, 21699, 8, 449, 128257, 198, 128256, 78191, 198, 697, 418, 3742, 527, 304, 12544, 25, 763, 2144, 11, 927, 220, 1691, 4, 315, 64873, 458, 9606, 527, 21699, 449, 52609, 15603, 11, 4184, 311, 264, 1176, 8838, 12, 1220, 60806, 3728, 15813, 315, 810, 1109, 220, 605, 11, 931, 9606, 13, 578, 14955, 1501, 430, 1063, 64873, 3742, 11, 2737, 1690, 9606, 315, 14425, 20720, 3742, 323, 72503, 11, 1397, 34771, 29711, 9045, 311, 5471, 872, 52609, 13, 330, 791, 3135, 315, 279, 3728, 64873, 458, 15813, 8450, 279, 1205, 311, 23091, 709, 3728, 9045, 311, 78548, 1124, 1359, 1071, 4007, 1080, 31307, 1013, 34221, 39760, 11, 315, 279, 7327, 9323, 369, 279, 45435, 315, 22037, 13, 330, 18433, 64873, 3742, 527, 779, 17226, 11, 814, 3663, 264, 7029, 2134, 315, 18208, 4028, 264, 8205, 315, 71699, 13, 330, 32, 62387, 582, 25489, 1957, 3197, 374, 5995, 311, 6144, 1521, 9606, 11, 449, 682, 279, 41993, 3925, 814, 4097, 1210, 578, 4007, 574, 4756, 8079, 304, 279, 14734, 79804, 8013, 8486, 22037, 13, 19723, 12283, 2019, 279, 1948, 18208, 311, 64873, 3742, 2586, 505, 30029, 11, 8558, 11, 16036, 4500, 323, 53354, 9606, 11, 8051, 814, 25670, 430, 279, 5326, 430, 10182, 2349, 34103, 374, 36218, 13, 763, 682, 11, 315, 279, 220, 605, 11, 5162, 9606, 32448, 11, 814, 1766, 430, 520, 3325, 220, 16, 11, 26218, 320, 1691, 11587, 315, 9606, 1051, 21699, 449, 52609, 320, 66, 58711, 439, 1694, 20134, 11, 52356, 477, 41440, 52356, 570, 25611, 20720, 3742, 323, 72503, 527, 4315, 279, 1455, 520, 46570, 9606, 11, 449, 220, 3226, 13, 24, 4, 323, 220, 1135, 4, 315, 1884, 32448, 1234, 6023, 11, 15947, 13, 4427, 1695, 3754, 25, 578, 3495, 10675, 430, 9045, 2736, 38199, 311, 78548, 21699, 56669, 11, 20229, 323, 89022, 5493, 527, 810, 4461, 1109, 3685, 311, 1101, 8935, 1690, 21699, 64873, 3742, 13, 19723, 12283, 2019, 430, 1690, 315, 279, 15635, 430, 64873, 3742, 3663, 527, 4528, 311, 1884, 17011, 555, 1884, 1023, 10065, 5315, 323, 4284, 430, 29711, 9045, 311, 6144, 1521, 5315, 76070, 39646, 35093, 323, 26991, 53354, 9606, 2345, 18864, 617, 1101, 56128, 64873, 3742, 13, 330, 9673, 4007, 3135, 1501, 430, 64873, 458, 29711, 3495, 912, 5129, 3966, 311, 387, 85305, 291, 555, 430, 315, 89022, 5493, 11, 20229, 323, 56669, 13, 1102, 374, 18815, 11, 3582, 11, 430, 810, 1109, 264, 18172, 315, 682, 3967, 64873, 458, 9606, 527, 21699, 1359, 1071, 4488, 362, 24520, 7911, 315, 279, 45903, 5848, 8483, 16730, 304, 13789, 77, 11, 10057, 13, 763, 5369, 311, 72503, 323, 14425, 20720, 3742, 11, 64873, 3742, 304, 279, 4007, 5343, 326, 35191, 11, 57196, 323, 9964, 266, 5169, 11, 279, 1193, 5496, 4562, 315, 264, 65009, 430, 28995, 304, 279, 12639, 65444, 4261, 220, 1049, 3610, 311, 220, 5154, 3610, 1667, 4227, 13, 330, 8607, 64873, 3742, 11, 1093, 279, 9964, 266, 5169, 477, 24623, 5392, 20158, 37189, 11, 527, 1093, 5496, 81473, 11, 6832, 4814, 1053, 13141, 279, 842, 315, 539, 1120, 9606, 430, 1514, 5016, 26031, 13073, 11, 719, 1101, 1690, 33151, 315, 1667, 315, 41993, 3925, 11, 1071, 11519, 43822, 18022, 11, 315, 279, 45903, 5848, 13581, 315, 7295, 13, 330, 35897, 3938, 20237, 14117, 389, 603, 10917, 7138, 520, 279, 4851, 315, 682, 584, 656, 1210, 13596, 6335, 11, 11583, 96672, 100138, 3520, 11, 264, 2068, 7690, 520, 279, 5165, 10170, 5114, 11, 1071, 430, 330, 1820, 4754, 4814, 315, 832, 2269, 58710, 315, 682, 64873, 458, 9606, 35710, 603, 1268, 1790, 315, 9420, 596, 73119, 374, 67503, 11, 264, 11501, 430, 374, 27903, 682, 9606, 11, 2737, 12966, 1210, 220, 128257, 198 ]

2,127

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract When a hurricane strikes land, the destruction of property and the environment and the loss of life are largely confined to a narrow coastal area. This is because hurricanes are fuelled by moisture from the ocean 1 , 2 , 3 , and so hurricane intensity decays rapidly after striking land 4 , 5 . In contrast to the effect of a warming climate on hurricane intensification, many aspects of which are fairly well understood 6 , 7 , 8 , 9 , 10 , little is known of its effect on hurricane decay. Here we analyse intensity data for North Atlantic landfalling hurricanes 11 over the past 50 years and show that hurricane decay has slowed, and that the slowdown in the decay over time is in direct proportion to a contemporaneous rise in the sea surface temperature 12 . Thus, whereas in the late 1960s a typical hurricane lost about 75 per cent of its intensity in the first day past landfall, now the corresponding decay is only about 50 per cent. We also show, using computational simulations, that warmer sea surface temperatures induce a slower decay by increasing the stock of moisture that a hurricane carries as it hits land. This stored moisture constitutes a source of heat that is not considered in theoretical models of decay 13 , 14 , 15 . Additionally, we show that climate-modulated changes in hurricane tracks 16 , 17 contribute to the increasingly slow decay. Our findings suggest that as the world continues to warm, the destructive power of hurricanes will extend progressively farther inland. Main Hurricanes thrive on moisture. Moisture from warm tropical oceans fuels the intense winds of a hurricane heat engine 2 , 3 . In a warming world, the moisture supply is enhanced. Warmer oceans supply more moisture, and warmer air, according to the Clausius–Clapeyron relation 18 , holds more moisture. As a result, we expect the maximum intensity a hurricane can achieve over its lifetime to increase 6 , 9 . Indeed, as the world warms, the strongest hurricanes (which, compared with the weaker ones, are less affected by impeding factors, for example, wind shear) are getting stronger, with the most pronounced intensification seen for the North Atlantic hurricanes 8 . Without moisture, hurricanes wither. A landfall severs 1 , 19 , 20 a hurricane from the ocean, its moisture source. Consequently, the intensity decays rapidly. (When the intensity drops below 33 m s −1 , the hurricane, according to the Saffir–Simpson scale 21 , is termed a tropical storm; however, for simplicity, we refer to tropical storms also as hurricanes.) How might hurricane decay rates change in a warming world? In contrast to the extensive studies of hurricanes over ocean, this question has attracted scant attention. Decay timescale τ We study North Atlantic landfalling hurricanes (Fig. 1a ) over 1967–2018 using the best-track database Atlantic HURDAT2 (ref. 11 ), widely considered the most reliable database of all ocean basin databases. (See Methods for further discussion on the data.) For each hurricane, we analyse the intensity, V , during the first day past landfall, the period over which the hurricane inflicts most of the destruction. Over this period, V decays exponentially 4 , 5 : V ( t ) = V (0)e − t / τ , where t is the time past landfall and τ , the decay timescale, is a single parameter that characterizes the rate of decay. (After the first day, V ( t ) can no longer be characterized by a single parameter; see Methods .) The larger the τ , the slower the decay, and therefore, the stronger the hurricane. We focus on the variation—if any—of τ over the past half-century. Fig. 1: Effect of SST on the decay of North Atlantic landfalling hurricanes. We analyse 71 landfall events over 1967–2018 (see Methods ). a , Hurricane tracks over 1967–1992 (in blue) and 1993-2018 (in red); see panel b for the corresponding distribution of τ . The dotted box, bounded by 10° N, 35° N, 75° W and 100° W, shows the pre-landfall region in which we compute the SST; also see Extended Data Figs 1 c, d and 2e . The map is from the MATLAB function worldmap . b , Histogram and probability density of τ . The average τ increases from 21.1 ± 1.3 h (1967–1992, 26 events) to 27.6 ± 2.3 h (1993–2018, 45 events), for which we also note ±1 standard error of the mean (s.e.m.). The error bars in the histogram are computed using the bootstrap sampling method and correspond to ±1 standard deviation (s.d.) in each bin (see Methods ). c – f , Time series of τ and SST. c , τ versus year (grey line); d , SST versus year (blue line); e , superposed τ versus year (grey line) and SST versus year (blue line); f , τ versus SST. We note that the τ time series echoes the SST time series with Pearson correlation r = 0.72. In panels c , d and f , we also show the error bars (which correspond to ±1 s.e.m.; see Methods ), the linear regression line (solid black line), and the 95% confidence band about the regression line (dotted black lines). The increase in τ and SST over time and the relationship between τ and SST are statistically significant (at 95% CI) and robust to the specifics of smoothing (Methods; Extended Data Tables 2 and 3 ). Source data Full size image For each landfall event, we compute τ using V ( t ); see Methods . From one event to another, the value of τ varies considerably. This value for any particular event is influenced by many factors, including non-climatic ones, such as the terrain underneath the hurricane 4 , 5 , 22 , 23 . To discern any potential effect of the climate on τ , we first analyse the distribution of τ on a multi-decadal timescale. In Fig. 1b", "role": "user" }, { "content": "Climate change is causing hurricanes that make landfall to take more time to weaken, reports a study published 11th November 2020 in the journal Nature. The researchers showed that hurricanes that develop over warmer oceans carry more moisture and therefore stay stronger for longer after hitting land. This means that in the future, as the world continues to warm, hurricanes are more likely to reach communities farther inland and be more destructive. \"The implications are very important, especially when considering policies that are put in place to cope with global warming,\" said Professor Pinaki Chakraborty, senior author of the study and head of the Fluid Mechanics Unit at the Okinawa Institute of Science and Technology Graduate University (OIST). \"We know that coastal areas need to ready themselves for more intense hurricanes, but inland communities, who may not have the know-how or infrastructure to cope with such intense winds or heavy rainfall, also need to be prepared.\" Many studies have shown that climate change can intensify hurricanes—known as cyclones or typhoons in other regions of the world—over the open ocean. But this is the first study to establish a clear link between a warming climate and the smaller subset of hurricanes that have made landfall. The scientists analyzed North Atlantic hurricanes that made landfall over the past half a century. They found that during the course of the first day after landfall, hurricanes weakened almost twice as slowly now than they did 50 years ago. \"When we plotted the data, we could clearly see that the amount of time it took for a hurricane to weaken was increasing with the years. But it wasn't a straight line—it was undulating—and we found that these ups and downs matched the same ups and downs seen in sea surface temperature,\" said Lin Li, first author and Ph.D. student in the OIST Fluid Mechanics Unit. The scientists tested the link between warmer sea surface temperature and slower weakening past landfall by creating computer simulations of four different hurricanes and setting different temperatures for the surface of the sea. Once each virtual hurricane reached category 4 strength, the scientists simulated landfall by cutting off the supply of moisture from beneath. Li explained: \"Hurricanes are heat engines, just like engines in cars. In car engines, fuel is combusted, and that heat energy is converted into mechanical work. For hurricanes, the moisture taken up from the surface of the ocean is the 'fuel' that intensifies and sustains a hurricane's destructive power, with heat energy from the moisture converted into powerful winds. Making landfall is equivalent to stopping the fuel supply to the engine of a car. Without fuel, the car will decelerate, and without its moisture source, the hurricane will decay.\" The researchers found that even though each simulated hurricane made landfall at the same intensity, the ones that developed over warmer waters took more time to weaken. The scientists found a strong correlation between the time it took for a hurricane to weaken after landfall and sea surface temperature, when both were plotted by year Credit: OIST \"These simulations proved what our analysis of past hurricanes had suggested: warmer oceans significantly impact the rate that hurricanes decay, even when their connection with the ocean's surface is severed. The question is why,\" said Prof. Chakraborty. Using additional simulations, the scientists found that \"stored moisture\" was the missing link. The researchers explained that when hurricanes make landfall, even though they can no longer access the ocean's supply of moisture, they still carry a stock of moisture that slowly depletes. When the scientists created virtual hurricanes that lacked this stored moisture after hitting land, they found that the sea surface temperature no longer had any impact on the rate of decay. \"This shows that stored moisture is the key factor that gives each hurricane in the simulation its own unique identity,\" said Li. \"Hurricanes that develop over warmer oceans can take up and store more moisture, which sustains them for longer and prevents them from weakening as quickly.\" The increased level of stored moisture also makes hurricanes \"wetter\"—an outcome already being felt as recent hurricanes have unleashed devastatingly high volumes of rainfall on coastal and inland communities. This research highlights the importance for climate models to carefully account for stored moisture when predicting the impact of warmer oceans on hurricanes. The study also pinpoints issues with the simple theoretical models widely used to understand how hurricanes decay. \"Current models of hurricane decay don't consider moisture—they just view hurricanes that have made landfall as a dry vortex that rubs against the land and is slowed down by friction. Our work shows these models are incomplete, which is why this clear signature of climate change wasn't previously captured,\" said Li. The researchers now plan to study hurricane data from other regions of the world to determine whether the impact of a warming climate on hurricane decay is occurring around the globe. Prof. Chakraborty concluded: \"Overall, the implications of this work are stark. If we don't curb global warming, landfalling hurricanes will continue to weaken more slowly. Their destruction will no longer be confined to coastal areas, causing higher levels of economic damage and costing more lives.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract When a hurricane strikes land, the destruction of property and the environment and the loss of life are largely confined to a narrow coastal area. This is because hurricanes are fuelled by moisture from the ocean 1 , 2 , 3 , and so hurricane intensity decays rapidly after striking land 4 , 5 . In contrast to the effect of a warming climate on hurricane intensification, many aspects of which are fairly well understood 6 , 7 , 8 , 9 , 10 , little is known of its effect on hurricane decay. Here we analyse intensity data for North Atlantic landfalling hurricanes 11 over the past 50 years and show that hurricane decay has slowed, and that the slowdown in the decay over time is in direct proportion to a contemporaneous rise in the sea surface temperature 12 . Thus, whereas in the late 1960s a typical hurricane lost about 75 per cent of its intensity in the first day past landfall, now the corresponding decay is only about 50 per cent. We also show, using computational simulations, that warmer sea surface temperatures induce a slower decay by increasing the stock of moisture that a hurricane carries as it hits land. This stored moisture constitutes a source of heat that is not considered in theoretical models of decay 13 , 14 , 15 . Additionally, we show that climate-modulated changes in hurricane tracks 16 , 17 contribute to the increasingly slow decay. Our findings suggest that as the world continues to warm, the destructive power of hurricanes will extend progressively farther inland. Main Hurricanes thrive on moisture. Moisture from warm tropical oceans fuels the intense winds of a hurricane heat engine 2 , 3 . In a warming world, the moisture supply is enhanced. Warmer oceans supply more moisture, and warmer air, according to the Clausius–Clapeyron relation 18 , holds more moisture. As a result, we expect the maximum intensity a hurricane can achieve over its lifetime to increase 6 , 9 . Indeed, as the world warms, the strongest hurricanes (which, compared with the weaker ones, are less affected by impeding factors, for example, wind shear) are getting stronger, with the most pronounced intensification seen for the North Atlantic hurricanes 8 . Without moisture, hurricanes wither. A landfall severs 1 , 19 , 20 a hurricane from the ocean, its moisture source. Consequently, the intensity decays rapidly. (When the intensity drops below 33 m s −1 , the hurricane, according to the Saffir–Simpson scale 21 , is termed a tropical storm; however, for simplicity, we refer to tropical storms also as hurricanes.) How might hurricane decay rates change in a warming world? In contrast to the extensive studies of hurricanes over ocean, this question has attracted scant attention. Decay timescale τ We study North Atlantic landfalling hurricanes (Fig. 1a ) over 1967–2018 using the best-track database Atlantic HURDAT2 (ref. 11 ), widely considered the most reliable database of all ocean basin databases. (See Methods for further discussion on the data.) For each hurricane, we analyse the intensity, V , during the first day past landfall, the period over which the hurricane inflicts most of the destruction. Over this period, V decays exponentially 4 , 5 : V ( t ) = V (0)e − t / τ , where t is the time past landfall and τ , the decay timescale, is a single parameter that characterizes the rate of decay. (After the first day, V ( t ) can no longer be characterized by a single parameter; see Methods .) The larger the τ , the slower the decay, and therefore, the stronger the hurricane. We focus on the variation—if any—of τ over the past half-century. Fig. 1: Effect of SST on the decay of North Atlantic landfalling hurricanes. We analyse 71 landfall events over 1967–2018 (see Methods ). a , Hurricane tracks over 1967–1992 (in blue) and 1993-2018 (in red); see panel b for the corresponding distribution of τ . The dotted box, bounded by 10° N, 35° N, 75° W and 100° W, shows the pre-landfall region in which we compute the SST; also see Extended Data Figs 1 c, d and 2e . The map is from the MATLAB function worldmap . b , Histogram and probability density of τ . The average τ increases from 21.1 ± 1.3 h (1967–1992, 26 events) to 27.6 ± 2.3 h (1993–2018, 45 events), for which we also note ±1 standard error of the mean (s.e.m.). The error bars in the histogram are computed using the bootstrap sampling method and correspond to ±1 standard deviation (s.d.) in each bin (see Methods ). c – f , Time series of τ and SST. c , τ versus year (grey line); d , SST versus year (blue line); e , superposed τ versus year (grey line) and SST versus year (blue line); f , τ versus SST. We note that the τ time series echoes the SST time series with Pearson correlation r = 0.72. In panels c , d and f , we also show the error bars (which correspond to ±1 s.e.m.; see Methods ), the linear regression line (solid black line), and the 95% confidence band about the regression line (dotted black lines). The increase in τ and SST over time and the relationship between τ and SST are statistically significant (at 95% CI) and robust to the specifics of smoothing (Methods; Extended Data Tables 2 and 3 ). Source data Full size image For each landfall event, we compute τ using V ( t ); see Methods . From one event to another, the value of τ varies considerably. This value for any particular event is influenced by many factors, including non-climatic ones, such as the terrain underneath the hurricane 4 , 5 , 22 , 23 . To discern any potential effect of the climate on τ , we first analyse the distribution of τ on a multi-decadal timescale. In Fig. 1b<|im_end|> <|im_start|>assistant Climate change is causing hurricanes that make landfall to take more time to weaken, reports a study published 11th November 2020 in the journal Nature. The researchers showed that hurricanes that develop over warmer oceans carry more moisture and therefore stay stronger for longer after hitting land. This means that in the future, as the world continues to warm, hurricanes are more likely to reach communities farther inland and be more destructive. "The implications are very important, especially when considering policies that are put in place to cope with global warming," said Professor Pinaki Chakraborty, senior author of the study and head of the Fluid Mechanics Unit at the Okinawa Institute of Science and Technology Graduate University (OIST). "We know that coastal areas need to ready themselves for more intense hurricanes, but inland communities, who may not have the know-how or infrastructure to cope with such intense winds or heavy rainfall, also need to be prepared." Many studies have shown that climate change can intensify hurricanes—known as cyclones or typhoons in other regions of the world—over the open ocean. But this is the first study to establish a clear link between a warming climate and the smaller subset of hurricanes that have made landfall. The scientists analyzed North Atlantic hurricanes that made landfall over the past half a century. They found that during the course of the first day after landfall, hurricanes weakened almost twice as slowly now than they did 50 years ago. "When we plotted the data, we could clearly see that the amount of time it took for a hurricane to weaken was increasing with the years. But it wasn't a straight line—it was undulating—and we found that these ups and downs matched the same ups and downs seen in sea surface temperature," said Lin Li, first author and Ph.D. student in the OIST Fluid Mechanics Unit. The scientists tested the link between warmer sea surface temperature and slower weakening past landfall by creating computer simulations of four different hurricanes and setting different temperatures for the surface of the sea. Once each virtual hurricane reached category 4 strength, the scientists simulated landfall by cutting off the supply of moisture from beneath. Li explained: "Hurricanes are heat engines, just like engines in cars. In car engines, fuel is combusted, and that heat energy is converted into mechanical work. For hurricanes, the moisture taken up from the surface of the ocean is the 'fuel' that intensifies and sustains a hurricane's destructive power, with heat energy from the moisture converted into powerful winds. Making landfall is equivalent to stopping the fuel supply to the engine of a car. Without fuel, the car will decelerate, and without its moisture source, the hurricane will decay." The researchers found that even though each simulated hurricane made landfall at the same intensity, the ones that developed over warmer waters took more time to weaken. The scientists found a strong correlation between the time it took for a hurricane to weaken after landfall and sea surface temperature, when both were plotted by year Credit: OIST "These simulations proved what our analysis of past hurricanes had suggested: warmer oceans significantly impact the rate that hurricanes decay, even when their connection with the ocean's surface is severed. The question is why," said Prof. Chakraborty. Using additional simulations, the scientists found that "stored moisture" was the missing link. The researchers explained that when hurricanes make landfall, even though they can no longer access the ocean's supply of moisture, they still carry a stock of moisture that slowly depletes. When the scientists created virtual hurricanes that lacked this stored moisture after hitting land, they found that the sea surface temperature no longer had any impact on the rate of decay. "This shows that stored moisture is the key factor that gives each hurricane in the simulation its own unique identity," said Li. "Hurricanes that develop over warmer oceans can take up and store more moisture, which sustains them for longer and prevents them from weakening as quickly." The increased level of stored moisture also makes hurricanes "wetter"—an outcome already being felt as recent hurricanes have unleashed devastatingly high volumes of rainfall on coastal and inland communities. This research highlights the importance for climate models to carefully account for stored moisture when predicting the impact of warmer oceans on hurricanes. The study also pinpoints issues with the simple theoretical models widely used to understand how hurricanes decay. "Current models of hurricane decay don't consider moisture—they just view hurricanes that have made landfall as a dry vortex that rubs against the land and is slowed down by friction. Our work shows these models are incomplete, which is why this clear signature of climate change wasn't previously captured," said Li. The researchers now plan to study hurricane data from other regions of the world to determine whether the impact of a warming climate on hurricane decay is occurring around the globe. Prof. Chakraborty concluded: "Overall, the implications of this work are stark. If we don't curb global warming, landfalling hurricanes will continue to weaken more slowly. Their destruction will no longer be confined to coastal areas, causing higher levels of economic damage and costing more lives." <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 3277, 264, 49784, 23170, 4363, 11, 279, 19814, 315, 3424, 323, 279, 4676, 323, 279, 4814, 315, 2324, 527, 14090, 45408, 311, 264, 15376, 35335, 3158, 13, 1115, 374, 1606, 90127, 527, 10633, 839, 555, 32257, 505, 279, 18435, 220, 16, 1174, 220, 17, 1174, 220, 18, 1174, 323, 779, 49784, 21261, 1654, 954, 19019, 1306, 21933, 4363, 220, 19, 1174, 220, 20, 662, 763, 13168, 311, 279, 2515, 315, 264, 24808, 10182, 389, 49784, 25228, 2461, 11, 1690, 13878, 315, 902, 527, 14470, 1664, 16365, 220, 21, 1174, 220, 22, 1174, 220, 23, 1174, 220, 24, 1174, 220, 605, 1174, 2697, 374, 3967, 315, 1202, 2515, 389, 49784, 31815, 13, 5810, 584, 49586, 21261, 828, 369, 4892, 23179, 4363, 13772, 287, 90127, 220, 806, 927, 279, 3347, 220, 1135, 1667, 323, 1501, 430, 49784, 31815, 706, 48946, 11, 323, 430, 279, 75017, 304, 279, 31815, 927, 892, 374, 304, 2167, 21801, 311, 264, 59504, 18133, 10205, 304, 279, 9581, 7479, 9499, 220, 717, 662, 14636, 11, 20444, 304, 279, 3389, 220, 5162, 15, 82, 264, 14595, 49784, 5675, 922, 220, 2075, 824, 2960, 315, 1202, 21261, 304, 279, 1176, 1938, 3347, 4363, 13772, 11, 1457, 279, 12435, 31815, 374, 1193, 922, 220, 1135, 824, 2960, 13, 1226, 1101, 1501, 11, 1701, 55580, 47590, 11, 430, 46039, 9581, 7479, 20472, 49853, 264, 29493, 31815, 555, 7859, 279, 5708, 315, 32257, 430, 264, 49784, 24266, 439, 433, 13280, 4363, 13, 1115, 9967, 32257, 42675, 264, 2592, 315, 8798, 430, 374, 539, 6646, 304, 32887, 4211, 315, 31815, 220, 1032, 1174, 220, 975, 1174, 220, 868, 662, 23212, 11, 584, 1501, 430, 10182, 17515, 7913, 4442, 304, 49784, 14242, 220, 845, 1174, 220, 1114, 17210, 311, 279, 15098, 6435, 31815, 13, 5751, 14955, 4284, 430, 439, 279, 1917, 9731, 311, 8369, 11, 279, 40652, 2410, 315, 90127, 690, 13334, 72859, 43726, 77289, 13, 4802, 89603, 41972, 389, 32257, 13, 82804, 554, 505, 8369, 35148, 54280, 40373, 279, 19428, 29592, 315, 264, 49784, 8798, 4817, 220, 17, 1174, 220, 18, 662, 763, 264, 24808, 1917, 11, 279, 32257, 8312, 374, 24872, 13, 5111, 1195, 54280, 8312, 810, 32257, 11, 323, 46039, 3805, 11, 4184, 311, 279, 68119, 9334, 4235, 5176, 2070, 88, 2298, 12976, 220, 972, 1174, 10187, 810, 32257, 13, 1666, 264, 1121, 11, 584, 1755, 279, 7340, 21261, 264, 49784, 649, 11322, 927, 1202, 19569, 311, 5376, 220, 21, 1174, 220, 24, 662, 23150, 11, 439, 279, 1917, 4208, 1026, 11, 279, 31005, 90127, 320, 8370, 11, 7863, 449, 279, 43383, 6305, 11, 527, 2753, 11754, 555, 3242, 16490, 9547, 11, 369, 3187, 11, 10160, 65344, 8, 527, 3794, 16643, 11, 449, 279, 1455, 38617, 25228, 2461, 3970, 369, 279, 4892, 23179, 90127, 220, 23, 662, 17586, 32257, 11, 90127, 449, 261, 13, 362, 4363, 13772, 513, 3078, 220, 16, 1174, 220, 777, 1174, 220, 508, 264, 49784, 505, 279, 18435, 11, 1202, 32257, 2592, 13, 53123, 11, 279, 21261, 1654, 954, 19019, 13, 320, 4599, 279, 21261, 21701, 3770, 220, 1644, 296, 274, 25173, 16, 1174, 279, 49784, 11, 4184, 311, 279, 328, 2715, 404, 4235, 50, 6802, 942, 5569, 220, 1691, 1174, 374, 61937, 264, 35148, 13766, 26, 4869, 11, 369, 40075, 11, 584, 8464, 311, 35148, 44583, 1101, 439, 90127, 6266, 2650, 2643, 49784, 31815, 7969, 2349, 304, 264, 24808, 1917, 30, 763, 13168, 311, 279, 16781, 7978, 315, 90127, 927, 18435, 11, 420, 3488, 706, 29123, 84955, 6666, 13, 98386, 3115, 2296, 39570, 1226, 4007, 4892, 23179, 4363, 13772, 287, 90127, 320, 30035, 13, 220, 16, 64, 883, 927, 220, 5162, 22, 4235, 679, 23, 1701, 279, 1888, 54566, 4729, 23179, 473, 1539, 48992, 17, 320, 1116, 13, 220, 806, 7026, 13882, 6646, 279, 1455, 15062, 4729, 315, 682, 18435, 58309, 32906, 13, 320, 10031, 19331, 369, 4726, 10430, 389, 279, 828, 6266, 1789, 1855, 49784, 11, 584, 49586, 279, 21261, 11, 650, 1174, 2391, 279, 1176, 1938, 3347, 4363, 13772, 11, 279, 4261, 927, 902, 279, 49784, 4225, 57545, 1455, 315, 279, 19814, 13, 6193, 420, 4261, 11, 650, 1654, 954, 75251, 220, 19, 1174, 220, 20, 551, 650, 320, 259, 883, 284, 650, 320, 15, 53021, 25173, 259, 611, 39570, 1174, 1405, 259, 374, 279, 892, 3347, 4363, 13772, 323, 39570, 1174, 279, 31815, 3115, 2296, 11, 374, 264, 3254, 5852, 430, 3752, 4861, 279, 4478, 315, 31815, 13, 320, 6153, 279, 1176, 1938, 11, 650, 320, 259, 883, 649, 912, 5129, 387, 32971, 555, 264, 3254, 5852, 26, 1518, 19331, 662, 8, 578, 8294, 279, 39570, 1174, 279, 29493, 279, 31815, 11, 323, 9093, 11, 279, 16643, 279, 49784, 13, 1226, 5357, 389, 279, 23851, 90863, 904, 2345, 1073, 39570, 927, 279, 3347, 4376, 34457, 13, 23966, 13, 220, 16, 25, 13756, 315, 92516, 389, 279, 31815, 315, 4892, 23179, 4363, 13772, 287, 90127, 13, 1226, 49586, 220, 6028, 4363, 13772, 4455, 927, 220, 5162, 22, 4235, 679, 23, 320, 4151, 19331, 7609, 264, 1174, 38201, 14242, 927, 220, 5162, 22, 4235, 2550, 17, 320, 258, 6437, 8, 323, 220, 2550, 18, 12, 679, 23, 320, 258, 2579, 1237, 1518, 7090, 293, 369, 279, 12435, 8141, 315, 39570, 662, 578, 59201, 3830, 11, 62215, 555, 220, 605, 11877, 452, 11, 220, 1758, 11877, 452, 11, 220, 2075, 11877, 468, 323, 220, 1041, 11877, 468, 11, 5039, 279, 864, 12, 1974, 13772, 5654, 304, 902, 584, 12849, 279, 92516, 26, 1101, 1518, 41665, 2956, 435, 14801, 220, 16, 272, 11, 294, 323, 220, 17, 68, 662, 578, 2472, 374, 505, 279, 50447, 734, 1917, 2235, 662, 293, 1174, 83238, 323, 19463, 17915, 315, 39570, 662, 578, 5578, 39570, 12992, 505, 220, 1691, 13, 16, 20903, 220, 16, 13, 18, 305, 320, 5162, 22, 4235, 2550, 17, 11, 220, 1627, 4455, 8, 311, 220, 1544, 13, 21, 20903, 220, 17, 13, 18, 305, 320, 2550, 18, 4235, 679, 23, 11, 220, 1774, 4455, 705, 369, 902, 584, 1101, 5296, 20903, 16, 5410, 1493, 315, 279, 3152, 320, 82, 1770, 749, 36434, 578, 1493, 16283, 304, 279, 31381, 527, 25157, 1701, 279, 28023, 25936, 1749, 323, 8024, 311, 20903, 16, 5410, 38664, 320, 82, 962, 6266, 304, 1855, 9736, 320, 4151, 19331, 7609, 272, 1389, 282, 1174, 4212, 4101, 315, 39570, 323, 92516, 13, 272, 1174, 39570, 19579, 1060, 320, 35671, 1584, 1237, 294, 1174, 92516, 19579, 1060, 320, 12481, 1584, 1237, 384, 1174, 2307, 3950, 39570, 19579, 1060, 320, 35671, 1584, 8, 323, 92516, 19579, 1060, 320, 12481, 1584, 1237, 282, 1174, 39570, 19579, 92516, 13, 1226, 5296, 430, 279, 39570, 892, 4101, 71057, 279, 92516, 892, 4101, 449, 59642, 26670, 436, 284, 220, 15, 13, 5332, 13, 763, 21988, 272, 1174, 294, 323, 282, 1174, 584, 1101, 1501, 279, 1493, 16283, 320, 8370, 8024, 311, 20903, 16, 274, 1770, 749, 16016, 1518, 19331, 7026, 279, 13790, 31649, 1584, 320, 32127, 3776, 1584, 705, 323, 279, 220, 2721, 4, 12410, 7200, 922, 279, 31649, 1584, 320, 67, 15889, 3776, 5238, 570, 578, 5376, 304, 39570, 323, 92516, 927, 892, 323, 279, 5133, 1990, 39570, 323, 92516, 527, 47952, 5199, 320, 266, 220, 2721, 4, 21351, 8, 323, 22514, 311, 279, 49449, 315, 63061, 320, 18337, 26, 41665, 2956, 43252, 220, 17, 323, 220, 18, 7609, 8922, 828, 8797, 1404, 2217, 1789, 1855, 4363, 13772, 1567, 11, 584, 12849, 39570, 1701, 650, 320, 259, 7048, 1518, 19331, 662, 5659, 832, 1567, 311, 2500, 11, 279, 907, 315, 39570, 35327, 33452, 13, 1115, 907, 369, 904, 4040, 1567, 374, 28160, 555, 1690, 9547, 11, 2737, 2536, 31717, 318, 780, 6305, 11, 1778, 439, 279, 25911, 30456, 279, 49784, 220, 19, 1174, 220, 20, 1174, 220, 1313, 1174, 220, 1419, 662, 2057, 42645, 904, 4754, 2515, 315, 279, 10182, 389, 39570, 1174, 584, 1176, 49586, 279, 8141, 315, 39570, 389, 264, 7447, 6953, 35555, 278, 3115, 2296, 13, 763, 23966, 13, 220, 16, 65, 128257, 198, 128256, 78191, 198, 83146, 2349, 374, 14718, 90127, 430, 1304, 4363, 13772, 311, 1935, 810, 892, 311, 33556, 11, 6821, 264, 4007, 4756, 220, 806, 339, 6841, 220, 2366, 15, 304, 279, 8486, 22037, 13, 578, 12074, 8710, 430, 90127, 430, 2274, 927, 46039, 54280, 6920, 810, 32257, 323, 9093, 4822, 16643, 369, 5129, 1306, 20129, 4363, 13, 1115, 3445, 430, 304, 279, 3938, 11, 439, 279, 1917, 9731, 311, 8369, 11, 90127, 527, 810, 4461, 311, 5662, 10977, 43726, 77289, 323, 387, 810, 40652, 13, 330, 791, 25127, 527, 1633, 3062, 11, 5423, 994, 13126, 10396, 430, 527, 2231, 304, 2035, 311, 37586, 449, 3728, 24808, 1359, 1071, 17054, 17929, 14966, 921, 587, 81, 47799, 88, 11, 10195, 3229, 315, 279, 4007, 323, 2010, 315, 279, 60696, 77923, 8113, 520, 279, 7777, 258, 14406, 10181, 315, 10170, 323, 12053, 44825, 3907, 320, 46, 3931, 570, 330, 1687, 1440, 430, 35335, 5789, 1205, 311, 5644, 5694, 369, 810, 19428, 90127, 11, 719, 77289, 10977, 11, 889, 1253, 539, 617, 279, 1440, 58523, 477, 14054, 311, 37586, 449, 1778, 19428, 29592, 477, 8987, 53958, 11, 1101, 1205, 311, 387, 10235, 1210, 9176, 7978, 617, 6982, 430, 10182, 2349, 649, 25228, 1463, 90127, 2345, 5391, 439, 32343, 3233, 477, 13892, 764, 29639, 304, 1023, 13918, 315, 279, 1917, 2345, 2017, 279, 1825, 18435, 13, 2030, 420, 374, 279, 1176, 4007, 311, 5813, 264, 2867, 2723, 1990, 264, 24808, 10182, 323, 279, 9333, 27084, 315, 90127, 430, 617, 1903, 4363, 13772, 13, 578, 14248, 30239, 4892, 23179, 90127, 430, 1903, 4363, 13772, 927, 279, 3347, 4376, 264, 9478, 13, 2435, 1766, 430, 2391, 279, 3388, 315, 279, 1176, 1938, 1306, 4363, 13772, 11, 90127, 58764, 4661, 11157, 439, 14297, 1457, 1109, 814, 1550, 220, 1135, 1667, 4227, 13, 330, 4599, 584, 68683, 279, 828, 11, 584, 1436, 9539, 1518, 430, 279, 3392, 315, 892, 433, 3952, 369, 264, 49784, 311, 33556, 574, 7859, 449, 279, 1667, 13, 2030, 433, 5828, 956, 264, 7833, 1584, 44603, 574, 2073, 15853, 17223, 584, 1766, 430, 1521, 33834, 323, 40291, 18545, 279, 1890, 33834, 323, 40291, 3970, 304, 9581, 7479, 9499, 1359, 1071, 8732, 14851, 11, 1176, 3229, 323, 2405, 920, 13, 5575, 304, 279, 507, 3931, 60696, 77923, 8113, 13, 578, 14248, 12793, 279, 2723, 1990, 46039, 9581, 7479, 9499, 323, 29493, 83526, 3347, 4363, 13772, 555, 6968, 6500, 47590, 315, 3116, 2204, 90127, 323, 6376, 2204, 20472, 369, 279, 7479, 315, 279, 9581, 13, 9843, 1855, 4200, 49784, 8813, 5699, 220, 19, 8333, 11, 279, 14248, 46836, 4363, 13772, 555, 14713, 1022, 279, 8312, 315, 32257, 505, 24923, 13, 14851, 11497, 25, 330, 98428, 56295, 527, 8798, 21787, 11, 1120, 1093, 21787, 304, 9515, 13, 763, 1841, 21787, 11, 10633, 374, 3698, 28244, 11, 323, 430, 8798, 4907, 374, 16489, 1139, 22936, 990, 13, 1789, 90127, 11, 279, 32257, 4529, 709, 505, 279, 7479, 315, 279, 18435, 374, 279, 364, 64475, 6, 430, 25228, 9803, 323, 10446, 1771, 264, 49784, 596, 40652, 2410, 11, 449, 8798, 4907, 505, 279, 32257, 16489, 1139, 8147, 29592, 13, 25274, 4363, 13772, 374, 13890, 311, 23351, 279, 10633, 8312, 311, 279, 4817, 315, 264, 1841, 13, 17586, 10633, 11, 279, 1841, 690, 1654, 8023, 349, 11, 323, 2085, 1202, 32257, 2592, 11, 279, 49784, 690, 31815, 1210, 578, 12074, 1766, 430, 1524, 3582, 1855, 46836, 49784, 1903, 4363, 13772, 520, 279, 1890, 21261, 11, 279, 6305, 430, 8040, 927, 46039, 21160, 3952, 810, 892, 311, 33556, 13, 578, 14248, 1766, 264, 3831, 26670, 1990, 279, 892, 433, 3952, 369, 264, 49784, 311, 33556, 1306, 4363, 13772, 323, 9581, 7479, 9499, 11, 994, 2225, 1051, 68683, 555, 1060, 16666, 25, 507, 3931, 330, 9673, 47590, 19168, 1148, 1057, 6492, 315, 3347, 90127, 1047, 12090, 25, 46039, 54280, 12207, 5536, 279, 4478, 430, 90127, 31815, 11, 1524, 994, 872, 3717, 449, 279, 18435, 596, 7479, 374, 84450, 13, 578, 3488, 374, 3249, 1359, 1071, 8626, 13, 921, 587, 81, 47799, 88, 13, 12362, 5217, 47590, 11, 279, 14248, 1766, 430, 330, 72349, 32257, 1, 574, 279, 7554, 2723, 13, 578, 12074, 11497, 430, 994, 90127, 1304, 4363, 13772, 11, 1524, 3582, 814, 649, 912, 5129, 2680, 279, 18435, 596, 8312, 315, 32257, 11, 814, 2103, 6920, 264, 5708, 315, 32257, 430, 14297, 409, 698, 2392, 13, 3277, 279, 14248, 3549, 4200, 90127, 430, 49101, 420, 9967, 32257, 1306, 20129, 4363, 11, 814, 1766, 430, 279, 9581, 7479, 9499, 912, 5129, 1047, 904, 5536, 389, 279, 4478, 315, 31815, 13, 330, 2028, 5039, 430, 9967, 32257, 374, 279, 1401, 8331, 430, 6835, 1855, 49784, 304, 279, 19576, 1202, 1866, 5016, 9764, 1359, 1071, 14851, 13, 330, 98428, 56295, 430, 2274, 927, 46039, 54280, 649, 1935, 709, 323, 3637, 810, 32257, 11, 902, 10446, 1771, 1124, 369, 5129, 323, 29034, 1124, 505, 83526, 439, 6288, 1210, 578, 7319, 2237, 315, 9967, 32257, 1101, 3727, 90127, 330, 86, 22120, 66101, 276, 15632, 2736, 1694, 6612, 439, 3293, 90127, 617, 69364, 33318, 398, 1579, 27378, 315, 53958, 389, 35335, 323, 77289, 10977, 13, 1115, 3495, 22020, 279, 12939, 369, 10182, 4211, 311, 15884, 2759, 369, 9967, 32257, 994, 52997, 279, 5536, 315, 46039, 54280, 389, 90127, 13, 578, 4007, 1101, 9160, 7862, 4819, 449, 279, 4382, 32887, 4211, 13882, 1511, 311, 3619, 1268, 90127, 31815, 13, 330, 5520, 4211, 315, 49784, 31815, 1541, 956, 2980, 32257, 71201, 1120, 1684, 90127, 430, 617, 1903, 4363, 13772, 439, 264, 9235, 87627, 430, 10485, 82, 2403, 279, 4363, 323, 374, 48946, 1523, 555, 39676, 13, 5751, 990, 5039, 1521, 4211, 527, 33243, 11, 902, 374, 3249, 420, 2867, 12223, 315, 10182, 2349, 5828, 956, 8767, 17439, 1359, 1071, 14851, 13, 578, 12074, 1457, 3197, 311, 4007, 49784, 828, 505, 1023, 13918, 315, 279, 1917, 311, 8417, 3508, 279, 5536, 315, 264, 24808, 10182, 389, 49784, 31815, 374, 31965, 2212, 279, 24867, 13, 8626, 13, 921, 587, 81, 47799, 88, 20536, 25, 330, 28589, 11, 279, 25127, 315, 420, 990, 527, 38246, 13, 1442, 584, 1541, 956, 44962, 3728, 24808, 11, 4363, 13772, 287, 90127, 690, 3136, 311, 33556, 810, 14297, 13, 11205, 19814, 690, 912, 5129, 387, 45408, 311, 35335, 5789, 11, 14718, 5190, 5990, 315, 7100, 5674, 323, 54824, 810, 6439, 1210, 220, 128257, 198 ]

2,379

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Loss of seed-coat impermeability was essential in the domestication of many leguminous crops to promote the production of their highly nutritious seeds. Here we show that seed-coat impermeability in wild soybean is controlled by a single gene, GmHs1-1 , which encodes a calcineurin-like metallophosphoesterase transmembrane protein. GmHs1-1 is primarily expressed in the Malpighian layer of the seed coat and is associated with calcium content. The transition from impermeability to permeability in domesticated soybean was caused by artificial selection of a point mutation in GmHs1-1 . Interestingly, a number of soybean landraces evaded selection for permeability because of an alternative selection for seed-coat cracking that also enables seed imbibition. Despite the single origin of the mutant allele Gmhs1-1 , the distribution pattern of allelic variants in the context of soybean population structure and the detected signature of genomic introgression between wild and cultivated soybeans suggest that Gmhs1-1 may have experienced reselection for seed-coat permeability. Main Many wild leguminous species produce seeds with variable seed-coat impermeability or hard-seededness as a mechanism for maintaining seed dormancy and viability for long periods 1 , 2 , and hard-seededness is considered essential for the long-term survival of wild species 3 , 4 . However, hard-seededness impedes seed production in agriculture. Therefore, seed-coat permeability, which allows for rapid and uniform seed germination, was one of the key traits targeted in the domestication of many leguminous crops 5 , 6 , 7 , 8 , 9 , 10 . One of these was soybean, which is now the most economically important crop in the world. It is believed that soybean was domesticated from its wild relative Glycine soja in China ∼ 5,000 years ago, resulting in a diversity of landraces with permeable seed coats 11 , 12 , 13 . Today, hard-seededness continues to impede the utilization of wild germplasm for cultivar enhancement. However, a moderate level of hard-seededness is important for the quality of stored soybeans and for their viability in the southern United States and the tropics, where seeds lose viability within a short period of time after being harvested 11 , 14 . In addition, hard-seededness is associated with calcium content in the seed coat 15 , 16 , 17 and thus can potentially enhance the nutritional value of soy-based foods. Previous studies mapped a common quantitative trait locus (QTL) underlying hard-seededness to an overlapping region on soybean chromosome 2 (refs. 8 , 11 , 17 , 18 ), but the genes responsible for hard-seededness have not been identified in any species. To understand the molecular basis of hard-seededness, we crossed the permeable soybean cultivar Williams 82 with each of two hard-seeded G. soja accessions, PI 468916 and PI 479752, and obtained two F 2 populations. The F 1:2 seeds, whose coats developed from the maternal tissues of the F 1 plants, were hard-seeded ( Fig. 1a,b ). Phenotyping of F 2:3 seeds from individual F 2 plants from the two populations revealed 3:1 ratios of hard-seededness to permeability ( Fig. 1c,d and Supplementary Table 1 ), suggesting that the former is dominant over the latter, and showed that the trait was controlled mainly by a single locus, designated GmHs1-1 . Figure 1: Hard-seededness and seed-coat permeability of parental soybean lines and their progeny. ( a ) Photographic illustration of hard-seededness of PI 468916 ( G. soja ), seed-coat permeability of Williams 82 ( G. max ) and hard-seededness of F 1:2 seeds from a (Williams 82 × PI 468916) F 1 plant at 0, 2 and 4 h. ( b ) Proportions of seeds from Williams 82 plants (purple diamonds), PI 468916 plants (blue circles) and their F 1:2 progeny (pink triangles) that imbibed water at multiple time points over the course of 12 d. ( c , d ) Phenotypic segregation of hard-seededness and seed-coat permeability in two subsets of the mapping population used in initial mapping of the GmHs1-1 locus. Full size image An initial scan revealed a linkage between GmHs1-1 and the markers defining the common QTL region on chromosome 2 (refs. 8 , 11 , 17 , 18 ) ( Supplementary Table 2 ), suggesting that the hard-seededness investigated in this and previous studies is likely to be controlled by the same locus. Additional markers were used to identify recombinants between markers and the GmHs1-1 locus in the two populations ( Fig. 2a ), and finally to fine map GmHs1-1 to a 22-kb region harboring two genes, Glyma02g43700.1 and Glyma02g43710.1 ( Fig. 2a ), according to the Williams 82 reference genome 19 . Figure 2: Map-based cloning of the GmHs1-1 locus and candidate gene–association analysis. ( a ) Physical locations of markers defining the GmHs1-1 region that harbors two genes according to the soybean reference genome, numbers of recombinants carrying crossovers as determined by molecular markers and phenotypes of individual recombinants, and seven sites in the coding region of the GmHs1-1 candidate locus showing nucleotide differences between Williams 82 and the two G. soja parental lines that resulted in amino acid changes. Pink and black boxes indicate exons, gray boxes indicate 3′ untranslated regions (UTRs) and the gray boxes ending in arrowheads indicate 3′ UTRs and the transcriptional orientations of the two genes. ( b ) Sequence comparison of the candidate GmHs1-1 locus between Williams 82 and ten G. soja accessions. Sequence variations in exons and introns, sequence variations in flanking regions 2.5 kb upstream and 1.5 kb downstream and the frequencies of these variations in the ten G. soja accessions are indicated by purple, blue and gray bars, respectively. The seven sites shown in a are marked here in the same order by asterisks. ( c ) Expression levels of Glyma02g43700.1 relative to those of an actin-expressing gene in the two parental lines at five seed developmental time points as detected by quantitative real-time PCR. Expression levels shown are the mean ± s.e.m. of three biological replicates. WPA, weeks post-anthesis. ( d ) Predicted conserved metallophosphatase-phosphodiesterase/alkaline phosphatase D (MPP_PhoD) domain in the Glyma02g43700.1 protein. The asterisk indicates", "role": "user" }, { "content": "Purdue University researchers have pinpointed the gene that controls whether soybean seed coats are hard or permeable, a finding that could be used to develop better varieties for southern and tropical regions, enrich the crop's genetic diversity and boost the nutritional value of soybeans. Jianxin Ma (Jen-SHIN' Ma), associate professor of agronomy, and fellow researchers found that a mutation in the gene GmHs1-1 causes the tough seed coats of wild soybeans to become permeable. Farmers selected that trait about 5,000 years ago in a key step to domesticating soybeans from their hard-seeded relative Glycine soja. The gene could be modified to produce improved varieties for growing regions in which seed permeability can be a handicap, Ma said. GmHs1-1 is also associated with the calcium content of soybeans, offering a genetic target for enhancing the nutrition of soy food products. Understanding the mechanism that determines seed permeability could also give researchers better access to the largely untapped genetic diversity of wild soybeans to enrich cultivated varieties, whose lack of genetic richness has curbed improvements in yields. \"This is the first gene associated with hard seededness to be identified in any plant species,\" Ma said. \"This discovery could help us quickly pinpoint genes that control this trait in many other plants. We're also excited about the potential applications for modifying the calcium concentration in seed coats. This could be transformative as we identify similar genes that control calcium levels in other legumes.\" Hard seededness enables the long-term survival of many wild plant species by protecting seeds in severe conditions and inhospitable environments, allowing them to remain dormant until conditions are right for germination. Encased in a water- and airtight coat, seeds can remain viable for extended periods of time, in some cases, more than 100 years. But the hard skin that lends wild seeds their resilience is a problem in agricultural production. It prevents seeds from germinating quickly and in a uniform, predictable pattern. Wild soybean seeds take from several weeks to months to germinate whereas cultivated soybean seeds can begin absorbing water in 15 minutes. Millennia ago, farmers in Asia recognized the value of seed permeability and artificially selected the trait to produce the predecessors of modern cultivated soybean varieties, Ma said. But the genetic factors underpinning seed coat permeability remained a mystery until Ma and his team used a map-based cloning approach to hone in on GmHs1-1 as the gene responsible for hard seededness. The team found that a mutation in a single pair of nucleotides in the gene causes seed coat permeability - that is, a change in one pair out of the approximately 1 billion base pairs that make up the soybean genome. \"We finally understand the genetic change that allowed the domestication of soybeans,\" he said. \"When we make this kind of discovery, we're always very excited.\" Ma said modifying the gene could produce hardier seeds for the southern U.S. and the tropics, regions in which the soft coats of cultivated soybeans reduce their viability shortly after harvest. The discovery could also help researchers improve the cooking quality of soybeans and other legumes, such as the common bean, whose varying levels of hard seededness make consistent quality difficult to achieve. The team's next goal is to identify genes that interact with GmHs1-1 and understand how they work together to control calcium and possibly other mineral content. The paper was published in Nature Genetics on Monday (June 22) and is available at dx.doi.org/10.1038/ng.3339 ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Loss of seed-coat impermeability was essential in the domestication of many leguminous crops to promote the production of their highly nutritious seeds. Here we show that seed-coat impermeability in wild soybean is controlled by a single gene, GmHs1-1 , which encodes a calcineurin-like metallophosphoesterase transmembrane protein. GmHs1-1 is primarily expressed in the Malpighian layer of the seed coat and is associated with calcium content. The transition from impermeability to permeability in domesticated soybean was caused by artificial selection of a point mutation in GmHs1-1 . Interestingly, a number of soybean landraces evaded selection for permeability because of an alternative selection for seed-coat cracking that also enables seed imbibition. Despite the single origin of the mutant allele Gmhs1-1 , the distribution pattern of allelic variants in the context of soybean population structure and the detected signature of genomic introgression between wild and cultivated soybeans suggest that Gmhs1-1 may have experienced reselection for seed-coat permeability. Main Many wild leguminous species produce seeds with variable seed-coat impermeability or hard-seededness as a mechanism for maintaining seed dormancy and viability for long periods 1 , 2 , and hard-seededness is considered essential for the long-term survival of wild species 3 , 4 . However, hard-seededness impedes seed production in agriculture. Therefore, seed-coat permeability, which allows for rapid and uniform seed germination, was one of the key traits targeted in the domestication of many leguminous crops 5 , 6 , 7 , 8 , 9 , 10 . One of these was soybean, which is now the most economically important crop in the world. It is believed that soybean was domesticated from its wild relative Glycine soja in China ∼ 5,000 years ago, resulting in a diversity of landraces with permeable seed coats 11 , 12 , 13 . Today, hard-seededness continues to impede the utilization of wild germplasm for cultivar enhancement. However, a moderate level of hard-seededness is important for the quality of stored soybeans and for their viability in the southern United States and the tropics, where seeds lose viability within a short period of time after being harvested 11 , 14 . In addition, hard-seededness is associated with calcium content in the seed coat 15 , 16 , 17 and thus can potentially enhance the nutritional value of soy-based foods. Previous studies mapped a common quantitative trait locus (QTL) underlying hard-seededness to an overlapping region on soybean chromosome 2 (refs. 8 , 11 , 17 , 18 ), but the genes responsible for hard-seededness have not been identified in any species. To understand the molecular basis of hard-seededness, we crossed the permeable soybean cultivar Williams 82 with each of two hard-seeded G. soja accessions, PI 468916 and PI 479752, and obtained two F 2 populations. The F 1:2 seeds, whose coats developed from the maternal tissues of the F 1 plants, were hard-seeded ( Fig. 1a,b ). Phenotyping of F 2:3 seeds from individual F 2 plants from the two populations revealed 3:1 ratios of hard-seededness to permeability ( Fig. 1c,d and Supplementary Table 1 ), suggesting that the former is dominant over the latter, and showed that the trait was controlled mainly by a single locus, designated GmHs1-1 . Figure 1: Hard-seededness and seed-coat permeability of parental soybean lines and their progeny. ( a ) Photographic illustration of hard-seededness of PI 468916 ( G. soja ), seed-coat permeability of Williams 82 ( G. max ) and hard-seededness of F 1:2 seeds from a (Williams 82 × PI 468916) F 1 plant at 0, 2 and 4 h. ( b ) Proportions of seeds from Williams 82 plants (purple diamonds), PI 468916 plants (blue circles) and their F 1:2 progeny (pink triangles) that imbibed water at multiple time points over the course of 12 d. ( c , d ) Phenotypic segregation of hard-seededness and seed-coat permeability in two subsets of the mapping population used in initial mapping of the GmHs1-1 locus. Full size image An initial scan revealed a linkage between GmHs1-1 and the markers defining the common QTL region on chromosome 2 (refs. 8 , 11 , 17 , 18 ) ( Supplementary Table 2 ), suggesting that the hard-seededness investigated in this and previous studies is likely to be controlled by the same locus. Additional markers were used to identify recombinants between markers and the GmHs1-1 locus in the two populations ( Fig. 2a ), and finally to fine map GmHs1-1 to a 22-kb region harboring two genes, Glyma02g43700.1 and Glyma02g43710.1 ( Fig. 2a ), according to the Williams 82 reference genome 19 . Figure 2: Map-based cloning of the GmHs1-1 locus and candidate gene–association analysis. ( a ) Physical locations of markers defining the GmHs1-1 region that harbors two genes according to the soybean reference genome, numbers of recombinants carrying crossovers as determined by molecular markers and phenotypes of individual recombinants, and seven sites in the coding region of the GmHs1-1 candidate locus showing nucleotide differences between Williams 82 and the two G. soja parental lines that resulted in amino acid changes. Pink and black boxes indicate exons, gray boxes indicate 3′ untranslated regions (UTRs) and the gray boxes ending in arrowheads indicate 3′ UTRs and the transcriptional orientations of the two genes. ( b ) Sequence comparison of the candidate GmHs1-1 locus between Williams 82 and ten G. soja accessions. Sequence variations in exons and introns, sequence variations in flanking regions 2.5 kb upstream and 1.5 kb downstream and the frequencies of these variations in the ten G. soja accessions are indicated by purple, blue and gray bars, respectively. The seven sites shown in a are marked here in the same order by asterisks. ( c ) Expression levels of Glyma02g43700.1 relative to those of an actin-expressing gene in the two parental lines at five seed developmental time points as detected by quantitative real-time PCR. Expression levels shown are the mean ± s.e.m. of three biological replicates. WPA, weeks post-anthesis. ( d ) Predicted conserved metallophosphatase-phosphodiesterase/alkaline phosphatase D (MPP_PhoD) domain in the Glyma02g43700.1 protein. The asterisk indicates<|im_end|> <|im_start|>assistant Purdue University researchers have pinpointed the gene that controls whether soybean seed coats are hard or permeable, a finding that could be used to develop better varieties for southern and tropical regions, enrich the crop's genetic diversity and boost the nutritional value of soybeans. Jianxin Ma (Jen-SHIN' Ma), associate professor of agronomy, and fellow researchers found that a mutation in the gene GmHs1-1 causes the tough seed coats of wild soybeans to become permeable. Farmers selected that trait about 5,000 years ago in a key step to domesticating soybeans from their hard-seeded relative Glycine soja. The gene could be modified to produce improved varieties for growing regions in which seed permeability can be a handicap, Ma said. GmHs1-1 is also associated with the calcium content of soybeans, offering a genetic target for enhancing the nutrition of soy food products. Understanding the mechanism that determines seed permeability could also give researchers better access to the largely untapped genetic diversity of wild soybeans to enrich cultivated varieties, whose lack of genetic richness has curbed improvements in yields. "This is the first gene associated with hard seededness to be identified in any plant species," Ma said. "This discovery could help us quickly pinpoint genes that control this trait in many other plants. We're also excited about the potential applications for modifying the calcium concentration in seed coats. This could be transformative as we identify similar genes that control calcium levels in other legumes." Hard seededness enables the long-term survival of many wild plant species by protecting seeds in severe conditions and inhospitable environments, allowing them to remain dormant until conditions are right for germination. Encased in a water- and airtight coat, seeds can remain viable for extended periods of time, in some cases, more than 100 years. But the hard skin that lends wild seeds their resilience is a problem in agricultural production. It prevents seeds from germinating quickly and in a uniform, predictable pattern. Wild soybean seeds take from several weeks to months to germinate whereas cultivated soybean seeds can begin absorbing water in 15 minutes. Millennia ago, farmers in Asia recognized the value of seed permeability and artificially selected the trait to produce the predecessors of modern cultivated soybean varieties, Ma said. But the genetic factors underpinning seed coat permeability remained a mystery until Ma and his team used a map-based cloning approach to hone in on GmHs1-1 as the gene responsible for hard seededness. The team found that a mutation in a single pair of nucleotides in the gene causes seed coat permeability - that is, a change in one pair out of the approximately 1 billion base pairs that make up the soybean genome. "We finally understand the genetic change that allowed the domestication of soybeans," he said. "When we make this kind of discovery, we're always very excited." Ma said modifying the gene could produce hardier seeds for the southern U.S. and the tropics, regions in which the soft coats of cultivated soybeans reduce their viability shortly after harvest. The discovery could also help researchers improve the cooking quality of soybeans and other legumes, such as the common bean, whose varying levels of hard seededness make consistent quality difficult to achieve. The team's next goal is to identify genes that interact with GmHs1-1 and understand how they work together to control calcium and possibly other mineral content. The paper was published in Nature Genetics on Monday (June 22) and is available at dx.doi.org/10.1038/ng.3339 <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 25733, 315, 10533, 23283, 266, 17190, 2727, 2968, 574, 7718, 304, 279, 13018, 367, 315, 1690, 2531, 10318, 788, 31665, 311, 12192, 279, 5788, 315, 872, 7701, 78216, 19595, 13, 5810, 584, 1501, 430, 10533, 23283, 266, 17190, 2727, 2968, 304, 8545, 29839, 17937, 374, 14400, 555, 264, 3254, 15207, 11, 480, 76, 39, 82, 16, 12, 16, 1174, 902, 3289, 2601, 264, 10241, 483, 324, 258, 12970, 9501, 385, 764, 24527, 78, 5302, 521, 1380, 10759, 88554, 13128, 13, 480, 76, 39, 82, 16, 12, 16, 374, 15871, 13605, 304, 279, 8560, 79, 1108, 1122, 6324, 315, 279, 10533, 23724, 323, 374, 5938, 449, 35719, 2262, 13, 578, 9320, 505, 17190, 2727, 2968, 311, 55424, 2968, 304, 13018, 660, 29839, 17937, 574, 9057, 555, 21075, 6727, 315, 264, 1486, 27472, 304, 480, 76, 39, 82, 16, 12, 16, 662, 58603, 11, 264, 1396, 315, 29839, 17937, 4363, 81, 2492, 3721, 14589, 6727, 369, 55424, 2968, 1606, 315, 459, 10778, 6727, 369, 10533, 23283, 266, 52829, 430, 1101, 20682, 10533, 737, 58380, 684, 13, 18185, 279, 3254, 6371, 315, 279, 61618, 70510, 480, 76, 5104, 16, 12, 16, 1174, 279, 8141, 5497, 315, 12584, 416, 27103, 304, 279, 2317, 315, 29839, 17937, 7187, 6070, 323, 279, 16914, 12223, 315, 81064, 20285, 30840, 1990, 8545, 323, 67166, 29839, 28440, 4284, 430, 480, 76, 5104, 16, 12, 16, 1253, 617, 10534, 312, 24536, 369, 10533, 23283, 266, 55424, 2968, 13, 4802, 9176, 8545, 2531, 10318, 788, 9606, 8356, 19595, 449, 3977, 10533, 23283, 266, 17190, 2727, 2968, 477, 2653, 7962, 31035, 2136, 439, 264, 17383, 369, 20958, 10533, 30209, 6709, 323, 68507, 369, 1317, 18852, 220, 16, 1174, 220, 17, 1174, 323, 2653, 7962, 31035, 2136, 374, 6646, 7718, 369, 279, 1317, 9860, 20237, 315, 8545, 9606, 220, 18, 1174, 220, 19, 662, 4452, 11, 2653, 7962, 31035, 2136, 50502, 288, 10533, 5788, 304, 30029, 13, 15636, 11, 10533, 23283, 266, 55424, 2968, 11, 902, 6276, 369, 11295, 323, 14113, 10533, 17684, 33196, 11, 574, 832, 315, 279, 1401, 25022, 17550, 304, 279, 13018, 367, 315, 1690, 2531, 10318, 788, 31665, 220, 20, 1174, 220, 21, 1174, 220, 22, 1174, 220, 23, 1174, 220, 24, 1174, 220, 605, 662, 3861, 315, 1521, 574, 29839, 17937, 11, 902, 374, 1457, 279, 1455, 47379, 3062, 19641, 304, 279, 1917, 13, 1102, 374, 11846, 430, 29839, 17937, 574, 13018, 660, 505, 1202, 8545, 8844, 79183, 66, 483, 779, 5697, 304, 5734, 12264, 120, 220, 20, 11, 931, 1667, 4227, 11, 13239, 304, 264, 20057, 315, 4363, 81, 2492, 449, 55424, 481, 10533, 56737, 220, 806, 1174, 220, 717, 1174, 220, 1032, 662, 11450, 11, 2653, 7962, 31035, 2136, 9731, 311, 3242, 15686, 279, 50549, 315, 8545, 82986, 501, 10753, 369, 27981, 277, 27886, 13, 4452, 11, 264, 24070, 2237, 315, 2653, 7962, 31035, 2136, 374, 3062, 369, 279, 4367, 315, 9967, 29839, 28440, 323, 369, 872, 68507, 304, 279, 18561, 3723, 4273, 323, 279, 21965, 1233, 11, 1405, 19595, 9229, 68507, 2949, 264, 2875, 4261, 315, 892, 1306, 1694, 67572, 220, 806, 1174, 220, 975, 662, 763, 5369, 11, 2653, 7962, 31035, 2136, 374, 5938, 449, 35719, 2262, 304, 279, 10533, 23724, 220, 868, 1174, 220, 845, 1174, 220, 1114, 323, 8617, 649, 13893, 18885, 279, 43226, 907, 315, 29839, 6108, 15657, 13, 30013, 7978, 24784, 264, 4279, 47616, 18027, 79257, 320, 48, 13778, 8, 16940, 2653, 7962, 31035, 2136, 311, 459, 50917, 5654, 389, 29839, 17937, 51815, 220, 17, 320, 16541, 13, 220, 23, 1174, 220, 806, 1174, 220, 1114, 1174, 220, 972, 7026, 719, 279, 21389, 8647, 369, 2653, 7962, 31035, 2136, 617, 539, 1027, 11054, 304, 904, 9606, 13, 2057, 3619, 279, 31206, 8197, 315, 2653, 7962, 31035, 2136, 11, 584, 28129, 279, 55424, 481, 29839, 17937, 27981, 277, 13926, 220, 6086, 449, 1855, 315, 1403, 2653, 7962, 31035, 480, 13, 779, 5697, 2680, 919, 11, 23396, 220, 20304, 24487, 323, 23396, 220, 21848, 23644, 11, 323, 12457, 1403, 435, 220, 17, 22673, 13, 578, 435, 220, 16, 25, 17, 19595, 11, 6832, 56737, 8040, 505, 279, 50150, 39881, 315, 279, 435, 220, 16, 11012, 11, 1051, 2653, 7962, 31035, 320, 23966, 13, 220, 16, 64, 8568, 7609, 69883, 67247, 315, 435, 220, 17, 25, 18, 19595, 505, 3927, 435, 220, 17, 11012, 505, 279, 1403, 22673, 10675, 220, 18, 25, 16, 42338, 315, 2653, 7962, 31035, 2136, 311, 55424, 2968, 320, 23966, 13, 220, 16, 66, 12260, 323, 99371, 6771, 220, 16, 7026, 23377, 430, 279, 4846, 374, 25462, 927, 279, 15629, 11, 323, 8710, 430, 279, 18027, 574, 14400, 14918, 555, 264, 3254, 79257, 11, 24073, 480, 76, 39, 82, 16, 12, 16, 662, 19575, 220, 16, 25, 11481, 7962, 31035, 2136, 323, 10533, 23283, 266, 55424, 2968, 315, 46679, 29839, 17937, 5238, 323, 872, 84360, 88, 13, 320, 264, 883, 18235, 12968, 40134, 315, 2653, 7962, 31035, 2136, 315, 23396, 220, 20304, 24487, 320, 480, 13, 779, 5697, 7026, 10533, 23283, 266, 55424, 2968, 315, 13926, 220, 6086, 320, 480, 13, 1973, 883, 323, 2653, 7962, 31035, 2136, 315, 435, 220, 16, 25, 17, 19595, 505, 264, 320, 62939, 220, 6086, 25800, 23396, 220, 20304, 24487, 8, 435, 220, 16, 6136, 520, 220, 15, 11, 220, 17, 323, 220, 19, 305, 13, 320, 293, 883, 1322, 403, 919, 315, 19595, 505, 13926, 220, 6086, 11012, 320, 57607, 49151, 705, 23396, 220, 20304, 24487, 11012, 320, 12481, 26432, 8, 323, 872, 435, 220, 16, 25, 17, 84360, 88, 320, 64349, 43546, 8, 430, 737, 58380, 291, 3090, 520, 5361, 892, 3585, 927, 279, 3388, 315, 220, 717, 294, 13, 320, 272, 1174, 294, 883, 69883, 37941, 292, 64244, 315, 2653, 7962, 31035, 2136, 323, 10533, 23283, 266, 55424, 2968, 304, 1403, 75605, 315, 279, 13021, 7187, 1511, 304, 2926, 13021, 315, 279, 480, 76, 39, 82, 16, 12, 16, 79257, 13, 8797, 1404, 2217, 1556, 2926, 8737, 10675, 264, 72541, 1990, 480, 76, 39, 82, 16, 12, 16, 323, 279, 24915, 27409, 279, 4279, 1229, 13778, 5654, 389, 51815, 220, 17, 320, 16541, 13, 220, 23, 1174, 220, 806, 1174, 220, 1114, 1174, 220, 972, 883, 320, 99371, 6771, 220, 17, 7026, 23377, 430, 279, 2653, 7962, 31035, 2136, 27313, 304, 420, 323, 3766, 7978, 374, 4461, 311, 387, 14400, 555, 279, 1890, 79257, 13, 24086, 24915, 1051, 1511, 311, 10765, 38301, 7006, 1821, 1990, 24915, 323, 279, 480, 76, 39, 82, 16, 12, 16, 79257, 304, 279, 1403, 22673, 320, 23966, 13, 220, 17, 64, 7026, 323, 5616, 311, 7060, 2472, 480, 76, 39, 82, 16, 12, 16, 311, 264, 220, 1313, 12934, 65, 5654, 69566, 5620, 1403, 21389, 11, 79183, 1764, 2437, 70, 18318, 410, 13, 16, 323, 79183, 1764, 2437, 70, 18318, 605, 13, 16, 320, 23966, 13, 220, 17, 64, 7026, 4184, 311, 279, 13926, 220, 6086, 5905, 33869, 220, 777, 662, 19575, 220, 17, 25, 5135, 6108, 78966, 315, 279, 480, 76, 39, 82, 16, 12, 16, 79257, 323, 9322, 15207, 4235, 55565, 6492, 13, 320, 264, 883, 28479, 10687, 315, 24915, 27409, 279, 480, 76, 39, 82, 16, 12, 16, 5654, 430, 69566, 1105, 1403, 21389, 4184, 311, 279, 29839, 17937, 5905, 33869, 11, 5219, 315, 38301, 7006, 1821, 15691, 272, 33312, 3078, 439, 11075, 555, 31206, 24915, 323, 14345, 22583, 315, 3927, 38301, 7006, 1821, 11, 323, 8254, 6732, 304, 279, 11058, 5654, 315, 279, 480, 76, 39, 82, 16, 12, 16, 9322, 79257, 9204, 31484, 69044, 12062, 1990, 13926, 220, 6086, 323, 279, 1403, 480, 13, 779, 5697, 46679, 5238, 430, 19543, 304, 42500, 13935, 4442, 13, 27211, 323, 3776, 15039, 13519, 506, 2439, 11, 18004, 15039, 13519, 220, 18, 39615, 91448, 13918, 320, 1406, 43427, 8, 323, 279, 18004, 15039, 13696, 304, 18404, 36910, 13519, 220, 18, 39615, 549, 2434, 82, 323, 279, 46940, 278, 89935, 315, 279, 1403, 21389, 13, 320, 293, 883, 29971, 12593, 315, 279, 9322, 480, 76, 39, 82, 16, 12, 16, 79257, 1990, 13926, 220, 6086, 323, 5899, 480, 13, 779, 5697, 2680, 919, 13, 29971, 27339, 304, 506, 2439, 323, 10805, 2439, 11, 8668, 27339, 304, 1344, 33434, 13918, 220, 17, 13, 20, 39753, 42830, 323, 220, 16, 13, 20, 39753, 52452, 323, 279, 34873, 315, 1521, 27339, 304, 279, 5899, 480, 13, 779, 5697, 2680, 919, 527, 16717, 555, 25977, 11, 6437, 323, 18004, 16283, 11, 15947, 13, 578, 8254, 6732, 6982, 304, 264, 527, 13160, 1618, 304, 279, 1890, 2015, 555, 35037, 93934, 13, 320, 272, 883, 16783, 5990, 315, 79183, 1764, 2437, 70, 18318, 410, 13, 16, 8844, 311, 1884, 315, 459, 1180, 258, 10397, 1911, 287, 15207, 304, 279, 1403, 46679, 5238, 520, 4330, 10533, 48006, 892, 3585, 439, 16914, 555, 47616, 1972, 7394, 67791, 13, 16783, 5990, 6982, 527, 279, 3152, 20903, 274, 1770, 749, 13, 315, 2380, 24156, 29641, 988, 13, 468, 8201, 11, 5672, 1772, 19415, 13491, 13, 320, 294, 883, 33810, 291, 1615, 2841, 9501, 385, 764, 24527, 266, 521, 63837, 24527, 31559, 5302, 521, 14, 1727, 278, 483, 33088, 266, 521, 423, 320, 44, 4505, 1106, 6292, 35, 8, 8106, 304, 279, 79183, 1764, 2437, 70, 18318, 410, 13, 16, 13128, 13, 578, 35037, 3267, 15151, 128257, 198, 128256, 78191, 198, 47, 16468, 361, 3907, 12074, 617, 67638, 291, 279, 15207, 430, 11835, 3508, 29839, 17937, 10533, 56737, 527, 2653, 477, 55424, 481, 11, 264, 9455, 430, 1436, 387, 1511, 311, 2274, 2731, 36680, 369, 18561, 323, 35148, 13918, 11, 31518, 279, 19641, 596, 19465, 20057, 323, 7916, 279, 43226, 907, 315, 29839, 28440, 13, 88404, 59866, 11583, 320, 41, 268, 6354, 39, 691, 6, 11583, 705, 22712, 14561, 315, 40574, 17404, 11, 323, 12637, 12074, 1766, 430, 264, 27472, 304, 279, 15207, 480, 76, 39, 82, 16, 12, 16, 11384, 279, 11292, 10533, 56737, 315, 8545, 29839, 28440, 311, 3719, 55424, 481, 13, 63422, 4183, 430, 18027, 922, 220, 20, 11, 931, 1667, 4227, 304, 264, 1401, 3094, 311, 13018, 1113, 29839, 28440, 505, 872, 2653, 7962, 31035, 8844, 79183, 66, 483, 779, 5697, 13, 578, 15207, 1436, 387, 11041, 311, 8356, 13241, 36680, 369, 7982, 13918, 304, 902, 10533, 55424, 2968, 649, 387, 264, 75379, 11, 11583, 1071, 13, 480, 76, 39, 82, 16, 12, 16, 374, 1101, 5938, 449, 279, 35719, 2262, 315, 29839, 28440, 11, 10209, 264, 19465, 2218, 369, 47594, 279, 26677, 315, 29839, 3691, 3956, 13, 46551, 279, 17383, 430, 27667, 10533, 55424, 2968, 1436, 1101, 3041, 12074, 2731, 2680, 311, 279, 14090, 13365, 5795, 19465, 20057, 315, 8545, 29839, 28440, 311, 31518, 67166, 36680, 11, 6832, 6996, 315, 19465, 90030, 706, 2917, 2788, 18637, 304, 36508, 13, 330, 2028, 374, 279, 1176, 15207, 5938, 449, 2653, 90916, 2136, 311, 387, 11054, 304, 904, 6136, 9606, 1359, 11583, 1071, 13, 330, 2028, 18841, 1436, 1520, 603, 6288, 67638, 21389, 430, 2585, 420, 18027, 304, 1690, 1023, 11012, 13, 1226, 2351, 1101, 12304, 922, 279, 4754, 8522, 369, 47141, 279, 35719, 20545, 304, 10533, 56737, 13, 1115, 1436, 387, 87435, 439, 584, 10765, 4528, 21389, 430, 2585, 35719, 5990, 304, 1023, 2531, 19131, 1210, 11481, 90916, 2136, 20682, 279, 1317, 9860, 20237, 315, 1690, 8545, 6136, 9606, 555, 22973, 19595, 304, 15748, 4787, 323, 60537, 4890, 15729, 22484, 11, 10923, 1124, 311, 7293, 89460, 3156, 4787, 527, 1314, 369, 17684, 33196, 13, 10984, 1503, 304, 264, 3090, 12, 323, 264, 2154, 492, 23724, 11, 19595, 649, 7293, 31528, 369, 11838, 18852, 315, 892, 11, 304, 1063, 5157, 11, 810, 1109, 220, 1041, 1667, 13, 2030, 279, 2653, 6930, 430, 79018, 8545, 19595, 872, 56062, 374, 264, 3575, 304, 29149, 5788, 13, 1102, 29034, 19595, 505, 17684, 65383, 6288, 323, 304, 264, 14113, 11, 45207, 5497, 13, 13944, 29839, 17937, 19595, 1935, 505, 3892, 5672, 311, 4038, 311, 17684, 35116, 20444, 67166, 29839, 17937, 19595, 649, 3240, 70275, 3090, 304, 220, 868, 4520, 13, 52428, 689, 4227, 11, 20957, 304, 13936, 15324, 279, 907, 315, 10533, 55424, 2968, 323, 78220, 4183, 279, 18027, 311, 8356, 279, 62540, 315, 6617, 67166, 29839, 17937, 36680, 11, 11583, 1071, 13, 2030, 279, 19465, 9547, 1234, 13576, 1251, 10533, 23724, 55424, 2968, 14958, 264, 23347, 3156, 11583, 323, 813, 2128, 1511, 264, 2472, 6108, 78966, 5603, 311, 52122, 304, 389, 480, 76, 39, 82, 16, 12, 16, 439, 279, 15207, 8647, 369, 2653, 90916, 2136, 13, 578, 2128, 1766, 430, 264, 27472, 304, 264, 3254, 6857, 315, 31484, 354, 3422, 304, 279, 15207, 11384, 10533, 23724, 55424, 2968, 482, 430, 374, 11, 264, 2349, 304, 832, 6857, 704, 315, 279, 13489, 220, 16, 7239, 2385, 13840, 430, 1304, 709, 279, 29839, 17937, 33869, 13, 330, 1687, 5616, 3619, 279, 19465, 2349, 430, 5535, 279, 13018, 367, 315, 29839, 28440, 1359, 568, 1071, 13, 330, 4599, 584, 1304, 420, 3169, 315, 18841, 11, 584, 2351, 2744, 1633, 12304, 1210, 11583, 1071, 47141, 279, 15207, 1436, 8356, 2653, 1291, 19595, 369, 279, 18561, 549, 815, 13, 323, 279, 21965, 1233, 11, 13918, 304, 902, 279, 8579, 56737, 315, 67166, 29839, 28440, 8108, 872, 68507, 20193, 1306, 24322, 13, 578, 18841, 1436, 1101, 1520, 12074, 7417, 279, 17677, 4367, 315, 29839, 28440, 323, 1023, 2531, 19131, 11, 1778, 439, 279, 4279, 21059, 11, 6832, 29865, 5990, 315, 2653, 90916, 2136, 1304, 13263, 4367, 5107, 311, 11322, 13, 578, 2128, 596, 1828, 5915, 374, 311, 10765, 21389, 430, 16681, 449, 480, 76, 39, 82, 16, 12, 16, 323, 3619, 1268, 814, 990, 3871, 311, 2585, 35719, 323, 11000, 1023, 25107, 2262, 13, 578, 5684, 574, 4756, 304, 22037, 84386, 389, 7159, 320, 28259, 220, 1313, 8, 323, 374, 2561, 520, 14142, 962, 6870, 2726, 14, 605, 13, 6889, 23, 45143, 13, 8765, 24, 220, 128257, 198 ]

2,300

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Conventional computers based on the von Neumann architecture perform computation by repeatedly transferring data between their physically separated processing and memory units. As computation becomes increasingly data centric and the scalability limits in terms of performance and power are being reached, alternative computing paradigms with collocated computation and storage are actively being sought. A fascinating such approach is that of computational memory where the physics of nanoscale memory devices are used to perform certain computational tasks within the memory unit in a non-von Neumann manner. We present an experimental demonstration using one million phase change memory devices organized to perform a high-level computational primitive by exploiting the crystallization dynamics. Its result is imprinted in the conductance states of the memory devices. The results of using such a computational memory for processing real-world data sets show that this co-existence of computation and storage at the nanometer scale could enable ultra-dense, low-power, and massively-parallel computing systems. Introduction In today’s computing systems based on the conventional von Neumann architecture (Fig. 1a ), there are distinct memory and processing units. The processing unit comprises the arithmetic and logic unit (ALU), a control unit and a limited amount of cache memory. The memory unit typically comprises dynamic random-access memory (DRAM), where information is stored in the charge state of a capacitor. Performing an operation (such as an arithmetic or logic operation), f , over a set of data stored in the memory, A , to obtain the result, f ( A ), requires a sequence of steps in which the data must be obtained from the memory, transferred to the processing unit, processed, and stored back to the memory. This results in a significant amount of data being moved back and forth between the physically separated memory and processing units. This costs time and energy, and constitutes an inherent bottleneck in performance. Fig. 1 The concept of computational memory. a Schematic of the von Neumann computer architecture, where the memory and computing units are physically separated. A denotes information stored in a memory location. To perform a computational operation, f ( A ), and to store the result in the same memory location, data is shuttled back and forth between the memory and the processing unit. b An alternative architecture where f ( A ) is performed in place in the same memory location. c One way to realize computational memory is by relying on the state dynamics of a large collection of memristive devices. Depending on the operation to be performed, a suitable electrical signal is applied to the memory devices. The conductance of the devices evolves in accordance with the electrical input, and the result of the operation can be retrieved by reading the conductance at an appropriate time instance Full size image To overcome this, a tantalizing prospect is that of transitioning to a hybrid architecture where certain operations, such as f , can be performed at the same physical location as where the data is stored (Fig. 1b ). Such a memory unit that facilitates collocated computation is referred to as computational memory. The essential idea is not to treat memory as a passive storage entity, but to exploit the physical attributes of the memory devices to realize computation exactly at the place where the data is stored. One example of computational memory is a recent demonstration of the use of DRAM to perform bulk bit-wise operations 1 and fast row copying 2 within the DRAM chip. A new class of emerging nanocale devices, namely, resistive memory or memristive devices with their non-volatile storage capability, is particularly well suited for computational memory. In these devices, information is stored in their resistance/conductance states 3 , 4 , 5 , 6 . An early proposal for the use of memristive devices for in-place computing was the realization of certain logical operations using a circuit based on TiO x -based memory devices 7 . The same memory devices were used simultaneously to store the inputs, perform the logic operation, and store the resulting output. Subsequently, more complex logic units based on this initial concept have been proposed 8 , 9 , 10 . In addition to performing logical operations, resistive memory devices, when arranged in a cross-bar configuration, can be used to perform matrix–vector multiplications in an analog manner. This exploits the multi-level storage capability as well as Ohm’s law and Kirchhoff’s law. Hardware accelerators based on this concept are now becoming an important subject of research 11 , 12 , 13 , 14 , 15 , 16 , 17 . However, in these applications, the cross-bar array of resistive memory devices serves as a non-von Neumann computing core and the results of the computation are not necessarily stored in the memory array. Besides the ability to perform logical operations and matrix–vector multiplications, another tantalizing prospect of computational memory is that of realizing higher-level computational primitives by exploiting the rich dynamic behavior of its constituent devices. The dynamic evolution of the conductance levels of those devices upon application of electrical signals can be used to perform in-place computing. A schematic illustration of this concept is shown in Fig. 1c . Depending on the operation to be performed, a suitable electrical signal is applied to the memory devices. The conductance of the devices evolves in accordance with the electrical input, and the result of the computation is imprinted in the memory array. One early demonstration of this concept was that of finding factors of numbers using phase change memory (PCM) devices, a type of resistive memory devices 18 , 19 , 20 . However, this procedure is rather sensitive to device variabilities and thus experimental demonstrations were confined to a small number of devices. Hence, a large-scale experimental demonstration of a high-level computational primitive that exploits the memristive device dynamics and is robust to device variabilities across an array is still lacking. In this paper, we present an algorithm to detect temporal correlations between event-based data streams using computational memory. The crystallization dynamics of", "role": "user" }, { "content": "\"In-memory computing\" or \"computational memory\" is an emerging concept that uses the physical properties of memory devices for both storing and processing information. This is counter to current von Neumann systems and devices, such as standard desktop computers, laptops and even cellphones, which shuttle data back and forth between memory and the computing unit, thus making them slower and less energy efficient. Today, IBM Research is announcing that its scientists have demonstrated that an unsupervised machine-learning algorithm, running on one million phase change memory (PCM) devices, successfully found temporal correlations in unknown data streams. When compared to state-of-the-art classical computers, this prototype technology is expected to yield 200x improvements in both speed and energy efficiency, making it highly suitable for enabling ultra-dense, low-power, and massively-parallel computing systems for applications in AI. The researchers used PCM devices made from a germanium antimony telluride alloy, which is stacked and sandwiched between two electrodes. When the scientists apply a tiny electric current to the material, they heat it, which alters its state from amorphous (with a disordered atomic arrangement) to crystalline (with an ordered atomic configuration). The IBM researchers have used the crystallization dynamics to perform computation in place. \"This is an important step forward in our research of the physics of AI, which explores new hardware materials, devices and architectures,\" says Dr. Evangelos Eleftheriou, an IBM Fellow and co-author of the paper. \"As the CMOS scaling laws break down because of technological limits, a radical departure from the processor-memory dichotomy is needed to circumvent the limitations of today's computers. Given the simplicity, high speed and low energy of our in-memory computing approach, it's remarkable that our results are so similar to our benchmark classical approach run on a von Neumann computer.\" Credit: IBM Blog Research The details are explained in their paper appearing today in the peer-review journal Nature Communications. To demonstrate the technology, the authors chose two time-based examples and compared their results with traditional machine-learning methods such as k-means clustering: Simulated Data: one million binary (0 or 1) random processes organized on a 2-D grid based on a 1000 x 1000 pixel, black and white, profile drawing of famed British mathematician Alan Turing. The IBM scientists then made the pixels blink on and off with the same rate, but the black pixels turned on and off in a weakly correlated manner. This means that when a black pixel blinks, there is a slightly higher probability that another black pixel will also blink. The random processes were assigned to a million PCM devices, and a simple learning algorithm was implemented. With each blink, the PCM array learned, and the PCM devices corresponding to the correlated processes went to a high conductance state. In this way, the conductance map of the PCM devices recreates the drawing of Alan Turing. (see image above)Real-World Data: actual rainfall data, collected over a period of six months from 270 weather stations across the USA in one hour intervals. If rained within the hour, it was labelled \"1\" and if it didn't \"0\". Classical k-means clustering and the in-memory computing approach agreed on the classification of 245 out of the 270 weather stations. In-memory computing classified 12 stations as uncorrelated that had been marked correlated by the k-means clustering approach. Similarly, the in-memory computing approach classified 13 stations as correlated that had been marked uncorrelated by k-means clustering. \"Memory has so far been viewed as a place where we merely store information. But in this work, we conclusively show how we can exploit the physics of these memory devices to also perform a rather high-level computational primitive. The result of the computation is also stored in the memory devices, and in this sense the concept is loosely inspired by how the brain computes.\" said Dr. Abu Sebastian, exploratory memory and cognitive technologies scientist, IBM Research and lead author of the paper. A schematic illustration of the in-memory computing algorithm. Credit: IBM Research ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Conventional computers based on the von Neumann architecture perform computation by repeatedly transferring data between their physically separated processing and memory units. As computation becomes increasingly data centric and the scalability limits in terms of performance and power are being reached, alternative computing paradigms with collocated computation and storage are actively being sought. A fascinating such approach is that of computational memory where the physics of nanoscale memory devices are used to perform certain computational tasks within the memory unit in a non-von Neumann manner. We present an experimental demonstration using one million phase change memory devices organized to perform a high-level computational primitive by exploiting the crystallization dynamics. Its result is imprinted in the conductance states of the memory devices. The results of using such a computational memory for processing real-world data sets show that this co-existence of computation and storage at the nanometer scale could enable ultra-dense, low-power, and massively-parallel computing systems. Introduction In today’s computing systems based on the conventional von Neumann architecture (Fig. 1a ), there are distinct memory and processing units. The processing unit comprises the arithmetic and logic unit (ALU), a control unit and a limited amount of cache memory. The memory unit typically comprises dynamic random-access memory (DRAM), where information is stored in the charge state of a capacitor. Performing an operation (such as an arithmetic or logic operation), f , over a set of data stored in the memory, A , to obtain the result, f ( A ), requires a sequence of steps in which the data must be obtained from the memory, transferred to the processing unit, processed, and stored back to the memory. This results in a significant amount of data being moved back and forth between the physically separated memory and processing units. This costs time and energy, and constitutes an inherent bottleneck in performance. Fig. 1 The concept of computational memory. a Schematic of the von Neumann computer architecture, where the memory and computing units are physically separated. A denotes information stored in a memory location. To perform a computational operation, f ( A ), and to store the result in the same memory location, data is shuttled back and forth between the memory and the processing unit. b An alternative architecture where f ( A ) is performed in place in the same memory location. c One way to realize computational memory is by relying on the state dynamics of a large collection of memristive devices. Depending on the operation to be performed, a suitable electrical signal is applied to the memory devices. The conductance of the devices evolves in accordance with the electrical input, and the result of the operation can be retrieved by reading the conductance at an appropriate time instance Full size image To overcome this, a tantalizing prospect is that of transitioning to a hybrid architecture where certain operations, such as f , can be performed at the same physical location as where the data is stored (Fig. 1b ). Such a memory unit that facilitates collocated computation is referred to as computational memory. The essential idea is not to treat memory as a passive storage entity, but to exploit the physical attributes of the memory devices to realize computation exactly at the place where the data is stored. One example of computational memory is a recent demonstration of the use of DRAM to perform bulk bit-wise operations 1 and fast row copying 2 within the DRAM chip. A new class of emerging nanocale devices, namely, resistive memory or memristive devices with their non-volatile storage capability, is particularly well suited for computational memory. In these devices, information is stored in their resistance/conductance states 3 , 4 , 5 , 6 . An early proposal for the use of memristive devices for in-place computing was the realization of certain logical operations using a circuit based on TiO x -based memory devices 7 . The same memory devices were used simultaneously to store the inputs, perform the logic operation, and store the resulting output. Subsequently, more complex logic units based on this initial concept have been proposed 8 , 9 , 10 . In addition to performing logical operations, resistive memory devices, when arranged in a cross-bar configuration, can be used to perform matrix–vector multiplications in an analog manner. This exploits the multi-level storage capability as well as Ohm’s law and Kirchhoff’s law. Hardware accelerators based on this concept are now becoming an important subject of research 11 , 12 , 13 , 14 , 15 , 16 , 17 . However, in these applications, the cross-bar array of resistive memory devices serves as a non-von Neumann computing core and the results of the computation are not necessarily stored in the memory array. Besides the ability to perform logical operations and matrix–vector multiplications, another tantalizing prospect of computational memory is that of realizing higher-level computational primitives by exploiting the rich dynamic behavior of its constituent devices. The dynamic evolution of the conductance levels of those devices upon application of electrical signals can be used to perform in-place computing. A schematic illustration of this concept is shown in Fig. 1c . Depending on the operation to be performed, a suitable electrical signal is applied to the memory devices. The conductance of the devices evolves in accordance with the electrical input, and the result of the computation is imprinted in the memory array. One early demonstration of this concept was that of finding factors of numbers using phase change memory (PCM) devices, a type of resistive memory devices 18 , 19 , 20 . However, this procedure is rather sensitive to device variabilities and thus experimental demonstrations were confined to a small number of devices. Hence, a large-scale experimental demonstration of a high-level computational primitive that exploits the memristive device dynamics and is robust to device variabilities across an array is still lacking. In this paper, we present an algorithm to detect temporal correlations between event-based data streams using computational memory. The crystallization dynamics of<|im_end|> <|im_start|>assistant "In-memory computing" or "computational memory" is an emerging concept that uses the physical properties of memory devices for both storing and processing information. This is counter to current von Neumann systems and devices, such as standard desktop computers, laptops and even cellphones, which shuttle data back and forth between memory and the computing unit, thus making them slower and less energy efficient. Today, IBM Research is announcing that its scientists have demonstrated that an unsupervised machine-learning algorithm, running on one million phase change memory (PCM) devices, successfully found temporal correlations in unknown data streams. When compared to state-of-the-art classical computers, this prototype technology is expected to yield 200x improvements in both speed and energy efficiency, making it highly suitable for enabling ultra-dense, low-power, and massively-parallel computing systems for applications in AI. The researchers used PCM devices made from a germanium antimony telluride alloy, which is stacked and sandwiched between two electrodes. When the scientists apply a tiny electric current to the material, they heat it, which alters its state from amorphous (with a disordered atomic arrangement) to crystalline (with an ordered atomic configuration). The IBM researchers have used the crystallization dynamics to perform computation in place. "This is an important step forward in our research of the physics of AI, which explores new hardware materials, devices and architectures," says Dr. Evangelos Eleftheriou, an IBM Fellow and co-author of the paper. "As the CMOS scaling laws break down because of technological limits, a radical departure from the processor-memory dichotomy is needed to circumvent the limitations of today's computers. Given the simplicity, high speed and low energy of our in-memory computing approach, it's remarkable that our results are so similar to our benchmark classical approach run on a von Neumann computer." Credit: IBM Blog Research The details are explained in their paper appearing today in the peer-review journal Nature Communications. To demonstrate the technology, the authors chose two time-based examples and compared their results with traditional machine-learning methods such as k-means clustering: Simulated Data: one million binary (0 or 1) random processes organized on a 2-D grid based on a 1000 x 1000 pixel, black and white, profile drawing of famed British mathematician Alan Turing. The IBM scientists then made the pixels blink on and off with the same rate, but the black pixels turned on and off in a weakly correlated manner. This means that when a black pixel blinks, there is a slightly higher probability that another black pixel will also blink. The random processes were assigned to a million PCM devices, and a simple learning algorithm was implemented. With each blink, the PCM array learned, and the PCM devices corresponding to the correlated processes went to a high conductance state. In this way, the conductance map of the PCM devices recreates the drawing of Alan Turing. (see image above)Real-World Data: actual rainfall data, collected over a period of six months from 270 weather stations across the USA in one hour intervals. If rained within the hour, it was labelled "1" and if it didn't "0". Classical k-means clustering and the in-memory computing approach agreed on the classification of 245 out of the 270 weather stations. In-memory computing classified 12 stations as uncorrelated that had been marked correlated by the k-means clustering approach. Similarly, the in-memory computing approach classified 13 stations as correlated that had been marked uncorrelated by k-means clustering. "Memory has so far been viewed as a place where we merely store information. But in this work, we conclusively show how we can exploit the physics of these memory devices to also perform a rather high-level computational primitive. The result of the computation is also stored in the memory devices, and in this sense the concept is loosely inspired by how the brain computes." said Dr. Abu Sebastian, exploratory memory and cognitive technologies scientist, IBM Research and lead author of the paper. A schematic illustration of the in-memory computing algorithm. Credit: IBM Research <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 1221, 44322, 19002, 3196, 389, 279, 6675, 4275, 64607, 18112, 2804, 35547, 555, 19352, 51051, 828, 1990, 872, 22655, 19180, 8863, 323, 5044, 8316, 13, 1666, 35547, 9221, 15098, 828, 2960, 2265, 323, 279, 94840, 13693, 304, 3878, 315, 5178, 323, 2410, 527, 1694, 8813, 11, 10778, 25213, 28417, 343, 1026, 449, 1400, 40563, 35547, 323, 5942, 527, 22815, 1694, 16495, 13, 362, 27387, 1778, 5603, 374, 430, 315, 55580, 5044, 1405, 279, 22027, 315, 20622, 437, 2296, 5044, 7766, 527, 1511, 311, 2804, 3738, 55580, 9256, 2949, 279, 5044, 5089, 304, 264, 2536, 8437, 263, 4275, 64607, 11827, 13, 1226, 3118, 459, 22772, 30816, 1701, 832, 3610, 10474, 2349, 5044, 7766, 17057, 311, 2804, 264, 1579, 11852, 55580, 28694, 555, 71701, 279, 64568, 2065, 30295, 13, 11699, 1121, 374, 737, 53313, 304, 279, 6929, 685, 5415, 315, 279, 5044, 7766, 13, 578, 3135, 315, 1701, 1778, 264, 55580, 5044, 369, 8863, 1972, 31184, 828, 7437, 1501, 430, 420, 1080, 10397, 81624, 315, 35547, 323, 5942, 520, 279, 20622, 21037, 5569, 1436, 7431, 24955, 1773, 1137, 11, 3428, 27624, 11, 323, 64807, 12, 47203, 25213, 6067, 13, 29438, 763, 3432, 753, 25213, 6067, 3196, 389, 279, 21349, 6675, 4275, 64607, 18112, 320, 30035, 13, 220, 16, 64, 7026, 1070, 527, 12742, 5044, 323, 8863, 8316, 13, 578, 8863, 5089, 41095, 279, 35884, 323, 12496, 5089, 320, 984, 52, 705, 264, 2585, 5089, 323, 264, 7347, 3392, 315, 6636, 5044, 13, 578, 5044, 5089, 11383, 41095, 8915, 4288, 43256, 5044, 320, 79860, 705, 1405, 2038, 374, 9967, 304, 279, 6900, 1614, 315, 264, 85525, 13, 70748, 459, 5784, 320, 21470, 439, 459, 35884, 477, 12496, 5784, 705, 282, 1174, 927, 264, 743, 315, 828, 9967, 304, 279, 5044, 11, 362, 1174, 311, 6994, 279, 1121, 11, 282, 320, 362, 7026, 7612, 264, 8668, 315, 7504, 304, 902, 279, 828, 2011, 387, 12457, 505, 279, 5044, 11, 23217, 311, 279, 8863, 5089, 11, 15590, 11, 323, 9967, 1203, 311, 279, 5044, 13, 1115, 3135, 304, 264, 5199, 3392, 315, 828, 1694, 7882, 1203, 323, 13544, 1990, 279, 22655, 19180, 5044, 323, 8863, 8316, 13, 1115, 7194, 892, 323, 4907, 11, 323, 42675, 459, 38088, 88938, 304, 5178, 13, 23966, 13, 220, 16, 578, 7434, 315, 55580, 5044, 13, 264, 328, 82149, 315, 279, 6675, 4275, 64607, 6500, 18112, 11, 1405, 279, 5044, 323, 25213, 8316, 527, 22655, 19180, 13, 362, 72214, 2038, 9967, 304, 264, 5044, 3813, 13, 2057, 2804, 264, 55580, 5784, 11, 282, 320, 362, 7026, 323, 311, 3637, 279, 1121, 304, 279, 1890, 5044, 3813, 11, 828, 374, 9495, 83, 839, 1203, 323, 13544, 1990, 279, 5044, 323, 279, 8863, 5089, 13, 293, 1556, 10778, 18112, 1405, 282, 320, 362, 883, 374, 10887, 304, 2035, 304, 279, 1890, 5044, 3813, 13, 272, 3861, 1648, 311, 13383, 55580, 5044, 374, 555, 39661, 389, 279, 1614, 30295, 315, 264, 3544, 4526, 315, 1871, 2889, 535, 7766, 13, 40730, 389, 279, 5784, 311, 387, 10887, 11, 264, 14791, 20314, 8450, 374, 9435, 311, 279, 5044, 7766, 13, 578, 6929, 685, 315, 279, 7766, 93054, 304, 18859, 449, 279, 20314, 1988, 11, 323, 279, 1121, 315, 279, 5784, 649, 387, 31503, 555, 5403, 279, 6929, 685, 520, 459, 8475, 892, 2937, 8797, 1404, 2217, 2057, 23075, 420, 11, 264, 95685, 4954, 22199, 374, 430, 315, 73194, 311, 264, 26038, 18112, 1405, 3738, 7677, 11, 1778, 439, 282, 1174, 649, 387, 10887, 520, 279, 1890, 7106, 3813, 439, 1405, 279, 828, 374, 9967, 320, 30035, 13, 220, 16, 65, 7609, 15483, 264, 5044, 5089, 430, 73633, 1400, 40563, 35547, 374, 14183, 311, 439, 55580, 5044, 13, 578, 7718, 4623, 374, 539, 311, 4322, 5044, 439, 264, 28979, 5942, 5502, 11, 719, 311, 33294, 279, 7106, 8365, 315, 279, 5044, 7766, 311, 13383, 35547, 7041, 520, 279, 2035, 1405, 279, 828, 374, 9967, 13, 3861, 3187, 315, 55580, 5044, 374, 264, 3293, 30816, 315, 279, 1005, 315, 14644, 1428, 311, 2804, 20155, 2766, 45539, 7677, 220, 16, 323, 5043, 2872, 32139, 220, 17, 2949, 279, 14644, 1428, 16797, 13, 362, 502, 538, 315, 24084, 20622, 37411, 7766, 11, 32125, 11, 22884, 535, 5044, 477, 1871, 2889, 535, 7766, 449, 872, 2536, 8437, 26598, 5942, 23099, 11, 374, 8104, 1664, 32599, 369, 55580, 5044, 13, 763, 1521, 7766, 11, 2038, 374, 9967, 304, 872, 13957, 32336, 1076, 685, 5415, 220, 18, 1174, 220, 19, 1174, 220, 20, 1174, 220, 21, 662, 1556, 4216, 14050, 369, 279, 1005, 315, 1871, 2889, 535, 7766, 369, 304, 42761, 25213, 574, 279, 49803, 315, 3738, 20406, 7677, 1701, 264, 16622, 3196, 389, 23126, 46, 865, 482, 31039, 5044, 7766, 220, 22, 662, 578, 1890, 5044, 7766, 1051, 1511, 25291, 311, 3637, 279, 11374, 11, 2804, 279, 12496, 5784, 11, 323, 3637, 279, 13239, 2612, 13, 3804, 39742, 11, 810, 6485, 12496, 8316, 3196, 389, 420, 2926, 7434, 617, 1027, 11223, 220, 23, 1174, 220, 24, 1174, 220, 605, 662, 763, 5369, 311, 16785, 20406, 7677, 11, 22884, 535, 5044, 7766, 11, 994, 28902, 304, 264, 5425, 16150, 6683, 11, 649, 387, 1511, 311, 2804, 6303, 4235, 3295, 12842, 10939, 304, 459, 24291, 11827, 13, 1115, 63488, 279, 7447, 11852, 5942, 23099, 439, 1664, 439, 8840, 76, 753, 2383, 323, 26608, 331, 94404, 753, 2383, 13, 37865, 14511, 3046, 3196, 389, 420, 7434, 527, 1457, 10671, 459, 3062, 3917, 315, 3495, 220, 806, 1174, 220, 717, 1174, 220, 1032, 1174, 220, 975, 1174, 220, 868, 1174, 220, 845, 1174, 220, 1114, 662, 4452, 11, 304, 1521, 8522, 11, 279, 5425, 16150, 1358, 315, 22884, 535, 5044, 7766, 17482, 439, 264, 2536, 8437, 263, 4275, 64607, 25213, 6332, 323, 279, 3135, 315, 279, 35547, 527, 539, 14647, 9967, 304, 279, 5044, 1358, 13, 31909, 279, 5845, 311, 2804, 20406, 7677, 323, 6303, 4235, 3295, 12842, 10939, 11, 2500, 95685, 4954, 22199, 315, 55580, 5044, 374, 430, 315, 44114, 5190, 11852, 55580, 72294, 555, 71701, 279, 9257, 8915, 7865, 315, 1202, 75164, 7766, 13, 578, 8915, 15740, 315, 279, 6929, 685, 5990, 315, 1884, 7766, 5304, 3851, 315, 20314, 17738, 649, 387, 1511, 311, 2804, 304, 42761, 25213, 13, 362, 68144, 40134, 315, 420, 7434, 374, 6982, 304, 23966, 13, 220, 16, 66, 662, 40730, 389, 279, 5784, 311, 387, 10887, 11, 264, 14791, 20314, 8450, 374, 9435, 311, 279, 5044, 7766, 13, 578, 6929, 685, 315, 279, 7766, 93054, 304, 18859, 449, 279, 20314, 1988, 11, 323, 279, 1121, 315, 279, 35547, 374, 737, 53313, 304, 279, 5044, 1358, 13, 3861, 4216, 30816, 315, 420, 7434, 574, 430, 315, 9455, 9547, 315, 5219, 1701, 10474, 2349, 5044, 320, 89611, 8, 7766, 11, 264, 955, 315, 22884, 535, 5044, 7766, 220, 972, 1174, 220, 777, 1174, 220, 508, 662, 4452, 11, 420, 10537, 374, 4856, 16614, 311, 3756, 4244, 8623, 323, 8617, 22772, 44895, 1051, 45408, 311, 264, 2678, 1396, 315, 7766, 13, 32140, 11, 264, 3544, 13230, 22772, 30816, 315, 264, 1579, 11852, 55580, 28694, 430, 63488, 279, 1871, 2889, 535, 3756, 30295, 323, 374, 22514, 311, 3756, 4244, 8623, 4028, 459, 1358, 374, 2103, 32161, 13, 763, 420, 5684, 11, 584, 3118, 459, 12384, 311, 11388, 37015, 69916, 1990, 1567, 6108, 828, 23914, 1701, 55580, 5044, 13, 578, 64568, 2065, 30295, 315, 128257, 198, 128256, 78191, 198, 33703, 65196, 25213, 1, 477, 330, 66047, 1697, 5044, 1, 374, 459, 24084, 7434, 430, 5829, 279, 7106, 6012, 315, 5044, 7766, 369, 2225, 28672, 323, 8863, 2038, 13, 1115, 374, 5663, 311, 1510, 6675, 4275, 64607, 6067, 323, 7766, 11, 1778, 439, 5410, 17963, 19002, 11, 48985, 323, 1524, 2849, 17144, 11, 902, 45641, 828, 1203, 323, 13544, 1990, 5044, 323, 279, 25213, 5089, 11, 8617, 3339, 1124, 29493, 323, 2753, 4907, 11297, 13, 11450, 11, 29022, 8483, 374, 38787, 430, 1202, 14248, 617, 21091, 430, 459, 7120, 455, 79090, 5780, 71856, 12384, 11, 4401, 389, 832, 3610, 10474, 2349, 5044, 320, 89611, 8, 7766, 11, 7946, 1766, 37015, 69916, 304, 9987, 828, 23914, 13, 3277, 7863, 311, 1614, 8838, 10826, 38921, 29924, 19002, 11, 420, 25018, 5557, 374, 3685, 311, 7692, 220, 1049, 87, 18637, 304, 2225, 4732, 323, 4907, 15374, 11, 3339, 433, 7701, 14791, 369, 28462, 24955, 1773, 1137, 11, 3428, 27624, 11, 323, 64807, 12, 47203, 25213, 6067, 369, 8522, 304, 15592, 13, 578, 12074, 1511, 76107, 7766, 1903, 505, 264, 43627, 2411, 3276, 65556, 3371, 324, 579, 46964, 11, 902, 374, 42415, 323, 28974, 291, 1990, 1403, 80390, 13, 3277, 279, 14248, 3881, 264, 13987, 9249, 1510, 311, 279, 3769, 11, 814, 8798, 433, 11, 902, 88687, 1202, 1614, 505, 1097, 16751, 788, 320, 4291, 264, 834, 10767, 25524, 27204, 8, 311, 64568, 483, 320, 4291, 459, 11713, 25524, 6683, 570, 578, 29022, 12074, 617, 1511, 279, 64568, 2065, 30295, 311, 2804, 35547, 304, 2035, 13, 330, 2028, 374, 459, 3062, 3094, 4741, 304, 1057, 3495, 315, 279, 22027, 315, 15592, 11, 902, 41424, 502, 12035, 7384, 11, 7766, 323, 78335, 1359, 2795, 2999, 13, 55806, 437, 27039, 69, 700, 99355, 11, 459, 29022, 37946, 323, 1080, 43802, 315, 279, 5684, 13, 330, 2170, 279, 18582, 3204, 28041, 7016, 1464, 1523, 1606, 315, 30116, 13693, 11, 264, 18336, 25959, 505, 279, 18121, 65196, 29953, 85995, 374, 4460, 311, 10408, 688, 279, 9669, 315, 3432, 596, 19002, 13, 16644, 279, 40075, 11, 1579, 4732, 323, 3428, 4907, 315, 1057, 304, 65196, 25213, 5603, 11, 433, 596, 23649, 430, 1057, 3135, 527, 779, 4528, 311, 1057, 29531, 29924, 5603, 1629, 389, 264, 6675, 4275, 64607, 6500, 1210, 16666, 25, 29022, 14496, 8483, 578, 3649, 527, 11497, 304, 872, 5684, 26449, 3432, 304, 279, 14734, 46821, 8486, 22037, 26545, 13, 2057, 20461, 279, 5557, 11, 279, 12283, 14896, 1403, 892, 6108, 10507, 323, 7863, 872, 3135, 449, 8776, 5780, 71856, 5528, 1778, 439, 597, 35073, 598, 59454, 25, 4567, 7913, 2956, 25, 832, 3610, 8026, 320, 15, 477, 220, 16, 8, 4288, 11618, 17057, 389, 264, 220, 17, 9607, 5950, 3196, 389, 264, 220, 1041, 15, 865, 220, 1041, 15, 13252, 11, 3776, 323, 4251, 11, 5643, 13633, 315, 61403, 8013, 21651, 1122, 26349, 95530, 13, 578, 29022, 14248, 1243, 1903, 279, 16128, 34231, 389, 323, 1022, 449, 279, 1890, 4478, 11, 719, 279, 3776, 16128, 6656, 389, 323, 1022, 304, 264, 7621, 398, 49393, 11827, 13, 1115, 3445, 430, 994, 264, 3776, 13252, 1529, 15872, 11, 1070, 374, 264, 10284, 5190, 19463, 430, 2500, 3776, 13252, 690, 1101, 34231, 13, 578, 4288, 11618, 1051, 12893, 311, 264, 3610, 76107, 7766, 11, 323, 264, 4382, 6975, 12384, 574, 11798, 13, 3161, 1855, 34231, 11, 279, 76107, 1358, 9687, 11, 323, 279, 76107, 7766, 12435, 311, 279, 49393, 11618, 4024, 311, 264, 1579, 6929, 685, 1614, 13, 763, 420, 1648, 11, 279, 6929, 685, 2472, 315, 279, 76107, 7766, 23671, 988, 279, 13633, 315, 26349, 95530, 13, 320, 4151, 2217, 3485, 8, 13058, 12, 10343, 2956, 25, 5150, 53958, 828, 11, 14890, 927, 264, 4261, 315, 4848, 4038, 505, 220, 10914, 9282, 17789, 4028, 279, 7427, 304, 832, 6596, 28090, 13, 1442, 436, 2692, 2949, 279, 6596, 11, 433, 574, 61336, 330, 16, 1, 323, 422, 433, 3287, 956, 330, 15, 3343, 68533, 597, 35073, 598, 59454, 323, 279, 304, 65196, 25213, 5603, 7378, 389, 279, 24790, 315, 220, 13078, 704, 315, 279, 220, 10914, 9282, 17789, 13, 763, 65196, 25213, 21771, 220, 717, 17789, 439, 653, 6133, 9920, 430, 1047, 1027, 13160, 49393, 555, 279, 597, 35073, 598, 59454, 5603, 13, 35339, 11, 279, 304, 65196, 25213, 5603, 21771, 220, 1032, 17789, 439, 49393, 430, 1047, 1027, 13160, 653, 6133, 9920, 555, 597, 35073, 598, 59454, 13, 330, 10869, 706, 779, 3117, 1027, 19894, 439, 264, 2035, 1405, 584, 16632, 3637, 2038, 13, 2030, 304, 420, 990, 11, 584, 84082, 3210, 1501, 1268, 584, 649, 33294, 279, 22027, 315, 1521, 5044, 7766, 311, 1101, 2804, 264, 4856, 1579, 11852, 55580, 28694, 13, 578, 1121, 315, 279, 35547, 374, 1101, 9967, 304, 279, 5044, 7766, 11, 323, 304, 420, 5647, 279, 7434, 374, 63557, 14948, 555, 1268, 279, 8271, 58303, 1210, 1071, 2999, 13, 31229, 44609, 11, 48539, 5382, 5044, 323, 25702, 14645, 28568, 11, 29022, 8483, 323, 3063, 3229, 315, 279, 5684, 13, 362, 68144, 40134, 315, 279, 304, 65196, 25213, 12384, 13, 16666, 25, 29022, 8483, 220, 128257, 198 ]

2,073

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract The COVID–19 pandemic has caused considerable interest worldwide in antiviral surfaces, and there has been a dramatic increase in the research and development of innovative material systems to reduce virus transmission in the past few years. The International Organization for Standardization (ISO) norms 18,184 and 21,702 are two standard methods to characterize the antiviral properties of porous and non-porous surfaces. However, during the last years of the pandemic, a need for faster and inexpensive characterization of antiviral material was identified. Therefore, a complementary method based on an Inactivated Virus System (InViS) was developed to facilitate the early-stage development of antiviral technologies and quality surveillance of the production of antiviral materials safely and efficiently. The InViS is loaded with a self-quenched fluorescent dye that produces a measurable increase in fluorescence when the viral envelope disintegrates. In the present work, the sensitivity of InViS to viral disintegration by known antiviral agents is demonstrated and its potential to characterize novel materials and surfaces is explored. Finally, the InViS is used to determine the fate of viral particles within facemasks layers, rendering it an interesting tool to support the development of antiviral surface systems for technical and medical applications. Introduction What started as a mysterious and unknown lung disease in Wuhan in December 2019 has evolved into a serious pandemic similar to the \"Spanish flu\": COVID-19. The trigger is the beta-coronavirus SARS-CoV-2, which is responsible for various symptoms such as inflammation of the throat and respiratory tract, coughing, shortness of breath, fatigue, fever, myalgia, conjunctivitis, loss of smell and impaired taste. In severe cases, it can lead to acute lung failure, multi-organ failure and death 1 . As of June 2022, the number of confirmed COVID-19 cases worldwide has reached 529 million and the number of deaths has risen to over 6 million 2 . Although effective vaccines and better treatment strategies have been developed in the meantime, new highly contagious mutations and low vaccination rates in poor countries continue to force the health care systems to their limits. Therefore, non-pharmaceutical interventions such as contact reduction, hygiene and facemasks remain important to keep the propagation of the virus at bay 3 . The overall goal of these measures is to slow down disease transmission between people. COVID-19 spreads mainly by respiratory droplets among people who are in close contact with each other 4 . However, also other mechanisms of disease transmission are also possible. For example, aerosol transmission can occur indoors in crowded and poorly ventilated spaces, and it is also possible to catch COVID-19 indirectly through touching surfaces or objects contaminated with the virus from infected people, followed by touching the eyes, nose or mouth (fomite transmission) 4 . It has been shown that SARS-CoV-2 is stable from a few hours to days depending on the chemistry of the surface on which the virus is deposited. For example, van Doremalen et al . demonstrated that SARS-CoV-2 remained stable on plastic and stainless steel surfaces for several hours. Viable virus could be detected up to 72 h after application to these surfaces, and the half-life of SARS-CoV-2 was estimated to be 5.6 h on stainless steel and to 6.8 h on plastic 5 . In contrast, no viable virus could be detected on cardboard surfaces after 24 h, and copper surfaces tended to inactivate the virus within 4 hours 5 . Chin et al . confirmed that SARS-CoV-2 is more stable on smooth and hydrophobic surfaces. While no infectious virus could be recovered from printing and tissue culture papers after 3 h, viable and infectious virus was still present on treated smooth surfaces (glass and banknotes) after 2 days, on stainless steel and plastic after 4 days and on the hydrophobic outer layer of a surgical mask after 7 days 6 . Since this high surface stability increases the risk of smear infection, it would be highly beneficial if virus particles that reach vulnerable surfaces such as touch screens, doorknobs, ventilation filters, textiles, train seats or handrails could be inactivated immediately without further disinfection processes. The same applies also to virus particles deposited on facemasks, since inappropriate mask handling is a commonly faced problem. Therefore, the development of antiviral materials, coatings and facemasks is of tremendous importance not only to fight COVID-19, but also to prevent similar pandemic or epidemic outbreaks in the future. There are several ways to inactivate or even destroy viruses. The most known are detergents or ethanol solutions which disintegrate the lipid and protein structure of the virus 7 , 8 , 9 , 10 , radiation such as ultraviolet light with wavelength between 200 and 300 nm (UVC) 11 , 12 , 13 , thermal treatment like autoclaving 14 , 15 , oxidation 16 , 17 or high positive surface charge 18 , 19 . When new antiviral materials are developed, it is crucial to investigate and quantify their potential to trap, inactivate and/or kill the viruses. Currently, there are two ISO norms available, which regulate the measurement of antiviral activity on plastics and other non-porous surfaces (ISO 21702) and the determination of antiviral activity of textile products (ISO 18184). In both norms, the infectious virus titer needs to be determined by either a plaque assay or the Median Tissue Culture Infectious Dose (TCID 50 ) method. Both of these assays require working with the real infectious virus and are based on the principle that cytopathic effects caused by the virus can be visibly assessed in vitro. Although these assays deliver reliable and comparable results on the antiviral activity of the materials, they have several disadvantages: working with real viruses such as e.g. SARS-CoV-2 requires special infrastructure (e.g. biosafety level 3 equipped labs) and trained employees. This prevents the widespread use of these analyses in most industrial and research settings and consequently delays the rapid development of novel antiviral materials as observed during the current COVID-pandemic. Consequently, novel characterisation methods are urgently needed to facilitate the fast, cheap and safe pre-screening of a large number of materials and", "role": "user" }, { "content": "Using a new analytical method, Empa researchers have tracked viruses as they pass through face masks and compared their failure on the filter layers of different types of masks. The new method should now accelerate the development of surfaces that can kill viruses, the team writes in the journal Scientific Reports. Using high pressure, the apparatus pushes artificial saliva fluid, colored in red, with test particles through a stretched mask. This is how the researchers simulate the process of a droplet infection. The new method established at Empa is currently used by certified test centers to ensure the quality of textile face masks because a safe and effective protective mask must meet demanding requirements: It must keep out germs, withstand splashing drops of saliva, and at the same time allow air to pass through. Now Empa researchers are going one step further: \"Images taken using a transmission electron microscope show that a few virus particles manage to make their way into the innermost layer of the mask, close to the face. However, the images do not always reveal whether these viruses are still infectious,\" says Peter Wick of Empa's Particles-Biology Interactions lab in St. Gallen. The researchers' goal: They want to find out where exactly a virus particle is held back within a multilayer face mask during droplet infection, and which mask components should be more efficient. \"We needed new analytical methods to precisely understand the protective function of newly developed technologies such as virus-killing coatings,\" says Empa researcher René Rossi of the Biomimetic Membranes and Textiles lab in St. Gallen. After all, this is precisely one of the goals of the ReMask project, in which research, industry and health care experts are teaming up with Empa in the fight against the pandemic to develop new concepts for better, more comfortable and more sustainable face masks. The new method is a fluorescent approach to detect viral disintegration caused by antiviral materials. Credit: Scientific Reports / Empa Dying beauty The new process relies on a dye, rhodamine R18, which emits colored light. Non-hazardous, inactivated test viruses are used, which are coupled to R18 and thus become dying beauties: They light up as soon as they are damaged. \"The fluorescence indicates reliably, quickly and inexpensively when viruses have been killed,\" Wick says. Based on the intensity with which a mask layer glows, the team found that for fabric and hygiene masks, most viruses fail in the mid layer between the inner and outer layers of the mask. In FFP2 masks, the third of six layers glowed the most—again, the central layer trapped a particularly large number of viruses. These findings can now be used to optimize facial masks. In addition, the new process can accelerate the development of virus-killing surfaces. \"Surfaces with antiviral properties must comply with certain ISO standards, which entail laborious standard tests,\" Wick explains. The Empa researchers' fluorescence method, on the other hand, could be a simpler, faster and more cost-effective way of determining whether a new type of coating can reliably kill viruses, as a supplement to current standards. This would be of interest both for smooth surfaces, such as on worktops or handles, and for coatings on textiles with a porous surface, such as masks or filter systems. And with the new method, this knowledge could already be integrated into the development process of technical and medical applications at a very early stage. According to Wick, this will speed up the introduction of new products, as only promising candidates will have to undergo the time-consuming and cost-intensive standardization tests. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract The COVID–19 pandemic has caused considerable interest worldwide in antiviral surfaces, and there has been a dramatic increase in the research and development of innovative material systems to reduce virus transmission in the past few years. The International Organization for Standardization (ISO) norms 18,184 and 21,702 are two standard methods to characterize the antiviral properties of porous and non-porous surfaces. However, during the last years of the pandemic, a need for faster and inexpensive characterization of antiviral material was identified. Therefore, a complementary method based on an Inactivated Virus System (InViS) was developed to facilitate the early-stage development of antiviral technologies and quality surveillance of the production of antiviral materials safely and efficiently. The InViS is loaded with a self-quenched fluorescent dye that produces a measurable increase in fluorescence when the viral envelope disintegrates. In the present work, the sensitivity of InViS to viral disintegration by known antiviral agents is demonstrated and its potential to characterize novel materials and surfaces is explored. Finally, the InViS is used to determine the fate of viral particles within facemasks layers, rendering it an interesting tool to support the development of antiviral surface systems for technical and medical applications. Introduction What started as a mysterious and unknown lung disease in Wuhan in December 2019 has evolved into a serious pandemic similar to the "Spanish flu": COVID-19. The trigger is the beta-coronavirus SARS-CoV-2, which is responsible for various symptoms such as inflammation of the throat and respiratory tract, coughing, shortness of breath, fatigue, fever, myalgia, conjunctivitis, loss of smell and impaired taste. In severe cases, it can lead to acute lung failure, multi-organ failure and death 1 . As of June 2022, the number of confirmed COVID-19 cases worldwide has reached 529 million and the number of deaths has risen to over 6 million 2 . Although effective vaccines and better treatment strategies have been developed in the meantime, new highly contagious mutations and low vaccination rates in poor countries continue to force the health care systems to their limits. Therefore, non-pharmaceutical interventions such as contact reduction, hygiene and facemasks remain important to keep the propagation of the virus at bay 3 . The overall goal of these measures is to slow down disease transmission between people. COVID-19 spreads mainly by respiratory droplets among people who are in close contact with each other 4 . However, also other mechanisms of disease transmission are also possible. For example, aerosol transmission can occur indoors in crowded and poorly ventilated spaces, and it is also possible to catch COVID-19 indirectly through touching surfaces or objects contaminated with the virus from infected people, followed by touching the eyes, nose or mouth (fomite transmission) 4 . It has been shown that SARS-CoV-2 is stable from a few hours to days depending on the chemistry of the surface on which the virus is deposited. For example, van Doremalen et al . demonstrated that SARS-CoV-2 remained stable on plastic and stainless steel surfaces for several hours. Viable virus could be detected up to 72 h after application to these surfaces, and the half-life of SARS-CoV-2 was estimated to be 5.6 h on stainless steel and to 6.8 h on plastic 5 . In contrast, no viable virus could be detected on cardboard surfaces after 24 h, and copper surfaces tended to inactivate the virus within 4 hours 5 . Chin et al . confirmed that SARS-CoV-2 is more stable on smooth and hydrophobic surfaces. While no infectious virus could be recovered from printing and tissue culture papers after 3 h, viable and infectious virus was still present on treated smooth surfaces (glass and banknotes) after 2 days, on stainless steel and plastic after 4 days and on the hydrophobic outer layer of a surgical mask after 7 days 6 . Since this high surface stability increases the risk of smear infection, it would be highly beneficial if virus particles that reach vulnerable surfaces such as touch screens, doorknobs, ventilation filters, textiles, train seats or handrails could be inactivated immediately without further disinfection processes. The same applies also to virus particles deposited on facemasks, since inappropriate mask handling is a commonly faced problem. Therefore, the development of antiviral materials, coatings and facemasks is of tremendous importance not only to fight COVID-19, but also to prevent similar pandemic or epidemic outbreaks in the future. There are several ways to inactivate or even destroy viruses. The most known are detergents or ethanol solutions which disintegrate the lipid and protein structure of the virus 7 , 8 , 9 , 10 , radiation such as ultraviolet light with wavelength between 200 and 300 nm (UVC) 11 , 12 , 13 , thermal treatment like autoclaving 14 , 15 , oxidation 16 , 17 or high positive surface charge 18 , 19 . When new antiviral materials are developed, it is crucial to investigate and quantify their potential to trap, inactivate and/or kill the viruses. Currently, there are two ISO norms available, which regulate the measurement of antiviral activity on plastics and other non-porous surfaces (ISO 21702) and the determination of antiviral activity of textile products (ISO 18184). In both norms, the infectious virus titer needs to be determined by either a plaque assay or the Median Tissue Culture Infectious Dose (TCID 50 ) method. Both of these assays require working with the real infectious virus and are based on the principle that cytopathic effects caused by the virus can be visibly assessed in vitro. Although these assays deliver reliable and comparable results on the antiviral activity of the materials, they have several disadvantages: working with real viruses such as e.g. SARS-CoV-2 requires special infrastructure (e.g. biosafety level 3 equipped labs) and trained employees. This prevents the widespread use of these analyses in most industrial and research settings and consequently delays the rapid development of novel antiviral materials as observed during the current COVID-pandemic. Consequently, novel characterisation methods are urgently needed to facilitate the fast, cheap and safe pre-screening of a large number of materials and<|im_end|> <|im_start|>assistant Using a new analytical method, Empa researchers have tracked viruses as they pass through face masks and compared their failure on the filter layers of different types of masks. The new method should now accelerate the development of surfaces that can kill viruses, the team writes in the journal Scientific Reports. Using high pressure, the apparatus pushes artificial saliva fluid, colored in red, with test particles through a stretched mask. This is how the researchers simulate the process of a droplet infection. The new method established at Empa is currently used by certified test centers to ensure the quality of textile face masks because a safe and effective protective mask must meet demanding requirements: It must keep out germs, withstand splashing drops of saliva, and at the same time allow air to pass through. Now Empa researchers are going one step further: "Images taken using a transmission electron microscope show that a few virus particles manage to make their way into the innermost layer of the mask, close to the face. However, the images do not always reveal whether these viruses are still infectious," says Peter Wick of Empa's Particles-Biology Interactions lab in St. Gallen. The researchers' goal: They want to find out where exactly a virus particle is held back within a multilayer face mask during droplet infection, and which mask components should be more efficient. "We needed new analytical methods to precisely understand the protective function of newly developed technologies such as virus-killing coatings," says Empa researcher René Rossi of the Biomimetic Membranes and Textiles lab in St. Gallen. After all, this is precisely one of the goals of the ReMask project, in which research, industry and health care experts are teaming up with Empa in the fight against the pandemic to develop new concepts for better, more comfortable and more sustainable face masks. The new method is a fluorescent approach to detect viral disintegration caused by antiviral materials. Credit: Scientific Reports / Empa Dying beauty The new process relies on a dye, rhodamine R18, which emits colored light. Non-hazardous, inactivated test viruses are used, which are coupled to R18 and thus become dying beauties: They light up as soon as they are damaged. "The fluorescence indicates reliably, quickly and inexpensively when viruses have been killed," Wick says. Based on the intensity with which a mask layer glows, the team found that for fabric and hygiene masks, most viruses fail in the mid layer between the inner and outer layers of the mask. In FFP2 masks, the third of six layers glowed the most—again, the central layer trapped a particularly large number of viruses. These findings can now be used to optimize facial masks. In addition, the new process can accelerate the development of virus-killing surfaces. "Surfaces with antiviral properties must comply with certain ISO standards, which entail laborious standard tests," Wick explains. The Empa researchers' fluorescence method, on the other hand, could be a simpler, faster and more cost-effective way of determining whether a new type of coating can reliably kill viruses, as a supplement to current standards. This would be of interest both for smooth surfaces, such as on worktops or handles, and for coatings on textiles with a porous surface, such as masks or filter systems. And with the new method, this knowledge could already be integrated into the development process of technical and medical applications at a very early stage. According to Wick, this will speed up the introduction of new products, as only promising candidates will have to undergo the time-consuming and cost-intensive standardization tests. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 578, 20562, 4235, 777, 28522, 706, 9057, 24779, 2802, 15603, 304, 3276, 344, 37478, 27529, 11, 323, 1070, 706, 1027, 264, 22520, 5376, 304, 279, 3495, 323, 4500, 315, 18699, 3769, 6067, 311, 8108, 17188, 18874, 304, 279, 3347, 2478, 1667, 13, 578, 7327, 21021, 369, 12028, 2065, 320, 25141, 8, 40851, 220, 972, 11, 10336, 323, 220, 1691, 11, 20253, 527, 1403, 5410, 5528, 311, 70755, 279, 3276, 344, 37478, 6012, 315, 94761, 323, 2536, 2320, 20857, 27529, 13, 4452, 11, 2391, 279, 1566, 1667, 315, 279, 28522, 11, 264, 1205, 369, 10819, 323, 44252, 60993, 315, 3276, 344, 37478, 3769, 574, 11054, 13, 15636, 11, 264, 58535, 1749, 3196, 389, 459, 763, 31262, 65092, 744, 320, 644, 36644, 50, 8, 574, 8040, 311, 28696, 279, 4216, 51256, 4500, 315, 3276, 344, 37478, 14645, 323, 4367, 22156, 315, 279, 5788, 315, 3276, 344, 37478, 7384, 21676, 323, 30820, 13, 578, 763, 36644, 50, 374, 6799, 449, 264, 659, 74801, 268, 2454, 74864, 54631, 430, 19159, 264, 66303, 5376, 304, 97332, 994, 279, 29962, 35498, 834, 81829, 988, 13, 763, 279, 3118, 990, 11, 279, 27541, 315, 763, 36644, 50, 311, 29962, 834, 61268, 555, 3967, 3276, 344, 37478, 13307, 374, 21091, 323, 1202, 4754, 311, 70755, 11775, 7384, 323, 27529, 374, 36131, 13, 17830, 11, 279, 763, 36644, 50, 374, 1511, 311, 8417, 279, 25382, 315, 29962, 19252, 2949, 3547, 336, 4707, 13931, 11, 21568, 433, 459, 7185, 5507, 311, 1862, 279, 4500, 315, 3276, 344, 37478, 7479, 6067, 369, 11156, 323, 6593, 8522, 13, 29438, 3639, 3940, 439, 264, 26454, 323, 9987, 21271, 8624, 304, 37230, 10118, 304, 6790, 220, 679, 24, 706, 28995, 1139, 264, 6129, 28522, 4528, 311, 279, 330, 62897, 20236, 794, 20562, 12, 777, 13, 578, 8346, 374, 279, 13746, 46713, 263, 24713, 328, 17485, 87271, 53, 12, 17, 11, 902, 374, 8647, 369, 5370, 13803, 1778, 439, 37140, 315, 279, 28691, 323, 42631, 42929, 11, 40700, 287, 11, 2875, 2136, 315, 11745, 11, 36709, 11, 34653, 11, 856, 24823, 689, 11, 16898, 20526, 344, 20000, 11, 4814, 315, 22843, 323, 50160, 12945, 13, 763, 15748, 5157, 11, 433, 649, 3063, 311, 30883, 21271, 8060, 11, 7447, 12, 8629, 8060, 323, 4648, 220, 16, 662, 1666, 315, 5651, 220, 2366, 17, 11, 279, 1396, 315, 11007, 20562, 12, 777, 5157, 15603, 706, 8813, 220, 21618, 3610, 323, 279, 1396, 315, 16779, 706, 41482, 311, 927, 220, 21, 3610, 220, 17, 662, 10541, 7524, 40300, 323, 2731, 6514, 15174, 617, 1027, 8040, 304, 279, 33953, 11, 502, 7701, 89534, 34684, 323, 3428, 47165, 7969, 304, 8009, 5961, 3136, 311, 5457, 279, 2890, 2512, 6067, 311, 872, 13693, 13, 15636, 11, 2536, 63837, 2227, 26191, 39455, 1778, 439, 3729, 14278, 11, 53056, 323, 3547, 336, 4707, 7293, 3062, 311, 2567, 279, 54743, 315, 279, 17188, 520, 23542, 220, 18, 662, 578, 8244, 5915, 315, 1521, 11193, 374, 311, 6435, 1523, 8624, 18874, 1990, 1274, 13, 20562, 12, 777, 43653, 14918, 555, 42631, 7118, 90592, 4315, 1274, 889, 527, 304, 3345, 3729, 449, 1855, 1023, 220, 19, 662, 4452, 11, 1101, 1023, 24717, 315, 8624, 18874, 527, 1101, 3284, 13, 1789, 3187, 11, 49825, 337, 18874, 649, 12446, 55154, 304, 39313, 323, 31555, 71702, 660, 12908, 11, 323, 433, 374, 1101, 3284, 311, 2339, 20562, 12, 777, 46345, 1555, 31687, 27529, 477, 6302, 52673, 449, 279, 17188, 505, 29374, 1274, 11, 8272, 555, 31687, 279, 6548, 11, 19689, 477, 11013, 320, 69, 86903, 18874, 8, 220, 19, 662, 1102, 706, 1027, 6982, 430, 328, 17485, 87271, 53, 12, 17, 374, 15528, 505, 264, 2478, 4207, 311, 2919, 11911, 389, 279, 30903, 315, 279, 7479, 389, 902, 279, 17188, 374, 54568, 13, 1789, 3187, 11, 5355, 423, 13475, 36749, 1880, 453, 662, 21091, 430, 328, 17485, 87271, 53, 12, 17, 14958, 15528, 389, 12466, 323, 25468, 9699, 27529, 369, 3892, 4207, 13, 650, 2205, 17188, 1436, 387, 16914, 709, 311, 220, 5332, 305, 1306, 3851, 311, 1521, 27529, 11, 323, 279, 4376, 26928, 315, 328, 17485, 87271, 53, 12, 17, 574, 13240, 311, 387, 220, 20, 13, 21, 305, 389, 25468, 9699, 323, 311, 220, 21, 13, 23, 305, 389, 12466, 220, 20, 662, 763, 13168, 11, 912, 31528, 17188, 1436, 387, 16914, 389, 55043, 27529, 1306, 220, 1187, 305, 11, 323, 24166, 27529, 49890, 311, 304, 17281, 279, 17188, 2949, 220, 19, 4207, 220, 20, 662, 49335, 1880, 453, 662, 11007, 430, 328, 17485, 87271, 53, 12, 17, 374, 810, 15528, 389, 11113, 323, 17055, 764, 31906, 27529, 13, 6104, 912, 50600, 17188, 1436, 387, 26403, 505, 18991, 323, 20438, 7829, 16064, 1306, 220, 18, 305, 11, 31528, 323, 50600, 17188, 574, 2103, 3118, 389, 12020, 11113, 27529, 320, 59536, 323, 6201, 18790, 8, 1306, 220, 17, 2919, 11, 389, 25468, 9699, 323, 12466, 1306, 220, 19, 2919, 323, 389, 279, 17055, 764, 31906, 16335, 6324, 315, 264, 34933, 7056, 1306, 220, 22, 2919, 220, 21, 662, 8876, 420, 1579, 7479, 20334, 12992, 279, 5326, 315, 81603, 19405, 11, 433, 1053, 387, 7701, 24629, 422, 17188, 19252, 430, 5662, 20134, 27529, 1778, 439, 5916, 15670, 11, 656, 672, 77, 5598, 11, 56234, 13711, 11, 94082, 11, 5542, 16712, 477, 1450, 38445, 1436, 387, 304, 31262, 7214, 2085, 4726, 64842, 13421, 11618, 13, 578, 1890, 17208, 1101, 311, 17188, 19252, 54568, 389, 3547, 336, 4707, 11, 2533, 33781, 7056, 11850, 374, 264, 17037, 17011, 3575, 13, 15636, 11, 279, 4500, 315, 3276, 344, 37478, 7384, 11, 92025, 323, 3547, 336, 4707, 374, 315, 28040, 12939, 539, 1193, 311, 4465, 20562, 12, 777, 11, 719, 1101, 311, 5471, 4528, 28522, 477, 42620, 77871, 304, 279, 3938, 13, 2684, 527, 3892, 5627, 311, 304, 17281, 477, 1524, 7066, 42068, 13, 578, 1455, 3967, 527, 4130, 70, 812, 477, 62772, 10105, 902, 834, 396, 58117, 279, 68700, 323, 13128, 6070, 315, 279, 17188, 220, 22, 1174, 220, 23, 1174, 220, 24, 1174, 220, 605, 1174, 25407, 1778, 439, 37232, 85311, 3177, 449, 46406, 1990, 220, 1049, 323, 220, 3101, 26807, 320, 52, 11539, 8, 220, 806, 1174, 220, 717, 1174, 220, 1032, 1174, 29487, 6514, 1093, 57253, 75, 2370, 220, 975, 1174, 220, 868, 1174, 71162, 220, 845, 1174, 220, 1114, 477, 1579, 6928, 7479, 6900, 220, 972, 1174, 220, 777, 662, 3277, 502, 3276, 344, 37478, 7384, 527, 8040, 11, 433, 374, 16996, 311, 19874, 323, 76498, 872, 4754, 311, 23709, 11, 304, 17281, 323, 5255, 5622, 279, 42068, 13, 25122, 11, 1070, 527, 1403, 22705, 40851, 2561, 11, 902, 37377, 279, 19179, 315, 3276, 344, 37478, 5820, 389, 68386, 323, 1023, 2536, 2320, 20857, 27529, 320, 25141, 220, 13460, 2437, 8, 323, 279, 26314, 315, 3276, 344, 37478, 5820, 315, 66638, 3956, 320, 25141, 220, 10562, 5833, 570, 763, 2225, 40851, 11, 279, 50600, 17188, 259, 2058, 3966, 311, 387, 11075, 555, 3060, 264, 61464, 65033, 477, 279, 63690, 350, 11407, 21023, 88911, 1245, 423, 974, 320, 7905, 926, 220, 1135, 883, 1749, 13, 11995, 315, 1521, 99592, 1397, 3318, 449, 279, 1972, 50600, 17188, 323, 527, 3196, 389, 279, 17966, 430, 9693, 3565, 589, 292, 6372, 9057, 555, 279, 17188, 649, 387, 74106, 32448, 304, 55004, 13, 10541, 1521, 99592, 6493, 15062, 323, 30139, 3135, 389, 279, 3276, 344, 37478, 5820, 315, 279, 7384, 11, 814, 617, 3892, 64725, 25, 3318, 449, 1972, 42068, 1778, 439, 384, 1326, 13, 328, 17485, 87271, 53, 12, 17, 7612, 3361, 14054, 320, 68, 1326, 13, 49554, 39718, 2237, 220, 18, 19167, 51048, 8, 323, 16572, 8420, 13, 1115, 29034, 279, 24716, 1005, 315, 1521, 29060, 304, 1455, 13076, 323, 3495, 5110, 323, 52394, 32174, 279, 11295, 4500, 315, 11775, 3276, 344, 37478, 7384, 439, 13468, 2391, 279, 1510, 20562, 2320, 438, 8274, 13, 53123, 11, 11775, 3752, 8082, 5528, 527, 77720, 4460, 311, 28696, 279, 5043, 11, 12136, 323, 6220, 864, 30360, 287, 315, 264, 3544, 1396, 315, 7384, 323, 128257, 198, 128256, 78191, 198, 16834, 264, 502, 44064, 1749, 11, 13714, 64, 12074, 617, 34156, 42068, 439, 814, 1522, 1555, 3663, 27227, 323, 7863, 872, 8060, 389, 279, 4141, 13931, 315, 2204, 4595, 315, 27227, 13, 578, 502, 1749, 1288, 1457, 43880, 279, 4500, 315, 27529, 430, 649, 5622, 42068, 11, 279, 2128, 14238, 304, 279, 8486, 38130, 29140, 13, 12362, 1579, 7410, 11, 279, 41705, 41802, 21075, 85657, 15962, 11, 28296, 304, 2579, 11, 449, 1296, 19252, 1555, 264, 41398, 7056, 13, 1115, 374, 1268, 279, 12074, 38553, 279, 1920, 315, 264, 7118, 11053, 19405, 13, 578, 502, 1749, 9749, 520, 13714, 64, 374, 5131, 1511, 555, 23759, 1296, 19169, 311, 6106, 279, 4367, 315, 66638, 3663, 27227, 1606, 264, 6220, 323, 7524, 29219, 7056, 2011, 3449, 26192, 8670, 25, 1102, 2011, 2567, 704, 17684, 1026, 11, 51571, 12786, 19587, 21701, 315, 85657, 11, 323, 520, 279, 1890, 892, 2187, 3805, 311, 1522, 1555, 13, 4800, 13714, 64, 12074, 527, 2133, 832, 3094, 4726, 25, 330, 14562, 4529, 1701, 264, 18874, 17130, 73757, 1501, 430, 264, 2478, 17188, 19252, 10299, 311, 1304, 872, 1648, 1139, 279, 9358, 3646, 6324, 315, 279, 7056, 11, 3345, 311, 279, 3663, 13, 4452, 11, 279, 5448, 656, 539, 2744, 16805, 3508, 1521, 42068, 527, 2103, 50600, 1359, 2795, 11291, 75206, 315, 13714, 64, 596, 3744, 4440, 7826, 31226, 5783, 4109, 10278, 304, 800, 13, 25919, 268, 13, 578, 12074, 6, 5915, 25, 2435, 1390, 311, 1505, 704, 1405, 7041, 264, 17188, 19320, 374, 5762, 1203, 2949, 264, 2814, 321, 1155, 3663, 7056, 2391, 7118, 11053, 19405, 11, 323, 902, 7056, 6956, 1288, 387, 810, 11297, 13, 330, 1687, 4460, 502, 44064, 5528, 311, 24559, 3619, 279, 29219, 734, 315, 13945, 8040, 14645, 1778, 439, 17188, 12934, 9585, 92025, 1359, 2795, 13714, 64, 32185, 14094, 978, 77169, 315, 279, 91608, 318, 5411, 13862, 1347, 14997, 323, 2991, 3742, 10278, 304, 800, 13, 25919, 268, 13, 4740, 682, 11, 420, 374, 24559, 832, 315, 279, 9021, 315, 279, 1050, 12975, 2447, 11, 304, 902, 3495, 11, 5064, 323, 2890, 2512, 11909, 527, 2128, 287, 709, 449, 13714, 64, 304, 279, 4465, 2403, 279, 28522, 311, 2274, 502, 19476, 369, 2731, 11, 810, 10882, 323, 810, 22556, 3663, 27227, 13, 578, 502, 1749, 374, 264, 74864, 5603, 311, 11388, 29962, 834, 61268, 9057, 555, 3276, 344, 37478, 7384, 13, 16666, 25, 38130, 29140, 611, 13714, 64, 423, 7169, 13444, 578, 502, 1920, 34744, 389, 264, 54631, 11, 22408, 347, 20588, 432, 972, 11, 902, 73880, 28296, 3177, 13, 11842, 2902, 58757, 788, 11, 304, 31262, 1296, 42068, 527, 1511, 11, 902, 527, 34356, 311, 432, 972, 323, 8617, 3719, 23069, 5017, 552, 25, 2435, 3177, 709, 439, 5246, 439, 814, 527, 20727, 13, 330, 791, 97332, 15151, 57482, 11, 6288, 323, 34678, 28014, 994, 42068, 617, 1027, 7577, 1359, 75206, 2795, 13, 20817, 389, 279, 21261, 449, 902, 264, 7056, 6324, 2840, 4336, 11, 279, 2128, 1766, 430, 369, 13354, 323, 53056, 27227, 11, 1455, 42068, 3775, 304, 279, 5209, 6324, 1990, 279, 9358, 323, 16335, 13931, 315, 279, 7056, 13, 763, 435, 11960, 17, 27227, 11, 279, 4948, 315, 4848, 13931, 2840, 13111, 279, 1455, 2345, 33871, 11, 279, 8792, 6324, 31691, 264, 8104, 3544, 1396, 315, 42068, 13, 4314, 14955, 649, 1457, 387, 1511, 311, 30536, 28900, 27227, 13, 763, 5369, 11, 279, 502, 1920, 649, 43880, 279, 4500, 315, 17188, 12934, 9585, 27529, 13, 330, 23912, 7760, 449, 3276, 344, 37478, 6012, 2011, 26069, 449, 3738, 22705, 10886, 11, 902, 87092, 9511, 1245, 5410, 7177, 1359, 75206, 15100, 13, 578, 13714, 64, 12074, 6, 97332, 1749, 11, 389, 279, 1023, 1450, 11, 1436, 387, 264, 35388, 11, 10819, 323, 810, 2853, 53421, 1648, 315, 26679, 3508, 264, 502, 955, 315, 41394, 649, 57482, 5622, 42068, 11, 439, 264, 22822, 311, 1510, 10886, 13, 1115, 1053, 387, 315, 2802, 2225, 369, 11113, 27529, 11, 1778, 439, 389, 990, 3565, 82, 477, 13777, 11, 323, 369, 92025, 389, 94082, 449, 264, 94761, 7479, 11, 1778, 439, 27227, 477, 4141, 6067, 13, 1628, 449, 279, 502, 1749, 11, 420, 6677, 1436, 2736, 387, 18751, 1139, 279, 4500, 1920, 315, 11156, 323, 6593, 8522, 520, 264, 1633, 4216, 6566, 13, 10771, 311, 75206, 11, 420, 690, 4732, 709, 279, 17219, 315, 502, 3956, 11, 439, 1193, 26455, 11426, 690, 617, 311, 37771, 279, 892, 70840, 323, 2853, 88092, 5410, 2065, 7177, 13, 220, 128257, 198 ]

2,082

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract We are performing whole-genome sequencing of families with autism spectrum disorder (ASD) to build a resource (MSSNG) for subcategorizing the phenotypes and underlying genetic factors involved. Here we report sequencing of 5,205 samples from families with ASD, accompanied by clinical information, creating a database accessible on a cloud platform and through a controlled-access internet portal. We found an average of 73.8 de novo single nucleotide variants and 12.6 de novo insertions and deletions or copy number variations per ASD subject. We identified 18 new candidate ASD-risk genes and found that participants bearing mutations in susceptibility genes had significantly lower adaptive ability ( P = 6 × 10 −4 ). In 294 of 2,620 (11.2%) of ASD cases, a molecular basis could be determined and 7.2% of these carried copy number variations and/or chromosomal abnormalities, emphasizing the importance of detecting all forms of genetic variation as diagnostic and therapeutic targets in ASD. Main Autism is a term coined about a century ago, derived from the Greek root referring to 'self', and describes a wide range of human interpersonal behaviors 1 . Autistic tendencies may be recognized in many individuals as part of human variation 2 , but these features can be severe and therefore disabling 3 , 4 , 5 . The most recent Diagnostic and Statistical Manual of Mental Disorders , the fifth edition (DSM-5), uses the single omnibus classification 'autism spectrum disorder' (ASD) to encompass what once were considered several distinct diagnostic entities (such as autistic disorder, Asperger's disorder and pervasive developmental disorder not otherwise specified). The spectrum concept reflects both the diversity among individuals in severity of symptoms, from mild to severe, and the recognition of overlap among a collection of clinically described disorders 6 , 7 , 8 . Features of this neurodevelopmental disorder, which has a worldwide population prevalence of ∼ 1%, typically include impaired communication and social interaction, repetitive behaviors and restricted interests; these may also be associated with psychiatric, neurological or physical comorbidities and/or intellectual disability. Despite the unitary diagnostic classification, ASD is a heterogeneous spectrum, both in clinical presentation and in terms of the underlying etiology. Individuals with ASD are increasingly seen in clinical genetics services, and ∼ 10% have an identifiable genetic condition 4 , 9 . In fact, there are over 100 genetic disorders that can exhibit features of ASD (for example, Rett and Fragile X syndromes) 10 . Clearly, ASD is strongly associated with genetic factors. Dozens of susceptibility genes (for example, SHANK - and NRXN -family genes) 11 , 12 and copy number variation (CNV) loci (for example, 16p11.2 deletion and 15q11-q13 duplication) facilitate a molecular diagnosis in ∼ 5–40% of ASD cases. The variation largely depends on the cohort examined (for example, syndromic or idiopathic) and the technology used (i.e., karyotyping, microarray, whole-exome sequencing) 5 , 9 , 13 , 14 , 15 , 16 , 17 . In fact, the genetic predisposition toward ASD may be different for almost every individual 18 , making this a prime candidate for the coming age of precision medicine 6 , 7 , 19 . The first beneficiaries of a genetic diagnosis are young children, in whom formal diagnosis based on early developmental signs can be challenging but who benefit most from earlier behavioral intervention 3 , 8 . Understanding the genetic subtypes of ASD can also potentially inform prognosis, medical management and assessment of familial recurrence risk, and in the future, it may facilitate pharmacologic-intervention trials through stratification based on pathway profiles 14 . The vast heterogeneity also means that meticulous approaches are needed to catalog all the genetic factors that contribute to the phenotype and to consider how these interact with one another and with nongenomic elements. To move forward toward the goal of understanding all of the genetic factors involved in ASD, we recognize the need to scan the genome in its entirety using whole genome sequencing (WGS) 14 , 18 , 20 , 21 on thousands of samples, if not tens of thousands (or more) 13 , 22 , 23 , 24 . Risk variants that remain undiscovered to this point are expected to be individually rare 9 , 18 , 22 , possibly involved in complex combinations 18 , 25 and include single nucleotide variants (SNVs), small insertions and deletions (indels), more complex CNVs 14 , 18 , 20 and other structural alterations 15 , 26 . Some will reside in the ∼ 98% noncoding genome largely unexplored by other microarray and exome sequencing studies 21 , 27 , 28 . Abundant genome sequences may help to resolve the role of common variants in ASD 2 , 29 , and integrating these data with those on rare variants will aid understanding of the issues of penetrance, variable expressivity and pleiotropic effects 4 , 6 . Such research brings us to the realm of 'big data': massive sequence datasets from multitudes of individuals, requiring fast and intensive searches for meaningful patterns 30 . This is where cloud-based computing excels. Its capacity for bulk data storage, with efficient processing and built-in security, is ushering in a new model for data sharing, enabling access and collaboration across continents 31 , 32 . In our MSSNG initiative (where omission of letters from the name represents the information about autism that is missing and yet to be uncovered), we are collecting whole genome sequences and detailed phenotypic information from individuals with ASD and their families and making these data widely available to the research community ( Fig. 1 ). Here we describe the MSSNG infrastructure, new analyses of the first 5,205 genomes and examples of how to use the resource. Figure 1: Schematic of sample and data processing in MSSNG. An executive committee oversees the project. The parameters for DNA sample selection and (genetic and phenotypic) data are managed by the committee, including consenting and ethics protocols. Coded identifiers for samples selected for WGS are posted as they are identified at MSSNG portal ( ), so the ASD research community", "role": "user" }, { "content": "The newest study from the Autism Speaks MSSNG project - the world's largest autism genome sequencing program - identified an additional 18 gene variations that appear to increase the risk of autism. The new report appears this week in the journal Nature Neuroscience. It involved the analysis of 5,205 whole genomes from families affected by autism - making it the largest whole genome study of autism to date. The omitted letters in MSSNG (pronounced 'missing') represent the missing information about autism that the research program seeks to deliver. \"It's noteworthy that we're still finding new autism genes, let alone 18 of them, after a decade of intense focus,\" says study co-author Mathew Pletcher, Ph.D., Autism Speaks' vice president for genomic discovery. \"With each new gene discovery, we're able to explain more cases of autism, each with its own set of behavioral effects and many with associated medical concerns.\" To date, research using the MSSNG genomic database has identified 61 genetic variations that affect autism risk. The research has associated several of these with additional medical conditions that often accompany autism. The goal, Dr. Pletcher says, \"is to advance personalized treatments for autism by deepening our understanding of the condition's many subtypes.\" The findings also illustrate how whole genome sequencing can guide medical care today. For example, at least two of the autism-associated gene changes described in the paper were associated with increased risk for seizures. Another has been linked to increased risk for cardiac defects, and yet another with adult diabetes. The findings illustrate how whole genome sequencing for autism can provide additional medical guidance to individuals, families and their physicians, the investigators say. The researchers also determined that many of the 18 newly identified autism genes affect the operation of a small subset of biological pathways in the brain. All of these pathways affect how brain cells develop and communicate with each other. \"In all, 80 percent of the 61 gene variations discovered through MSSNG affect biochemical pathways that have clear potential as targets for future medicines,\" Dr. Pletcher says. Increasingly, autism researchers are predicting that personalized, more effective treatments will come from understanding these common brain pathways - and how different gene variations alter them. \"The unprecedented MSSNG database is enabling research into the many 'autisms' that make up the autism spectrum,\" says the study's senior investigator, Stephen Scherer, Ph.D. For instance, some of the genetic alterations found in the study occurred in families with one person severely affected by autism and others on the milder end of the spectrum, Dr. Scherer notes. \"This reinforces the significant neurodiversity involved in this complex condition,\" he explains. \"In addition, the depth of the MSSNG database allowed us to identify resilient individuals who carry autism-associated gene variations without developing autism. We believe that this, too, is an important part of the neurodiversity story.\" Dr. Scherer is the research director for the MSSNG project and directs The Centre for Applied Genomics at the Hospital for Sick Children (SickKids), in Toronto. MSSNG is a collaboration between the hospital, Autism Speaks and Verily (formerly Google Life Sciences), which hosts the MSSNG database on its cloud platform. Traditional genetic analysis looks for mutations, or \"spelling changes,\" in the 1 percent of our DNA that spells out our genes. By contrast, the MSSNG database allows researchers to analyze the entire 3 billion DNA base pairs that make up each person's genome. In their new study, the investigators went even further - looking beyond DNA \"spelling\" variations to find other types of genetic changes associated with autism. These included copy number variations (repeated or deleted stretches of DNA) and chromosomal abnormalities. Chromosomes are the threadlike cell structures that package and organize our genes. The researchers found copy number variations and chromosomal abnormalities to be particularly common in the genomes of people affected by autism. In addition, many of the copy number variations turned up in areas of the genome once considered \"junk DNA.\" Though this genetic \"dark matter\" exists outside of our genes, scientists now appreciate that it helps control when and where our genes switch on and off. The precise coordination of genetic activity appears to be particularly crucial to brain development and function. Through its research platform on the Google Cloud, Autism Speaks is making all of MSSNG's fully sequenced genomes directly available to researchers free of charge, along with analytic tools. In the coming weeks, the MSSNG team will be uploading an additional 2,000 fully sequenced autism genomes, bringing the total over 7,000. Currently, more than 90 investigators at 40 academic and medical institutions are using the MSSNG database to advance autism research around the world. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract We are performing whole-genome sequencing of families with autism spectrum disorder (ASD) to build a resource (MSSNG) for subcategorizing the phenotypes and underlying genetic factors involved. Here we report sequencing of 5,205 samples from families with ASD, accompanied by clinical information, creating a database accessible on a cloud platform and through a controlled-access internet portal. We found an average of 73.8 de novo single nucleotide variants and 12.6 de novo insertions and deletions or copy number variations per ASD subject. We identified 18 new candidate ASD-risk genes and found that participants bearing mutations in susceptibility genes had significantly lower adaptive ability ( P = 6 × 10 −4 ). In 294 of 2,620 (11.2%) of ASD cases, a molecular basis could be determined and 7.2% of these carried copy number variations and/or chromosomal abnormalities, emphasizing the importance of detecting all forms of genetic variation as diagnostic and therapeutic targets in ASD. Main Autism is a term coined about a century ago, derived from the Greek root referring to 'self', and describes a wide range of human interpersonal behaviors 1 . Autistic tendencies may be recognized in many individuals as part of human variation 2 , but these features can be severe and therefore disabling 3 , 4 , 5 . The most recent Diagnostic and Statistical Manual of Mental Disorders , the fifth edition (DSM-5), uses the single omnibus classification 'autism spectrum disorder' (ASD) to encompass what once were considered several distinct diagnostic entities (such as autistic disorder, Asperger's disorder and pervasive developmental disorder not otherwise specified). The spectrum concept reflects both the diversity among individuals in severity of symptoms, from mild to severe, and the recognition of overlap among a collection of clinically described disorders 6 , 7 , 8 . Features of this neurodevelopmental disorder, which has a worldwide population prevalence of ∼ 1%, typically include impaired communication and social interaction, repetitive behaviors and restricted interests; these may also be associated with psychiatric, neurological or physical comorbidities and/or intellectual disability. Despite the unitary diagnostic classification, ASD is a heterogeneous spectrum, both in clinical presentation and in terms of the underlying etiology. Individuals with ASD are increasingly seen in clinical genetics services, and ∼ 10% have an identifiable genetic condition 4 , 9 . In fact, there are over 100 genetic disorders that can exhibit features of ASD (for example, Rett and Fragile X syndromes) 10 . Clearly, ASD is strongly associated with genetic factors. Dozens of susceptibility genes (for example, SHANK - and NRXN -family genes) 11 , 12 and copy number variation (CNV) loci (for example, 16p11.2 deletion and 15q11-q13 duplication) facilitate a molecular diagnosis in ∼ 5–40% of ASD cases. The variation largely depends on the cohort examined (for example, syndromic or idiopathic) and the technology used (i.e., karyotyping, microarray, whole-exome sequencing) 5 , 9 , 13 , 14 , 15 , 16 , 17 . In fact, the genetic predisposition toward ASD may be different for almost every individual 18 , making this a prime candidate for the coming age of precision medicine 6 , 7 , 19 . The first beneficiaries of a genetic diagnosis are young children, in whom formal diagnosis based on early developmental signs can be challenging but who benefit most from earlier behavioral intervention 3 , 8 . Understanding the genetic subtypes of ASD can also potentially inform prognosis, medical management and assessment of familial recurrence risk, and in the future, it may facilitate pharmacologic-intervention trials through stratification based on pathway profiles 14 . The vast heterogeneity also means that meticulous approaches are needed to catalog all the genetic factors that contribute to the phenotype and to consider how these interact with one another and with nongenomic elements. To move forward toward the goal of understanding all of the genetic factors involved in ASD, we recognize the need to scan the genome in its entirety using whole genome sequencing (WGS) 14 , 18 , 20 , 21 on thousands of samples, if not tens of thousands (or more) 13 , 22 , 23 , 24 . Risk variants that remain undiscovered to this point are expected to be individually rare 9 , 18 , 22 , possibly involved in complex combinations 18 , 25 and include single nucleotide variants (SNVs), small insertions and deletions (indels), more complex CNVs 14 , 18 , 20 and other structural alterations 15 , 26 . Some will reside in the ∼ 98% noncoding genome largely unexplored by other microarray and exome sequencing studies 21 , 27 , 28 . Abundant genome sequences may help to resolve the role of common variants in ASD 2 , 29 , and integrating these data with those on rare variants will aid understanding of the issues of penetrance, variable expressivity and pleiotropic effects 4 , 6 . Such research brings us to the realm of 'big data': massive sequence datasets from multitudes of individuals, requiring fast and intensive searches for meaningful patterns 30 . This is where cloud-based computing excels. Its capacity for bulk data storage, with efficient processing and built-in security, is ushering in a new model for data sharing, enabling access and collaboration across continents 31 , 32 . In our MSSNG initiative (where omission of letters from the name represents the information about autism that is missing and yet to be uncovered), we are collecting whole genome sequences and detailed phenotypic information from individuals with ASD and their families and making these data widely available to the research community ( Fig. 1 ). Here we describe the MSSNG infrastructure, new analyses of the first 5,205 genomes and examples of how to use the resource. Figure 1: Schematic of sample and data processing in MSSNG. An executive committee oversees the project. The parameters for DNA sample selection and (genetic and phenotypic) data are managed by the committee, including consenting and ethics protocols. Coded identifiers for samples selected for WGS are posted as they are identified at MSSNG portal ( ), so the ASD research community<|im_end|> <|im_start|>assistant The newest study from the Autism Speaks MSSNG project - the world's largest autism genome sequencing program - identified an additional 18 gene variations that appear to increase the risk of autism. The new report appears this week in the journal Nature Neuroscience. It involved the analysis of 5,205 whole genomes from families affected by autism - making it the largest whole genome study of autism to date. The omitted letters in MSSNG (pronounced 'missing') represent the missing information about autism that the research program seeks to deliver. "It's noteworthy that we're still finding new autism genes, let alone 18 of them, after a decade of intense focus," says study co-author Mathew Pletcher, Ph.D., Autism Speaks' vice president for genomic discovery. "With each new gene discovery, we're able to explain more cases of autism, each with its own set of behavioral effects and many with associated medical concerns." To date, research using the MSSNG genomic database has identified 61 genetic variations that affect autism risk. The research has associated several of these with additional medical conditions that often accompany autism. The goal, Dr. Pletcher says, "is to advance personalized treatments for autism by deepening our understanding of the condition's many subtypes." The findings also illustrate how whole genome sequencing can guide medical care today. For example, at least two of the autism-associated gene changes described in the paper were associated with increased risk for seizures. Another has been linked to increased risk for cardiac defects, and yet another with adult diabetes. The findings illustrate how whole genome sequencing for autism can provide additional medical guidance to individuals, families and their physicians, the investigators say. The researchers also determined that many of the 18 newly identified autism genes affect the operation of a small subset of biological pathways in the brain. All of these pathways affect how brain cells develop and communicate with each other. "In all, 80 percent of the 61 gene variations discovered through MSSNG affect biochemical pathways that have clear potential as targets for future medicines," Dr. Pletcher says. Increasingly, autism researchers are predicting that personalized, more effective treatments will come from understanding these common brain pathways - and how different gene variations alter them. "The unprecedented MSSNG database is enabling research into the many 'autisms' that make up the autism spectrum," says the study's senior investigator, Stephen Scherer, Ph.D. For instance, some of the genetic alterations found in the study occurred in families with one person severely affected by autism and others on the milder end of the spectrum, Dr. Scherer notes. "This reinforces the significant neurodiversity involved in this complex condition," he explains. "In addition, the depth of the MSSNG database allowed us to identify resilient individuals who carry autism-associated gene variations without developing autism. We believe that this, too, is an important part of the neurodiversity story." Dr. Scherer is the research director for the MSSNG project and directs The Centre for Applied Genomics at the Hospital for Sick Children (SickKids), in Toronto. MSSNG is a collaboration between the hospital, Autism Speaks and Verily (formerly Google Life Sciences), which hosts the MSSNG database on its cloud platform. Traditional genetic analysis looks for mutations, or "spelling changes," in the 1 percent of our DNA that spells out our genes. By contrast, the MSSNG database allows researchers to analyze the entire 3 billion DNA base pairs that make up each person's genome. In their new study, the investigators went even further - looking beyond DNA "spelling" variations to find other types of genetic changes associated with autism. These included copy number variations (repeated or deleted stretches of DNA) and chromosomal abnormalities. Chromosomes are the threadlike cell structures that package and organize our genes. The researchers found copy number variations and chromosomal abnormalities to be particularly common in the genomes of people affected by autism. In addition, many of the copy number variations turned up in areas of the genome once considered "junk DNA." Though this genetic "dark matter" exists outside of our genes, scientists now appreciate that it helps control when and where our genes switch on and off. The precise coordination of genetic activity appears to be particularly crucial to brain development and function. Through its research platform on the Google Cloud, Autism Speaks is making all of MSSNG's fully sequenced genomes directly available to researchers free of charge, along with analytic tools. In the coming weeks, the MSSNG team will be uploading an additional 2,000 fully sequenced autism genomes, bringing the total over 7,000. Currently, more than 90 investigators at 40 academic and medical institutions are using the MSSNG database to advance autism research around the world. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 1226, 527, 16785, 4459, 37564, 638, 62119, 315, 8689, 449, 38281, 20326, 19823, 320, 1950, 35, 8, 311, 1977, 264, 5211, 320, 44, 1242, 6269, 8, 369, 1207, 66, 7747, 4954, 279, 14345, 22583, 323, 16940, 19465, 9547, 6532, 13, 5810, 584, 1934, 62119, 315, 220, 20, 11, 10866, 10688, 505, 8689, 449, 78294, 11, 24895, 555, 14830, 2038, 11, 6968, 264, 4729, 15987, 389, 264, 9624, 5452, 323, 1555, 264, 14400, 43256, 7757, 24007, 13, 1226, 1766, 459, 5578, 315, 220, 5958, 13, 23, 409, 39423, 3254, 31484, 69044, 27103, 323, 220, 717, 13, 21, 409, 39423, 5774, 919, 323, 19825, 919, 477, 3048, 1396, 27339, 824, 78294, 3917, 13, 1226, 11054, 220, 972, 502, 9322, 78294, 46570, 21389, 323, 1766, 430, 13324, 18534, 34684, 304, 88636, 21389, 1047, 12207, 4827, 48232, 5845, 320, 393, 284, 220, 21, 25800, 220, 605, 25173, 19, 7609, 763, 220, 17168, 315, 220, 17, 11, 17416, 320, 806, 13, 17, 11587, 315, 78294, 5157, 11, 264, 31206, 8197, 1436, 387, 11075, 323, 220, 22, 13, 17, 4, 315, 1521, 11953, 3048, 1396, 27339, 323, 5255, 22083, 96108, 75815, 11, 82003, 279, 12939, 315, 54626, 682, 7739, 315, 19465, 23851, 439, 15439, 323, 37471, 11811, 304, 78294, 13, 4802, 78763, 374, 264, 4751, 78718, 922, 264, 9478, 4227, 11, 14592, 505, 279, 18341, 3789, 22797, 311, 364, 726, 518, 323, 16964, 264, 7029, 2134, 315, 3823, 74958, 28198, 220, 16, 662, 9648, 4633, 61555, 1253, 387, 15324, 304, 1690, 7931, 439, 961, 315, 3823, 23851, 220, 17, 1174, 719, 1521, 4519, 649, 387, 15748, 323, 9093, 61584, 220, 18, 1174, 220, 19, 1174, 220, 20, 662, 578, 1455, 3293, 51088, 323, 66794, 14881, 315, 38895, 73133, 1174, 279, 18172, 14002, 320, 6061, 44, 12, 20, 705, 5829, 279, 3254, 50197, 34495, 24790, 364, 2784, 2191, 20326, 19823, 6, 320, 1950, 35, 8, 311, 38632, 1148, 3131, 1051, 6646, 3892, 12742, 15439, 15086, 320, 21470, 439, 81391, 19823, 11, 1666, 716, 1414, 596, 19823, 323, 71867, 48006, 19823, 539, 6062, 5300, 570, 578, 20326, 7434, 27053, 2225, 279, 20057, 4315, 7931, 304, 31020, 315, 13803, 11, 505, 23900, 311, 15748, 11, 323, 279, 18324, 315, 28347, 4315, 264, 4526, 315, 70432, 7633, 24673, 220, 21, 1174, 220, 22, 1174, 220, 23, 662, 20289, 315, 420, 18247, 30671, 278, 19823, 11, 902, 706, 264, 15603, 7187, 38009, 315, 12264, 120, 220, 16, 13689, 11383, 2997, 50160, 10758, 323, 3674, 16628, 11, 59177, 28198, 323, 22486, 12034, 26, 1521, 1253, 1101, 387, 5938, 449, 47657, 11, 64908, 477, 7106, 470, 269, 21301, 1385, 323, 5255, 20207, 28353, 13, 18185, 279, 5089, 661, 15439, 24790, 11, 78294, 374, 264, 98882, 20326, 11, 2225, 304, 14830, 15864, 323, 304, 3878, 315, 279, 16940, 1880, 31226, 13, 62525, 449, 78294, 527, 15098, 3970, 304, 14830, 56104, 3600, 11, 323, 12264, 120, 220, 605, 4, 617, 459, 72450, 19465, 3044, 220, 19, 1174, 220, 24, 662, 763, 2144, 11, 1070, 527, 927, 220, 1041, 19465, 24673, 430, 649, 31324, 4519, 315, 78294, 320, 2000, 3187, 11, 432, 7211, 323, 59189, 458, 1630, 22013, 442, 288, 8, 220, 605, 662, 54504, 11, 78294, 374, 16917, 5938, 449, 19465, 9547, 13, 3234, 19059, 315, 88636, 21389, 320, 2000, 3187, 11, 6570, 16395, 482, 323, 40395, 55, 45, 482, 19521, 21389, 8, 220, 806, 1174, 220, 717, 323, 3048, 1396, 23851, 320, 29768, 53, 8, 1353, 72, 320, 2000, 3187, 11, 220, 845, 79, 806, 13, 17, 37166, 323, 220, 868, 80, 806, 52708, 1032, 67633, 8, 28696, 264, 31206, 23842, 304, 12264, 120, 220, 20, 4235, 1272, 4, 315, 78294, 5157, 13, 578, 23851, 14090, 14117, 389, 279, 41944, 25078, 320, 2000, 3187, 11, 22013, 442, 292, 477, 41760, 62209, 8, 323, 279, 5557, 1511, 320, 72, 1770, 2637, 597, 661, 67247, 11, 8162, 1686, 11, 4459, 10397, 638, 62119, 8, 220, 20, 1174, 220, 24, 1174, 220, 1032, 1174, 220, 975, 1174, 220, 868, 1174, 220, 845, 1174, 220, 1114, 662, 763, 2144, 11, 279, 19465, 80632, 3571, 9017, 78294, 1253, 387, 2204, 369, 4661, 1475, 3927, 220, 972, 1174, 3339, 420, 264, 10461, 9322, 369, 279, 5108, 4325, 315, 16437, 16088, 220, 21, 1174, 220, 22, 1174, 220, 777, 662, 578, 1176, 61668, 315, 264, 19465, 23842, 527, 3995, 2911, 11, 304, 8884, 16287, 23842, 3196, 389, 4216, 48006, 12195, 649, 387, 17436, 719, 889, 8935, 1455, 505, 6931, 36695, 21623, 220, 18, 1174, 220, 23, 662, 46551, 279, 19465, 1207, 9426, 315, 78294, 649, 1101, 13893, 6179, 95350, 11, 6593, 6373, 323, 15813, 315, 98304, 76293, 5326, 11, 323, 304, 279, 3938, 11, 433, 1253, 28696, 36449, 39227, 20653, 47698, 19622, 1555, 44397, 2461, 3196, 389, 38970, 21542, 220, 975, 662, 578, 13057, 30548, 76730, 1101, 3445, 430, 96278, 20414, 527, 4460, 311, 16808, 682, 279, 19465, 9547, 430, 17210, 311, 279, 82423, 323, 311, 2980, 1268, 1521, 16681, 449, 832, 2500, 323, 449, 308, 647, 268, 3151, 5540, 13, 2057, 3351, 4741, 9017, 279, 5915, 315, 8830, 682, 315, 279, 19465, 9547, 6532, 304, 78294, 11, 584, 15641, 279, 1205, 311, 8737, 279, 33869, 304, 1202, 49017, 1701, 4459, 33869, 62119, 320, 54, 16929, 8, 220, 975, 1174, 220, 972, 1174, 220, 508, 1174, 220, 1691, 389, 9214, 315, 10688, 11, 422, 539, 22781, 315, 9214, 320, 269, 810, 8, 220, 1032, 1174, 220, 1313, 1174, 220, 1419, 1174, 220, 1187, 662, 32388, 27103, 430, 7293, 82037, 21468, 311, 420, 1486, 527, 3685, 311, 387, 32399, 9024, 220, 24, 1174, 220, 972, 1174, 220, 1313, 1174, 11000, 6532, 304, 6485, 28559, 220, 972, 1174, 220, 914, 323, 2997, 3254, 31484, 69044, 27103, 320, 19503, 52837, 705, 2678, 5774, 919, 323, 19825, 919, 320, 485, 2053, 705, 810, 6485, 25914, 52837, 220, 975, 1174, 220, 972, 1174, 220, 508, 323, 1023, 24693, 61086, 220, 868, 1174, 220, 1627, 662, 4427, 690, 48383, 304, 279, 12264, 120, 220, 3264, 4, 2536, 49467, 33869, 14090, 653, 69331, 1171, 555, 1023, 8162, 1686, 323, 506, 638, 62119, 7978, 220, 1691, 1174, 220, 1544, 1174, 220, 1591, 662, 3765, 1263, 519, 33869, 24630, 1253, 1520, 311, 9006, 279, 3560, 315, 4279, 27103, 304, 78294, 220, 17, 1174, 220, 1682, 1174, 323, 54952, 1521, 828, 449, 1884, 389, 9024, 27103, 690, 12576, 8830, 315, 279, 4819, 315, 44805, 685, 11, 3977, 3237, 1968, 323, 7245, 11345, 45036, 6372, 220, 19, 1174, 220, 21, 662, 15483, 3495, 12716, 603, 311, 279, 22651, 315, 364, 16548, 828, 1232, 11191, 8668, 30525, 505, 2814, 21237, 315, 7931, 11, 23537, 5043, 323, 37295, 27573, 369, 23222, 12912, 220, 966, 662, 1115, 374, 1405, 9624, 6108, 25213, 3521, 2053, 13, 11699, 8824, 369, 20155, 828, 5942, 11, 449, 11297, 8863, 323, 5918, 3502, 4868, 11, 374, 64260, 287, 304, 264, 502, 1646, 369, 828, 11821, 11, 28462, 2680, 323, 20632, 4028, 66959, 220, 2148, 1174, 220, 843, 662, 763, 1057, 92749, 6269, 20770, 320, 2940, 84218, 315, 12197, 505, 279, 836, 11105, 279, 2038, 922, 38281, 430, 374, 7554, 323, 3686, 311, 387, 43522, 705, 584, 527, 26984, 4459, 33869, 24630, 323, 11944, 14345, 37941, 292, 2038, 505, 7931, 449, 78294, 323, 872, 8689, 323, 3339, 1521, 828, 13882, 2561, 311, 279, 3495, 4029, 320, 23966, 13, 220, 16, 7609, 5810, 584, 7664, 279, 92749, 6269, 14054, 11, 502, 29060, 315, 279, 1176, 220, 20, 11, 10866, 85381, 323, 10507, 315, 1268, 311, 1005, 279, 5211, 13, 19575, 220, 16, 25, 328, 82149, 315, 6205, 323, 828, 8863, 304, 92749, 6269, 13, 1556, 11145, 13093, 71945, 279, 2447, 13, 578, 5137, 369, 15922, 6205, 6727, 323, 320, 4469, 5411, 323, 14345, 37941, 292, 8, 828, 527, 9152, 555, 279, 13093, 11, 2737, 93501, 323, 32008, 32885, 13, 356, 6879, 48316, 369, 10688, 4183, 369, 468, 16929, 527, 8621, 439, 814, 527, 11054, 520, 92749, 6269, 24007, 320, 7026, 779, 279, 78294, 3495, 4029, 128257, 198, 128256, 78191, 198, 791, 24519, 4007, 505, 279, 78763, 12587, 10011, 92749, 6269, 2447, 482, 279, 1917, 596, 7928, 38281, 33869, 62119, 2068, 482, 11054, 459, 5217, 220, 972, 15207, 27339, 430, 5101, 311, 5376, 279, 5326, 315, 38281, 13, 578, 502, 1934, 8111, 420, 2046, 304, 279, 8486, 22037, 85879, 13, 1102, 6532, 279, 6492, 315, 220, 20, 11, 10866, 4459, 85381, 505, 8689, 11754, 555, 38281, 482, 3339, 433, 279, 7928, 4459, 33869, 4007, 315, 38281, 311, 2457, 13, 578, 40542, 12197, 304, 92749, 6269, 320, 72239, 20018, 364, 31716, 873, 4097, 279, 7554, 2038, 922, 38281, 430, 279, 3495, 2068, 26737, 311, 6493, 13, 330, 2181, 596, 67479, 430, 584, 2351, 2103, 9455, 502, 38281, 21389, 11, 1095, 7636, 220, 972, 315, 1124, 11, 1306, 264, 13515, 315, 19428, 5357, 1359, 2795, 4007, 1080, 43802, 4242, 365, 393, 61620, 11, 2405, 920, 2637, 78763, 12587, 10011, 6, 17192, 4872, 369, 81064, 18841, 13, 330, 2409, 1855, 502, 15207, 18841, 11, 584, 2351, 3025, 311, 10552, 810, 5157, 315, 38281, 11, 1855, 449, 1202, 1866, 743, 315, 36695, 6372, 323, 1690, 449, 5938, 6593, 10742, 1210, 2057, 2457, 11, 3495, 1701, 279, 92749, 6269, 81064, 4729, 706, 11054, 220, 5547, 19465, 27339, 430, 7958, 38281, 5326, 13, 578, 3495, 706, 5938, 3892, 315, 1521, 449, 5217, 6593, 4787, 430, 3629, 19780, 38281, 13, 578, 5915, 11, 2999, 13, 393, 61620, 2795, 11, 330, 285, 311, 12178, 35649, 22972, 369, 38281, 555, 5655, 6147, 1057, 8830, 315, 279, 3044, 596, 1690, 1207, 9426, 1210, 578, 14955, 1101, 41468, 1268, 4459, 33869, 62119, 649, 8641, 6593, 2512, 3432, 13, 1789, 3187, 11, 520, 3325, 1403, 315, 279, 38281, 75968, 15207, 4442, 7633, 304, 279, 5684, 1051, 5938, 449, 7319, 5326, 369, 55998, 13, 13596, 706, 1027, 10815, 311, 7319, 5326, 369, 47345, 42655, 11, 323, 3686, 2500, 449, 6822, 20335, 13, 578, 14955, 41468, 1268, 4459, 33869, 62119, 369, 38281, 649, 3493, 5217, 6593, 19351, 311, 7931, 11, 8689, 323, 872, 35944, 11, 279, 26453, 2019, 13, 578, 12074, 1101, 11075, 430, 1690, 315, 279, 220, 972, 13945, 11054, 38281, 21389, 7958, 279, 5784, 315, 264, 2678, 27084, 315, 24156, 44014, 304, 279, 8271, 13, 2052, 315, 1521, 44014, 7958, 1268, 8271, 7917, 2274, 323, 19570, 449, 1855, 1023, 13, 330, 644, 682, 11, 220, 1490, 3346, 315, 279, 220, 5547, 15207, 27339, 11352, 1555, 92749, 6269, 7958, 93532, 44014, 430, 617, 2867, 4754, 439, 11811, 369, 3938, 39653, 1359, 2999, 13, 393, 61620, 2795, 13, 74540, 398, 11, 38281, 12074, 527, 52997, 430, 35649, 11, 810, 7524, 22972, 690, 2586, 505, 8830, 1521, 4279, 8271, 44014, 482, 323, 1268, 2204, 15207, 27339, 11857, 1124, 13, 330, 791, 31069, 92749, 6269, 4729, 374, 28462, 3495, 1139, 279, 1690, 364, 2784, 13978, 6, 430, 1304, 709, 279, 38281, 20326, 1359, 2795, 279, 4007, 596, 10195, 49581, 11, 18587, 5124, 91117, 11, 2405, 920, 13, 1789, 2937, 11, 1063, 315, 279, 19465, 61086, 1766, 304, 279, 4007, 10222, 304, 8689, 449, 832, 1732, 35906, 11754, 555, 38281, 323, 3885, 389, 279, 296, 21439, 842, 315, 279, 20326, 11, 2999, 13, 5124, 91117, 8554, 13, 330, 2028, 95593, 279, 5199, 18247, 614, 388, 488, 6532, 304, 420, 6485, 3044, 1359, 568, 15100, 13, 330, 644, 5369, 11, 279, 8149, 315, 279, 92749, 6269, 4729, 5535, 603, 311, 10765, 59780, 7931, 889, 6920, 38281, 75968, 15207, 27339, 2085, 11469, 38281, 13, 1226, 4510, 430, 420, 11, 2288, 11, 374, 459, 3062, 961, 315, 279, 18247, 614, 388, 488, 3446, 1210, 2999, 13, 5124, 91117, 374, 279, 3495, 7690, 369, 279, 92749, 6269, 2447, 323, 67146, 578, 14821, 369, 43608, 9500, 24203, 520, 279, 15429, 369, 82411, 15394, 320, 50, 875, 70533, 705, 304, 14974, 13, 92749, 6269, 374, 264, 20632, 1990, 279, 8952, 11, 78763, 12587, 10011, 323, 6383, 1570, 320, 70614, 5195, 9601, 23199, 705, 902, 18939, 279, 92749, 6269, 4729, 389, 1202, 9624, 5452, 13, 46560, 19465, 6492, 5992, 369, 34684, 11, 477, 330, 2203, 6427, 4442, 1359, 304, 279, 220, 16, 3346, 315, 1057, 15922, 430, 26701, 704, 1057, 21389, 13, 3296, 13168, 11, 279, 92749, 6269, 4729, 6276, 12074, 311, 24564, 279, 4553, 220, 18, 7239, 15922, 2385, 13840, 430, 1304, 709, 1855, 1732, 596, 33869, 13, 763, 872, 502, 4007, 11, 279, 26453, 4024, 1524, 4726, 482, 3411, 7953, 15922, 330, 2203, 6427, 1, 27339, 311, 1505, 1023, 4595, 315, 19465, 4442, 5938, 449, 38281, 13, 4314, 5343, 3048, 1396, 27339, 320, 265, 43054, 477, 11309, 50699, 315, 15922, 8, 323, 22083, 96108, 75815, 13, 35318, 58375, 527, 279, 4617, 4908, 2849, 14726, 430, 6462, 323, 31335, 1057, 21389, 13, 578, 12074, 1766, 3048, 1396, 27339, 323, 22083, 96108, 75815, 311, 387, 8104, 4279, 304, 279, 85381, 315, 1274, 11754, 555, 38281, 13, 763, 5369, 11, 1690, 315, 279, 3048, 1396, 27339, 6656, 709, 304, 5789, 315, 279, 33869, 3131, 6646, 330, 73, 3200, 15922, 1210, 18056, 420, 19465, 330, 23449, 5030, 1, 6866, 4994, 315, 1057, 21389, 11, 14248, 1457, 15763, 430, 433, 8779, 2585, 994, 323, 1405, 1057, 21389, 3480, 389, 323, 1022, 13, 578, 24473, 38793, 315, 19465, 5820, 8111, 311, 387, 8104, 16996, 311, 8271, 4500, 323, 734, 13, 17331, 1202, 3495, 5452, 389, 279, 5195, 15161, 11, 78763, 12587, 10011, 374, 3339, 682, 315, 92749, 6269, 596, 7373, 11506, 5886, 85381, 6089, 2561, 311, 12074, 1949, 315, 6900, 11, 3235, 449, 79136, 7526, 13, 763, 279, 5108, 5672, 11, 279, 92749, 6269, 2128, 690, 387, 48429, 459, 5217, 220, 17, 11, 931, 7373, 11506, 5886, 38281, 85381, 11, 12967, 279, 2860, 927, 220, 22, 11, 931, 13, 25122, 11, 810, 1109, 220, 1954, 26453, 520, 220, 1272, 14584, 323, 6593, 14673, 527, 1701, 279, 92749, 6269, 4729, 311, 12178, 38281, 3495, 2212, 279, 1917, 13, 220, 128257, 198 ]

2,303

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract The yak is remarkable for its adaptation to high altitude and occupies a central place in the economies of the mountainous regions of Asia. At lower elevations, it is common to hybridize yaks with cattle to combine the yak's hardiness with the productivity of cattle. Hybrid males are sterile, however, preventing the establishment of stable hybrid populations, but not a limited introgression after backcrossing several generations of female hybrids to male yaks. Here we inferred bovine haplotypes in the genomes of 76 Mongolian yaks using high-density SNP genotyping and whole-genome sequencing. These yaks inherited ∼ 1.3% of their genome from bovine ancestors after nearly continuous admixture over at least the last 1,500 years. The introgressed regions are enriched in genes involved in nervous system development and function, and particularly in glutamate metabolism and neurotransmission. We also identified a novel mutation associated with a polled (hornless) phenotype originating from Mongolian Turano cattle. Our results suggest that introgressive hybridization contributed to the improvement of yak management and breeding. Main Hybridization is not unusual in nature. Although interspecific hybrids are rare at the population level, around 10% of animals and 25% of plants are known to occasionally hybridize with other species 1 . Evaluation of the genome-wide magnitude of this phenomenon has only recently become possible. The first results from such evaluations show that limited introgressions of the genome are widespread with a potentially important role in environmental adaptation, as is suggested by incorporation of genetic material from local species into the genomes of colonizing species (for example, incorporation of Neanderthal DNA into the genome of non-African humans 2 , 3 and Zea mays mexicana DNA into the maize genome 4 ). Successful analyses have identified genes under selection, but, because of some limitations, they were rarely able to determine precisely the nature of the selective pressure, identify genetic pathways under selection and pinpoint causative polymorphisms. Yak and cattle diverged approximately 4.9 million years ago 5 . Despite anatomical and physiological differences, both species are raised in mixed herds in Central Asia and are maintained using similar husbandry practices. Recent studies have reported several examples of gene flow from cattle to yaks 6 , 7 , 8 , and the existence of polled (hornless) animals in both species that do not carry the previously reported Celtic and Friesian POLLED locus mutations 9 , 10 , 11 , 12 ( Supplementary Table 1 ) raises the possibility of a common origin for this phenotype. For this reason, and because of the large genomic data sets available for cattle, analysis of bovine introgression in Mongolian yaks represents an appealing model to identify exchange of traits of interest between domesticated species. To assess bovine introgression in Mongolian yaks, we initially sequenced two individual genomes (YAK13, homozygous for the POLLED mutation and YAK40, horned) and plotted the frequency of yak and bovine alleles for all positions of yak-specific SNPs in 70-kb sliding windows (Online Methods and Supplementary Fig. 1 ). Considering yak-specific variants to be variants that were (i) homozygous for the alternate allele in the yak reference genome 5 (hereafter referred to as YAKQIU) and (ii) absent from 235 bovine genomes ( Supplementary Table 2 ) (ref. 13 ), we estimated that at least 1.73% and 1.22% of the YAK13 and YAK40 genomes were of bovine origin ( Supplementary Fig. 1 ). To identify introgression in YAKQIU, we used the number of yak-specific SNPs per 70-kb interval as an indicator and estimated a bovine proportion of 1.06% even in the yak reference sequence. To validate our whole-genome sequencing (WGS) approach for inference of local ancestry, two regions suggestive of homozygous cattle introgression in YAKQIU were PCR amplified and sequenced in YAK13 and in 12 species related to yak ( Supplementary Table 3 ). Multiple-sequence alignment and phylogenetic analyses of 2,191 bp of sequence clustered YAK13 with gaur, banteng, bison and wisent, in accordance with the phylogeny of the Bovini tribe 14 , whereas YAKQIU clustered with Mongolian Turano cattle, thus confirming cattle introgression in the yak reference genome ( Fig. 1 and Supplementary Table 4 ). Figure 1: Phylogenetic analyses of sequence data on chromosomes 9 and 25 confirm bovine introgression in the yak that was sequenced to generate the yak reference genome. ( a ) Bovine introgression plots constructed on the basis of WGS data. Blue and red dots show the relative frequencies of homozygous and heterozygous genotypes, respectively, for yak-specific polymorphisms from the sequencing results used to generate the yak reference genome. Each dot represents the number of genotypes in a 70-kb sliding window divided by the expected (genome-wide) number of polymorphisms in a 70-kb window. The background of each interval is shaded according to read depth, the mean number of reads per 70-kb window, ranging from 0 (dark gray) to >40 (white). Genotype frequencies from intervals with a white background are likely to be affected by artifacts from repeat expansions in yaks and those from dark-shaded intervals are likely to be affected by poor mappability or deletions; intervals with a neutral gray background are regarded as more robust. Introgressed intervals are identified by a break in the red line (circular binary segmentation of mean homozygous genotype frequency) and a drop in the frequency of homozygous genotypes for yak-specific alleles. Heterozygous genotypes for yak-specific alleles and the yellow line (circular binary segmentation of mean heterozygous genotype frequency) serve as a control to distinguish homozygous from heterozygous cattle introgression in the yak genome. These statistics suggest homozygous cattle introgression in two regions (BTA09:68.495–70.115 Mb and BTA25:17.345–19.995 Mb) in the individual that was sequenced to generate the yak reference genome. ( b ) Magnification of these two regions and details for five exons (blue rectangles) and flanking sequences from four genes ( L3MBTL3 , SAMD3 , ACSM2B and MGC134577 ) that were sequenced in 14 Bovini animals for validation of our introgression analysis based on WGS data ( Supplementary Table 4 ). The regions shown correspond to the intervals highlighted by dashed lines in a", "role": "user" }, { "content": "Though placid enough to be managed by humans, yaks are robust enough to survive at 4000 meters altitude. Genomic analyses by researchers of Ludwig-Maximilians-Universitaet (LMU) in Munich show that yak domestication began several millennia ago and was promoted by repeated crosses with cattle. The first systematic genome-wide comparison of the genetic heritage of yaks and cattle shows that about 1.5% of the genome of Mongolian yaks is derived from domesticated cattle. While male hybrids are sterile, hybrid females can be backcrossed to male yaks for several generations, which allows for the stable introgression of short regions of bovine chromosomes into the yak genome. The results of the new study suggest that yak hybridization began thousands of years ago. Dr. Ivica Medugorac, who heads a research group in population genomics at the Chair of Animal Genetics and Husbandry at LMU, is the first and corresponding author on the new paper, which appears in the journal Nature Genetics. \"Our results indicate that hybridization between yaks and cattle began more than 1500 years ago, and has continued with varying intensity ever since,\" Medugorac says, and points out that written records also testify to early hybridization of yaks by Mongolian breeders. In collaboration with Dr. Aurélien Capitan of the Université Paris-Saclay, Dr. Stefan Krebs of the Laboratory for Functional Genome Analysis at LMU's Gene Center and colleagues from other European, American and Mongolian institutions, Medugorac has mapped the distribution of cattle genes in the yak genome. \"Many of the genetic variants in the yak that can be traced back to cattle are found at gene loci that are known to play roles in the development and function of the nervous system. They have an impact on sensory perception, cognition and social behavior. Evidently, over a period of several thousands of years, Mongolian breeders succeeded in speeding up the domestication of the yak by crossing them with cattle, which had been domesticated thousands of years before,\" he explains. Furthermore, the traits that enable yaks to survive at high altitudes, in mountain ranges such as the Altai, the Pamirs and the Himalayas have obviously been retained during this process. In the course of the study, the researchers identified a gene variant in Mongolian cattle and yaks that is responsible for the loss of horns. \"We were able to show that this variant had been introduced into yaks from the domesticated Mongolian Turano cattle long ago,\" Medugorac says. Lack of horns (known as 'polledness') is, however, only one of the traits with which yak breeders attempted to tame the ferocious temper of the yaks. Interestingly, the polled variant in the Mongolian Turano cattle differs from the mutations known to be responsible for polledness in European cattle, which had previously been molecularly characterized by Medugorac's group in 2012 and 2014. These findings are already being exploited by breeders worldwide to select for polled cattle in order to avoid the painful procedure of dehorning. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract The yak is remarkable for its adaptation to high altitude and occupies a central place in the economies of the mountainous regions of Asia. At lower elevations, it is common to hybridize yaks with cattle to combine the yak's hardiness with the productivity of cattle. Hybrid males are sterile, however, preventing the establishment of stable hybrid populations, but not a limited introgression after backcrossing several generations of female hybrids to male yaks. Here we inferred bovine haplotypes in the genomes of 76 Mongolian yaks using high-density SNP genotyping and whole-genome sequencing. These yaks inherited ∼ 1.3% of their genome from bovine ancestors after nearly continuous admixture over at least the last 1,500 years. The introgressed regions are enriched in genes involved in nervous system development and function, and particularly in glutamate metabolism and neurotransmission. We also identified a novel mutation associated with a polled (hornless) phenotype originating from Mongolian Turano cattle. Our results suggest that introgressive hybridization contributed to the improvement of yak management and breeding. Main Hybridization is not unusual in nature. Although interspecific hybrids are rare at the population level, around 10% of animals and 25% of plants are known to occasionally hybridize with other species 1 . Evaluation of the genome-wide magnitude of this phenomenon has only recently become possible. The first results from such evaluations show that limited introgressions of the genome are widespread with a potentially important role in environmental adaptation, as is suggested by incorporation of genetic material from local species into the genomes of colonizing species (for example, incorporation of Neanderthal DNA into the genome of non-African humans 2 , 3 and Zea mays mexicana DNA into the maize genome 4 ). Successful analyses have identified genes under selection, but, because of some limitations, they were rarely able to determine precisely the nature of the selective pressure, identify genetic pathways under selection and pinpoint causative polymorphisms. Yak and cattle diverged approximately 4.9 million years ago 5 . Despite anatomical and physiological differences, both species are raised in mixed herds in Central Asia and are maintained using similar husbandry practices. Recent studies have reported several examples of gene flow from cattle to yaks 6 , 7 , 8 , and the existence of polled (hornless) animals in both species that do not carry the previously reported Celtic and Friesian POLLED locus mutations 9 , 10 , 11 , 12 ( Supplementary Table 1 ) raises the possibility of a common origin for this phenotype. For this reason, and because of the large genomic data sets available for cattle, analysis of bovine introgression in Mongolian yaks represents an appealing model to identify exchange of traits of interest between domesticated species. To assess bovine introgression in Mongolian yaks, we initially sequenced two individual genomes (YAK13, homozygous for the POLLED mutation and YAK40, horned) and plotted the frequency of yak and bovine alleles for all positions of yak-specific SNPs in 70-kb sliding windows (Online Methods and Supplementary Fig. 1 ). Considering yak-specific variants to be variants that were (i) homozygous for the alternate allele in the yak reference genome 5 (hereafter referred to as YAKQIU) and (ii) absent from 235 bovine genomes ( Supplementary Table 2 ) (ref. 13 ), we estimated that at least 1.73% and 1.22% of the YAK13 and YAK40 genomes were of bovine origin ( Supplementary Fig. 1 ). To identify introgression in YAKQIU, we used the number of yak-specific SNPs per 70-kb interval as an indicator and estimated a bovine proportion of 1.06% even in the yak reference sequence. To validate our whole-genome sequencing (WGS) approach for inference of local ancestry, two regions suggestive of homozygous cattle introgression in YAKQIU were PCR amplified and sequenced in YAK13 and in 12 species related to yak ( Supplementary Table 3 ). Multiple-sequence alignment and phylogenetic analyses of 2,191 bp of sequence clustered YAK13 with gaur, banteng, bison and wisent, in accordance with the phylogeny of the Bovini tribe 14 , whereas YAKQIU clustered with Mongolian Turano cattle, thus confirming cattle introgression in the yak reference genome ( Fig. 1 and Supplementary Table 4 ). Figure 1: Phylogenetic analyses of sequence data on chromosomes 9 and 25 confirm bovine introgression in the yak that was sequenced to generate the yak reference genome. ( a ) Bovine introgression plots constructed on the basis of WGS data. Blue and red dots show the relative frequencies of homozygous and heterozygous genotypes, respectively, for yak-specific polymorphisms from the sequencing results used to generate the yak reference genome. Each dot represents the number of genotypes in a 70-kb sliding window divided by the expected (genome-wide) number of polymorphisms in a 70-kb window. The background of each interval is shaded according to read depth, the mean number of reads per 70-kb window, ranging from 0 (dark gray) to >40 (white). Genotype frequencies from intervals with a white background are likely to be affected by artifacts from repeat expansions in yaks and those from dark-shaded intervals are likely to be affected by poor mappability or deletions; intervals with a neutral gray background are regarded as more robust. Introgressed intervals are identified by a break in the red line (circular binary segmentation of mean homozygous genotype frequency) and a drop in the frequency of homozygous genotypes for yak-specific alleles. Heterozygous genotypes for yak-specific alleles and the yellow line (circular binary segmentation of mean heterozygous genotype frequency) serve as a control to distinguish homozygous from heterozygous cattle introgression in the yak genome. These statistics suggest homozygous cattle introgression in two regions (BTA09:68.495–70.115 Mb and BTA25:17.345–19.995 Mb) in the individual that was sequenced to generate the yak reference genome. ( b ) Magnification of these two regions and details for five exons (blue rectangles) and flanking sequences from four genes ( L3MBTL3 , SAMD3 , ACSM2B and MGC134577 ) that were sequenced in 14 Bovini animals for validation of our introgression analysis based on WGS data ( Supplementary Table 4 ). The regions shown correspond to the intervals highlighted by dashed lines in a<|im_end|> <|im_start|>assistant Though placid enough to be managed by humans, yaks are robust enough to survive at 4000 meters altitude. Genomic analyses by researchers of Ludwig-Maximilians-Universitaet (LMU) in Munich show that yak domestication began several millennia ago and was promoted by repeated crosses with cattle. The first systematic genome-wide comparison of the genetic heritage of yaks and cattle shows that about 1.5% of the genome of Mongolian yaks is derived from domesticated cattle. While male hybrids are sterile, hybrid females can be backcrossed to male yaks for several generations, which allows for the stable introgression of short regions of bovine chromosomes into the yak genome. The results of the new study suggest that yak hybridization began thousands of years ago. Dr. Ivica Medugorac, who heads a research group in population genomics at the Chair of Animal Genetics and Husbandry at LMU, is the first and corresponding author on the new paper, which appears in the journal Nature Genetics. "Our results indicate that hybridization between yaks and cattle began more than 1500 years ago, and has continued with varying intensity ever since," Medugorac says, and points out that written records also testify to early hybridization of yaks by Mongolian breeders. In collaboration with Dr. Aurélien Capitan of the Université Paris-Saclay, Dr. Stefan Krebs of the Laboratory for Functional Genome Analysis at LMU's Gene Center and colleagues from other European, American and Mongolian institutions, Medugorac has mapped the distribution of cattle genes in the yak genome. "Many of the genetic variants in the yak that can be traced back to cattle are found at gene loci that are known to play roles in the development and function of the nervous system. They have an impact on sensory perception, cognition and social behavior. Evidently, over a period of several thousands of years, Mongolian breeders succeeded in speeding up the domestication of the yak by crossing them with cattle, which had been domesticated thousands of years before," he explains. Furthermore, the traits that enable yaks to survive at high altitudes, in mountain ranges such as the Altai, the Pamirs and the Himalayas have obviously been retained during this process. In the course of the study, the researchers identified a gene variant in Mongolian cattle and yaks that is responsible for the loss of horns. "We were able to show that this variant had been introduced into yaks from the domesticated Mongolian Turano cattle long ago," Medugorac says. Lack of horns (known as 'polledness') is, however, only one of the traits with which yak breeders attempted to tame the ferocious temper of the yaks. Interestingly, the polled variant in the Mongolian Turano cattle differs from the mutations known to be responsible for polledness in European cattle, which had previously been molecularly characterized by Medugorac's group in 2012 and 2014. These findings are already being exploited by breeders worldwide to select for polled cattle in order to avoid the painful procedure of dehorning. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 578, 74778, 374, 23649, 369, 1202, 34185, 311, 1579, 36958, 323, 76854, 264, 8792, 2035, 304, 279, 37671, 315, 279, 16700, 788, 13918, 315, 13936, 13, 2468, 4827, 12231, 811, 11, 433, 374, 4279, 311, 26038, 553, 379, 10011, 449, 36952, 311, 16343, 279, 74778, 596, 2653, 1918, 449, 279, 26206, 315, 36952, 13, 50727, 25000, 527, 82743, 11, 4869, 11, 27252, 279, 21967, 315, 15528, 26038, 22673, 11, 719, 539, 264, 7347, 20285, 30840, 1306, 1203, 29942, 287, 3892, 22540, 315, 8954, 97205, 311, 8762, 379, 10011, 13, 5810, 584, 68695, 712, 62301, 46900, 9363, 1842, 304, 279, 85381, 315, 220, 4767, 44539, 89108, 379, 10011, 1701, 1579, 89131, 60418, 4173, 67247, 323, 4459, 37564, 638, 62119, 13, 4314, 379, 10011, 28088, 12264, 120, 220, 16, 13, 18, 4, 315, 872, 33869, 505, 712, 62301, 38618, 1306, 7154, 19815, 14933, 13025, 927, 520, 3325, 279, 1566, 220, 16, 11, 2636, 1667, 13, 578, 20285, 2542, 291, 13918, 527, 69671, 304, 21389, 6532, 304, 23418, 1887, 4500, 323, 734, 11, 323, 8104, 304, 35169, 92166, 39097, 323, 90351, 2796, 13, 1226, 1101, 11054, 264, 11775, 27472, 5938, 449, 264, 84721, 320, 51984, 1752, 8, 82423, 71373, 505, 44539, 89108, 8877, 5770, 36952, 13, 5751, 3135, 4284, 430, 20285, 47819, 26038, 2065, 20162, 311, 279, 16048, 315, 74778, 6373, 323, 40308, 13, 4802, 50727, 2065, 374, 539, 19018, 304, 7138, 13, 10541, 82019, 15934, 97205, 527, 9024, 520, 279, 7187, 2237, 11, 2212, 220, 605, 4, 315, 10099, 323, 220, 914, 4, 315, 11012, 527, 3967, 311, 23781, 26038, 553, 449, 1023, 9606, 220, 16, 662, 40388, 315, 279, 33869, 25480, 26703, 315, 420, 25885, 706, 1193, 6051, 3719, 3284, 13, 578, 1176, 3135, 505, 1778, 56181, 1501, 430, 7347, 20285, 2542, 919, 315, 279, 33869, 527, 24716, 449, 264, 13893, 3062, 3560, 304, 12434, 34185, 11, 439, 374, 12090, 555, 88465, 315, 19465, 3769, 505, 2254, 9606, 1139, 279, 85381, 315, 15235, 4954, 9606, 320, 2000, 3187, 11, 88465, 315, 4275, 8363, 31392, 15922, 1139, 279, 33869, 315, 2536, 6830, 48893, 12966, 220, 17, 1174, 220, 18, 323, 10120, 64, 296, 954, 38049, 99605, 15922, 1139, 279, 93307, 33869, 220, 19, 7609, 46626, 29060, 617, 11054, 21389, 1234, 6727, 11, 719, 11, 1606, 315, 1063, 9669, 11, 814, 1051, 19029, 3025, 311, 8417, 24559, 279, 7138, 315, 279, 44010, 7410, 11, 10765, 19465, 44014, 1234, 6727, 323, 67638, 25540, 1413, 46033, 16751, 13978, 13, 71968, 323, 36952, 37441, 3640, 13489, 220, 19, 13, 24, 3610, 1667, 4227, 220, 20, 662, 18185, 75893, 950, 323, 53194, 12062, 11, 2225, 9606, 527, 9408, 304, 9709, 1077, 5469, 304, 10913, 13936, 323, 527, 18908, 1701, 4528, 10177, 894, 12659, 13, 35390, 7978, 617, 5068, 3892, 10507, 315, 15207, 6530, 505, 36952, 311, 379, 10011, 220, 21, 1174, 220, 22, 1174, 220, 23, 1174, 323, 279, 14209, 315, 84721, 320, 51984, 1752, 8, 10099, 304, 2225, 9606, 430, 656, 539, 6920, 279, 8767, 5068, 55764, 323, 435, 4108, 1122, 32740, 13953, 79257, 34684, 220, 24, 1174, 220, 605, 1174, 220, 806, 1174, 220, 717, 320, 99371, 6771, 220, 16, 883, 25930, 279, 13336, 315, 264, 4279, 6371, 369, 420, 82423, 13, 1789, 420, 2944, 11, 323, 1606, 315, 279, 3544, 81064, 828, 7437, 2561, 369, 36952, 11, 6492, 315, 712, 62301, 20285, 30840, 304, 44539, 89108, 379, 10011, 11105, 459, 33352, 1646, 311, 10765, 9473, 315, 25022, 315, 2802, 1990, 13018, 660, 9606, 13, 2057, 8720, 712, 62301, 20285, 30840, 304, 44539, 89108, 379, 10011, 11, 584, 15453, 11506, 5886, 1403, 3927, 85381, 320, 56, 12173, 1032, 11, 55513, 4341, 70, 788, 369, 279, 32740, 13953, 27472, 323, 816, 12173, 1272, 11, 21281, 291, 8, 323, 68683, 279, 11900, 315, 74778, 323, 712, 62301, 98260, 369, 682, 10093, 315, 74778, 19440, 18407, 21051, 304, 220, 2031, 12934, 65, 34932, 11276, 320, 20171, 19331, 323, 99371, 23966, 13, 220, 16, 7609, 56877, 74778, 19440, 27103, 311, 387, 27103, 430, 1051, 320, 72, 8, 55513, 4341, 70, 788, 369, 279, 25631, 70510, 304, 279, 74778, 5905, 33869, 220, 20, 320, 6881, 10924, 14183, 311, 439, 816, 12173, 48, 81100, 8, 323, 320, 3893, 8, 28310, 505, 220, 12422, 712, 62301, 85381, 320, 99371, 6771, 220, 17, 883, 320, 1116, 13, 220, 1032, 7026, 584, 13240, 430, 520, 3325, 220, 16, 13, 5958, 4, 323, 220, 16, 13, 1313, 4, 315, 279, 816, 12173, 1032, 323, 816, 12173, 1272, 85381, 1051, 315, 712, 62301, 6371, 320, 99371, 23966, 13, 220, 16, 7609, 2057, 10765, 20285, 30840, 304, 816, 12173, 48, 81100, 11, 584, 1511, 279, 1396, 315, 74778, 19440, 18407, 21051, 824, 220, 2031, 12934, 65, 10074, 439, 459, 21070, 323, 13240, 264, 712, 62301, 21801, 315, 220, 16, 13, 2705, 4, 1524, 304, 279, 74778, 5905, 8668, 13, 2057, 9788, 1057, 4459, 37564, 638, 62119, 320, 54, 16929, 8, 5603, 369, 45478, 315, 2254, 66004, 11, 1403, 13918, 99578, 315, 55513, 4341, 70, 788, 36952, 20285, 30840, 304, 816, 12173, 48, 81100, 1051, 67791, 83598, 323, 11506, 5886, 304, 816, 12173, 1032, 323, 304, 220, 717, 9606, 5552, 311, 74778, 320, 99371, 6771, 220, 18, 7609, 29911, 7962, 4474, 17632, 323, 37555, 86945, 5411, 29060, 315, 220, 17, 11, 7529, 27783, 315, 8668, 93858, 816, 12173, 1032, 449, 342, 4202, 11, 293, 519, 833, 11, 293, 3416, 323, 19112, 306, 11, 304, 18859, 449, 279, 37555, 848, 33495, 315, 279, 426, 869, 6729, 34671, 220, 975, 1174, 20444, 816, 12173, 48, 81100, 93858, 449, 44539, 89108, 8877, 5770, 36952, 11, 8617, 50096, 36952, 20285, 30840, 304, 279, 74778, 5905, 33869, 320, 23966, 13, 220, 16, 323, 99371, 6771, 220, 19, 7609, 19575, 220, 16, 25, 93682, 86945, 5411, 29060, 315, 8668, 828, 389, 83181, 220, 24, 323, 220, 914, 7838, 712, 62301, 20285, 30840, 304, 279, 74778, 430, 574, 11506, 5886, 311, 7068, 279, 74778, 5905, 33869, 13, 320, 264, 883, 426, 869, 483, 20285, 30840, 31794, 20968, 389, 279, 8197, 315, 468, 16929, 828, 13, 8868, 323, 2579, 32094, 1501, 279, 8844, 34873, 315, 55513, 4341, 70, 788, 323, 30548, 76523, 70, 788, 4173, 22583, 11, 15947, 11, 369, 74778, 19440, 46033, 16751, 13978, 505, 279, 62119, 3135, 1511, 311, 7068, 279, 74778, 5905, 33869, 13, 9062, 13046, 11105, 279, 1396, 315, 4173, 22583, 304, 264, 220, 2031, 12934, 65, 34932, 3321, 18255, 555, 279, 3685, 320, 89045, 25480, 8, 1396, 315, 46033, 16751, 13978, 304, 264, 220, 2031, 12934, 65, 3321, 13, 578, 4092, 315, 1855, 10074, 374, 92866, 4184, 311, 1373, 8149, 11, 279, 3152, 1396, 315, 16181, 824, 220, 2031, 12934, 65, 3321, 11, 24950, 505, 220, 15, 320, 23449, 18004, 8, 311, 871, 1272, 320, 5902, 570, 9500, 4249, 34873, 505, 28090, 449, 264, 4251, 4092, 527, 4461, 311, 387, 11754, 555, 36136, 505, 13454, 78588, 304, 379, 10011, 323, 1884, 505, 6453, 7666, 14589, 28090, 527, 4461, 311, 387, 11754, 555, 8009, 296, 680, 2968, 477, 19825, 919, 26, 28090, 449, 264, 21277, 18004, 4092, 527, 27458, 439, 810, 22514, 13, 53086, 2542, 291, 28090, 527, 11054, 555, 264, 1464, 304, 279, 2579, 1584, 320, 66, 22190, 8026, 60852, 315, 3152, 55513, 4341, 70, 788, 80285, 11900, 8, 323, 264, 6068, 304, 279, 11900, 315, 55513, 4341, 70, 788, 4173, 22583, 369, 74778, 19440, 98260, 13, 473, 1430, 76523, 70, 788, 4173, 22583, 369, 74778, 19440, 98260, 323, 279, 14071, 1584, 320, 66, 22190, 8026, 60852, 315, 3152, 30548, 76523, 70, 788, 80285, 11900, 8, 8854, 439, 264, 2585, 311, 33137, 55513, 4341, 70, 788, 505, 30548, 76523, 70, 788, 36952, 20285, 30840, 304, 279, 74778, 33869, 13, 4314, 13443, 4284, 55513, 4341, 70, 788, 36952, 20285, 30840, 304, 1403, 13918, 320, 33, 15559, 2545, 25, 2614, 13, 21038, 4235, 2031, 13, 7322, 51365, 323, 426, 15559, 914, 25, 1114, 13, 12901, 4235, 777, 13, 22101, 51365, 8, 304, 279, 3927, 430, 574, 11506, 5886, 311, 7068, 279, 74778, 5905, 33869, 13, 320, 293, 883, 20918, 2461, 315, 1521, 1403, 13918, 323, 3649, 369, 4330, 506, 2439, 320, 12481, 77292, 8, 323, 1344, 33434, 24630, 505, 3116, 21389, 320, 445, 18, 8578, 13778, 18, 1174, 47687, 35, 18, 1174, 79184, 44, 17, 33, 323, 386, 23710, 9565, 23411, 883, 430, 1051, 11506, 5886, 304, 220, 975, 426, 869, 6729, 10099, 369, 10741, 315, 1057, 20285, 30840, 6492, 3196, 389, 468, 16929, 828, 320, 99371, 6771, 220, 19, 7609, 578, 13918, 6982, 8024, 311, 279, 28090, 27463, 555, 67822, 5238, 304, 264, 128257, 198, 128256, 78191, 198, 27831, 29960, 307, 3403, 311, 387, 9152, 555, 12966, 11, 379, 10011, 527, 22514, 3403, 311, 18167, 520, 220, 3443, 15, 20645, 36958, 13, 9500, 3151, 29060, 555, 12074, 315, 85550, 5364, 710, 318, 26707, 12, 65715, 6388, 295, 320, 11237, 52, 8, 304, 47304, 1501, 430, 74778, 13018, 367, 6137, 3892, 96731, 4227, 323, 574, 30026, 555, 11763, 50535, 449, 36952, 13, 578, 1176, 37538, 33869, 25480, 12593, 315, 279, 19465, 28948, 315, 379, 10011, 323, 36952, 5039, 430, 922, 220, 16, 13, 20, 4, 315, 279, 33869, 315, 44539, 89108, 379, 10011, 374, 14592, 505, 13018, 660, 36952, 13, 6104, 8762, 97205, 527, 82743, 11, 26038, 28585, 649, 387, 1203, 29942, 291, 311, 8762, 379, 10011, 369, 3892, 22540, 11, 902, 6276, 369, 279, 15528, 20285, 30840, 315, 2875, 13918, 315, 712, 62301, 83181, 1139, 279, 74778, 33869, 13, 578, 3135, 315, 279, 502, 4007, 4284, 430, 74778, 26038, 2065, 6137, 9214, 315, 1667, 4227, 13, 2999, 13, 34583, 3074, 3344, 773, 269, 582, 11, 889, 14971, 264, 3495, 1912, 304, 7187, 4173, 24203, 520, 279, 16478, 315, 21995, 84386, 323, 74459, 894, 520, 47514, 52, 11, 374, 279, 1176, 323, 12435, 3229, 389, 279, 502, 5684, 11, 902, 8111, 304, 279, 8486, 22037, 84386, 13, 330, 8140, 3135, 13519, 430, 26038, 2065, 1990, 379, 10011, 323, 36952, 6137, 810, 1109, 220, 3965, 15, 1667, 4227, 11, 323, 706, 8738, 449, 29865, 21261, 3596, 2533, 1359, 3344, 773, 269, 582, 2795, 11, 323, 3585, 704, 430, 5439, 7576, 1101, 49262, 311, 4216, 26038, 2065, 315, 379, 10011, 555, 44539, 89108, 28875, 388, 13, 763, 20632, 449, 2999, 13, 35731, 73511, 268, 8171, 13145, 315, 279, 15915, 13109, 12366, 6354, 48836, 352, 11, 2999, 13, 50002, 30718, 1302, 315, 279, 32184, 369, 55550, 82917, 18825, 520, 47514, 52, 596, 24983, 5955, 323, 18105, 505, 1023, 7665, 11, 3778, 323, 44539, 89108, 14673, 11, 3344, 773, 269, 582, 706, 24784, 279, 8141, 315, 36952, 21389, 304, 279, 74778, 33869, 13, 330, 8607, 315, 279, 19465, 27103, 304, 279, 74778, 430, 649, 387, 51400, 1203, 311, 36952, 527, 1766, 520, 15207, 1353, 72, 430, 527, 3967, 311, 1514, 13073, 304, 279, 4500, 323, 734, 315, 279, 23418, 1887, 13, 2435, 617, 459, 5536, 389, 49069, 21063, 11, 75310, 323, 3674, 7865, 13, 469, 1325, 4501, 11, 927, 264, 4261, 315, 3892, 9214, 315, 1667, 11, 44539, 89108, 28875, 388, 26399, 304, 58675, 709, 279, 13018, 367, 315, 279, 74778, 555, 27736, 1124, 449, 36952, 11, 902, 1047, 1027, 13018, 660, 9214, 315, 1667, 1603, 1359, 568, 15100, 13, 24296, 11, 279, 25022, 430, 7431, 379, 10011, 311, 18167, 520, 1579, 4902, 21237, 11, 304, 16700, 21986, 1778, 439, 279, 24610, 2192, 11, 279, 44513, 17260, 323, 279, 76438, 98440, 617, 14224, 1027, 35363, 2391, 420, 1920, 13, 763, 279, 3388, 315, 279, 4007, 11, 279, 12074, 11054, 264, 15207, 11678, 304, 44539, 89108, 36952, 323, 379, 10011, 430, 374, 8647, 369, 279, 4814, 315, 61084, 13, 330, 1687, 1051, 3025, 311, 1501, 430, 420, 11678, 1047, 1027, 11784, 1139, 379, 10011, 505, 279, 13018, 660, 44539, 89108, 8877, 5770, 36952, 1317, 4227, 1359, 3344, 773, 269, 582, 2795, 13, 68502, 315, 61084, 320, 5391, 439, 364, 10097, 839, 2136, 873, 374, 11, 4869, 11, 1193, 832, 315, 279, 25022, 449, 902, 74778, 28875, 388, 17644, 311, 82923, 279, 18728, 78287, 6940, 315, 279, 379, 10011, 13, 58603, 11, 279, 84721, 11678, 304, 279, 44539, 89108, 8877, 5770, 36952, 44642, 505, 279, 34684, 3967, 311, 387, 8647, 369, 84721, 2136, 304, 7665, 36952, 11, 902, 1047, 8767, 1027, 31206, 398, 32971, 555, 3344, 773, 269, 582, 596, 1912, 304, 220, 679, 17, 323, 220, 679, 19, 13, 4314, 14955, 527, 2736, 1694, 51763, 555, 28875, 388, 15603, 311, 3373, 369, 84721, 36952, 304, 2015, 311, 5766, 279, 26175, 10537, 315, 409, 20100, 1251, 13, 220, 128257, 198 ]

2,085

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Background Effective conservation management of highly mobile species depends upon detailed knowledge of movements of individuals across their range; yet, data are rarely available at appropriate spatiotemporal scales. Flying-foxes ( Pteropus spp.) are large bats that forage by night on floral resources and rest by day in arboreal roosts that may contain colonies of many thousands of individuals. They are the largest mammals capable of powered flight, and are highly mobile, which makes them key seed and pollen dispersers in forest ecosystems. However, their mobility also facilitates transmission of zoonotic diseases and brings them in conflict with humans, and so they require a precarious balancing of conservation and management concerns throughout their Old World range. Here, we analyze the Australia-wide movements of 201 satellite-tracked individuals, providing unprecedented detail on the inter-roost movements of three flying-fox species: Pteropus alecto , P . poliocephalus , and P . scapulatus across jurisdictions over up to 5 years. Results Individuals were estimated to travel long distances annually among a network of 755 roosts ( P . alecto , 1427–1887 km; P . poliocephalus , 2268–2564 km; and P . scapulatus , 3782–6073 km), but with little uniformity among their directions of travel. This indicates that flying-fox populations are composed of extremely mobile individuals that move nomadically and at species-specific rates. Individuals of all three species exhibited very low fidelity to roosts locally, resulting in very high estimated daily colony turnover rates ( P . alecto , 11.9 ± 1.3%; P . poliocephalus , 17.5 ± 1.3%; and P . scapulatus , 36.4 ± 6.5%). This indicates that flying-fox roosts form nodes in a vast continental network of highly dynamic “staging posts” through which extremely mobile individuals travel far and wide across their species ranges. Conclusions The extreme inter-roost mobility reported here demonstrates the extent of the ecological linkages that nomadic flying-foxes provide across Australia’s contemporary fragmented landscape, with profound implications for the ecosystem services and zoonotic dynamics of flying-fox populations. In addition, the extreme mobility means that impacts from local management actions can readily reverberate across jurisdictions throughout the species ranges; therefore, local management actions need to be assessed with reference to actions elsewhere and hence require national coordination. These findings underscore the need for sound understanding of animal movement dynamics to support evidence-based, transboundary conservation and management policy, tailored to the unique movement ecologies of species. Background Conventional conservation approaches, which typically view species as organized around discrete local populations, are inadequate for highly mobile species [ 1 ], particularly in the context of environmental change [ 2 ]. Highly mobile species often require multiple habitats to obtain different resources at different stages of their life cycles, and their persistence depends on the availability and accessibility of the requisite suite of habitats [ 3 , 4 ]. The unpredictable movements of nomadic species make it particularly difficult to decide where and how to act to mitigate threatening processes [ 5 ]. This can be further complicated when such species cross jurisdictional boundaries within or between countries [ 6 ], making a unified program of conservation management much more difficult to achieve. For effective conservation management, it is essential to have a robust understanding of the movement ecology of highly mobile species, but this can only be accomplished by following numerous individuals within a population, across multiple habitats within the species’ range [ 7 , 8 ]. Australian flying-foxes ( Pteropus spp.) are large bats that forage by night on floral resources and rest by day in arboreal roosts that may contain colonies of many thousands of individuals [ 9 ] with a complex social architecture [ 10 , 11 ]. Roost locations can be stable for decades [ 12 ], and while “traditional” sites are mostly occupied seasonally, more recent, urban roosts are occupied permanently [ 13 ], albeit with great seasonal variation in local numbers [ 14 ]. The prevailing assumption is that flying-foxes are organized around local “resident” populations that show (seasonal) fidelity to a particular site [ 13 ]. However, like other large pteropodids elsewhere (e.g., [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ]), Australian flying-fox individuals can be highly mobile, with movements ranging from small relocations within roosts and foraging sites [ 10 ] to nightly foraging trips of up to 80 km [ 23 , 24 ] and long-distance movements of several thousand kilometers [ 25 , 26 ]. Therefore, how flying-fox populations are locally organized is critically dependent on the extent and seasonal dynamics of movements among roosts. To date, as for the other large pteropodids elsewhere (e.g., [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ]), movement studies of Australian flying-foxes are limited to small samples of radio- [ 23 , 27 , 28 , 29 ] and satellite-tracked [ 21 , 25 , 26 ] individuals, so the extent and seasonal dynamics of movements among roosts have never been formally assessed, hampering effective conservation and management of these ecologically important species. The mobility of flying-foxes is thought to enable them to exploit Australia’s ephemeral floral resources [ 30 ] and makes them key long-distance pollen and seed dispersers [ 31 , 32 , 33 ]. Long-distance seed and pollen dispersal by all four Australian mainland Pteropus species ( Pteropus alecto , P . poliocephalus , P . scapulatus , and P . conspicillatus ) would be of crucial conservation significance as it promotes gene flow between impoverished forest patches and facilitates range shifts of forage trees under climate change [ 34 , 35 ]. Knowledge on the extent and seasonal dynamics of movements among roosts is thus key for understanding the linkages that flying-foxes provide in Australia’s contemporary fragmented landscape. The mobility of flying-foxes is also thought to underpin their role in the ecology of several emerging infectious diseases. In Australia, flying-foxes are the recognized natural hosts for various viral agents that threaten livestock and/or human health,", "role": "user" }, { "content": "New research led by scientists at Western Sydney University and published in BMC Biology shows that flying-foxes are always on the move among a vast network of roosts, creating key challenges for their management and conservation in Australia. Australia's flying-foxes are amongst the largest mammals in the world that are capable of powered flight. They are highly mobile, which is thought to make them key seed and pollen dispersers in Australia's fragmented forest ecosystems. However, their mobility also facilitates transmission of disease and often brings them in conflict with humans, and so they require a precarious balancing of conservation and management concern. To gain a detailed understanding of flying-fox mobility at the landscape scale, the researchers analyzed the movements of 201 satellite-tracked individuals across eastern Australia, for up to five years. Three species were monitored including 109 gray-headed flying-foxes (P. poliocephalus), 80 black flying-foxes (Pteropus alecto) and 12 little red flying-foxes (P. scapulatus). The tracked flying-foxes used a total of 755 roost sites between them, of which more than half were previously unrecorded. One roost site, the Hervey Bay Botanic Gardens, was visited by tracked individuals from all three species. Individuals traveled thousands of kilometers among many of those roosts each year, with one gray-headed flying-fox covering at least 12,337 km between 123 roosts in 37 local government areas over 1,629 tracking days. Associate Professor Justin Welbergen, the lead author, said: \"Our findings indicate that flying-fox roosts are better viewed as parts of a network of 'staging posts' that provide temporary shelters to extremely mobile individuals that wander nomadically throughout much of eastern Australia. This contrasts with the conventional portrayal of a roost as being home to a resident population made up of the same individuals. It has long been recognized that flying-foxes have the capacity to travel long distances; however, the vast scale of the movements among roosts shown by our study indicates that nomadism is in fact a fundamental aspect of flying-fox biology. This necessitates a re-evaluation of how these fascinating animals are managed and conserved.\" While the extreme mobility has profound implications for the roles of flying-foxes as seed and pollen dispersers, it also means that negative impacts from localized management actions can easily reverberate throughout the species ranges. Coordinated management and conservation efforts should therefore be implemented across Australia to protect these ecologically important species. The research is published in BMC Biology. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Background Effective conservation management of highly mobile species depends upon detailed knowledge of movements of individuals across their range; yet, data are rarely available at appropriate spatiotemporal scales. Flying-foxes ( Pteropus spp.) are large bats that forage by night on floral resources and rest by day in arboreal roosts that may contain colonies of many thousands of individuals. They are the largest mammals capable of powered flight, and are highly mobile, which makes them key seed and pollen dispersers in forest ecosystems. However, their mobility also facilitates transmission of zoonotic diseases and brings them in conflict with humans, and so they require a precarious balancing of conservation and management concerns throughout their Old World range. Here, we analyze the Australia-wide movements of 201 satellite-tracked individuals, providing unprecedented detail on the inter-roost movements of three flying-fox species: Pteropus alecto , P . poliocephalus , and P . scapulatus across jurisdictions over up to 5 years. Results Individuals were estimated to travel long distances annually among a network of 755 roosts ( P . alecto , 1427–1887 km; P . poliocephalus , 2268–2564 km; and P . scapulatus , 3782–6073 km), but with little uniformity among their directions of travel. This indicates that flying-fox populations are composed of extremely mobile individuals that move nomadically and at species-specific rates. Individuals of all three species exhibited very low fidelity to roosts locally, resulting in very high estimated daily colony turnover rates ( P . alecto , 11.9 ± 1.3%; P . poliocephalus , 17.5 ± 1.3%; and P . scapulatus , 36.4 ± 6.5%). This indicates that flying-fox roosts form nodes in a vast continental network of highly dynamic “staging posts” through which extremely mobile individuals travel far and wide across their species ranges. Conclusions The extreme inter-roost mobility reported here demonstrates the extent of the ecological linkages that nomadic flying-foxes provide across Australia’s contemporary fragmented landscape, with profound implications for the ecosystem services and zoonotic dynamics of flying-fox populations. In addition, the extreme mobility means that impacts from local management actions can readily reverberate across jurisdictions throughout the species ranges; therefore, local management actions need to be assessed with reference to actions elsewhere and hence require national coordination. These findings underscore the need for sound understanding of animal movement dynamics to support evidence-based, transboundary conservation and management policy, tailored to the unique movement ecologies of species. Background Conventional conservation approaches, which typically view species as organized around discrete local populations, are inadequate for highly mobile species [ 1 ], particularly in the context of environmental change [ 2 ]. Highly mobile species often require multiple habitats to obtain different resources at different stages of their life cycles, and their persistence depends on the availability and accessibility of the requisite suite of habitats [ 3 , 4 ]. The unpredictable movements of nomadic species make it particularly difficult to decide where and how to act to mitigate threatening processes [ 5 ]. This can be further complicated when such species cross jurisdictional boundaries within or between countries [ 6 ], making a unified program of conservation management much more difficult to achieve. For effective conservation management, it is essential to have a robust understanding of the movement ecology of highly mobile species, but this can only be accomplished by following numerous individuals within a population, across multiple habitats within the species’ range [ 7 , 8 ]. Australian flying-foxes ( Pteropus spp.) are large bats that forage by night on floral resources and rest by day in arboreal roosts that may contain colonies of many thousands of individuals [ 9 ] with a complex social architecture [ 10 , 11 ]. Roost locations can be stable for decades [ 12 ], and while “traditional” sites are mostly occupied seasonally, more recent, urban roosts are occupied permanently [ 13 ], albeit with great seasonal variation in local numbers [ 14 ]. The prevailing assumption is that flying-foxes are organized around local “resident” populations that show (seasonal) fidelity to a particular site [ 13 ]. However, like other large pteropodids elsewhere (e.g., [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ]), Australian flying-fox individuals can be highly mobile, with movements ranging from small relocations within roosts and foraging sites [ 10 ] to nightly foraging trips of up to 80 km [ 23 , 24 ] and long-distance movements of several thousand kilometers [ 25 , 26 ]. Therefore, how flying-fox populations are locally organized is critically dependent on the extent and seasonal dynamics of movements among roosts. To date, as for the other large pteropodids elsewhere (e.g., [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ]), movement studies of Australian flying-foxes are limited to small samples of radio- [ 23 , 27 , 28 , 29 ] and satellite-tracked [ 21 , 25 , 26 ] individuals, so the extent and seasonal dynamics of movements among roosts have never been formally assessed, hampering effective conservation and management of these ecologically important species. The mobility of flying-foxes is thought to enable them to exploit Australia’s ephemeral floral resources [ 30 ] and makes them key long-distance pollen and seed dispersers [ 31 , 32 , 33 ]. Long-distance seed and pollen dispersal by all four Australian mainland Pteropus species ( Pteropus alecto , P . poliocephalus , P . scapulatus , and P . conspicillatus ) would be of crucial conservation significance as it promotes gene flow between impoverished forest patches and facilitates range shifts of forage trees under climate change [ 34 , 35 ]. Knowledge on the extent and seasonal dynamics of movements among roosts is thus key for understanding the linkages that flying-foxes provide in Australia’s contemporary fragmented landscape. The mobility of flying-foxes is also thought to underpin their role in the ecology of several emerging infectious diseases. In Australia, flying-foxes are the recognized natural hosts for various viral agents that threaten livestock and/or human health,<|im_end|> <|im_start|>assistant New research led by scientists at Western Sydney University and published in BMC Biology shows that flying-foxes are always on the move among a vast network of roosts, creating key challenges for their management and conservation in Australia. Australia's flying-foxes are amongst the largest mammals in the world that are capable of powered flight. They are highly mobile, which is thought to make them key seed and pollen dispersers in Australia's fragmented forest ecosystems. However, their mobility also facilitates transmission of disease and often brings them in conflict with humans, and so they require a precarious balancing of conservation and management concern. To gain a detailed understanding of flying-fox mobility at the landscape scale, the researchers analyzed the movements of 201 satellite-tracked individuals across eastern Australia, for up to five years. Three species were monitored including 109 gray-headed flying-foxes (P. poliocephalus), 80 black flying-foxes (Pteropus alecto) and 12 little red flying-foxes (P. scapulatus). The tracked flying-foxes used a total of 755 roost sites between them, of which more than half were previously unrecorded. One roost site, the Hervey Bay Botanic Gardens, was visited by tracked individuals from all three species. Individuals traveled thousands of kilometers among many of those roosts each year, with one gray-headed flying-fox covering at least 12,337 km between 123 roosts in 37 local government areas over 1,629 tracking days. Associate Professor Justin Welbergen, the lead author, said: "Our findings indicate that flying-fox roosts are better viewed as parts of a network of 'staging posts' that provide temporary shelters to extremely mobile individuals that wander nomadically throughout much of eastern Australia. This contrasts with the conventional portrayal of a roost as being home to a resident population made up of the same individuals. It has long been recognized that flying-foxes have the capacity to travel long distances; however, the vast scale of the movements among roosts shown by our study indicates that nomadism is in fact a fundamental aspect of flying-fox biology. This necessitates a re-evaluation of how these fascinating animals are managed and conserved." While the extreme mobility has profound implications for the roles of flying-foxes as seed and pollen dispersers, it also means that negative impacts from localized management actions can easily reverberate throughout the species ranges. Coordinated management and conservation efforts should therefore be implemented across Australia to protect these ecologically important species. The research is published in BMC Biology. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 25837, 48023, 29711, 6373, 315, 7701, 6505, 9606, 14117, 5304, 11944, 6677, 315, 19567, 315, 7931, 4028, 872, 2134, 26, 3686, 11, 828, 527, 19029, 2561, 520, 8475, 993, 9491, 354, 3342, 10020, 29505, 13, 47152, 12, 15361, 288, 320, 393, 466, 46970, 91799, 6266, 527, 3544, 43308, 430, 369, 425, 555, 3814, 389, 46119, 5070, 323, 2800, 555, 1938, 304, 59588, 90868, 938, 537, 82, 430, 1253, 6782, 49028, 315, 1690, 9214, 315, 7931, 13, 2435, 527, 279, 7928, 56669, 13171, 315, 23134, 11213, 11, 323, 527, 7701, 6505, 11, 902, 3727, 1124, 1401, 10533, 323, 79784, 79835, 388, 304, 13952, 61951, 13, 4452, 11, 872, 31139, 1101, 73633, 18874, 315, 1167, 9186, 14546, 19338, 323, 12716, 1124, 304, 12324, 449, 12966, 11, 323, 779, 814, 1397, 264, 93222, 44463, 315, 29711, 323, 6373, 10742, 6957, 872, 10846, 4435, 2134, 13, 5810, 11, 584, 24564, 279, 8494, 25480, 19567, 315, 220, 679, 24088, 10398, 11440, 7931, 11, 8405, 31069, 7872, 389, 279, 958, 53034, 537, 19567, 315, 2380, 16706, 12, 15361, 9606, 25, 393, 466, 46970, 264, 772, 78, 1174, 393, 662, 1499, 822, 59822, 87227, 1174, 323, 393, 662, 1156, 391, 360, 1015, 4028, 56043, 927, 709, 311, 220, 20, 1667, 13, 18591, 62525, 1051, 13240, 311, 5944, 1317, 27650, 30171, 4315, 264, 4009, 315, 220, 23532, 938, 537, 82, 320, 393, 662, 264, 772, 78, 1174, 220, 10239, 22, 4235, 9367, 22, 13437, 26, 393, 662, 1499, 822, 59822, 87227, 1174, 220, 14057, 23, 4235, 4146, 19, 13437, 26, 323, 393, 662, 1156, 391, 360, 1015, 1174, 220, 19166, 17, 4235, 21996, 18, 13437, 705, 719, 449, 2697, 14113, 488, 4315, 872, 18445, 315, 5944, 13, 1115, 15151, 430, 16706, 12, 15361, 22673, 527, 24306, 315, 9193, 6505, 7931, 430, 3351, 9859, 329, 2740, 323, 520, 9606, 19440, 7969, 13, 62525, 315, 682, 2380, 9606, 51713, 1633, 3428, 83604, 311, 938, 537, 82, 24392, 11, 13239, 304, 1633, 1579, 13240, 7446, 42036, 48639, 7969, 320, 393, 662, 264, 772, 78, 1174, 220, 806, 13, 24, 20903, 220, 16, 13, 18, 16571, 393, 662, 1499, 822, 59822, 87227, 1174, 220, 1114, 13, 20, 20903, 220, 16, 13, 18, 16571, 323, 393, 662, 1156, 391, 360, 1015, 1174, 220, 1927, 13, 19, 20903, 220, 21, 13, 20, 53172, 1115, 15151, 430, 16706, 12, 15361, 938, 537, 82, 1376, 7954, 304, 264, 13057, 58636, 4009, 315, 7701, 8915, 1054, 267, 4210, 8158, 863, 1555, 902, 9193, 6505, 7931, 5944, 3117, 323, 7029, 4028, 872, 9606, 21986, 13, 1221, 24436, 578, 14560, 958, 53034, 537, 31139, 5068, 1618, 32216, 279, 13112, 315, 279, 50953, 2723, 1154, 430, 9859, 37314, 16706, 12, 15361, 288, 3493, 4028, 8494, 753, 19225, 87195, 18921, 11, 449, 28254, 25127, 369, 279, 26031, 3600, 323, 1167, 9186, 14546, 30295, 315, 16706, 12, 15361, 22673, 13, 763, 5369, 11, 279, 14560, 31139, 3445, 430, 25949, 505, 2254, 6373, 6299, 649, 31368, 36237, 655, 349, 4028, 56043, 6957, 279, 9606, 21986, 26, 9093, 11, 2254, 6373, 6299, 1205, 311, 387, 32448, 449, 5905, 311, 6299, 18403, 323, 16472, 1397, 5426, 38793, 13, 4314, 14955, 53209, 279, 1205, 369, 5222, 8830, 315, 10065, 7351, 30295, 311, 1862, 6029, 6108, 11, 1380, 66280, 29711, 323, 6373, 4947, 11, 41891, 311, 279, 5016, 7351, 12208, 9268, 315, 9606, 13, 25837, 1221, 44322, 29711, 20414, 11, 902, 11383, 1684, 9606, 439, 17057, 2212, 44279, 2254, 22673, 11, 527, 46579, 369, 7701, 6505, 9606, 510, 220, 16, 10881, 8104, 304, 279, 2317, 315, 12434, 2349, 510, 220, 17, 21087, 53485, 6505, 9606, 3629, 1397, 5361, 71699, 311, 6994, 2204, 5070, 520, 2204, 18094, 315, 872, 2324, 25492, 11, 323, 872, 42056, 14117, 389, 279, 18539, 323, 40800, 315, 279, 82780, 16578, 315, 71699, 510, 220, 18, 1174, 220, 19, 21087, 578, 50235, 19567, 315, 9859, 37314, 9606, 1304, 433, 8104, 5107, 311, 10491, 1405, 323, 1268, 311, 1180, 311, 50460, 27903, 11618, 510, 220, 20, 21087, 1115, 649, 387, 4726, 17395, 994, 1778, 9606, 5425, 29101, 278, 23546, 2949, 477, 1990, 5961, 510, 220, 21, 10881, 3339, 264, 43790, 2068, 315, 29711, 6373, 1790, 810, 5107, 311, 11322, 13, 1789, 7524, 29711, 6373, 11, 433, 374, 7718, 311, 617, 264, 22514, 8830, 315, 279, 7351, 72546, 315, 7701, 6505, 9606, 11, 719, 420, 649, 1193, 387, 27332, 555, 2768, 12387, 7931, 2949, 264, 7187, 11, 4028, 5361, 71699, 2949, 279, 9606, 529, 2134, 510, 220, 22, 1174, 220, 23, 21087, 13673, 16706, 12, 15361, 288, 320, 393, 466, 46970, 91799, 6266, 527, 3544, 43308, 430, 369, 425, 555, 3814, 389, 46119, 5070, 323, 2800, 555, 1938, 304, 59588, 90868, 938, 537, 82, 430, 1253, 6782, 49028, 315, 1690, 9214, 315, 7931, 510, 220, 24, 2331, 449, 264, 6485, 3674, 18112, 510, 220, 605, 1174, 220, 806, 21087, 12093, 537, 10687, 649, 387, 15528, 369, 11026, 510, 220, 717, 10881, 323, 1418, 1054, 88008, 863, 6732, 527, 10213, 25366, 3280, 750, 11, 810, 3293, 11, 16036, 938, 537, 82, 527, 25366, 31859, 510, 220, 1032, 10881, 43169, 449, 2294, 36899, 23851, 304, 2254, 5219, 510, 220, 975, 21087, 578, 61129, 25329, 374, 430, 16706, 12, 15361, 288, 527, 17057, 2212, 2254, 1054, 40631, 863, 22673, 430, 1501, 320, 17217, 278, 8, 83604, 311, 264, 4040, 2816, 510, 220, 1032, 21087, 4452, 11, 1093, 1023, 3544, 281, 466, 454, 347, 3447, 18403, 320, 68, 1326, 2637, 510, 220, 868, 1174, 220, 845, 1174, 220, 1114, 1174, 220, 972, 1174, 220, 777, 1174, 220, 508, 1174, 220, 1691, 1174, 220, 1313, 2331, 705, 13673, 16706, 12, 15361, 7931, 649, 387, 7701, 6505, 11, 449, 19567, 24950, 505, 2678, 312, 32409, 2949, 938, 537, 82, 323, 369, 4210, 6732, 510, 220, 605, 2331, 311, 75860, 369, 4210, 23277, 315, 709, 311, 220, 1490, 13437, 510, 220, 1419, 1174, 220, 1187, 2331, 323, 1317, 74908, 19567, 315, 3892, 16579, 41668, 510, 220, 914, 1174, 220, 1627, 21087, 15636, 11, 1268, 16706, 12, 15361, 22673, 527, 24392, 17057, 374, 41440, 18222, 389, 279, 13112, 323, 36899, 30295, 315, 19567, 4315, 938, 537, 82, 13, 2057, 2457, 11, 439, 369, 279, 1023, 3544, 281, 466, 454, 347, 3447, 18403, 320, 68, 1326, 2637, 510, 220, 868, 1174, 220, 845, 1174, 220, 1114, 1174, 220, 972, 1174, 220, 777, 1174, 220, 508, 1174, 220, 1691, 1174, 220, 1313, 2331, 705, 7351, 7978, 315, 13673, 16706, 12, 15361, 288, 527, 7347, 311, 2678, 10688, 315, 9063, 12, 510, 220, 1419, 1174, 220, 1544, 1174, 220, 1591, 1174, 220, 1682, 2331, 323, 24088, 10398, 11440, 510, 220, 1691, 1174, 220, 914, 1174, 220, 1627, 2331, 7931, 11, 779, 279, 13112, 323, 36899, 30295, 315, 19567, 4315, 938, 537, 82, 617, 2646, 1027, 37402, 32448, 11, 13824, 61818, 7524, 29711, 323, 6373, 315, 1521, 12208, 30450, 3062, 9606, 13, 578, 31139, 315, 16706, 12, 15361, 288, 374, 3463, 311, 7431, 1124, 311, 33294, 8494, 753, 83234, 3333, 46119, 5070, 510, 220, 966, 2331, 323, 3727, 1124, 1401, 1317, 74908, 79784, 323, 10533, 79835, 388, 510, 220, 2148, 1174, 220, 843, 1174, 220, 1644, 21087, 5843, 74908, 10533, 323, 79784, 79835, 278, 555, 682, 3116, 13673, 51115, 393, 466, 46970, 9606, 320, 393, 466, 46970, 264, 772, 78, 1174, 393, 662, 1499, 822, 59822, 87227, 1174, 393, 662, 1156, 391, 360, 1015, 1174, 323, 393, 662, 75315, 484, 1015, 883, 1053, 387, 315, 16996, 29711, 26431, 439, 433, 39990, 15207, 6530, 1990, 88398, 13952, 29760, 323, 73633, 2134, 29735, 315, 369, 425, 12690, 1234, 10182, 2349, 510, 220, 1958, 1174, 220, 1758, 21087, 33025, 389, 279, 13112, 323, 36899, 30295, 315, 19567, 4315, 938, 537, 82, 374, 8617, 1401, 369, 8830, 279, 2723, 1154, 430, 16706, 12, 15361, 288, 3493, 304, 8494, 753, 19225, 87195, 18921, 13, 578, 31139, 315, 16706, 12, 15361, 288, 374, 1101, 3463, 311, 1234, 13576, 872, 3560, 304, 279, 72546, 315, 3892, 24084, 50600, 19338, 13, 763, 8494, 11, 16706, 12, 15361, 288, 527, 279, 15324, 5933, 18939, 369, 5370, 29962, 13307, 430, 40250, 51876, 323, 5255, 3823, 2890, 11, 128257, 198, 128256, 78191, 198, 3648, 3495, 6197, 555, 14248, 520, 11104, 21972, 3907, 323, 4756, 304, 82806, 40023, 5039, 430, 16706, 12, 15361, 288, 527, 2744, 389, 279, 3351, 4315, 264, 13057, 4009, 315, 938, 537, 82, 11, 6968, 1401, 11774, 369, 872, 6373, 323, 29711, 304, 8494, 13, 8494, 596, 16706, 12, 15361, 288, 527, 24059, 279, 7928, 56669, 304, 279, 1917, 430, 527, 13171, 315, 23134, 11213, 13, 2435, 527, 7701, 6505, 11, 902, 374, 3463, 311, 1304, 1124, 1401, 10533, 323, 79784, 79835, 388, 304, 8494, 596, 87195, 13952, 61951, 13, 4452, 11, 872, 31139, 1101, 73633, 18874, 315, 8624, 323, 3629, 12716, 1124, 304, 12324, 449, 12966, 11, 323, 779, 814, 1397, 264, 93222, 44463, 315, 29711, 323, 6373, 4747, 13, 2057, 8895, 264, 11944, 8830, 315, 16706, 12, 15361, 31139, 520, 279, 18921, 5569, 11, 279, 12074, 30239, 279, 19567, 315, 220, 679, 24088, 10398, 11440, 7931, 4028, 24024, 8494, 11, 369, 709, 311, 4330, 1667, 13, 14853, 9606, 1051, 41223, 2737, 220, 7743, 18004, 62166, 16706, 12, 15361, 288, 320, 47, 13, 1499, 822, 59822, 87227, 705, 220, 1490, 3776, 16706, 12, 15361, 288, 320, 47, 466, 46970, 264, 772, 78, 8, 323, 220, 717, 2697, 2579, 16706, 12, 15361, 288, 320, 47, 13, 1156, 391, 360, 1015, 570, 578, 34156, 16706, 12, 15361, 288, 1511, 264, 2860, 315, 220, 23532, 938, 537, 6732, 1990, 1124, 11, 315, 902, 810, 1109, 4376, 1051, 8767, 653, 8716, 291, 13, 3861, 938, 537, 2816, 11, 279, 6385, 5735, 9332, 23869, 32370, 43143, 11, 574, 12263, 555, 34156, 7931, 505, 682, 2380, 9606, 13, 62525, 31796, 9214, 315, 41668, 4315, 1690, 315, 1884, 938, 537, 82, 1855, 1060, 11, 449, 832, 18004, 62166, 16706, 12, 15361, 18702, 520, 3325, 220, 717, 11, 17609, 13437, 1990, 220, 4513, 938, 537, 82, 304, 220, 1806, 2254, 3109, 5789, 927, 220, 16, 11, 24239, 15194, 2919, 13, 33468, 17054, 23278, 26056, 655, 4469, 11, 279, 3063, 3229, 11, 1071, 25, 330, 8140, 14955, 13519, 430, 16706, 12, 15361, 938, 537, 82, 527, 2731, 19894, 439, 5596, 315, 264, 4009, 315, 364, 267, 4210, 8158, 6, 430, 3493, 13643, 52888, 311, 9193, 6505, 7931, 430, 40320, 9859, 329, 2740, 6957, 1790, 315, 24024, 8494, 13, 1115, 83379, 449, 279, 21349, 75033, 315, 264, 938, 537, 439, 1694, 2162, 311, 264, 19504, 7187, 1903, 709, 315, 279, 1890, 7931, 13, 1102, 706, 1317, 1027, 15324, 430, 16706, 12, 15361, 288, 617, 279, 8824, 311, 5944, 1317, 27650, 26, 4869, 11, 279, 13057, 5569, 315, 279, 19567, 4315, 938, 537, 82, 6982, 555, 1057, 4007, 15151, 430, 9859, 329, 2191, 374, 304, 2144, 264, 16188, 13189, 315, 16706, 12, 15361, 34458, 13, 1115, 4541, 82829, 264, 312, 5773, 24756, 315, 1268, 1521, 27387, 10099, 527, 9152, 323, 1615, 2841, 1210, 6104, 279, 14560, 31139, 706, 28254, 25127, 369, 279, 13073, 315, 16706, 12, 15361, 288, 439, 10533, 323, 79784, 79835, 388, 11, 433, 1101, 3445, 430, 8389, 25949, 505, 44589, 6373, 6299, 649, 6847, 36237, 655, 349, 6957, 279, 9606, 21986, 13, 3623, 83569, 6373, 323, 29711, 9045, 1288, 9093, 387, 11798, 4028, 8494, 311, 6144, 1521, 12208, 30450, 3062, 9606, 13, 578, 3495, 374, 4756, 304, 82806, 40023, 13, 220, 128257, 198 ]

1,904

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Societies value the marine environment for its health-promoting potential. In this preregistered study, we used cross-sectional, secondary data from the Seas, Oceans, and Public Health In Europe (SOPHIE) and Australia (SOPHIA) surveys to investigate: (a) relationships of self-reported home coastal proximity and coastal visits with self-reported general health; (b) the potential of both to buffer income-related health inequalities; and (c) the generalizability of these propositions across 15 countries ( n = 11,916–14,702). We find broad cross-country generalizability that living nearer to the coast and visiting it more often are associated with better self-reported general health. These results suggest that coastal access may be a viable and generalized route to promote public health across Europe and Australia. However, the relationships are not strongest among individuals with low household incomes, thereby challenging widespread assumptions of equigenesis that access to coastal environments can buffer income-related health inequalities. Introduction Societies value the marine environment for various reasons, including its health-promoting potential. Five single-country studies from the United Kingdom 1 , 2 , 3 , Belgium 4 , and Spain 5 (for details, see Supplementary Notes 1 ) found that individuals who lived nearer to the coast reported better health than those living further away. Supporting this cross-sectional research, a longitudinal study in England 6 showed that individuals reported better general health in years when they lived within 5 km of the coast compared to years when they lived further away. The relationship between living nearer to the coast and better health may result from reduced exposure to some environmental hazards (e.g., air pollution, but the evidence is mixed 4 ), more physical activity (e.g., walking 1 , 7 ), and/or opportunities for indirect contact (e.g., views from home) which are associated with lower psychological distress 8 . Moreover, living nearer to the coast is associated with more frequent coastal visits 9 . Coastal visit frequency may benefit health because it promotes longer bouts of and/or higher intensity forms of physical activity 10 , social interactions, and psychological restoration from stress 11 , which can help reduce allostatic load 6 . Given that coastal visit frequency drops exponentially as a function of home distance, these benefits are likely to show diminishing marginal returns with increasing home distance 4 . Despite these studies, a systematic review in 2017 7 concluded that the evidence for the relationship between exposure (especially visits) to blue spaces (including coastal environments) and a range of different health metrics was insufficient, in part because it was based on relatively few single-country studies with inconsistent health outcomes. Furthermore, previous research into marine settings and health has mainly focused on the direct relationship between nature contact and health, while its role as a potential modifier is under-researched 12 . One modifier of interest relates to the equigenesis hypothesis 13 , which posits that contact with nature more generally may mitigate or buffer adverse relationships between health risk factors (e.g., low area or household income) and health outcomes 12 , 14 . Buffering and mitigating in this article do not imply causality but mean that a relationship (e.g., between income and health) is weaker under certain circumstances (e.g., with more frequent nature contact). Consistent with the equigenesis hypothesis, a recent systematic review 15 and several studies 13 found that green spaces seemed to buffer the relationship of socioeconomic status and income with health outcomes. Other studies showed no effect 15 or a reverse effect, such that green spaces were associated with poorer health in low-income suburban areas 16 . Regarding coastal contact, two studies from England suggest that living nearer to the coast mitigates the relationship between income deprivation and both self-reported general 3 and mental 17 health. In this study, we investigated: (a) relationships of both self-reported home coastal proximity and coastal visits with self-reported general health; (b) the potential of both to buffer income-related health inequalities; and (c) the generalizability of these propositions across 15 countries, using a Bayesian approach to quantify the relative support for or against any relationships. We analyzed cross-sectional, secondary data from the Seas, Oceans, and Public Health In Europe (SOPHIE) and Australia (SOPHIA) surveys which collected samples representative in terms of age, sex, and region from 14 European countries and Australia, respectively. We expected that both living nearer to the coast (Hypothesis 1) and visiting it more often (Hypothesis 2) would predict better self-reported general health. We also expected that living nearer to the coast (Hypothesis 3) and visiting it more often (Hypothesis 4) would mitigate any adverse relationship between household income and health, such that this relationship would be weaker when individuals live nearer to the coast or visit it more often. We additionally examined generalization across countries in terms of both the proposed relationships (Research Question 1) and the potential modifier (Research Question 2). The present work advances research in four key ways. First, this study goes beyond the relationship of self-reported general health with home coastal proximity to explore its relationship with direct coastal contact (coastal visits). Second, this study investigates the potential modifying role of coastal proximity and visits on the relationship between household income and health. Investigating coastal contact as a potential modifier is important because it may provide “leverage points for intervention” 12 to reduce income-related health inequalities, in addition to policies that focus on reducing income inequality directly. Third, in contrast to previous single-country studies, this study includes samples from 14 European countries and Australia, representative in terms of age, sex, and region. This allows us to test the generalizability of any relationships found across countries. Lastly, we use a Bayesian analytical approach which allows for quantifying the relative support for or against any relationships, provides rich information about the strength of evidence, and is valid for every sample size, including large samples 18 . This approach paves the way for future studies to use the current findings (posterior distributions) as prior knowledge (prior distributions) for an informed and accumulated estimation of the effects 19 . This way, the present", "role": "user" }, { "content": "Seaside residents and holidaymakers have felt it for centuries, but scientists have only recently started to investigate possible health benefits of the coast. Using data from 15 countries, new research led by Sandra Geiger from the Environmental Psychology Group at the University of Vienna confirms public intuition: Living near—but especially visiting—the seaside is associated with better health regardless of country or personal income. The idea that being near the ocean may boost health is not new. As early as 1660, doctors in England began promoting sea bathing and coastal walks for health benefits. By the mid-1800s, taking \"the waters\" or \"sea air\" were widely promoted as health treatments among wealthier European citizens. Technological advances in medicine in the early 20th century led to the decline in such practices, which are only recently gaining popularity again among the medical profession. As part of the project \"Seas, Oceans, and Public Health In Europe,\" led by Professor Lora Fleming, Geiger and colleagues from the Universities of Vienna, Exeter, and Birmingham, as well as Seascape Belgium and the European Marine Board, surveyed over 15,000 participants across 14 European countries (Belgium, Bulgaria, Czechia, France, Germany, Greece, Ireland, Italy, the Netherlands, Norway, Poland, Portugal, Spain, the United Kingdom) and Australia about their opinions on various marine-related activities and their own health. The findings, published in the journal Communications Earth & Environment, surprised the team. Lead author Geiger said, \"It is striking to see such consistent and clear patterns across all 15 countries. We also now demonstrate that everybody seems to benefit from being near the seaside, not just the wealthy. Although the associations are relatively small, living near and especially visiting the coast can still have substantial effects on population health.\" Understanding the potential benefits of coastal access for all members of society is key for policymaking. Dr. Paula Kellett from the European Marine Board said, \"The substantial health benefits of equal and sustainable access to our coasts should be considered when countries develop their marine spatial plans, consider future housing needs, and develop public transportation links.\" But what does this mean for landlocked residents like Geiger and her colleagues in Austria? \"Austrians and other central Europeans visit the coasts in their millions during the summer months, so they too get to experience some of these benefits. Besides, we are also starting to appreciate the similar health benefits offered by inland waters such as lakes and natural pools.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Societies value the marine environment for its health-promoting potential. In this preregistered study, we used cross-sectional, secondary data from the Seas, Oceans, and Public Health In Europe (SOPHIE) and Australia (SOPHIA) surveys to investigate: (a) relationships of self-reported home coastal proximity and coastal visits with self-reported general health; (b) the potential of both to buffer income-related health inequalities; and (c) the generalizability of these propositions across 15 countries ( n = 11,916–14,702). We find broad cross-country generalizability that living nearer to the coast and visiting it more often are associated with better self-reported general health. These results suggest that coastal access may be a viable and generalized route to promote public health across Europe and Australia. However, the relationships are not strongest among individuals with low household incomes, thereby challenging widespread assumptions of equigenesis that access to coastal environments can buffer income-related health inequalities. Introduction Societies value the marine environment for various reasons, including its health-promoting potential. Five single-country studies from the United Kingdom 1 , 2 , 3 , Belgium 4 , and Spain 5 (for details, see Supplementary Notes 1 ) found that individuals who lived nearer to the coast reported better health than those living further away. Supporting this cross-sectional research, a longitudinal study in England 6 showed that individuals reported better general health in years when they lived within 5 km of the coast compared to years when they lived further away. The relationship between living nearer to the coast and better health may result from reduced exposure to some environmental hazards (e.g., air pollution, but the evidence is mixed 4 ), more physical activity (e.g., walking 1 , 7 ), and/or opportunities for indirect contact (e.g., views from home) which are associated with lower psychological distress 8 . Moreover, living nearer to the coast is associated with more frequent coastal visits 9 . Coastal visit frequency may benefit health because it promotes longer bouts of and/or higher intensity forms of physical activity 10 , social interactions, and psychological restoration from stress 11 , which can help reduce allostatic load 6 . Given that coastal visit frequency drops exponentially as a function of home distance, these benefits are likely to show diminishing marginal returns with increasing home distance 4 . Despite these studies, a systematic review in 2017 7 concluded that the evidence for the relationship between exposure (especially visits) to blue spaces (including coastal environments) and a range of different health metrics was insufficient, in part because it was based on relatively few single-country studies with inconsistent health outcomes. Furthermore, previous research into marine settings and health has mainly focused on the direct relationship between nature contact and health, while its role as a potential modifier is under-researched 12 . One modifier of interest relates to the equigenesis hypothesis 13 , which posits that contact with nature more generally may mitigate or buffer adverse relationships between health risk factors (e.g., low area or household income) and health outcomes 12 , 14 . Buffering and mitigating in this article do not imply causality but mean that a relationship (e.g., between income and health) is weaker under certain circumstances (e.g., with more frequent nature contact). Consistent with the equigenesis hypothesis, a recent systematic review 15 and several studies 13 found that green spaces seemed to buffer the relationship of socioeconomic status and income with health outcomes. Other studies showed no effect 15 or a reverse effect, such that green spaces were associated with poorer health in low-income suburban areas 16 . Regarding coastal contact, two studies from England suggest that living nearer to the coast mitigates the relationship between income deprivation and both self-reported general 3 and mental 17 health. In this study, we investigated: (a) relationships of both self-reported home coastal proximity and coastal visits with self-reported general health; (b) the potential of both to buffer income-related health inequalities; and (c) the generalizability of these propositions across 15 countries, using a Bayesian approach to quantify the relative support for or against any relationships. We analyzed cross-sectional, secondary data from the Seas, Oceans, and Public Health In Europe (SOPHIE) and Australia (SOPHIA) surveys which collected samples representative in terms of age, sex, and region from 14 European countries and Australia, respectively. We expected that both living nearer to the coast (Hypothesis 1) and visiting it more often (Hypothesis 2) would predict better self-reported general health. We also expected that living nearer to the coast (Hypothesis 3) and visiting it more often (Hypothesis 4) would mitigate any adverse relationship between household income and health, such that this relationship would be weaker when individuals live nearer to the coast or visit it more often. We additionally examined generalization across countries in terms of both the proposed relationships (Research Question 1) and the potential modifier (Research Question 2). The present work advances research in four key ways. First, this study goes beyond the relationship of self-reported general health with home coastal proximity to explore its relationship with direct coastal contact (coastal visits). Second, this study investigates the potential modifying role of coastal proximity and visits on the relationship between household income and health. Investigating coastal contact as a potential modifier is important because it may provide “leverage points for intervention” 12 to reduce income-related health inequalities, in addition to policies that focus on reducing income inequality directly. Third, in contrast to previous single-country studies, this study includes samples from 14 European countries and Australia, representative in terms of age, sex, and region. This allows us to test the generalizability of any relationships found across countries. Lastly, we use a Bayesian analytical approach which allows for quantifying the relative support for or against any relationships, provides rich information about the strength of evidence, and is valid for every sample size, including large samples 18 . This approach paves the way for future studies to use the current findings (posterior distributions) as prior knowledge (prior distributions) for an informed and accumulated estimation of the effects 19 . This way, the present<|im_end|> <|im_start|>assistant Seaside residents and holidaymakers have felt it for centuries, but scientists have only recently started to investigate possible health benefits of the coast. Using data from 15 countries, new research led by Sandra Geiger from the Environmental Psychology Group at the University of Vienna confirms public intuition: Living near—but especially visiting—the seaside is associated with better health regardless of country or personal income. The idea that being near the ocean may boost health is not new. As early as 1660, doctors in England began promoting sea bathing and coastal walks for health benefits. By the mid-1800s, taking "the waters" or "sea air" were widely promoted as health treatments among wealthier European citizens. Technological advances in medicine in the early 20th century led to the decline in such practices, which are only recently gaining popularity again among the medical profession. As part of the project "Seas, Oceans, and Public Health In Europe," led by Professor Lora Fleming, Geiger and colleagues from the Universities of Vienna, Exeter, and Birmingham, as well as Seascape Belgium and the European Marine Board, surveyed over 15,000 participants across 14 European countries (Belgium, Bulgaria, Czechia, France, Germany, Greece, Ireland, Italy, the Netherlands, Norway, Poland, Portugal, Spain, the United Kingdom) and Australia about their opinions on various marine-related activities and their own health. The findings, published in the journal Communications Earth & Environment, surprised the team. Lead author Geiger said, "It is striking to see such consistent and clear patterns across all 15 countries. We also now demonstrate that everybody seems to benefit from being near the seaside, not just the wealthy. Although the associations are relatively small, living near and especially visiting the coast can still have substantial effects on population health." Understanding the potential benefits of coastal access for all members of society is key for policymaking. Dr. Paula Kellett from the European Marine Board said, "The substantial health benefits of equal and sustainable access to our coasts should be considered when countries develop their marine spatial plans, consider future housing needs, and develop public transportation links." But what does this mean for landlocked residents like Geiger and her colleagues in Austria? "Austrians and other central Europeans visit the coasts in their millions during the summer months, so they too get to experience some of these benefits. Besides, we are also starting to appreciate the similar health benefits offered by inland waters such as lakes and natural pools." <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 42509, 26640, 907, 279, 29691, 4676, 369, 1202, 2890, 66271, 11780, 4754, 13, 763, 420, 45001, 70, 1601, 291, 4007, 11, 584, 1511, 5425, 97319, 11, 14580, 828, 505, 279, 93496, 11, 507, 43320, 11, 323, 3142, 6401, 763, 4606, 320, 50, 3143, 39, 5484, 8, 323, 8494, 320, 50, 3143, 39, 5987, 8, 32313, 311, 19874, 25, 320, 64, 8, 12135, 315, 659, 85296, 2162, 35335, 37843, 323, 35335, 21728, 449, 659, 85296, 4689, 2890, 26, 320, 65, 8, 279, 4754, 315, 2225, 311, 4240, 8070, 14228, 2890, 93334, 26, 323, 320, 66, 8, 279, 4689, 450, 2968, 315, 1521, 84373, 4028, 220, 868, 5961, 320, 308, 284, 220, 806, 11, 24487, 4235, 975, 11, 20253, 570, 1226, 1505, 7353, 5425, 56971, 4689, 450, 2968, 430, 5496, 87920, 311, 279, 13962, 323, 17136, 433, 810, 3629, 527, 5938, 449, 2731, 659, 85296, 4689, 2890, 13, 4314, 3135, 4284, 430, 35335, 2680, 1253, 387, 264, 31528, 323, 67217, 6149, 311, 12192, 586, 2890, 4028, 4606, 323, 8494, 13, 4452, 11, 279, 12135, 527, 539, 31005, 4315, 7931, 449, 3428, 14048, 46791, 11, 28592, 17436, 24716, 32946, 315, 3312, 6569, 14093, 430, 2680, 311, 35335, 22484, 649, 4240, 8070, 14228, 2890, 93334, 13, 29438, 42509, 26640, 907, 279, 29691, 4676, 369, 5370, 8125, 11, 2737, 1202, 2890, 66271, 11780, 4754, 13, 21594, 3254, 56971, 7978, 505, 279, 3723, 15422, 220, 16, 1174, 220, 17, 1174, 220, 18, 1174, 34061, 220, 19, 1174, 323, 18157, 220, 20, 320, 2000, 3649, 11, 1518, 99371, 18559, 220, 16, 883, 1766, 430, 7931, 889, 12439, 87920, 311, 279, 13962, 5068, 2731, 2890, 1109, 1884, 5496, 4726, 3201, 13, 75096, 420, 5425, 97319, 3495, 11, 264, 68102, 4007, 304, 9635, 220, 21, 8710, 430, 7931, 5068, 2731, 4689, 2890, 304, 1667, 994, 814, 12439, 2949, 220, 20, 13437, 315, 279, 13962, 7863, 311, 1667, 994, 814, 12439, 4726, 3201, 13, 578, 5133, 1990, 5496, 87920, 311, 279, 13962, 323, 2731, 2890, 1253, 1121, 505, 11293, 14675, 311, 1063, 12434, 52642, 320, 68, 1326, 2637, 3805, 25793, 11, 719, 279, 6029, 374, 9709, 220, 19, 7026, 810, 7106, 5820, 320, 68, 1326, 2637, 11689, 220, 16, 1174, 220, 22, 7026, 323, 5255, 10708, 369, 25636, 3729, 320, 68, 1326, 2637, 6325, 505, 2162, 8, 902, 527, 5938, 449, 4827, 24064, 35104, 220, 23, 662, 23674, 11, 5496, 87920, 311, 279, 13962, 374, 5938, 449, 810, 21420, 35335, 21728, 220, 24, 662, 72658, 4034, 11900, 1253, 8935, 2890, 1606, 433, 39990, 5129, 96271, 315, 323, 5255, 5190, 21261, 7739, 315, 7106, 5820, 220, 605, 1174, 3674, 22639, 11, 323, 24064, 35093, 505, 8631, 220, 806, 1174, 902, 649, 1520, 8108, 63747, 2020, 2865, 220, 21, 662, 16644, 430, 35335, 4034, 11900, 21701, 75251, 439, 264, 734, 315, 2162, 6138, 11, 1521, 7720, 527, 4461, 311, 1501, 84153, 32873, 4780, 449, 7859, 2162, 6138, 220, 19, 662, 18185, 1521, 7978, 11, 264, 37538, 3477, 304, 220, 679, 22, 220, 22, 20536, 430, 279, 6029, 369, 279, 5133, 1990, 14675, 320, 36046, 21728, 8, 311, 6437, 12908, 320, 16564, 35335, 22484, 8, 323, 264, 2134, 315, 2204, 2890, 17150, 574, 39413, 11, 304, 961, 1606, 433, 574, 3196, 389, 12309, 2478, 3254, 56971, 7978, 449, 40240, 2890, 20124, 13, 24296, 11, 3766, 3495, 1139, 29691, 5110, 323, 2890, 706, 14918, 10968, 389, 279, 2167, 5133, 1990, 7138, 3729, 323, 2890, 11, 1418, 1202, 3560, 439, 264, 4754, 23575, 374, 1234, 5621, 1874, 291, 220, 717, 662, 3861, 23575, 315, 2802, 36716, 311, 279, 3312, 6569, 14093, 31178, 220, 1032, 1174, 902, 1153, 1220, 430, 3729, 449, 7138, 810, 8965, 1253, 50460, 477, 4240, 31959, 12135, 1990, 2890, 5326, 9547, 320, 68, 1326, 2637, 3428, 3158, 477, 14048, 8070, 8, 323, 2890, 20124, 220, 717, 1174, 220, 975, 662, 10525, 287, 323, 36090, 1113, 304, 420, 4652, 656, 539, 34608, 25540, 2786, 719, 3152, 430, 264, 5133, 320, 68, 1326, 2637, 1990, 8070, 323, 2890, 8, 374, 43383, 1234, 3738, 13463, 320, 68, 1326, 2637, 449, 810, 21420, 7138, 3729, 570, 7440, 18620, 449, 279, 3312, 6569, 14093, 31178, 11, 264, 3293, 37538, 3477, 220, 868, 323, 3892, 7978, 220, 1032, 1766, 430, 6307, 12908, 9508, 311, 4240, 279, 5133, 315, 80431, 2704, 323, 8070, 449, 2890, 20124, 13, 7089, 7978, 8710, 912, 2515, 220, 868, 477, 264, 10134, 2515, 11, 1778, 430, 6307, 12908, 1051, 5938, 449, 66281, 2890, 304, 3428, 32197, 46318, 5789, 220, 845, 662, 73773, 35335, 3729, 11, 1403, 7978, 505, 9635, 4284, 430, 5496, 87920, 311, 279, 13962, 36090, 988, 279, 5133, 1990, 8070, 69764, 323, 2225, 659, 85296, 4689, 220, 18, 323, 10723, 220, 1114, 2890, 13, 763, 420, 4007, 11, 584, 27313, 25, 320, 64, 8, 12135, 315, 2225, 659, 85296, 2162, 35335, 37843, 323, 35335, 21728, 449, 659, 85296, 4689, 2890, 26, 320, 65, 8, 279, 4754, 315, 2225, 311, 4240, 8070, 14228, 2890, 93334, 26, 323, 320, 66, 8, 279, 4689, 450, 2968, 315, 1521, 84373, 4028, 220, 868, 5961, 11, 1701, 264, 99234, 5603, 311, 76498, 279, 8844, 1862, 369, 477, 2403, 904, 12135, 13, 1226, 30239, 5425, 97319, 11, 14580, 828, 505, 279, 93496, 11, 507, 43320, 11, 323, 3142, 6401, 763, 4606, 320, 50, 3143, 39, 5484, 8, 323, 8494, 320, 50, 3143, 39, 5987, 8, 32313, 902, 14890, 10688, 18740, 304, 3878, 315, 4325, 11, 1877, 11, 323, 5654, 505, 220, 975, 7665, 5961, 323, 8494, 11, 15947, 13, 1226, 3685, 430, 2225, 5496, 87920, 311, 279, 13962, 320, 39, 60400, 13491, 220, 16, 8, 323, 17136, 433, 810, 3629, 320, 39, 60400, 13491, 220, 17, 8, 1053, 7168, 2731, 659, 85296, 4689, 2890, 13, 1226, 1101, 3685, 430, 5496, 87920, 311, 279, 13962, 320, 39, 60400, 13491, 220, 18, 8, 323, 17136, 433, 810, 3629, 320, 39, 60400, 13491, 220, 19, 8, 1053, 50460, 904, 31959, 5133, 1990, 14048, 8070, 323, 2890, 11, 1778, 430, 420, 5133, 1053, 387, 43383, 994, 7931, 3974, 87920, 311, 279, 13962, 477, 4034, 433, 810, 3629, 13, 1226, 37938, 25078, 4689, 2065, 4028, 5961, 304, 3878, 315, 2225, 279, 11223, 12135, 320, 28528, 16225, 220, 16, 8, 323, 279, 4754, 23575, 320, 28528, 16225, 220, 17, 570, 578, 3118, 990, 31003, 3495, 304, 3116, 1401, 5627, 13, 5629, 11, 420, 4007, 5900, 7953, 279, 5133, 315, 659, 85296, 4689, 2890, 449, 2162, 35335, 37843, 311, 13488, 1202, 5133, 449, 2167, 35335, 3729, 320, 1030, 561, 278, 21728, 570, 10657, 11, 420, 4007, 84363, 279, 4754, 47141, 3560, 315, 35335, 37843, 323, 21728, 389, 279, 5133, 1990, 14048, 8070, 323, 2890, 13, 33180, 1113, 35335, 3729, 439, 264, 4754, 23575, 374, 3062, 1606, 433, 1253, 3493, 1054, 273, 4453, 3585, 369, 21623, 863, 220, 717, 311, 8108, 8070, 14228, 2890, 93334, 11, 304, 5369, 311, 10396, 430, 5357, 389, 18189, 8070, 32305, 6089, 13, 21530, 11, 304, 13168, 311, 3766, 3254, 56971, 7978, 11, 420, 4007, 5764, 10688, 505, 220, 975, 7665, 5961, 323, 8494, 11, 18740, 304, 3878, 315, 4325, 11, 1877, 11, 323, 5654, 13, 1115, 6276, 603, 311, 1296, 279, 4689, 450, 2968, 315, 904, 12135, 1766, 4028, 5961, 13, 71809, 11, 584, 1005, 264, 99234, 44064, 5603, 902, 6276, 369, 10484, 7922, 279, 8844, 1862, 369, 477, 2403, 904, 12135, 11, 5825, 9257, 2038, 922, 279, 8333, 315, 6029, 11, 323, 374, 2764, 369, 1475, 6205, 1404, 11, 2737, 3544, 10688, 220, 972, 662, 1115, 5603, 281, 4798, 279, 1648, 369, 3938, 7978, 311, 1005, 279, 1510, 14955, 320, 2252, 14917, 43785, 8, 439, 4972, 6677, 320, 65333, 43785, 8, 369, 459, 16369, 323, 41165, 42304, 315, 279, 6372, 220, 777, 662, 1115, 1648, 11, 279, 3118, 128257, 198, 128256, 78191, 198, 1542, 29612, 11062, 323, 13560, 20481, 617, 6612, 433, 369, 24552, 11, 719, 14248, 617, 1193, 6051, 3940, 311, 19874, 3284, 2890, 7720, 315, 279, 13962, 13, 12362, 828, 505, 220, 868, 5961, 11, 502, 3495, 6197, 555, 56786, 4323, 7420, 505, 279, 25027, 36673, 5856, 520, 279, 3907, 315, 47387, 43496, 586, 57351, 25, 19048, 3221, 38542, 5423, 17136, 22416, 93876, 374, 5938, 449, 2731, 2890, 15851, 315, 3224, 477, 4443, 8070, 13, 578, 4623, 430, 1694, 3221, 279, 18435, 1253, 7916, 2890, 374, 539, 502, 13, 1666, 4216, 439, 220, 11247, 15, 11, 16410, 304, 9635, 6137, 22923, 9581, 73509, 323, 35335, 23291, 369, 2890, 7720, 13, 3296, 279, 5209, 12, 5245, 15, 82, 11, 4737, 330, 1820, 21160, 1, 477, 330, 37541, 3805, 1, 1051, 13882, 30026, 439, 2890, 22972, 4315, 12205, 1291, 7665, 10495, 13, 7146, 5848, 31003, 304, 16088, 304, 279, 4216, 220, 508, 339, 9478, 6197, 311, 279, 18174, 304, 1778, 12659, 11, 902, 527, 1193, 6051, 30240, 23354, 1578, 4315, 279, 6593, 4913, 13, 1666, 961, 315, 279, 2447, 330, 1542, 300, 11, 507, 43320, 11, 323, 3142, 6401, 763, 4606, 1359, 6197, 555, 17054, 445, 6347, 86297, 11, 4323, 7420, 323, 18105, 505, 279, 75898, 315, 47387, 11, 1398, 1430, 11, 323, 36937, 11, 439, 1664, 439, 93496, 5443, 34061, 323, 279, 7665, 23820, 8925, 11, 49098, 927, 220, 868, 11, 931, 13324, 4028, 220, 975, 7665, 5961, 320, 22404, 90339, 11, 59819, 11, 34250, 689, 11, 9822, 11, 10057, 11, 25431, 11, 14990, 11, 15704, 11, 279, 26746, 11, 32603, 11, 28702, 11, 34411, 11, 18157, 11, 279, 3723, 15422, 8, 323, 8494, 922, 872, 18463, 389, 5370, 29691, 14228, 7640, 323, 872, 1866, 2890, 13, 578, 14955, 11, 4756, 304, 279, 8486, 26545, 9420, 612, 11847, 11, 14792, 279, 2128, 13, 30982, 3229, 4323, 7420, 1071, 11, 330, 2181, 374, 21933, 311, 1518, 1778, 13263, 323, 2867, 12912, 4028, 682, 220, 868, 5961, 13, 1226, 1101, 1457, 20461, 430, 16470, 5084, 311, 8935, 505, 1694, 3221, 279, 93876, 11, 539, 1120, 279, 28994, 13, 10541, 279, 30257, 527, 12309, 2678, 11, 5496, 3221, 323, 5423, 17136, 279, 13962, 649, 2103, 617, 12190, 6372, 389, 7187, 2890, 1210, 46551, 279, 4754, 7720, 315, 35335, 2680, 369, 682, 3697, 315, 8396, 374, 1401, 369, 62518, 1802, 13, 2999, 13, 62253, 28263, 28163, 505, 279, 7665, 23820, 8925, 1071, 11, 330, 791, 12190, 2890, 7720, 315, 6273, 323, 22556, 2680, 311, 1057, 1080, 12019, 1288, 387, 6646, 994, 5961, 2274, 872, 29691, 29079, 6787, 11, 2980, 3938, 11983, 3966, 11, 323, 2274, 586, 18386, 7902, 1210, 2030, 1148, 1587, 420, 3152, 369, 4363, 25656, 11062, 1093, 4323, 7420, 323, 1077, 18105, 304, 35998, 30, 330, 32, 592, 36268, 323, 1023, 8792, 51607, 4034, 279, 1080, 12019, 304, 872, 11990, 2391, 279, 7474, 4038, 11, 779, 814, 2288, 636, 311, 3217, 1063, 315, 1521, 7720, 13, 31909, 11, 584, 527, 1101, 6041, 311, 15763, 279, 4528, 2890, 7720, 9076, 555, 77289, 21160, 1778, 439, 44236, 323, 5933, 34239, 1210, 220, 128257, 198 ]

1,816

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Developmental genes are frequently controlled by multiple enhancers sharing similar specificities. As a result, deletions of such regulatory elements have often failed to reveal their full function. Here, we use the Pitx1 testbed locus to characterize in detail the regulatory and cellular identity alterations following the deletion of one of its enhancers ( Pen ). By combining single cell transcriptomics and an in-embryo cell tracing approach, we observe an increased fraction of Pitx1 non/low-expressing cells and a decreased fraction of Pitx1 high-expressing cells. We find that the over-representation of Pitx1 non/low-expressing cells originates from a failure of the Pitx1 locus to coordinate enhancer activities and 3D chromatin changes. This locus mis -activation induces a localized heterochrony and a concurrent loss of irregular connective tissue, eventually leading to a clubfoot phenotype. This data suggests that, in some cases, redundant enhancers may be used to locally enforce a robust activation of their host regulatory landscapes. Introduction Alteration in the enhancer composition of regulatory landscapes at developmental genes can lead to pathologies by modifying the dosage and/or distribution of gene transcription 1 . Indeed, over the past years, losses of single regulatory units within complex and partially redundant regulatory landscapes were shown to have clear phenotypical outcomes despite inducing only partial decreases in average transcription 2 , 3 , 4 , 5 . As the alterations in the regulatory mechanisms following enhancer deletion have mostly been characterized using bulk tissue analysis, it has been difficult to determine the cell-specific variability behind the loss of expression that accounts for phenotypes. In order to understand the precise molecular origin of these phenotypes, it is therefore essential to characterize how a single enhancer contributes to the activation of entire regulatory landscapes in specific cell populations. An effective model system to address these unsolved questions is the limb bud, where organogenesis requires a tight control of gene transcription to achieve correct patterning 6 . Critical to this is Pitx1 , a transcription factor coding gene that is normally expressed in developing hindlimb buds, but not forelimbs, which channels the limb development program to differentiate into a leg 7 , 8 , 9 . Consequently, forelimb Pitx1 gain-of-function can induce an arm-to-leg transformation, featured by the appearance of an ectopic patella as well as complex changes in the muscular and tendons wiring 10 , 11 . In contrast, Pitx1 knock out has been shown to induce partial leg-to-arm transformations with the disappearance of the patella as well as long bone dysplasia and polydactyly 10 , 12 , 13 . Unexpectedly, bulk transcriptomics strategies have only revealed marginal downstream gene expression changes upon Pitx1 loss, suggesting that an interplay between these changes and the growth rate of limb cell subpopulations collectively result in the various phenotypes 8 , 10 , 11 , 13 , 14 . As for many developmental genes, several enhancers coordinate Pitx1 expression in hindlimbs and other tissues. So far, four enhancers have been identified in mammals: PelB which drives a distal reporter pattern in hindlimbs, PDE that drives expression in the mandibular arch, RA4 that can drive reporters in a subset of fore- and hindlimb cells and finally, Pen , a mesenchymal enhancer that drives expression in both fore- and hindlimbs 11 , 15 , 16 . Only the activity of Pen was so far shown to strongly contribute to Pitx1 function in the hindlimb as its deletion leads to a 35–50% reduction of Pitx1 expression 11 . The deletion of Pen has no impact on bone length or digit numbers but induces a partially penetrant clubfoot phenotype, similar to the one observed in mice and humans upon Pitx1 haploinsufficiency 11 , 14 . One particularity to the Pitx1 locus is that it establishes fundamentally different 3D chromatin conformations in transcriptionally active hindlimbs and inactive forelimbs. In active hindlimbs, Pitx1 forms chromatin interactions with cognate cis -regulatory regions spread over 400 kbs, including Pen as well as PDE, RA4 , and PelB . In contrast, in inactive forelimbs these interactions are absent and the Pitx1 gene forms a contact with the polycomb-repressed gene Neurog1 11 . In this work, we use a combination of single cell transcriptomics (scRNA-seq), a fluorescent cell-tracing approach and genomic technologies to define the contribution of a single enhancer ( Pen ) in establishing the epigenetically- and structurally-active Pitx1 regulatory landscape. Moreover, we investigate whether changes in enhancer activities or 3D structure fundamentally associate with transcription or if those can be functionally disconnected of the transcriptional process. Finally, we assess if Pitx1 expression is homogenous across limb cell populations and if distinct expression levels rely on different enhancer repertoires or, alternatively, in progressive changes in cis-regulatory landscape activities. Results Two approaches to track Pitx1 activities suggest a bimodal cis -regulatory behavior In order to characterise transcriptional, chromatin and structural changes following the Pen enhancer deletion, we combined genetic manipulation of the Pitx1 locus with scRNA-seq and chromatin analysis of sorted limb cell populations. Both approaches enabled characterization of complementary features of gene transcriptional regulation following alterations of the cis -regulatory landscape. First, to define the hindlimb cell types that are expressing Pitx1 and to assess how the Pen enhancer regulates its expression in these cells, we generated single-cell preparations from wildtype ( Pitx1 +/+ ) fore- and hindlimb buds as well as Pen enhancer deleted ( Pitx1 Pen−/Pen− ) or Pitx1 knocked-out ( Pitx1 −/− ) hindlimbs (Fig. 1A ). We performed 10× genomics in duplicates from E12.5 limb buds as these correspond to a transition stage between patterning and cell-differentiation phases. By performing unsupervised clustering of all the wildtype and mutant single cell transcriptomic datasets, we identified five clusters, to which all the dataset contributed, corresponding to the main populations of the limb: one mesenchymal cluster ( Prrx1 + , Prrx2 + , Twist1 +; 89% of the cells) and four non-mesenchymal satellite clusters including muscle ( Myod1 +, Ttn +; Myh3 +; 4% of the cells), epithelium ( Wnt6 +, Krt14 + ; 5% of the cells), endothelium", "role": "user" }, { "content": "Embryonic development follows delicate stages: For everything to go well, many genes must coordinate their activity according to a very meticulous scheme and tempo. This precision mechanism sometimes fails, leading to more or less disabling malformations. By studying the Pitx1 gene, one of the genes involved in the construction of the lower limbs, a team from the University of Geneva (UNIGE), in Switzerland, has discovered how a small disturbance in the activation process of this gene is at the origin of clubfoot, a common foot malformation. Indeed, even a fully functional gene cannot act properly without one of its genetic switches. These short DNA sequences provide the signal for the transcription of DNA into RNA, and are essential for this mechanism. And when just one of these switches is missing, the proportion of cells where the gene is active decreases, preventing the lower limbs from being built properly. These results, published in the journal Nature Communications, highlight the hitherto largely underestimated role of genetic switches in developmental disorders. During embryonic development, hundreds of genes must be precisely activated or repressed for organs to build properly. This control of activity is directed by short DNA sequences that, by binding certain proteins in the cell nucleus, act as true ON/OFF switches. \"When the switch is turned on, it initiates the transcription of a gene into RNA, which in turn is translated into a protein that can then perform a specific task,\" explains Guillaume Andrey, professor in the Department of Genetic and Developmental Medicine at the UNIGE Faculty of Medicine, who led this research. \"Without this, genes would be continuously switched on or off, and therefore unable to act selectively, in the right place and at the right time.\" In general, each gene has several switches to ensure that the mechanism is robust. \"However, could the loss of one of these switches have consequences? This is what we wanted to test here by taking as a model the Pitx1 gene, whose role in the construction of the lower limbs is well known,\" says Raquel Rouco, a post-doctoral researcher in Guillaume Andrey's laboratory and co-first author of this study. A decrease in cellular activation that leads to clubfoot To do this, the scientists modified mouse stem cells using the genetic engineering tool CRISPR-CAS 9, which makes it possible to add or remove specific elements of the genome. \"Here, we removed one of Pitx1's switches, called Pen, and added a fluorescence marker that allows us to visualize the gene activation,\" explains Olimpia Bompadre, a doctoral student in the research team and co-first author. \"These modified cells are then aggregated with mouse embryonic cells for us to study their early stages of development.\" Usually, about 90 percent of cells in future legs activate the Pitx1 gene, while 10 percent of cells do not. \"However, when we removed the Pen switch, we found that the proportion of cells that did not activate Pitx1 rose from 10 to 20 percent, which was enough to modify the construction of the musculoskeletal system and to induce a clubfoot,\" explains Guillaume Andrey. The proportion of inactive cells increased particularly in the immature cells of the lower limbs and in the irregular connective tissue, a tissue that is essential for building the musculoskeletal system. The same mechanism in many genes Beyond the Pitx1 gene and clubfoot, the UNIGE scientists have discovered a general principle whose mechanism could be found in a large number of genes. Flawed genetic switches could thus be at the origin of numerous malformations or developmental diseases. Moreover, a gene does not control the development of a single organ in the body, but is usually involved in the construction of a wide range of organs. \"A non-lethal malformation, such as clubfoot for example, could be an indicator of disorders elsewhere in the body that, while not immediately visible, could be much more dangerous. If we can accurately interpret the action of each mutation, we could not only read the information in the genome to find the root cause of a malformation, but also predict effects in other organs, which would silently develop, in order to intervene as early as possible,\" the authors conclude. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Developmental genes are frequently controlled by multiple enhancers sharing similar specificities. As a result, deletions of such regulatory elements have often failed to reveal their full function. Here, we use the Pitx1 testbed locus to characterize in detail the regulatory and cellular identity alterations following the deletion of one of its enhancers ( Pen ). By combining single cell transcriptomics and an in-embryo cell tracing approach, we observe an increased fraction of Pitx1 non/low-expressing cells and a decreased fraction of Pitx1 high-expressing cells. We find that the over-representation of Pitx1 non/low-expressing cells originates from a failure of the Pitx1 locus to coordinate enhancer activities and 3D chromatin changes. This locus mis -activation induces a localized heterochrony and a concurrent loss of irregular connective tissue, eventually leading to a clubfoot phenotype. This data suggests that, in some cases, redundant enhancers may be used to locally enforce a robust activation of their host regulatory landscapes. Introduction Alteration in the enhancer composition of regulatory landscapes at developmental genes can lead to pathologies by modifying the dosage and/or distribution of gene transcription 1 . Indeed, over the past years, losses of single regulatory units within complex and partially redundant regulatory landscapes were shown to have clear phenotypical outcomes despite inducing only partial decreases in average transcription 2 , 3 , 4 , 5 . As the alterations in the regulatory mechanisms following enhancer deletion have mostly been characterized using bulk tissue analysis, it has been difficult to determine the cell-specific variability behind the loss of expression that accounts for phenotypes. In order to understand the precise molecular origin of these phenotypes, it is therefore essential to characterize how a single enhancer contributes to the activation of entire regulatory landscapes in specific cell populations. An effective model system to address these unsolved questions is the limb bud, where organogenesis requires a tight control of gene transcription to achieve correct patterning 6 . Critical to this is Pitx1 , a transcription factor coding gene that is normally expressed in developing hindlimb buds, but not forelimbs, which channels the limb development program to differentiate into a leg 7 , 8 , 9 . Consequently, forelimb Pitx1 gain-of-function can induce an arm-to-leg transformation, featured by the appearance of an ectopic patella as well as complex changes in the muscular and tendons wiring 10 , 11 . In contrast, Pitx1 knock out has been shown to induce partial leg-to-arm transformations with the disappearance of the patella as well as long bone dysplasia and polydactyly 10 , 12 , 13 . Unexpectedly, bulk transcriptomics strategies have only revealed marginal downstream gene expression changes upon Pitx1 loss, suggesting that an interplay between these changes and the growth rate of limb cell subpopulations collectively result in the various phenotypes 8 , 10 , 11 , 13 , 14 . As for many developmental genes, several enhancers coordinate Pitx1 expression in hindlimbs and other tissues. So far, four enhancers have been identified in mammals: PelB which drives a distal reporter pattern in hindlimbs, PDE that drives expression in the mandibular arch, RA4 that can drive reporters in a subset of fore- and hindlimb cells and finally, Pen , a mesenchymal enhancer that drives expression in both fore- and hindlimbs 11 , 15 , 16 . Only the activity of Pen was so far shown to strongly contribute to Pitx1 function in the hindlimb as its deletion leads to a 35–50% reduction of Pitx1 expression 11 . The deletion of Pen has no impact on bone length or digit numbers but induces a partially penetrant clubfoot phenotype, similar to the one observed in mice and humans upon Pitx1 haploinsufficiency 11 , 14 . One particularity to the Pitx1 locus is that it establishes fundamentally different 3D chromatin conformations in transcriptionally active hindlimbs and inactive forelimbs. In active hindlimbs, Pitx1 forms chromatin interactions with cognate cis -regulatory regions spread over 400 kbs, including Pen as well as PDE, RA4 , and PelB . In contrast, in inactive forelimbs these interactions are absent and the Pitx1 gene forms a contact with the polycomb-repressed gene Neurog1 11 . In this work, we use a combination of single cell transcriptomics (scRNA-seq), a fluorescent cell-tracing approach and genomic technologies to define the contribution of a single enhancer ( Pen ) in establishing the epigenetically- and structurally-active Pitx1 regulatory landscape. Moreover, we investigate whether changes in enhancer activities or 3D structure fundamentally associate with transcription or if those can be functionally disconnected of the transcriptional process. Finally, we assess if Pitx1 expression is homogenous across limb cell populations and if distinct expression levels rely on different enhancer repertoires or, alternatively, in progressive changes in cis-regulatory landscape activities. Results Two approaches to track Pitx1 activities suggest a bimodal cis -regulatory behavior In order to characterise transcriptional, chromatin and structural changes following the Pen enhancer deletion, we combined genetic manipulation of the Pitx1 locus with scRNA-seq and chromatin analysis of sorted limb cell populations. Both approaches enabled characterization of complementary features of gene transcriptional regulation following alterations of the cis -regulatory landscape. First, to define the hindlimb cell types that are expressing Pitx1 and to assess how the Pen enhancer regulates its expression in these cells, we generated single-cell preparations from wildtype ( Pitx1 +/+ ) fore- and hindlimb buds as well as Pen enhancer deleted ( Pitx1 Pen−/Pen− ) or Pitx1 knocked-out ( Pitx1 −/− ) hindlimbs (Fig. 1A ). We performed 10× genomics in duplicates from E12.5 limb buds as these correspond to a transition stage between patterning and cell-differentiation phases. By performing unsupervised clustering of all the wildtype and mutant single cell transcriptomic datasets, we identified five clusters, to which all the dataset contributed, corresponding to the main populations of the limb: one mesenchymal cluster ( Prrx1 + , Prrx2 + , Twist1 +; 89% of the cells) and four non-mesenchymal satellite clusters including muscle ( Myod1 +, Ttn +; Myh3 +; 4% of the cells), epithelium ( Wnt6 +, Krt14 + ; 5% of the cells), endothelium<|im_end|> <|im_start|>assistant Embryonic development follows delicate stages: For everything to go well, many genes must coordinate their activity according to a very meticulous scheme and tempo. This precision mechanism sometimes fails, leading to more or less disabling malformations. By studying the Pitx1 gene, one of the genes involved in the construction of the lower limbs, a team from the University of Geneva (UNIGE), in Switzerland, has discovered how a small disturbance in the activation process of this gene is at the origin of clubfoot, a common foot malformation. Indeed, even a fully functional gene cannot act properly without one of its genetic switches. These short DNA sequences provide the signal for the transcription of DNA into RNA, and are essential for this mechanism. And when just one of these switches is missing, the proportion of cells where the gene is active decreases, preventing the lower limbs from being built properly. These results, published in the journal Nature Communications, highlight the hitherto largely underestimated role of genetic switches in developmental disorders. During embryonic development, hundreds of genes must be precisely activated or repressed for organs to build properly. This control of activity is directed by short DNA sequences that, by binding certain proteins in the cell nucleus, act as true ON/OFF switches. "When the switch is turned on, it initiates the transcription of a gene into RNA, which in turn is translated into a protein that can then perform a specific task," explains Guillaume Andrey, professor in the Department of Genetic and Developmental Medicine at the UNIGE Faculty of Medicine, who led this research. "Without this, genes would be continuously switched on or off, and therefore unable to act selectively, in the right place and at the right time." In general, each gene has several switches to ensure that the mechanism is robust. "However, could the loss of one of these switches have consequences? This is what we wanted to test here by taking as a model the Pitx1 gene, whose role in the construction of the lower limbs is well known," says Raquel Rouco, a post-doctoral researcher in Guillaume Andrey's laboratory and co-first author of this study. A decrease in cellular activation that leads to clubfoot To do this, the scientists modified mouse stem cells using the genetic engineering tool CRISPR-CAS 9, which makes it possible to add or remove specific elements of the genome. "Here, we removed one of Pitx1's switches, called Pen, and added a fluorescence marker that allows us to visualize the gene activation," explains Olimpia Bompadre, a doctoral student in the research team and co-first author. "These modified cells are then aggregated with mouse embryonic cells for us to study their early stages of development." Usually, about 90 percent of cells in future legs activate the Pitx1 gene, while 10 percent of cells do not. "However, when we removed the Pen switch, we found that the proportion of cells that did not activate Pitx1 rose from 10 to 20 percent, which was enough to modify the construction of the musculoskeletal system and to induce a clubfoot," explains Guillaume Andrey. The proportion of inactive cells increased particularly in the immature cells of the lower limbs and in the irregular connective tissue, a tissue that is essential for building the musculoskeletal system. The same mechanism in many genes Beyond the Pitx1 gene and clubfoot, the UNIGE scientists have discovered a general principle whose mechanism could be found in a large number of genes. Flawed genetic switches could thus be at the origin of numerous malformations or developmental diseases. Moreover, a gene does not control the development of a single organ in the body, but is usually involved in the construction of a wide range of organs. "A non-lethal malformation, such as clubfoot for example, could be an indicator of disorders elsewhere in the body that, while not immediately visible, could be much more dangerous. If we can accurately interpret the action of each mutation, we could not only read the information in the genome to find the root cause of a malformation, but also predict effects in other organs, which would silently develop, in order to intervene as early as possible," the authors conclude. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 11050, 278, 21389, 527, 14134, 14400, 555, 5361, 8833, 32842, 11821, 4528, 3230, 1385, 13, 1666, 264, 1121, 11, 19825, 919, 315, 1778, 23331, 5540, 617, 3629, 4745, 311, 16805, 872, 2539, 734, 13, 5810, 11, 584, 1005, 279, 40079, 87, 16, 1296, 2788, 79257, 311, 70755, 304, 7872, 279, 23331, 323, 35693, 9764, 61086, 2768, 279, 37166, 315, 832, 315, 1202, 8833, 32842, 320, 13597, 7609, 3296, 35271, 3254, 2849, 36815, 24203, 323, 459, 304, 12, 9034, 97234, 2849, 46515, 5603, 11, 584, 23846, 459, 7319, 19983, 315, 40079, 87, 16, 2536, 14, 10516, 10397, 1911, 287, 7917, 323, 264, 25983, 19983, 315, 40079, 87, 16, 1579, 10397, 1911, 287, 7917, 13, 1226, 1505, 430, 279, 927, 5621, 45025, 315, 40079, 87, 16, 2536, 14, 10516, 10397, 1911, 287, 7917, 99970, 505, 264, 8060, 315, 279, 40079, 87, 16, 79257, 311, 16580, 8833, 11967, 7640, 323, 220, 18, 35, 22083, 15111, 4442, 13, 1115, 79257, 5906, 482, 23863, 90974, 264, 44589, 30548, 5059, 2298, 88, 323, 264, 35135, 4814, 315, 42408, 4667, 535, 20438, 11, 9778, 6522, 311, 264, 6469, 5447, 82423, 13, 1115, 828, 13533, 430, 11, 304, 1063, 5157, 11, 48832, 8833, 32842, 1253, 387, 1511, 311, 24392, 29262, 264, 22514, 15449, 315, 872, 3552, 23331, 55890, 13, 29438, 43951, 367, 304, 279, 8833, 11967, 18528, 315, 23331, 55890, 520, 48006, 21389, 649, 3063, 311, 1853, 9268, 555, 47141, 279, 47040, 323, 5255, 8141, 315, 15207, 46940, 220, 16, 662, 23150, 11, 927, 279, 3347, 1667, 11, 18151, 315, 3254, 23331, 8316, 2949, 6485, 323, 26310, 48832, 23331, 55890, 1051, 6982, 311, 617, 2867, 14345, 88167, 20124, 8994, 96811, 1193, 7276, 43154, 304, 5578, 46940, 220, 17, 1174, 220, 18, 1174, 220, 19, 1174, 220, 20, 662, 1666, 279, 61086, 304, 279, 23331, 24717, 2768, 8833, 11967, 37166, 617, 10213, 1027, 32971, 1701, 20155, 20438, 6492, 11, 433, 706, 1027, 5107, 311, 8417, 279, 2849, 19440, 54709, 4920, 279, 4814, 315, 7645, 430, 9815, 369, 14345, 22583, 13, 763, 2015, 311, 3619, 279, 24473, 31206, 6371, 315, 1521, 14345, 22583, 11, 433, 374, 9093, 7718, 311, 70755, 1268, 264, 3254, 8833, 11967, 44072, 311, 279, 15449, 315, 4553, 23331, 55890, 304, 3230, 2849, 22673, 13, 1556, 7524, 1646, 1887, 311, 2686, 1521, 7120, 8905, 4860, 374, 279, 48694, 37808, 11, 1405, 2942, 52379, 7612, 264, 10508, 2585, 315, 15207, 46940, 311, 11322, 4495, 93093, 1251, 220, 21, 662, 35761, 311, 420, 374, 40079, 87, 16, 1174, 264, 46940, 8331, 11058, 15207, 430, 374, 14614, 13605, 304, 11469, 48419, 4763, 65, 68543, 11, 719, 539, 2291, 4763, 1302, 11, 902, 12006, 279, 48694, 4500, 2068, 311, 54263, 1139, 264, 2531, 220, 22, 1174, 220, 23, 1174, 220, 24, 662, 53123, 11, 2291, 4763, 65, 40079, 87, 16, 8895, 8838, 34849, 649, 49853, 459, 6916, 4791, 62223, 18475, 11, 15109, 555, 279, 11341, 315, 459, 77594, 25847, 3352, 6985, 439, 1664, 439, 6485, 4442, 304, 279, 52192, 323, 8541, 2439, 19358, 220, 605, 1174, 220, 806, 662, 763, 13168, 11, 40079, 87, 16, 14459, 704, 706, 1027, 6982, 311, 49853, 7276, 2531, 4791, 67918, 54070, 449, 279, 52979, 315, 279, 3352, 6985, 439, 1664, 439, 1317, 17685, 22709, 501, 36259, 323, 10062, 67, 533, 88, 398, 220, 605, 1174, 220, 717, 1174, 220, 1032, 662, 71500, 398, 11, 20155, 36815, 24203, 15174, 617, 1193, 10675, 32873, 52452, 15207, 7645, 4442, 5304, 40079, 87, 16, 4814, 11, 23377, 430, 459, 958, 1387, 1990, 1521, 4442, 323, 279, 6650, 4478, 315, 48694, 2849, 1207, 8539, 7607, 45925, 1121, 304, 279, 5370, 14345, 22583, 220, 23, 1174, 220, 605, 1174, 220, 806, 1174, 220, 1032, 1174, 220, 975, 662, 1666, 369, 1690, 48006, 21389, 11, 3892, 8833, 32842, 16580, 40079, 87, 16, 7645, 304, 48419, 4763, 1302, 323, 1023, 39881, 13, 2100, 3117, 11, 3116, 8833, 32842, 617, 1027, 11054, 304, 56669, 25, 24587, 33, 902, 20722, 264, 1612, 278, 19496, 5497, 304, 48419, 4763, 1302, 11, 393, 1170, 430, 20722, 7645, 304, 279, 11837, 581, 1299, 5438, 11, 29556, 19, 430, 649, 6678, 19578, 304, 264, 27084, 315, 2291, 12, 323, 48419, 4763, 65, 7917, 323, 5616, 11, 13597, 1174, 264, 11083, 20345, 1631, 278, 8833, 11967, 430, 20722, 7645, 304, 2225, 2291, 12, 323, 48419, 4763, 1302, 220, 806, 1174, 220, 868, 1174, 220, 845, 662, 8442, 279, 5820, 315, 13597, 574, 779, 3117, 6982, 311, 16917, 17210, 311, 40079, 87, 16, 734, 304, 279, 48419, 4763, 65, 439, 1202, 37166, 11767, 311, 264, 220, 1758, 4235, 1135, 4, 14278, 315, 40079, 87, 16, 7645, 220, 806, 662, 578, 37166, 315, 13597, 706, 912, 5536, 389, 17685, 3160, 477, 16099, 5219, 719, 90974, 264, 26310, 44805, 519, 6469, 5447, 82423, 11, 4528, 311, 279, 832, 13468, 304, 24548, 323, 12966, 5304, 40079, 87, 16, 46900, 385, 1354, 1386, 10603, 220, 806, 1174, 220, 975, 662, 3861, 4040, 488, 311, 279, 40079, 87, 16, 79257, 374, 430, 433, 64664, 43593, 2204, 220, 18, 35, 22083, 15111, 26965, 811, 304, 46940, 750, 4642, 48419, 4763, 1302, 323, 32899, 2291, 4763, 1302, 13, 763, 4642, 48419, 4763, 1302, 11, 40079, 87, 16, 7739, 22083, 15111, 22639, 449, 19329, 349, 67504, 482, 1610, 38220, 13918, 9041, 927, 220, 3443, 597, 1302, 11, 2737, 13597, 439, 1664, 439, 393, 1170, 11, 29556, 19, 1174, 323, 24587, 33, 662, 763, 13168, 11, 304, 32899, 2291, 4763, 1302, 1521, 22639, 527, 28310, 323, 279, 40079, 87, 16, 15207, 7739, 264, 3729, 449, 279, 10062, 22631, 5621, 14655, 15207, 32359, 70, 16, 220, 806, 662, 763, 420, 990, 11, 584, 1005, 264, 10824, 315, 3254, 2849, 36815, 24203, 320, 2445, 31820, 7962, 80, 705, 264, 74864, 2849, 10398, 4628, 5603, 323, 81064, 14645, 311, 7124, 279, 19035, 315, 264, 3254, 8833, 11967, 320, 13597, 883, 304, 31692, 279, 4248, 6569, 37774, 12, 323, 2080, 43024, 32344, 40079, 87, 16, 23331, 18921, 13, 23674, 11, 584, 19874, 3508, 4442, 304, 8833, 11967, 7640, 477, 220, 18, 35, 6070, 43593, 22712, 449, 46940, 477, 422, 1884, 649, 387, 734, 750, 40186, 315, 279, 46940, 278, 1920, 13, 17830, 11, 584, 8720, 422, 40079, 87, 16, 7645, 374, 5105, 53595, 4028, 48694, 2849, 22673, 323, 422, 12742, 7645, 5990, 17631, 389, 2204, 8833, 11967, 2109, 14200, 3946, 477, 11, 69487, 11, 304, 23053, 4442, 304, 67504, 33263, 38220, 18921, 7640, 13, 18591, 9220, 20414, 311, 3839, 40079, 87, 16, 7640, 4284, 264, 293, 318, 58697, 67504, 482, 1610, 38220, 7865, 763, 2015, 311, 3752, 1082, 46940, 278, 11, 22083, 15111, 323, 24693, 4442, 2768, 279, 13597, 8833, 11967, 37166, 11, 584, 11093, 19465, 34786, 315, 279, 40079, 87, 16, 79257, 449, 1156, 31820, 7962, 80, 323, 22083, 15111, 6492, 315, 10839, 48694, 2849, 22673, 13, 11995, 20414, 9147, 60993, 315, 58535, 4519, 315, 15207, 46940, 278, 19812, 2768, 61086, 315, 279, 67504, 482, 1610, 38220, 18921, 13, 5629, 11, 311, 7124, 279, 48419, 4763, 65, 2849, 4595, 430, 527, 37810, 40079, 87, 16, 323, 311, 8720, 1268, 279, 13597, 8833, 11967, 80412, 1202, 7645, 304, 1521, 7917, 11, 584, 8066, 3254, 33001, 47979, 505, 8545, 1337, 320, 40079, 87, 16, 489, 62751, 883, 2291, 12, 323, 48419, 4763, 65, 68543, 439, 1664, 439, 13597, 8833, 11967, 11309, 320, 40079, 87, 16, 13597, 34363, 14, 29305, 34363, 883, 477, 40079, 87, 16, 33085, 9994, 320, 40079, 87, 16, 25173, 14, 34363, 883, 48419, 4763, 1302, 320, 30035, 13, 220, 16, 32, 7609, 1226, 10887, 220, 605, 18028, 4173, 24203, 304, 43428, 505, 469, 717, 13, 20, 48694, 68543, 439, 1521, 8024, 311, 264, 9320, 6566, 1990, 93093, 1251, 323, 2849, 1773, 18780, 7246, 35530, 13, 3296, 16785, 7120, 455, 79090, 59454, 315, 682, 279, 8545, 1337, 323, 61618, 3254, 2849, 36815, 3151, 30525, 11, 584, 11054, 4330, 28066, 11, 311, 902, 682, 279, 10550, 20162, 11, 12435, 311, 279, 1925, 22673, 315, 279, 48694, 25, 832, 11083, 20345, 1631, 278, 10879, 320, 393, 637, 87, 16, 489, 1174, 393, 637, 87, 17, 489, 1174, 74474, 16, 489, 26, 220, 4578, 4, 315, 279, 7917, 8, 323, 3116, 2536, 1474, 288, 20345, 1631, 278, 24088, 28066, 2737, 16124, 320, 3092, 347, 16, 489, 11, 350, 1546, 489, 26, 3092, 71, 18, 489, 26, 220, 19, 4, 315, 279, 7917, 705, 64779, 301, 2411, 320, 468, 406, 21, 489, 11, 735, 3423, 975, 489, 2652, 220, 20, 4, 315, 279, 7917, 705, 93329, 301, 2411, 128257, 198, 128256, 78191, 198, 99886, 894, 14338, 4500, 11263, 36301, 18094, 25, 1789, 4395, 311, 733, 1664, 11, 1690, 21389, 2011, 16580, 872, 5820, 4184, 311, 264, 1633, 96278, 13155, 323, 24108, 13, 1115, 16437, 17383, 7170, 14865, 11, 6522, 311, 810, 477, 2753, 61584, 8811, 630, 811, 13, 3296, 21630, 279, 40079, 87, 16, 15207, 11, 832, 315, 279, 21389, 6532, 304, 279, 8246, 315, 279, 4827, 49695, 11, 264, 2128, 505, 279, 3907, 315, 45345, 320, 1899, 1953, 36, 705, 304, 30221, 11, 706, 11352, 1268, 264, 2678, 65858, 304, 279, 15449, 1920, 315, 420, 15207, 374, 520, 279, 6371, 315, 6469, 5447, 11, 264, 4279, 4579, 8811, 1659, 13, 23150, 11, 1524, 264, 7373, 16003, 15207, 4250, 1180, 10489, 2085, 832, 315, 1202, 19465, 32267, 13, 4314, 2875, 15922, 24630, 3493, 279, 8450, 369, 279, 46940, 315, 15922, 1139, 41214, 11, 323, 527, 7718, 369, 420, 17383, 13, 1628, 994, 1120, 832, 315, 1521, 32267, 374, 7554, 11, 279, 21801, 315, 7917, 1405, 279, 15207, 374, 4642, 43154, 11, 27252, 279, 4827, 49695, 505, 1694, 5918, 10489, 13, 4314, 3135, 11, 4756, 304, 279, 8486, 22037, 26545, 11, 11415, 279, 305, 411, 14200, 14090, 87136, 3560, 315, 19465, 32267, 304, 48006, 24673, 13, 12220, 44481, 14338, 4500, 11, 11758, 315, 21389, 2011, 387, 24559, 22756, 477, 312, 14655, 369, 36853, 311, 1977, 10489, 13, 1115, 2585, 315, 5820, 374, 15910, 555, 2875, 15922, 24630, 430, 11, 555, 11212, 3738, 28896, 304, 279, 2849, 62607, 11, 1180, 439, 837, 6328, 17991, 1785, 32267, 13, 330, 4599, 279, 3480, 374, 6656, 389, 11, 433, 12961, 988, 279, 46940, 315, 264, 15207, 1139, 41214, 11, 902, 304, 2543, 374, 25548, 1139, 264, 13128, 430, 649, 1243, 2804, 264, 3230, 3465, 1359, 15100, 4673, 99112, 1628, 8233, 11, 14561, 304, 279, 6011, 315, 75226, 323, 11050, 278, 19152, 520, 279, 6781, 1953, 36, 42904, 315, 19152, 11, 889, 6197, 420, 3495, 13, 330, 27131, 420, 11, 21389, 1053, 387, 31978, 30975, 389, 477, 1022, 11, 323, 9093, 12153, 311, 1180, 82775, 11, 304, 279, 1314, 2035, 323, 520, 279, 1314, 892, 1210, 763, 4689, 11, 1855, 15207, 706, 3892, 32267, 311, 6106, 430, 279, 17383, 374, 22514, 13, 330, 11458, 11, 1436, 279, 4814, 315, 832, 315, 1521, 32267, 617, 16296, 30, 1115, 374, 1148, 584, 4934, 311, 1296, 1618, 555, 4737, 439, 264, 1646, 279, 40079, 87, 16, 15207, 11, 6832, 3560, 304, 279, 8246, 315, 279, 4827, 49695, 374, 1664, 3967, 1359, 2795, 18989, 43014, 29622, 1030, 11, 264, 1772, 30659, 5009, 278, 32185, 304, 4673, 99112, 1628, 8233, 596, 27692, 323, 1080, 38043, 3229, 315, 420, 4007, 13, 362, 18979, 304, 35693, 15449, 430, 11767, 311, 6469, 5447, 2057, 656, 420, 11, 279, 14248, 11041, 8814, 19646, 7917, 1701, 279, 19465, 15009, 5507, 12904, 1669, 6616, 7813, 1950, 220, 24, 11, 902, 3727, 433, 3284, 311, 923, 477, 4148, 3230, 5540, 315, 279, 33869, 13, 330, 8586, 11, 584, 7108, 832, 315, 40079, 87, 16, 596, 32267, 11, 2663, 13597, 11, 323, 3779, 264, 97332, 11381, 430, 6276, 603, 311, 51187, 279, 15207, 15449, 1359, 15100, 507, 4763, 79, 689, 48452, 13545, 265, 11, 264, 74657, 5575, 304, 279, 3495, 2128, 323, 1080, 38043, 3229, 13, 330, 9673, 11041, 7917, 527, 1243, 71922, 449, 8814, 44481, 14338, 7917, 369, 603, 311, 4007, 872, 4216, 18094, 315, 4500, 1210, 34067, 11, 922, 220, 1954, 3346, 315, 7917, 304, 3938, 14535, 20891, 279, 40079, 87, 16, 15207, 11, 1418, 220, 605, 3346, 315, 7917, 656, 539, 13, 330, 11458, 11, 994, 584, 7108, 279, 13597, 3480, 11, 584, 1766, 430, 279, 21801, 315, 7917, 430, 1550, 539, 20891, 40079, 87, 16, 16392, 505, 220, 605, 311, 220, 508, 3346, 11, 902, 574, 3403, 311, 5719, 279, 8246, 315, 279, 3167, 79134, 86255, 1887, 323, 311, 49853, 264, 6469, 5447, 1359, 15100, 4673, 99112, 1628, 8233, 13, 578, 21801, 315, 32899, 7917, 7319, 8104, 304, 279, 86525, 7917, 315, 279, 4827, 49695, 323, 304, 279, 42408, 4667, 535, 20438, 11, 264, 20438, 430, 374, 7718, 369, 4857, 279, 3167, 79134, 86255, 1887, 13, 578, 1890, 17383, 304, 1690, 21389, 31886, 279, 40079, 87, 16, 15207, 323, 6469, 5447, 11, 279, 6781, 1953, 36, 14248, 617, 11352, 264, 4689, 17966, 6832, 17383, 1436, 387, 1766, 304, 264, 3544, 1396, 315, 21389, 13, 3061, 675, 291, 19465, 32267, 1436, 8617, 387, 520, 279, 6371, 315, 12387, 8811, 630, 811, 477, 48006, 19338, 13, 23674, 11, 264, 15207, 1587, 539, 2585, 279, 4500, 315, 264, 3254, 2942, 304, 279, 2547, 11, 719, 374, 6118, 6532, 304, 279, 8246, 315, 264, 7029, 2134, 315, 36853, 13, 330, 32, 2536, 31307, 31392, 8811, 1659, 11, 1778, 439, 6469, 5447, 369, 3187, 11, 1436, 387, 459, 21070, 315, 24673, 18403, 304, 279, 2547, 430, 11, 1418, 539, 7214, 9621, 11, 1436, 387, 1790, 810, 11660, 13, 1442, 584, 649, 30357, 14532, 279, 1957, 315, 1855, 27472, 11, 584, 1436, 539, 1193, 1373, 279, 2038, 304, 279, 33869, 311, 1505, 279, 3789, 5353, 315, 264, 8811, 1659, 11, 719, 1101, 7168, 6372, 304, 1023, 36853, 11, 902, 1053, 50494, 2274, 11, 304, 2015, 311, 55579, 439, 4216, 439, 3284, 1359, 279, 12283, 32194, 13, 220, 128257, 198 ]

2,295

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Electron emission is critical for a host of modern fabrication and analysis applications including mass spectrometry, electron imaging and nanopatterning. Here, we report that monolayers of diamondoids effectively confer dramatically enhanced field emission properties to metal surfaces. We attribute the improved emission to a significant reduction of the work function rather than a geometric enhancement. This effect depends on the particular diamondoid isomer, with [121]tetramantane-2-thiol reducing gold's work function from ∼ 5.1 eV to 1.60 ± 0.3 eV, corresponding to an increase in current by a factor of over 13,000. This reduction in work function is the largest reported for any organic species and also the largest for any air-stable compound 1 , 2 , 3 . This effect was not observed for sp 3 -hybridized alkanes, nor for smaller diamondoid molecules. The magnitude of the enhancement, molecule specificity and elimination of gold metal rearrangement precludes geometric factors as the dominant contribution. Instead, we attribute this effect to the stable radical cation of diamondoids. Our computed enhancement due to a positively charged radical cation was in agreement with the measured work functions to within ±0.3 eV, suggesting a new paradigm for low-work-function coatings based on the design of nanoparticles with stable radical cations. Main Field emission from sharp-tipped cathodes is very dependent on the nanoscale geometry of the tip, so slight changes in the structure of the emitter can lead to dramatic differences in the current. Lowering the material work function is preferable to using sharp tips. However, this requires the application of surface coatings such as Cs or Ba alkali metals, but these are highly reactive and volatile, which largely precludes their application. Nanoscale materials or coatings that could achieve similar emission properties without environmental sensitivity or reactivity would thus be a significant step towards engineering electron emission surfaces. Diamond films have previously been used for field- 4 , 5 , 6 and thermionic-emission 7 , 8 devices, but the emission can be restricted by the poor conductivity of bulk diamond, requiring a complex mixture of sp 3 diamond and sp 2 graphite to achieve adequate performance. Furthermore, the role of these nanoscale material inhomogeneities in the emission process is still not fully understood 4 , 6 , 9 . Here, we report that monolayers of diamondoids—nanoscale diamond molecules—effectively confer significantly enhanced field-emission properties to metal surfaces. More generally, this approach provides an avenue for the design of new nanoscale materials by modulating surface work functions far beyond the typical ∼ 1 eV dipolar effects. Diamondoids are nanometre-scale cage sp 3 hydrocarbons with a diamond bonding structure and fully terminated with hydrogen 10 , 11 . Their properties are an interesting blend of those of diamond nanoparticles and small molecules 12 , and the high structural rigidity, chemical stability and low dielectric constant 13 of diamond, yet can be purified, organized 14 , 15 and chemically functionalized 16 , 17 , 18 in a manner similar to small molecules. Diamondoids exhibit a number of unexpected properties, including monochromatic secondary electron emission 19 , 20 , extraordinarily long carbon–carbon bonds 21 , 22 and a lack of quantum confinement in the unoccupied states 23 . They are interesting candidates for field emission as they represent the ultimate limit in diamond grain size reduction, which has previously been correlated with improved electron emission 6 . Thiol-modified versions of the diamondoids 18 were organized into self-assembled monolayers on Au or Ag, with thicknesses ranging from 0.5 nm (for adamantane-thiol) to 0.9 nm (for [121]tetramantane-6-thiol). By using diamondoid monolayers on metallic surfaces we avoid the conductivity problems associated with bulk diamond, precluding the need for mixed sp 2 / sp 3 materials. The lack of sp 2 carbon or bulk defect states in the diamondoids also presents an ideal test case to assess the role of defects compared to bulk diamond films. Here, the field-emission current for diamondoid-modified Au surfaces was investigated for a series of different sizes and orientations of alkane and diamondoid-thiol monolayers ( Fig. 1 ). We chose the diamondoid thiols adamantane-1-thiol (ADT), diamantane-4-thiol (4DT), triamantane-9-thiol (9TrT), [121]tetramantane-6-thiol (6TT), [121]tetramantane-2-thiol (2TT), as well as the methyl- and carboxyl-terminated linear alkanethiols dodecane-1-thiol (DDT) and 16-mercapto hexadecanoic-1-acid (16MHDA) as control samples. Synthesis of the thiol-modified diamondoids has been described previously 18 . Two different [121]tetramantane thiol orientations were investigated, one with the thiol on an apical carbon (6TT) for an ‘upright’ configuration, and one on a medial carbon (2TT) for a horizontal orientation on the Au surface. Diamondoid self-assembled monolayers (SAMs) were formed by immersing the Au substrate in 1 mM diamondoid in 9:1 toluene/ethyl alcohol (vol/vol) solution for ∼ 24–48 h, rinsing with toluene to remove excess molecules and blowing dry. These materials were air-stable after synthesis and could be stored for a period longer than a week without degradation. The field-emission current as a function of applied voltage was tested in a parallel plate configuration in an ultrahigh-vacuum system ( Fig. 2 ) by assembling the diamondoid thiols onto Au-coated Ge nanowires. Nanowires were used to obtain reasonable voltage levels for electron emission and to reduce the electrical arcing observed in planar samples, typically reducing the necessary voltage by a factor of ∼ 150. Figure 1: Field emission apparatus. a , Schematic of field emission set-up. b , Scanning electron microscopy image of the vertically oriented Ge nanowires on the Ge (111) surface. The wires are ∼ 25 µm in length. Scale bars: 10 µm (main image) and 500 nm (inset). c , Structures of the molecules tested, including diamondoid thiols with one to five cages and linear-chain alkane thiols with methyl and carboxyl terminations. Hydrogen atoms are not shown for clarity. Full size image Figure 2: Diamondoid field emission. a , Schematic of the diamondoid functionalization enhancing electron emission from Au-coated Ge nanowire emitters. b , Current–voltage traces from the nanowire emitters before functionalizing with 6TT (blue), after functionalizing with 6TT (green) and after desorbing 6TT (red). c , Fowler–Nordheim plots of the data from b . Full", "role": "user" }, { "content": "They sound like futuristic weapons, but electron guns are actually workhorse tools for research and industry: They emit streams of electrons for electron microscopes, semiconductor patterning equipment and particle accelerators, to name a few important uses. Now scientists at Stanford University and the Department of Energy's SLAC National Accelerator Laboratory have figured out how to increase these electron flows 13,000-fold by applying a single layer of diamondoids – tiny, perfect diamond cages – to an electron gun's sharp gold tip. The results, published today in Nature Nanotechnology, suggest a whole new approach for increasing the power of these devices. They also provide an avenue for designing other types of electron emitters with atom-by-atom precision, said Nick Melosh, an associate professor at SLAC and Stanford who led the study. Diamondoids are interlocking cages made of carbon and hydrogen atoms. They're the smallest possible bits of diamond, each weighing less than a billionth of a billionth of a carat. That small size, along with their rigid, sturdy structure and high chemical purity, give them useful properties that larger diamonds lack. SLAC and Stanford have become one of the world's leading centers for diamondoid research. Studies are carried out through SIMES, the Stanford Institute for Materials and Energy Sciences, and a lab at SLAC is devoted to extracting diamondoids from petroleum. In 2007, a team led by many of the same SIMES researchers showed that a single layer of diamondoids on a metal surface could emit and focus electrons into a tiny beam with a very narrow range of energies. The research team used tiny nanopillars of germanium wire as stand-ins for the tips of electron guns in experiments aimed at improving electron emission. This image was made with a scanning electron microscope – one of a number of devices that use emitted electrons. Credit: Karthik Narasimha/Stanford The new study looked at whether a diamondoid coating could also improve emissions from electron guns. One way to increase the power of an electron gun is to make the tip really sharp, which makes it easier to get the electrons out, Melosh said. But these sharp tips are unstable; even tiny irregularities can affect their performance. Researchers have tried to get around this by coating the tips with chemicals that boost electron emission, but this can be problematic because some of the most effective ones burst into flames when exposed to air. For this study, the scientists used tiny nanopillars of germanium wire as stand-ins for electron gun tips. They coated the wires with gold and then with diamondoids of various sizes. Germanium nanopillars were coated with gold and then with diamondoids of various sizes. The scientists got the best results by coating the pillars with diamondoid molecules that consist of four “cages;” this increased the emission of electrons from the tips 13,000-fold. Credit: Karthik Narasimha/Stanford When the scientists applied a voltage to the nanowires to stimulate the release of electrons from the tips, they found they got the best results from tips coated with diamondoids that consist of four \"cages.\" These released a whopping 13,000 times more electrons than bare gold tips. Further tests and computer simulations suggest that the increase was not due to changes in the shape of the tip or in the underlying gold surface. Instead, it looks like some of the diamondoid molecules in the tip lost a single electron – it's not clear exactly how. This created a positive charge that attracted electrons from the underlying surface and made it easier for them to flow out of the tip, Melosh said. \"Most other molecules would not be stable if you removed an electron; they'd fall apart,\" he said. \"But the cage-like nature of the diamondoid makes it unusually stable, and that's why this process works. Now that we understand what's going on, we may be able to use that knowledge to engineer other materials that are really good at emitting electrons.\" Diamondoid structures tested in the experiment; the two on the bottom, which consist of four “cages” with carbon atoms at each corner, produced the biggest gains in electron emission. The chemical tags at the bottom of each molecule were added to help the diamondoids stick to the gold surface of the nanopillars. Credit: Karthik Narasimha/Stanford SIMES researchers Nick Melosh, left, and Jeremy Dahl in a Stanford laboratory with equipment used to perform diamondoid experiments. Credit: SLAC National Accelerator Laboratory ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Electron emission is critical for a host of modern fabrication and analysis applications including mass spectrometry, electron imaging and nanopatterning. Here, we report that monolayers of diamondoids effectively confer dramatically enhanced field emission properties to metal surfaces. We attribute the improved emission to a significant reduction of the work function rather than a geometric enhancement. This effect depends on the particular diamondoid isomer, with [121]tetramantane-2-thiol reducing gold's work function from ∼ 5.1 eV to 1.60 ± 0.3 eV, corresponding to an increase in current by a factor of over 13,000. This reduction in work function is the largest reported for any organic species and also the largest for any air-stable compound 1 , 2 , 3 . This effect was not observed for sp 3 -hybridized alkanes, nor for smaller diamondoid molecules. The magnitude of the enhancement, molecule specificity and elimination of gold metal rearrangement precludes geometric factors as the dominant contribution. Instead, we attribute this effect to the stable radical cation of diamondoids. Our computed enhancement due to a positively charged radical cation was in agreement with the measured work functions to within ±0.3 eV, suggesting a new paradigm for low-work-function coatings based on the design of nanoparticles with stable radical cations. Main Field emission from sharp-tipped cathodes is very dependent on the nanoscale geometry of the tip, so slight changes in the structure of the emitter can lead to dramatic differences in the current. Lowering the material work function is preferable to using sharp tips. However, this requires the application of surface coatings such as Cs or Ba alkali metals, but these are highly reactive and volatile, which largely precludes their application. Nanoscale materials or coatings that could achieve similar emission properties without environmental sensitivity or reactivity would thus be a significant step towards engineering electron emission surfaces. Diamond films have previously been used for field- 4 , 5 , 6 and thermionic-emission 7 , 8 devices, but the emission can be restricted by the poor conductivity of bulk diamond, requiring a complex mixture of sp 3 diamond and sp 2 graphite to achieve adequate performance. Furthermore, the role of these nanoscale material inhomogeneities in the emission process is still not fully understood 4 , 6 , 9 . Here, we report that monolayers of diamondoids—nanoscale diamond molecules—effectively confer significantly enhanced field-emission properties to metal surfaces. More generally, this approach provides an avenue for the design of new nanoscale materials by modulating surface work functions far beyond the typical ∼ 1 eV dipolar effects. Diamondoids are nanometre-scale cage sp 3 hydrocarbons with a diamond bonding structure and fully terminated with hydrogen 10 , 11 . Their properties are an interesting blend of those of diamond nanoparticles and small molecules 12 , and the high structural rigidity, chemical stability and low dielectric constant 13 of diamond, yet can be purified, organized 14 , 15 and chemically functionalized 16 , 17 , 18 in a manner similar to small molecules. Diamondoids exhibit a number of unexpected properties, including monochromatic secondary electron emission 19 , 20 , extraordinarily long carbon–carbon bonds 21 , 22 and a lack of quantum confinement in the unoccupied states 23 . They are interesting candidates for field emission as they represent the ultimate limit in diamond grain size reduction, which has previously been correlated with improved electron emission 6 . Thiol-modified versions of the diamondoids 18 were organized into self-assembled monolayers on Au or Ag, with thicknesses ranging from 0.5 nm (for adamantane-thiol) to 0.9 nm (for [121]tetramantane-6-thiol). By using diamondoid monolayers on metallic surfaces we avoid the conductivity problems associated with bulk diamond, precluding the need for mixed sp 2 / sp 3 materials. The lack of sp 2 carbon or bulk defect states in the diamondoids also presents an ideal test case to assess the role of defects compared to bulk diamond films. Here, the field-emission current for diamondoid-modified Au surfaces was investigated for a series of different sizes and orientations of alkane and diamondoid-thiol monolayers ( Fig. 1 ). We chose the diamondoid thiols adamantane-1-thiol (ADT), diamantane-4-thiol (4DT), triamantane-9-thiol (9TrT), [121]tetramantane-6-thiol (6TT), [121]tetramantane-2-thiol (2TT), as well as the methyl- and carboxyl-terminated linear alkanethiols dodecane-1-thiol (DDT) and 16-mercapto hexadecanoic-1-acid (16MHDA) as control samples. Synthesis of the thiol-modified diamondoids has been described previously 18 . Two different [121]tetramantane thiol orientations were investigated, one with the thiol on an apical carbon (6TT) for an ‘upright’ configuration, and one on a medial carbon (2TT) for a horizontal orientation on the Au surface. Diamondoid self-assembled monolayers (SAMs) were formed by immersing the Au substrate in 1 mM diamondoid in 9:1 toluene/ethyl alcohol (vol/vol) solution for ∼ 24–48 h, rinsing with toluene to remove excess molecules and blowing dry. These materials were air-stable after synthesis and could be stored for a period longer than a week without degradation. The field-emission current as a function of applied voltage was tested in a parallel plate configuration in an ultrahigh-vacuum system ( Fig. 2 ) by assembling the diamondoid thiols onto Au-coated Ge nanowires. Nanowires were used to obtain reasonable voltage levels for electron emission and to reduce the electrical arcing observed in planar samples, typically reducing the necessary voltage by a factor of ∼ 150. Figure 1: Field emission apparatus. a , Schematic of field emission set-up. b , Scanning electron microscopy image of the vertically oriented Ge nanowires on the Ge (111) surface. The wires are ∼ 25 µm in length. Scale bars: 10 µm (main image) and 500 nm (inset). c , Structures of the molecules tested, including diamondoid thiols with one to five cages and linear-chain alkane thiols with methyl and carboxyl terminations. Hydrogen atoms are not shown for clarity. Full size image Figure 2: Diamondoid field emission. a , Schematic of the diamondoid functionalization enhancing electron emission from Au-coated Ge nanowire emitters. b , Current–voltage traces from the nanowire emitters before functionalizing with 6TT (blue), after functionalizing with 6TT (green) and after desorbing 6TT (red). c , Fowler–Nordheim plots of the data from b . Full<|im_end|> <|im_start|>assistant They sound like futuristic weapons, but electron guns are actually workhorse tools for research and industry: They emit streams of electrons for electron microscopes, semiconductor patterning equipment and particle accelerators, to name a few important uses. Now scientists at Stanford University and the Department of Energy's SLAC National Accelerator Laboratory have figured out how to increase these electron flows 13,000-fold by applying a single layer of diamondoids – tiny, perfect diamond cages – to an electron gun's sharp gold tip. The results, published today in Nature Nanotechnology, suggest a whole new approach for increasing the power of these devices. They also provide an avenue for designing other types of electron emitters with atom-by-atom precision, said Nick Melosh, an associate professor at SLAC and Stanford who led the study. Diamondoids are interlocking cages made of carbon and hydrogen atoms. They're the smallest possible bits of diamond, each weighing less than a billionth of a billionth of a carat. That small size, along with their rigid, sturdy structure and high chemical purity, give them useful properties that larger diamonds lack. SLAC and Stanford have become one of the world's leading centers for diamondoid research. Studies are carried out through SIMES, the Stanford Institute for Materials and Energy Sciences, and a lab at SLAC is devoted to extracting diamondoids from petroleum. In 2007, a team led by many of the same SIMES researchers showed that a single layer of diamondoids on a metal surface could emit and focus electrons into a tiny beam with a very narrow range of energies. The research team used tiny nanopillars of germanium wire as stand-ins for the tips of electron guns in experiments aimed at improving electron emission. This image was made with a scanning electron microscope – one of a number of devices that use emitted electrons. Credit: Karthik Narasimha/Stanford The new study looked at whether a diamondoid coating could also improve emissions from electron guns. One way to increase the power of an electron gun is to make the tip really sharp, which makes it easier to get the electrons out, Melosh said. But these sharp tips are unstable; even tiny irregularities can affect their performance. Researchers have tried to get around this by coating the tips with chemicals that boost electron emission, but this can be problematic because some of the most effective ones burst into flames when exposed to air. For this study, the scientists used tiny nanopillars of germanium wire as stand-ins for electron gun tips. They coated the wires with gold and then with diamondoids of various sizes. Germanium nanopillars were coated with gold and then with diamondoids of various sizes. The scientists got the best results by coating the pillars with diamondoid molecules that consist of four “cages;” this increased the emission of electrons from the tips 13,000-fold. Credit: Karthik Narasimha/Stanford When the scientists applied a voltage to the nanowires to stimulate the release of electrons from the tips, they found they got the best results from tips coated with diamondoids that consist of four "cages." These released a whopping 13,000 times more electrons than bare gold tips. Further tests and computer simulations suggest that the increase was not due to changes in the shape of the tip or in the underlying gold surface. Instead, it looks like some of the diamondoid molecules in the tip lost a single electron – it's not clear exactly how. This created a positive charge that attracted electrons from the underlying surface and made it easier for them to flow out of the tip, Melosh said. "Most other molecules would not be stable if you removed an electron; they'd fall apart," he said. "But the cage-like nature of the diamondoid makes it unusually stable, and that's why this process works. Now that we understand what's going on, we may be able to use that knowledge to engineer other materials that are really good at emitting electrons." Diamondoid structures tested in the experiment; the two on the bottom, which consist of four “cages” with carbon atoms at each corner, produced the biggest gains in electron emission. The chemical tags at the bottom of each molecule were added to help the diamondoids stick to the gold surface of the nanopillars. Credit: Karthik Narasimha/Stanford SIMES researchers Nick Melosh, left, and Jeremy Dahl in a Stanford laboratory with equipment used to perform diamondoid experiments. Credit: SLAC National Accelerator Laboratory <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 77976, 41353, 374, 9200, 369, 264, 3552, 315, 6617, 59251, 323, 6492, 8522, 2737, 3148, 9618, 442, 15501, 11, 17130, 32758, 323, 76307, 1683, 1251, 13, 5810, 11, 584, 1934, 430, 1647, 337, 5184, 315, 22996, 17390, 13750, 49843, 29057, 24872, 2115, 41353, 6012, 311, 9501, 27529, 13, 1226, 7180, 279, 13241, 41353, 311, 264, 5199, 14278, 315, 279, 990, 734, 4856, 1109, 264, 53584, 27886, 13, 1115, 2515, 14117, 389, 279, 4040, 22996, 590, 374, 26429, 11, 449, 510, 7994, 60, 73542, 2453, 519, 2194, 12, 17, 7716, 25947, 18189, 6761, 596, 990, 734, 505, 12264, 120, 220, 20, 13, 16, 384, 53, 311, 220, 16, 13, 1399, 20903, 220, 15, 13, 18, 384, 53, 11, 12435, 311, 459, 5376, 304, 1510, 555, 264, 8331, 315, 927, 220, 1032, 11, 931, 13, 1115, 14278, 304, 990, 734, 374, 279, 7928, 5068, 369, 904, 17808, 9606, 323, 1101, 279, 7928, 369, 904, 3805, 5594, 481, 24549, 220, 16, 1174, 220, 17, 1174, 220, 18, 662, 1115, 2515, 574, 539, 13468, 369, 993, 220, 18, 482, 8671, 16621, 1534, 453, 8826, 288, 11, 6463, 369, 9333, 22996, 590, 35715, 13, 578, 26703, 315, 279, 27886, 11, 43030, 76041, 323, 44032, 315, 6761, 9501, 56427, 57733, 864, 7548, 53584, 9547, 439, 279, 25462, 19035, 13, 12361, 11, 584, 7180, 420, 2515, 311, 279, 15528, 18336, 272, 367, 315, 22996, 17390, 13, 5751, 25157, 27886, 4245, 311, 264, 40646, 11684, 18336, 272, 367, 574, 304, 9306, 449, 279, 17303, 990, 5865, 311, 2949, 20903, 15, 13, 18, 384, 53, 11, 23377, 264, 502, 49340, 369, 3428, 29721, 34849, 92025, 3196, 389, 279, 2955, 315, 94753, 449, 15528, 18336, 272, 811, 13, 4802, 8771, 41353, 505, 17676, 2442, 6586, 31747, 2601, 374, 1633, 18222, 389, 279, 20622, 437, 2296, 17484, 315, 279, 11813, 11, 779, 8275, 4442, 304, 279, 6070, 315, 279, 48363, 649, 3063, 311, 22520, 12062, 304, 279, 1510, 13, 28636, 287, 279, 3769, 990, 734, 374, 70668, 311, 1701, 17676, 10631, 13, 4452, 11, 420, 7612, 279, 3851, 315, 7479, 92025, 1778, 439, 68432, 477, 14659, 58998, 8115, 37182, 11, 719, 1521, 527, 7701, 56563, 323, 17509, 11, 902, 14090, 864, 7548, 872, 3851, 13, 33242, 437, 2296, 7384, 477, 92025, 430, 1436, 11322, 4528, 41353, 6012, 2085, 12434, 27541, 477, 312, 7323, 1053, 8617, 387, 264, 5199, 3094, 7119, 15009, 17130, 41353, 27529, 13, 25328, 12631, 617, 8767, 1027, 1511, 369, 2115, 12, 220, 19, 1174, 220, 20, 1174, 220, 21, 323, 30945, 21427, 37612, 7711, 220, 22, 1174, 220, 23, 7766, 11, 719, 279, 41353, 649, 387, 22486, 555, 279, 8009, 98971, 315, 20155, 22996, 11, 23537, 264, 6485, 21655, 315, 993, 220, 18, 22996, 323, 993, 220, 17, 95273, 311, 11322, 26613, 5178, 13, 24296, 11, 279, 3560, 315, 1521, 20622, 437, 2296, 3769, 304, 35940, 34224, 1385, 304, 279, 41353, 1920, 374, 2103, 539, 7373, 16365, 220, 19, 1174, 220, 21, 1174, 220, 24, 662, 5810, 11, 584, 1934, 430, 1647, 337, 5184, 315, 22996, 17390, 2345, 19285, 437, 2296, 22996, 35715, 2345, 27153, 3210, 49843, 12207, 24872, 2115, 37612, 7711, 6012, 311, 9501, 27529, 13, 4497, 8965, 11, 420, 5603, 5825, 459, 62803, 369, 279, 2955, 315, 502, 20622, 437, 2296, 7384, 555, 1491, 15853, 7479, 990, 5865, 3117, 7953, 279, 14595, 12264, 120, 220, 16, 384, 53, 24522, 7569, 6372, 13, 25328, 17390, 527, 20622, 4512, 265, 13230, 36460, 993, 220, 18, 17055, 7063, 47620, 449, 264, 22996, 64186, 6070, 323, 7373, 32372, 449, 35784, 220, 605, 1174, 220, 806, 662, 11205, 6012, 527, 459, 7185, 20955, 315, 1884, 315, 22996, 94753, 323, 2678, 35715, 220, 717, 1174, 323, 279, 1579, 24693, 13552, 19025, 11, 11742, 20334, 323, 3428, 2815, 47262, 6926, 220, 1032, 315, 22996, 11, 3686, 649, 387, 92600, 11, 17057, 220, 975, 1174, 220, 868, 323, 8590, 2740, 16003, 1534, 220, 845, 1174, 220, 1114, 1174, 220, 972, 304, 264, 11827, 4528, 311, 2678, 35715, 13, 25328, 17390, 31324, 264, 1396, 315, 16907, 6012, 11, 2737, 1647, 5059, 99866, 14580, 17130, 41353, 220, 777, 1174, 220, 508, 1174, 76024, 1317, 12782, 4235, 74441, 27460, 220, 1691, 1174, 220, 1313, 323, 264, 6996, 315, 31228, 66678, 304, 279, 653, 41456, 5415, 220, 1419, 662, 2435, 527, 7185, 11426, 369, 2115, 41353, 439, 814, 4097, 279, 17139, 4017, 304, 22996, 24875, 1404, 14278, 11, 902, 706, 8767, 1027, 49393, 449, 13241, 17130, 41353, 220, 21, 662, 666, 25947, 17515, 1908, 11028, 315, 279, 22996, 17390, 220, 972, 1051, 17057, 1139, 659, 33534, 26994, 1647, 337, 5184, 389, 33150, 477, 4701, 11, 449, 26839, 288, 24950, 505, 220, 15, 13, 20, 26807, 320, 2000, 84388, 2194, 7716, 25947, 8, 311, 220, 15, 13, 24, 26807, 320, 2000, 510, 7994, 60, 73542, 2453, 519, 2194, 12, 21, 7716, 25947, 570, 3296, 1701, 22996, 590, 1647, 337, 5184, 389, 46258, 27529, 584, 5766, 279, 98971, 5435, 5938, 449, 20155, 22996, 11, 864, 11150, 279, 1205, 369, 9709, 993, 220, 17, 611, 993, 220, 18, 7384, 13, 578, 6996, 315, 993, 220, 17, 12782, 477, 20155, 23011, 5415, 304, 279, 22996, 17390, 1101, 18911, 459, 10728, 1296, 1162, 311, 8720, 279, 3560, 315, 42655, 7863, 311, 20155, 22996, 12631, 13, 5810, 11, 279, 2115, 37612, 7711, 1510, 369, 22996, 590, 17515, 1908, 33150, 27529, 574, 27313, 369, 264, 4101, 315, 2204, 12562, 323, 89935, 315, 58998, 2194, 323, 22996, 590, 7716, 25947, 1647, 337, 5184, 320, 23966, 13, 220, 16, 7609, 1226, 14896, 279, 22996, 590, 62428, 3145, 84388, 2194, 12, 16, 7716, 25947, 320, 1846, 51, 705, 13047, 519, 2194, 12, 19, 7716, 25947, 320, 19, 10822, 705, 2463, 309, 519, 2194, 12, 24, 7716, 25947, 320, 24, 1305, 51, 705, 510, 7994, 60, 73542, 2453, 519, 2194, 12, 21, 7716, 25947, 320, 21, 15249, 705, 510, 7994, 60, 73542, 2453, 519, 2194, 12, 17, 7716, 25947, 320, 17, 15249, 705, 439, 1664, 439, 279, 79574, 12, 323, 1841, 2054, 4010, 12, 69759, 13790, 453, 8826, 774, 72, 3145, 294, 536, 66, 2194, 12, 16, 7716, 25947, 320, 4195, 51, 8, 323, 220, 845, 12, 1195, 11600, 998, 12651, 329, 762, 5770, 292, 12, 16, 38698, 307, 320, 845, 49302, 6486, 8, 439, 2585, 10688, 13, 24028, 13491, 315, 279, 270, 25947, 17515, 1908, 22996, 17390, 706, 1027, 7633, 8767, 220, 972, 662, 9220, 2204, 510, 7994, 60, 73542, 2453, 519, 2194, 270, 25947, 89935, 1051, 27313, 11, 832, 449, 279, 270, 25947, 389, 459, 1469, 950, 12782, 320, 21, 15249, 8, 369, 459, 3451, 455, 1315, 529, 6683, 11, 323, 832, 389, 264, 97348, 12782, 320, 17, 15249, 8, 369, 264, 16600, 17140, 389, 279, 33150, 7479, 13, 25328, 590, 659, 33534, 26994, 1647, 337, 5184, 320, 87434, 82, 8, 1051, 14454, 555, 4998, 388, 287, 279, 33150, 54057, 304, 220, 16, 84317, 22996, 590, 304, 220, 24, 25, 16, 311, 10036, 1994, 14, 42972, 13200, 320, 12821, 5574, 337, 8, 6425, 369, 12264, 120, 220, 1187, 4235, 2166, 305, 11, 97139, 287, 449, 311, 10036, 1994, 311, 4148, 13937, 35715, 323, 41442, 9235, 13, 4314, 7384, 1051, 3805, 5594, 481, 1306, 39975, 323, 1436, 387, 9967, 369, 264, 4261, 5129, 1109, 264, 2046, 2085, 53568, 13, 578, 2115, 37612, 7711, 1510, 439, 264, 734, 315, 9435, 22465, 574, 12793, 304, 264, 15638, 12235, 6683, 304, 459, 37232, 1494, 1108, 8437, 582, 21066, 1887, 320, 23966, 13, 220, 17, 883, 555, 81759, 279, 22996, 590, 62428, 3145, 8800, 33150, 23283, 660, 4323, 20622, 363, 3946, 13, 33242, 363, 3946, 1051, 1511, 311, 6994, 13579, 22465, 5990, 369, 17130, 41353, 323, 311, 8108, 279, 20314, 802, 6253, 13468, 304, 3197, 277, 10688, 11, 11383, 18189, 279, 5995, 22465, 555, 264, 8331, 315, 12264, 120, 220, 3965, 13, 19575, 220, 16, 25, 8771, 41353, 41705, 13, 264, 1174, 328, 82149, 315, 2115, 41353, 743, 5352, 13, 293, 1174, 2522, 6073, 17130, 92914, 2217, 315, 279, 52035, 42208, 4323, 20622, 363, 3946, 389, 279, 4323, 320, 5037, 8, 7479, 13, 578, 36108, 527, 12264, 120, 220, 914, 64012, 76, 304, 3160, 13, 25635, 16283, 25, 220, 605, 64012, 76, 320, 3902, 2217, 8, 323, 220, 2636, 26807, 320, 258, 751, 570, 272, 1174, 71150, 315, 279, 35715, 12793, 11, 2737, 22996, 590, 62428, 3145, 449, 832, 311, 4330, 81947, 323, 13790, 66286, 58998, 2194, 62428, 3145, 449, 79574, 323, 1841, 2054, 4010, 10415, 811, 13, 40602, 4469, 33299, 527, 539, 6982, 369, 32373, 13, 8797, 1404, 2217, 19575, 220, 17, 25, 25328, 590, 2115, 41353, 13, 264, 1174, 328, 82149, 315, 279, 22996, 590, 16003, 2065, 47594, 17130, 41353, 505, 33150, 23283, 660, 4323, 20622, 363, 556, 991, 29163, 13, 293, 1174, 9303, 4235, 85, 27587, 35483, 505, 279, 20622, 363, 556, 991, 29163, 1603, 16003, 4954, 449, 220, 21, 15249, 320, 12481, 705, 1306, 16003, 4954, 449, 220, 21, 15249, 320, 13553, 8, 323, 1306, 951, 269, 7278, 220, 21, 15249, 320, 1171, 570, 272, 1174, 75243, 4235, 45, 541, 21215, 31794, 315, 279, 828, 505, 293, 662, 8797, 128257, 198, 128256, 78191, 198, 7009, 5222, 1093, 80320, 10094, 11, 719, 17130, 16766, 527, 3604, 990, 60775, 7526, 369, 3495, 323, 5064, 25, 2435, 17105, 23914, 315, 57678, 369, 17130, 8162, 82025, 11, 87836, 93093, 1251, 7241, 323, 19320, 14511, 3046, 11, 311, 836, 264, 2478, 3062, 5829, 13, 4800, 14248, 520, 31788, 3907, 323, 279, 6011, 315, 12634, 596, 17216, 1741, 5165, 48005, 859, 32184, 617, 25720, 704, 1268, 311, 5376, 1521, 17130, 28555, 220, 1032, 11, 931, 24325, 555, 19486, 264, 3254, 6324, 315, 22996, 17390, 1389, 13987, 11, 4832, 22996, 81947, 1389, 311, 459, 17130, 6166, 596, 17676, 6761, 11813, 13, 578, 3135, 11, 4756, 3432, 304, 22037, 33242, 52536, 11, 4284, 264, 4459, 502, 5603, 369, 7859, 279, 2410, 315, 1521, 7766, 13, 2435, 1101, 3493, 459, 62803, 369, 30829, 1023, 4595, 315, 17130, 991, 29163, 449, 19670, 14656, 12, 22612, 16437, 11, 1071, 15341, 11220, 9451, 11, 459, 22712, 14561, 520, 17216, 1741, 323, 31788, 889, 6197, 279, 4007, 13, 25328, 17390, 527, 958, 90582, 81947, 1903, 315, 12782, 323, 35784, 33299, 13, 2435, 2351, 279, 25655, 3284, 9660, 315, 22996, 11, 1855, 47826, 2753, 1109, 264, 7239, 339, 315, 264, 7239, 339, 315, 264, 1841, 266, 13, 3011, 2678, 1404, 11, 3235, 449, 872, 33956, 11, 45652, 6070, 323, 1579, 11742, 53500, 11, 3041, 1124, 5505, 6012, 430, 8294, 49151, 6996, 13, 17216, 1741, 323, 31788, 617, 3719, 832, 315, 279, 1917, 596, 6522, 19169, 369, 22996, 590, 3495, 13, 19241, 527, 11953, 704, 1555, 23739, 1600, 11, 279, 31788, 10181, 369, 32009, 323, 12634, 23199, 11, 323, 264, 10278, 520, 17216, 1741, 374, 29329, 311, 60508, 22996, 17390, 505, 60063, 13, 763, 220, 1049, 22, 11, 264, 2128, 6197, 555, 1690, 315, 279, 1890, 23739, 1600, 12074, 8710, 430, 264, 3254, 6324, 315, 22996, 17390, 389, 264, 9501, 7479, 1436, 17105, 323, 5357, 57678, 1139, 264, 13987, 24310, 449, 264, 1633, 15376, 2134, 315, 49969, 13, 578, 3495, 2128, 1511, 13987, 76307, 484, 1590, 315, 43627, 2411, 9244, 439, 2559, 22610, 369, 279, 10631, 315, 17130, 16766, 304, 21896, 20034, 520, 18899, 17130, 41353, 13, 1115, 2217, 574, 1903, 449, 264, 36201, 17130, 73757, 1389, 832, 315, 264, 1396, 315, 7766, 430, 1005, 48042, 57678, 13, 16666, 25, 13528, 339, 1609, 29853, 300, 318, 4317, 14, 52059, 8350, 578, 502, 4007, 7111, 520, 3508, 264, 22996, 590, 41394, 1436, 1101, 7417, 20748, 505, 17130, 16766, 13, 3861, 1648, 311, 5376, 279, 2410, 315, 459, 17130, 6166, 374, 311, 1304, 279, 11813, 2216, 17676, 11, 902, 3727, 433, 8831, 311, 636, 279, 57678, 704, 11, 11220, 9451, 1071, 13, 2030, 1521, 17676, 10631, 527, 45311, 26, 1524, 13987, 42408, 1385, 649, 7958, 872, 5178, 13, 59250, 617, 6818, 311, 636, 2212, 420, 555, 41394, 279, 10631, 449, 26333, 430, 7916, 17130, 41353, 11, 719, 420, 649, 387, 36033, 1606, 1063, 315, 279, 1455, 7524, 6305, 21165, 1139, 39885, 994, 15246, 311, 3805, 13, 1789, 420, 4007, 11, 279, 14248, 1511, 13987, 76307, 484, 1590, 315, 43627, 2411, 9244, 439, 2559, 22610, 369, 17130, 6166, 10631, 13, 2435, 49482, 279, 36108, 449, 6761, 323, 1243, 449, 22996, 17390, 315, 5370, 12562, 13, 6063, 2411, 76307, 484, 1590, 1051, 49482, 449, 6761, 323, 1243, 449, 22996, 17390, 315, 5370, 12562, 13, 578, 14248, 2751, 279, 1888, 3135, 555, 41394, 279, 64982, 449, 22996, 590, 35715, 430, 6824, 315, 3116, 1054, 66, 1154, 26, 863, 420, 7319, 279, 41353, 315, 57678, 505, 279, 10631, 220, 1032, 11, 931, 24325, 13, 16666, 25, 13528, 339, 1609, 29853, 300, 318, 4317, 14, 52059, 8350, 3277, 279, 14248, 9435, 264, 22465, 311, 279, 20622, 363, 3946, 311, 51077, 279, 4984, 315, 57678, 505, 279, 10631, 11, 814, 1766, 814, 2751, 279, 1888, 3135, 505, 10631, 49482, 449, 22996, 17390, 430, 6824, 315, 3116, 330, 66, 1154, 1210, 4314, 6004, 264, 63969, 220, 1032, 11, 931, 3115, 810, 57678, 1109, 12743, 6761, 10631, 13, 15903, 7177, 323, 6500, 47590, 4284, 430, 279, 5376, 574, 539, 4245, 311, 4442, 304, 279, 6211, 315, 279, 11813, 477, 304, 279, 16940, 6761, 7479, 13, 12361, 11, 433, 5992, 1093, 1063, 315, 279, 22996, 590, 35715, 304, 279, 11813, 5675, 264, 3254, 17130, 1389, 433, 596, 539, 2867, 7041, 1268, 13, 1115, 3549, 264, 6928, 6900, 430, 29123, 57678, 505, 279, 16940, 7479, 323, 1903, 433, 8831, 369, 1124, 311, 6530, 704, 315, 279, 11813, 11, 11220, 9451, 1071, 13, 330, 13622, 1023, 35715, 1053, 539, 387, 15528, 422, 499, 7108, 459, 17130, 26, 814, 4265, 4498, 10980, 1359, 568, 1071, 13, 330, 4071, 279, 36460, 12970, 7138, 315, 279, 22996, 590, 3727, 433, 57899, 15528, 11, 323, 430, 596, 3249, 420, 1920, 4375, 13, 4800, 430, 584, 3619, 1148, 596, 2133, 389, 11, 584, 1253, 387, 3025, 311, 1005, 430, 6677, 311, 24490, 1023, 7384, 430, 527, 2216, 1695, 520, 90556, 57678, 1210, 25328, 590, 14726, 12793, 304, 279, 9526, 26, 279, 1403, 389, 279, 5740, 11, 902, 6824, 315, 3116, 1054, 66, 1154, 863, 449, 12782, 33299, 520, 1855, 9309, 11, 9124, 279, 8706, 20192, 304, 17130, 41353, 13, 578, 11742, 9681, 520, 279, 5740, 315, 1855, 43030, 1051, 3779, 311, 1520, 279, 22996, 17390, 9396, 311, 279, 6761, 7479, 315, 279, 76307, 484, 1590, 13, 16666, 25, 13528, 339, 1609, 29853, 300, 318, 4317, 14, 52059, 8350, 23739, 1600, 12074, 15341, 11220, 9451, 11, 2163, 11, 323, 28217, 87967, 304, 264, 31788, 27692, 449, 7241, 1511, 311, 2804, 22996, 590, 21896, 13, 16666, 25, 17216, 1741, 5165, 48005, 859, 32184, 220, 128257, 198 ]

2,447

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract This paper reports design, fabrication, and characterization of an air-actuated microvalve and a micropump made of thermoplastic materials. The bonding process was carried out by thermal fusion process with no particular surface treatment. The developed microvalve was used as a reversible switch for controlling both liquid flow and electrical field. Bonding strength of the fabricated microvalves could withstand liquid and air pressures of up to 600 kPa with no burst failure. The micropump made of three connected microvalves, actuated by compressed air, could generate a liquid flow rate of up to 85 µl/min. The proposed microvalve and micropump can be used as pre-fabricated off-the-shelf microfluidic functional elements for easy and rapid integration with thermoplastic microfluidic circuitries in a plug-and-play arrangement. Access provided by DEAL DE / Springer Compact Clearingstelle Uni Freiburg _ Working on a manuscript? Avoid the common mistakes 1 Introduction Because of essential role of flow control and manipulation for microfluidic applications, many investigations have been carried out to develop various designs of microvalves (Oh and Ahn 2006 ; Zhu et al. 2012 ; Jiang and Erickson 2013 ; Kang et al. 2013 ; Shiraki et al. 2015 ) and micropumps (Nguyen et al. 2002 ; Yobas et al. 2008 ; Qin et al. 2009 ; Zhang et al. 2015 ). Examples of deploying microvalves can be found for cell culture assays (Gómez-Sjöberg et al. 2007 ; Wu et al. 2008 ; Frimat et al. 2011 ), microfluidic drug screening (Ma et al. 2009 ; Nguyen et al. 2013 ), single-cell analysis (Irimia 2010 ), and droplet microfluidics (Zeng et al. 2009 ). Silicon-based microvalves and micropumps were developed at the early stages of microfluidic progress using surface and bulk micromachining technologies (Oh and Ahn 2006 ). But for the last 15 years, different polymers have been adopted for the development of microvalves and micropumps taking advantage of cheaper materials and easier fabrication methods. Generally, a microvalve is made of a flexible diaphragm sandwiched between a control chamber and a liquid chamber (control chamber/diaphragm/liquid chamber). Upon the deformation of the diaphragm by an external means, flow inside the fluidic chamber can be manipulated. In terms of fabrication process, microvalves are generally categorized into (1) built-in microvalves and (2) pre-fabricated microvalves. For built-in microvalves, diaphragm is generally made of polydimethylsiloxane (PDMS). Control chambers and the liquid chambers can be made of PDMS, polymethylmethacrylate (PMMA) and cyclic olefin copolymer (COC) during the course of chip fabrication in the following arrangements: (PDMS/PDMS/PDMS) (Unger et al. 2000 ; Gómez-Sjöberg et al. 2007 ; Gu et al. 2010 ), (PMMA/PDMS/PMMA) (Zhang et al. 2009 ), and (COC/PDMS/COC) (Gu et al. 2010 ). Because of small footprint of such microvalves, e.g., 100 µm × 100 µm (Unger et al. 2000 ), built-in microvalve concept enables microfluidic large-scale integration (Melin and Quake 2007 ) with pneumatic actuation, suitable for high-throughput cell culture and single-cell analysis (Wu et al. 2004 ; Gómez-Sjöberg et al. 2007 ; Lii et al. 2008 ). It has been reported that PDMS with no surface treatment can absorb some small hydrophobic molecules, i.e., estrogen, during microfluidic drug screening (Regehr et al. 2009 ; Berthier et al. 2012 ). In addition, some uncured oligomer compounds from the polymeric network of PDMS can leach into the microchannel media affecting cell membrane during cell culture (Regehr et al. 2009 ; Berthier et al. 2012 ). Also, some organic solvents swell PDMS or dissolve PDMS compounds (Lee et al. 2003 ). Such features of PDMS can hinder some applications, particularly microfluidic organ-on-chip devices for drug screening. In order to mitigate the mentioned problems of using PDMS for microvalve fabrication, other elastomers including Teflon (Teflon/Teflon/Teflon) (Grover et al. 2008 ), Viton ® (PMMA/Viton ® /PMMA) or (COC/Viton ® /COC) (Ogilvie et al. 2011 ) have been explored for built-in microvalves. Pre-fabricated microvalves (Elizabeth Hulme et al. 2009 ) can be made in advance and then integrated with a pre-fabricated microfluidic chip. In contrast to built-in microvalves, these microvalves have larger footprints at millimeter scale. Therefore, because of ease of incorporation, such microvalves are suitable for plug-and-play applications where low-density integration of microfluidic components is required. Some explored applications are gradient generators (Elizabeth Hulme et al. 2009 ), immunoassay (Weibel et al. 2005 ) and on-chip lifelong observation of C. elegans (Hulme et al. 2010 ). Depending on the microvalve design, a pre-fabricated microvalve can be actuated manually by a screw (Weibel et al. 2005 ; Hulme et al. 2010 ), electrically by a solenoid actuator (Weibel et al. 2005 ), or pneumatically (Elizabeth Hulme et al. 2009 ). Pre-fabricated valves are mainly made of PDMS in large quantities. They are embedded into microfluidic chips during the casting of the master-made PDMS (Hulme et al. 2010 ). Pre-fabricated valves made from PDMS are suitable for PDMS-based microfluidic devices. Therefore, there is a lack of microvalves for user-friendly integration with microfluidic chips made of thermoplastic materials. In recent years, thermoplastic materials have gained significant popularity for microfluidic applications (Tsao and DeVoe 2009 ) suitable for high volume, low-cost production (Chin et al. 2012 ). Also, they have lower oxygen permeability compared to PDMS (Ochs et al. 2014 ). Materials with low oxygen permeability are required for making devices to create oxygen-controlled conditions on a microfluidic chip for tumor microenvironment and hypoxia (Byrne et al. 2014 ). In this paper, we reported a systematic approach for design, fabrication, and characterization of a plug-and-play pre-fabricated microvalve and a micropump for easy integration with microfluidic chips made of thermoplastic materials. As shown in Fig. 1 , the normally open microvalve was made of a flexible diaphragm, thermoplastic polyurethane (TPU), sandwiched between a liquid chamber and an air chamber both made of PMMA. Upon increasing air pressure inside the control chamber, the diaphragm was deformed downward at the liquid chamber (displacement chamber) to stop the liquid passing through the microvalve. Different layers of microvalve were bonded together through thermal fusion process with no particular surface treatment. Fig. 1 a Concept design", "role": "user" }, { "content": "The elusive 'lab on a chip' capable of shrinking and integrating operations normally performed in a chemical or medical laboratory on to a single chip smaller than a credit card, may soon be realized thanks to disposable, plug-and-play microfluidic devices developed by A*STAR researchers1. Microfluidic systems use networks of channels much narrower than a human hair to control the movement of miniscule amounts of fluids. Recent advances in microfluidics technology have proven invaluable for immediate point-of-care diagnosis of diseases and have greatly improved enzymatic and DNA analysis. High throughput microfluidic systems are also being employed in stem cell studies and for the discovery of new drugs. A stumbling block for successful miniaturization and commercialization of fully integrated microfluidic systems, however, has been the development of reliable microfluidic components, such as microvalves and micropumps. Zhenfeng Wang and colleagues from the Singapore Institute of Manufacturing Technology (SIMTech), A*STAR have removed that obstacle by developing an efficient and scalable method to fabricate disposable plug-and-play microfluidic devices. \"Integrating valves and pumps into thermoplastic devices is usually challenging and costly because the fabrication process is very complicated,\" says Wang. \"Mass-producing the microvalve module separately from the main device, however, makes the fabrication of the main device relatively simple and robust.\" Microvalves consist of a flexible diaphragm sandwiched between a control chamber and liquid chamber, and by applying pressure from an external mechanical pump, or through electrostatic or pneumatic forces, the diaphragm can be deformed allowing for the manipulation of fluidic flow within the chamber. The researchers fabricated a micropump consisting of three microvalves, but had to find a suitable material for the microvalve membranes, which must be flexible, but also easily bonded to other parts of the microvalve without the use of adhesives. \"We found that thermoplastic polyurethane film works well as the membrane and can be bonded tightly with the main body, which is made from polymethyl methacrylate,\" explains Wang. The design of the microvalve also presented a challenge to the researchers, which they overcame by using finite element method simulation—a numerical tool used to solve complex structural problems—to generate the design guidelines, which were then verified by experimentation. Using the SIMTech Microfluidics Foundry, the researchers are currently developing a number of 'on chip' modules and are expanding their capabilities in the design, prototyping and manufacture of polymer based microfluidic devices. \"Further miniaturizing the size of microvalve modules could increase the scale of integration and broaden the range of potential applications,\" says Wang. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract This paper reports design, fabrication, and characterization of an air-actuated microvalve and a micropump made of thermoplastic materials. The bonding process was carried out by thermal fusion process with no particular surface treatment. The developed microvalve was used as a reversible switch for controlling both liquid flow and electrical field. Bonding strength of the fabricated microvalves could withstand liquid and air pressures of up to 600 kPa with no burst failure. The micropump made of three connected microvalves, actuated by compressed air, could generate a liquid flow rate of up to 85 µl/min. The proposed microvalve and micropump can be used as pre-fabricated off-the-shelf microfluidic functional elements for easy and rapid integration with thermoplastic microfluidic circuitries in a plug-and-play arrangement. Access provided by DEAL DE / Springer Compact Clearingstelle Uni Freiburg _ Working on a manuscript? Avoid the common mistakes 1 Introduction Because of essential role of flow control and manipulation for microfluidic applications, many investigations have been carried out to develop various designs of microvalves (Oh and Ahn 2006 ; Zhu et al. 2012 ; Jiang and Erickson 2013 ; Kang et al. 2013 ; Shiraki et al. 2015 ) and micropumps (Nguyen et al. 2002 ; Yobas et al. 2008 ; Qin et al. 2009 ; Zhang et al. 2015 ). Examples of deploying microvalves can be found for cell culture assays (Gómez-Sjöberg et al. 2007 ; Wu et al. 2008 ; Frimat et al. 2011 ), microfluidic drug screening (Ma et al. 2009 ; Nguyen et al. 2013 ), single-cell analysis (Irimia 2010 ), and droplet microfluidics (Zeng et al. 2009 ). Silicon-based microvalves and micropumps were developed at the early stages of microfluidic progress using surface and bulk micromachining technologies (Oh and Ahn 2006 ). But for the last 15 years, different polymers have been adopted for the development of microvalves and micropumps taking advantage of cheaper materials and easier fabrication methods. Generally, a microvalve is made of a flexible diaphragm sandwiched between a control chamber and a liquid chamber (control chamber/diaphragm/liquid chamber). Upon the deformation of the diaphragm by an external means, flow inside the fluidic chamber can be manipulated. In terms of fabrication process, microvalves are generally categorized into (1) built-in microvalves and (2) pre-fabricated microvalves. For built-in microvalves, diaphragm is generally made of polydimethylsiloxane (PDMS). Control chambers and the liquid chambers can be made of PDMS, polymethylmethacrylate (PMMA) and cyclic olefin copolymer (COC) during the course of chip fabrication in the following arrangements: (PDMS/PDMS/PDMS) (Unger et al. 2000 ; Gómez-Sjöberg et al. 2007 ; Gu et al. 2010 ), (PMMA/PDMS/PMMA) (Zhang et al. 2009 ), and (COC/PDMS/COC) (Gu et al. 2010 ). Because of small footprint of such microvalves, e.g., 100 µm × 100 µm (Unger et al. 2000 ), built-in microvalve concept enables microfluidic large-scale integration (Melin and Quake 2007 ) with pneumatic actuation, suitable for high-throughput cell culture and single-cell analysis (Wu et al. 2004 ; Gómez-Sjöberg et al. 2007 ; Lii et al. 2008 ). It has been reported that PDMS with no surface treatment can absorb some small hydrophobic molecules, i.e., estrogen, during microfluidic drug screening (Regehr et al. 2009 ; Berthier et al. 2012 ). In addition, some uncured oligomer compounds from the polymeric network of PDMS can leach into the microchannel media affecting cell membrane during cell culture (Regehr et al. 2009 ; Berthier et al. 2012 ). Also, some organic solvents swell PDMS or dissolve PDMS compounds (Lee et al. 2003 ). Such features of PDMS can hinder some applications, particularly microfluidic organ-on-chip devices for drug screening. In order to mitigate the mentioned problems of using PDMS for microvalve fabrication, other elastomers including Teflon (Teflon/Teflon/Teflon) (Grover et al. 2008 ), Viton ® (PMMA/Viton ® /PMMA) or (COC/Viton ® /COC) (Ogilvie et al. 2011 ) have been explored for built-in microvalves. Pre-fabricated microvalves (Elizabeth Hulme et al. 2009 ) can be made in advance and then integrated with a pre-fabricated microfluidic chip. In contrast to built-in microvalves, these microvalves have larger footprints at millimeter scale. Therefore, because of ease of incorporation, such microvalves are suitable for plug-and-play applications where low-density integration of microfluidic components is required. Some explored applications are gradient generators (Elizabeth Hulme et al. 2009 ), immunoassay (Weibel et al. 2005 ) and on-chip lifelong observation of C. elegans (Hulme et al. 2010 ). Depending on the microvalve design, a pre-fabricated microvalve can be actuated manually by a screw (Weibel et al. 2005 ; Hulme et al. 2010 ), electrically by a solenoid actuator (Weibel et al. 2005 ), or pneumatically (Elizabeth Hulme et al. 2009 ). Pre-fabricated valves are mainly made of PDMS in large quantities. They are embedded into microfluidic chips during the casting of the master-made PDMS (Hulme et al. 2010 ). Pre-fabricated valves made from PDMS are suitable for PDMS-based microfluidic devices. Therefore, there is a lack of microvalves for user-friendly integration with microfluidic chips made of thermoplastic materials. In recent years, thermoplastic materials have gained significant popularity for microfluidic applications (Tsao and DeVoe 2009 ) suitable for high volume, low-cost production (Chin et al. 2012 ). Also, they have lower oxygen permeability compared to PDMS (Ochs et al. 2014 ). Materials with low oxygen permeability are required for making devices to create oxygen-controlled conditions on a microfluidic chip for tumor microenvironment and hypoxia (Byrne et al. 2014 ). In this paper, we reported a systematic approach for design, fabrication, and characterization of a plug-and-play pre-fabricated microvalve and a micropump for easy integration with microfluidic chips made of thermoplastic materials. As shown in Fig. 1 , the normally open microvalve was made of a flexible diaphragm, thermoplastic polyurethane (TPU), sandwiched between a liquid chamber and an air chamber both made of PMMA. Upon increasing air pressure inside the control chamber, the diaphragm was deformed downward at the liquid chamber (displacement chamber) to stop the liquid passing through the microvalve. Different layers of microvalve were bonded together through thermal fusion process with no particular surface treatment. Fig. 1 a Concept design<|im_end|> <|im_start|>assistant The elusive 'lab on a chip' capable of shrinking and integrating operations normally performed in a chemical or medical laboratory on to a single chip smaller than a credit card, may soon be realized thanks to disposable, plug-and-play microfluidic devices developed by A*STAR researchers1. Microfluidic systems use networks of channels much narrower than a human hair to control the movement of miniscule amounts of fluids. Recent advances in microfluidics technology have proven invaluable for immediate point-of-care diagnosis of diseases and have greatly improved enzymatic and DNA analysis. High throughput microfluidic systems are also being employed in stem cell studies and for the discovery of new drugs. A stumbling block for successful miniaturization and commercialization of fully integrated microfluidic systems, however, has been the development of reliable microfluidic components, such as microvalves and micropumps. Zhenfeng Wang and colleagues from the Singapore Institute of Manufacturing Technology (SIMTech), A*STAR have removed that obstacle by developing an efficient and scalable method to fabricate disposable plug-and-play microfluidic devices. "Integrating valves and pumps into thermoplastic devices is usually challenging and costly because the fabrication process is very complicated," says Wang. "Mass-producing the microvalve module separately from the main device, however, makes the fabrication of the main device relatively simple and robust." Microvalves consist of a flexible diaphragm sandwiched between a control chamber and liquid chamber, and by applying pressure from an external mechanical pump, or through electrostatic or pneumatic forces, the diaphragm can be deformed allowing for the manipulation of fluidic flow within the chamber. The researchers fabricated a micropump consisting of three microvalves, but had to find a suitable material for the microvalve membranes, which must be flexible, but also easily bonded to other parts of the microvalve without the use of adhesives. "We found that thermoplastic polyurethane film works well as the membrane and can be bonded tightly with the main body, which is made from polymethyl methacrylate," explains Wang. The design of the microvalve also presented a challenge to the researchers, which they overcame by using finite element method simulation—a numerical tool used to solve complex structural problems—to generate the design guidelines, which were then verified by experimentation. Using the SIMTech Microfluidics Foundry, the researchers are currently developing a number of 'on chip' modules and are expanding their capabilities in the design, prototyping and manufacture of polymer based microfluidic devices. "Further miniaturizing the size of microvalve modules could increase the scale of integration and broaden the range of potential applications," says Wang. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 1115, 5684, 6821, 2955, 11, 59251, 11, 323, 60993, 315, 459, 3805, 12, 533, 13148, 8162, 838, 588, 323, 264, 19748, 897, 1538, 1903, 315, 30945, 454, 52279, 7384, 13, 578, 64186, 1920, 574, 11953, 704, 555, 29487, 37608, 1920, 449, 912, 4040, 7479, 6514, 13, 578, 8040, 8162, 838, 588, 574, 1511, 439, 264, 81193, 3480, 369, 26991, 2225, 14812, 6530, 323, 20314, 2115, 13, 24537, 287, 8333, 315, 279, 70554, 8162, 838, 2396, 1436, 51571, 14812, 323, 3805, 40850, 315, 709, 311, 220, 5067, 597, 20908, 449, 912, 21165, 8060, 13, 578, 19748, 897, 1538, 1903, 315, 2380, 8599, 8162, 838, 2396, 11, 1180, 13148, 555, 31749, 3805, 11, 1436, 7068, 264, 14812, 6530, 4478, 315, 709, 311, 220, 5313, 64012, 75, 45273, 13, 578, 11223, 8162, 838, 588, 323, 19748, 897, 1538, 649, 387, 1511, 439, 864, 2269, 29997, 660, 1022, 10826, 7666, 491, 8162, 67125, 292, 16003, 5540, 369, 4228, 323, 11295, 18052, 449, 30945, 454, 52279, 8162, 67125, 292, 16622, 4108, 304, 264, 20206, 9976, 27642, 27204, 13, 9742, 3984, 555, 26571, 3467, 611, 67915, 55882, 12292, 287, 267, 6853, 49966, 7730, 581, 5673, 721, 22938, 389, 264, 47913, 30, 35106, 279, 4279, 21294, 220, 16, 29438, 9393, 315, 7718, 3560, 315, 6530, 2585, 323, 34786, 369, 8162, 67125, 292, 8522, 11, 1690, 26969, 617, 1027, 11953, 704, 311, 2274, 5370, 14769, 315, 8162, 838, 2396, 320, 12174, 323, 16770, 77, 220, 1049, 21, 2652, 68844, 1880, 453, 13, 220, 679, 17, 2652, 61922, 323, 81015, 942, 220, 679, 18, 2652, 55376, 1880, 453, 13, 220, 679, 18, 2652, 50356, 14966, 1880, 453, 13, 220, 679, 20, 883, 323, 19748, 897, 12055, 320, 21567, 38855, 1880, 453, 13, 220, 1049, 17, 2652, 816, 677, 300, 1880, 453, 13, 220, 1049, 23, 2652, 74451, 1880, 453, 13, 220, 1049, 24, 2652, 37120, 1880, 453, 13, 220, 679, 20, 7609, 26379, 315, 61417, 8162, 838, 2396, 649, 387, 1766, 369, 2849, 7829, 99592, 320, 38, 1832, 83256, 6354, 73, 3029, 7881, 1880, 453, 13, 220, 1049, 22, 2652, 37230, 1880, 453, 13, 220, 1049, 23, 2652, 2939, 78432, 1880, 453, 13, 220, 679, 16, 7026, 8162, 67125, 292, 5623, 23061, 320, 30635, 1880, 453, 13, 220, 1049, 24, 2652, 64261, 1880, 453, 13, 220, 679, 18, 7026, 3254, 33001, 6492, 320, 40, 6417, 689, 220, 679, 15, 7026, 323, 7118, 11053, 8162, 67125, 1233, 320, 57, 833, 1880, 453, 13, 220, 1049, 24, 7609, 38250, 6108, 8162, 838, 2396, 323, 19748, 897, 12055, 1051, 8040, 520, 279, 4216, 18094, 315, 8162, 67125, 292, 5208, 1701, 7479, 323, 20155, 19748, 442, 613, 5859, 14645, 320, 12174, 323, 16770, 77, 220, 1049, 21, 7609, 2030, 369, 279, 1566, 220, 868, 1667, 11, 2204, 46033, 388, 617, 1027, 18306, 369, 279, 4500, 315, 8162, 838, 2396, 323, 19748, 897, 12055, 4737, 9610, 315, 23917, 7384, 323, 8831, 59251, 5528, 13, 44493, 11, 264, 8162, 838, 588, 374, 1903, 315, 264, 19303, 1891, 95896, 76, 28974, 291, 1990, 264, 2585, 25199, 323, 264, 14812, 25199, 320, 2935, 25199, 3529, 72, 95896, 76, 14, 54737, 25199, 570, 30538, 279, 91621, 315, 279, 1891, 95896, 76, 555, 459, 9434, 3445, 11, 6530, 4871, 279, 15962, 292, 25199, 649, 387, 55315, 13, 763, 3878, 315, 59251, 1920, 11, 8162, 838, 2396, 527, 8965, 71974, 1139, 320, 16, 8, 5918, 3502, 8162, 838, 2396, 323, 320, 17, 8, 864, 2269, 29997, 660, 8162, 838, 2396, 13, 1789, 5918, 3502, 8162, 838, 2396, 11, 1891, 95896, 76, 374, 8965, 1903, 315, 10062, 13223, 42972, 35904, 5241, 2194, 320, 23891, 4931, 570, 7935, 53279, 323, 279, 14812, 53279, 649, 387, 1903, 315, 27572, 4931, 11, 46033, 42972, 69991, 582, 894, 5185, 320, 8971, 4940, 8, 323, 77102, 32878, 5589, 6293, 5849, 1195, 320, 34, 7767, 8, 2391, 279, 3388, 315, 16797, 59251, 304, 279, 2768, 28904, 25, 320, 23891, 4931, 16744, 35, 4931, 16744, 35, 4931, 8, 320, 52, 65167, 1880, 453, 13, 220, 1049, 15, 2652, 480, 1832, 83256, 6354, 73, 3029, 7881, 1880, 453, 13, 220, 1049, 22, 2652, 4673, 1880, 453, 13, 220, 679, 15, 7026, 320, 8971, 4940, 16744, 35, 4931, 14, 8971, 4940, 8, 320, 57, 21313, 1880, 453, 13, 220, 1049, 24, 7026, 323, 320, 34, 7767, 16744, 35, 4931, 11547, 7767, 8, 320, 17198, 1880, 453, 13, 220, 679, 15, 7609, 9393, 315, 2678, 43972, 315, 1778, 8162, 838, 2396, 11, 384, 1326, 2637, 220, 1041, 64012, 76, 25800, 220, 1041, 64012, 76, 320, 52, 65167, 1880, 453, 13, 220, 1049, 15, 7026, 5918, 3502, 8162, 838, 588, 7434, 20682, 8162, 67125, 292, 3544, 13230, 18052, 320, 44, 33830, 323, 3489, 731, 220, 1049, 22, 883, 449, 44626, 33030, 1180, 4090, 11, 14791, 369, 1579, 43847, 631, 2849, 7829, 323, 3254, 33001, 6492, 320, 54, 84, 1880, 453, 13, 220, 1049, 19, 2652, 480, 1832, 83256, 6354, 73, 3029, 7881, 1880, 453, 13, 220, 1049, 22, 2652, 445, 3893, 1880, 453, 13, 220, 1049, 23, 7609, 1102, 706, 1027, 5068, 430, 27572, 4931, 449, 912, 7479, 6514, 649, 35406, 1063, 2678, 17055, 764, 31906, 35715, 11, 602, 1770, 2637, 70180, 11, 2391, 8162, 67125, 292, 5623, 23061, 320, 697, 713, 4171, 1880, 453, 13, 220, 1049, 24, 2652, 9084, 339, 1291, 1880, 453, 13, 220, 679, 17, 7609, 763, 5369, 11, 1063, 21482, 3149, 55984, 26429, 32246, 505, 279, 10062, 2165, 4009, 315, 27572, 4931, 649, 514, 613, 1139, 279, 8162, 10327, 3772, 28987, 2849, 39654, 2391, 2849, 7829, 320, 697, 713, 4171, 1880, 453, 13, 220, 1049, 24, 2652, 9084, 339, 1291, 1880, 453, 13, 220, 679, 17, 7609, 7429, 11, 1063, 17808, 2092, 48764, 78353, 27572, 4931, 477, 73739, 27572, 4931, 32246, 320, 55088, 1880, 453, 13, 220, 1049, 18, 7609, 15483, 4519, 315, 27572, 4931, 649, 57780, 1063, 8522, 11, 8104, 8162, 67125, 292, 2942, 10539, 11843, 575, 7766, 369, 5623, 23061, 13, 763, 2015, 311, 50460, 279, 9932, 5435, 315, 1701, 27572, 4931, 369, 8162, 838, 588, 59251, 11, 1023, 92185, 69638, 2737, 350, 830, 12490, 320, 51, 830, 12490, 17146, 830, 12490, 17146, 830, 12490, 8, 320, 77435, 424, 1880, 453, 13, 220, 1049, 23, 7026, 29560, 263, 61579, 320, 8971, 4940, 28332, 63537, 61579, 611, 8971, 4940, 8, 477, 320, 34, 7767, 28332, 63537, 61579, 611, 34, 7767, 8, 320, 46, 61887, 64519, 1880, 453, 13, 220, 679, 16, 883, 617, 1027, 36131, 369, 5918, 3502, 8162, 838, 2396, 13, 5075, 2269, 29997, 660, 8162, 838, 2396, 320, 76637, 473, 360, 2727, 1880, 453, 13, 220, 1049, 24, 883, 649, 387, 1903, 304, 12178, 323, 1243, 18751, 449, 264, 864, 2269, 29997, 660, 8162, 67125, 292, 16797, 13, 763, 13168, 311, 5918, 3502, 8162, 838, 2396, 11, 1521, 8162, 838, 2396, 617, 8294, 4579, 26822, 520, 2606, 26402, 5569, 13, 15636, 11, 1606, 315, 14553, 315, 88465, 11, 1778, 8162, 838, 2396, 527, 14791, 369, 20206, 9976, 27642, 8522, 1405, 3428, 89131, 18052, 315, 8162, 67125, 292, 6956, 374, 2631, 13, 4427, 36131, 8522, 527, 20779, 44163, 320, 76637, 473, 360, 2727, 1880, 453, 13, 220, 1049, 24, 7026, 4998, 16711, 395, 352, 320, 1687, 69695, 1880, 453, 13, 220, 1049, 20, 883, 323, 389, 11843, 575, 51263, 22695, 315, 356, 13, 18190, 598, 320, 39, 360, 2727, 1880, 453, 13, 220, 679, 15, 7609, 40730, 389, 279, 8162, 838, 588, 2955, 11, 264, 864, 2269, 29997, 660, 8162, 838, 588, 649, 387, 1180, 13148, 20684, 555, 264, 22733, 320, 1687, 69695, 1880, 453, 13, 220, 1049, 20, 2652, 473, 360, 2727, 1880, 453, 13, 220, 679, 15, 7026, 9249, 750, 555, 264, 2092, 268, 590, 1180, 46262, 320, 1687, 69695, 1880, 453, 13, 220, 1049, 20, 7026, 477, 57223, 7167, 320, 76637, 473, 360, 2727, 1880, 453, 13, 220, 1049, 24, 7609, 5075, 2269, 29997, 660, 64100, 527, 14918, 1903, 315, 27572, 4931, 304, 3544, 33776, 13, 2435, 527, 23711, 1139, 8162, 67125, 292, 24512, 2391, 279, 25146, 315, 279, 7491, 27975, 27572, 4931, 320, 39, 360, 2727, 1880, 453, 13, 220, 679, 15, 7609, 5075, 2269, 29997, 660, 64100, 1903, 505, 27572, 4931, 527, 14791, 369, 27572, 4931, 6108, 8162, 67125, 292, 7766, 13, 15636, 11, 1070, 374, 264, 6996, 315, 8162, 838, 2396, 369, 1217, 22658, 18052, 449, 8162, 67125, 292, 24512, 1903, 315, 30945, 454, 52279, 7384, 13, 763, 3293, 1667, 11, 30945, 454, 52279, 7384, 617, 18661, 5199, 23354, 369, 8162, 67125, 292, 8522, 320, 53893, 3524, 323, 73696, 4748, 220, 1049, 24, 883, 14791, 369, 1579, 8286, 11, 3428, 41238, 5788, 320, 1163, 258, 1880, 453, 13, 220, 679, 17, 7609, 7429, 11, 814, 617, 4827, 24463, 55424, 2968, 7863, 311, 27572, 4931, 320, 46, 56557, 1880, 453, 13, 220, 679, 19, 7609, 32009, 449, 3428, 24463, 55424, 2968, 527, 2631, 369, 3339, 7766, 311, 1893, 24463, 41370, 4787, 389, 264, 8162, 67125, 292, 16797, 369, 36254, 8162, 24175, 323, 9950, 5241, 689, 320, 1383, 67020, 1880, 453, 13, 220, 679, 19, 7609, 763, 420, 5684, 11, 584, 5068, 264, 37538, 5603, 369, 2955, 11, 59251, 11, 323, 60993, 315, 264, 20206, 9976, 27642, 864, 2269, 29997, 660, 8162, 838, 588, 323, 264, 19748, 897, 1538, 369, 4228, 18052, 449, 8162, 67125, 292, 24512, 1903, 315, 30945, 454, 52279, 7384, 13, 1666, 6982, 304, 23966, 13, 220, 16, 1174, 279, 14614, 1825, 8162, 838, 588, 574, 1903, 315, 264, 19303, 1891, 95896, 76, 11, 30945, 454, 52279, 10062, 554, 86185, 320, 4334, 52, 705, 28974, 291, 1990, 264, 14812, 25199, 323, 459, 3805, 25199, 2225, 1903, 315, 5975, 4940, 13, 30538, 7859, 3805, 7410, 4871, 279, 2585, 25199, 11, 279, 1891, 95896, 76, 574, 409, 10365, 45578, 520, 279, 14812, 25199, 320, 4338, 16491, 25199, 8, 311, 3009, 279, 14812, 12579, 1555, 279, 8162, 838, 588, 13, 34496, 13931, 315, 8162, 838, 588, 1051, 70241, 3871, 1555, 29487, 37608, 1920, 449, 912, 4040, 7479, 6514, 13, 23966, 13, 220, 16, 264, 35455, 2955, 128257, 198, 128256, 78191, 198, 791, 66684, 364, 14717, 389, 264, 16797, 6, 13171, 315, 63185, 323, 54952, 7677, 14614, 10887, 304, 264, 11742, 477, 6593, 27692, 389, 311, 264, 3254, 16797, 9333, 1109, 264, 6807, 3786, 11, 1253, 5246, 387, 15393, 9523, 311, 44890, 11, 20206, 9976, 27642, 8162, 67125, 292, 7766, 8040, 555, 362, 9, 68161, 12074, 16, 13, 18654, 67125, 292, 6067, 1005, 14488, 315, 12006, 1790, 91529, 1109, 264, 3823, 7013, 311, 2585, 279, 7351, 315, 1332, 3510, 1130, 15055, 315, 56406, 13, 35390, 31003, 304, 8162, 67125, 1233, 5557, 617, 17033, 56193, 369, 14247, 1486, 8838, 41206, 23842, 315, 19338, 323, 617, 19407, 13241, 32011, 780, 323, 15922, 6492, 13, 5234, 64862, 8162, 67125, 292, 6067, 527, 1101, 1694, 20011, 304, 19646, 2849, 7978, 323, 369, 279, 18841, 315, 502, 11217, 13, 362, 88455, 2565, 369, 6992, 13726, 2693, 2065, 323, 8518, 2065, 315, 7373, 18751, 8162, 67125, 292, 6067, 11, 4869, 11, 706, 1027, 279, 4500, 315, 15062, 8162, 67125, 292, 6956, 11, 1778, 439, 8162, 838, 2396, 323, 19748, 897, 12055, 13, 1901, 12301, 69, 833, 29346, 323, 18105, 505, 279, 21181, 10181, 315, 42177, 12053, 320, 47716, 35197, 705, 362, 9, 68161, 617, 7108, 430, 33287, 555, 11469, 459, 11297, 323, 69311, 1749, 311, 13354, 349, 44890, 20206, 9976, 27642, 8162, 67125, 292, 7766, 13, 330, 1090, 14750, 1113, 64100, 323, 43875, 1139, 30945, 454, 52279, 7766, 374, 6118, 17436, 323, 34348, 1606, 279, 59251, 1920, 374, 1633, 17395, 1359, 2795, 29346, 13, 330, 26909, 90375, 279, 8162, 838, 588, 4793, 26214, 505, 279, 1925, 3756, 11, 4869, 11, 3727, 279, 59251, 315, 279, 1925, 3756, 12309, 4382, 323, 22514, 1210, 18654, 838, 2396, 6824, 315, 264, 19303, 1891, 95896, 76, 28974, 291, 1990, 264, 2585, 25199, 323, 14812, 25199, 11, 323, 555, 19486, 7410, 505, 459, 9434, 22936, 14155, 11, 477, 1555, 25396, 2020, 477, 44626, 33030, 8603, 11, 279, 1891, 95896, 76, 649, 387, 409, 10365, 10923, 369, 279, 34786, 315, 15962, 292, 6530, 2949, 279, 25199, 13, 578, 12074, 70554, 264, 19748, 897, 1538, 31706, 315, 2380, 8162, 838, 2396, 11, 719, 1047, 311, 1505, 264, 14791, 3769, 369, 279, 8162, 838, 588, 79348, 11, 902, 2011, 387, 19303, 11, 719, 1101, 6847, 70241, 311, 1023, 5596, 315, 279, 8162, 838, 588, 2085, 279, 1005, 315, 1008, 17082, 1924, 13, 330, 1687, 1766, 430, 30945, 454, 52279, 10062, 554, 86185, 4632, 4375, 1664, 439, 279, 39654, 323, 649, 387, 70241, 40069, 449, 279, 1925, 2547, 11, 902, 374, 1903, 505, 46033, 42972, 21747, 582, 894, 5185, 1359, 15100, 29346, 13, 578, 2955, 315, 279, 8162, 838, 588, 1101, 10666, 264, 8815, 311, 279, 12074, 11, 902, 814, 927, 6142, 555, 1701, 35326, 2449, 1749, 19576, 29096, 35876, 5507, 1511, 311, 11886, 6485, 24693, 5435, 50617, 7068, 279, 2955, 17959, 11, 902, 1051, 1243, 24884, 555, 66196, 13, 12362, 279, 23739, 35197, 18654, 67125, 1233, 12595, 894, 11, 279, 12074, 527, 5131, 11469, 264, 1396, 315, 364, 263, 16797, 6, 13761, 323, 527, 24050, 872, 17357, 304, 279, 2955, 11, 1760, 67247, 323, 30847, 315, 47393, 3196, 8162, 67125, 292, 7766, 13, 330, 31428, 13726, 2693, 4954, 279, 1404, 315, 8162, 838, 588, 13761, 1436, 5376, 279, 5569, 315, 18052, 323, 84713, 279, 2134, 315, 4754, 8522, 1359, 2795, 29346, 13, 220, 128257, 198 ]

2,233

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Dry etching of ternary metal carbides TiAlC has been first developed by transferring from wet etching to dry etching using a floating wire (FW)-assisted Ar/ammonium hydroxide vapor plasma. FW-assisted non-halogen vapor plasma generated at medium pressure can produce high-density reactive radicals (NH, H, and OH) for TiAlC surface modifications such as hydrogenation and methylamination. A proposed mechanism for dry etching of TiAlC is considered with the formation of the volatile products from the modified layer. Introduction In a fin-type or nanosheet field effect transistor (FET) of a logic semiconductor device, it has been proposed to use metal gate materials, for examples, metal carbides (TiC, TiAlC) and metal nitrides (TiN, TaN, AlN, TiAlN) 1 , 2 , 3 , 4 , 5 . Ternary metal compound such as TiAlC belongs to high-melting point, high-hardness, and high-wear resistance materials 1 , 6 , 7 . Conventionally, the TiAlC film and TiC film in semiconductor devices are etched by wet etching using H 2 O 2 mixtures 5 , 8 , 9 , 10 . However, a poor metal removability in wet etching requires a prolonged etching time to fully remove the target metals, and in the worst case, the metal gate can be damaged 5 . In order to fabricate the next generation FETs in semiconductor industries, it is strongly demanded to develop an etching method that enables to control the selective and isotropic removal of metal carbides (TiAlC, TiC, and AlC) at an atomic layer level 5 , 9 , 10 . No dry etching (plasma etching) of ternary material TiAlC with atomic level control has been developed yet. Atmospheric pressure plasma (APP) and medium-pressure plasma techniques with a large difference in chemical kinetics compared to low-pressure plasma are able to miniaturize equipment size, fabrication cost, and energy consumption 11 , 12 , 13 , 14 , 15 , 16 , 17 . Medium-pressure plasma (0.2–50 kPa) can produce higher plasma density compared to vacuum plasma and larger plasma volume compared to APP 18 , 19 , 20 . In order to improve the plasma density at a remote region where the substrate is placed, we have inserted a long floating metal wire inside the discharge tube to enhance the electric field not only near the copper coil region, but also at a remote region. Therefore, a rich radical source (10 14 cm −3 ) near the sample surface that is far from the coil region can be obtained 15 . The generated rich radical source can produce a large amount of etchant or co-reactant species to enhance the reaction rate with sample surface. This radical-rich environment plays an important role in controlling isotropic etching of 3D multilayer semiconductor devices. Here we have first developed a new dry etching method for metal carbides such as ternary material TiAlC by using a floating wire (FW)-assisted vapor plasma of Ar gas mixed with vapor sources of NH 4 OH-based mixtures at medium pressure. Although the mechanism of wet etching and dry etching can be different because the formed compounds are dissolved in solutions in wet etching, and for plasma etching, the formed compounds should be volatile in the gas phase, the wet etching brings lots of useful ideas to develop new etching chemistries for traditional materials or dry etching methods for new materials. In this study, we aim to develop a new etching method (wet-dry etching or wet-like plasma etching) that can combine the advantages of wet etching (high isotropy and selectivity) and dry etching (high controllability) for new materials or hard-to-etch materials. Surface reaction plays a key role in developing atomic layer etching (ALE) processes, which normally are proceeded in multi-steps including surface modification to reduce the surface energy of sample surface in the first step, and then removal of modified layer in the next step. Here the surface modification, such as hydrogenation and methylamination, of the TiAlC film, was obtained by controlling the active radicals, such as NH, H, and OH. The treated TiAlC surface can be removed via the formation of modifed layers. Lastly, the mechanism for plasma etching of metal carbides (TiAlC, TiC, AlC) is proposed. The new etching method will be explored for etching metals and metal compounds such as nitrides, carbides, and oxides to determine if the selectivity and isotropy commonly seen in wet etching will also occur in dry etching. Materials and methods Sample preparation TiAlC films were prepared on Si wafer by vacuum evaporation with the Ti, Al sources, and C 2 H 2 gas. TiAlC/Si samples were prepared with the size of 15 mm × 15 mm (for wet etching) and 15 mm × 20 mm (for dry etching). TiAlC films were analyzed by using an ellipsometry (M-2000, J.A. Woolam Co.) with a Xe arc light source (FLS-300). A model was used for spectral fitting of ellipsometric data of TiAlC sample including a top layer (native oxide, deposited layer, or modified layer), a TiAlC layer, an interface layer, and Si substrate, as shown in Fig. 1 a. The pristine TiAlC film on Si substrate (TiAlC/Si) has a thickness of around 35 nm. Figure 1 ( a ) A model for spectral fitting of ellipsometric data. A stratified layer model is constructed by a structure of TiAlC sample including top layer (native oxide, deposited layer, or modified layer), TiAlC layer, interface layer, and Si wafer. ( b ) Dispersions of refractive index and extinction coefficient of TiAlC film as functions of wavelength obtained by the Gen-Osc model with fitted parameters as listed in Table 1 . Full size image Table 1 Best-fit parameters of TiAlC layer obtained by Gen-Osc model. Full size table The dielectric function of the TiAlC film is expressed by the Gen-Osc model involving one Drude and three Lorentz oscillators 21 . The Gen-Osc model with the best-fit parameters is shown in Table 1 . Dispersions of optical constants including refractive index (n) and extinction coefficient (k) of TiAlC film as functions of the wavelength ranged from 245 to 1000 nm", "role": "user" }, { "content": "In circuitry, etching is used to remove the deformed layer created during the grinding and polishing of metal components by selective chemical reactions. Now, a research group at Nagoya University in Japan has developed a new method called \"wet-like plasma etching\" that combines the selectivity of wet etching with the controllability of dry etching. This technique will make it possible to etch new and hard-to-etch materials, enabling higher performance and lower power consumption of the silicon semiconductor integrated circuits used in smartphones and data centers. The researchers' findings were published in the journal Scientific Reports. In the race to create the fastest and most energy-efficient circuits for computing devices, scientists are constantly looking for new transistor designs. Recently, there has been a shift from FinFET-type transistors, so-called because the gate is raised above the silicon plane like a shark's fin to gate-all-around transistors, in which the fin is replaced by a stack of horizontal sheets that look like a pagoda in a Buddhist temple. In this type, the sheets surround the channel to reduce leakage and increase the drive current. To fabricate these complex structures, metal carbides consisting of titanium (Ti) and aluminum (Al), such as TiC or TiAlC, are used as metal gates where the voltage is applied. TiAlC is a ternary material with high hardness, high wear resistance, high melting point, and excellent electrochemical performance. There are two ways to etch such materials. Wet etching uses chemical solutions, while dry etching uses gases. Conventionally, TiAlC films used in semiconductor devices are etched by wet etching using hydrogen peroxide liquid mixtures. However, this process requires a long etching time to completely remove the target metals. It also runs the risk of chemically damaging the metal gate. Additionally, the liquids used can create surface tension at the atomic level, destroying important features. In order to develop an advanced etching process for the selective removal of TiAlC over other Ti compounds, non-halogen etching has been tested as a possible solution. Currently, there is no non-halogen dry etching process for metal carbides made of the three elements. Now, a research group led by Professors Masaru Hori, Kenji Ishikawa, and Thi-Thuy-Nga Nguyen at the Center for Low-Temperature Plasma Science at Nagoya University, in collaboration with the companies Hitachi, Ltd. and Hitachi High-Tech Corp., has developed a new dry etching method for metal carbides. This method uses a floating wire-assisted vapor plasma of argon gas mixed with vapor sources of ammonium hydroxide-based mixtures at medium pressure. In the circuit, the plasma is generated by adding energy to the gas, so the additional floating wire can enhance the generation of high-density plasma. Since this process generates active radicals of H, NH, and OH from the ammonium hydroxide gas (NH4OH), the treated surface of TiAlC can be removed after surface modifications of the TiAlC film. \"Atmospheric pressure plasma and medium-pressure plasma techniques are used to miniaturize equipment size, fabrication cost, and energy consumption,\" explained Ishikawa. \"It is difficult to etch off compounds involving multiple elements. Therefore, control of surface modification plays a key role. \"Our group investigated the use of various radicals for surface modification and developed a method for generating such radicals using floating wire plasma and a vapor supplement. This provides a rich radical source of NH, H, and OH, which react with the TiAlC surface to form volatile products and etch the TiAlC surface. \"This floating wire-assisted plasma technique is expected to be available for highly selective etching of metals and metal compounds used in semiconductor device fabrication,\" Ishikawa continued. \"Metal carbides are promising gate electrode materials for advanced silicon semiconductors, and our joint research group was the first in the world to succeed in chemical dry etching of non-silicon semiconductor materials. \"This achievement is important for the development of atomic layer-level etching technology, which has been difficult to achieve so far. Our results represent an important milestone, and a dramatic technological leap forward, in microfabrication technology.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Dry etching of ternary metal carbides TiAlC has been first developed by transferring from wet etching to dry etching using a floating wire (FW)-assisted Ar/ammonium hydroxide vapor plasma. FW-assisted non-halogen vapor plasma generated at medium pressure can produce high-density reactive radicals (NH, H, and OH) for TiAlC surface modifications such as hydrogenation and methylamination. A proposed mechanism for dry etching of TiAlC is considered with the formation of the volatile products from the modified layer. Introduction In a fin-type or nanosheet field effect transistor (FET) of a logic semiconductor device, it has been proposed to use metal gate materials, for examples, metal carbides (TiC, TiAlC) and metal nitrides (TiN, TaN, AlN, TiAlN) 1 , 2 , 3 , 4 , 5 . Ternary metal compound such as TiAlC belongs to high-melting point, high-hardness, and high-wear resistance materials 1 , 6 , 7 . Conventionally, the TiAlC film and TiC film in semiconductor devices are etched by wet etching using H 2 O 2 mixtures 5 , 8 , 9 , 10 . However, a poor metal removability in wet etching requires a prolonged etching time to fully remove the target metals, and in the worst case, the metal gate can be damaged 5 . In order to fabricate the next generation FETs in semiconductor industries, it is strongly demanded to develop an etching method that enables to control the selective and isotropic removal of metal carbides (TiAlC, TiC, and AlC) at an atomic layer level 5 , 9 , 10 . No dry etching (plasma etching) of ternary material TiAlC with atomic level control has been developed yet. Atmospheric pressure plasma (APP) and medium-pressure plasma techniques with a large difference in chemical kinetics compared to low-pressure plasma are able to miniaturize equipment size, fabrication cost, and energy consumption 11 , 12 , 13 , 14 , 15 , 16 , 17 . Medium-pressure plasma (0.2–50 kPa) can produce higher plasma density compared to vacuum plasma and larger plasma volume compared to APP 18 , 19 , 20 . In order to improve the plasma density at a remote region where the substrate is placed, we have inserted a long floating metal wire inside the discharge tube to enhance the electric field not only near the copper coil region, but also at a remote region. Therefore, a rich radical source (10 14 cm −3 ) near the sample surface that is far from the coil region can be obtained 15 . The generated rich radical source can produce a large amount of etchant or co-reactant species to enhance the reaction rate with sample surface. This radical-rich environment plays an important role in controlling isotropic etching of 3D multilayer semiconductor devices. Here we have first developed a new dry etching method for metal carbides such as ternary material TiAlC by using a floating wire (FW)-assisted vapor plasma of Ar gas mixed with vapor sources of NH 4 OH-based mixtures at medium pressure. Although the mechanism of wet etching and dry etching can be different because the formed compounds are dissolved in solutions in wet etching, and for plasma etching, the formed compounds should be volatile in the gas phase, the wet etching brings lots of useful ideas to develop new etching chemistries for traditional materials or dry etching methods for new materials. In this study, we aim to develop a new etching method (wet-dry etching or wet-like plasma etching) that can combine the advantages of wet etching (high isotropy and selectivity) and dry etching (high controllability) for new materials or hard-to-etch materials. Surface reaction plays a key role in developing atomic layer etching (ALE) processes, which normally are proceeded in multi-steps including surface modification to reduce the surface energy of sample surface in the first step, and then removal of modified layer in the next step. Here the surface modification, such as hydrogenation and methylamination, of the TiAlC film, was obtained by controlling the active radicals, such as NH, H, and OH. The treated TiAlC surface can be removed via the formation of modifed layers. Lastly, the mechanism for plasma etching of metal carbides (TiAlC, TiC, AlC) is proposed. The new etching method will be explored for etching metals and metal compounds such as nitrides, carbides, and oxides to determine if the selectivity and isotropy commonly seen in wet etching will also occur in dry etching. Materials and methods Sample preparation TiAlC films were prepared on Si wafer by vacuum evaporation with the Ti, Al sources, and C 2 H 2 gas. TiAlC/Si samples were prepared with the size of 15 mm × 15 mm (for wet etching) and 15 mm × 20 mm (for dry etching). TiAlC films were analyzed by using an ellipsometry (M-2000, J.A. Woolam Co.) with a Xe arc light source (FLS-300). A model was used for spectral fitting of ellipsometric data of TiAlC sample including a top layer (native oxide, deposited layer, or modified layer), a TiAlC layer, an interface layer, and Si substrate, as shown in Fig. 1 a. The pristine TiAlC film on Si substrate (TiAlC/Si) has a thickness of around 35 nm. Figure 1 ( a ) A model for spectral fitting of ellipsometric data. A stratified layer model is constructed by a structure of TiAlC sample including top layer (native oxide, deposited layer, or modified layer), TiAlC layer, interface layer, and Si wafer. ( b ) Dispersions of refractive index and extinction coefficient of TiAlC film as functions of wavelength obtained by the Gen-Osc model with fitted parameters as listed in Table 1 . Full size image Table 1 Best-fit parameters of TiAlC layer obtained by Gen-Osc model. Full size table The dielectric function of the TiAlC film is expressed by the Gen-Osc model involving one Drude and three Lorentz oscillators 21 . The Gen-Osc model with the best-fit parameters is shown in Table 1 . Dispersions of optical constants including refractive index (n) and extinction coefficient (k) of TiAlC film as functions of the wavelength ranged from 245 to 1000 nm<|im_end|> <|im_start|>assistant In circuitry, etching is used to remove the deformed layer created during the grinding and polishing of metal components by selective chemical reactions. Now, a research group at Nagoya University in Japan has developed a new method called "wet-like plasma etching" that combines the selectivity of wet etching with the controllability of dry etching. This technique will make it possible to etch new and hard-to-etch materials, enabling higher performance and lower power consumption of the silicon semiconductor integrated circuits used in smartphones and data centers. The researchers' findings were published in the journal Scientific Reports. In the race to create the fastest and most energy-efficient circuits for computing devices, scientists are constantly looking for new transistor designs. Recently, there has been a shift from FinFET-type transistors, so-called because the gate is raised above the silicon plane like a shark's fin to gate-all-around transistors, in which the fin is replaced by a stack of horizontal sheets that look like a pagoda in a Buddhist temple. In this type, the sheets surround the channel to reduce leakage and increase the drive current. To fabricate these complex structures, metal carbides consisting of titanium (Ti) and aluminum (Al), such as TiC or TiAlC, are used as metal gates where the voltage is applied. TiAlC is a ternary material with high hardness, high wear resistance, high melting point, and excellent electrochemical performance. There are two ways to etch such materials. Wet etching uses chemical solutions, while dry etching uses gases. Conventionally, TiAlC films used in semiconductor devices are etched by wet etching using hydrogen peroxide liquid mixtures. However, this process requires a long etching time to completely remove the target metals. It also runs the risk of chemically damaging the metal gate. Additionally, the liquids used can create surface tension at the atomic level, destroying important features. In order to develop an advanced etching process for the selective removal of TiAlC over other Ti compounds, non-halogen etching has been tested as a possible solution. Currently, there is no non-halogen dry etching process for metal carbides made of the three elements. Now, a research group led by Professors Masaru Hori, Kenji Ishikawa, and Thi-Thuy-Nga Nguyen at the Center for Low-Temperature Plasma Science at Nagoya University, in collaboration with the companies Hitachi, Ltd. and Hitachi High-Tech Corp., has developed a new dry etching method for metal carbides. This method uses a floating wire-assisted vapor plasma of argon gas mixed with vapor sources of ammonium hydroxide-based mixtures at medium pressure. In the circuit, the plasma is generated by adding energy to the gas, so the additional floating wire can enhance the generation of high-density plasma. Since this process generates active radicals of H, NH, and OH from the ammonium hydroxide gas (NH4OH), the treated surface of TiAlC can be removed after surface modifications of the TiAlC film. "Atmospheric pressure plasma and medium-pressure plasma techniques are used to miniaturize equipment size, fabrication cost, and energy consumption," explained Ishikawa. "It is difficult to etch off compounds involving multiple elements. Therefore, control of surface modification plays a key role. "Our group investigated the use of various radicals for surface modification and developed a method for generating such radicals using floating wire plasma and a vapor supplement. This provides a rich radical source of NH, H, and OH, which react with the TiAlC surface to form volatile products and etch the TiAlC surface. "This floating wire-assisted plasma technique is expected to be available for highly selective etching of metals and metal compounds used in semiconductor device fabrication," Ishikawa continued. "Metal carbides are promising gate electrode materials for advanced silicon semiconductors, and our joint research group was the first in the world to succeed in chemical dry etching of non-silicon semiconductor materials. "This achievement is important for the development of atomic layer-level etching technology, which has been difficult to achieve so far. Our results represent an important milestone, and a dramatic technological leap forward, in microfabrication technology." <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 31941, 1880, 28075, 315, 72717, 661, 9501, 35872, 3422, 23126, 2149, 34, 706, 1027, 1176, 8040, 555, 51051, 505, 14739, 1880, 28075, 311, 9235, 1880, 28075, 1701, 264, 19596, 9244, 320, 18723, 7435, 395, 13539, 1676, 56517, 1677, 2411, 17055, 87, 579, 38752, 32426, 13, 49129, 35915, 13539, 2536, 2902, 278, 11968, 38752, 32426, 8066, 520, 11298, 7410, 649, 8356, 1579, 89131, 56563, 74356, 320, 52371, 11, 473, 11, 323, 29822, 8, 369, 23126, 2149, 34, 7479, 29882, 1778, 439, 35784, 367, 323, 79574, 27935, 13, 362, 11223, 17383, 369, 9235, 1880, 28075, 315, 23126, 2149, 34, 374, 6646, 449, 279, 18488, 315, 279, 17509, 3956, 505, 279, 11041, 6324, 13, 29438, 763, 264, 1913, 10827, 477, 20622, 437, 3759, 2115, 2515, 99041, 320, 37, 1372, 8, 315, 264, 12496, 87836, 3756, 11, 433, 706, 1027, 11223, 311, 1005, 9501, 18618, 7384, 11, 369, 10507, 11, 9501, 35872, 3422, 320, 46451, 34, 11, 23126, 2149, 34, 8, 323, 9501, 25719, 18746, 320, 46451, 45, 11, 24172, 45, 11, 1708, 45, 11, 23126, 2149, 45, 8, 220, 16, 1174, 220, 17, 1174, 220, 18, 1174, 220, 19, 1174, 220, 20, 662, 350, 944, 661, 9501, 24549, 1778, 439, 23126, 2149, 34, 17623, 311, 1579, 1474, 301, 1303, 1486, 11, 1579, 71845, 2136, 11, 323, 1579, 2695, 686, 13957, 7384, 220, 16, 1174, 220, 21, 1174, 220, 22, 662, 26958, 750, 11, 279, 23126, 2149, 34, 4632, 323, 23126, 34, 4632, 304, 87836, 7766, 527, 1880, 2454, 555, 14739, 1880, 28075, 1701, 473, 220, 17, 507, 220, 17, 6651, 19020, 220, 20, 1174, 220, 23, 1174, 220, 24, 1174, 220, 605, 662, 4452, 11, 264, 8009, 9501, 1323, 869, 2968, 304, 14739, 1880, 28075, 7612, 264, 44387, 1880, 28075, 892, 311, 7373, 4148, 279, 2218, 37182, 11, 323, 304, 279, 12047, 1162, 11, 279, 9501, 18618, 649, 387, 20727, 220, 20, 662, 763, 2015, 311, 13354, 349, 279, 1828, 9659, 435, 1372, 82, 304, 87836, 19647, 11, 433, 374, 16917, 30526, 311, 2274, 459, 1880, 28075, 1749, 430, 20682, 311, 2585, 279, 44010, 323, 69551, 45036, 17065, 315, 9501, 35872, 3422, 320, 46451, 2149, 34, 11, 23126, 34, 11, 323, 1708, 34, 8, 520, 459, 25524, 6324, 2237, 220, 20, 1174, 220, 24, 1174, 220, 605, 662, 2360, 9235, 1880, 28075, 320, 501, 23390, 1880, 28075, 8, 315, 72717, 661, 3769, 23126, 2149, 34, 449, 25524, 2237, 2585, 706, 1027, 8040, 3686, 13, 87597, 7410, 32426, 320, 15049, 8, 323, 11298, 89561, 32426, 12823, 449, 264, 3544, 6811, 304, 11742, 91468, 7863, 311, 3428, 89561, 32426, 527, 3025, 311, 13726, 2693, 553, 7241, 1404, 11, 59251, 2853, 11, 323, 4907, 15652, 220, 806, 1174, 220, 717, 1174, 220, 1032, 1174, 220, 975, 1174, 220, 868, 1174, 220, 845, 1174, 220, 1114, 662, 25352, 89561, 32426, 320, 15, 13, 17, 4235, 1135, 597, 20908, 8, 649, 8356, 5190, 32426, 17915, 7863, 311, 29302, 32426, 323, 8294, 32426, 8286, 7863, 311, 18395, 220, 972, 1174, 220, 777, 1174, 220, 508, 662, 763, 2015, 311, 7417, 279, 32426, 17915, 520, 264, 8870, 5654, 1405, 279, 54057, 374, 9277, 11, 584, 617, 22306, 264, 1317, 19596, 9501, 9244, 4871, 279, 32643, 14019, 311, 18885, 279, 9249, 2115, 539, 1193, 3221, 279, 24166, 40760, 5654, 11, 719, 1101, 520, 264, 8870, 5654, 13, 15636, 11, 264, 9257, 18336, 2592, 320, 605, 220, 975, 10166, 25173, 18, 883, 3221, 279, 6205, 7479, 430, 374, 3117, 505, 279, 40760, 5654, 649, 387, 12457, 220, 868, 662, 578, 8066, 9257, 18336, 2592, 649, 8356, 264, 3544, 3392, 315, 1880, 11943, 477, 1080, 31696, 519, 9606, 311, 18885, 279, 13010, 4478, 449, 6205, 7479, 13, 1115, 18336, 41947, 4676, 11335, 459, 3062, 3560, 304, 26991, 69551, 45036, 1880, 28075, 315, 220, 18, 35, 2814, 321, 1155, 87836, 7766, 13, 5810, 584, 617, 1176, 8040, 264, 502, 9235, 1880, 28075, 1749, 369, 9501, 35872, 3422, 1778, 439, 72717, 661, 3769, 23126, 2149, 34, 555, 1701, 264, 19596, 9244, 320, 18723, 7435, 395, 13539, 38752, 32426, 315, 1676, 6962, 9709, 449, 38752, 8336, 315, 35931, 220, 19, 29822, 6108, 6651, 19020, 520, 11298, 7410, 13, 10541, 279, 17383, 315, 14739, 1880, 28075, 323, 9235, 1880, 28075, 649, 387, 2204, 1606, 279, 14454, 32246, 527, 56767, 304, 10105, 304, 14739, 1880, 28075, 11, 323, 369, 32426, 1880, 28075, 11, 279, 14454, 32246, 1288, 387, 17509, 304, 279, 6962, 10474, 11, 279, 14739, 1880, 28075, 12716, 10283, 315, 5505, 6848, 311, 2274, 502, 1880, 28075, 8590, 380, 4108, 369, 8776, 7384, 477, 9235, 1880, 28075, 5528, 369, 502, 7384, 13, 763, 420, 4007, 11, 584, 9395, 311, 2274, 264, 502, 1880, 28075, 1749, 320, 86, 295, 1773, 894, 1880, 28075, 477, 14739, 12970, 32426, 1880, 28075, 8, 430, 649, 16343, 279, 22934, 315, 14739, 1880, 28075, 320, 12156, 69551, 18237, 323, 3373, 1968, 8, 323, 9235, 1880, 28075, 320, 12156, 687, 1119, 2968, 8, 369, 502, 7384, 477, 2653, 4791, 12, 3068, 7384, 13, 28061, 13010, 11335, 264, 1401, 3560, 304, 11469, 25524, 6324, 1880, 28075, 320, 25940, 8, 11618, 11, 902, 14614, 527, 45374, 304, 7447, 5594, 7270, 2737, 7479, 17466, 311, 8108, 279, 7479, 4907, 315, 6205, 7479, 304, 279, 1176, 3094, 11, 323, 1243, 17065, 315, 11041, 6324, 304, 279, 1828, 3094, 13, 5810, 279, 7479, 17466, 11, 1778, 439, 35784, 367, 323, 79574, 27935, 11, 315, 279, 23126, 2149, 34, 4632, 11, 574, 12457, 555, 26991, 279, 4642, 74356, 11, 1778, 439, 35931, 11, 473, 11, 323, 29822, 13, 578, 12020, 23126, 2149, 34, 7479, 649, 387, 7108, 4669, 279, 18488, 315, 1491, 333, 291, 13931, 13, 71809, 11, 279, 17383, 369, 32426, 1880, 28075, 315, 9501, 35872, 3422, 320, 46451, 2149, 34, 11, 23126, 34, 11, 1708, 34, 8, 374, 11223, 13, 578, 502, 1880, 28075, 1749, 690, 387, 36131, 369, 1880, 28075, 37182, 323, 9501, 32246, 1778, 439, 25719, 18746, 11, 35872, 3422, 11, 323, 19488, 3422, 311, 8417, 422, 279, 3373, 1968, 323, 69551, 18237, 17037, 3970, 304, 14739, 1880, 28075, 690, 1101, 12446, 304, 9235, 1880, 28075, 13, 32009, 323, 5528, 19690, 18459, 23126, 2149, 34, 12631, 1051, 10235, 389, 12095, 10667, 809, 555, 29302, 3721, 96649, 449, 279, 23126, 11, 1708, 8336, 11, 323, 356, 220, 17, 473, 220, 17, 6962, 13, 23126, 2149, 34, 11628, 72, 10688, 1051, 10235, 449, 279, 1404, 315, 220, 868, 9653, 25800, 220, 868, 9653, 320, 2000, 14739, 1880, 28075, 8, 323, 220, 868, 9653, 25800, 220, 508, 9653, 320, 2000, 9235, 1880, 28075, 570, 23126, 2149, 34, 12631, 1051, 30239, 555, 1701, 459, 26689, 3153, 7133, 320, 44, 12, 1049, 15, 11, 622, 885, 13, 47400, 309, 3623, 6266, 449, 264, 1630, 68, 15952, 3177, 2592, 320, 6254, 50, 12, 3101, 570, 362, 1646, 574, 1511, 369, 57077, 27442, 315, 26689, 3153, 24264, 828, 315, 23126, 2149, 34, 6205, 2737, 264, 1948, 6324, 320, 30838, 51180, 11, 54568, 6324, 11, 477, 11041, 6324, 705, 264, 23126, 2149, 34, 6324, 11, 459, 3834, 6324, 11, 323, 12095, 54057, 11, 439, 6982, 304, 23966, 13, 220, 16, 264, 13, 578, 66085, 23126, 2149, 34, 4632, 389, 12095, 54057, 320, 46451, 2149, 34, 11628, 72, 8, 706, 264, 26839, 315, 2212, 220, 1758, 26807, 13, 19575, 220, 16, 320, 264, 883, 362, 1646, 369, 57077, 27442, 315, 26689, 3153, 24264, 828, 13, 362, 44397, 1908, 6324, 1646, 374, 20968, 555, 264, 6070, 315, 23126, 2149, 34, 6205, 2737, 1948, 6324, 320, 30838, 51180, 11, 54568, 6324, 11, 477, 11041, 6324, 705, 23126, 2149, 34, 6324, 11, 3834, 6324, 11, 323, 12095, 10667, 809, 13, 320, 293, 883, 4185, 32390, 919, 315, 19914, 3104, 1963, 323, 52609, 36706, 315, 23126, 2149, 34, 4632, 439, 5865, 315, 46406, 12457, 555, 279, 9500, 24540, 2445, 1646, 449, 29441, 5137, 439, 10212, 304, 6771, 220, 16, 662, 8797, 1404, 2217, 6771, 220, 16, 7252, 50660, 5137, 315, 23126, 2149, 34, 6324, 12457, 555, 9500, 24540, 2445, 1646, 13, 8797, 1404, 2007, 578, 2815, 47262, 734, 315, 279, 23126, 2149, 34, 4632, 374, 13605, 555, 279, 9500, 24540, 2445, 1646, 16239, 832, 2999, 799, 323, 2380, 54333, 406, 89, 43524, 3046, 220, 1691, 662, 578, 9500, 24540, 2445, 1646, 449, 279, 1888, 50660, 5137, 374, 6982, 304, 6771, 220, 16, 662, 4185, 32390, 919, 315, 29393, 18508, 2737, 19914, 3104, 1963, 320, 77, 8, 323, 52609, 36706, 320, 74, 8, 315, 23126, 2149, 34, 4632, 439, 5865, 315, 279, 46406, 41829, 505, 220, 13078, 311, 220, 1041, 15, 26807, 128257, 198, 128256, 78191, 198, 644, 16622, 894, 11, 1880, 28075, 374, 1511, 311, 4148, 279, 409, 10365, 6324, 3549, 2391, 279, 17282, 323, 85563, 315, 9501, 6956, 555, 44010, 11742, 25481, 13, 4800, 11, 264, 3495, 1912, 520, 30162, 47162, 3907, 304, 6457, 706, 8040, 264, 502, 1749, 2663, 330, 86, 295, 12970, 32426, 1880, 28075, 1, 430, 33511, 279, 3373, 1968, 315, 14739, 1880, 28075, 449, 279, 687, 1119, 2968, 315, 9235, 1880, 28075, 13, 1115, 15105, 690, 1304, 433, 3284, 311, 1880, 331, 502, 323, 2653, 4791, 12, 3068, 7384, 11, 28462, 5190, 5178, 323, 4827, 2410, 15652, 315, 279, 51692, 87836, 18751, 46121, 1511, 304, 36122, 323, 828, 19169, 13, 578, 12074, 6, 14955, 1051, 4756, 304, 279, 8486, 38130, 29140, 13, 763, 279, 7102, 311, 1893, 279, 26731, 323, 1455, 4907, 73916, 46121, 369, 25213, 7766, 11, 14248, 527, 15320, 3411, 369, 502, 99041, 14769, 13, 42096, 11, 1070, 706, 1027, 264, 6541, 505, 5767, 37, 1372, 10827, 1380, 380, 1105, 11, 779, 19434, 1606, 279, 18618, 374, 9408, 3485, 279, 51692, 11277, 1093, 264, 44892, 596, 1913, 311, 18618, 23148, 46716, 1380, 380, 1105, 11, 304, 902, 279, 1913, 374, 12860, 555, 264, 5729, 315, 16600, 25112, 430, 1427, 1093, 264, 15117, 14320, 304, 264, 47841, 27850, 13, 763, 420, 955, 11, 279, 25112, 9172, 279, 5613, 311, 8108, 81373, 323, 5376, 279, 6678, 1510, 13, 2057, 13354, 349, 1521, 6485, 14726, 11, 9501, 35872, 3422, 31706, 315, 71404, 320, 46451, 8, 323, 25674, 320, 2149, 705, 1778, 439, 23126, 34, 477, 23126, 2149, 34, 11, 527, 1511, 439, 9501, 35634, 1405, 279, 22465, 374, 9435, 13, 23126, 2149, 34, 374, 264, 72717, 661, 3769, 449, 1579, 72003, 11, 1579, 10051, 13957, 11, 1579, 50684, 1486, 11, 323, 9250, 25396, 32056, 5178, 13, 2684, 527, 1403, 5627, 311, 1880, 331, 1778, 7384, 13, 45956, 1880, 28075, 5829, 11742, 10105, 11, 1418, 9235, 1880, 28075, 5829, 45612, 13, 26958, 750, 11, 23126, 2149, 34, 12631, 1511, 304, 87836, 7766, 527, 1880, 2454, 555, 14739, 1880, 28075, 1701, 35784, 824, 55189, 14812, 6651, 19020, 13, 4452, 11, 420, 1920, 7612, 264, 1317, 1880, 28075, 892, 311, 6724, 4148, 279, 2218, 37182, 13, 1102, 1101, 8640, 279, 5326, 315, 8590, 2740, 34446, 279, 9501, 18618, 13, 23212, 11, 279, 67849, 1511, 649, 1893, 7479, 24408, 520, 279, 25524, 2237, 11, 33812, 3062, 4519, 13, 763, 2015, 311, 2274, 459, 11084, 1880, 28075, 1920, 369, 279, 44010, 17065, 315, 23126, 2149, 34, 927, 1023, 23126, 32246, 11, 2536, 2902, 278, 11968, 1880, 28075, 706, 1027, 12793, 439, 264, 3284, 6425, 13, 25122, 11, 1070, 374, 912, 2536, 2902, 278, 11968, 9235, 1880, 28075, 1920, 369, 9501, 35872, 3422, 1903, 315, 279, 2380, 5540, 13, 4800, 11, 264, 3495, 1912, 6197, 555, 8626, 434, 1105, 20459, 31244, 473, 13915, 11, 14594, 7910, 57704, 1609, 14406, 11, 323, 60223, 71626, 4168, 11500, 6885, 64261, 520, 279, 5955, 369, 12310, 9469, 94825, 65632, 10170, 520, 30162, 47162, 3907, 11, 304, 20632, 449, 279, 5220, 16261, 31464, 11, 12604, 13, 323, 16261, 31464, 5234, 9469, 4842, 22621, 2637, 706, 8040, 264, 502, 9235, 1880, 28075, 1749, 369, 9501, 35872, 3422, 13, 1115, 1749, 5829, 264, 19596, 9244, 35915, 13539, 38752, 32426, 315, 1417, 263, 6962, 9709, 449, 38752, 8336, 315, 69911, 2411, 17055, 87, 579, 6108, 6651, 19020, 520, 11298, 7410, 13, 763, 279, 16622, 11, 279, 32426, 374, 8066, 555, 7999, 4907, 311, 279, 6962, 11, 779, 279, 5217, 19596, 9244, 649, 18885, 279, 9659, 315, 1579, 89131, 32426, 13, 8876, 420, 1920, 27983, 4642, 74356, 315, 473, 11, 35931, 11, 323, 29822, 505, 279, 69911, 2411, 17055, 87, 579, 6962, 320, 52371, 19, 47861, 705, 279, 12020, 7479, 315, 23126, 2149, 34, 649, 387, 7108, 1306, 7479, 29882, 315, 279, 23126, 2149, 34, 4632, 13, 330, 1688, 8801, 33349, 7410, 32426, 323, 11298, 89561, 32426, 12823, 527, 1511, 311, 13726, 2693, 553, 7241, 1404, 11, 59251, 2853, 11, 323, 4907, 15652, 1359, 11497, 57704, 1609, 14406, 13, 330, 2181, 374, 5107, 311, 1880, 331, 1022, 32246, 16239, 5361, 5540, 13, 15636, 11, 2585, 315, 7479, 17466, 11335, 264, 1401, 3560, 13, 330, 8140, 1912, 27313, 279, 1005, 315, 5370, 74356, 369, 7479, 17466, 323, 8040, 264, 1749, 369, 24038, 1778, 74356, 1701, 19596, 9244, 32426, 323, 264, 38752, 22822, 13, 1115, 5825, 264, 9257, 18336, 2592, 315, 35931, 11, 473, 11, 323, 29822, 11, 902, 14085, 449, 279, 23126, 2149, 34, 7479, 311, 1376, 17509, 3956, 323, 1880, 331, 279, 23126, 2149, 34, 7479, 13, 330, 2028, 19596, 9244, 35915, 13539, 32426, 15105, 374, 3685, 311, 387, 2561, 369, 7701, 44010, 1880, 28075, 315, 37182, 323, 9501, 32246, 1511, 304, 87836, 3756, 59251, 1359, 57704, 1609, 14406, 8738, 13, 330, 66761, 35872, 3422, 527, 26455, 18618, 72048, 7384, 369, 11084, 51692, 5347, 1965, 1076, 1105, 11, 323, 1057, 10496, 3495, 1912, 574, 279, 1176, 304, 279, 1917, 311, 12265, 304, 11742, 9235, 1880, 28075, 315, 2536, 1355, 321, 1965, 87836, 7384, 13, 330, 2028, 26501, 374, 3062, 369, 279, 4500, 315, 25524, 6324, 11852, 1880, 28075, 5557, 11, 902, 706, 1027, 5107, 311, 11322, 779, 3117, 13, 5751, 3135, 4097, 459, 3062, 43291, 11, 323, 264, 22520, 30116, 32571, 4741, 11, 304, 8162, 86254, 367, 5557, 1210, 220, 128257, 198 ]

2,316

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Histone-modifying enzymes are required for cell identity and lineage commitment, however little is known about the regulatory origins of the epigenome during embryonic development. Here we generate a comprehensive set of epigenome reference maps, which we use to determine the extent to which maternal factors shape chromatin state in Xenopus embryos. Using α-amanitin to inhibit zygotic transcription, we find that the majority of H3K4me3- and H3K27me3-enriched regions form a maternally defined epigenetic regulatory space with an underlying logic of hypomethylated islands. This maternal regulatory space extends to a substantial proportion of neurula stage-activated promoters. In contrast, p300 recruitment to distal regulatory regions requires embryonic transcription at most loci. The results show that H3K4me3 and H3K27me3 are part of a regulatory space that exerts an extended maternal control well into post-gastrulation development, and highlight the combinatorial action of maternal and zygotic factors through proximal and distal regulatory sequences. Introduction During early embryonic development cells differentiate, acquiring specific transcription and protein expression profiles. Histone modifications can control the activity of genes through regulatory elements in a cell-type-specific manner 1 , 2 , 3 , 4 . Recent advances have been made in the annotation of functional genomic elements of mammalian cells, Drosophila and Caenorhabditis through genome-wide profiling of chromatin marks 5 , 6 . Immediately after fertilization, the embryonic genome is transcriptionally silent, and zygotic genome activation (ZGA) occurs after a number of mitotic cycles 7 . In Drosophila and zebrafish ( Danio rerio ) ZGA starts after 8 and 9 mitotic cycles, respectively, in mammals transcription starts at the two-cell stage 8 , 9 , whereas in Xenopus this happens after the first 12 cleavages at the mid-blastula transition (MBT) 10 , 11 , 12 . Permissive H3K4me3 and repressive H3K27me3 histone modifications emerge during blastula and gastrula stages 13 , 14 , 15 , 16 . To date, little is known about the origin and specification of the epigenome in embryonic development of vertebrates, which is essential for understanding physiological cell lineage commitment and differentiation. To explore the developmental origins of epigenetic regulation we have generated epigenome reference maps during early development of Xenopus tropicalis embryos and assessed the need for embryonic transcription in their acquisition. We find a hierarchical appearance of histone modifications, with a priority for promoter marks which are deposited hours before transcription activation on regions with hypomethylated DNA. Surprisingly, the promoter H3K4me3 and the Polycomb H3K27me3 modifications are largely maternally defined (MaD), providing maternal epigenetic control of gene activation that extends well into neurula and tailbud stages. By contrast, p300 recruitment to distal regulatory elements is largely under the control of zygotic factors. Moreover, this maternal-proximal and zygotic-distal dichotomy of gene regulatory sequences also differentiates between early and late Wnt signalling target genes, suggesting that different levels of permissiveness are involved in temporal target gene selection. Results Progressive specification of chromatin state We have performed chromatin immunoprecipitation (ChIP) sequencing of eight histone modifications, RNA polymerase II (RNAPII) and the enhancer protein p300 at five stages of development: blastula (st. 9), gastrula (st. 10.5, 12.5), neurula (st. 16) and tailbud (st. 30). These experiments allow identification of enhancers (H3K4me1, p300) 17 , 18 , 19 , 20 , promoters (H3K4me3, H3K9ac) 14 , 21 , 22 , 23 , transcribed regions (H3K36me3, RNAPII) 22 and repressed and heterochromatic domains (H3K27me3, H3K9me2, H3K9me3 and H4K20me3) 1 , 14 , 24 , 25 . In addition we generated pre-MBT (st. 8) maps for three histone modifications (H3K4me3, H3K9ac and H3K27me3) and single-base resolution DNA methylome maps using whole-genome bisulfite sequencing of blastula and gastrula (st. 9 and 10.5) embryos ( Fig. 1 ; Supplementary Fig. 1 ). Our data set consists of 2.7 billion aligned sequence reads representing the most comprehensive set of epigenome reference maps of vertebrate embryos to date. Using a Hidden Markov Model approach 26 we have identified 19 chromatin states based on co-occurring ChIP signals ( Fig. 2a ). This analysis identifies combinations of ChIP signals at specific genomic sequences without distinguishing between overlapping histone modifications that result from regional or cell-type specificity and co-occurrence in the same cells 14 . Seven main groups were recognized, namely (i) Polycomb (H3K27me3, deposited by Polycomb Repressive Complex 2 (PRC2)), (ii) poised enhancers, (iii) p300-bound enhancers, (iv) transcribed regions, (v) promoters, (vi) heterochromatin and (vii) unmodified regions ( Fig. 2a ; Supplementary Fig. 2 ). Alluvial plots of state coverage per stage show that all states increase in coverage during development, except for the unmodified state ( Fig. 2b ; Supplementary Fig. 2a ). Unmodified regions decrease in coverage during development, however, even at tailbud stage 67% of the total epigenome remains naive for the modifications and bound proteins in our data set ( Supplementary Fig. 2b ). Promoter coverage remains relatively constant during development from blastula to tailbud stages, in contrast to the Polycomb state which increases in coverage during gastrulation. P300-bound enhancers are highly dynamic during development ( Fig. 2b ). Global enrichment levels of modified regions show similar dynamics, and reveal a priority for promoter marking at or before the blastula stage, followed by enhancer activation and heterochromatic repression during late blastula and gastrulation stages ( Supplementary Fig. 3a,b ). A detailed time course between fertilization and early gastrulation shows that both H3K4me3 and H3K9ac emerge hours before the start of embryonic transcription ( Supplementary Fig. 3c ). We and others have previously reported that H3K4me3 is acquired during blastula stages 14 . Indeed, H3K4me3 and H3K9ac levels increase strongly before the MBT, well before embryonic transcription starts. This however raises the question to what extent histone modifications are regulated by maternal or embryonic factors. Figure 1: Reference epigenome maps of Xenopus tropicalis development. ( a ) Genome-wide profiles were generated for stages 8 and 9 (blastula, before and after MBT), 10.5 and 12.5 (gastrula), 16 (neurula) and 30 (tailbud). Adapted from Tan, M.H. et al . Genome Res. 23 , 201–216 (2013), under a Creative Commons License (Attribution-NonCommercial 3.0 Unported License), as described", "role": "user" }, { "content": "Frog embryos do not fully control which genes they can turn on or off in the beginning of their development – but their mother does, through specific proteins in the egg cell. Molecular developmental biologists at Radboud University publish these results in Nature Communications on December 18. Frog embryos do not only receive half of the genetic information from their mother, but also the instructions on how to use that DNA. That is what molecular developmental biologist Saartje Hontelez and her colleagues, led by Gert Jan Veenstra at the Radboud Institute for Molecular Life Sciences, have discovered. For a long time, scientist believed that the gene regulation is not inheritable. Mother's tools How does the influence of the mother work exactly? Hontelez explains: 'The mother delivers all kinds of tools like proteins and RNA which control the gene regulation of the embryo. And because these tools are very specific, the embryo is limited in its possibilities. The mother sets strict boundaries regarding which genes can be turned on and which cannot. It is only after the twelfth cell division that the embryo can produce its own RNA and thus have some influence on the gene regulation. But this process is still largely controlled by the mother until much later in the embryonic development.' Surprise 'The amount of influence the mother has, surprised us. We always thought that gene regulation is not inheritable and therefore expected that the embryo is in control of it. But when we shut down the embryo's RNA production, this had surprisingly little effect. That was not only the case for important genes during early embryonic development, but also much later, well into the stages of organogenesis. This shows very clearly that the mother is responsible for the early stages of embryonic development, and that her influence is still strongly present in later stages as well.' Fast development For this publication, Hontelez and her colleagues investigated embryos of the western clawed frog (Xenopus tropicalis), because their embryonic development occurs very rapidly: there are only six hours between fertilization and the moment that the embryo's RNA production starts. For comparison: mammal embryos start producing their own RNA after twenty-four hours. 'When you consider the amount of eggs a frog lays, and how many of those eggs successfully develop into frogs, it is not surprising that embryos get a little help from their mother', Hontelez explains. 'It is a pre-programmed system, making sure that early embryonic development usually succeeds.' Can these results now be compared to the development of mice, or even humans? 'Yes, it probably works roughly the same. The biggest difference is that mammalian embryos start producing their own RNA after the first cell division. But the time until that moment takes much longer than in frogs. It is also worth noting that the genes involved in setting up the epigenome are all involved in human cancer.' ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Histone-modifying enzymes are required for cell identity and lineage commitment, however little is known about the regulatory origins of the epigenome during embryonic development. Here we generate a comprehensive set of epigenome reference maps, which we use to determine the extent to which maternal factors shape chromatin state in Xenopus embryos. Using α-amanitin to inhibit zygotic transcription, we find that the majority of H3K4me3- and H3K27me3-enriched regions form a maternally defined epigenetic regulatory space with an underlying logic of hypomethylated islands. This maternal regulatory space extends to a substantial proportion of neurula stage-activated promoters. In contrast, p300 recruitment to distal regulatory regions requires embryonic transcription at most loci. The results show that H3K4me3 and H3K27me3 are part of a regulatory space that exerts an extended maternal control well into post-gastrulation development, and highlight the combinatorial action of maternal and zygotic factors through proximal and distal regulatory sequences. Introduction During early embryonic development cells differentiate, acquiring specific transcription and protein expression profiles. Histone modifications can control the activity of genes through regulatory elements in a cell-type-specific manner 1 , 2 , 3 , 4 . Recent advances have been made in the annotation of functional genomic elements of mammalian cells, Drosophila and Caenorhabditis through genome-wide profiling of chromatin marks 5 , 6 . Immediately after fertilization, the embryonic genome is transcriptionally silent, and zygotic genome activation (ZGA) occurs after a number of mitotic cycles 7 . In Drosophila and zebrafish ( Danio rerio ) ZGA starts after 8 and 9 mitotic cycles, respectively, in mammals transcription starts at the two-cell stage 8 , 9 , whereas in Xenopus this happens after the first 12 cleavages at the mid-blastula transition (MBT) 10 , 11 , 12 . Permissive H3K4me3 and repressive H3K27me3 histone modifications emerge during blastula and gastrula stages 13 , 14 , 15 , 16 . To date, little is known about the origin and specification of the epigenome in embryonic development of vertebrates, which is essential for understanding physiological cell lineage commitment and differentiation. To explore the developmental origins of epigenetic regulation we have generated epigenome reference maps during early development of Xenopus tropicalis embryos and assessed the need for embryonic transcription in their acquisition. We find a hierarchical appearance of histone modifications, with a priority for promoter marks which are deposited hours before transcription activation on regions with hypomethylated DNA. Surprisingly, the promoter H3K4me3 and the Polycomb H3K27me3 modifications are largely maternally defined (MaD), providing maternal epigenetic control of gene activation that extends well into neurula and tailbud stages. By contrast, p300 recruitment to distal regulatory elements is largely under the control of zygotic factors. Moreover, this maternal-proximal and zygotic-distal dichotomy of gene regulatory sequences also differentiates between early and late Wnt signalling target genes, suggesting that different levels of permissiveness are involved in temporal target gene selection. Results Progressive specification of chromatin state We have performed chromatin immunoprecipitation (ChIP) sequencing of eight histone modifications, RNA polymerase II (RNAPII) and the enhancer protein p300 at five stages of development: blastula (st. 9), gastrula (st. 10.5, 12.5), neurula (st. 16) and tailbud (st. 30). These experiments allow identification of enhancers (H3K4me1, p300) 17 , 18 , 19 , 20 , promoters (H3K4me3, H3K9ac) 14 , 21 , 22 , 23 , transcribed regions (H3K36me3, RNAPII) 22 and repressed and heterochromatic domains (H3K27me3, H3K9me2, H3K9me3 and H4K20me3) 1 , 14 , 24 , 25 . In addition we generated pre-MBT (st. 8) maps for three histone modifications (H3K4me3, H3K9ac and H3K27me3) and single-base resolution DNA methylome maps using whole-genome bisulfite sequencing of blastula and gastrula (st. 9 and 10.5) embryos ( Fig. 1 ; Supplementary Fig. 1 ). Our data set consists of 2.7 billion aligned sequence reads representing the most comprehensive set of epigenome reference maps of vertebrate embryos to date. Using a Hidden Markov Model approach 26 we have identified 19 chromatin states based on co-occurring ChIP signals ( Fig. 2a ). This analysis identifies combinations of ChIP signals at specific genomic sequences without distinguishing between overlapping histone modifications that result from regional or cell-type specificity and co-occurrence in the same cells 14 . Seven main groups were recognized, namely (i) Polycomb (H3K27me3, deposited by Polycomb Repressive Complex 2 (PRC2)), (ii) poised enhancers, (iii) p300-bound enhancers, (iv) transcribed regions, (v) promoters, (vi) heterochromatin and (vii) unmodified regions ( Fig. 2a ; Supplementary Fig. 2 ). Alluvial plots of state coverage per stage show that all states increase in coverage during development, except for the unmodified state ( Fig. 2b ; Supplementary Fig. 2a ). Unmodified regions decrease in coverage during development, however, even at tailbud stage 67% of the total epigenome remains naive for the modifications and bound proteins in our data set ( Supplementary Fig. 2b ). Promoter coverage remains relatively constant during development from blastula to tailbud stages, in contrast to the Polycomb state which increases in coverage during gastrulation. P300-bound enhancers are highly dynamic during development ( Fig. 2b ). Global enrichment levels of modified regions show similar dynamics, and reveal a priority for promoter marking at or before the blastula stage, followed by enhancer activation and heterochromatic repression during late blastula and gastrulation stages ( Supplementary Fig. 3a,b ). A detailed time course between fertilization and early gastrulation shows that both H3K4me3 and H3K9ac emerge hours before the start of embryonic transcription ( Supplementary Fig. 3c ). We and others have previously reported that H3K4me3 is acquired during blastula stages 14 . Indeed, H3K4me3 and H3K9ac levels increase strongly before the MBT, well before embryonic transcription starts. This however raises the question to what extent histone modifications are regulated by maternal or embryonic factors. Figure 1: Reference epigenome maps of Xenopus tropicalis development. ( a ) Genome-wide profiles were generated for stages 8 and 9 (blastula, before and after MBT), 10.5 and 12.5 (gastrula), 16 (neurula) and 30 (tailbud). Adapted from Tan, M.H. et al . Genome Res. 23 , 201–216 (2013), under a Creative Commons License (Attribution-NonCommercial 3.0 Unported License), as described<|im_end|> <|im_start|>assistant Frog embryos do not fully control which genes they can turn on or off in the beginning of their development – but their mother does, through specific proteins in the egg cell. Molecular developmental biologists at Radboud University publish these results in Nature Communications on December 18. Frog embryos do not only receive half of the genetic information from their mother, but also the instructions on how to use that DNA. That is what molecular developmental biologist Saartje Hontelez and her colleagues, led by Gert Jan Veenstra at the Radboud Institute for Molecular Life Sciences, have discovered. For a long time, scientist believed that the gene regulation is not inheritable. Mother's tools How does the influence of the mother work exactly? Hontelez explains: 'The mother delivers all kinds of tools like proteins and RNA which control the gene regulation of the embryo. And because these tools are very specific, the embryo is limited in its possibilities. The mother sets strict boundaries regarding which genes can be turned on and which cannot. It is only after the twelfth cell division that the embryo can produce its own RNA and thus have some influence on the gene regulation. But this process is still largely controlled by the mother until much later in the embryonic development.' Surprise 'The amount of influence the mother has, surprised us. We always thought that gene regulation is not inheritable and therefore expected that the embryo is in control of it. But when we shut down the embryo's RNA production, this had surprisingly little effect. That was not only the case for important genes during early embryonic development, but also much later, well into the stages of organogenesis. This shows very clearly that the mother is responsible for the early stages of embryonic development, and that her influence is still strongly present in later stages as well.' Fast development For this publication, Hontelez and her colleagues investigated embryos of the western clawed frog (Xenopus tropicalis), because their embryonic development occurs very rapidly: there are only six hours between fertilization and the moment that the embryo's RNA production starts. For comparison: mammal embryos start producing their own RNA after twenty-four hours. 'When you consider the amount of eggs a frog lays, and how many of those eggs successfully develop into frogs, it is not surprising that embryos get a little help from their mother', Hontelez explains. 'It is a pre-programmed system, making sure that early embryonic development usually succeeds.' Can these results now be compared to the development of mice, or even humans? 'Yes, it probably works roughly the same. The biggest difference is that mammalian embryos start producing their own RNA after the first cell division. But the time until that moment takes much longer than in frogs. It is also worth noting that the genes involved in setting up the epigenome are all involved in human cancer.' <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 67005, 606, 17515, 7922, 56067, 527, 2631, 369, 2849, 9764, 323, 65009, 15507, 11, 4869, 2697, 374, 3967, 922, 279, 23331, 33472, 315, 279, 4248, 6569, 638, 2391, 44481, 14338, 4500, 13, 5810, 584, 7068, 264, 16195, 743, 315, 4248, 6569, 638, 5905, 14370, 11, 902, 584, 1005, 311, 8417, 279, 13112, 311, 902, 50150, 9547, 6211, 22083, 15111, 1614, 304, 49329, 46970, 89873, 13, 12362, 19581, 12, 13005, 85986, 311, 69033, 1167, 49865, 14546, 46940, 11, 584, 1505, 430, 279, 8857, 315, 473, 18, 42, 19, 2727, 18, 12, 323, 473, 18, 42, 1544, 2727, 18, 21430, 14172, 291, 13918, 1376, 264, 5634, 944, 750, 4613, 4248, 6569, 5411, 23331, 3634, 449, 459, 16940, 12496, 315, 9950, 316, 42972, 660, 30100, 13, 1115, 50150, 23331, 3634, 2289, 311, 264, 12190, 21801, 315, 21850, 5724, 6566, 12, 31262, 95260, 13, 763, 13168, 11, 281, 3101, 34102, 311, 1612, 278, 23331, 13918, 7612, 44481, 14338, 46940, 520, 1455, 1353, 72, 13, 578, 3135, 1501, 430, 473, 18, 42, 19, 2727, 18, 323, 473, 18, 42, 1544, 2727, 18, 527, 961, 315, 264, 23331, 3634, 430, 506, 15916, 459, 11838, 50150, 2585, 1664, 1139, 1772, 2427, 21100, 2987, 4500, 11, 323, 11415, 279, 3698, 17720, 532, 1957, 315, 50150, 323, 1167, 49865, 14546, 9547, 1555, 22267, 2931, 323, 1612, 278, 23331, 24630, 13, 29438, 12220, 4216, 44481, 14338, 4500, 7917, 54263, 11, 42990, 3230, 46940, 323, 13128, 7645, 21542, 13, 67005, 606, 29882, 649, 2585, 279, 5820, 315, 21389, 1555, 23331, 5540, 304, 264, 2849, 10827, 19440, 11827, 220, 16, 1174, 220, 17, 1174, 220, 18, 1174, 220, 19, 662, 35390, 31003, 617, 1027, 1903, 304, 279, 21917, 315, 16003, 81064, 5540, 315, 36041, 10700, 7917, 11, 423, 3714, 5237, 10746, 323, 14751, 99831, 10796, 18225, 285, 1555, 33869, 25480, 56186, 315, 22083, 15111, 15785, 220, 20, 1174, 220, 21, 662, 69352, 1306, 36214, 2065, 11, 279, 44481, 14338, 33869, 374, 46940, 750, 21737, 11, 323, 1167, 49865, 14546, 33869, 15449, 320, 57, 16519, 8, 13980, 1306, 264, 1396, 315, 5568, 14546, 25492, 220, 22, 662, 763, 423, 3714, 5237, 10746, 323, 1167, 3141, 15817, 819, 320, 11824, 822, 49647, 822, 883, 1901, 16519, 8638, 1306, 220, 23, 323, 220, 24, 5568, 14546, 25492, 11, 15947, 11, 304, 56669, 46940, 8638, 520, 279, 1403, 33001, 6566, 220, 23, 1174, 220, 24, 1174, 20444, 304, 49329, 46970, 420, 8741, 1306, 279, 1176, 220, 717, 11551, 402, 1154, 520, 279, 5209, 1481, 4354, 5724, 9320, 320, 8578, 51, 8, 220, 605, 1174, 220, 806, 1174, 220, 717, 662, 3700, 58028, 473, 18, 42, 19, 2727, 18, 323, 312, 69563, 473, 18, 42, 1544, 2727, 18, 13034, 606, 29882, 34044, 2391, 21327, 5724, 323, 56780, 5724, 18094, 220, 1032, 1174, 220, 975, 1174, 220, 868, 1174, 220, 845, 662, 2057, 2457, 11, 2697, 374, 3967, 922, 279, 6371, 323, 26185, 315, 279, 4248, 6569, 638, 304, 44481, 14338, 4500, 315, 67861, 99868, 11, 902, 374, 7718, 369, 8830, 53194, 2849, 65009, 15507, 323, 60038, 13, 2057, 13488, 279, 48006, 33472, 315, 4248, 6569, 5411, 19812, 584, 617, 8066, 4248, 6569, 638, 5905, 14370, 2391, 4216, 4500, 315, 49329, 46970, 35148, 285, 89873, 323, 32448, 279, 1205, 369, 44481, 14338, 46940, 304, 872, 24279, 13, 1226, 1505, 264, 70994, 11341, 315, 13034, 606, 29882, 11, 449, 264, 10844, 369, 66642, 15785, 902, 527, 54568, 4207, 1603, 46940, 15449, 389, 13918, 449, 9950, 316, 42972, 660, 15922, 13, 8242, 49264, 11, 279, 66642, 473, 18, 42, 19, 2727, 18, 323, 279, 19294, 22631, 473, 18, 42, 1544, 2727, 18, 29882, 527, 14090, 5634, 944, 750, 4613, 320, 30635, 35, 705, 8405, 50150, 4248, 6569, 5411, 2585, 315, 15207, 15449, 430, 2289, 1664, 1139, 21850, 5724, 323, 9986, 71027, 18094, 13, 3296, 13168, 11, 281, 3101, 34102, 311, 1612, 278, 23331, 5540, 374, 14090, 1234, 279, 2585, 315, 1167, 49865, 14546, 9547, 13, 23674, 11, 420, 50150, 10039, 87, 2931, 323, 1167, 49865, 14546, 88359, 278, 29953, 85995, 315, 15207, 23331, 24630, 1101, 2204, 43398, 1990, 4216, 323, 3389, 468, 406, 91977, 2218, 21389, 11, 23377, 430, 2204, 5990, 315, 824, 1869, 13071, 527, 6532, 304, 37015, 2218, 15207, 6727, 13, 18591, 52870, 26185, 315, 22083, 15111, 1614, 1226, 617, 10887, 22083, 15111, 33119, 454, 2827, 575, 7709, 320, 1163, 3378, 8, 62119, 315, 8223, 13034, 606, 29882, 11, 41214, 47393, 521, 8105, 320, 51295, 7227, 40, 8, 323, 279, 8833, 11967, 13128, 281, 3101, 520, 4330, 18094, 315, 4500, 25, 21327, 5724, 320, 267, 13, 220, 24, 705, 56780, 5724, 320, 267, 13, 220, 605, 13, 20, 11, 220, 717, 13, 20, 705, 21850, 5724, 320, 267, 13, 220, 845, 8, 323, 9986, 71027, 320, 267, 13, 220, 966, 570, 4314, 21896, 2187, 22654, 315, 8833, 32842, 320, 39, 18, 42, 19, 2727, 16, 11, 281, 3101, 8, 220, 1114, 1174, 220, 972, 1174, 220, 777, 1174, 220, 508, 1174, 95260, 320, 39, 18, 42, 19, 2727, 18, 11, 473, 18, 42, 24, 582, 8, 220, 975, 1174, 220, 1691, 1174, 220, 1313, 1174, 220, 1419, 1174, 1380, 17890, 13918, 320, 39, 18, 42, 1927, 2727, 18, 11, 46916, 7227, 40, 8, 220, 1313, 323, 312, 14655, 323, 30548, 5059, 99866, 31576, 320, 39, 18, 42, 1544, 2727, 18, 11, 473, 18, 42, 24, 2727, 17, 11, 473, 18, 42, 24, 2727, 18, 323, 473, 19, 42, 508, 2727, 18, 8, 220, 16, 1174, 220, 975, 1174, 220, 1187, 1174, 220, 914, 662, 763, 5369, 584, 8066, 864, 5364, 18066, 320, 267, 13, 220, 23, 8, 14370, 369, 2380, 13034, 606, 29882, 320, 39, 18, 42, 19, 2727, 18, 11, 473, 18, 42, 24, 582, 323, 473, 18, 42, 1544, 2727, 18, 8, 323, 3254, 31113, 11175, 15922, 79574, 638, 14370, 1701, 4459, 37564, 638, 15184, 14643, 635, 62119, 315, 21327, 5724, 323, 56780, 5724, 320, 267, 13, 220, 24, 323, 220, 605, 13, 20, 8, 89873, 320, 23966, 13, 220, 16, 2652, 99371, 23966, 13, 220, 16, 7609, 5751, 828, 743, 17610, 315, 220, 17, 13, 22, 7239, 27210, 8668, 16181, 14393, 279, 1455, 16195, 743, 315, 4248, 6569, 638, 5905, 14370, 315, 67861, 65216, 89873, 311, 2457, 13, 12362, 264, 35342, 4488, 869, 5008, 5603, 220, 1627, 584, 617, 11054, 220, 777, 22083, 15111, 5415, 3196, 389, 1080, 12, 511, 46839, 921, 3378, 17738, 320, 23966, 13, 220, 17, 64, 7609, 1115, 6492, 36611, 28559, 315, 921, 3378, 17738, 520, 3230, 81064, 24630, 2085, 86055, 1990, 50917, 13034, 606, 29882, 430, 1121, 505, 15481, 477, 2849, 10827, 76041, 323, 1080, 12, 14310, 21201, 304, 279, 1890, 7917, 220, 975, 662, 31048, 1925, 5315, 1051, 15324, 11, 32125, 320, 72, 8, 19294, 22631, 320, 39, 18, 42, 1544, 2727, 18, 11, 54568, 555, 19294, 22631, 3402, 49053, 22872, 220, 17, 320, 6616, 34, 17, 5850, 320, 3893, 8, 54946, 8833, 32842, 11, 320, 35694, 8, 281, 3101, 50962, 8833, 32842, 11, 320, 344, 8, 1380, 17890, 13918, 11, 320, 85, 8, 95260, 11, 320, 10176, 8, 30548, 5059, 442, 15111, 323, 320, 85, 3893, 8, 653, 28261, 13918, 320, 23966, 13, 220, 17, 64, 2652, 99371, 23966, 13, 220, 17, 7609, 2052, 12328, 532, 31794, 315, 1614, 10401, 824, 6566, 1501, 430, 682, 5415, 5376, 304, 10401, 2391, 4500, 11, 3734, 369, 279, 653, 28261, 1614, 320, 23966, 13, 220, 17, 65, 2652, 99371, 23966, 13, 220, 17, 64, 7609, 1252, 28261, 13918, 18979, 304, 10401, 2391, 4500, 11, 4869, 11, 1524, 520, 9986, 71027, 6566, 220, 3080, 4, 315, 279, 2860, 4248, 6569, 638, 8625, 50765, 369, 279, 29882, 323, 6965, 28896, 304, 1057, 828, 743, 320, 99371, 23966, 13, 220, 17, 65, 7609, 18042, 26464, 10401, 8625, 12309, 6926, 2391, 4500, 505, 21327, 5724, 311, 9986, 71027, 18094, 11, 304, 13168, 311, 279, 19294, 22631, 1614, 902, 12992, 304, 10401, 2391, 56780, 2987, 13, 393, 3101, 50962, 8833, 32842, 527, 7701, 8915, 2391, 4500, 320, 23966, 13, 220, 17, 65, 7609, 8121, 70272, 5990, 315, 11041, 13918, 1501, 4528, 30295, 11, 323, 16805, 264, 10844, 369, 66642, 36024, 520, 477, 1603, 279, 21327, 5724, 6566, 11, 8272, 555, 8833, 11967, 15449, 323, 30548, 5059, 99866, 72498, 2391, 3389, 21327, 5724, 323, 56780, 2987, 18094, 320, 99371, 23966, 13, 220, 18, 64, 8568, 7609, 362, 11944, 892, 3388, 1990, 36214, 2065, 323, 4216, 56780, 2987, 5039, 430, 2225, 473, 18, 42, 19, 2727, 18, 323, 473, 18, 42, 24, 582, 34044, 4207, 1603, 279, 1212, 315, 44481, 14338, 46940, 320, 99371, 23966, 13, 220, 18, 66, 7609, 1226, 323, 3885, 617, 8767, 5068, 430, 473, 18, 42, 19, 2727, 18, 374, 19426, 2391, 21327, 5724, 18094, 220, 975, 662, 23150, 11, 473, 18, 42, 19, 2727, 18, 323, 473, 18, 42, 24, 582, 5990, 5376, 16917, 1603, 279, 13642, 51, 11, 1664, 1603, 44481, 14338, 46940, 8638, 13, 1115, 4869, 25930, 279, 3488, 311, 1148, 13112, 13034, 606, 29882, 527, 35319, 555, 50150, 477, 44481, 14338, 9547, 13, 19575, 220, 16, 25, 17650, 4248, 6569, 638, 14370, 315, 49329, 46970, 35148, 285, 4500, 13, 320, 264, 883, 82917, 25480, 21542, 1051, 8066, 369, 18094, 220, 23, 323, 220, 24, 320, 64417, 5724, 11, 1603, 323, 1306, 13642, 51, 705, 220, 605, 13, 20, 323, 220, 717, 13, 20, 320, 6885, 496, 5724, 705, 220, 845, 320, 818, 324, 5724, 8, 323, 220, 966, 320, 14928, 71027, 570, 59531, 291, 505, 25566, 11, 386, 3924, 13, 1880, 453, 662, 82917, 1838, 13, 220, 1419, 1174, 220, 679, 4235, 12463, 320, 679, 18, 705, 1234, 264, 25248, 26667, 1914, 320, 20241, 1516, 12, 8284, 60816, 220, 18, 13, 15, 1252, 36626, 1914, 705, 439, 7633, 128257, 198, 128256, 78191, 198, 37, 12184, 89873, 656, 539, 7373, 2585, 902, 21389, 814, 649, 2543, 389, 477, 1022, 304, 279, 7314, 315, 872, 4500, 1389, 719, 872, 6691, 1587, 11, 1555, 3230, 28896, 304, 279, 19151, 2849, 13, 60825, 48006, 6160, 22012, 520, 21254, 65, 3023, 3907, 3498, 1521, 3135, 304, 22037, 26545, 389, 6790, 220, 972, 13, 72519, 89873, 656, 539, 1193, 5371, 4376, 315, 279, 19465, 2038, 505, 872, 6691, 11, 719, 1101, 279, 11470, 389, 1268, 311, 1005, 430, 15922, 13, 3011, 374, 1148, 31206, 48006, 88704, 16233, 472, 3841, 473, 546, 114360, 323, 1077, 18105, 11, 6197, 555, 480, 531, 4448, 650, 15258, 13645, 520, 279, 21254, 65, 3023, 10181, 369, 60825, 9601, 23199, 11, 617, 11352, 13, 1789, 264, 1317, 892, 11, 28568, 11846, 430, 279, 15207, 19812, 374, 539, 24683, 481, 13, 21720, 596, 7526, 2650, 1587, 279, 10383, 315, 279, 6691, 990, 7041, 30, 473, 546, 114360, 15100, 25, 364, 791, 6691, 28421, 682, 13124, 315, 7526, 1093, 28896, 323, 41214, 902, 2585, 279, 15207, 19812, 315, 279, 87701, 13, 1628, 1606, 1521, 7526, 527, 1633, 3230, 11, 279, 87701, 374, 7347, 304, 1202, 24525, 13, 578, 6691, 7437, 7452, 23546, 9002, 902, 21389, 649, 387, 6656, 389, 323, 902, 4250, 13, 1102, 374, 1193, 1306, 279, 4483, 88798, 2849, 13096, 430, 279, 87701, 649, 8356, 1202, 1866, 41214, 323, 8617, 617, 1063, 10383, 389, 279, 15207, 19812, 13, 2030, 420, 1920, 374, 2103, 14090, 14400, 555, 279, 6691, 3156, 1790, 3010, 304, 279, 44481, 14338, 4500, 3238, 85584, 364, 791, 3392, 315, 10383, 279, 6691, 706, 11, 14792, 603, 13, 1226, 2744, 3463, 430, 15207, 19812, 374, 539, 24683, 481, 323, 9093, 3685, 430, 279, 87701, 374, 304, 2585, 315, 433, 13, 2030, 994, 584, 9495, 1523, 279, 87701, 596, 41214, 5788, 11, 420, 1047, 29392, 2697, 2515, 13, 3011, 574, 539, 1193, 279, 1162, 369, 3062, 21389, 2391, 4216, 44481, 14338, 4500, 11, 719, 1101, 1790, 3010, 11, 1664, 1139, 279, 18094, 315, 2942, 52379, 13, 1115, 5039, 1633, 9539, 430, 279, 6691, 374, 8647, 369, 279, 4216, 18094, 315, 44481, 14338, 4500, 11, 323, 430, 1077, 10383, 374, 2103, 16917, 3118, 304, 3010, 18094, 439, 1664, 3238, 17737, 4500, 1789, 420, 17009, 11, 473, 546, 114360, 323, 1077, 18105, 27313, 89873, 315, 279, 19001, 57590, 291, 60981, 320, 55, 268, 46970, 35148, 285, 705, 1606, 872, 44481, 14338, 4500, 13980, 1633, 19019, 25, 1070, 527, 1193, 4848, 4207, 1990, 36214, 2065, 323, 279, 4545, 430, 279, 87701, 596, 41214, 5788, 8638, 13, 1789, 12593, 25, 36041, 278, 89873, 1212, 17843, 872, 1866, 41214, 1306, 17510, 42117, 4207, 13, 364, 4599, 499, 2980, 279, 3392, 315, 19335, 264, 60981, 57622, 11, 323, 1268, 1690, 315, 1884, 19335, 7946, 2274, 1139, 90546, 11, 433, 374, 539, 15206, 430, 89873, 636, 264, 2697, 1520, 505, 872, 6691, 518, 473, 546, 114360, 15100, 13, 364, 2181, 374, 264, 864, 67120, 2106, 1887, 11, 3339, 2771, 430, 4216, 44481, 14338, 4500, 6118, 51181, 3238, 3053, 1521, 3135, 1457, 387, 7863, 311, 279, 4500, 315, 24548, 11, 477, 1524, 12966, 30, 364, 9642, 11, 433, 4762, 4375, 17715, 279, 1890, 13, 578, 8706, 6811, 374, 430, 36041, 10700, 89873, 1212, 17843, 872, 1866, 41214, 1306, 279, 1176, 2849, 13096, 13, 2030, 279, 892, 3156, 430, 4545, 5097, 1790, 5129, 1109, 304, 90546, 13, 1102, 374, 1101, 5922, 27401, 430, 279, 21389, 6532, 304, 6376, 709, 279, 4248, 6569, 638, 527, 682, 6532, 304, 3823, 9572, 3238, 220, 128257, 198 ]

2,217

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract With phenotypic heterogeneity in whole cell populations widely recognised, the demand for quantitative and temporal analysis approaches to characterise single cell morphology and dynamics has increased. We present CellPhe, a pattern recognition toolkit for the unbiased characterisation of cellular phenotypes within time-lapse videos. CellPhe imports tracking information from multiple segmentation and tracking algorithms to provide automated cell phenotyping from different imaging modalities, including fluorescence. To maximise data quality for downstream analysis, our toolkit includes automated recognition and removal of erroneous cell boundaries induced by inaccurate tracking and segmentation. We provide an extensive list of features extracted from individual cell time series, with custom feature selection to identify variables that provide greatest discrimination for the analysis in question. Using ensemble classification for accurate prediction of cellular phenotype and clustering algorithms for the characterisation of heterogeneous subsets, we validate and prove adaptability using different cell types and experimental conditions. Introduction Heterogeneity in whole cell populations is a long-standing area of interest 1 , 2 , 3 and previous studies have identified cell-to-cell phenotypic and genotypic diversity even within clonally derived populations 4 . The emergence of methods such as single-cell RNA sequencing has enabled characterisation of subsets within a population from gene expression profiles 5 , yet these methods involve collection of data at discrete time points, missing the subtle temporal changes in gene expression on a continuous scale. Such methods exclude information on single-cell morphology and dynamics, yet cellular phenotype plays a crucial role in determining cell function 6 , 7 , disease progression 8 , and response to treatment 9 . There remains a demand for quantitative and temporal analysis approaches to describe the subtleties of single-cell heterogeneity and the complexities of cell behaviour. Modern microscopy advancements facilitate the ability to produce information-rich images of cells and tissue, at high-throughput and of high quality. Temporal changes in cell behaviour can be observed through time-lapse imaging and features describing the cells’ behaviour over time can be extracted for analysis. However, the task of identifying individual cells and following them over time is an ongoing computer vision challenge 10 , 11 . Initial processing requires segmentation, the detection of cells as regions of interest (ROIs) distinguished from background, and tracking, with each cell given a unique identifier that is retained over subsequent frames. Recent work using the similarity between cell metrics on consecutive frames highlighted the importance of accurate tracking to follow cell lineage 12 . Imaging artefacts vary between experiments and issues such as background noise, inhomogeneity of cell size and overlapping cells are still challenges for biomedical research 13 . Reliable cell segmentation protocols are non-deterministic and experiment-specific 14 but user-friendly software systems that use machine learning algorithms are emerging to provide objective, high-throughput cell segmentation and tracking 15 , 16 . Recent developments to TrackMate 17 allow the results of various segmentation software to be integrated with flexible tracking algorithms and provide visualisation tools to assess both segmentation and cell tracks. Although the time series for certain cell properties, such as cell area and circularity, can be displayed, the extraction and analysis of descriptive time series is not within the scope of the TrackMate software. Comparison of the tracked cells behaviour is challenging as cells are tracked for different numbers of frames with frames missing where cells leave the field of view. This has meant that analysis of any extracted features has been limited to visualisation. CellPhe interpolates the time series and then calculates a fixed number of variables that characterise each feature’s time series- the features of features! Here we present CellPhe, a pattern recognition toolkit that uses the output of segmentation and tracking software to provide an extensive list of features that characterise changes in the cells’ appearance and behaviour over time. Customised feature selection allows the most discriminatory variables for a particular objective to be identified. These extracted variables quantify cell morphology, texture and dynamics and describe temporal changes and can be used to reliably characterise and classify individual cells as well as cell populations. To ensure precise quantification of cell morphology and motility, and to monitor major cellular events such as mitosis and apoptosis, it is vital that instances of erroneous segmentation and tracking are removed from data sets prior to downstream analysis methods 18 . Manual removal of such errors is heavily labour-intensive, particularly when time-lapses take place over several days. To maximise data quality for downstream analysis, CellPhe includes the recognition and removal of erroneous cell boundaries induced by inaccurate segmentation and tracking. We demonstrate the use of ensemble classification for accurate prediction of cellular phenotype and clustering algorithms for identification of heterogeneous subsets. We exemplify CellPhe by characterising the behaviour of untreated and chemotherapy-treated breast cancer cells from ptychographic time-lapse videos. Quantitative phase images (QPI) 19 , 20 , 21 avoid any fluorescence-induced perturbation of the cells but segmentation accuracy can be affected by reduced differences in intensity between cells and background in comparison to fluorescent labelling. We show that our methods successfully recognise and remove a population of erroneously segmented cells, improving data set quality. Morphological and dynamical changes induced by chemotherapeutics, particularly at low drug concentration, are often more subtle than those that discriminate distinct cell types and we demonstrate the ability of CellPhe to automatically identify time series differences induced by chemotherapy treatment, with the chosen variables proving statistically significant even when not observable by eye. The complexities of heterogeneous drug response and the problem of drug resistance further motivate our chosen application. The ability to identify discriminatory features between treated and untreated cells can allow automated detection of “non-conforming” cells such as those that possess cellular drug resistance. Further investigation of such features could elucidate the underlying biological mechanisms responsible for chemotherapy resistance and cancer recurrence. We validate the adaptability of CellPhe with both a different cell type and a different drug treatment and show that variables are selected according to experimental conditions, tailored to properties of the cell type and drug mechanism of action. CellPhe is", "role": "user" }, { "content": "Being able to observe and track the way cells change and develop over time is a vital part of scientific and medical research. Time-lapse studies of cells can show us how cells have mutated in certain environments or their reactions to external influences, such as medical treatment. This information can shine a light on how disease spreads and why some patients' cells do not respond to treatment such as chemotherapy. Tracking the development of specific cell features is a difficult process however, scientists at the departments of Biology and Mathematics at the University of York have now created a free digital tool which can help. The software package, called CellPhe, is the first of its kind as it can extract a series of features from a cell in a time-lapse study and characterize the cells based on their behavior and internal structure. The package also automatically removes errors in cell tracking to improve data quality. In a study published April 3 in Nature Communications, CellPhe correctly identified two different sets of breast cancer cells—one which was treated with chemotherapy drugs and the other which was not. Comparing the two groups, CellPhe was also able to identify a potentially resistant subset of treated cells. Data like this is particularly important in understanding breast cancer and designing its treatment, as chemoresistance commonly leads to relapse in breast cancer patients. CellPhe could also have further practical applications in processes such as drug screening and the prediction of disease prognosis. Laura Wiggins from the Department of Biology said, \"It is hugely exciting to be able to quantify cell behavior over time in such unprecedented detail. \"A lot of hard work has gone into making CellPhe user-friendly and adaptable to new applications so we look forward to seeing how our toolkit will be used by the community. We foresee CellPhe playing a pivotal role in our understanding of cellular drug response as well as the ways in which cells communicate with one another, via signaling as well as through direct contact.\" CellPhe is freely available online and will run on any operating system and comes with a manual and an instruction video. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract With phenotypic heterogeneity in whole cell populations widely recognised, the demand for quantitative and temporal analysis approaches to characterise single cell morphology and dynamics has increased. We present CellPhe, a pattern recognition toolkit for the unbiased characterisation of cellular phenotypes within time-lapse videos. CellPhe imports tracking information from multiple segmentation and tracking algorithms to provide automated cell phenotyping from different imaging modalities, including fluorescence. To maximise data quality for downstream analysis, our toolkit includes automated recognition and removal of erroneous cell boundaries induced by inaccurate tracking and segmentation. We provide an extensive list of features extracted from individual cell time series, with custom feature selection to identify variables that provide greatest discrimination for the analysis in question. Using ensemble classification for accurate prediction of cellular phenotype and clustering algorithms for the characterisation of heterogeneous subsets, we validate and prove adaptability using different cell types and experimental conditions. Introduction Heterogeneity in whole cell populations is a long-standing area of interest 1 , 2 , 3 and previous studies have identified cell-to-cell phenotypic and genotypic diversity even within clonally derived populations 4 . The emergence of methods such as single-cell RNA sequencing has enabled characterisation of subsets within a population from gene expression profiles 5 , yet these methods involve collection of data at discrete time points, missing the subtle temporal changes in gene expression on a continuous scale. Such methods exclude information on single-cell morphology and dynamics, yet cellular phenotype plays a crucial role in determining cell function 6 , 7 , disease progression 8 , and response to treatment 9 . There remains a demand for quantitative and temporal analysis approaches to describe the subtleties of single-cell heterogeneity and the complexities of cell behaviour. Modern microscopy advancements facilitate the ability to produce information-rich images of cells and tissue, at high-throughput and of high quality. Temporal changes in cell behaviour can be observed through time-lapse imaging and features describing the cells’ behaviour over time can be extracted for analysis. However, the task of identifying individual cells and following them over time is an ongoing computer vision challenge 10 , 11 . Initial processing requires segmentation, the detection of cells as regions of interest (ROIs) distinguished from background, and tracking, with each cell given a unique identifier that is retained over subsequent frames. Recent work using the similarity between cell metrics on consecutive frames highlighted the importance of accurate tracking to follow cell lineage 12 . Imaging artefacts vary between experiments and issues such as background noise, inhomogeneity of cell size and overlapping cells are still challenges for biomedical research 13 . Reliable cell segmentation protocols are non-deterministic and experiment-specific 14 but user-friendly software systems that use machine learning algorithms are emerging to provide objective, high-throughput cell segmentation and tracking 15 , 16 . Recent developments to TrackMate 17 allow the results of various segmentation software to be integrated with flexible tracking algorithms and provide visualisation tools to assess both segmentation and cell tracks. Although the time series for certain cell properties, such as cell area and circularity, can be displayed, the extraction and analysis of descriptive time series is not within the scope of the TrackMate software. Comparison of the tracked cells behaviour is challenging as cells are tracked for different numbers of frames with frames missing where cells leave the field of view. This has meant that analysis of any extracted features has been limited to visualisation. CellPhe interpolates the time series and then calculates a fixed number of variables that characterise each feature’s time series- the features of features! Here we present CellPhe, a pattern recognition toolkit that uses the output of segmentation and tracking software to provide an extensive list of features that characterise changes in the cells’ appearance and behaviour over time. Customised feature selection allows the most discriminatory variables for a particular objective to be identified. These extracted variables quantify cell morphology, texture and dynamics and describe temporal changes and can be used to reliably characterise and classify individual cells as well as cell populations. To ensure precise quantification of cell morphology and motility, and to monitor major cellular events such as mitosis and apoptosis, it is vital that instances of erroneous segmentation and tracking are removed from data sets prior to downstream analysis methods 18 . Manual removal of such errors is heavily labour-intensive, particularly when time-lapses take place over several days. To maximise data quality for downstream analysis, CellPhe includes the recognition and removal of erroneous cell boundaries induced by inaccurate segmentation and tracking. We demonstrate the use of ensemble classification for accurate prediction of cellular phenotype and clustering algorithms for identification of heterogeneous subsets. We exemplify CellPhe by characterising the behaviour of untreated and chemotherapy-treated breast cancer cells from ptychographic time-lapse videos. Quantitative phase images (QPI) 19 , 20 , 21 avoid any fluorescence-induced perturbation of the cells but segmentation accuracy can be affected by reduced differences in intensity between cells and background in comparison to fluorescent labelling. We show that our methods successfully recognise and remove a population of erroneously segmented cells, improving data set quality. Morphological and dynamical changes induced by chemotherapeutics, particularly at low drug concentration, are often more subtle than those that discriminate distinct cell types and we demonstrate the ability of CellPhe to automatically identify time series differences induced by chemotherapy treatment, with the chosen variables proving statistically significant even when not observable by eye. The complexities of heterogeneous drug response and the problem of drug resistance further motivate our chosen application. The ability to identify discriminatory features between treated and untreated cells can allow automated detection of “non-conforming” cells such as those that possess cellular drug resistance. Further investigation of such features could elucidate the underlying biological mechanisms responsible for chemotherapy resistance and cancer recurrence. We validate the adaptability of CellPhe with both a different cell type and a different drug treatment and show that variables are selected according to experimental conditions, tailored to properties of the cell type and drug mechanism of action. CellPhe is<|im_end|> <|im_start|>assistant Being able to observe and track the way cells change and develop over time is a vital part of scientific and medical research. Time-lapse studies of cells can show us how cells have mutated in certain environments or their reactions to external influences, such as medical treatment. This information can shine a light on how disease spreads and why some patients' cells do not respond to treatment such as chemotherapy. Tracking the development of specific cell features is a difficult process however, scientists at the departments of Biology and Mathematics at the University of York have now created a free digital tool which can help. The software package, called CellPhe, is the first of its kind as it can extract a series of features from a cell in a time-lapse study and characterize the cells based on their behavior and internal structure. The package also automatically removes errors in cell tracking to improve data quality. In a study published April 3 in Nature Communications, CellPhe correctly identified two different sets of breast cancer cells—one which was treated with chemotherapy drugs and the other which was not. Comparing the two groups, CellPhe was also able to identify a potentially resistant subset of treated cells. Data like this is particularly important in understanding breast cancer and designing its treatment, as chemoresistance commonly leads to relapse in breast cancer patients. CellPhe could also have further practical applications in processes such as drug screening and the prediction of disease prognosis. Laura Wiggins from the Department of Biology said, "It is hugely exciting to be able to quantify cell behavior over time in such unprecedented detail. "A lot of hard work has gone into making CellPhe user-friendly and adaptable to new applications so we look forward to seeing how our toolkit will be used by the community. We foresee CellPhe playing a pivotal role in our understanding of cellular drug response as well as the ways in which cells communicate with one another, via signaling as well as through direct contact." CellPhe is freely available online and will run on any operating system and comes with a manual and an instruction video. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 3161, 14345, 37941, 292, 30548, 76730, 304, 4459, 2849, 22673, 13882, 39764, 11, 279, 7631, 369, 47616, 323, 37015, 6492, 20414, 311, 3752, 1082, 3254, 2849, 79612, 323, 30295, 706, 7319, 13, 1226, 3118, 14299, 47, 383, 11, 264, 5497, 18324, 66994, 369, 279, 74315, 3752, 8082, 315, 35693, 14345, 22583, 2949, 892, 2922, 7629, 6946, 13, 14299, 47, 383, 15557, 15194, 2038, 505, 5361, 60852, 323, 15194, 26249, 311, 3493, 28598, 2849, 14345, 67247, 505, 2204, 32758, 13531, 1385, 11, 2737, 97332, 13, 2057, 31127, 1082, 828, 4367, 369, 52452, 6492, 11, 1057, 66994, 5764, 28598, 18324, 323, 17065, 315, 77772, 2849, 23546, 36572, 555, 50504, 15194, 323, 60852, 13, 1226, 3493, 459, 16781, 1160, 315, 4519, 28532, 505, 3927, 2849, 892, 4101, 11, 449, 2587, 4668, 6727, 311, 10765, 7482, 430, 3493, 12474, 21934, 369, 279, 6492, 304, 3488, 13, 12362, 40126, 24790, 369, 13687, 20212, 315, 35693, 82423, 323, 59454, 26249, 369, 279, 3752, 8082, 315, 98882, 75605, 11, 584, 9788, 323, 12391, 10737, 2968, 1701, 2204, 2849, 4595, 323, 22772, 4787, 13, 29438, 473, 1430, 76730, 304, 4459, 2849, 22673, 374, 264, 1317, 56703, 3158, 315, 2802, 220, 16, 1174, 220, 17, 1174, 220, 18, 323, 3766, 7978, 617, 11054, 2849, 4791, 33001, 14345, 37941, 292, 323, 4173, 37941, 292, 20057, 1524, 2949, 1206, 263, 750, 14592, 22673, 220, 19, 662, 578, 49179, 315, 5528, 1778, 439, 3254, 33001, 41214, 62119, 706, 9147, 3752, 8082, 315, 75605, 2949, 264, 7187, 505, 15207, 7645, 21542, 220, 20, 1174, 3686, 1521, 5528, 21736, 4526, 315, 828, 520, 44279, 892, 3585, 11, 7554, 279, 27545, 37015, 4442, 304, 15207, 7645, 389, 264, 19815, 5569, 13, 15483, 5528, 22429, 2038, 389, 3254, 33001, 79612, 323, 30295, 11, 3686, 35693, 82423, 11335, 264, 16996, 3560, 304, 26679, 2849, 734, 220, 21, 1174, 220, 22, 1174, 8624, 33824, 220, 23, 1174, 323, 2077, 311, 6514, 220, 24, 662, 2684, 8625, 264, 7631, 369, 47616, 323, 37015, 6492, 20414, 311, 7664, 279, 42129, 1169, 552, 315, 3254, 33001, 30548, 76730, 323, 279, 84140, 315, 2849, 17432, 13, 18766, 92914, 83787, 28696, 279, 5845, 311, 8356, 2038, 41947, 5448, 315, 7917, 323, 20438, 11, 520, 1579, 43847, 631, 323, 315, 1579, 4367, 13, 20539, 10020, 4442, 304, 2849, 17432, 649, 387, 13468, 1555, 892, 2922, 7629, 32758, 323, 4519, 23524, 279, 7917, 529, 17432, 927, 892, 649, 387, 28532, 369, 6492, 13, 4452, 11, 279, 3465, 315, 25607, 3927, 7917, 323, 2768, 1124, 927, 892, 374, 459, 14529, 6500, 11376, 8815, 220, 605, 1174, 220, 806, 662, 4220, 8863, 7612, 60852, 11, 279, 18468, 315, 7917, 439, 13918, 315, 2802, 320, 1308, 3957, 8, 39575, 505, 4092, 11, 323, 15194, 11, 449, 1855, 2849, 2728, 264, 5016, 13110, 430, 374, 35363, 927, 17876, 14418, 13, 35390, 990, 1701, 279, 38723, 1990, 2849, 17150, 389, 24871, 14418, 27463, 279, 12939, 315, 13687, 15194, 311, 1833, 2849, 65009, 220, 717, 662, 65606, 52448, 69153, 13592, 1990, 21896, 323, 4819, 1778, 439, 4092, 12248, 11, 304, 35940, 76730, 315, 2849, 1404, 323, 50917, 7917, 527, 2103, 11774, 369, 94612, 3495, 220, 1032, 662, 92663, 2849, 60852, 32885, 527, 2536, 1773, 16890, 4633, 323, 9526, 19440, 220, 975, 719, 1217, 22658, 3241, 6067, 430, 1005, 5780, 6975, 26249, 527, 24084, 311, 3493, 16945, 11, 1579, 43847, 631, 2849, 60852, 323, 15194, 220, 868, 1174, 220, 845, 662, 35390, 26006, 311, 20371, 97742, 220, 1114, 2187, 279, 3135, 315, 5370, 60852, 3241, 311, 387, 18751, 449, 19303, 15194, 26249, 323, 3493, 9302, 8082, 7526, 311, 8720, 2225, 60852, 323, 2849, 14242, 13, 10541, 279, 892, 4101, 369, 3738, 2849, 6012, 11, 1778, 439, 2849, 3158, 323, 28029, 488, 11, 649, 387, 12882, 11, 279, 33289, 323, 6492, 315, 53944, 892, 4101, 374, 539, 2949, 279, 7036, 315, 279, 20371, 97742, 3241, 13, 43551, 315, 279, 34156, 7917, 17432, 374, 17436, 439, 7917, 527, 34156, 369, 2204, 5219, 315, 14418, 449, 14418, 7554, 1405, 7917, 5387, 279, 2115, 315, 1684, 13, 1115, 706, 8967, 430, 6492, 315, 904, 28532, 4519, 706, 1027, 7347, 311, 9302, 8082, 13, 14299, 47, 383, 23725, 988, 279, 892, 4101, 323, 1243, 48517, 264, 8521, 1396, 315, 7482, 430, 3752, 1082, 1855, 4668, 753, 892, 4101, 12, 279, 4519, 315, 4519, 0, 5810, 584, 3118, 14299, 47, 383, 11, 264, 5497, 18324, 66994, 430, 5829, 279, 2612, 315, 60852, 323, 15194, 3241, 311, 3493, 459, 16781, 1160, 315, 4519, 430, 3752, 1082, 4442, 304, 279, 7917, 529, 11341, 323, 17432, 927, 892, 13, 8572, 4147, 4668, 6727, 6276, 279, 1455, 68763, 7482, 369, 264, 4040, 16945, 311, 387, 11054, 13, 4314, 28532, 7482, 76498, 2849, 79612, 11, 10651, 323, 30295, 323, 7664, 37015, 4442, 323, 649, 387, 1511, 311, 57482, 3752, 1082, 323, 49229, 3927, 7917, 439, 1664, 439, 2849, 22673, 13, 2057, 6106, 24473, 10484, 2461, 315, 2849, 79612, 323, 3937, 1429, 11, 323, 311, 8891, 3682, 35693, 4455, 1778, 439, 5568, 10934, 323, 95874, 11, 433, 374, 16595, 430, 13422, 315, 77772, 60852, 323, 15194, 527, 7108, 505, 828, 7437, 4972, 311, 52452, 6492, 5528, 220, 972, 662, 14881, 17065, 315, 1778, 6103, 374, 17345, 23791, 88092, 11, 8104, 994, 892, 2922, 79390, 1935, 2035, 927, 3892, 2919, 13, 2057, 31127, 1082, 828, 4367, 369, 52452, 6492, 11, 14299, 47, 383, 5764, 279, 18324, 323, 17065, 315, 77772, 2849, 23546, 36572, 555, 50504, 60852, 323, 15194, 13, 1226, 20461, 279, 1005, 315, 40126, 24790, 369, 13687, 20212, 315, 35693, 82423, 323, 59454, 26249, 369, 22654, 315, 98882, 75605, 13, 1226, 39039, 1463, 14299, 47, 383, 555, 3752, 3876, 279, 17432, 315, 83920, 323, 62730, 88186, 17659, 9572, 7917, 505, 281, 1919, 331, 12968, 892, 2922, 7629, 6946, 13, 32541, 22018, 10474, 5448, 320, 48, 1932, 8, 220, 777, 1174, 220, 508, 1174, 220, 1691, 5766, 904, 97332, 38973, 18713, 65916, 315, 279, 7917, 719, 60852, 13708, 649, 387, 11754, 555, 11293, 12062, 304, 21261, 1990, 7917, 323, 4092, 304, 12593, 311, 74864, 10278, 6427, 13, 1226, 1501, 430, 1057, 5528, 7946, 44917, 323, 4148, 264, 7187, 315, 58889, 7162, 86045, 7917, 11, 18899, 828, 743, 4367, 13, 75740, 5848, 323, 18003, 950, 4442, 36572, 555, 8590, 1605, 88886, 11, 8104, 520, 3428, 5623, 20545, 11, 527, 3629, 810, 27545, 1109, 1884, 430, 60541, 12742, 2849, 4595, 323, 584, 20461, 279, 5845, 315, 14299, 47, 383, 311, 9651, 10765, 892, 4101, 12062, 36572, 555, 62730, 6514, 11, 449, 279, 12146, 7482, 39858, 47952, 5199, 1524, 994, 539, 40635, 555, 8071, 13, 578, 84140, 315, 98882, 5623, 2077, 323, 279, 3575, 315, 5623, 13957, 4726, 62425, 1057, 12146, 3851, 13, 578, 5845, 311, 10765, 68763, 4519, 1990, 12020, 323, 83920, 7917, 649, 2187, 28598, 18468, 315, 1054, 6414, 15204, 55857, 863, 7917, 1778, 439, 1884, 430, 15575, 35693, 5623, 13957, 13, 15903, 8990, 315, 1778, 4519, 1436, 97298, 349, 279, 16940, 24156, 24717, 8647, 369, 62730, 13957, 323, 9572, 76293, 13, 1226, 9788, 279, 10737, 2968, 315, 14299, 47, 383, 449, 2225, 264, 2204, 2849, 955, 323, 264, 2204, 5623, 6514, 323, 1501, 430, 7482, 527, 4183, 4184, 311, 22772, 4787, 11, 41891, 311, 6012, 315, 279, 2849, 955, 323, 5623, 17383, 315, 1957, 13, 14299, 47, 383, 374, 128257, 198, 128256, 78191, 198, 34242, 3025, 311, 23846, 323, 3839, 279, 1648, 7917, 2349, 323, 2274, 927, 892, 374, 264, 16595, 961, 315, 12624, 323, 6593, 3495, 13, 4212, 2922, 7629, 7978, 315, 7917, 649, 1501, 603, 1268, 7917, 617, 85922, 304, 3738, 22484, 477, 872, 25481, 311, 9434, 34453, 11, 1778, 439, 6593, 6514, 13, 1115, 2038, 649, 33505, 264, 3177, 389, 1268, 8624, 43653, 323, 3249, 1063, 6978, 6, 7917, 656, 539, 6013, 311, 6514, 1778, 439, 62730, 13, 47170, 279, 4500, 315, 3230, 2849, 4519, 374, 264, 5107, 1920, 4869, 11, 14248, 520, 279, 26280, 315, 40023, 323, 50895, 520, 279, 3907, 315, 4356, 617, 1457, 3549, 264, 1949, 7528, 5507, 902, 649, 1520, 13, 578, 3241, 6462, 11, 2663, 14299, 47, 383, 11, 374, 279, 1176, 315, 1202, 3169, 439, 433, 649, 8819, 264, 4101, 315, 4519, 505, 264, 2849, 304, 264, 892, 2922, 7629, 4007, 323, 70755, 279, 7917, 3196, 389, 872, 7865, 323, 5419, 6070, 13, 578, 6462, 1101, 9651, 29260, 6103, 304, 2849, 15194, 311, 7417, 828, 4367, 13, 763, 264, 4007, 4756, 5936, 220, 18, 304, 22037, 26545, 11, 14299, 47, 383, 12722, 11054, 1403, 2204, 7437, 315, 17659, 9572, 7917, 87671, 902, 574, 12020, 449, 62730, 11217, 323, 279, 1023, 902, 574, 539, 13, 23611, 287, 279, 1403, 5315, 11, 14299, 47, 383, 574, 1101, 3025, 311, 10765, 264, 13893, 31785, 27084, 315, 12020, 7917, 13, 2956, 1093, 420, 374, 8104, 3062, 304, 8830, 17659, 9572, 323, 30829, 1202, 6514, 11, 439, 8590, 4692, 4011, 17037, 11767, 311, 1375, 7629, 304, 17659, 9572, 6978, 13, 14299, 47, 383, 1436, 1101, 617, 4726, 15325, 8522, 304, 11618, 1778, 439, 5623, 23061, 323, 279, 20212, 315, 8624, 95350, 13, 30928, 468, 53026, 505, 279, 6011, 315, 40023, 1071, 11, 330, 2181, 374, 49737, 13548, 311, 387, 3025, 311, 76498, 2849, 7865, 927, 892, 304, 1778, 31069, 7872, 13, 330, 32, 2763, 315, 2653, 990, 706, 8208, 1139, 3339, 14299, 47, 383, 1217, 22658, 323, 94848, 311, 502, 8522, 779, 584, 1427, 4741, 311, 9298, 1268, 1057, 66994, 690, 387, 1511, 555, 279, 4029, 13, 1226, 57791, 14299, 47, 383, 5737, 264, 60850, 3560, 304, 1057, 8830, 315, 35693, 5623, 2077, 439, 1664, 439, 279, 5627, 304, 902, 7917, 19570, 449, 832, 2500, 11, 4669, 43080, 439, 1664, 439, 1555, 2167, 3729, 1210, 14299, 47, 383, 374, 26662, 2561, 2930, 323, 690, 1629, 389, 904, 10565, 1887, 323, 4131, 449, 264, 11630, 323, 459, 7754, 2835, 13, 220, 128257, 198 ]

1,645

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract A great challenge in current quantum science and technology research is to realize artificial systems of a large number of individually controlled quantum bits for applications in quantum computing and quantum simulation. Many experimental platforms are being explored, including solid-state systems, such as superconducting circuits 1 or quantum dots 2 , and atomic, molecular and optical systems, such as photons, trapped ions or neutral atoms 3 , 4 , 5 , 6 , 7 . The latter offer inherently identical qubits that are well decoupled from the environment and could provide synthetic structures scalable to hundreds of qubits or more 8 . Quantum-gas microscopes 9 allow the realization of two-dimensional regular lattices of hundreds of atoms, and large, fully loaded arrays of about 50 microtraps (or ‘optical tweezers’) with individual control are already available in one 10 and two 11 dimensions. Ultimately, however, accessing the third dimension while keeping single-atom control will be required, both for scaling to large numbers and for extending the range of models amenable to quantum simulation. Here we report the assembly of defect-free, arbitrarily shaped three-dimensional arrays, containing up to 72 single atoms. We use holographic methods and fast, programmable moving tweezers to arrange—atom by atom and plane by plane—initially disordered arrays into target structures of almost any geometry. These results present the prospect of quantum simulation with tens of qubits arbitrarily arranged in space and show that realizing systems of hundreds of individually controlled qubits is within reach using current technology. Main Three-dimensional atomic arrays at half filling have been obtained using optical lattices with large spacings 12 , which facilitate single-site addressability and atom manipulation 13 . As an alternative approach, here we use programmable holographic optical tweezers to create three-dimensional (3D) arrays of traps. Holographic methods offer the advantage of higher tunability of the lattice geometry because the design of optical potential landscapes is reconfigurable and only limited by diffraction 14 , 15 , 16 . In our experiment 14 , arbitrarily designed arrays of up to about 120 traps are generated by imprinting a phase pattern on a dipole trap beam at 850 nm with a spatial light modulator (Fig. 1a ). This phase mask is calculated using the 3D Gerchberg–Saxton algorithm, simplified for the case of point traps 17 . The beam is then focused with a high-numerical-aperture (0.5) aspheric lens under vacuum, creating individual optical tweezers with a measured 1/e 2 radius of about 1.1 μm and a Rayleigh length of approximately 5 μm. After recollimation with a second aspheric lens, the intensity of the trapping light is measured using a standard charge-coupled device (CCD) camera. An electrically tunable lens (ETL1) in the imaging path allows us to acquire series of stack images along the optical axis z , from which we reconstruct the full 3D intensity distribution. The imaging system covers a z -direction scan range of 200 μm. Fig. 1: Experimental setup and trap images. a , We combine a spatial light modulator (SLM) and a high-numerical-aperture aspheric lens (AL) under vacuum to generate arbitrary 3D arrays of traps. The intensity distribution in the focal plane is measured with the aid of a second aspheric lens, a mirror (M) and a diagnostics CCD camera (d-CCD). The fluorescence of the atoms in the traps at 780 nm is separated from the dipole trap beam with a dichroic mirror (DM) and detected using an electron-multiplying CCD camera (EMCCD). For atom assembly we use moving tweezers superimposed on the trap beam with a polarizing beam splitter (PBS). This extra beam is deflected in the plane perpendicular to the beam propagation with a 2D acousto-optical deflector (AOD), and its focus can be displaced axially by changing the focal length of an electrically tunable lens (ETL3). The remaining electrically tunable lenses (ETL1 and ETL2) in the camera paths allow imaging of different planes along z . The inset depicts the intensity distribution of the trap light forming a bilayer array (red) and the action of the moving tweezers on an individual atom (purple). b–d , Intensity reconstructions of exemplary 3D patterns obtained from a collection of z -stack images taken with the diagnostics CCD camera. The regions of maximum intensity form a trefoil knot ( b ), a 5 × 5 × 5 cubic array ( c ) and a C 320 fullerene-like structure ( d ). The dimensions, L x , L y , L z , of the images are the same in all the examples. Full size image Figure 1b–d shows some examples of patterns suitable for experiments with single atoms. The images are reconstructed using a maximum-intensity projection method 18 from 200 z images obtained with the diagnostics CCD camera. With about 3.5 mW of power per trap we reach depths of U 0 / k B ≈ 1 mK, where k B is the Boltzmann constant, and radial (longitudinal) trapping frequencies of around 100 kHz (20 kHz). We produce highly uniform microtrap potentials (with peak intensities differing by less than 5% root mean square) via a closed-loop optimization 14 . Rubidium-87 atoms are then loaded in the traps from a magneto-optical trap (MOT), with a final temperature of 25 μK. We detect the occupancy of each trap by collecting the fluorescence of the atoms at 780 nm with an electron-multiplying CCD camera for 50 ms. A second tunable lens (ETL2) in the imaging path is used to focus the fluorescence of different atom planes. In Fig. 2 we show the fluorescence of single atoms trapped in various complex 3D structures, some of which are relevant, for instance, to the study of non-trivial properties of Chern insulators 19 , 20 , 21 . Each example is reconstructed from a series of 100 z -stack images covering an axial range of about 120 μm. With no further action, these arrays are randomly loaded with a filling fraction of about 0.5; we thus average the fluorescence signal over 300 frames to reveal the geometry of the structures. Fig. 2:", "role": "user" }, { "content": "A team of researchers at Centre National de la Recherche Scientifique (CNRS) in France has developed a technique for arranging cold atoms into useful 3-D arrayed structures. In their paper published in the journal Nature, the group describes their technique and the ways the structures could be useful. As work toward the development of a functional quantum computer continues, groups of scientists have worked on technologies required for the development of such a machine. One such requirement is the development of atomic structures—if atoms are to serve as qubits, they must be arranged in precise and useful ways that allow for interactions between one another. Most envision such arrangements to consist of 3-D arrayed structures. In this new effort, the researchers report on a technique they have developed to build 3-D atomic structures in arrayed shapes likely to be needed for quantum computer applications. The technique involves building microtraps using spatially modulated light. Such traps and other instruments use the energy in light to move single neutral atoms around in desired ways and then to hold them in place. To build a desired structure, the group moved a small mass of rubidium atoms into a trap that filled it up just halfway. Doing so situated the atoms in random spots inside the trap. They then activated deflectors that used both sound and light to serve as tweezers that they used to move the atoms in the trap in desired ways. After that, they used the tweezers to grab single atoms outside of the trap and placed them into desired spots inside the trap. The end result was a 3-D structure in a desired shape. The researchers note that their technique allows for creating 3-D structures in a variety of shapes, all of which are precisely ordered. Notably, the results are free of defects because each atom is placed individually into the structure. To prove the effectiveness of their technique, the researchers bathed a structure they had built with light and studied the result with a CCD camera—it was able to highlight the fluorescence of the rubidium atoms showing their locations within the microtrap. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract A great challenge in current quantum science and technology research is to realize artificial systems of a large number of individually controlled quantum bits for applications in quantum computing and quantum simulation. Many experimental platforms are being explored, including solid-state systems, such as superconducting circuits 1 or quantum dots 2 , and atomic, molecular and optical systems, such as photons, trapped ions or neutral atoms 3 , 4 , 5 , 6 , 7 . The latter offer inherently identical qubits that are well decoupled from the environment and could provide synthetic structures scalable to hundreds of qubits or more 8 . Quantum-gas microscopes 9 allow the realization of two-dimensional regular lattices of hundreds of atoms, and large, fully loaded arrays of about 50 microtraps (or ‘optical tweezers’) with individual control are already available in one 10 and two 11 dimensions. Ultimately, however, accessing the third dimension while keeping single-atom control will be required, both for scaling to large numbers and for extending the range of models amenable to quantum simulation. Here we report the assembly of defect-free, arbitrarily shaped three-dimensional arrays, containing up to 72 single atoms. We use holographic methods and fast, programmable moving tweezers to arrange—atom by atom and plane by plane—initially disordered arrays into target structures of almost any geometry. These results present the prospect of quantum simulation with tens of qubits arbitrarily arranged in space and show that realizing systems of hundreds of individually controlled qubits is within reach using current technology. Main Three-dimensional atomic arrays at half filling have been obtained using optical lattices with large spacings 12 , which facilitate single-site addressability and atom manipulation 13 . As an alternative approach, here we use programmable holographic optical tweezers to create three-dimensional (3D) arrays of traps. Holographic methods offer the advantage of higher tunability of the lattice geometry because the design of optical potential landscapes is reconfigurable and only limited by diffraction 14 , 15 , 16 . In our experiment 14 , arbitrarily designed arrays of up to about 120 traps are generated by imprinting a phase pattern on a dipole trap beam at 850 nm with a spatial light modulator (Fig. 1a ). This phase mask is calculated using the 3D Gerchberg–Saxton algorithm, simplified for the case of point traps 17 . The beam is then focused with a high-numerical-aperture (0.5) aspheric lens under vacuum, creating individual optical tweezers with a measured 1/e 2 radius of about 1.1 μm and a Rayleigh length of approximately 5 μm. After recollimation with a second aspheric lens, the intensity of the trapping light is measured using a standard charge-coupled device (CCD) camera. An electrically tunable lens (ETL1) in the imaging path allows us to acquire series of stack images along the optical axis z , from which we reconstruct the full 3D intensity distribution. The imaging system covers a z -direction scan range of 200 μm. Fig. 1: Experimental setup and trap images. a , We combine a spatial light modulator (SLM) and a high-numerical-aperture aspheric lens (AL) under vacuum to generate arbitrary 3D arrays of traps. The intensity distribution in the focal plane is measured with the aid of a second aspheric lens, a mirror (M) and a diagnostics CCD camera (d-CCD). The fluorescence of the atoms in the traps at 780 nm is separated from the dipole trap beam with a dichroic mirror (DM) and detected using an electron-multiplying CCD camera (EMCCD). For atom assembly we use moving tweezers superimposed on the trap beam with a polarizing beam splitter (PBS). This extra beam is deflected in the plane perpendicular to the beam propagation with a 2D acousto-optical deflector (AOD), and its focus can be displaced axially by changing the focal length of an electrically tunable lens (ETL3). The remaining electrically tunable lenses (ETL1 and ETL2) in the camera paths allow imaging of different planes along z . The inset depicts the intensity distribution of the trap light forming a bilayer array (red) and the action of the moving tweezers on an individual atom (purple). b–d , Intensity reconstructions of exemplary 3D patterns obtained from a collection of z -stack images taken with the diagnostics CCD camera. The regions of maximum intensity form a trefoil knot ( b ), a 5 × 5 × 5 cubic array ( c ) and a C 320 fullerene-like structure ( d ). The dimensions, L x , L y , L z , of the images are the same in all the examples. Full size image Figure 1b–d shows some examples of patterns suitable for experiments with single atoms. The images are reconstructed using a maximum-intensity projection method 18 from 200 z images obtained with the diagnostics CCD camera. With about 3.5 mW of power per trap we reach depths of U 0 / k B ≈ 1 mK, where k B is the Boltzmann constant, and radial (longitudinal) trapping frequencies of around 100 kHz (20 kHz). We produce highly uniform microtrap potentials (with peak intensities differing by less than 5% root mean square) via a closed-loop optimization 14 . Rubidium-87 atoms are then loaded in the traps from a magneto-optical trap (MOT), with a final temperature of 25 μK. We detect the occupancy of each trap by collecting the fluorescence of the atoms at 780 nm with an electron-multiplying CCD camera for 50 ms. A second tunable lens (ETL2) in the imaging path is used to focus the fluorescence of different atom planes. In Fig. 2 we show the fluorescence of single atoms trapped in various complex 3D structures, some of which are relevant, for instance, to the study of non-trivial properties of Chern insulators 19 , 20 , 21 . Each example is reconstructed from a series of 100 z -stack images covering an axial range of about 120 μm. With no further action, these arrays are randomly loaded with a filling fraction of about 0.5; we thus average the fluorescence signal over 300 frames to reveal the geometry of the structures. Fig. 2:<|im_end|> <|im_start|>assistant A team of researchers at Centre National de la Recherche Scientifique (CNRS) in France has developed a technique for arranging cold atoms into useful 3-D arrayed structures. In their paper published in the journal Nature, the group describes their technique and the ways the structures could be useful. As work toward the development of a functional quantum computer continues, groups of scientists have worked on technologies required for the development of such a machine. One such requirement is the development of atomic structures—if atoms are to serve as qubits, they must be arranged in precise and useful ways that allow for interactions between one another. Most envision such arrangements to consist of 3-D arrayed structures. In this new effort, the researchers report on a technique they have developed to build 3-D atomic structures in arrayed shapes likely to be needed for quantum computer applications. The technique involves building microtraps using spatially modulated light. Such traps and other instruments use the energy in light to move single neutral atoms around in desired ways and then to hold them in place. To build a desired structure, the group moved a small mass of rubidium atoms into a trap that filled it up just halfway. Doing so situated the atoms in random spots inside the trap. They then activated deflectors that used both sound and light to serve as tweezers that they used to move the atoms in the trap in desired ways. After that, they used the tweezers to grab single atoms outside of the trap and placed them into desired spots inside the trap. The end result was a 3-D structure in a desired shape. The researchers note that their technique allows for creating 3-D structures in a variety of shapes, all of which are precisely ordered. Notably, the results are free of defects because each atom is placed individually into the structure. To prove the effectiveness of their technique, the researchers bathed a structure they had built with light and studied the result with a CCD camera—it was able to highlight the fluorescence of the rubidium atoms showing their locations within the microtrap. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 362, 2294, 8815, 304, 1510, 31228, 8198, 323, 5557, 3495, 374, 311, 13383, 21075, 6067, 315, 264, 3544, 1396, 315, 32399, 14400, 31228, 9660, 369, 8522, 304, 31228, 25213, 323, 31228, 19576, 13, 9176, 22772, 15771, 527, 1694, 36131, 11, 2737, 6573, 21395, 6067, 11, 1778, 439, 2307, 77752, 287, 46121, 220, 16, 477, 31228, 32094, 220, 17, 1174, 323, 25524, 11, 31206, 323, 29393, 6067, 11, 1778, 439, 89235, 11, 31691, 65125, 477, 21277, 33299, 220, 18, 1174, 220, 19, 1174, 220, 20, 1174, 220, 21, 1174, 220, 22, 662, 578, 15629, 3085, 49188, 20086, 2874, 82502, 430, 527, 1664, 1654, 283, 50185, 505, 279, 4676, 323, 1436, 3493, 28367, 14726, 69311, 311, 11758, 315, 2874, 82502, 477, 810, 220, 23, 662, 56413, 2427, 300, 8162, 82025, 220, 24, 2187, 279, 49803, 315, 1403, 33520, 5912, 326, 1617, 1238, 315, 11758, 315, 33299, 11, 323, 3544, 11, 7373, 6799, 18893, 315, 922, 220, 1135, 8162, 376, 2690, 320, 269, 3451, 2985, 950, 14887, 10333, 388, 96206, 449, 3927, 2585, 527, 2736, 2561, 304, 832, 220, 605, 323, 1403, 220, 806, 15696, 13, 55106, 11, 4869, 11, 32888, 279, 4948, 13167, 1418, 10494, 3254, 12, 22612, 2585, 690, 387, 2631, 11, 2225, 369, 28041, 311, 3544, 5219, 323, 369, 33459, 279, 2134, 315, 4211, 1097, 12837, 311, 31228, 19576, 13, 5810, 584, 1934, 279, 14956, 315, 23011, 12862, 11, 86757, 27367, 2380, 33520, 18893, 11, 8649, 709, 311, 220, 5332, 3254, 33299, 13, 1226, 1005, 72927, 79173, 5528, 323, 5043, 11, 56586, 481, 7366, 14887, 10333, 388, 311, 31993, 2345, 22612, 555, 19670, 323, 11277, 555, 11277, 2345, 9613, 398, 834, 10767, 18893, 1139, 2218, 14726, 315, 4661, 904, 17484, 13, 4314, 3135, 3118, 279, 22199, 315, 31228, 19576, 449, 22781, 315, 2874, 82502, 86757, 28902, 304, 3634, 323, 1501, 430, 44114, 6067, 315, 11758, 315, 32399, 14400, 2874, 82502, 374, 2949, 5662, 1701, 1510, 5557, 13, 4802, 14853, 33520, 25524, 18893, 520, 4376, 21973, 617, 1027, 12457, 1701, 29393, 326, 1617, 1238, 449, 3544, 100108, 826, 220, 717, 1174, 902, 28696, 3254, 29654, 2686, 2968, 323, 19670, 34786, 220, 1032, 662, 1666, 459, 10778, 5603, 11, 1618, 584, 1005, 56586, 481, 72927, 79173, 29393, 14887, 10333, 388, 311, 1893, 2380, 33520, 320, 18, 35, 8, 18893, 315, 45660, 13, 473, 1640, 79173, 5528, 3085, 279, 9610, 315, 5190, 11716, 2968, 315, 279, 55372, 17484, 1606, 279, 2955, 315, 29393, 4754, 55890, 374, 312, 1710, 18835, 323, 1193, 7347, 555, 3722, 16597, 220, 975, 1174, 220, 868, 1174, 220, 845, 662, 763, 1057, 9526, 220, 975, 1174, 86757, 6319, 18893, 315, 709, 311, 922, 220, 4364, 45660, 527, 8066, 555, 79967, 287, 264, 10474, 5497, 389, 264, 24522, 1286, 23709, 24310, 520, 220, 16217, 26807, 449, 264, 29079, 3177, 1491, 10733, 320, 30035, 13, 220, 16, 64, 7609, 1115, 10474, 7056, 374, 16997, 1701, 279, 220, 18, 35, 20524, 331, 7881, 4235, 50, 710, 783, 12384, 11, 44899, 369, 279, 1162, 315, 1486, 45660, 220, 1114, 662, 578, 24310, 374, 1243, 10968, 449, 264, 1579, 32294, 261, 950, 46256, 42947, 320, 15, 13, 20, 8, 439, 33349, 18848, 1234, 29302, 11, 6968, 3927, 29393, 14887, 10333, 388, 449, 264, 17303, 220, 16, 16954, 220, 17, 10801, 315, 922, 220, 16, 13, 16, 33983, 76, 323, 264, 13558, 64069, 3160, 315, 13489, 220, 20, 33983, 76, 13, 4740, 1421, 980, 5582, 449, 264, 2132, 439, 33349, 18848, 11, 279, 21261, 315, 279, 93669, 3177, 374, 17303, 1701, 264, 5410, 6900, 1824, 283, 50185, 3756, 320, 3791, 35, 8, 6382, 13, 1556, 9249, 750, 11716, 481, 18848, 320, 1372, 43, 16, 8, 304, 279, 32758, 1853, 6276, 603, 311, 21953, 4101, 315, 5729, 5448, 3235, 279, 29393, 8183, 1167, 1174, 505, 902, 584, 44928, 279, 2539, 220, 18, 35, 21261, 8141, 13, 578, 32758, 1887, 14861, 264, 1167, 482, 19612, 8737, 2134, 315, 220, 1049, 33983, 76, 13, 23966, 13, 220, 16, 25, 57708, 6642, 323, 23709, 5448, 13, 264, 1174, 1226, 16343, 264, 29079, 3177, 1491, 10733, 320, 8143, 44, 8, 323, 264, 1579, 32294, 261, 950, 46256, 42947, 439, 33349, 18848, 320, 984, 8, 1234, 29302, 311, 7068, 25142, 220, 18, 35, 18893, 315, 45660, 13, 578, 21261, 8141, 304, 279, 42199, 11277, 374, 17303, 449, 279, 12576, 315, 264, 2132, 439, 33349, 18848, 11, 264, 18327, 320, 44, 8, 323, 264, 50518, 93833, 6382, 320, 67, 12, 3791, 35, 570, 578, 97332, 315, 279, 33299, 304, 279, 45660, 520, 220, 19423, 26807, 374, 19180, 505, 279, 24522, 1286, 23709, 24310, 449, 264, 29953, 299, 292, 18327, 320, 8561, 8, 323, 16914, 1701, 459, 17130, 1474, 10046, 6852, 93833, 6382, 320, 2783, 3791, 35, 570, 1789, 19670, 14956, 584, 1005, 7366, 14887, 10333, 388, 2307, 318, 3950, 389, 279, 23709, 24310, 449, 264, 25685, 4954, 24310, 74086, 320, 83609, 570, 1115, 5066, 24310, 374, 711, 2258, 304, 279, 11277, 77933, 311, 279, 24310, 54743, 449, 264, 220, 17, 35, 1645, 26169, 78, 57212, 950, 711, 28769, 320, 32, 2114, 705, 323, 1202, 5357, 649, 387, 49246, 3944, 34575, 555, 10223, 279, 42199, 3160, 315, 459, 9249, 750, 11716, 481, 18848, 320, 1372, 43, 18, 570, 578, 9861, 9249, 750, 11716, 481, 36057, 320, 1372, 43, 16, 323, 469, 13778, 17, 8, 304, 279, 6382, 13006, 2187, 32758, 315, 2204, 25761, 3235, 1167, 662, 578, 55959, 62991, 279, 21261, 8141, 315, 279, 23709, 3177, 30164, 264, 20934, 1155, 1358, 320, 1171, 8, 323, 279, 1957, 315, 279, 7366, 14887, 10333, 388, 389, 459, 3927, 19670, 320, 57607, 570, 293, 4235, 67, 1174, 1357, 8127, 16456, 20232, 315, 77381, 220, 18, 35, 12912, 12457, 505, 264, 4526, 315, 1167, 482, 7848, 5448, 4529, 449, 279, 50518, 93833, 6382, 13, 578, 13918, 315, 7340, 21261, 1376, 264, 4353, 100057, 51900, 320, 293, 7026, 264, 220, 20, 25800, 220, 20, 25800, 220, 20, 41999, 1358, 320, 272, 883, 323, 264, 356, 220, 9588, 88018, 1994, 12970, 6070, 320, 294, 7609, 578, 15696, 11, 445, 865, 1174, 445, 379, 1174, 445, 1167, 1174, 315, 279, 5448, 527, 279, 1890, 304, 682, 279, 10507, 13, 8797, 1404, 2217, 19575, 220, 16, 65, 4235, 67, 5039, 1063, 10507, 315, 12912, 14791, 369, 21896, 449, 3254, 33299, 13, 578, 5448, 527, 83104, 1701, 264, 7340, 20653, 8127, 22343, 1749, 220, 972, 505, 220, 1049, 1167, 5448, 12457, 449, 279, 50518, 93833, 6382, 13, 3161, 922, 220, 18, 13, 20, 296, 54, 315, 2410, 824, 23709, 584, 5662, 43957, 315, 549, 220, 15, 611, 597, 426, 118792, 220, 16, 296, 42, 11, 1405, 597, 426, 374, 279, 47047, 89, 18022, 6926, 11, 323, 57936, 320, 4930, 13138, 992, 8, 93669, 34873, 315, 2212, 220, 1041, 70726, 320, 508, 70726, 570, 1226, 8356, 7701, 14113, 8162, 57014, 95358, 320, 4291, 16557, 25228, 1385, 61469, 555, 2753, 1109, 220, 20, 4, 3789, 3152, 9518, 8, 4669, 264, 8036, 61766, 26329, 220, 975, 662, 13134, 307, 2411, 12, 4044, 33299, 527, 1243, 6799, 304, 279, 45660, 505, 264, 8622, 11269, 57212, 950, 23709, 320, 44, 1831, 705, 449, 264, 1620, 9499, 315, 220, 914, 33983, 42, 13, 1226, 11388, 279, 66419, 315, 1855, 23709, 555, 26984, 279, 97332, 315, 279, 33299, 520, 220, 19423, 26807, 449, 459, 17130, 1474, 10046, 6852, 93833, 6382, 369, 220, 1135, 10030, 13, 362, 2132, 11716, 481, 18848, 320, 1372, 43, 17, 8, 304, 279, 32758, 1853, 374, 1511, 311, 5357, 279, 97332, 315, 2204, 19670, 25761, 13, 763, 23966, 13, 220, 17, 584, 1501, 279, 97332, 315, 3254, 33299, 31691, 304, 5370, 6485, 220, 18, 35, 14726, 11, 1063, 315, 902, 527, 9959, 11, 369, 2937, 11, 311, 279, 4007, 315, 2536, 10398, 27756, 6012, 315, 91759, 1672, 42391, 220, 777, 1174, 220, 508, 1174, 220, 1691, 662, 9062, 3187, 374, 83104, 505, 264, 4101, 315, 220, 1041, 1167, 482, 7848, 5448, 18702, 459, 98280, 2134, 315, 922, 220, 4364, 33983, 76, 13, 3161, 912, 4726, 1957, 11, 1521, 18893, 527, 27716, 6799, 449, 264, 21973, 19983, 315, 922, 220, 15, 13, 20, 26, 584, 8617, 5578, 279, 97332, 8450, 927, 220, 3101, 14418, 311, 16805, 279, 17484, 315, 279, 14726, 13, 23966, 13, 220, 17, 25, 128257, 198, 128256, 78191, 198, 32, 2128, 315, 12074, 520, 14821, 5165, 409, 1208, 1050, 30610, 21302, 52760, 320, 29768, 11706, 8, 304, 9822, 706, 8040, 264, 15105, 369, 77218, 9439, 33299, 1139, 5505, 220, 18, 9607, 1358, 291, 14726, 13, 763, 872, 5684, 4756, 304, 279, 8486, 22037, 11, 279, 1912, 16964, 872, 15105, 323, 279, 5627, 279, 14726, 1436, 387, 5505, 13, 1666, 990, 9017, 279, 4500, 315, 264, 16003, 31228, 6500, 9731, 11, 5315, 315, 14248, 617, 6575, 389, 14645, 2631, 369, 279, 4500, 315, 1778, 264, 5780, 13, 3861, 1778, 16686, 374, 279, 4500, 315, 25524, 14726, 90863, 33299, 527, 311, 8854, 439, 2874, 82502, 11, 814, 2011, 387, 28902, 304, 24473, 323, 5505, 5627, 430, 2187, 369, 22639, 1990, 832, 2500, 13, 7648, 48146, 1778, 28904, 311, 6824, 315, 220, 18, 9607, 1358, 291, 14726, 13, 763, 420, 502, 5149, 11, 279, 12074, 1934, 389, 264, 15105, 814, 617, 8040, 311, 1977, 220, 18, 9607, 25524, 14726, 304, 1358, 291, 21483, 4461, 311, 387, 4460, 369, 31228, 6500, 8522, 13, 578, 15105, 18065, 4857, 8162, 376, 2690, 1701, 29079, 398, 1491, 7913, 3177, 13, 15483, 45660, 323, 1023, 24198, 1005, 279, 4907, 304, 3177, 311, 3351, 3254, 21277, 33299, 2212, 304, 12974, 5627, 323, 1243, 311, 3412, 1124, 304, 2035, 13, 2057, 1977, 264, 12974, 6070, 11, 279, 1912, 7882, 264, 2678, 3148, 315, 10485, 307, 2411, 33299, 1139, 264, 23709, 430, 10409, 433, 709, 1120, 42436, 13, 44245, 779, 31183, 279, 33299, 304, 4288, 19300, 4871, 279, 23709, 13, 2435, 1243, 22756, 84040, 1105, 430, 1511, 2225, 5222, 323, 3177, 311, 8854, 439, 14887, 10333, 388, 430, 814, 1511, 311, 3351, 279, 33299, 304, 279, 23709, 304, 12974, 5627, 13, 4740, 430, 11, 814, 1511, 279, 14887, 10333, 388, 311, 11894, 3254, 33299, 4994, 315, 279, 23709, 323, 9277, 1124, 1139, 12974, 19300, 4871, 279, 23709, 13, 578, 842, 1121, 574, 264, 220, 18, 9607, 6070, 304, 264, 12974, 6211, 13, 578, 12074, 5296, 430, 872, 15105, 6276, 369, 6968, 220, 18, 9607, 14726, 304, 264, 8205, 315, 21483, 11, 682, 315, 902, 527, 24559, 11713, 13, 2876, 2915, 11, 279, 3135, 527, 1949, 315, 42655, 1606, 1855, 19670, 374, 9277, 32399, 1139, 279, 6070, 13, 2057, 12391, 279, 27375, 315, 872, 15105, 11, 279, 12074, 9061, 291, 264, 6070, 814, 1047, 5918, 449, 3177, 323, 20041, 279, 1121, 449, 264, 93833, 6382, 44603, 574, 3025, 311, 11415, 279, 97332, 315, 279, 10485, 307, 2411, 33299, 9204, 872, 10687, 2949, 279, 8162, 57014, 13, 220, 128257, 198 ]

1,808

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract The near-Earth asteroid (3200) Phaethon is the parent body of the Geminid meteor stream. Phaethon is also an active asteroid with a very blue spectrum. We conducted polarimetric observations of this asteroid over a wide range of solar phase angles α during its close approach to the Earth in autumn 2016. Our observation revealed that Phaethon exhibits extremely large linear polarization: P = 50.0 ± 1.1% at α = 106.5°, and its maximum is even larger. The strong polarization implies that Phaethon’s geometric albedo is lower than the current estimate obtained through radiometric observation. This possibility stems from the potential uncertainty in Phaethon’s absolute magnitude. An alternative possibility is that relatively large grains (~300 μm in diameter, presumably due to extensive heating near its perihelion) dominate this asteroid’s surface. In addition, the asteroid’s surface porosity, if it is substantially large, can also be an effective cause of this polarization. Introduction (3200) Phaethon is a well-studied near-Earth asteroid. Ever since its discovery by a survey using the Infrared Astronomical Satellite (IRAS) in 1983 1 , this asteroid has exhibited several interesting characteristics of small solar system bodies. Phaethon is an Apollo-type near-Earth asteroid that has large inclination \$(i \\sim 22^\\circ )\$ , large eccentricity \$(e \\sim 0.89)\$ , and small perihelion distance \$(q \\sim 0.14{\\kern 1pt} {\\mathrm{au}})\$ . This asteroid is also recognized as the parent body of the Geminid meteor stream due to the orbital similarities they share 2 , 3 , but no cometary activities such as coma have been detected 4 , 5 unlike in the parent bodies of other meteor streams. On the other hand, this asteroid exhibits weak but certain dust ejections near its perihelion passages 6 , 7 , which is the reason why it is now regarded as an active asteroid 8 . A feature that makes Phaethon intriguing is its very blue spectrum 9 , 10 . This asteroid’s spectrum is categorized into B-type in the SMASS II (Bus) classification 11 and F-type in the Tholen classification 3 , characterized by a negative slope over 0.5–0.8 μm without any diagnostic absorption bands in the visible to near-infrared wavelengths 12 . Phaethon’s blue spectrum is also similar to that of the Pallas family asteroids, particularly in the near-infrared wavelengths 9 , 10 . This is one item of evidence of the connection between this asteroid and the Pallas family. It is suggested that thermally metamorphosed CI/CM chondrites 12 or CK4 chondrites 10 , 13 are the meteorite analogue of Phaethon due to their spectral similarity. Another interesting aspect of Phaethon is that, this asteroid seems to possess at least one disruption fragment, (155140) 2005 UD, deduced from the two asteroids’ strong orbital similarity and their surface color affinities 14 , 15 , 16 . Multicolor photometry of (155140) 2005 UD indicates that the surface color of this object is inhomogeneous 16 . The surface heterogeneity of this fragment may be related to the spectral variability recognized on Phaethon’s surface 12 , serving as evidence of the past breakup event that split them. The curious surface property of this asteroid, together with the existence of a fragment, is an important clue for understanding the dynamical and thermal evolution of the near-Earth asteroids in this orbital category, and not just of Phaethon, whose dynamical lifetime is generally as short as some million years 17 , 18 . However, it is also true that many unknowns and uncertainties remain to be cleared up. For example, we still have little understanding of what microscopic structure or physical process yields such very blue spectra of Phaethon. The details of the mechanism that causes the sporadic dust ejections from Phaethon, and the mechanism that made the fragment split from the parent body, are not well understood either, although it is suggested that strong solar heating is involved 19 . We can solve several of the above-stated enigmas of Phaethon (and those of the B-type asteroids collectively) by investigating their surface polarimetric properties. Polarimetric studies of airless bodies are generally useful for understanding their surface physical properties, particularly geometric albedo and grain size. For example, we know that geometric albedo and polarization degree of the small solar system bodies have a strong correlation 20 . Also, the maximum values of the linear polarization degree ( P max ) and the solar phase angle ( α ) where P max happens are correlated with grain size 21 , 22 . While spectroscopic observation measures the reflected spectrum from the surface of the object, its result depends not only on the surface texture but also chemical composition of the surface material. In general it is not easy to decouple these combined effects just from spectroscopic observation. Therefore, polarimetric observation that directly measures the status of light scattering, which strongly depends on the surface texture, is complementary to and sometimes superior to spectroscopic observation in terms of studies of the small solar system bodies. So far, most polarimetric studies of the small solar system bodies have been performed at small to moderate solar phase angles such as α < 35° 23 . Polarimetric measurement of the small bodies at a large solar phase angle is technically difficult, not only because the observational opportunities are limited to some near-Earth asteroids that get inside Earth’s orbits, but also because the observation should be conducted at small solar elongation angles. However, as polarimetric measurement of the small bodies over a wide range of α better reveals their surface material property, its implementation is always desirable whenever it is feasible. In this paper, we report the result of our series of polarimetric observations of Phaethon over a wide range of solar phase angles. Our observation revealed that this asteroid exhibits a very strong linear polarization (>50%). This implies that Phaethon’s geometric albedo is lower than the current estimate. An alternative is that relatively large grains (~300 μm in diameter) dominate this asteroid’s surface. Results Dependence of polarization on solar phase angle We carried out our series of", "role": "user" }, { "content": "For the first time, astronomers have directly observed the magnetism in one of astronomy's most studied objects: the remains of Supernova 1987A (SN 1987A), a dying star that appeared in our skies over thirty years ago. In addition to being an impressive observational achievement, the detection provides insight into the early stages of the evolution of supernova remnants and the cosmic magnetism within them. \"The magnetism we've detected is around 50,000 times weaker than a fridge magnet,\" says Prof. Bryan Gaensler. \"And we've been able to measure this from a distance of around 1.6 million trillion kilometres.\" \"This is the earliest possible detection of the magnetic field formed after the explosion of a massive star,\" says Dr. Giovanna Zanardo. Gaensler is Director of the Dunlap Institute for Astronomy & Astrophysics at the University of Toronto, and a co-author on the paper announcing the discovery being published in the Astrophysical Journal on June 29th. The lead author, Zanardo, and co-author Prof. Lister Staveley-Smith are both from the University of Western Australia's node of the International Centre for Radio Astronomy Research. SN 1987A was co-discovered by University of Toronto astronomer Ian Shelton in February 1987 from the then Southern Observatory of the University of Toronto in northern Chile. It is located in the Large Magellanic Cloud, a dwarf galaxy companion to the Milky Way Galaxy, at a distance of 168,000 light-years from Earth. It was the first naked-eye supernova to be observed since the astronomer Johannes Kepler witnessed a supernova over 400 years ago. A map of the SN 1987A remnant with short orange lines showing the orientation of the magnetic field. Credit: Giovanna Zanardo In the thirty years since the supernova occurred, material expelled by the blast, as well as the shockwave from the star's death throes, have been travelling outward through the gas and dust that surrounded the star before it exploded. Today, when we look at the remnant, we see rings of material set aglow by the supernova's expanding debris and shockwave. Using the Australia Telescope Compact Array at the Paul Wild Observatory, Gaensler and his colleagues observed the magnetic field by studying the radiation coming from the object. By analyzing the properties of this radiation, they were able to trace the magnetic field. \"The picture shows what it would look like if you could sprinkle iron filings over the expanding cloud of debris, 170 thousand light years away\", says Gaensler. What they found was that the remnant's magnetic field was not chaotic but already showed a degree of order. Astronomers have known that as supernova remnants get older, their magnetic fields are stretched and aligned into ordered patterns. So, the team's observation showed that a supernova remnant can bring order to a magnetic field in the relatively short period of thirty years. The magnetic field lines of the Earth run north and south, causing a compass to point to the Earth's poles. By comparison, the magnetic field lines associated with SN 1987A are like the spokes of a bicycle wheel aligned from the centre out. \"At such a young age,\" says Zanardo, \"everything in the stellar remnant is moving incredibly fast and changing rapidly, but the magnetic field looks nicely combed out all the way to the edge of the shell.\" Gaensler and his colleagues will continue to observe the constantly evolving remnant. \"As it continues to expand and evolve,\" says Gaensler, \"we will be watching the shape of the magnetic field to see how it changes as the shock wave and debris cloud run into new material.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract The near-Earth asteroid (3200) Phaethon is the parent body of the Geminid meteor stream. Phaethon is also an active asteroid with a very blue spectrum. We conducted polarimetric observations of this asteroid over a wide range of solar phase angles α during its close approach to the Earth in autumn 2016. Our observation revealed that Phaethon exhibits extremely large linear polarization: P = 50.0 ± 1.1% at α = 106.5°, and its maximum is even larger. The strong polarization implies that Phaethon’s geometric albedo is lower than the current estimate obtained through radiometric observation. This possibility stems from the potential uncertainty in Phaethon’s absolute magnitude. An alternative possibility is that relatively large grains (~300 μm in diameter, presumably due to extensive heating near its perihelion) dominate this asteroid’s surface. In addition, the asteroid’s surface porosity, if it is substantially large, can also be an effective cause of this polarization. Introduction (3200) Phaethon is a well-studied near-Earth asteroid. Ever since its discovery by a survey using the Infrared Astronomical Satellite (IRAS) in 1983 1 , this asteroid has exhibited several interesting characteristics of small solar system bodies. Phaethon is an Apollo-type near-Earth asteroid that has large inclination $(i \sim 22^\circ )$ , large eccentricity $(e \sim 0.89)$ , and small perihelion distance $(q \sim 0.14{\kern 1pt} {\mathrm{au}})$ . This asteroid is also recognized as the parent body of the Geminid meteor stream due to the orbital similarities they share 2 , 3 , but no cometary activities such as coma have been detected 4 , 5 unlike in the parent bodies of other meteor streams. On the other hand, this asteroid exhibits weak but certain dust ejections near its perihelion passages 6 , 7 , which is the reason why it is now regarded as an active asteroid 8 . A feature that makes Phaethon intriguing is its very blue spectrum 9 , 10 . This asteroid’s spectrum is categorized into B-type in the SMASS II (Bus) classification 11 and F-type in the Tholen classification 3 , characterized by a negative slope over 0.5–0.8 μm without any diagnostic absorption bands in the visible to near-infrared wavelengths 12 . Phaethon’s blue spectrum is also similar to that of the Pallas family asteroids, particularly in the near-infrared wavelengths 9 , 10 . This is one item of evidence of the connection between this asteroid and the Pallas family. It is suggested that thermally metamorphosed CI/CM chondrites 12 or CK4 chondrites 10 , 13 are the meteorite analogue of Phaethon due to their spectral similarity. Another interesting aspect of Phaethon is that, this asteroid seems to possess at least one disruption fragment, (155140) 2005 UD, deduced from the two asteroids’ strong orbital similarity and their surface color affinities 14 , 15 , 16 . Multicolor photometry of (155140) 2005 UD indicates that the surface color of this object is inhomogeneous 16 . The surface heterogeneity of this fragment may be related to the spectral variability recognized on Phaethon’s surface 12 , serving as evidence of the past breakup event that split them. The curious surface property of this asteroid, together with the existence of a fragment, is an important clue for understanding the dynamical and thermal evolution of the near-Earth asteroids in this orbital category, and not just of Phaethon, whose dynamical lifetime is generally as short as some million years 17 , 18 . However, it is also true that many unknowns and uncertainties remain to be cleared up. For example, we still have little understanding of what microscopic structure or physical process yields such very blue spectra of Phaethon. The details of the mechanism that causes the sporadic dust ejections from Phaethon, and the mechanism that made the fragment split from the parent body, are not well understood either, although it is suggested that strong solar heating is involved 19 . We can solve several of the above-stated enigmas of Phaethon (and those of the B-type asteroids collectively) by investigating their surface polarimetric properties. Polarimetric studies of airless bodies are generally useful for understanding their surface physical properties, particularly geometric albedo and grain size. For example, we know that geometric albedo and polarization degree of the small solar system bodies have a strong correlation 20 . Also, the maximum values of the linear polarization degree ( P max ) and the solar phase angle ( α ) where P max happens are correlated with grain size 21 , 22 . While spectroscopic observation measures the reflected spectrum from the surface of the object, its result depends not only on the surface texture but also chemical composition of the surface material. In general it is not easy to decouple these combined effects just from spectroscopic observation. Therefore, polarimetric observation that directly measures the status of light scattering, which strongly depends on the surface texture, is complementary to and sometimes superior to spectroscopic observation in terms of studies of the small solar system bodies. So far, most polarimetric studies of the small solar system bodies have been performed at small to moderate solar phase angles such as α < 35° 23 . Polarimetric measurement of the small bodies at a large solar phase angle is technically difficult, not only because the observational opportunities are limited to some near-Earth asteroids that get inside Earth’s orbits, but also because the observation should be conducted at small solar elongation angles. However, as polarimetric measurement of the small bodies over a wide range of α better reveals their surface material property, its implementation is always desirable whenever it is feasible. In this paper, we report the result of our series of polarimetric observations of Phaethon over a wide range of solar phase angles. Our observation revealed that this asteroid exhibits a very strong linear polarization (>50%). This implies that Phaethon’s geometric albedo is lower than the current estimate. An alternative is that relatively large grains (~300 μm in diameter) dominate this asteroid’s surface. Results Dependence of polarization on solar phase angle We carried out our series of<|im_end|> <|im_start|>assistant For the first time, astronomers have directly observed the magnetism in one of astronomy's most studied objects: the remains of Supernova 1987A (SN 1987A), a dying star that appeared in our skies over thirty years ago. In addition to being an impressive observational achievement, the detection provides insight into the early stages of the evolution of supernova remnants and the cosmic magnetism within them. "The magnetism we've detected is around 50,000 times weaker than a fridge magnet," says Prof. Bryan Gaensler. "And we've been able to measure this from a distance of around 1.6 million trillion kilometres." "This is the earliest possible detection of the magnetic field formed after the explosion of a massive star," says Dr. Giovanna Zanardo. Gaensler is Director of the Dunlap Institute for Astronomy & Astrophysics at the University of Toronto, and a co-author on the paper announcing the discovery being published in the Astrophysical Journal on June 29th. The lead author, Zanardo, and co-author Prof. Lister Staveley-Smith are both from the University of Western Australia's node of the International Centre for Radio Astronomy Research. SN 1987A was co-discovered by University of Toronto astronomer Ian Shelton in February 1987 from the then Southern Observatory of the University of Toronto in northern Chile. It is located in the Large Magellanic Cloud, a dwarf galaxy companion to the Milky Way Galaxy, at a distance of 168,000 light-years from Earth. It was the first naked-eye supernova to be observed since the astronomer Johannes Kepler witnessed a supernova over 400 years ago. A map of the SN 1987A remnant with short orange lines showing the orientation of the magnetic field. Credit: Giovanna Zanardo In the thirty years since the supernova occurred, material expelled by the blast, as well as the shockwave from the star's death throes, have been travelling outward through the gas and dust that surrounded the star before it exploded. Today, when we look at the remnant, we see rings of material set aglow by the supernova's expanding debris and shockwave. Using the Australia Telescope Compact Array at the Paul Wild Observatory, Gaensler and his colleagues observed the magnetic field by studying the radiation coming from the object. By analyzing the properties of this radiation, they were able to trace the magnetic field. "The picture shows what it would look like if you could sprinkle iron filings over the expanding cloud of debris, 170 thousand light years away", says Gaensler. What they found was that the remnant's magnetic field was not chaotic but already showed a degree of order. Astronomers have known that as supernova remnants get older, their magnetic fields are stretched and aligned into ordered patterns. So, the team's observation showed that a supernova remnant can bring order to a magnetic field in the relatively short period of thirty years. The magnetic field lines of the Earth run north and south, causing a compass to point to the Earth's poles. By comparison, the magnetic field lines associated with SN 1987A are like the spokes of a bicycle wheel aligned from the centre out. "At such a young age," says Zanardo, "everything in the stellar remnant is moving incredibly fast and changing rapidly, but the magnetic field looks nicely combed out all the way to the edge of the shell." Gaensler and his colleagues will continue to observe the constantly evolving remnant. "As it continues to expand and evolve," says Gaensler, "we will be watching the shape of the magnetic field to see how it changes as the shock wave and debris cloud run into new material." <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 578, 3221, 13737, 47601, 55479, 320, 9588, 15, 8, 2405, 64, 774, 263, 374, 279, 2748, 2547, 315, 279, 480, 26768, 307, 42142, 4365, 13, 2405, 64, 774, 263, 374, 1101, 459, 4642, 55479, 449, 264, 1633, 6437, 20326, 13, 1226, 13375, 25685, 318, 16743, 24654, 315, 420, 55479, 927, 264, 7029, 2134, 315, 13238, 10474, 27030, 19581, 2391, 1202, 3345, 5603, 311, 279, 9420, 304, 42774, 220, 679, 21, 13, 5751, 22695, 10675, 430, 2405, 64, 774, 263, 50829, 9193, 3544, 13790, 83245, 25, 393, 284, 220, 1135, 13, 15, 20903, 220, 16, 13, 16, 4, 520, 19581, 284, 220, 7461, 13, 20, 11877, 11, 323, 1202, 7340, 374, 1524, 8294, 13, 578, 3831, 83245, 24897, 430, 2405, 64, 774, 263, 753, 53584, 453, 90087, 374, 4827, 1109, 279, 1510, 16430, 12457, 1555, 12164, 24264, 22695, 13, 1115, 13336, 44814, 505, 279, 4754, 27924, 304, 2405, 64, 774, 263, 753, 10973, 26703, 13, 1556, 10778, 13336, 374, 430, 12309, 3544, 41936, 31857, 3101, 33983, 76, 304, 23899, 11, 36548, 4245, 311, 16781, 24494, 3221, 1202, 824, 7141, 301, 290, 8, 41836, 420, 55479, 753, 7479, 13, 763, 5369, 11, 279, 55479, 753, 7479, 4247, 22828, 11, 422, 433, 374, 32302, 3544, 11, 649, 1101, 387, 459, 7524, 5353, 315, 420, 83245, 13, 29438, 320, 9588, 15, 8, 2405, 64, 774, 263, 374, 264, 1664, 5594, 664, 1142, 3221, 13737, 47601, 55479, 13, 18374, 2533, 1202, 18841, 555, 264, 10795, 1701, 279, 763, 82482, 39616, 14609, 950, 61657, 320, 2871, 1950, 8, 304, 220, 3753, 18, 220, 16, 1174, 420, 55479, 706, 51713, 3892, 7185, 17910, 315, 2678, 13238, 1887, 13162, 13, 2405, 64, 774, 263, 374, 459, 36250, 10827, 3221, 13737, 47601, 55479, 430, 706, 3544, 77004, 1144, 1209, 72, 1144, 15124, 220, 1313, 25928, 44398, 883, 58858, 1174, 3544, 55920, 488, 1144, 1209, 68, 1144, 15124, 220, 15, 13, 4578, 10929, 8, 1174, 323, 2678, 824, 7141, 301, 290, 6138, 1144, 1209, 80, 1144, 15124, 220, 15, 13, 975, 36802, 74, 944, 220, 16, 418, 92, 29252, 92650, 90, 2933, 3500, 10929, 8, 662, 1115, 55479, 374, 1101, 15324, 439, 279, 2748, 2547, 315, 279, 480, 26768, 307, 42142, 4365, 4245, 311, 279, 65691, 43874, 814, 4430, 220, 17, 1174, 220, 18, 1174, 719, 912, 470, 16238, 7640, 1778, 439, 70398, 617, 1027, 16914, 220, 19, 1174, 220, 20, 20426, 304, 279, 2748, 13162, 315, 1023, 42142, 23914, 13, 1952, 279, 1023, 1450, 11, 420, 55479, 50829, 7621, 719, 3738, 16174, 384, 25593, 3221, 1202, 824, 7141, 301, 290, 47869, 220, 21, 1174, 220, 22, 1174, 902, 374, 279, 2944, 3249, 433, 374, 1457, 27458, 439, 459, 4642, 55479, 220, 23, 662, 362, 4668, 430, 3727, 2405, 64, 774, 263, 41765, 374, 1202, 1633, 6437, 20326, 220, 24, 1174, 220, 605, 662, 1115, 55479, 753, 20326, 374, 71974, 1139, 426, 10827, 304, 279, 96996, 1242, 8105, 320, 15423, 8, 24790, 220, 806, 323, 435, 10827, 304, 279, 666, 17648, 24790, 220, 18, 1174, 32971, 555, 264, 8389, 31332, 927, 220, 15, 13, 20, 4235, 15, 13, 23, 33983, 76, 2085, 904, 15439, 44225, 21562, 304, 279, 9621, 311, 3221, 3502, 82482, 93959, 220, 717, 662, 2405, 64, 774, 263, 753, 6437, 20326, 374, 1101, 4528, 311, 430, 315, 279, 393, 16242, 3070, 85322, 11, 8104, 304, 279, 3221, 3502, 82482, 93959, 220, 24, 1174, 220, 605, 662, 1115, 374, 832, 1537, 315, 6029, 315, 279, 3717, 1990, 420, 55479, 323, 279, 393, 16242, 3070, 13, 1102, 374, 12090, 430, 30945, 750, 88848, 16751, 20158, 21351, 14, 10190, 523, 2159, 24143, 220, 717, 477, 31166, 19, 523, 2159, 24143, 220, 605, 1174, 220, 1032, 527, 279, 42142, 635, 91343, 315, 2405, 64, 774, 263, 4245, 311, 872, 57077, 38723, 13, 13596, 7185, 13189, 315, 2405, 64, 774, 263, 374, 430, 11, 420, 55479, 5084, 311, 15575, 520, 3325, 832, 44219, 12569, 11, 320, 9992, 6860, 8, 220, 1049, 20, 79651, 11, 7836, 24921, 505, 279, 1403, 85322, 529, 3831, 65691, 38723, 323, 872, 7479, 1933, 3611, 258, 1385, 220, 975, 1174, 220, 868, 1174, 220, 845, 662, 22950, 74909, 4604, 7133, 315, 320, 9992, 6860, 8, 220, 1049, 20, 79651, 15151, 430, 279, 7479, 1933, 315, 420, 1665, 374, 304, 35940, 49122, 220, 845, 662, 578, 7479, 30548, 76730, 315, 420, 12569, 1253, 387, 5552, 311, 279, 57077, 54709, 15324, 389, 2405, 64, 774, 263, 753, 7479, 220, 717, 1174, 13788, 439, 6029, 315, 279, 3347, 85598, 1567, 430, 6859, 1124, 13, 578, 22999, 7479, 3424, 315, 420, 55479, 11, 3871, 449, 279, 14209, 315, 264, 12569, 11, 374, 459, 3062, 31089, 369, 8830, 279, 18003, 950, 323, 29487, 15740, 315, 279, 3221, 13737, 47601, 85322, 304, 420, 65691, 5699, 11, 323, 539, 1120, 315, 2405, 64, 774, 263, 11, 6832, 18003, 950, 19569, 374, 8965, 439, 2875, 439, 1063, 3610, 1667, 220, 1114, 1174, 220, 972, 662, 4452, 11, 433, 374, 1101, 837, 430, 1690, 9987, 82, 323, 69867, 7293, 311, 387, 23803, 709, 13, 1789, 3187, 11, 584, 2103, 617, 2697, 8830, 315, 1148, 90090, 6070, 477, 7106, 1920, 36508, 1778, 1633, 6437, 63697, 315, 2405, 64, 774, 263, 13, 578, 3649, 315, 279, 17383, 430, 11384, 279, 62016, 37314, 16174, 384, 25593, 505, 2405, 64, 774, 263, 11, 323, 279, 17383, 430, 1903, 279, 12569, 6859, 505, 279, 2748, 2547, 11, 527, 539, 1664, 16365, 3060, 11, 8051, 433, 374, 12090, 430, 3831, 13238, 24494, 374, 6532, 220, 777, 662, 1226, 649, 11886, 3892, 315, 279, 3485, 5594, 660, 665, 343, 7044, 315, 2405, 64, 774, 263, 320, 438, 1884, 315, 279, 426, 10827, 85322, 45925, 8, 555, 24834, 872, 7479, 25685, 318, 16743, 6012, 13, 56996, 318, 16743, 7978, 315, 3805, 1752, 13162, 527, 8965, 5505, 369, 8830, 872, 7479, 7106, 6012, 11, 8104, 53584, 453, 90087, 323, 24875, 1404, 13, 1789, 3187, 11, 584, 1440, 430, 53584, 453, 90087, 323, 83245, 8547, 315, 279, 2678, 13238, 1887, 13162, 617, 264, 3831, 26670, 220, 508, 662, 7429, 11, 279, 7340, 2819, 315, 279, 13790, 83245, 8547, 320, 393, 1973, 883, 323, 279, 13238, 10474, 9392, 320, 19581, 883, 1405, 393, 1973, 8741, 527, 49393, 449, 24875, 1404, 220, 1691, 1174, 220, 1313, 662, 6104, 66425, 58510, 22695, 11193, 279, 27000, 20326, 505, 279, 7479, 315, 279, 1665, 11, 1202, 1121, 14117, 539, 1193, 389, 279, 7479, 10651, 719, 1101, 11742, 18528, 315, 279, 7479, 3769, 13, 763, 4689, 433, 374, 539, 4228, 311, 1654, 85489, 1521, 11093, 6372, 1120, 505, 66425, 58510, 22695, 13, 15636, 11, 25685, 318, 16743, 22695, 430, 6089, 11193, 279, 2704, 315, 3177, 72916, 11, 902, 16917, 14117, 389, 279, 7479, 10651, 11, 374, 58535, 311, 323, 7170, 16757, 311, 66425, 58510, 22695, 304, 3878, 315, 7978, 315, 279, 2678, 13238, 1887, 13162, 13, 2100, 3117, 11, 1455, 25685, 318, 16743, 7978, 315, 279, 2678, 13238, 1887, 13162, 617, 1027, 10887, 520, 2678, 311, 24070, 13238, 10474, 27030, 1778, 439, 19581, 366, 220, 1758, 11877, 220, 1419, 662, 56996, 318, 16743, 19179, 315, 279, 2678, 13162, 520, 264, 3544, 13238, 10474, 9392, 374, 32654, 5107, 11, 539, 1193, 1606, 279, 90380, 10708, 527, 7347, 311, 1063, 3221, 13737, 47601, 85322, 430, 636, 4871, 9420, 753, 86228, 11, 719, 1101, 1606, 279, 22695, 1288, 387, 13375, 520, 2678, 13238, 74595, 367, 27030, 13, 4452, 11, 439, 25685, 318, 16743, 19179, 315, 279, 2678, 13162, 927, 264, 7029, 2134, 315, 19581, 2731, 21667, 872, 7479, 3769, 3424, 11, 1202, 8292, 374, 2744, 35946, 15716, 433, 374, 43303, 13, 763, 420, 5684, 11, 584, 1934, 279, 1121, 315, 1057, 4101, 315, 25685, 318, 16743, 24654, 315, 2405, 64, 774, 263, 927, 264, 7029, 2134, 315, 13238, 10474, 27030, 13, 5751, 22695, 10675, 430, 420, 55479, 50829, 264, 1633, 3831, 13790, 83245, 77952, 1135, 53172, 1115, 24897, 430, 2405, 64, 774, 263, 753, 53584, 453, 90087, 374, 4827, 1109, 279, 1510, 16430, 13, 1556, 10778, 374, 430, 12309, 3544, 41936, 31857, 3101, 33983, 76, 304, 23899, 8, 41836, 420, 55479, 753, 7479, 13, 18591, 99428, 768, 315, 83245, 389, 13238, 10474, 9392, 1226, 11953, 704, 1057, 4101, 315, 128257, 198, 128256, 78191, 198, 2520, 279, 1176, 892, 11, 87887, 617, 6089, 13468, 279, 33297, 2191, 304, 832, 315, 82213, 596, 1455, 20041, 6302, 25, 279, 8625, 315, 97048, 12949, 220, 3753, 22, 32, 320, 19503, 220, 3753, 22, 32, 705, 264, 23069, 6917, 430, 9922, 304, 1057, 50393, 927, 27219, 1667, 4227, 13, 763, 5369, 311, 1694, 459, 16358, 90380, 26501, 11, 279, 18468, 5825, 20616, 1139, 279, 4216, 18094, 315, 279, 15740, 315, 39887, 12949, 73440, 323, 279, 55801, 33297, 2191, 2949, 1124, 13, 330, 791, 33297, 2191, 584, 3077, 16914, 374, 2212, 220, 1135, 11, 931, 3115, 43383, 1109, 264, 38681, 33297, 1359, 2795, 8626, 13, 37453, 18879, 729, 1565, 13, 330, 3112, 584, 3077, 1027, 3025, 311, 6767, 420, 505, 264, 6138, 315, 2212, 220, 16, 13, 21, 3610, 32610, 52957, 1210, 330, 2028, 374, 279, 30758, 3284, 18468, 315, 279, 24924, 2115, 14454, 1306, 279, 25176, 315, 264, 11191, 6917, 1359, 2795, 2999, 13, 61678, 12930, 1901, 276, 21106, 13, 18879, 729, 1565, 374, 10783, 315, 279, 29838, 16338, 10181, 369, 95803, 612, 94202, 17688, 520, 279, 3907, 315, 14974, 11, 323, 264, 1080, 43802, 389, 279, 5684, 38787, 279, 18841, 1694, 4756, 304, 279, 94202, 19506, 10139, 389, 5651, 220, 1682, 339, 13, 578, 3063, 3229, 11, 1901, 276, 21106, 11, 323, 1080, 43802, 8626, 13, 445, 1601, 800, 525, 3258, 97338, 527, 2225, 505, 279, 3907, 315, 11104, 8494, 596, 2494, 315, 279, 7327, 14821, 369, 13792, 95803, 8483, 13, 18407, 220, 3753, 22, 32, 574, 1080, 10694, 21468, 555, 3907, 315, 14974, 46382, 261, 29335, 37940, 783, 304, 7552, 220, 3753, 22, 505, 279, 1243, 16642, 58974, 315, 279, 3907, 315, 14974, 304, 18671, 34100, 13, 1102, 374, 7559, 304, 279, 20902, 7023, 616, 32370, 15161, 11, 264, 50561, 34261, 22489, 311, 279, 89819, 12424, 20238, 11, 520, 264, 6138, 315, 220, 8953, 11, 931, 3177, 57188, 505, 9420, 13, 1102, 574, 279, 1176, 19557, 47797, 39887, 12949, 311, 387, 13468, 2533, 279, 46382, 261, 55205, 98843, 32126, 264, 39887, 12949, 927, 220, 3443, 1667, 4227, 13, 362, 2472, 315, 279, 18407, 220, 3753, 22, 32, 1323, 52985, 449, 2875, 19087, 5238, 9204, 279, 17140, 315, 279, 24924, 2115, 13, 16666, 25, 61678, 12930, 1901, 276, 21106, 763, 279, 27219, 1667, 2533, 279, 39887, 12949, 10222, 11, 3769, 67331, 555, 279, 21327, 11, 439, 1664, 439, 279, 10988, 31498, 505, 279, 6917, 596, 4648, 60187, 288, 11, 617, 1027, 31829, 52046, 1555, 279, 6962, 323, 16174, 430, 23712, 279, 6917, 1603, 433, 44913, 13, 11450, 11, 994, 584, 1427, 520, 279, 1323, 52985, 11, 584, 1518, 25562, 315, 3769, 743, 945, 10516, 555, 279, 39887, 12949, 596, 24050, 35098, 323, 10988, 31498, 13, 12362, 279, 8494, 87062, 55882, 2982, 520, 279, 7043, 13944, 58974, 11, 18879, 729, 1565, 323, 813, 18105, 13468, 279, 24924, 2115, 555, 21630, 279, 25407, 5108, 505, 279, 1665, 13, 3296, 42118, 279, 6012, 315, 420, 25407, 11, 814, 1051, 3025, 311, 11917, 279, 24924, 2115, 13, 330, 791, 6945, 5039, 1148, 433, 1053, 1427, 1093, 422, 499, 1436, 85947, 11245, 68248, 927, 279, 24050, 9624, 315, 35098, 11, 220, 8258, 16579, 3177, 1667, 3201, 498, 2795, 18879, 729, 1565, 13, 3639, 814, 1766, 574, 430, 279, 1323, 52985, 596, 24924, 2115, 574, 539, 53087, 719, 2736, 8710, 264, 8547, 315, 2015, 13, 39616, 14609, 388, 617, 3967, 430, 439, 39887, 12949, 73440, 636, 9191, 11, 872, 24924, 5151, 527, 41398, 323, 27210, 1139, 11713, 12912, 13, 2100, 11, 279, 2128, 596, 22695, 8710, 430, 264, 39887, 12949, 1323, 52985, 649, 4546, 2015, 311, 264, 24924, 2115, 304, 279, 12309, 2875, 4261, 315, 27219, 1667, 13, 578, 24924, 2115, 5238, 315, 279, 9420, 1629, 10411, 323, 10007, 11, 14718, 264, 24653, 311, 1486, 311, 279, 9420, 596, 51879, 13, 3296, 12593, 11, 279, 24924, 2115, 5238, 5938, 449, 18407, 220, 3753, 22, 32, 527, 1093, 279, 11449, 315, 264, 36086, 13587, 27210, 505, 279, 12541, 704, 13, 330, 1688, 1778, 264, 3995, 4325, 1359, 2795, 1901, 276, 21106, 11, 330, 73826, 304, 279, 48317, 1323, 52985, 374, 7366, 17235, 5043, 323, 10223, 19019, 11, 719, 279, 24924, 2115, 5992, 29921, 470, 2788, 704, 682, 279, 1648, 311, 279, 6964, 315, 279, 12811, 1210, 18879, 729, 1565, 323, 813, 18105, 690, 3136, 311, 23846, 279, 15320, 42028, 1323, 52985, 13, 330, 2170, 433, 9731, 311, 9407, 323, 38680, 1359, 2795, 18879, 729, 1565, 11, 330, 906, 690, 387, 10307, 279, 6211, 315, 279, 24924, 2115, 311, 1518, 1268, 433, 4442, 439, 279, 10988, 12330, 323, 35098, 9624, 1629, 1139, 502, 3769, 1210, 220, 128257, 198 ]

2,144

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Optically active nanomaterials promise to advance a range of biophotonic techniques through nanoscale optical effects and integration of multiple imaging and therapeutic modalities. Here, we report the development of porphysomes; nanovesicles formed from self-assembled porphyrin bilayers that generated large, tunable extinction coefficients, structure-dependent fluorescence self-quenching and unique photothermal and photoacoustic properties. Porphysomes enabled the sensitive visualization of lymphatic systems using photoacoustic tomography. Near-infrared fluorescence generation could be restored on dissociation, creating opportunities for low-background fluorescence imaging. As a result of their organic nature, porphysomes were enzymatically biodegradable and induced minimal acute toxicity in mice with intravenous doses of 1,000 mg kg −1 . In a similar manner to liposomes, the large aqueous core of porphysomes could be passively or actively loaded. Following systemic administration, porphysomes accumulated in tumours of xenograft-bearing mice and laser irradiation induced photothermal tumour ablation. The optical properties and biocompatibility of porphysomes demonstrate the multimodal potential of organic nanoparticles for biophotonic imaging and therapy. Main Therapeutic and diagnostic techniques benefiting from components that efficiently absorb light include fluorescent and colorimetric detection 1 , 2 , photothermal and photodynamic therapy 3 , 4 , 5 , photoacoustic tomography (also known as optoacoustic tomography) 6 , 7 , 8 , 9 , optical frequency domain imaging 10 and multimodal techniques 11 , among others. As inorganic nanoparticles often interact strongly with light, they can be used as agents for these techniques. For instance, quantum dots are valuable fluorescent probes and have extinction coefficients in the range of 10 5 –10 6 M −1 cm −1 (ref. 12 ). Gold nanoparticles are useful for colorimetric detection, photothermal and photoacoustic techniques owing to their much higher extinction coefficients, of the order of 10 9 –10 11 M −1 cm −1 (ref. 13 ). Despite recent progress 14 , optically active inorganic nanoparticles have not yet achieved broad clinical implementation, possibly stemming from drug loading typically being limited to the nanoparticle surface and concerns regarding long-term safety 15 , 16 , 17 , 18 . In contrast, organic nanoparticles (including liposomes, lipoproteins, micelles, nanospheres and polymersomes) have found many human therapeutic applications as a result of robust biocompatibility and drug-delivery capacity 18 . However, as these organic nanoparticles generally do not intrinsically absorb light in the near-infrared region, they have been of limited use for biophotonics. Although supramolecular assemblies can be formed entirely by porphyrin conjugates, intensely light-absorbing organic small molecules, these constructs have not been thoroughly explored as biophotonic tools owing to a lack of stability, solubility or biological utility 19 . Here we introduce ‘porphysomes’; organicnanoparticles self-assembled from phospholipid–porphyrin conjugates that exhibit liposome-like structure and loading capacity, high absorption of near-infrared light, structure-dependent fluorescence quenching and excellent biocompatibility, and show promise for diverse biophotonic applications. Porphysomes were formed by supramolecular self-assembly. The porphysome subunits consisted of porphyrin–lipid conjugates generated by an acylation reaction between lysophosphatidylcholine and pyropheophorbide, a chlorophyll-derived porphyrin analogue. This hydrophobic chromophore was positioned in place of an alkyl side chain, maintaining an amphipathic structure ( Fig. 1 a). This conjugate could be self-assembled in aqueous buffer with extrusion to form porphysomes. A concentration of 5 molar% polyethylene glycol (PEG)–lipid was included in the formulation to enhance in vivo pharmacokinetics 20 . Transmission electron microscopy showed that these porphysomes were spherical vesicles of 100 nm in diameter ( Fig. 1 b). At higher magnifications, the porphysome structure was revealed as two layers of higher-density material separated by a 2 nm gap, corresponding to two separate monolayers of porphyrin. Pyropheophorbide porphysomes exhibited two absorption peaks, one at 400 nm and one in the near-infrared window at 680 nm ( Fig. 1 c). Further redshifted porphysomes (760 nm) were produced by using subunits generated from another type of porphyrin; a bacteriochlorophyll analogue that was synthesized in the same manner as pyropheophorbide–lipid. Alternatively, a protocol was developed to insert metal ions into the porphyrin–lipid structure, resulting in shifted optical density bands (440 nm and 670 nm) and demonstrating the unique phenomenon that porphysomes can form metal-chelating bilayers. These different types of porphysome could be useful in scenarios in which specific operating wavelengths are required (for example, to match a given laser excitation source). To verify that the absorbance spectra corresponded to light absorption, rather than scattering, we compared porphysomes with wavelength-matched gold nanorods (with 680 nm extinction peaks) using resonance scattering 21 . Porphysomes exhibited up to 100 times less resonance light scatter at the optical density wavelength peak at which the samples were normalized ( Fig. 1 d). The monodisperse 100 nm sizes exhibited by various types of porphysome ( Fig. 1 e) are in a suitable range to take advantage of the enhanced permeability and retention effect for passive accumulation in tumours 22 , 23 . Flexibility in size control was demonstrated as sonication of porphyrin–lipid in water produced smaller, 30 nm, nanoparticles ( Supplementary Fig. S1 ), which could be useful for applications requiring smaller nanoparticle sizes. Geometric calculations for vesicles of 100 nm in diameter composed of subunits with phosphatidylcholine headgroups indicate that there are approximately 8×10 4 porphyrin conjugates per porphysome 24 . On the basis of pyropheophorbide absorbance (accounting for differences in the absorbance of the intact porphysome measured in PBS and the dissociated porphyrin–lipid obtained by diluting 1–2 μl of porphysomes in 1 ml of methanol, as shown in Supplementary Fig. S2 ), we estimate a pyropheophorbide-porphysome extinction coefficient, ɛ 680 , of 2.9×10 9 M −1 cm −1 . This large, near-infrared extinction coefficient is a reflection of the dense porphyrin packing in the bilayer that generates the unique nanoscale optical behaviour of porphysomes. Figure 1: Porphysomes are optically active nanovesicles formed from porphyrin bilayers. a , Schematic representation of a pyropheophorbide–lipid porphysome. The phospholipid headgroup (red) and porphyrin (blue) are highlighted in the subunit (left) and assembled nanovesicle (right). b , Electron micrographs of negatively stained porphysomes (5% PEG–lipid, 95% pyropheophorbide–lipid). c , Absorbance of the porphyrin–lipid subunits incorporated in porphysomes formed from pyropheophorbide (blue), zinc-pyropheophorbide (orange) and bacteriochlorophyll (red) in", "role": "user" }, { "content": "A team of scientists from Princess Margaret Hospital have created an organic nanoparticle that is completely non-toxic, biodegradable and nimble in the way it uses light and heat to treat cancer and deliver drugs. (A nanoparticle is a minute molecule with novel properties). The findings, published online today in Nature Materials are significant because unlike other nanoparticles, the new nanoparticle has a unique and versatile structure that could potentially change the way tumors are treated, says principal investigator Dr. Gang Zheng, Senior Scientist, Ontario Cancer Institute (OCI), Princess Margaret Hospital at University Health Network. Dr. Zheng says: \"In the lab, we combined two naturally occurring molecules (chlorophyll and lipid) to create a unique nanoparticle that shows promise for numerous diverse light-based (biophotonic) applications. The structure of the nanoparticle, which is like a miniature and colorful water balloon, means it can also be filled with drugs to treat the tumor it is targeting.\" It works this way, explains first author Jonathan Lovell, a doctoral student at OCI: \"Photothermal therapy uses light and heat to destroy tumors. With the nanoparticle's ability to absorb so much light and accumulate in tumors, a laser can rapidly heat the tumor to a temperature of 60 degrees and destroy it. The nanoparticle can also be used for photoacoustic imaging, which combines light and sound to produce a very high-resolution image that can be used to find and target tumors.\" He adds that once the nanoparticle hits its tumor target, it becomes fluorescent to signal \"mission accomplished\". \"There are many nanoparticles out there, but this one is the complete package, a kind of one-stop shopping for various types of cancer imaging and treatment options that can now be mixed and matched in ways previously unimaginable. The unprecedented safety of this nanoparticle in the body is the icing on the cake. We are excited by the possibilities for its use in the clinic,\" says Dr. Zheng. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Optically active nanomaterials promise to advance a range of biophotonic techniques through nanoscale optical effects and integration of multiple imaging and therapeutic modalities. Here, we report the development of porphysomes; nanovesicles formed from self-assembled porphyrin bilayers that generated large, tunable extinction coefficients, structure-dependent fluorescence self-quenching and unique photothermal and photoacoustic properties. Porphysomes enabled the sensitive visualization of lymphatic systems using photoacoustic tomography. Near-infrared fluorescence generation could be restored on dissociation, creating opportunities for low-background fluorescence imaging. As a result of their organic nature, porphysomes were enzymatically biodegradable and induced minimal acute toxicity in mice with intravenous doses of 1,000 mg kg −1 . In a similar manner to liposomes, the large aqueous core of porphysomes could be passively or actively loaded. Following systemic administration, porphysomes accumulated in tumours of xenograft-bearing mice and laser irradiation induced photothermal tumour ablation. The optical properties and biocompatibility of porphysomes demonstrate the multimodal potential of organic nanoparticles for biophotonic imaging and therapy. Main Therapeutic and diagnostic techniques benefiting from components that efficiently absorb light include fluorescent and colorimetric detection 1 , 2 , photothermal and photodynamic therapy 3 , 4 , 5 , photoacoustic tomography (also known as optoacoustic tomography) 6 , 7 , 8 , 9 , optical frequency domain imaging 10 and multimodal techniques 11 , among others. As inorganic nanoparticles often interact strongly with light, they can be used as agents for these techniques. For instance, quantum dots are valuable fluorescent probes and have extinction coefficients in the range of 10 5 –10 6 M −1 cm −1 (ref. 12 ). Gold nanoparticles are useful for colorimetric detection, photothermal and photoacoustic techniques owing to their much higher extinction coefficients, of the order of 10 9 –10 11 M −1 cm −1 (ref. 13 ). Despite recent progress 14 , optically active inorganic nanoparticles have not yet achieved broad clinical implementation, possibly stemming from drug loading typically being limited to the nanoparticle surface and concerns regarding long-term safety 15 , 16 , 17 , 18 . In contrast, organic nanoparticles (including liposomes, lipoproteins, micelles, nanospheres and polymersomes) have found many human therapeutic applications as a result of robust biocompatibility and drug-delivery capacity 18 . However, as these organic nanoparticles generally do not intrinsically absorb light in the near-infrared region, they have been of limited use for biophotonics. Although supramolecular assemblies can be formed entirely by porphyrin conjugates, intensely light-absorbing organic small molecules, these constructs have not been thoroughly explored as biophotonic tools owing to a lack of stability, solubility or biological utility 19 . Here we introduce ‘porphysomes’; organicnanoparticles self-assembled from phospholipid–porphyrin conjugates that exhibit liposome-like structure and loading capacity, high absorption of near-infrared light, structure-dependent fluorescence quenching and excellent biocompatibility, and show promise for diverse biophotonic applications. Porphysomes were formed by supramolecular self-assembly. The porphysome subunits consisted of porphyrin–lipid conjugates generated by an acylation reaction between lysophosphatidylcholine and pyropheophorbide, a chlorophyll-derived porphyrin analogue. This hydrophobic chromophore was positioned in place of an alkyl side chain, maintaining an amphipathic structure ( Fig. 1 a). This conjugate could be self-assembled in aqueous buffer with extrusion to form porphysomes. A concentration of 5 molar% polyethylene glycol (PEG)–lipid was included in the formulation to enhance in vivo pharmacokinetics 20 . Transmission electron microscopy showed that these porphysomes were spherical vesicles of 100 nm in diameter ( Fig. 1 b). At higher magnifications, the porphysome structure was revealed as two layers of higher-density material separated by a 2 nm gap, corresponding to two separate monolayers of porphyrin. Pyropheophorbide porphysomes exhibited two absorption peaks, one at 400 nm and one in the near-infrared window at 680 nm ( Fig. 1 c). Further redshifted porphysomes (760 nm) were produced by using subunits generated from another type of porphyrin; a bacteriochlorophyll analogue that was synthesized in the same manner as pyropheophorbide–lipid. Alternatively, a protocol was developed to insert metal ions into the porphyrin–lipid structure, resulting in shifted optical density bands (440 nm and 670 nm) and demonstrating the unique phenomenon that porphysomes can form metal-chelating bilayers. These different types of porphysome could be useful in scenarios in which specific operating wavelengths are required (for example, to match a given laser excitation source). To verify that the absorbance spectra corresponded to light absorption, rather than scattering, we compared porphysomes with wavelength-matched gold nanorods (with 680 nm extinction peaks) using resonance scattering 21 . Porphysomes exhibited up to 100 times less resonance light scatter at the optical density wavelength peak at which the samples were normalized ( Fig. 1 d). The monodisperse 100 nm sizes exhibited by various types of porphysome ( Fig. 1 e) are in a suitable range to take advantage of the enhanced permeability and retention effect for passive accumulation in tumours 22 , 23 . Flexibility in size control was demonstrated as sonication of porphyrin–lipid in water produced smaller, 30 nm, nanoparticles ( Supplementary Fig. S1 ), which could be useful for applications requiring smaller nanoparticle sizes. Geometric calculations for vesicles of 100 nm in diameter composed of subunits with phosphatidylcholine headgroups indicate that there are approximately 8×10 4 porphyrin conjugates per porphysome 24 . On the basis of pyropheophorbide absorbance (accounting for differences in the absorbance of the intact porphysome measured in PBS and the dissociated porphyrin–lipid obtained by diluting 1–2 μl of porphysomes in 1 ml of methanol, as shown in Supplementary Fig. S2 ), we estimate a pyropheophorbide-porphysome extinction coefficient, ɛ 680 , of 2.9×10 9 M −1 cm −1 . This large, near-infrared extinction coefficient is a reflection of the dense porphyrin packing in the bilayer that generates the unique nanoscale optical behaviour of porphysomes. Figure 1: Porphysomes are optically active nanovesicles formed from porphyrin bilayers. a , Schematic representation of a pyropheophorbide–lipid porphysome. The phospholipid headgroup (red) and porphyrin (blue) are highlighted in the subunit (left) and assembled nanovesicle (right). b , Electron micrographs of negatively stained porphysomes (5% PEG–lipid, 95% pyropheophorbide–lipid). c , Absorbance of the porphyrin–lipid subunits incorporated in porphysomes formed from pyropheophorbide (blue), zinc-pyropheophorbide (orange) and bacteriochlorophyll (red) in<|im_end|> <|im_start|>assistant A team of scientists from Princess Margaret Hospital have created an organic nanoparticle that is completely non-toxic, biodegradable and nimble in the way it uses light and heat to treat cancer and deliver drugs. (A nanoparticle is a minute molecule with novel properties). The findings, published online today in Nature Materials are significant because unlike other nanoparticles, the new nanoparticle has a unique and versatile structure that could potentially change the way tumors are treated, says principal investigator Dr. Gang Zheng, Senior Scientist, Ontario Cancer Institute (OCI), Princess Margaret Hospital at University Health Network. Dr. Zheng says: "In the lab, we combined two naturally occurring molecules (chlorophyll and lipid) to create a unique nanoparticle that shows promise for numerous diverse light-based (biophotonic) applications. The structure of the nanoparticle, which is like a miniature and colorful water balloon, means it can also be filled with drugs to treat the tumor it is targeting." It works this way, explains first author Jonathan Lovell, a doctoral student at OCI: "Photothermal therapy uses light and heat to destroy tumors. With the nanoparticle's ability to absorb so much light and accumulate in tumors, a laser can rapidly heat the tumor to a temperature of 60 degrees and destroy it. The nanoparticle can also be used for photoacoustic imaging, which combines light and sound to produce a very high-resolution image that can be used to find and target tumors." He adds that once the nanoparticle hits its tumor target, it becomes fluorescent to signal "mission accomplished". "There are many nanoparticles out there, but this one is the complete package, a kind of one-stop shopping for various types of cancer imaging and treatment options that can now be mixed and matched in ways previously unimaginable. The unprecedented safety of this nanoparticle in the body is the icing on the cake. We are excited by the possibilities for its use in the clinic," says Dr. Zheng. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 16963, 2740, 4642, 20622, 316, 2229, 82, 11471, 311, 12178, 264, 2134, 315, 6160, 5237, 354, 14338, 12823, 1555, 20622, 437, 2296, 29393, 6372, 323, 18052, 315, 5361, 32758, 323, 37471, 13531, 1385, 13, 5810, 11, 584, 1934, 279, 4500, 315, 4247, 42305, 20969, 26, 20622, 10296, 4440, 14454, 505, 659, 33534, 26994, 4247, 764, 11160, 258, 20934, 5184, 430, 8066, 3544, 11, 11716, 481, 52609, 37929, 11, 6070, 43918, 97332, 659, 74801, 20345, 287, 323, 5016, 4604, 91096, 323, 6685, 582, 35415, 6012, 13, 393, 16751, 1065, 20969, 9147, 279, 16614, 42148, 315, 43745, 780, 6067, 1701, 6685, 582, 35415, 10390, 5814, 13, 31494, 3502, 82482, 97332, 9659, 1436, 387, 28101, 389, 91342, 367, 11, 6968, 10708, 369, 3428, 43034, 97332, 32758, 13, 1666, 264, 1121, 315, 872, 17808, 7138, 11, 4247, 42305, 20969, 1051, 32011, 7167, 6160, 536, 78130, 323, 36572, 17832, 30883, 58011, 304, 24548, 449, 10805, 81443, 35130, 315, 220, 16, 11, 931, 14060, 21647, 25173, 16, 662, 763, 264, 4528, 11827, 311, 19588, 58375, 11, 279, 3544, 66300, 788, 6332, 315, 4247, 42305, 20969, 1436, 387, 1522, 3210, 477, 22815, 6799, 13, 23548, 46417, 8735, 11, 4247, 42305, 20969, 41165, 304, 15756, 2530, 315, 53265, 540, 3017, 92253, 24548, 323, 21120, 76327, 367, 36572, 4604, 91096, 15756, 414, 671, 2354, 13, 578, 29393, 6012, 323, 6160, 12255, 54153, 315, 4247, 42305, 20969, 20461, 279, 80149, 58697, 4754, 315, 17808, 94753, 369, 6160, 5237, 354, 14338, 32758, 323, 15419, 13, 4802, 23258, 32486, 323, 15439, 12823, 84015, 505, 6956, 430, 30820, 35406, 3177, 2997, 74864, 323, 1933, 318, 16743, 18468, 220, 16, 1174, 220, 17, 1174, 4604, 91096, 323, 4604, 61002, 15419, 220, 18, 1174, 220, 19, 1174, 220, 20, 1174, 6685, 582, 35415, 10390, 5814, 320, 19171, 3967, 439, 3469, 78, 582, 35415, 10390, 5814, 8, 220, 21, 1174, 220, 22, 1174, 220, 23, 1174, 220, 24, 1174, 29393, 11900, 8106, 32758, 220, 605, 323, 80149, 58697, 12823, 220, 806, 1174, 4315, 3885, 13, 1666, 304, 61694, 94753, 3629, 16681, 16917, 449, 3177, 11, 814, 649, 387, 1511, 439, 13307, 369, 1521, 12823, 13, 1789, 2937, 11, 31228, 32094, 527, 15525, 74864, 63610, 323, 617, 52609, 37929, 304, 279, 2134, 315, 220, 605, 220, 20, 1389, 605, 220, 21, 386, 25173, 16, 10166, 25173, 16, 320, 1116, 13, 220, 717, 7609, 7573, 94753, 527, 5505, 369, 1933, 318, 16743, 18468, 11, 4604, 91096, 323, 6685, 582, 35415, 12823, 56612, 311, 872, 1790, 5190, 52609, 37929, 11, 315, 279, 2015, 315, 220, 605, 220, 24, 1389, 605, 220, 806, 386, 25173, 16, 10166, 25173, 16, 320, 1116, 13, 220, 1032, 7609, 18185, 3293, 5208, 220, 975, 1174, 3469, 2740, 4642, 304, 61694, 94753, 617, 539, 3686, 17427, 7353, 14830, 8292, 11, 11000, 77044, 505, 5623, 8441, 11383, 1694, 7347, 311, 279, 76307, 7203, 7479, 323, 10742, 9002, 1317, 9860, 7296, 220, 868, 1174, 220, 845, 1174, 220, 1114, 1174, 220, 972, 662, 763, 13168, 11, 17808, 94753, 320, 16564, 19588, 58375, 11, 19588, 454, 5646, 1354, 11, 19748, 37907, 11, 20622, 24527, 13213, 323, 46033, 388, 20969, 8, 617, 1766, 1690, 3823, 37471, 8522, 439, 264, 1121, 315, 22514, 6160, 12255, 54153, 323, 5623, 48226, 6633, 8824, 220, 972, 662, 4452, 11, 439, 1521, 17808, 94753, 8965, 656, 539, 10805, 1354, 2740, 35406, 3177, 304, 279, 3221, 3502, 82482, 5654, 11, 814, 617, 1027, 315, 7347, 1005, 369, 6160, 5237, 26934, 1233, 13, 10541, 1043, 2453, 43943, 62407, 649, 387, 14454, 11622, 555, 4247, 764, 11160, 258, 64380, 988, 11, 70733, 3177, 97510, 269, 7278, 17808, 2678, 35715, 11, 1521, 57327, 617, 539, 1027, 27461, 36131, 439, 6160, 5237, 354, 14338, 7526, 56612, 311, 264, 6996, 315, 20334, 11, 2092, 392, 1429, 477, 24156, 15919, 220, 777, 662, 5810, 584, 19678, 3451, 4406, 42305, 20969, 529, 26, 17808, 19285, 454, 16641, 659, 33534, 26994, 505, 33088, 337, 575, 307, 4235, 4406, 764, 11160, 258, 64380, 988, 430, 31324, 19588, 32554, 12970, 6070, 323, 8441, 8824, 11, 1579, 44225, 315, 3221, 3502, 82482, 3177, 11, 6070, 43918, 97332, 934, 20345, 287, 323, 9250, 6160, 12255, 54153, 11, 323, 1501, 11471, 369, 17226, 6160, 5237, 354, 14338, 8522, 13, 393, 16751, 1065, 20969, 1051, 14454, 555, 1043, 2453, 43943, 659, 12, 15343, 13, 578, 4247, 42305, 638, 1207, 26726, 44660, 315, 4247, 764, 11160, 258, 4235, 34215, 307, 64380, 988, 8066, 555, 459, 1645, 79933, 13010, 1990, 84495, 5237, 24527, 266, 307, 4010, 331, 22671, 323, 4611, 48983, 5237, 30986, 579, 11, 264, 37833, 5237, 25734, 72286, 4247, 764, 11160, 258, 91343, 13, 1115, 17055, 764, 31906, 22083, 5237, 461, 574, 35328, 304, 2035, 315, 459, 58998, 4010, 3185, 8957, 11, 20958, 459, 66092, 575, 589, 292, 6070, 320, 23966, 13, 220, 16, 264, 570, 1115, 64380, 349, 1436, 387, 659, 33534, 26994, 304, 66300, 788, 4240, 449, 11741, 7713, 311, 1376, 4247, 42305, 20969, 13, 362, 20545, 315, 220, 20, 296, 7569, 4, 10062, 88640, 37807, 2119, 320, 22836, 8, 4235, 34215, 307, 574, 5343, 304, 279, 55986, 311, 18885, 304, 41294, 36449, 79117, 25265, 220, 508, 662, 48125, 17130, 92914, 8710, 430, 1521, 4247, 42305, 20969, 1051, 65251, 65635, 4440, 315, 220, 1041, 26807, 304, 23899, 320, 23966, 13, 220, 16, 293, 570, 2468, 5190, 8622, 7174, 11, 279, 4247, 42305, 638, 6070, 574, 10675, 439, 1403, 13931, 315, 5190, 89131, 3769, 19180, 555, 264, 220, 17, 26807, 13225, 11, 12435, 311, 1403, 8821, 1647, 337, 5184, 315, 4247, 764, 11160, 258, 13, 5468, 48983, 5237, 30986, 579, 4247, 42305, 20969, 51713, 1403, 44225, 40035, 11, 832, 520, 220, 3443, 26807, 323, 832, 304, 279, 3221, 3502, 82482, 3321, 520, 220, 17814, 26807, 320, 23966, 13, 220, 16, 272, 570, 15903, 2579, 13724, 291, 4247, 42305, 20969, 320, 19104, 26807, 8, 1051, 9124, 555, 1701, 1207, 26726, 8066, 505, 2500, 955, 315, 4247, 764, 11160, 258, 26, 264, 17854, 822, 72967, 5237, 25734, 91343, 430, 574, 92106, 304, 279, 1890, 11827, 439, 4611, 48983, 5237, 30986, 579, 4235, 34215, 307, 13, 39578, 11, 264, 11766, 574, 8040, 311, 5774, 9501, 65125, 1139, 279, 4247, 764, 11160, 258, 4235, 34215, 307, 6070, 11, 13239, 304, 30073, 29393, 17915, 21562, 320, 14868, 26807, 323, 220, 21218, 26807, 8, 323, 45296, 279, 5016, 25885, 430, 4247, 42305, 20969, 649, 1376, 9501, 11843, 301, 1113, 20934, 5184, 13, 4314, 2204, 4595, 315, 4247, 42305, 638, 1436, 387, 5505, 304, 26350, 304, 902, 3230, 10565, 93959, 527, 2631, 320, 2000, 3187, 11, 311, 2489, 264, 2728, 21120, 3521, 7709, 2592, 570, 2057, 10356, 430, 279, 35406, 685, 63697, 8024, 291, 311, 3177, 44225, 11, 4856, 1109, 72916, 11, 584, 7863, 4247, 42305, 20969, 449, 46406, 1474, 35344, 6761, 20622, 269, 30797, 320, 4291, 220, 17814, 26807, 52609, 40035, 8, 1701, 58081, 72916, 220, 1691, 662, 393, 16751, 1065, 20969, 51713, 709, 311, 220, 1041, 3115, 2753, 58081, 3177, 45577, 520, 279, 29393, 17915, 46406, 16557, 520, 902, 279, 10688, 1051, 30510, 320, 23966, 13, 220, 16, 294, 570, 578, 1647, 347, 28470, 325, 220, 1041, 26807, 12562, 51713, 555, 5370, 4595, 315, 4247, 42305, 638, 320, 23966, 13, 220, 16, 384, 8, 527, 304, 264, 14791, 2134, 311, 1935, 9610, 315, 279, 24872, 55424, 2968, 323, 38231, 2515, 369, 28979, 46835, 304, 15756, 2530, 220, 1313, 1174, 220, 1419, 662, 27233, 3225, 304, 1404, 2585, 574, 21091, 439, 4538, 20901, 315, 4247, 764, 11160, 258, 4235, 34215, 307, 304, 3090, 9124, 9333, 11, 220, 966, 26807, 11, 94753, 320, 99371, 23966, 13, 328, 16, 7026, 902, 1436, 387, 5505, 369, 8522, 23537, 9333, 76307, 7203, 12562, 13, 4323, 24264, 29217, 369, 65635, 4440, 315, 220, 1041, 26807, 304, 23899, 24306, 315, 1207, 26726, 449, 33088, 266, 307, 4010, 331, 22671, 2010, 17171, 13519, 430, 1070, 527, 13489, 220, 23, 18028, 605, 220, 19, 4247, 764, 11160, 258, 64380, 988, 824, 4247, 42305, 638, 220, 1187, 662, 1952, 279, 8197, 315, 4611, 48983, 5237, 30986, 579, 35406, 685, 320, 4711, 287, 369, 12062, 304, 279, 35406, 685, 315, 279, 35539, 4247, 42305, 638, 17303, 304, 60145, 323, 279, 91342, 660, 4247, 764, 11160, 258, 4235, 34215, 307, 12457, 555, 19371, 10831, 220, 16, 4235, 17, 33983, 75, 315, 4247, 42305, 20969, 304, 220, 16, 16116, 315, 21747, 39710, 11, 439, 6982, 304, 99371, 23966, 13, 328, 17, 7026, 584, 16430, 264, 4611, 48983, 5237, 30986, 579, 2320, 16751, 1065, 638, 52609, 36706, 11, 220, 133, 249, 220, 17814, 1174, 315, 220, 17, 13, 24, 18028, 605, 220, 24, 386, 25173, 16, 10166, 25173, 16, 662, 1115, 3544, 11, 3221, 3502, 82482, 52609, 36706, 374, 264, 22599, 315, 279, 29050, 4247, 764, 11160, 258, 36813, 304, 279, 20934, 1155, 430, 27983, 279, 5016, 20622, 437, 2296, 29393, 17432, 315, 4247, 42305, 20969, 13, 19575, 220, 16, 25, 393, 16751, 1065, 20969, 527, 3469, 2740, 4642, 20622, 10296, 4440, 14454, 505, 4247, 764, 11160, 258, 20934, 5184, 13, 264, 1174, 328, 82149, 13340, 315, 264, 4611, 48983, 5237, 30986, 579, 4235, 34215, 307, 4247, 42305, 638, 13, 578, 33088, 337, 575, 307, 2010, 4166, 320, 1171, 8, 323, 4247, 764, 11160, 258, 320, 12481, 8, 527, 27463, 304, 279, 1207, 3928, 320, 2414, 8, 323, 35105, 20622, 10296, 2045, 320, 1315, 570, 293, 1174, 77976, 8162, 87286, 315, 48291, 61152, 4247, 42305, 20969, 320, 20, 4, 393, 9560, 4235, 34215, 307, 11, 220, 2721, 4, 4611, 48983, 5237, 30986, 579, 4235, 34215, 307, 570, 272, 1174, 22855, 30986, 685, 315, 279, 4247, 764, 11160, 258, 4235, 34215, 307, 1207, 26726, 32762, 304, 4247, 42305, 20969, 14454, 505, 4611, 48983, 5237, 30986, 579, 320, 12481, 705, 49601, 2320, 88, 48983, 5237, 30986, 579, 320, 35264, 8, 323, 17854, 822, 72967, 5237, 25734, 320, 1171, 8, 304, 128257, 198, 128256, 78191, 198, 32, 2128, 315, 14248, 505, 30389, 38649, 15429, 617, 3549, 459, 17808, 76307, 7203, 430, 374, 6724, 2536, 4791, 14668, 11, 6160, 536, 78130, 323, 46792, 901, 304, 279, 1648, 433, 5829, 3177, 323, 8798, 311, 4322, 9572, 323, 6493, 11217, 13, 320, 32, 76307, 7203, 374, 264, 9568, 43030, 449, 11775, 6012, 570, 578, 14955, 11, 4756, 2930, 3432, 304, 22037, 32009, 527, 5199, 1606, 20426, 1023, 94753, 11, 279, 502, 76307, 7203, 706, 264, 5016, 323, 33045, 6070, 430, 1436, 13893, 2349, 279, 1648, 56071, 527, 12020, 11, 2795, 12717, 49581, 2999, 13, 35517, 77547, 11, 19903, 68409, 11, 21193, 26211, 10181, 320, 65083, 705, 30389, 38649, 15429, 520, 3907, 6401, 8304, 13, 2999, 13, 77547, 2795, 25, 330, 644, 279, 10278, 11, 584, 11093, 1403, 18182, 31965, 35715, 320, 72967, 5237, 25734, 323, 68700, 8, 311, 1893, 264, 5016, 76307, 7203, 430, 5039, 11471, 369, 12387, 17226, 3177, 6108, 320, 8385, 5237, 354, 14338, 8, 8522, 13, 578, 6070, 315, 279, 76307, 7203, 11, 902, 374, 1093, 264, 57863, 323, 34966, 3090, 47856, 11, 3445, 433, 649, 1101, 387, 10409, 449, 11217, 311, 4322, 279, 36254, 433, 374, 25103, 1210, 1102, 4375, 420, 1648, 11, 15100, 1176, 3229, 24150, 35393, 616, 11, 264, 74657, 5575, 520, 93187, 25, 330, 53304, 91096, 15419, 5829, 3177, 323, 8798, 311, 7066, 56071, 13, 3161, 279, 76307, 7203, 596, 5845, 311, 35406, 779, 1790, 3177, 323, 47376, 304, 56071, 11, 264, 21120, 649, 19019, 8798, 279, 36254, 311, 264, 9499, 315, 220, 1399, 12628, 323, 7066, 433, 13, 578, 76307, 7203, 649, 1101, 387, 1511, 369, 6685, 582, 35415, 32758, 11, 902, 33511, 3177, 323, 5222, 311, 8356, 264, 1633, 1579, 64036, 2217, 430, 649, 387, 1511, 311, 1505, 323, 2218, 56071, 1210, 1283, 11621, 430, 3131, 279, 76307, 7203, 13280, 1202, 36254, 2218, 11, 433, 9221, 74864, 311, 8450, 330, 2796, 27332, 3343, 330, 3947, 527, 1690, 94753, 704, 1070, 11, 719, 420, 832, 374, 279, 4686, 6462, 11, 264, 3169, 315, 832, 42311, 12185, 369, 5370, 4595, 315, 9572, 32758, 323, 6514, 2671, 430, 649, 1457, 387, 9709, 323, 18545, 304, 5627, 8767, 87212, 481, 13, 578, 31069, 7296, 315, 420, 76307, 7203, 304, 279, 2547, 374, 279, 76106, 389, 279, 19692, 13, 1226, 527, 12304, 555, 279, 24525, 369, 1202, 1005, 304, 279, 28913, 1359, 2795, 2999, 13, 77547, 13, 220, 128257, 198 ]

2,045

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Objectives To assess self reported outcomes and adverse events after self sourced medical abortion through online telemedicine. Design Population based study. Setting Republic of Ireland and Northern Ireland, where abortion is unavailable through the formal healthcare system except in a few restricted circumstances. Population 1000 women who underwent self sourced medical abortion through Women on Web (WoW), an online telemedicine service, between 1 January 2010 and 31 December 2012. Main outcome measures Successful medical abortion: the proportion of women who reported ending their pregnancy without surgical intervention. Rates of adverse events: the proportion who reported treatment for adverse events, including receipt of antibiotics and blood transfusion, and deaths reported by family members, friends, or the authorities. Care seeking for symptoms of potential complications: the frequency with which women reported experiencing symptoms of a potentially serious complication and the proportion who reported seeking medical attention as advised. Results In 2010-12, abortion medications (mifepristone and misoprostol) were sent to 1636 women and follow-up information was obtained for 1158 (71%). Among these, 1023 women confirmed use of the medications, and follow-up information was available for 1000. At the time women requested help from WoW, 781 (78%) were <7 weeks pregnant and 219 (22%) were 7-9 weeks pregnant. Overall, 94.7% (95% confidence interval 93.1% to 96.0%) reported successfully ending their pregnancy without surgical intervention. Seven women (0.7%, 0.3% to 1.5%) reported receiving a blood transfusion, and 26 (2.6%, 1.7% to 3.8%) reported receiving antibiotics (route of administration (IV or oral) could not be determined). No deaths resulting from the intervention were reported by family, friends, the authorities, or the media. Ninety three women (9.3%, 7.6% to 11.3%) reported experiencing any symptom for which they were advised to seek medical advice, and, of these, 87 (95%, 87.8% to 98.2%) sought attention. None of the five women who did not seek medical attention reported experiencing an adverse outcome. Conclusions Self sourced medical abortion using online telemedicine can be highly effective, and outcomes compare favourably with in clinic protocols. Reported rates of adverse events are low. Women are able to self identify the symptoms of potentially serious complications, and most report seeking medical attention when advised. Results have important implications for women worldwide living in areas where access to abortion is restricted. Introduction About a quarter of the world’s population lives in countries with highly restrictive abortion laws. 1 Women in these countries often resort to unsafe methods to end their pregnancies. Globally, each year an estimated 43000 women die as a result of lack of access to safe legal abortion services through their countries’ formal healthcare systems. 2 Millions more have complications. 3 Worldwide, the fourth leading cause of maternal mortality is unsafe abortion. 4 Yet in many countries, self sourced medical abortion provides a vital alternative to dangerous methods such as using sharp objects or noxious substances. Women source mifepristone and misoprostol (or misoprostol alone) themselves and use the medications outside the formal healthcare system. In some settings, women buy the medications from pharmacies or markets. 5 In other settings, they can self source using online telemedicine initiatives that provide medications as well as help and support by email or instant messaging. 6 One setting in which online telemedicine has dramatically changed women’s access to abortion is in the Republic of Ireland and Northern Ireland. Abortion laws in both the Republic and Northern Ireland are among the most restrictive in the world. 1 Abortion is allowed only to save a women’s life and, in Northern Ireland only, her permanent physical and mental health. 7 8 Although Northern Ireland is part of the UK, the Northern Irish legislature did not adopt the 1967 Abortion Act, which legalised abortion carried out by registered medical practitioners in England, Scotland, and Wales. As a result, abortion under most circumstances remains illegal there under the Offences Against the Person Act of 1861, which provides a maximum penalty for the woman undergoing the abortion of life imprisonment. 9 Women from the Republic and Northern Ireland who do not want to, or feel they cannot, continue with a pregnancy have traditionally had three options: those with the requisite financial and logistical means can travel abroad to access abortion in a clinic, while those who do not must either self induce using an unsafe method or continue their unwanted pregnancy. For the past decade, however, women of all financial means have also had the option to self source early medical abortion through online telemedicine. 10 11 Despite having been used by thousands of women in the Republic and Northern Ireland 11 and tens of thousands of women worldwide, 12 little is known about the outcomes of these self sourced medical abortions. Two existing studies have examined data from telemedicine initiatives: one across various settings 6 and the other in Brazil. 13 These studies showed encouraging results with respect to efficacy but were limited by small sample sizes and relatively high losses to follow-up. Moreover, no study has examined whether women are able to safely manage their own abortions by identifying the symptoms of serious complications and presenting for medical advice when appropriate. Using data from an online telemedicine initiative, we conducted a population based analysis of women in the Republic of Ireland and Northern Ireland who self sourced medical abortion during a three year period. We examined self reported outcomes and complications after medical abortion through online telemedicine and assessed women’s ability to self screen for the symptoms of potentially serious complications of abortion and their propensity to seek medical attention. In light of current policy debates, 9 14 the Republic and Northern Ireland provide a particularly important and timely opportunity to examine women’s self reported outcomes. Methods We examined data from Women on Web (WoW), a non-profit organisation that provides early medical abortion through online telemedicine in countries where access to safe abortion is restricted. The service is currently available for women up to 10 weeks’ gestation at the time of request. To make a request, women fill out a consultation", "role": "user" }, { "content": "Women in Ireland and Northern Ireland acquiring medical abortion pills through online telemedicine report successful terminations with low rates of adverse effects, according to new research published in The BMJ by Princeton University, the University of Texas at Austin and Women on Web. The researchers examined self-reported outcomes following medical abortions conducted outside the formal healthcare setting through Women on Web (WoW), a nonprofit organization that provides access to medications used to induce abortion. The results show that 95 percent of self-sourced and self-managed medical abortions were successful. Less than one percent of the women required a blood transfusion, and three percent received antibiotics. Women were able to identify the symptoms of potentially serious complications, and almost all reported seeking in-person medical attention when advised. \"Our results show that telemedicine abortions provided by Women on Web are safe and effective,\" said co-author James Trussell, the Charles and Marie Robertson Professor of Public and International Affairs, Emeritus, and professor of economics and public affairs, emeritus, at Princeton University's Woodrow Wilson School of Public and International Affairs. Abortion laws in Ireland and Northern Ireland are among the most restrictive in the world, with abortion criminalized in most circumstances. However, online telemedicine has dramatically changed abortion access. \"Irish and Northern Irish people who access or help others to access this pathway are choosing an option that has similar effectiveness rates to medication abortion performed in a clinic and has lower rates of complications than continuing a pregnancy to delivery,\" said lead author Abigail Aiken, assistant professor at the University of Texas's Lyndon B. Johnson School of Public Affairs. \"This study shows that medication abortion self-sourced and self-managed outside the formal healthcare setting can be a safe and effective option for those who rely on or prefer it.\" Using data from WoW, researchers conducted a population based analysis of 1,000 women in the Republic of Ireland and Northern Ireland who self-sourced medical abortion during a three-year period. Aiken and Trussell, along with co-authors Rebecca Gomperts and Irena Digol from WoW, examined self-reported outcomes and complications, and assessed women's ability to self-screen for the symptoms of potentially serious complications, as well as their propensity to seek medical attention. The findings also have implications for other parts of the world where abortion is difficult to access. \"Following waves of restrictive legislation in the United States, the parallels between women seeking abortion in certain parts of the U.S. and Ireland and Northern Ireland are striking,\" Aiken said. \"Women in Ireland and Northern Ireland have three options when faced with a pregnancy they do not want or feel they cannot continue: travel long distances to access in-clinic abortion care, remain pregnant, or self-source their own abortion outside the formal healthcare setting. In the case of the United States, we already know women are self-sourcing, so there is a public health duty to help make it as safe and supported as possible.\" The researchers acknowledge the limitations of self-reporting, but also emphasize that in situations where women self-source their own abortions outside the formal healthcare setting, self-report is the only possible method of follow-up. The large sample size and high follow-up rate, which is comparable with or, in some cases, better than studies of abortion within the formal healthcare setting are also strengths of the study. The study, \"Self-Reported Outcomes and Adverse Events Following Medical Abortion via Online Telemedicine: A Population-based Study in Ireland and Northern Ireland,\" was published online May 16. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Objectives To assess self reported outcomes and adverse events after self sourced medical abortion through online telemedicine. Design Population based study. Setting Republic of Ireland and Northern Ireland, where abortion is unavailable through the formal healthcare system except in a few restricted circumstances. Population 1000 women who underwent self sourced medical abortion through Women on Web (WoW), an online telemedicine service, between 1 January 2010 and 31 December 2012. Main outcome measures Successful medical abortion: the proportion of women who reported ending their pregnancy without surgical intervention. Rates of adverse events: the proportion who reported treatment for adverse events, including receipt of antibiotics and blood transfusion, and deaths reported by family members, friends, or the authorities. Care seeking for symptoms of potential complications: the frequency with which women reported experiencing symptoms of a potentially serious complication and the proportion who reported seeking medical attention as advised. Results In 2010-12, abortion medications (mifepristone and misoprostol) were sent to 1636 women and follow-up information was obtained for 1158 (71%). Among these, 1023 women confirmed use of the medications, and follow-up information was available for 1000. At the time women requested help from WoW, 781 (78%) were <7 weeks pregnant and 219 (22%) were 7-9 weeks pregnant. Overall, 94.7% (95% confidence interval 93.1% to 96.0%) reported successfully ending their pregnancy without surgical intervention. Seven women (0.7%, 0.3% to 1.5%) reported receiving a blood transfusion, and 26 (2.6%, 1.7% to 3.8%) reported receiving antibiotics (route of administration (IV or oral) could not be determined). No deaths resulting from the intervention were reported by family, friends, the authorities, or the media. Ninety three women (9.3%, 7.6% to 11.3%) reported experiencing any symptom for which they were advised to seek medical advice, and, of these, 87 (95%, 87.8% to 98.2%) sought attention. None of the five women who did not seek medical attention reported experiencing an adverse outcome. Conclusions Self sourced medical abortion using online telemedicine can be highly effective, and outcomes compare favourably with in clinic protocols. Reported rates of adverse events are low. Women are able to self identify the symptoms of potentially serious complications, and most report seeking medical attention when advised. Results have important implications for women worldwide living in areas where access to abortion is restricted. Introduction About a quarter of the world’s population lives in countries with highly restrictive abortion laws. 1 Women in these countries often resort to unsafe methods to end their pregnancies. Globally, each year an estimated 43000 women die as a result of lack of access to safe legal abortion services through their countries’ formal healthcare systems. 2 Millions more have complications. 3 Worldwide, the fourth leading cause of maternal mortality is unsafe abortion. 4 Yet in many countries, self sourced medical abortion provides a vital alternative to dangerous methods such as using sharp objects or noxious substances. Women source mifepristone and misoprostol (or misoprostol alone) themselves and use the medications outside the formal healthcare system. In some settings, women buy the medications from pharmacies or markets. 5 In other settings, they can self source using online telemedicine initiatives that provide medications as well as help and support by email or instant messaging. 6 One setting in which online telemedicine has dramatically changed women’s access to abortion is in the Republic of Ireland and Northern Ireland. Abortion laws in both the Republic and Northern Ireland are among the most restrictive in the world. 1 Abortion is allowed only to save a women’s life and, in Northern Ireland only, her permanent physical and mental health. 7 8 Although Northern Ireland is part of the UK, the Northern Irish legislature did not adopt the 1967 Abortion Act, which legalised abortion carried out by registered medical practitioners in England, Scotland, and Wales. As a result, abortion under most circumstances remains illegal there under the Offences Against the Person Act of 1861, which provides a maximum penalty for the woman undergoing the abortion of life imprisonment. 9 Women from the Republic and Northern Ireland who do not want to, or feel they cannot, continue with a pregnancy have traditionally had three options: those with the requisite financial and logistical means can travel abroad to access abortion in a clinic, while those who do not must either self induce using an unsafe method or continue their unwanted pregnancy. For the past decade, however, women of all financial means have also had the option to self source early medical abortion through online telemedicine. 10 11 Despite having been used by thousands of women in the Republic and Northern Ireland 11 and tens of thousands of women worldwide, 12 little is known about the outcomes of these self sourced medical abortions. Two existing studies have examined data from telemedicine initiatives: one across various settings 6 and the other in Brazil. 13 These studies showed encouraging results with respect to efficacy but were limited by small sample sizes and relatively high losses to follow-up. Moreover, no study has examined whether women are able to safely manage their own abortions by identifying the symptoms of serious complications and presenting for medical advice when appropriate. Using data from an online telemedicine initiative, we conducted a population based analysis of women in the Republic of Ireland and Northern Ireland who self sourced medical abortion during a three year period. We examined self reported outcomes and complications after medical abortion through online telemedicine and assessed women’s ability to self screen for the symptoms of potentially serious complications of abortion and their propensity to seek medical attention. In light of current policy debates, 9 14 the Republic and Northern Ireland provide a particularly important and timely opportunity to examine women’s self reported outcomes. Methods We examined data from Women on Web (WoW), a non-profit organisation that provides early medical abortion through online telemedicine in countries where access to safe abortion is restricted. The service is currently available for women up to 10 weeks’ gestation at the time of request. To make a request, women fill out a consultation<|im_end|> <|im_start|>assistant Women in Ireland and Northern Ireland acquiring medical abortion pills through online telemedicine report successful terminations with low rates of adverse effects, according to new research published in The BMJ by Princeton University, the University of Texas at Austin and Women on Web. The researchers examined self-reported outcomes following medical abortions conducted outside the formal healthcare setting through Women on Web (WoW), a nonprofit organization that provides access to medications used to induce abortion. The results show that 95 percent of self-sourced and self-managed medical abortions were successful. Less than one percent of the women required a blood transfusion, and three percent received antibiotics. Women were able to identify the symptoms of potentially serious complications, and almost all reported seeking in-person medical attention when advised. "Our results show that telemedicine abortions provided by Women on Web are safe and effective," said co-author James Trussell, the Charles and Marie Robertson Professor of Public and International Affairs, Emeritus, and professor of economics and public affairs, emeritus, at Princeton University's Woodrow Wilson School of Public and International Affairs. Abortion laws in Ireland and Northern Ireland are among the most restrictive in the world, with abortion criminalized in most circumstances. However, online telemedicine has dramatically changed abortion access. "Irish and Northern Irish people who access or help others to access this pathway are choosing an option that has similar effectiveness rates to medication abortion performed in a clinic and has lower rates of complications than continuing a pregnancy to delivery," said lead author Abigail Aiken, assistant professor at the University of Texas's Lyndon B. Johnson School of Public Affairs. "This study shows that medication abortion self-sourced and self-managed outside the formal healthcare setting can be a safe and effective option for those who rely on or prefer it." Using data from WoW, researchers conducted a population based analysis of 1,000 women in the Republic of Ireland and Northern Ireland who self-sourced medical abortion during a three-year period. Aiken and Trussell, along with co-authors Rebecca Gomperts and Irena Digol from WoW, examined self-reported outcomes and complications, and assessed women's ability to self-screen for the symptoms of potentially serious complications, as well as their propensity to seek medical attention. The findings also have implications for other parts of the world where abortion is difficult to access. "Following waves of restrictive legislation in the United States, the parallels between women seeking abortion in certain parts of the U.S. and Ireland and Northern Ireland are striking," Aiken said. "Women in Ireland and Northern Ireland have three options when faced with a pregnancy they do not want or feel they cannot continue: travel long distances to access in-clinic abortion care, remain pregnant, or self-source their own abortion outside the formal healthcare setting. In the case of the United States, we already know women are self-sourcing, so there is a public health duty to help make it as safe and supported as possible." The researchers acknowledge the limitations of self-reporting, but also emphasize that in situations where women self-source their own abortions outside the formal healthcare setting, self-report is the only possible method of follow-up. The large sample size and high follow-up rate, which is comparable with or, in some cases, better than studies of abortion within the formal healthcare setting are also strengths of the study. The study, "Self-Reported Outcomes and Adverse Events Following Medical Abortion via Online Telemedicine: A Population-based Study in Ireland and Northern Ireland," was published online May 16. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 3075, 1924, 2057, 8720, 659, 5068, 20124, 323, 31959, 4455, 1306, 659, 42211, 6593, 20710, 1555, 2930, 8122, 83543, 13, 7127, 40629, 3196, 4007, 13, 20638, 5545, 315, 14990, 323, 17355, 14990, 11, 1405, 20710, 374, 36087, 1555, 279, 16287, 18985, 1887, 3734, 304, 264, 2478, 22486, 13463, 13, 40629, 220, 1041, 15, 3278, 889, 55093, 659, 42211, 6593, 20710, 1555, 11215, 389, 5000, 320, 63862, 54, 705, 459, 2930, 8122, 83543, 2532, 11, 1990, 220, 16, 6186, 220, 679, 15, 323, 220, 2148, 6790, 220, 679, 17, 13, 4802, 15632, 11193, 46626, 6593, 20710, 25, 279, 21801, 315, 3278, 889, 5068, 13696, 872, 20209, 2085, 34933, 21623, 13, 48076, 315, 31959, 4455, 25, 279, 21801, 889, 5068, 6514, 369, 31959, 4455, 11, 2737, 23383, 315, 46850, 323, 6680, 20429, 7713, 11, 323, 16779, 5068, 555, 3070, 3697, 11, 4885, 11, 477, 279, 11527, 13, 10852, 11125, 369, 13803, 315, 4754, 36505, 25, 279, 11900, 449, 902, 3278, 5068, 25051, 13803, 315, 264, 13893, 6129, 86919, 323, 279, 21801, 889, 5068, 11125, 6593, 6666, 439, 26160, 13, 18591, 763, 220, 679, 15, 12, 717, 11, 20710, 31010, 320, 76, 1643, 652, 380, 606, 323, 5906, 454, 42602, 337, 8, 1051, 3288, 311, 220, 9892, 21, 3278, 323, 1833, 5352, 2038, 574, 12457, 369, 220, 7322, 23, 320, 6028, 53172, 22395, 1521, 11, 220, 4278, 18, 3278, 11007, 1005, 315, 279, 31010, 11, 323, 1833, 5352, 2038, 574, 2561, 369, 220, 1041, 15, 13, 2468, 279, 892, 3278, 11472, 1520, 505, 88745, 11, 220, 21893, 320, 2495, 11587, 1051, 366, 22, 5672, 20895, 323, 220, 13762, 320, 1313, 11587, 1051, 220, 22, 12, 24, 5672, 20895, 13, 28993, 11, 220, 6281, 13, 22, 4, 320, 2721, 4, 12410, 10074, 220, 6365, 13, 16, 4, 311, 220, 4161, 13, 15, 11587, 5068, 7946, 13696, 872, 20209, 2085, 34933, 21623, 13, 31048, 3278, 320, 15, 13, 22, 13689, 220, 15, 13, 18, 4, 311, 220, 16, 13, 20, 11587, 5068, 12588, 264, 6680, 20429, 7713, 11, 323, 220, 1627, 320, 17, 13, 21, 13689, 220, 16, 13, 22, 4, 311, 220, 18, 13, 23, 11587, 5068, 12588, 46850, 320, 9143, 315, 8735, 320, 3166, 477, 21308, 8, 1436, 539, 387, 11075, 570, 2360, 16779, 13239, 505, 279, 21623, 1051, 5068, 555, 3070, 11, 4885, 11, 279, 11527, 11, 477, 279, 3772, 13, 27825, 2676, 2380, 3278, 320, 24, 13, 18, 13689, 220, 22, 13, 21, 4, 311, 220, 806, 13, 18, 11587, 5068, 25051, 904, 49648, 369, 902, 814, 1051, 26160, 311, 6056, 6593, 9650, 11, 323, 11, 315, 1521, 11, 220, 4044, 320, 2721, 13689, 220, 4044, 13, 23, 4, 311, 220, 3264, 13, 17, 11587, 16495, 6666, 13, 2290, 315, 279, 4330, 3278, 889, 1550, 539, 6056, 6593, 6666, 5068, 25051, 459, 31959, 15632, 13, 1221, 24436, 10323, 42211, 6593, 20710, 1701, 2930, 8122, 83543, 649, 387, 7701, 7524, 11, 323, 20124, 9616, 12617, 2915, 449, 304, 28913, 32885, 13, 79711, 7969, 315, 31959, 4455, 527, 3428, 13, 11215, 527, 3025, 311, 659, 10765, 279, 13803, 315, 13893, 6129, 36505, 11, 323, 1455, 1934, 11125, 6593, 6666, 994, 26160, 13, 18591, 617, 3062, 25127, 369, 3278, 15603, 5496, 304, 5789, 1405, 2680, 311, 20710, 374, 22486, 13, 29438, 10180, 264, 8502, 315, 279, 1917, 753, 7187, 6439, 304, 5961, 449, 7701, 58096, 20710, 7016, 13, 220, 16, 11215, 304, 1521, 5961, 3629, 22541, 311, 20451, 5528, 311, 842, 872, 82308, 13, 63388, 750, 11, 1855, 1060, 459, 13240, 220, 14245, 410, 3278, 2815, 439, 264, 1121, 315, 6996, 315, 2680, 311, 6220, 5897, 20710, 3600, 1555, 872, 5961, 529, 16287, 18985, 6067, 13, 220, 17, 74418, 810, 617, 36505, 13, 220, 18, 53035, 11, 279, 11999, 6522, 5353, 315, 50150, 29528, 374, 20451, 20710, 13, 220, 19, 14968, 304, 1690, 5961, 11, 659, 42211, 6593, 20710, 5825, 264, 16595, 10778, 311, 11660, 5528, 1778, 439, 1701, 17676, 6302, 477, 912, 30351, 33155, 13, 11215, 2592, 296, 1643, 652, 380, 606, 323, 5906, 454, 42602, 337, 320, 269, 5906, 454, 42602, 337, 7636, 8, 5694, 323, 1005, 279, 31010, 4994, 279, 16287, 18985, 1887, 13, 763, 1063, 5110, 11, 3278, 3780, 279, 31010, 505, 77605, 477, 11987, 13, 220, 20, 763, 1023, 5110, 11, 814, 649, 659, 2592, 1701, 2930, 8122, 83543, 28271, 430, 3493, 31010, 439, 1664, 439, 1520, 323, 1862, 555, 2613, 477, 9888, 30622, 13, 220, 21, 3861, 6376, 304, 902, 2930, 8122, 83543, 706, 29057, 5614, 3278, 753, 2680, 311, 20710, 374, 304, 279, 5545, 315, 14990, 323, 17355, 14990, 13, 3765, 26973, 7016, 304, 2225, 279, 5545, 323, 17355, 14990, 527, 4315, 279, 1455, 58096, 304, 279, 1917, 13, 220, 16, 3765, 26973, 374, 5535, 1193, 311, 3665, 264, 3278, 753, 2324, 323, 11, 304, 17355, 14990, 1193, 11, 1077, 15690, 7106, 323, 10723, 2890, 13, 220, 22, 220, 23, 10541, 17355, 14990, 374, 961, 315, 279, 6560, 11, 279, 17355, 18088, 39856, 1550, 539, 11142, 279, 220, 5162, 22, 3765, 26973, 3298, 11, 902, 5897, 4147, 20710, 11953, 704, 555, 9879, 6593, 43195, 304, 9635, 11, 19627, 11, 323, 23782, 13, 1666, 264, 1121, 11, 20710, 1234, 1455, 13463, 8625, 12079, 1070, 1234, 279, 4206, 2436, 30241, 279, 7508, 3298, 315, 220, 9714, 16, 11, 902, 5825, 264, 7340, 16750, 369, 279, 5333, 47397, 279, 20710, 315, 2324, 43374, 13, 220, 24, 11215, 505, 279, 5545, 323, 17355, 14990, 889, 656, 539, 1390, 311, 11, 477, 2733, 814, 4250, 11, 3136, 449, 264, 20209, 617, 36342, 1047, 2380, 2671, 25, 1884, 449, 279, 82780, 6020, 323, 96968, 3445, 649, 5944, 22917, 311, 2680, 20710, 304, 264, 28913, 11, 1418, 1884, 889, 656, 539, 2011, 3060, 659, 49853, 1701, 459, 20451, 1749, 477, 3136, 872, 36021, 20209, 13, 1789, 279, 3347, 13515, 11, 4869, 11, 3278, 315, 682, 6020, 3445, 617, 1101, 1047, 279, 3072, 311, 659, 2592, 4216, 6593, 20710, 1555, 2930, 8122, 83543, 13, 220, 605, 220, 806, 18185, 3515, 1027, 1511, 555, 9214, 315, 3278, 304, 279, 5545, 323, 17355, 14990, 220, 806, 323, 22781, 315, 9214, 315, 3278, 15603, 11, 220, 717, 2697, 374, 3967, 922, 279, 20124, 315, 1521, 659, 42211, 6593, 54373, 13, 9220, 6484, 7978, 617, 25078, 828, 505, 8122, 83543, 28271, 25, 832, 4028, 5370, 5110, 220, 21, 323, 279, 1023, 304, 16327, 13, 220, 1032, 4314, 7978, 8710, 26921, 3135, 449, 5201, 311, 41265, 719, 1051, 7347, 555, 2678, 6205, 12562, 323, 12309, 1579, 18151, 311, 1833, 5352, 13, 23674, 11, 912, 4007, 706, 25078, 3508, 3278, 527, 3025, 311, 21676, 10299, 872, 1866, 54373, 555, 25607, 279, 13803, 315, 6129, 36505, 323, 32644, 369, 6593, 9650, 994, 8475, 13, 12362, 828, 505, 459, 2930, 8122, 83543, 20770, 11, 584, 13375, 264, 7187, 3196, 6492, 315, 3278, 304, 279, 5545, 315, 14990, 323, 17355, 14990, 889, 659, 42211, 6593, 20710, 2391, 264, 2380, 1060, 4261, 13, 1226, 25078, 659, 5068, 20124, 323, 36505, 1306, 6593, 20710, 1555, 2930, 8122, 83543, 323, 32448, 3278, 753, 5845, 311, 659, 4264, 369, 279, 13803, 315, 13893, 6129, 36505, 315, 20710, 323, 872, 95323, 311, 6056, 6593, 6666, 13, 763, 3177, 315, 1510, 4947, 37635, 11, 220, 24, 220, 975, 279, 5545, 323, 17355, 14990, 3493, 264, 8104, 3062, 323, 32100, 6776, 311, 21635, 3278, 753, 659, 5068, 20124, 13, 19331, 1226, 25078, 828, 505, 11215, 389, 5000, 320, 63862, 54, 705, 264, 2536, 28926, 22139, 430, 5825, 4216, 6593, 20710, 1555, 2930, 8122, 83543, 304, 5961, 1405, 2680, 311, 6220, 20710, 374, 22486, 13, 578, 2532, 374, 5131, 2561, 369, 3278, 709, 311, 220, 605, 5672, 529, 13033, 367, 520, 279, 892, 315, 1715, 13, 2057, 1304, 264, 1715, 11, 3278, 5266, 704, 264, 29173, 128257, 198, 128256, 78191, 198, 36190, 304, 14990, 323, 17355, 14990, 42990, 6593, 20710, 26153, 1555, 2930, 8122, 83543, 1934, 6992, 10415, 811, 449, 3428, 7969, 315, 31959, 6372, 11, 4184, 311, 502, 3495, 4756, 304, 578, 20387, 41, 555, 50421, 3907, 11, 279, 3907, 315, 8421, 520, 19816, 323, 11215, 389, 5000, 13, 578, 12074, 25078, 659, 85296, 20124, 2768, 6593, 54373, 13375, 4994, 279, 16287, 18985, 6376, 1555, 11215, 389, 5000, 320, 63862, 54, 705, 264, 33184, 7471, 430, 5825, 2680, 311, 31010, 1511, 311, 49853, 20710, 13, 578, 3135, 1501, 430, 220, 2721, 3346, 315, 659, 1355, 54492, 323, 659, 21110, 3359, 6593, 54373, 1051, 6992, 13, 9865, 1109, 832, 3346, 315, 279, 3278, 2631, 264, 6680, 20429, 7713, 11, 323, 2380, 3346, 4036, 46850, 13, 11215, 1051, 3025, 311, 10765, 279, 13803, 315, 13893, 6129, 36505, 11, 323, 4661, 682, 5068, 11125, 304, 29145, 6593, 6666, 994, 26160, 13, 330, 8140, 3135, 1501, 430, 8122, 83543, 54373, 3984, 555, 11215, 389, 5000, 527, 6220, 323, 7524, 1359, 1071, 1080, 43802, 7957, 1183, 1892, 616, 11, 279, 15274, 323, 33116, 53596, 17054, 315, 3142, 323, 7327, 23298, 11, 21185, 36891, 11, 323, 14561, 315, 28989, 323, 586, 22747, 11, 991, 261, 36891, 11, 520, 50421, 3907, 596, 12404, 654, 17882, 6150, 315, 3142, 323, 7327, 23298, 13, 3765, 26973, 7016, 304, 14990, 323, 17355, 14990, 527, 4315, 279, 1455, 58096, 304, 279, 1917, 11, 449, 20710, 9337, 1534, 304, 1455, 13463, 13, 4452, 11, 2930, 8122, 83543, 706, 29057, 5614, 20710, 2680, 13, 330, 49213, 819, 323, 17355, 18088, 1274, 889, 2680, 477, 1520, 3885, 311, 2680, 420, 38970, 527, 19301, 459, 3072, 430, 706, 4528, 27375, 7969, 311, 24099, 20710, 10887, 304, 264, 28913, 323, 706, 4827, 7969, 315, 36505, 1109, 14691, 264, 20209, 311, 9889, 1359, 1071, 3063, 3229, 3765, 85306, 362, 37533, 11, 18328, 14561, 520, 279, 3907, 315, 8421, 596, 16333, 86452, 426, 13, 11605, 6150, 315, 3142, 23298, 13, 330, 2028, 4007, 5039, 430, 24099, 20710, 659, 1355, 54492, 323, 659, 21110, 3359, 4994, 279, 16287, 18985, 6376, 649, 387, 264, 6220, 323, 7524, 3072, 369, 1884, 889, 17631, 389, 477, 10932, 433, 1210, 12362, 828, 505, 88745, 11, 12074, 13375, 264, 7187, 3196, 6492, 315, 220, 16, 11, 931, 3278, 304, 279, 5545, 315, 14990, 323, 17355, 14990, 889, 659, 1355, 54492, 6593, 20710, 2391, 264, 2380, 4771, 4261, 13, 362, 37533, 323, 1183, 1892, 616, 11, 3235, 449, 1080, 34603, 1105, 45557, 480, 14773, 15916, 323, 358, 23523, 39069, 337, 505, 88745, 11, 25078, 659, 85296, 20124, 323, 36505, 11, 323, 32448, 3278, 596, 5845, 311, 659, 30360, 369, 279, 13803, 315, 13893, 6129, 36505, 11, 439, 1664, 439, 872, 95323, 311, 6056, 6593, 6666, 13, 578, 14955, 1101, 617, 25127, 369, 1023, 5596, 315, 279, 1917, 1405, 20710, 374, 5107, 311, 2680, 13, 330, 28055, 17301, 315, 58096, 13543, 304, 279, 3723, 4273, 11, 279, 72474, 1990, 3278, 11125, 20710, 304, 3738, 5596, 315, 279, 549, 815, 13, 323, 14990, 323, 17355, 14990, 527, 21933, 1359, 362, 37533, 1071, 13, 330, 36190, 304, 14990, 323, 17355, 14990, 617, 2380, 2671, 994, 17011, 449, 264, 20209, 814, 656, 539, 1390, 477, 2733, 814, 4250, 3136, 25, 5944, 1317, 27650, 311, 2680, 304, 31717, 93435, 20710, 2512, 11, 7293, 20895, 11, 477, 659, 31874, 872, 1866, 20710, 4994, 279, 16287, 18985, 6376, 13, 763, 279, 1162, 315, 279, 3723, 4273, 11, 584, 2736, 1440, 3278, 527, 659, 1355, 43662, 11, 779, 1070, 374, 264, 586, 2890, 14523, 311, 1520, 1304, 433, 439, 6220, 323, 7396, 439, 3284, 1210, 578, 12074, 25670, 279, 9669, 315, 659, 48511, 287, 11, 719, 1101, 47032, 430, 304, 15082, 1405, 3278, 659, 31874, 872, 1866, 54373, 4994, 279, 16287, 18985, 6376, 11, 659, 48511, 374, 279, 1193, 3284, 1749, 315, 1833, 5352, 13, 578, 3544, 6205, 1404, 323, 1579, 1833, 5352, 4478, 11, 902, 374, 30139, 449, 477, 11, 304, 1063, 5157, 11, 2731, 1109, 7978, 315, 20710, 2949, 279, 16287, 18985, 6376, 527, 1101, 36486, 315, 279, 4007, 13, 578, 4007, 11, 330, 12363, 12, 10577, 291, 4470, 6716, 323, 2467, 4550, 18093, 23548, 13235, 3765, 26973, 4669, 8267, 13875, 83543, 25, 362, 40629, 6108, 19723, 304, 14990, 323, 17355, 14990, 1359, 574, 4756, 2930, 3297, 220, 845, 13, 220, 128257, 198 ]

2,025

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Metabolic reprogramming is a hallmark of cancer. Herein we discover that the key glycolytic enzyme pyruvate kinase M2 isoform (PKM2), but not the related isoform PKM1, is methylated by co-activator-associated arginine methyltransferase 1 (CARM1). PKM2 methylation reversibly shifts the balance of metabolism from oxidative phosphorylation to aerobic glycolysis in breast cancer cells. Oxidative phosphorylation depends on mitochondrial calcium concentration, which becomes critical for cancer cell survival when PKM2 methylation is blocked. By interacting with and suppressing the expression of inositol-1,4,5-trisphosphate receptors (InsP 3 Rs), methylated PKM2 inhibits the influx of calcium from the endoplasmic reticulum to mitochondria. Inhibiting PKM2 methylation with a competitive peptide delivered by nanoparticles perturbs the metabolic energy balance in cancer cells, leading to a decrease in cell proliferation, migration and metastasis. Collectively, the CARM1–PKM2 axis serves as a metabolic reprogramming mechanism in tumorigenesis, and inhibiting PKM2 methylation generates metabolic vulnerability to InsP 3 R-dependent mitochondrial functions. Main One hallmark of cancer 1 , 2 is the Warburg effect, whereby tumour cells rely mainly on aerobic glycolysis for adenosine-5′-triphosphate (ATP) production, even with sufficient oxygen 3 . However, metabolic adaptation in tumours extends beyond the Warburg effect, including balancing energy needs with equally important needs for macromolecular synthesis and redox homeostasis 1 , 2 , 4 . Emerging evidence suggests that mitochondrial respiration is crucial for tumorigenesis and presents a target for cancer therapy 5 , 6 , 7 , 8 . Pyruvate kinase (PK) catalyses the final step in glycolysis, converting phosphoenolpyruvate to pyruvate while phosphorylating ADP to produce ATP. The M1 and M2 isoforms of PK are produced by mutually exclusive alternative splicing of PKM pre-messenger RNA 9 . Although PKM1 and PKM2 differ by only 22 amino acids, PKM1 is not allosterically regulated and exists in a tetrameric form with high PK activity. PKM2 shifts between inactive dimeric and active tetrameric forms, modulated by phosphotyrosine signalling 10 , metabolic intermediates (for example, FBP, serine and SAICAR) 11 , 12 and post-translational modifications 13 . Switching PKM2 to PKM1 reverses aerobic glycolysis to oxidative phosphorylation and reduces tumour formation in nude mice 14 , identifying PKM2 as a potential cancer therapy target. However, a recent report challenged the PKM2-catalysed reaction as a rate-limiting step in cancer cell glycolysis 15 and a possible protein kinase activity of PKM2 remains controversial 16 . Co-activator-associated arginine methyltransferase 1 (CARM1), also known as PRMT4, is a type I protein arginine methyltransferase (PRMT) that asymmetrically dimethylates protein substrates including histones, transcriptional factors and co-regulators, splicing factors and RNA polymerase II 17 , 18 , 19 , 20 . CARM1 is overexpressed in breast cancer to promote cancer growth 21 , and elevated CARM1 expression correlates with poor prognosis 22 . Recently, we discovered that chromatin remodelling factor BAF155 methylation by CARM1 promotes breast cancer progression and metastasis 23 . However, whether CARM1 regulates energy metabolism in cancer cells remains unknown. Here, we discovered CARM1–PKM2 interaction as a major contributor to metabolic reprogramming in cancer. CARM1 methylates the dimeric form of PKM2 at Arg445/447/455. Methylated PKM2 promotes tumour cell proliferation, migration and lung metastasis by reprogramming oxidative phosphorylation to aerobic glycolysis, and this effect was reversed by a competitive PKM2 peptide delivered using nanoparticles. We showed that methylated PKM2 localized in mitochondria-associated endoplasmic reticulum membrane, through interaction with inositol 1,4,5-trisphosphate receptors (InsP 3 Rs), decreasing mitochondrial membrane potential (Δ Ψ m ) and Ca 2+ uptake, which is essential for activating pyruvate dehydrogenase (PDH) to support oxidative phosphorylation 24 . Blocking PKM2 methylation elevates InsP 3 R expression, increasing mitochondrial Ca 2+ uptake, PDH activation and oxidative phosphorylation. Thus, PKM2 methylation represents an important regulator of switching between oxidative phosphorylation to aerobic glycolysis in cancer cells. RESULTS CARM1 interacts with and methylates PKM2 Consistent with CARM1 promotion of tumour development and progression 21 , 23 , knocking out CARM1 decreased DNA synthesis in MCF7 cells ( Supplementary Fig. 1a ). CARM1 knockout (KO) also increased mitochondrial oxygen consumption rate (OCR) but decreased lactate production without affecting glucose uptake ( Supplementary Fig. 1b–f ). These results prompted us to test whether CARM1 modulates energy metabolism in breast cancer cells. We identified PKM2 as a putative CARM1-interacting protein by mass spectrometry when Halo-tagged CARM1 was overexpressed in HEK293T cells ( Supplementary Table 1 ). Endogenous CARM1–PKM2 interaction was confirmed by reciprocal co-immunoprecipitation in MCF7 cells ( Fig. 1a ). To determine whether CARM1 directly interacts with PKM2, we performed glutathione S -transferase (GST) pulldown using recombinant GST-tagged CARM1, Flag-tagged PKM2 and Flag-PABP1 (positive control) 25 and observed that GST-CARM1, but not GST alone, bound PKM2, indicating direct CARM1–PKM2 interaction ( Fig. 1b ). Interestingly, recombinant PKM1 also associated with CARM1 in vitro ( Fig. 1b ). To map the PKM2 region that binds CARM1, we expressed truncated Flag-PKM2 using in vitro transcription and translation and performed in vitro interaction assays with GST-CARM1. Deleting PKM2 domain C (Δ1) or N/A1 (Δ4) significantly decreased the interaction of PKM2 with CARM1, and truncation of both domains (Δ8) completely abolished the interaction, suggesting that the C and N/A1 domains are responsible for the interaction ( Fig. 1c, d ). Although these domains are identical between PKM1 and PKM2, intriguingly only PKM2, but not PKM1, can be methylated by CARM1 in vitro ( Fig. 1e ). Figure 1: Only the dimeric form of PKM2 is methylated by CARM1. ( a ) Reciprocal co-immunoprecipitation of PKM2 and CARM1 in MCF7 cells followed by western blot analysis. ( b ) Direct interaction of recombinant PKM1, PKM2 and PABP1 (positive control) proteins with CARM1 in GST pulldown assays. GST and GST-CARM1 were detected by anti-GST antibody, and Flag-tagged PKM1, PKM2 and PABP1 were detected by anti-Flag antibody, respectively. ( c , d ) Schematic showing truncations of PKM2 and in vitro interaction assays with CARM1 using full-length PKM and truncated proteins expressed by in vitro transcriptional and translational systems. ( e ) In vitro methylation assays using recombinant CARM1, GST-PKM1 or PKM2 protein in the presence of 3 H-SAM. (", "role": "user" }, { "content": "As cells with a propensity for cancer break down food for energy, they reach a fork in the road: They can either continue energy production as healthy cells, or shift to the energy production profile of cancer cells. In a new study published Monday in the journal Nature Cell Biology, University of Wisconsin-Madison researchers map out the molecular events that direct cells' energy metabolism down the cancerous path. The findings could lead to ways to interrupt the process. \"Cancer cells often change their nutrient utilization and energy production, so many efforts are being made to develop drug inhibitors of cancer cell metabolism to starve them,\" says senior author Wei Xu, the Marian A. Messerschmidt Professor in Cancer Research at the UW Carbone Cancer Center and McArdle Laboratory for Cancer Research. \"We have found that inhibiting a chemical modification of a cancer-associated metabolism protein is enough to inhibit the aggressive nature of cancer cells.\" Cancer biologists have identified nearly a dozen \"hallmarks of cancer,\" or large-scale changes that send a precancerous cell over the tipping point to become a cancerous one. One hallmark of cancer is the loss of properly regulated energy metabolism, a process referred to as the \"Warburg effect\" after the Nobel laureate, Otto Warburg, who identified it. Other hallmarks of cancer include continuous activation of growth pathways, the inability to respond to signals that put the brakes on cell growth, and a gain of invasion and spread to distant organs. \"My lab studies a protein, CARM1, which is associated with worse outcomes in breast cancer patients, though it has also been found expressed in many other cancer types,\" Xu says. \"CARM1 chemically modifies its target proteins to alter their function, and in doing so directly leads to the activation of several hallmarks of cancer.\" In the study, Xu and her colleagues found that CARM1 protein modifies a cell metabolism protein, PKM2, and changes its function. This drives the Warburg effect, activating a hallmark of cancer. Nearly a decade ago, researchers found that PKM2 was expressed at high levels in cancer cells, but how these levels translated to more aggressive cancers was not known. So, Xu and colleagues performed a protein interaction assay in a breast cancer cell line and found that CARM1 interacts with and chemically modifies PKM2. They also assessed whether CARM1-directed modifications of PKM2 might be responsible for leading cells down a cancerous pathway. By engineering cells to express \"normal\" PKM2 or a mutated form that was not modifiable, the researchers learned that PKM2 appears to be the deciding factor in picking the direction cell metabolism takes at that fork in the road. The CARM1-modified PKM2 shifted cells toward the cancer cell metabolism path while cells with PKM2 that could not be modified took the metabolic path associated with noncancerous cells. With a clearer picture of how cancer cells shift their metabolism, the researchers next used a mouse model of breast cancer and a competitor drug that prevents CARM1 from effectively modifying PKM2 to test what would happen. \"When we block PKM2 modification by CARM1, the metabolic energy balance in cancer cells is reversed, and we see a decrease of cell growth and cell spreading potential,\" Xu says. \"This study, then, identifies another therapeutic target to help reverse several hallmarks of cancer.\" In addition to targeting PKM2 modification by CARM1, Xu's lab is investigating how CARM1 recognizes all of its many target proteins, with the goal of disrupting those protein modifications from driving aggressive cancers. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Metabolic reprogramming is a hallmark of cancer. Herein we discover that the key glycolytic enzyme pyruvate kinase M2 isoform (PKM2), but not the related isoform PKM1, is methylated by co-activator-associated arginine methyltransferase 1 (CARM1). PKM2 methylation reversibly shifts the balance of metabolism from oxidative phosphorylation to aerobic glycolysis in breast cancer cells. Oxidative phosphorylation depends on mitochondrial calcium concentration, which becomes critical for cancer cell survival when PKM2 methylation is blocked. By interacting with and suppressing the expression of inositol-1,4,5-trisphosphate receptors (InsP 3 Rs), methylated PKM2 inhibits the influx of calcium from the endoplasmic reticulum to mitochondria. Inhibiting PKM2 methylation with a competitive peptide delivered by nanoparticles perturbs the metabolic energy balance in cancer cells, leading to a decrease in cell proliferation, migration and metastasis. Collectively, the CARM1–PKM2 axis serves as a metabolic reprogramming mechanism in tumorigenesis, and inhibiting PKM2 methylation generates metabolic vulnerability to InsP 3 R-dependent mitochondrial functions. Main One hallmark of cancer 1 , 2 is the Warburg effect, whereby tumour cells rely mainly on aerobic glycolysis for adenosine-5′-triphosphate (ATP) production, even with sufficient oxygen 3 . However, metabolic adaptation in tumours extends beyond the Warburg effect, including balancing energy needs with equally important needs for macromolecular synthesis and redox homeostasis 1 , 2 , 4 . Emerging evidence suggests that mitochondrial respiration is crucial for tumorigenesis and presents a target for cancer therapy 5 , 6 , 7 , 8 . Pyruvate kinase (PK) catalyses the final step in glycolysis, converting phosphoenolpyruvate to pyruvate while phosphorylating ADP to produce ATP. The M1 and M2 isoforms of PK are produced by mutually exclusive alternative splicing of PKM pre-messenger RNA 9 . Although PKM1 and PKM2 differ by only 22 amino acids, PKM1 is not allosterically regulated and exists in a tetrameric form with high PK activity. PKM2 shifts between inactive dimeric and active tetrameric forms, modulated by phosphotyrosine signalling 10 , metabolic intermediates (for example, FBP, serine and SAICAR) 11 , 12 and post-translational modifications 13 . Switching PKM2 to PKM1 reverses aerobic glycolysis to oxidative phosphorylation and reduces tumour formation in nude mice 14 , identifying PKM2 as a potential cancer therapy target. However, a recent report challenged the PKM2-catalysed reaction as a rate-limiting step in cancer cell glycolysis 15 and a possible protein kinase activity of PKM2 remains controversial 16 . Co-activator-associated arginine methyltransferase 1 (CARM1), also known as PRMT4, is a type I protein arginine methyltransferase (PRMT) that asymmetrically dimethylates protein substrates including histones, transcriptional factors and co-regulators, splicing factors and RNA polymerase II 17 , 18 , 19 , 20 . CARM1 is overexpressed in breast cancer to promote cancer growth 21 , and elevated CARM1 expression correlates with poor prognosis 22 . Recently, we discovered that chromatin remodelling factor BAF155 methylation by CARM1 promotes breast cancer progression and metastasis 23 . However, whether CARM1 regulates energy metabolism in cancer cells remains unknown. Here, we discovered CARM1–PKM2 interaction as a major contributor to metabolic reprogramming in cancer. CARM1 methylates the dimeric form of PKM2 at Arg445/447/455. Methylated PKM2 promotes tumour cell proliferation, migration and lung metastasis by reprogramming oxidative phosphorylation to aerobic glycolysis, and this effect was reversed by a competitive PKM2 peptide delivered using nanoparticles. We showed that methylated PKM2 localized in mitochondria-associated endoplasmic reticulum membrane, through interaction with inositol 1,4,5-trisphosphate receptors (InsP 3 Rs), decreasing mitochondrial membrane potential (Δ Ψ m ) and Ca 2+ uptake, which is essential for activating pyruvate dehydrogenase (PDH) to support oxidative phosphorylation 24 . Blocking PKM2 methylation elevates InsP 3 R expression, increasing mitochondrial Ca 2+ uptake, PDH activation and oxidative phosphorylation. Thus, PKM2 methylation represents an important regulator of switching between oxidative phosphorylation to aerobic glycolysis in cancer cells. RESULTS CARM1 interacts with and methylates PKM2 Consistent with CARM1 promotion of tumour development and progression 21 , 23 , knocking out CARM1 decreased DNA synthesis in MCF7 cells ( Supplementary Fig. 1a ). CARM1 knockout (KO) also increased mitochondrial oxygen consumption rate (OCR) but decreased lactate production without affecting glucose uptake ( Supplementary Fig. 1b–f ). These results prompted us to test whether CARM1 modulates energy metabolism in breast cancer cells. We identified PKM2 as a putative CARM1-interacting protein by mass spectrometry when Halo-tagged CARM1 was overexpressed in HEK293T cells ( Supplementary Table 1 ). Endogenous CARM1–PKM2 interaction was confirmed by reciprocal co-immunoprecipitation in MCF7 cells ( Fig. 1a ). To determine whether CARM1 directly interacts with PKM2, we performed glutathione S -transferase (GST) pulldown using recombinant GST-tagged CARM1, Flag-tagged PKM2 and Flag-PABP1 (positive control) 25 and observed that GST-CARM1, but not GST alone, bound PKM2, indicating direct CARM1–PKM2 interaction ( Fig. 1b ). Interestingly, recombinant PKM1 also associated with CARM1 in vitro ( Fig. 1b ). To map the PKM2 region that binds CARM1, we expressed truncated Flag-PKM2 using in vitro transcription and translation and performed in vitro interaction assays with GST-CARM1. Deleting PKM2 domain C (Δ1) or N/A1 (Δ4) significantly decreased the interaction of PKM2 with CARM1, and truncation of both domains (Δ8) completely abolished the interaction, suggesting that the C and N/A1 domains are responsible for the interaction ( Fig. 1c, d ). Although these domains are identical between PKM1 and PKM2, intriguingly only PKM2, but not PKM1, can be methylated by CARM1 in vitro ( Fig. 1e ). Figure 1: Only the dimeric form of PKM2 is methylated by CARM1. ( a ) Reciprocal co-immunoprecipitation of PKM2 and CARM1 in MCF7 cells followed by western blot analysis. ( b ) Direct interaction of recombinant PKM1, PKM2 and PABP1 (positive control) proteins with CARM1 in GST pulldown assays. GST and GST-CARM1 were detected by anti-GST antibody, and Flag-tagged PKM1, PKM2 and PABP1 were detected by anti-Flag antibody, respectively. ( c , d ) Schematic showing truncations of PKM2 and in vitro interaction assays with CARM1 using full-length PKM and truncated proteins expressed by in vitro transcriptional and translational systems. ( e ) In vitro methylation assays using recombinant CARM1, GST-PKM1 or PKM2 protein in the presence of 3 H-SAM. (<|im_end|> <|im_start|>assistant As cells with a propensity for cancer break down food for energy, they reach a fork in the road: They can either continue energy production as healthy cells, or shift to the energy production profile of cancer cells. In a new study published Monday in the journal Nature Cell Biology, University of Wisconsin-Madison researchers map out the molecular events that direct cells' energy metabolism down the cancerous path. The findings could lead to ways to interrupt the process. "Cancer cells often change their nutrient utilization and energy production, so many efforts are being made to develop drug inhibitors of cancer cell metabolism to starve them," says senior author Wei Xu, the Marian A. Messerschmidt Professor in Cancer Research at the UW Carbone Cancer Center and McArdle Laboratory for Cancer Research. "We have found that inhibiting a chemical modification of a cancer-associated metabolism protein is enough to inhibit the aggressive nature of cancer cells." Cancer biologists have identified nearly a dozen "hallmarks of cancer," or large-scale changes that send a precancerous cell over the tipping point to become a cancerous one. One hallmark of cancer is the loss of properly regulated energy metabolism, a process referred to as the "Warburg effect" after the Nobel laureate, Otto Warburg, who identified it. Other hallmarks of cancer include continuous activation of growth pathways, the inability to respond to signals that put the brakes on cell growth, and a gain of invasion and spread to distant organs. "My lab studies a protein, CARM1, which is associated with worse outcomes in breast cancer patients, though it has also been found expressed in many other cancer types," Xu says. "CARM1 chemically modifies its target proteins to alter their function, and in doing so directly leads to the activation of several hallmarks of cancer." In the study, Xu and her colleagues found that CARM1 protein modifies a cell metabolism protein, PKM2, and changes its function. This drives the Warburg effect, activating a hallmark of cancer. Nearly a decade ago, researchers found that PKM2 was expressed at high levels in cancer cells, but how these levels translated to more aggressive cancers was not known. So, Xu and colleagues performed a protein interaction assay in a breast cancer cell line and found that CARM1 interacts with and chemically modifies PKM2. They also assessed whether CARM1-directed modifications of PKM2 might be responsible for leading cells down a cancerous pathway. By engineering cells to express "normal" PKM2 or a mutated form that was not modifiable, the researchers learned that PKM2 appears to be the deciding factor in picking the direction cell metabolism takes at that fork in the road. The CARM1-modified PKM2 shifted cells toward the cancer cell metabolism path while cells with PKM2 that could not be modified took the metabolic path associated with noncancerous cells. With a clearer picture of how cancer cells shift their metabolism, the researchers next used a mouse model of breast cancer and a competitor drug that prevents CARM1 from effectively modifying PKM2 to test what would happen. "When we block PKM2 modification by CARM1, the metabolic energy balance in cancer cells is reversed, and we see a decrease of cell growth and cell spreading potential," Xu says. "This study, then, identifies another therapeutic target to help reverse several hallmarks of cancer." In addition to targeting PKM2 modification by CARM1, Xu's lab is investigating how CARM1 recognizes all of its many target proteins, with the goal of disrupting those protein modifications from driving aggressive cancers. <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 6344, 57565, 312, 92726, 374, 264, 98799, 315, 9572, 13, 5810, 258, 584, 7142, 430, 279, 1401, 37807, 2119, 70504, 49242, 4611, 2739, 85, 349, 82160, 386, 17, 34556, 630, 320, 23037, 44, 17, 705, 719, 539, 279, 5552, 34556, 630, 25864, 44, 16, 11, 374, 79574, 660, 555, 1080, 12, 9035, 859, 75968, 1417, 83334, 79574, 25163, 521, 220, 16, 320, 34, 18394, 16, 570, 25864, 44, 17, 21747, 79933, 17888, 6623, 29735, 279, 8335, 315, 39097, 505, 79401, 95089, 2354, 311, 91490, 37807, 2119, 4548, 304, 17659, 9572, 7917, 13, 51715, 307, 1413, 95089, 2354, 14117, 389, 72061, 35719, 20545, 11, 902, 9221, 9200, 369, 9572, 2849, 20237, 994, 25864, 44, 17, 21747, 79933, 374, 19857, 13, 3296, 45830, 449, 323, 98795, 279, 7645, 315, 304, 437, 27094, 12, 16, 11, 19, 11, 20, 10398, 285, 764, 93473, 44540, 320, 15841, 47, 220, 18, 19766, 705, 79574, 660, 25864, 44, 17, 20747, 1220, 279, 53952, 315, 35719, 505, 279, 842, 56178, 10753, 292, 2160, 292, 16903, 311, 55042, 4298, 13, 763, 5923, 5977, 25864, 44, 17, 21747, 79933, 449, 264, 15022, 72249, 12886, 555, 94753, 18713, 324, 1302, 279, 41861, 4907, 8335, 304, 9572, 7917, 11, 6522, 311, 264, 18979, 304, 2849, 53840, 11, 12172, 323, 68370, 10949, 13, 21153, 3210, 11, 279, 356, 18394, 16, 4235, 23037, 44, 17, 8183, 17482, 439, 264, 41861, 312, 92726, 17383, 304, 15756, 4775, 268, 14093, 11, 323, 20747, 5977, 25864, 44, 17, 21747, 79933, 27983, 41861, 34104, 311, 9925, 47, 220, 18, 432, 43918, 72061, 5865, 13, 4802, 3861, 98799, 315, 9572, 220, 16, 1174, 220, 17, 374, 279, 5111, 10481, 2515, 11, 49001, 15756, 414, 7917, 17631, 14918, 389, 91490, 37807, 2119, 4548, 369, 1008, 71970, 483, 12, 20, 39615, 12, 376, 15619, 93473, 320, 835, 47, 8, 5788, 11, 1524, 449, 14343, 24463, 220, 18, 662, 4452, 11, 41861, 34185, 304, 15756, 2530, 2289, 7953, 279, 5111, 10481, 2515, 11, 2737, 44463, 4907, 3966, 449, 18813, 3062, 3966, 369, 9155, 442, 43943, 39975, 323, 2579, 5241, 2162, 537, 10949, 220, 16, 1174, 220, 17, 1174, 220, 19, 662, 86148, 6029, 13533, 430, 72061, 594, 29579, 374, 16996, 369, 15756, 4775, 268, 14093, 323, 18911, 264, 2218, 369, 9572, 15419, 220, 20, 1174, 220, 21, 1174, 220, 22, 1174, 220, 23, 662, 5468, 2739, 85, 349, 82160, 320, 23037, 8, 34454, 73279, 279, 1620, 3094, 304, 37807, 2119, 4548, 11, 34537, 33088, 16355, 337, 3368, 2739, 85, 349, 311, 4611, 2739, 85, 349, 1418, 95089, 75, 1113, 9827, 47, 311, 8356, 67656, 13, 578, 386, 16, 323, 386, 17, 34556, 10008, 315, 25864, 527, 9124, 555, 53579, 14079, 10778, 993, 90214, 315, 25864, 44, 864, 1474, 41237, 41214, 220, 24, 662, 10541, 25864, 44, 16, 323, 25864, 44, 17, 1782, 555, 1193, 220, 1313, 42500, 33969, 11, 25864, 44, 16, 374, 539, 63747, 3751, 2740, 35319, 323, 6866, 304, 264, 28953, 2453, 11893, 1376, 449, 1579, 25864, 5820, 13, 25864, 44, 17, 29735, 1990, 32899, 294, 3212, 292, 323, 4642, 28953, 2453, 11893, 7739, 11, 1491, 7913, 555, 33088, 115966, 3714, 483, 91977, 220, 605, 1174, 41861, 55275, 988, 320, 2000, 3187, 11, 435, 27187, 11, 1446, 483, 323, 16998, 1341, 946, 8, 220, 806, 1174, 220, 717, 323, 1772, 39160, 75, 1697, 29882, 220, 1032, 662, 15958, 287, 25864, 44, 17, 311, 25864, 44, 16, 17888, 288, 91490, 37807, 2119, 4548, 311, 79401, 95089, 2354, 323, 26338, 15756, 414, 18488, 304, 20637, 24548, 220, 975, 1174, 25607, 25864, 44, 17, 439, 264, 4754, 9572, 15419, 2218, 13, 4452, 11, 264, 3293, 1934, 29991, 279, 25864, 44, 17, 1824, 4306, 1065, 291, 13010, 439, 264, 4478, 72259, 287, 3094, 304, 9572, 2849, 37807, 2119, 4548, 220, 868, 323, 264, 3284, 13128, 82160, 5820, 315, 25864, 44, 17, 8625, 20733, 220, 845, 662, 3623, 12, 9035, 859, 75968, 1417, 83334, 79574, 25163, 521, 220, 16, 320, 34, 18394, 16, 705, 1101, 3967, 439, 8743, 8673, 19, 11, 374, 264, 955, 358, 13128, 1417, 83334, 79574, 25163, 521, 320, 6616, 8673, 8, 430, 97929, 750, 5213, 42972, 988, 13128, 16146, 988, 2737, 13034, 3233, 11, 46940, 278, 9547, 323, 1080, 33263, 42391, 11, 993, 90214, 9547, 323, 41214, 47393, 521, 8105, 220, 1114, 1174, 220, 972, 1174, 220, 777, 1174, 220, 508, 662, 356, 18394, 16, 374, 927, 14107, 291, 304, 17659, 9572, 311, 12192, 9572, 6650, 220, 1691, 1174, 323, 32389, 356, 18394, 16, 7645, 97303, 449, 8009, 95350, 220, 1313, 662, 42096, 11, 584, 11352, 430, 22083, 15111, 1323, 347, 6427, 8331, 426, 8440, 9992, 21747, 79933, 555, 356, 18394, 16, 39990, 17659, 9572, 33824, 323, 68370, 10949, 220, 1419, 662, 4452, 11, 3508, 356, 18394, 16, 80412, 4907, 39097, 304, 9572, 7917, 8625, 9987, 13, 5810, 11, 584, 11352, 356, 18394, 16, 4235, 23037, 44, 17, 16628, 439, 264, 3682, 26373, 311, 41861, 312, 92726, 304, 9572, 13, 356, 18394, 16, 79574, 988, 279, 294, 3212, 292, 1376, 315, 25864, 44, 17, 520, 7793, 19697, 14, 20800, 14, 20325, 13, 386, 42972, 660, 25864, 44, 17, 39990, 15756, 414, 2849, 53840, 11, 12172, 323, 21271, 68370, 10949, 555, 312, 92726, 79401, 95089, 2354, 311, 91490, 37807, 2119, 4548, 11, 323, 420, 2515, 574, 28537, 555, 264, 15022, 25864, 44, 17, 72249, 12886, 1701, 94753, 13, 1226, 8710, 430, 79574, 660, 25864, 44, 17, 44589, 304, 55042, 4298, 75968, 842, 56178, 10753, 292, 2160, 292, 16903, 39654, 11, 1555, 16628, 449, 304, 437, 27094, 220, 16, 11, 19, 11, 20, 10398, 285, 764, 93473, 44540, 320, 15841, 47, 220, 18, 19766, 705, 44649, 72061, 39654, 4754, 320, 101561, 120184, 296, 883, 323, 14751, 220, 17, 10, 69575, 11, 902, 374, 7718, 369, 72192, 4611, 2739, 85, 349, 409, 67229, 4469, 521, 320, 23891, 39, 8, 311, 1862, 79401, 95089, 2354, 220, 1187, 662, 83045, 25864, 44, 17, 21747, 79933, 12231, 988, 9925, 47, 220, 18, 432, 7645, 11, 7859, 72061, 14751, 220, 17, 10, 69575, 11, 27572, 39, 15449, 323, 79401, 95089, 2354, 13, 14636, 11, 25864, 44, 17, 21747, 79933, 11105, 459, 3062, 40704, 315, 28865, 1990, 79401, 95089, 2354, 311, 91490, 37807, 2119, 4548, 304, 9572, 7917, 13, 54128, 356, 18394, 16, 84261, 449, 323, 79574, 988, 25864, 44, 17, 7440, 18620, 449, 356, 18394, 16, 20862, 315, 15756, 414, 4500, 323, 33824, 220, 1691, 1174, 220, 1419, 1174, 50244, 704, 356, 18394, 16, 25983, 15922, 39975, 304, 386, 9847, 22, 7917, 320, 99371, 23966, 13, 220, 16, 64, 7609, 356, 18394, 16, 77173, 320, 56047, 8, 1101, 7319, 72061, 24463, 15652, 4478, 320, 94595, 8, 719, 25983, 51644, 349, 5788, 2085, 28987, 34323, 69575, 320, 99371, 23966, 13, 220, 16, 65, 4235, 69, 7609, 4314, 3135, 29746, 603, 311, 1296, 3508, 356, 18394, 16, 1491, 24031, 4907, 39097, 304, 17659, 9572, 7917, 13, 1226, 11054, 25864, 44, 17, 439, 264, 2231, 1413, 356, 18394, 16, 45994, 36022, 13128, 555, 3148, 9618, 442, 15501, 994, 46349, 39304, 3640, 356, 18394, 16, 574, 927, 14107, 291, 304, 11947, 42, 17313, 51, 7917, 320, 99371, 6771, 220, 16, 7609, 4060, 53595, 356, 18394, 16, 4235, 23037, 44, 17, 16628, 574, 11007, 555, 87298, 1080, 64683, 359, 454, 2827, 575, 7709, 304, 386, 9847, 22, 7917, 320, 23966, 13, 220, 16, 64, 7609, 2057, 8417, 3508, 356, 18394, 16, 6089, 84261, 449, 25864, 44, 17, 11, 584, 10887, 35169, 589, 6473, 328, 482, 25163, 521, 320, 76620, 8, 7893, 509, 785, 1701, 38301, 7006, 519, 33934, 39304, 3640, 356, 18394, 16, 11, 23497, 39304, 3640, 25864, 44, 17, 323, 23497, 9483, 1905, 47, 16, 320, 31587, 2585, 8, 220, 914, 323, 13468, 430, 33934, 7813, 18394, 16, 11, 719, 539, 33934, 7636, 11, 6965, 25864, 44, 17, 11, 19392, 2167, 356, 18394, 16, 4235, 23037, 44, 17, 16628, 320, 23966, 13, 220, 16, 65, 7609, 58603, 11, 38301, 7006, 519, 25864, 44, 16, 1101, 5938, 449, 356, 18394, 16, 304, 55004, 320, 23966, 13, 220, 16, 65, 7609, 2057, 2472, 279, 25864, 44, 17, 5654, 430, 58585, 356, 18394, 16, 11, 584, 13605, 60856, 23497, 9483, 66751, 17, 1701, 304, 55004, 46940, 323, 14807, 323, 10887, 304, 55004, 16628, 99592, 449, 33934, 7813, 18394, 16, 13, 82950, 25864, 44, 17, 8106, 356, 320, 101561, 16, 8, 477, 452, 10576, 16, 320, 101561, 19, 8, 12207, 25983, 279, 16628, 315, 25864, 44, 17, 449, 356, 18394, 16, 11, 323, 63950, 367, 315, 2225, 31576, 320, 101561, 23, 8, 6724, 81081, 279, 16628, 11, 23377, 430, 279, 356, 323, 452, 10576, 16, 31576, 527, 8647, 369, 279, 16628, 320, 23966, 13, 220, 16, 66, 11, 294, 7609, 10541, 1521, 31576, 527, 20086, 1990, 25864, 44, 16, 323, 25864, 44, 17, 11, 41765, 398, 1193, 25864, 44, 17, 11, 719, 539, 25864, 44, 16, 11, 649, 387, 79574, 660, 555, 356, 18394, 16, 304, 55004, 320, 23966, 13, 220, 16, 68, 7609, 19575, 220, 16, 25, 8442, 279, 294, 3212, 292, 1376, 315, 25864, 44, 17, 374, 79574, 660, 555, 356, 18394, 16, 13, 320, 264, 883, 4158, 49889, 5531, 1080, 64683, 359, 454, 2827, 575, 7709, 315, 25864, 44, 17, 323, 356, 18394, 16, 304, 386, 9847, 22, 7917, 8272, 555, 19001, 81982, 6492, 13, 320, 293, 883, 7286, 16628, 315, 38301, 7006, 519, 25864, 44, 16, 11, 25864, 44, 17, 323, 393, 1905, 47, 16, 320, 31587, 2585, 8, 28896, 449, 356, 18394, 16, 304, 33934, 7893, 509, 785, 99592, 13, 33934, 323, 33934, 7813, 18394, 16, 1051, 16914, 555, 7294, 12279, 790, 63052, 11, 323, 23497, 39304, 3640, 25864, 44, 16, 11, 25864, 44, 17, 323, 393, 1905, 47, 16, 1051, 16914, 555, 7294, 12, 12409, 63052, 11, 15947, 13, 320, 272, 1174, 294, 883, 328, 82149, 9204, 63950, 811, 315, 25864, 44, 17, 323, 304, 55004, 16628, 99592, 449, 356, 18394, 16, 1701, 2539, 30425, 25864, 44, 323, 60856, 28896, 13605, 555, 304, 55004, 46940, 278, 323, 12215, 1697, 6067, 13, 320, 384, 883, 763, 55004, 21747, 79933, 99592, 1701, 38301, 7006, 519, 356, 18394, 16, 11, 33934, 9483, 66751, 16, 477, 25864, 44, 17, 13128, 304, 279, 9546, 315, 220, 18, 473, 6354, 1428, 13, 320, 128257, 198, 128256, 78191, 198, 2170, 7917, 449, 264, 95323, 369, 9572, 1464, 1523, 3691, 369, 4907, 11, 814, 5662, 264, 23243, 304, 279, 5754, 25, 2435, 649, 3060, 3136, 4907, 5788, 439, 9498, 7917, 11, 477, 6541, 311, 279, 4907, 5788, 5643, 315, 9572, 7917, 13, 763, 264, 502, 4007, 4756, 7159, 304, 279, 8486, 22037, 14299, 40023, 11, 3907, 315, 21073, 5364, 329, 3416, 12074, 2472, 704, 279, 31206, 4455, 430, 2167, 7917, 6, 4907, 39097, 1523, 279, 9572, 788, 1853, 13, 578, 14955, 1436, 3063, 311, 5627, 311, 12956, 279, 1920, 13, 330, 34, 11967, 7917, 3629, 2349, 872, 50123, 50549, 323, 4907, 5788, 11, 779, 1690, 9045, 527, 1694, 1903, 311, 2274, 5623, 68642, 315, 9572, 2849, 39097, 311, 6917, 588, 1124, 1359, 2795, 10195, 3229, 53548, 57514, 11, 279, 96519, 362, 13, 19234, 388, 331, 43401, 17054, 304, 26211, 8483, 520, 279, 66716, 3341, 20337, 26211, 5955, 323, 65813, 6634, 273, 32184, 369, 26211, 8483, 13, 330, 1687, 617, 1766, 430, 20747, 5977, 264, 11742, 17466, 315, 264, 9572, 75968, 39097, 13128, 374, 3403, 311, 69033, 279, 19738, 7138, 315, 9572, 7917, 1210, 26211, 6160, 22012, 617, 11054, 7154, 264, 21030, 330, 43341, 15914, 315, 9572, 1359, 477, 3544, 13230, 4442, 430, 3708, 264, 5956, 11967, 788, 2849, 927, 279, 72293, 1486, 311, 3719, 264, 9572, 788, 832, 13, 3861, 98799, 315, 9572, 374, 279, 4814, 315, 10489, 35319, 4907, 39097, 11, 264, 1920, 14183, 311, 439, 279, 330, 29784, 10481, 2515, 1, 1306, 279, 48078, 67185, 349, 11, 66991, 5111, 10481, 11, 889, 11054, 433, 13, 7089, 14321, 15914, 315, 9572, 2997, 19815, 15449, 315, 6650, 44014, 11, 279, 38550, 311, 6013, 311, 17738, 430, 2231, 279, 45664, 389, 2849, 6650, 11, 323, 264, 8895, 315, 30215, 323, 9041, 311, 29827, 36853, 13, 330, 5159, 10278, 7978, 264, 13128, 11, 356, 18394, 16, 11, 902, 374, 5938, 449, 11201, 20124, 304, 17659, 9572, 6978, 11, 3582, 433, 706, 1101, 1027, 1766, 13605, 304, 1690, 1023, 9572, 4595, 1359, 57514, 2795, 13, 330, 34, 18394, 16, 8590, 2740, 84049, 1202, 2218, 28896, 311, 11857, 872, 734, 11, 323, 304, 3815, 779, 6089, 11767, 311, 279, 15449, 315, 3892, 14321, 15914, 315, 9572, 1210, 763, 279, 4007, 11, 57514, 323, 1077, 18105, 1766, 430, 356, 18394, 16, 13128, 84049, 264, 2849, 39097, 13128, 11, 25864, 44, 17, 11, 323, 4442, 1202, 734, 13, 1115, 20722, 279, 5111, 10481, 2515, 11, 72192, 264, 98799, 315, 9572, 13, 49669, 264, 13515, 4227, 11, 12074, 1766, 430, 25864, 44, 17, 574, 13605, 520, 1579, 5990, 304, 9572, 7917, 11, 719, 1268, 1521, 5990, 25548, 311, 810, 19738, 51423, 574, 539, 3967, 13, 2100, 11, 57514, 323, 18105, 10887, 264, 13128, 16628, 65033, 304, 264, 17659, 9572, 2849, 1584, 323, 1766, 430, 356, 18394, 16, 84261, 449, 323, 8590, 2740, 84049, 25864, 44, 17, 13, 2435, 1101, 32448, 3508, 356, 18394, 16, 86855, 29882, 315, 25864, 44, 17, 2643, 387, 8647, 369, 6522, 7917, 1523, 264, 9572, 788, 38970, 13, 3296, 15009, 7917, 311, 3237, 330, 8416, 1, 25864, 44, 17, 477, 264, 85922, 1376, 430, 574, 539, 1491, 23444, 11, 279, 12074, 9687, 430, 25864, 44, 17, 8111, 311, 387, 279, 30230, 8331, 304, 21816, 279, 5216, 2849, 39097, 5097, 520, 430, 23243, 304, 279, 5754, 13, 578, 356, 18394, 16, 17515, 1908, 25864, 44, 17, 30073, 7917, 9017, 279, 9572, 2849, 39097, 1853, 1418, 7917, 449, 25864, 44, 17, 430, 1436, 539, 387, 11041, 3952, 279, 41861, 1853, 5938, 449, 2536, 66, 11967, 788, 7917, 13, 3161, 264, 49479, 6945, 315, 1268, 9572, 7917, 6541, 872, 39097, 11, 279, 12074, 1828, 1511, 264, 8814, 1646, 315, 17659, 9572, 323, 264, 43940, 5623, 430, 29034, 356, 18394, 16, 505, 13750, 47141, 25864, 44, 17, 311, 1296, 1148, 1053, 3621, 13, 330, 4599, 584, 2565, 25864, 44, 17, 17466, 555, 356, 18394, 16, 11, 279, 41861, 4907, 8335, 304, 9572, 7917, 374, 28537, 11, 323, 584, 1518, 264, 18979, 315, 2849, 6650, 323, 2849, 31135, 4754, 1359, 57514, 2795, 13, 330, 2028, 4007, 11, 1243, 11, 36611, 2500, 37471, 2218, 311, 1520, 10134, 3892, 14321, 15914, 315, 9572, 1210, 763, 5369, 311, 25103, 25864, 44, 17, 17466, 555, 356, 18394, 16, 11, 57514, 596, 10278, 374, 24834, 1268, 356, 18394, 16, 45799, 682, 315, 1202, 1690, 2218, 28896, 11, 449, 279, 5915, 315, 87843, 1884, 13128, 29882, 505, 10043, 19738, 51423, 13, 220, 128257, 198 ]

2,447

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Tumour cells evade immune surveillance by upregulating the surface expression of programmed death-ligand 1 (PD-L1), which interacts with programmed death-1 (PD-1) receptor on T cells to elicit the immune checkpoint response 1 , 2 . Anti-PD-1 antibodies have shown remarkable promise in treating tumours, including metastatic melanoma 2 , 3 , 4 . However, the patient response rate is low 4 , 5 . A better understanding of PD-L1-mediated immune evasion is needed to predict patient response and improve treatment efficacy. Here we report that metastatic melanomas release extracellular vesicles, mostly in the form of exosomes, that carry PD-L1 on their surface. Stimulation with interferon-γ (IFN-γ) increases the amount of PD-L1 on these vesicles, which suppresses the function of CD8 T cells and facilitates tumour growth. In patients with metastatic melanoma, the level of circulating exosomal PD-L1 positively correlates with that of IFN-γ, and varies during the course of anti-PD-1 therapy. The magnitudes of the increase in circulating exosomal PD-L1 during early stages of treatment, as an indicator of the adaptive response of the tumour cells to T cell reinvigoration, stratifies clinical responders from non-responders. Our study unveils a mechanism by which tumour cells systemically suppress the immune system, and provides a rationale for the application of exosomal PD-L1 as a predictor for anti-PD-1 therapy. Main Extracellular vesicles, such as exosomes and microvesicles (also known as shedding vesicles), carry bioactive molecules that influence the extracellular environment and the immune system 6 , 7 , 8 . We purified exosomes from a panel of human primary and metastatic melanoma cell lines by differential centrifugation 9 , 10 , 11 , 12 , and verified them by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA) (Fig. 1a, b ). Proteins associated with the exosomes were then analysed by reverse phase protein array (RPPA), a large-scale antibody-based quantitative proteomics technology 13 . Analysis by RPPA and western blot revealed the presence of PD-L1 in exosomes, and its level was significantly higher in exosomes derived from metastatic melanoma cells compared to those from primary melanoma cells (Fig. 1c, d , Extended Data Fig. 1a ) . Iodixanol density gradient centrifugation further confirmed the association of PD-L1 with the exosomes (Extended Data Fig. 1b ). PD-L1 was also detected in microvesicles, but at a lower level (Extended Data Fig. 1c–e ). PD-L1 was also detected in extracellular vesicles generated from mouse metastatic melanoma B16-F10 cells (Extended Data Fig. 1f ). Fig. 1: Extrafacial expression of PD-L1 on melanoma cell-derived exosomes and its regulation by IFN-γ. a , A representative TEM image of purified exosomes from WM9 cells. Scale bar, 50 nm. b , Characterization of purified exosomes using nanoparticle tracking. c , RPPA data showing the levels of PD-L1 in exosomes secreted by primary or metastatic melanoma cell lines ( n = 3 for WM1552C, WM902B, A375, WM164; n = 4 for WM35, WM793, UACC-903, WM9). See Extended Data Fig. 1a for statistical analysis. d , Immunoblots for PD-L1 in the whole cell lysate (W) and purified exosomes (E) from different metastatic melanoma cell lines. All lanes were loaded with the same amount of total protein. e , A representative TEM image of WM9 cell-derived exosomes immunogold-labelled with anti-PD-L1 antibodies. Arrowheads indicate 5-nm gold particles. Scale bar, 50 nm. f , Schematic (left) of ELISA to measure PD-L1 concentration (right) on the surface of exosomes isolated from indicated cell types. TMB, 3, 3′, 5, 5′-tetramethylbenzidine; SA-HRP, streptavidin–horseradish peroxidase. g , ELISA of PD-L1 on exosomes from melanoma cells, with or without IFN-γ treatment. h , PD-l binding of exosomes with IFN-γ or blocking PD-L1 antibody (PD-L1 Ab) (see Methods ). i , Western blot analysis of PD-L1 in whole cells and exosomes from IFN-γ-treated cells and control cells. All lanes were loaded with the same amount of total protein (left). Quantification of exosomal PD-L1 by western blotting (right). Results shown represent three ( a , b ) or two ( d , e ) independent experiments. Data are mean ± s.d. of three ( f , h , i ) or four ( g ) independent biological replicates. P values are from a two-sided unpaired t -test ( g , i ). Full gel source data ( d , i ) are shown in Supplementary Fig. 1 . Source Data Full size image Tumour cell surface PD-L1 can be upregulated in response to IFN-γ secreted by activated T cells, and PD-L1 binds to PD-1 through its extracellular domain to inactivate T cells 2 , 3 , 14 . Using immuno-electron microscopy and enzyme-linked immunosorbent assay (ELISA) (Fig. 1e–g ), we found that exosomal PD-L1 has the same membrane topology as cell surface PD-L1, with its extracellular domain exposed on the surface of the exosomes. Exosomal PD-L1 binds PD-1 in a concentration-dependent manner, and this interaction can be disrupted by PD-L1-blocking antibodies (Fig. 1h ). Furthermore, the level of exosomal PD-L1 secreted by melanoma cells increased markedly upon IFN-γ treatment (Fig. 1f, g, i ), and correspondingly, these exosomes displayed increased binding to PD-1 (Fig. 1h ). Exosomes are generated and released through a defined intracellular trafficking route 7 , 9 , 10 . Genetic knockdown of the ESCRT subunit Hrs, which mediates the recognition and sorting of exosomal cargos 15 , using short hairpin (sh)RNA led to a decrease in the level of PD-L1 in the exosomes and an increase of PD-L1 in the cell (Extended Data Fig. 1g, h ). In addition, PD-L1 co-immunoprecipitated with Hrs from cell lysates (Extended Data Fig. 1i ). PD-L1 co-localized with Hrs and CD63, an exosome marker, in melanoma cells (Extended Data Fig. 1j, k ). Knockdown of Rab27A, which mediates exosome release 16 , also blocked PD-L1 secretion via the exosomes (Extended Data Fig. 1l ). To investigate the secretion of exosomal PD-L1 by melanoma cells in vivo, we established human melanoma xenografts in nude mice. Blood from these mice was collected for exosome purification and subsequent detection of human PD-L1 proteins by ELISA (Fig.", "role": "user" }, { "content": "Cancer cells are more than a lump of cells growing out of control; they participate in active combat with the immune system for their own survival. Being able to evade the immune system is a hallmark of cancer. Cancer cells release biological \"drones\" to assist in that fight—small vesicles called exosomes circulating in the blood and armed with proteins called PD-L1 that cause T cells to tire before they have a chance to reach the tumor and do battle, according to researchers from the University of Pennsylvania. The work, published in the journal Nature, is a collaboration between Wei Guo, Ph.D., a professor of Biology in the School of Arts and Sciences, and Xiaowei Xu, MD, Ph.D., a professor of Pathology and Laboratory Medicine in the Perelman School of Medicine. While primarily focused on metastatic melanoma, the team found that breast and lung cancer also release the PD-L1-carrying exosomes. The research offers a paradigm-shifting picture of how cancers take a systemic approach to suppressing the immune system. In addition, it also points to a new way to predict which cancer patients will respond to anti-PD1 therapy that disrupts immune suppression to fight tumors and a means of tracking the effectiveness of such therapies. \"Immunotherapies are life-saving for many patients with metastatic melanoma, but about 70 percent of these patients don't respond,\" said Guo. \"These treatments are costly and have toxic side effects so it would be very helpful to know which patients are going to respond. Identification of a biomarker in the bloodstream could potentially help make early predictions about which patients will respond, and, later on, could offer patients and their doctors a way to monitor how well their treatment is working.\" \"Exosomes are tiny lipid-encapsulated vesicles with a diameter less than 1/100 of a red blood cell. What we have found with these circulating exosomes, is truly remarkable,\" said Xu. \"We collected blood samples from melanoma patients treated with anti-PD1 therapy. This type of liquid biopsy assay allows us to monitor tumor-related immune suppression with time. \" One of the most successful innovations in cancer therapy has been the use of checkpoint inhibitor drugs, which are designed to block attempts by cancer cells to suppress the immune system to allow tumors to thrive and spread. One of the primary targets for this class of drugs is PD-1, a protein on the surface of T cells. On tumor cells, they express a counterpart molecule called PD-L1, which interacts with the PD-1 protein on T cells, effectively turning off that cell's anti-cancer response. Blocking that interaction using checkpoint inhibitors reinvigorates T cells, allowing them to unleash their cancer-killing power on the tumor. While it was known that cancer cells carried PD-L1 on their surface, in this new work, the team found that exosomes from human melanoma cells also carried PD-L1 on their surface. Exosomal PD-L1 can directly bind to and inhibit T cell functions. Identification of the exosomal PD-L1 secreted by tumor cells provides a major update to the immune checkpoint mechanism, and offers novel insight into tumor immune evasion. \"Essentially exosomes secreted by melanoma cells are immunosuppressive.\" Guo said. \"We propose a model in which these exosomes act like drones to fight against T cells in circulation, even before the T cells get near to the tumor.\" Since a single tumor cell is able to secrete many copies of exosomes, the interaction between the PD-L1 exosomes and T cells provides a systemic and highly effective means to suppress anti-tumor immunity in the whole body. This may explain why cancer patients might have weakened immune system. Because exosomes circulate in the bloodstream, they present an accessible way of monitoring the cancer/T cell battle through a blood test, compared to the traditional more-invasive biopsy of tumors. After an acute phase of treatment, the researchers envision such a test as a way to monitor how well the drugs are keeping cancer cells in check. By measuring pre-treatment levels of PD-L1, oncologists may be able to predict the extent of tumor burden in a patient and associate that with treatment outcome. In addition, a blood test could measure the effectiveness of a treatment, for example, levels of exosomal PD-L1 could indicate the level of T cell invigoration by immune checkpoint inhibitors. \"In the future, I think we will begin to think about cancers as a chronic disease, like diabetes,\" says Guo. \"And just as diabetes patients use glucometers to measure their sugar levels, it's possible that monitoring PD-L1 and other biomarkers on the circulating exosomes could be a way for clinicians and cancer patients to keep tabs on the treatments. It's another step toward precision and personalized medicine.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Tumour cells evade immune surveillance by upregulating the surface expression of programmed death-ligand 1 (PD-L1), which interacts with programmed death-1 (PD-1) receptor on T cells to elicit the immune checkpoint response 1 , 2 . Anti-PD-1 antibodies have shown remarkable promise in treating tumours, including metastatic melanoma 2 , 3 , 4 . However, the patient response rate is low 4 , 5 . A better understanding of PD-L1-mediated immune evasion is needed to predict patient response and improve treatment efficacy. Here we report that metastatic melanomas release extracellular vesicles, mostly in the form of exosomes, that carry PD-L1 on their surface. Stimulation with interferon-γ (IFN-γ) increases the amount of PD-L1 on these vesicles, which suppresses the function of CD8 T cells and facilitates tumour growth. In patients with metastatic melanoma, the level of circulating exosomal PD-L1 positively correlates with that of IFN-γ, and varies during the course of anti-PD-1 therapy. The magnitudes of the increase in circulating exosomal PD-L1 during early stages of treatment, as an indicator of the adaptive response of the tumour cells to T cell reinvigoration, stratifies clinical responders from non-responders. Our study unveils a mechanism by which tumour cells systemically suppress the immune system, and provides a rationale for the application of exosomal PD-L1 as a predictor for anti-PD-1 therapy. Main Extracellular vesicles, such as exosomes and microvesicles (also known as shedding vesicles), carry bioactive molecules that influence the extracellular environment and the immune system 6 , 7 , 8 . We purified exosomes from a panel of human primary and metastatic melanoma cell lines by differential centrifugation 9 , 10 , 11 , 12 , and verified them by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA) (Fig. 1a, b ). Proteins associated with the exosomes were then analysed by reverse phase protein array (RPPA), a large-scale antibody-based quantitative proteomics technology 13 . Analysis by RPPA and western blot revealed the presence of PD-L1 in exosomes, and its level was significantly higher in exosomes derived from metastatic melanoma cells compared to those from primary melanoma cells (Fig. 1c, d , Extended Data Fig. 1a ) . Iodixanol density gradient centrifugation further confirmed the association of PD-L1 with the exosomes (Extended Data Fig. 1b ). PD-L1 was also detected in microvesicles, but at a lower level (Extended Data Fig. 1c–e ). PD-L1 was also detected in extracellular vesicles generated from mouse metastatic melanoma B16-F10 cells (Extended Data Fig. 1f ). Fig. 1: Extrafacial expression of PD-L1 on melanoma cell-derived exosomes and its regulation by IFN-γ. a , A representative TEM image of purified exosomes from WM9 cells. Scale bar, 50 nm. b , Characterization of purified exosomes using nanoparticle tracking. c , RPPA data showing the levels of PD-L1 in exosomes secreted by primary or metastatic melanoma cell lines ( n = 3 for WM1552C, WM902B, A375, WM164; n = 4 for WM35, WM793, UACC-903, WM9). See Extended Data Fig. 1a for statistical analysis. d , Immunoblots for PD-L1 in the whole cell lysate (W) and purified exosomes (E) from different metastatic melanoma cell lines. All lanes were loaded with the same amount of total protein. e , A representative TEM image of WM9 cell-derived exosomes immunogold-labelled with anti-PD-L1 antibodies. Arrowheads indicate 5-nm gold particles. Scale bar, 50 nm. f , Schematic (left) of ELISA to measure PD-L1 concentration (right) on the surface of exosomes isolated from indicated cell types. TMB, 3, 3′, 5, 5′-tetramethylbenzidine; SA-HRP, streptavidin–horseradish peroxidase. g , ELISA of PD-L1 on exosomes from melanoma cells, with or without IFN-γ treatment. h , PD-l binding of exosomes with IFN-γ or blocking PD-L1 antibody (PD-L1 Ab) (see Methods ). i , Western blot analysis of PD-L1 in whole cells and exosomes from IFN-γ-treated cells and control cells. All lanes were loaded with the same amount of total protein (left). Quantification of exosomal PD-L1 by western blotting (right). Results shown represent three ( a , b ) or two ( d , e ) independent experiments. Data are mean ± s.d. of three ( f , h , i ) or four ( g ) independent biological replicates. P values are from a two-sided unpaired t -test ( g , i ). Full gel source data ( d , i ) are shown in Supplementary Fig. 1 . Source Data Full size image Tumour cell surface PD-L1 can be upregulated in response to IFN-γ secreted by activated T cells, and PD-L1 binds to PD-1 through its extracellular domain to inactivate T cells 2 , 3 , 14 . Using immuno-electron microscopy and enzyme-linked immunosorbent assay (ELISA) (Fig. 1e–g ), we found that exosomal PD-L1 has the same membrane topology as cell surface PD-L1, with its extracellular domain exposed on the surface of the exosomes. Exosomal PD-L1 binds PD-1 in a concentration-dependent manner, and this interaction can be disrupted by PD-L1-blocking antibodies (Fig. 1h ). Furthermore, the level of exosomal PD-L1 secreted by melanoma cells increased markedly upon IFN-γ treatment (Fig. 1f, g, i ), and correspondingly, these exosomes displayed increased binding to PD-1 (Fig. 1h ). Exosomes are generated and released through a defined intracellular trafficking route 7 , 9 , 10 . Genetic knockdown of the ESCRT subunit Hrs, which mediates the recognition and sorting of exosomal cargos 15 , using short hairpin (sh)RNA led to a decrease in the level of PD-L1 in the exosomes and an increase of PD-L1 in the cell (Extended Data Fig. 1g, h ). In addition, PD-L1 co-immunoprecipitated with Hrs from cell lysates (Extended Data Fig. 1i ). PD-L1 co-localized with Hrs and CD63, an exosome marker, in melanoma cells (Extended Data Fig. 1j, k ). Knockdown of Rab27A, which mediates exosome release 16 , also blocked PD-L1 secretion via the exosomes (Extended Data Fig. 1l ). To investigate the secretion of exosomal PD-L1 by melanoma cells in vivo, we established human melanoma xenografts in nude mice. Blood from these mice was collected for exosome purification and subsequent detection of human PD-L1 proteins by ELISA (Fig.<|im_end|> <|im_start|>assistant Cancer cells are more than a lump of cells growing out of control; they participate in active combat with the immune system for their own survival. Being able to evade the immune system is a hallmark of cancer. Cancer cells release biological "drones" to assist in that fight—small vesicles called exosomes circulating in the blood and armed with proteins called PD-L1 that cause T cells to tire before they have a chance to reach the tumor and do battle, according to researchers from the University of Pennsylvania. The work, published in the journal Nature, is a collaboration between Wei Guo, Ph.D., a professor of Biology in the School of Arts and Sciences, and Xiaowei Xu, MD, Ph.D., a professor of Pathology and Laboratory Medicine in the Perelman School of Medicine. While primarily focused on metastatic melanoma, the team found that breast and lung cancer also release the PD-L1-carrying exosomes. The research offers a paradigm-shifting picture of how cancers take a systemic approach to suppressing the immune system. In addition, it also points to a new way to predict which cancer patients will respond to anti-PD1 therapy that disrupts immune suppression to fight tumors and a means of tracking the effectiveness of such therapies. "Immunotherapies are life-saving for many patients with metastatic melanoma, but about 70 percent of these patients don't respond," said Guo. "These treatments are costly and have toxic side effects so it would be very helpful to know which patients are going to respond. Identification of a biomarker in the bloodstream could potentially help make early predictions about which patients will respond, and, later on, could offer patients and their doctors a way to monitor how well their treatment is working." "Exosomes are tiny lipid-encapsulated vesicles with a diameter less than 1/100 of a red blood cell. What we have found with these circulating exosomes, is truly remarkable," said Xu. "We collected blood samples from melanoma patients treated with anti-PD1 therapy. This type of liquid biopsy assay allows us to monitor tumor-related immune suppression with time. " One of the most successful innovations in cancer therapy has been the use of checkpoint inhibitor drugs, which are designed to block attempts by cancer cells to suppress the immune system to allow tumors to thrive and spread. One of the primary targets for this class of drugs is PD-1, a protein on the surface of T cells. On tumor cells, they express a counterpart molecule called PD-L1, which interacts with the PD-1 protein on T cells, effectively turning off that cell's anti-cancer response. Blocking that interaction using checkpoint inhibitors reinvigorates T cells, allowing them to unleash their cancer-killing power on the tumor. While it was known that cancer cells carried PD-L1 on their surface, in this new work, the team found that exosomes from human melanoma cells also carried PD-L1 on their surface. Exosomal PD-L1 can directly bind to and inhibit T cell functions. Identification of the exosomal PD-L1 secreted by tumor cells provides a major update to the immune checkpoint mechanism, and offers novel insight into tumor immune evasion. "Essentially exosomes secreted by melanoma cells are immunosuppressive." Guo said. "We propose a model in which these exosomes act like drones to fight against T cells in circulation, even before the T cells get near to the tumor." Since a single tumor cell is able to secrete many copies of exosomes, the interaction between the PD-L1 exosomes and T cells provides a systemic and highly effective means to suppress anti-tumor immunity in the whole body. This may explain why cancer patients might have weakened immune system. Because exosomes circulate in the bloodstream, they present an accessible way of monitoring the cancer/T cell battle through a blood test, compared to the traditional more-invasive biopsy of tumors. After an acute phase of treatment, the researchers envision such a test as a way to monitor how well the drugs are keeping cancer cells in check. By measuring pre-treatment levels of PD-L1, oncologists may be able to predict the extent of tumor burden in a patient and associate that with treatment outcome. In addition, a blood test could measure the effectiveness of a treatment, for example, levels of exosomal PD-L1 could indicate the level of T cell invigoration by immune checkpoint inhibitors. "In the future, I think we will begin to think about cancers as a chronic disease, like diabetes," says Guo. "And just as diabetes patients use glucometers to measure their sugar levels, it's possible that monitoring PD-L1 and other biomarkers on the circulating exosomes could be a way for clinicians and cancer patients to keep tabs on the treatments. It's another step toward precision and personalized medicine." <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 350, 372, 414, 7917, 77753, 22852, 22156, 555, 709, 1610, 15853, 279, 7479, 7645, 315, 56168, 4648, 2922, 343, 438, 220, 16, 320, 23891, 8288, 16, 705, 902, 84261, 449, 56168, 4648, 12, 16, 320, 23891, 12, 16, 8, 35268, 389, 350, 7917, 311, 658, 19195, 279, 22852, 30395, 2077, 220, 16, 1174, 220, 17, 662, 23853, 9483, 35, 12, 16, 59854, 617, 6982, 23649, 11471, 304, 27723, 15756, 2530, 11, 2737, 68370, 780, 68012, 7942, 220, 17, 1174, 220, 18, 1174, 220, 19, 662, 4452, 11, 279, 8893, 2077, 4478, 374, 3428, 220, 19, 1174, 220, 20, 662, 362, 2731, 8830, 315, 27572, 8288, 16, 82076, 22852, 77832, 374, 4460, 311, 7168, 8893, 2077, 323, 7417, 6514, 41265, 13, 5810, 584, 1934, 430, 68370, 780, 68012, 23063, 4984, 11741, 65441, 65635, 4440, 11, 10213, 304, 279, 1376, 315, 506, 58375, 11, 430, 6920, 27572, 8288, 16, 389, 872, 7479, 13, 800, 61461, 449, 41305, 263, 12, 60474, 320, 2843, 45, 12, 60474, 8, 12992, 279, 3392, 315, 27572, 8288, 16, 389, 1521, 65635, 4440, 11, 902, 28321, 288, 279, 734, 315, 11325, 23, 350, 7917, 323, 73633, 15756, 414, 6650, 13, 763, 6978, 449, 68370, 780, 68012, 7942, 11, 279, 2237, 315, 54828, 506, 96108, 27572, 8288, 16, 40646, 97303, 449, 430, 315, 11812, 45, 12, 60474, 11, 323, 35327, 2391, 279, 3388, 315, 7294, 9483, 35, 12, 16, 15419, 13, 578, 8622, 21237, 315, 279, 5376, 304, 54828, 506, 96108, 27572, 8288, 16, 2391, 4216, 18094, 315, 6514, 11, 439, 459, 21070, 315, 279, 48232, 2077, 315, 279, 15756, 414, 7917, 311, 350, 2849, 312, 14386, 343, 7769, 11, 44397, 9803, 14830, 70639, 505, 2536, 12, 6961, 388, 13, 5751, 4007, 28847, 8839, 264, 17383, 555, 902, 15756, 414, 7917, 1887, 2740, 28321, 279, 22852, 1887, 11, 323, 5825, 264, 57916, 369, 279, 3851, 315, 506, 96108, 27572, 8288, 16, 439, 264, 62254, 369, 7294, 9483, 35, 12, 16, 15419, 13, 4802, 72334, 65441, 65635, 4440, 11, 1778, 439, 506, 58375, 323, 8162, 2396, 4440, 320, 19171, 3967, 439, 80417, 65635, 4440, 705, 6920, 17332, 3104, 35715, 430, 10383, 279, 11741, 65441, 4676, 323, 279, 22852, 1887, 220, 21, 1174, 220, 22, 1174, 220, 23, 662, 1226, 92600, 506, 58375, 505, 264, 7090, 315, 3823, 6156, 323, 68370, 780, 68012, 7942, 2849, 5238, 555, 41264, 74182, 773, 367, 220, 24, 1174, 220, 605, 1174, 220, 806, 1174, 220, 717, 1174, 323, 24884, 1124, 555, 18874, 17130, 92914, 320, 21695, 8, 323, 76307, 7203, 15194, 6492, 320, 6542, 32, 8, 320, 30035, 13, 220, 16, 64, 11, 293, 7609, 15542, 1354, 5938, 449, 279, 506, 58375, 1051, 1243, 67458, 555, 10134, 10474, 13128, 1358, 320, 49, 4505, 32, 705, 264, 3544, 13230, 63052, 6108, 47616, 5541, 24203, 5557, 220, 1032, 662, 18825, 555, 432, 4505, 32, 323, 19001, 81982, 10675, 279, 9546, 315, 27572, 8288, 16, 304, 506, 58375, 11, 323, 1202, 2237, 574, 12207, 5190, 304, 506, 58375, 14592, 505, 68370, 780, 68012, 7942, 7917, 7863, 311, 1884, 505, 6156, 68012, 7942, 7917, 320, 30035, 13, 220, 16, 66, 11, 294, 1174, 41665, 2956, 23966, 13, 220, 16, 64, 883, 662, 358, 347, 953, 39710, 17915, 20779, 74182, 773, 367, 4726, 11007, 279, 15360, 315, 27572, 8288, 16, 449, 279, 506, 58375, 320, 54290, 2956, 23966, 13, 220, 16, 65, 7609, 27572, 8288, 16, 574, 1101, 16914, 304, 8162, 2396, 4440, 11, 719, 520, 264, 4827, 2237, 320, 54290, 2956, 23966, 13, 220, 16, 66, 4235, 68, 7609, 27572, 8288, 16, 574, 1101, 16914, 304, 11741, 65441, 65635, 4440, 8066, 505, 8814, 68370, 780, 68012, 7942, 426, 845, 7424, 605, 7917, 320, 54290, 2956, 23966, 13, 220, 16, 69, 7609, 23966, 13, 220, 16, 25, 26041, 22974, 532, 7645, 315, 27572, 8288, 16, 389, 68012, 7942, 2849, 72286, 506, 58375, 323, 1202, 19812, 555, 11812, 45, 12, 60474, 13, 264, 1174, 362, 18740, 76770, 2217, 315, 92600, 506, 58375, 505, 24030, 24, 7917, 13, 25635, 3703, 11, 220, 1135, 26807, 13, 293, 1174, 16007, 2065, 315, 92600, 506, 58375, 1701, 76307, 7203, 15194, 13, 272, 1174, 432, 4505, 32, 828, 9204, 279, 5990, 315, 27572, 8288, 16, 304, 506, 58375, 6367, 291, 555, 6156, 477, 68370, 780, 68012, 7942, 2849, 5238, 320, 308, 284, 220, 18, 369, 24030, 9992, 17, 34, 11, 24030, 21026, 33, 11, 362, 12935, 11, 24030, 10513, 26, 308, 284, 220, 19, 369, 24030, 1758, 11, 24030, 24531, 11, 549, 30542, 12, 23305, 11, 24030, 24, 570, 3580, 41665, 2956, 23966, 13, 220, 16, 64, 369, 29564, 6492, 13, 294, 1174, 67335, 38834, 2469, 369, 27572, 8288, 16, 304, 279, 4459, 2849, 84495, 349, 320, 54, 8, 323, 92600, 506, 58375, 320, 36, 8, 505, 2204, 68370, 780, 68012, 7942, 2849, 5238, 13, 2052, 34125, 1051, 6799, 449, 279, 1890, 3392, 315, 2860, 13128, 13, 384, 1174, 362, 18740, 76770, 2217, 315, 24030, 24, 2849, 72286, 506, 58375, 33119, 540, 820, 32901, 449, 7294, 9483, 35, 8288, 16, 59854, 13, 34812, 36910, 13519, 220, 20, 5392, 76, 6761, 19252, 13, 25635, 3703, 11, 220, 1135, 26807, 13, 282, 1174, 328, 82149, 320, 2414, 8, 315, 17705, 35301, 311, 6767, 27572, 8288, 16, 20545, 320, 1315, 8, 389, 279, 7479, 315, 506, 58375, 25181, 505, 16717, 2849, 4595, 13, 350, 8578, 11, 220, 18, 11, 220, 18, 39615, 11, 220, 20, 11, 220, 20, 39615, 12, 73542, 2453, 42972, 8123, 89, 91073, 26, 16998, 11529, 22394, 11, 5527, 418, 15567, 258, 4235, 20100, 805, 329, 819, 824, 85078, 521, 13, 342, 1174, 17705, 35301, 315, 27572, 8288, 16, 389, 506, 58375, 505, 68012, 7942, 7917, 11, 449, 477, 2085, 11812, 45, 12, 60474, 6514, 13, 305, 1174, 27572, 2922, 11212, 315, 506, 58375, 449, 11812, 45, 12, 60474, 477, 22978, 27572, 8288, 16, 63052, 320, 23891, 8288, 16, 3765, 8, 320, 4151, 19331, 7609, 602, 1174, 11104, 81982, 6492, 315, 27572, 8288, 16, 304, 4459, 7917, 323, 506, 58375, 505, 11812, 45, 12, 60474, 88186, 7917, 323, 2585, 7917, 13, 2052, 34125, 1051, 6799, 449, 279, 1890, 3392, 315, 2860, 13128, 320, 2414, 570, 32541, 2461, 315, 506, 96108, 27572, 8288, 16, 555, 19001, 81982, 1303, 320, 1315, 570, 18591, 6982, 4097, 2380, 320, 264, 1174, 293, 883, 477, 1403, 320, 294, 1174, 384, 883, 9678, 21896, 13, 2956, 527, 3152, 20903, 274, 962, 13, 315, 2380, 320, 282, 1174, 305, 1174, 602, 883, 477, 3116, 320, 342, 883, 9678, 24156, 29641, 988, 13, 393, 2819, 527, 505, 264, 1403, 50858, 653, 77267, 259, 482, 1985, 320, 342, 1174, 602, 7609, 8797, 18316, 2592, 828, 320, 294, 1174, 602, 883, 527, 6982, 304, 99371, 23966, 13, 220, 16, 662, 8922, 2956, 8797, 1404, 2217, 350, 372, 414, 2849, 7479, 27572, 8288, 16, 649, 387, 709, 81722, 304, 2077, 311, 11812, 45, 12, 60474, 6367, 291, 555, 22756, 350, 7917, 11, 323, 27572, 8288, 16, 58585, 311, 27572, 12, 16, 1555, 1202, 11741, 65441, 8106, 311, 304, 17281, 350, 7917, 220, 17, 1174, 220, 18, 1174, 220, 975, 662, 12362, 4998, 16711, 37081, 2298, 92914, 323, 49242, 55514, 33119, 437, 30986, 306, 65033, 320, 2818, 35301, 8, 320, 30035, 13, 220, 16, 68, 4235, 70, 7026, 584, 1766, 430, 506, 96108, 27572, 8288, 16, 706, 279, 1890, 39654, 45982, 439, 2849, 7479, 27572, 8288, 16, 11, 449, 1202, 11741, 65441, 8106, 15246, 389, 279, 7479, 315, 279, 506, 58375, 13, 1398, 96108, 27572, 8288, 16, 58585, 27572, 12, 16, 304, 264, 20545, 43918, 11827, 11, 323, 420, 16628, 649, 387, 69627, 555, 27572, 8288, 16, 79861, 59854, 320, 30035, 13, 220, 16, 71, 7609, 24296, 11, 279, 2237, 315, 506, 96108, 27572, 8288, 16, 6367, 291, 555, 68012, 7942, 7917, 7319, 88101, 5304, 11812, 45, 12, 60474, 6514, 320, 30035, 13, 220, 16, 69, 11, 342, 11, 602, 7026, 323, 8024, 11559, 11, 1521, 506, 58375, 12882, 7319, 11212, 311, 27572, 12, 16, 320, 30035, 13, 220, 16, 71, 7609, 1398, 58375, 527, 8066, 323, 6004, 1555, 264, 4613, 10805, 65441, 34563, 6149, 220, 22, 1174, 220, 24, 1174, 220, 605, 662, 75226, 14459, 2996, 315, 279, 44374, 5463, 1207, 3928, 473, 5544, 11, 902, 25098, 988, 279, 18324, 323, 29373, 315, 506, 96108, 62762, 437, 220, 868, 1174, 1701, 2875, 7013, 13576, 320, 939, 8, 31820, 6197, 311, 264, 18979, 304, 279, 2237, 315, 27572, 8288, 16, 304, 279, 506, 58375, 323, 459, 5376, 315, 27572, 8288, 16, 304, 279, 2849, 320, 54290, 2956, 23966, 13, 220, 16, 70, 11, 305, 7609, 763, 5369, 11, 27572, 8288, 16, 1080, 64683, 359, 454, 2827, 575, 33337, 449, 473, 5544, 505, 2849, 84495, 988, 320, 54290, 2956, 23966, 13, 220, 16, 72, 7609, 27572, 8288, 16, 1080, 41160, 1534, 449, 473, 5544, 323, 11325, 5495, 11, 459, 506, 32554, 11381, 11, 304, 68012, 7942, 7917, 320, 54290, 2956, 23966, 13, 220, 16, 73, 11, 597, 7609, 64894, 2996, 315, 36824, 1544, 32, 11, 902, 25098, 988, 506, 32554, 4984, 220, 845, 1174, 1101, 19857, 27572, 8288, 16, 87067, 4669, 279, 506, 58375, 320, 54290, 2956, 23966, 13, 220, 16, 75, 7609, 2057, 19874, 279, 87067, 315, 506, 96108, 27572, 8288, 16, 555, 68012, 7942, 7917, 304, 41294, 11, 584, 9749, 3823, 68012, 7942, 53265, 540, 3017, 82, 304, 20637, 24548, 13, 20671, 505, 1521, 24548, 574, 14890, 369, 506, 32554, 94536, 323, 17876, 18468, 315, 3823, 27572, 8288, 16, 28896, 555, 17705, 35301, 320, 30035, 13, 128257, 198, 128256, 78191, 198, 34, 11967, 7917, 527, 810, 1109, 264, 49629, 315, 7917, 7982, 704, 315, 2585, 26, 814, 16136, 304, 4642, 12896, 449, 279, 22852, 1887, 369, 872, 1866, 20237, 13, 21347, 3025, 311, 77753, 279, 22852, 1887, 374, 264, 98799, 315, 9572, 13, 26211, 7917, 4984, 24156, 330, 67, 32921, 1, 311, 7945, 304, 430, 4465, 2345, 9181, 65635, 4440, 2663, 506, 58375, 54828, 304, 279, 6680, 323, 17903, 449, 28896, 2663, 27572, 8288, 16, 430, 5353, 350, 7917, 311, 28387, 1603, 814, 617, 264, 6140, 311, 5662, 279, 36254, 323, 656, 8209, 11, 4184, 311, 12074, 505, 279, 3907, 315, 20355, 13, 578, 990, 11, 4756, 304, 279, 8486, 22037, 11, 374, 264, 20632, 1990, 53548, 4673, 78, 11, 2405, 920, 2637, 264, 14561, 315, 40023, 304, 279, 6150, 315, 17979, 323, 23199, 11, 323, 41235, 363, 20568, 57514, 11, 14306, 11, 2405, 920, 2637, 264, 14561, 315, 8092, 2508, 323, 32184, 19152, 304, 279, 3700, 64641, 6150, 315, 19152, 13, 6104, 15871, 10968, 389, 68370, 780, 68012, 7942, 11, 279, 2128, 1766, 430, 17659, 323, 21271, 9572, 1101, 4984, 279, 27572, 8288, 16, 1824, 11687, 287, 506, 58375, 13, 578, 3495, 6209, 264, 49340, 7666, 18148, 6945, 315, 1268, 51423, 1935, 264, 46417, 5603, 311, 98795, 279, 22852, 1887, 13, 763, 5369, 11, 433, 1101, 3585, 311, 264, 502, 1648, 311, 7168, 902, 9572, 6978, 690, 6013, 311, 7294, 9483, 35, 16, 15419, 430, 24927, 82, 22852, 46735, 311, 4465, 56071, 323, 264, 3445, 315, 15194, 279, 27375, 315, 1778, 52312, 13, 330, 1453, 26046, 1605, 391, 552, 527, 2324, 59085, 369, 1690, 6978, 449, 68370, 780, 68012, 7942, 11, 719, 922, 220, 2031, 3346, 315, 1521, 6978, 1541, 956, 6013, 1359, 1071, 4673, 78, 13, 330, 9673, 22972, 527, 34348, 323, 617, 21503, 3185, 6372, 779, 433, 1053, 387, 1633, 11190, 311, 1440, 902, 6978, 527, 2133, 311, 6013, 13, 59776, 315, 264, 39538, 13152, 304, 279, 100216, 1436, 13893, 1520, 1304, 4216, 20492, 922, 902, 6978, 690, 6013, 11, 323, 11, 3010, 389, 11, 1436, 3085, 6978, 323, 872, 16410, 264, 1648, 311, 8891, 1268, 1664, 872, 6514, 374, 3318, 1210, 330, 849, 58375, 527, 13987, 68700, 12, 967, 2690, 7913, 65635, 4440, 449, 264, 23899, 2753, 1109, 220, 16, 14, 1041, 315, 264, 2579, 6680, 2849, 13, 3639, 584, 617, 1766, 449, 1521, 54828, 506, 58375, 11, 374, 9615, 23649, 1359, 1071, 57514, 13, 330, 1687, 14890, 6680, 10688, 505, 68012, 7942, 6978, 12020, 449, 7294, 9483, 35, 16, 15419, 13, 1115, 955, 315, 14812, 99647, 65033, 6276, 603, 311, 8891, 36254, 14228, 22852, 46735, 449, 892, 13, 330, 3861, 315, 279, 1455, 6992, 46045, 304, 9572, 15419, 706, 1027, 279, 1005, 315, 30395, 70785, 11217, 11, 902, 527, 6319, 311, 2565, 13865, 555, 9572, 7917, 311, 28321, 279, 22852, 1887, 311, 2187, 56071, 311, 41972, 323, 9041, 13, 3861, 315, 279, 6156, 11811, 369, 420, 538, 315, 11217, 374, 27572, 12, 16, 11, 264, 13128, 389, 279, 7479, 315, 350, 7917, 13, 1952, 36254, 7917, 11, 814, 3237, 264, 45116, 43030, 2663, 27572, 8288, 16, 11, 902, 84261, 449, 279, 27572, 12, 16, 13128, 389, 350, 7917, 11, 13750, 13353, 1022, 430, 2849, 596, 7294, 1824, 11967, 2077, 13, 83045, 430, 16628, 1701, 30395, 68642, 312, 14386, 71070, 988, 350, 7917, 11, 10923, 1124, 311, 78535, 872, 9572, 12934, 9585, 2410, 389, 279, 36254, 13, 6104, 433, 574, 3967, 430, 9572, 7917, 11953, 27572, 8288, 16, 389, 872, 7479, 11, 304, 420, 502, 990, 11, 279, 2128, 1766, 430, 506, 58375, 505, 3823, 68012, 7942, 7917, 1101, 11953, 27572, 8288, 16, 389, 872, 7479, 13, 1398, 96108, 27572, 8288, 16, 649, 6089, 10950, 311, 323, 69033, 350, 2849, 5865, 13, 59776, 315, 279, 506, 96108, 27572, 8288, 16, 6367, 291, 555, 36254, 7917, 5825, 264, 3682, 2713, 311, 279, 22852, 30395, 17383, 11, 323, 6209, 11775, 20616, 1139, 36254, 22852, 77832, 13, 330, 38538, 31668, 506, 58375, 6367, 291, 555, 68012, 7942, 7917, 527, 33119, 437, 455, 69563, 1210, 4673, 78, 1071, 13, 330, 1687, 30714, 264, 1646, 304, 902, 1521, 506, 58375, 1180, 1093, 38332, 311, 4465, 2403, 350, 7917, 304, 35855, 11, 1524, 1603, 279, 350, 7917, 636, 3221, 311, 279, 36254, 1210, 8876, 264, 3254, 36254, 2849, 374, 3025, 311, 513, 9537, 1690, 11236, 315, 506, 58375, 11, 279, 16628, 1990, 279, 27572, 8288, 16, 506, 58375, 323, 350, 7917, 5825, 264, 46417, 323, 7701, 7524, 3445, 311, 28321, 7294, 2442, 69361, 40368, 304, 279, 4459, 2547, 13, 1115, 1253, 10552, 3249, 9572, 6978, 2643, 617, 58764, 22852, 1887, 13, 9393, 506, 58375, 4319, 6468, 304, 279, 100216, 11, 814, 3118, 459, 15987, 1648, 315, 16967, 279, 9572, 17146, 2849, 8209, 1555, 264, 6680, 1296, 11, 7863, 311, 279, 8776, 810, 3502, 78134, 99647, 315, 56071, 13, 4740, 459, 30883, 10474, 315, 6514, 11, 279, 12074, 48146, 1778, 264, 1296, 439, 264, 1648, 311, 8891, 1268, 1664, 279, 11217, 527, 10494, 9572, 7917, 304, 1817, 13, 3296, 30090, 864, 2442, 35320, 5990, 315, 27572, 8288, 16, 11, 78970, 22012, 1253, 387, 3025, 311, 7168, 279, 13112, 315, 36254, 23104, 304, 264, 8893, 323, 22712, 430, 449, 6514, 15632, 13, 763, 5369, 11, 264, 6680, 1296, 1436, 6767, 279, 27375, 315, 264, 6514, 11, 369, 3187, 11, 5990, 315, 506, 96108, 27572, 8288, 16, 1436, 13519, 279, 2237, 315, 350, 2849, 1558, 343, 7769, 555, 22852, 30395, 68642, 13, 330, 644, 279, 3938, 11, 358, 1781, 584, 690, 3240, 311, 1781, 922, 51423, 439, 264, 21249, 8624, 11, 1093, 20335, 1359, 2795, 4673, 78, 13, 330, 3112, 1120, 439, 20335, 6978, 1005, 78376, 884, 2481, 311, 6767, 872, 13465, 5990, 11, 433, 596, 3284, 430, 16967, 27572, 8288, 16, 323, 1023, 39538, 91141, 389, 279, 54828, 506, 58375, 1436, 387, 264, 1648, 369, 78545, 323, 9572, 6978, 311, 2567, 23204, 389, 279, 22972, 13, 1102, 596, 2500, 3094, 9017, 16437, 323, 35649, 16088, 1210, 220, 128257, 198 ]

2,582

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Trypanosomes are protozoan parasites that cause infectious diseases, including African trypanosomiasis (sleeping sickness) in humans and nagana in economically important livestock 1 , 2 . An effective vaccine against trypanosomes would be an important control tool, but the parasite has evolved sophisticated immunoprotective mechanisms—including antigenic variation 3 —that present an apparently insurmountable barrier to vaccination. Here we show, using a systematic genome-led vaccinology approach and a mouse model of Trypanosoma vivax infection 4 , that protective invariant subunit vaccine antigens can be identified. Vaccination with a single recombinant protein comprising the extracellular region of a conserved cell-surface protein that is localized to the flagellum membrane (which we term ‘invariant flagellum antigen from T. vivax ’) induced long-lasting protection. Immunity was passively transferred with immune serum, and recombinant monoclonal antibodies to this protein could induce sterile protection and revealed several mechanisms of antibody-mediated immunity, including a major role for complement. Our discovery identifies a vaccine candidate for an important parasitic disease that has constrained socioeconomic development in countries in sub-Saharan Africa 5 , and provides evidence that highly protective vaccines against trypanosome infections can be achieved. Main African trypanosomiasis is an infectious disease that is caused by unicellular parasites of the genus Trypanosoma , which are transmitted by the bite of an infected tsetse fly. In humans, trypanosome infections cause sleeping sickness: a deadly disease that threatens the lives of millions of people who live in over 30 countries in sub-Saharan Africa 6 . Some species of trypanosome also infect important livestock animals (including cattle, goats and pigs) and cause the wasting disease nagana (animal African trypanosomiasis), which affects the livelihoods of people who rely on these animals for milk, food and draught power 1 . Approximately three million cattle die from this disease every year, which results in an estimated direct annual economic cost of many hundreds of millions of dollars 7 and represents a major barrier for the socioeconomic advancement of many countries in Africa. Nagana is primarily caused by T. vivax and Trypanosoma congolense and is currently managed with drugs, but resistance is increasing 8 . Previous attempts to develop subunit vaccines against African trypanosome infections have highlighted the difficulties in overcoming the immune evasion strategies that have been evolved by these parasites to enable them to survive in host blood 9 . These strategies include antigenic variation: the serial expression of an abundant allelically excluded variable surface glycoprotein (VSG), and the rapid removal of surface-bound antibodies by hydrodynamic sorting 3 , 10 . It is widely thought that the VSG forms a constantly changing, impenetrable surface coating that sterically shields other surface proteins from host antibodies, which leads to chronic infections characterized by oscillating parasitaemia; however, a careful analysis of recent structural information suggests that this model may not fully explain the protective role of the VSGs 11 . We therefore hypothesized that the VSGs may also subvert natural immunity by preventing the acquisition of high-titre antibody responses to protective antigens, suggesting that eliciting prophylactic unnatural host immunity by vaccination could be achieved. Here we report the identification of a conserved cell-surface protein that—when used as a subunit vaccine in a mouse model of T. vivax infection—is capable of eliciting highly protective immunity. A subunit vaccine induces immunity to T. vivax To identify subunit vaccine candidates for T. vivax , we established a genome-led vaccinology approach using a bioluminescent mouse model of infection 4 (Fig. 1a ). We determined that adoptive transfer of about 100 parasites intravenously into BALB/c mouse hosts resulted in an acute, reproducible infection that permitted sensitive and accurate quantification of parasitaemia using light-based imaging 12 . We selected subunit vaccine candidates by searching the T. vivax genome 13 for genes that encode predicted cell-surface and secreted proteins that are likely to be accessible to vaccine-elicited antibodies. We selected 60 candidates using the following criteria: (1) they did not belong to paralogous gene families (to minimize the risk of functional redundancy in different mammalian hosts) 14 ; (2) contained more than 300 amino acids in their predicted extracellular region (and so are likely to be accessible at the cell surface); and (3) had evidence of expression in the blood stages 15 (Supplementary Table 1 ). We synthesized gene sequences encoding the entire predicted extracellular region, and cloned them into a mammalian protein expression plasmid that contained an exogenous secretion peptide and purification tags. We expressed the candidates as soluble recombinant proteins in HEK293 cells to increase the chance that structurally critical posttranslational modifications were appropriately added. Of the 60 expression plasmids we tested, 39 yielded sufficient protein after purification for vaccination trials (Extended Data Fig. 1a ). For vaccination, we used a prime and two-boost regime that used alum as an adjuvant to bias host responses towards humoral immunity. To reduce any systemic adjuvant-elicited effects on disease progression, we rested the vaccinated mice for a minimum of four weeks following the final boost before parasite challenge (Extended Data Fig. 1b, c ). Trypanosoma vivax loses virulence once removed from donor mice, and so, to avoid confounding effects due to the loss of parasite viability during the infection procedure, we ensured that infections were comparable in control mice challenged before and after the vaccinated mice (Extended Data Fig. 1b ). Fig. 1: Candidate V23 (IFX) induces protective immunity in a mouse model of T. vivax infection. a , Schematic of the genome-led vaccinology approach. b , Summary of mean parasitaemia ( n ≥ 3 mice) quantified by bioluminescence in cohorts of vaccinated mice challenged with T. vivax . Although the V58 candidate had lower mean parasitaemia relative to controls on day 8, it rebounded on day 9 and so was not considered further. c , d , Bioluminescent images of adjuvant-only control (left panels) and mice vaccinated with V31 ( c right) and V23 ( d right); images were taken five (top panels) and eight (bottom panels) days after infection. Source data Full size image We determined the elicited antibody titres to each antigen,", "role": "user" }, { "content": "Scientists have identified a promising vaccine candidate for a parasitic disease that causes a chronic wasting disease in livestock animals across sub Saharan Africa. The disease, called Nagana, threatens the livelihoods of millions of people who depend on animals for milk, food and draft power. It's hoped the research—from the University of York and the Wellcome Sanger Institute—will help alleviate the socioeconomic hardship of people living in some of the most deprived regions in the world. Deadly The disease is caused by trypanosomes: insect-borne parasites that live in the blood which—in humans—are responsible for a deadly disease called African sleeping sickness. Millions of people living in sub-Saharan countries are at risk of trypanosome infections and the economic impact of the livestock disease is vast, with around three million cattle dying every year costing billions of dollars in lost productivity. Trypanosomes have evolved sophisticated protective mechanisms that allow them to thrive in blood and have so far presented a barrier to develop vaccines—which would be an important tool to control these diseases. The researchers identified a vaccine candidate that can elicit sterile immunity to T. vivax—one of the trypanosome parasites responsible for nagana. Parasites Researchers used an approach called \"reverse vaccinology\" to find new potential vaccines. Professor Gavin Wright from the Department of Biology and the York Biomedical Research Institute said: \"Vaccinating against trypanosomes has long been considered a low value option to tackle this awful disease which affects the lives and livelihoods of people living in some of the most deprived regions on the planet. Because of their protective molecular armory, developing a vaccine against these parasites seemed like trying to stop a tank with a peashooter. \"Our discovery identifies a vaccine candidate for an important parasitic disease that has constrained the socioeconomic development of sub-Saharan African countries and provides evidence that highly protective vaccines against trypanosome infections can be achieved.\" Infection The research was in collaboration with Dr. Andrew Jackson at the University of Liverpool. Dr. Jackson said: \"Vaccines against parasites are notoriously difficult to produce. For 40 years, researchers have used a trial-and-error approach to look for vaccine candidates that protect against infection, but there are thousands of possibilities. \"The real strength of this research is its reverse vaccinology method. It considers all the options and hones in on the protective antigens, taking the luck out of the search. Discovery of this vaccine candidate is a fantastic breakthrough, it removes a long-standing obstacle to progress and will fundamentally change our approach to preventing livestock trypanosomiasis.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Trypanosomes are protozoan parasites that cause infectious diseases, including African trypanosomiasis (sleeping sickness) in humans and nagana in economically important livestock 1 , 2 . An effective vaccine against trypanosomes would be an important control tool, but the parasite has evolved sophisticated immunoprotective mechanisms—including antigenic variation 3 —that present an apparently insurmountable barrier to vaccination. Here we show, using a systematic genome-led vaccinology approach and a mouse model of Trypanosoma vivax infection 4 , that protective invariant subunit vaccine antigens can be identified. Vaccination with a single recombinant protein comprising the extracellular region of a conserved cell-surface protein that is localized to the flagellum membrane (which we term ‘invariant flagellum antigen from T. vivax ’) induced long-lasting protection. Immunity was passively transferred with immune serum, and recombinant monoclonal antibodies to this protein could induce sterile protection and revealed several mechanisms of antibody-mediated immunity, including a major role for complement. Our discovery identifies a vaccine candidate for an important parasitic disease that has constrained socioeconomic development in countries in sub-Saharan Africa 5 , and provides evidence that highly protective vaccines against trypanosome infections can be achieved. Main African trypanosomiasis is an infectious disease that is caused by unicellular parasites of the genus Trypanosoma , which are transmitted by the bite of an infected tsetse fly. In humans, trypanosome infections cause sleeping sickness: a deadly disease that threatens the lives of millions of people who live in over 30 countries in sub-Saharan Africa 6 . Some species of trypanosome also infect important livestock animals (including cattle, goats and pigs) and cause the wasting disease nagana (animal African trypanosomiasis), which affects the livelihoods of people who rely on these animals for milk, food and draught power 1 . Approximately three million cattle die from this disease every year, which results in an estimated direct annual economic cost of many hundreds of millions of dollars 7 and represents a major barrier for the socioeconomic advancement of many countries in Africa. Nagana is primarily caused by T. vivax and Trypanosoma congolense and is currently managed with drugs, but resistance is increasing 8 . Previous attempts to develop subunit vaccines against African trypanosome infections have highlighted the difficulties in overcoming the immune evasion strategies that have been evolved by these parasites to enable them to survive in host blood 9 . These strategies include antigenic variation: the serial expression of an abundant allelically excluded variable surface glycoprotein (VSG), and the rapid removal of surface-bound antibodies by hydrodynamic sorting 3 , 10 . It is widely thought that the VSG forms a constantly changing, impenetrable surface coating that sterically shields other surface proteins from host antibodies, which leads to chronic infections characterized by oscillating parasitaemia; however, a careful analysis of recent structural information suggests that this model may not fully explain the protective role of the VSGs 11 . We therefore hypothesized that the VSGs may also subvert natural immunity by preventing the acquisition of high-titre antibody responses to protective antigens, suggesting that eliciting prophylactic unnatural host immunity by vaccination could be achieved. Here we report the identification of a conserved cell-surface protein that—when used as a subunit vaccine in a mouse model of T. vivax infection—is capable of eliciting highly protective immunity. A subunit vaccine induces immunity to T. vivax To identify subunit vaccine candidates for T. vivax , we established a genome-led vaccinology approach using a bioluminescent mouse model of infection 4 (Fig. 1a ). We determined that adoptive transfer of about 100 parasites intravenously into BALB/c mouse hosts resulted in an acute, reproducible infection that permitted sensitive and accurate quantification of parasitaemia using light-based imaging 12 . We selected subunit vaccine candidates by searching the T. vivax genome 13 for genes that encode predicted cell-surface and secreted proteins that are likely to be accessible to vaccine-elicited antibodies. We selected 60 candidates using the following criteria: (1) they did not belong to paralogous gene families (to minimize the risk of functional redundancy in different mammalian hosts) 14 ; (2) contained more than 300 amino acids in their predicted extracellular region (and so are likely to be accessible at the cell surface); and (3) had evidence of expression in the blood stages 15 (Supplementary Table 1 ). We synthesized gene sequences encoding the entire predicted extracellular region, and cloned them into a mammalian protein expression plasmid that contained an exogenous secretion peptide and purification tags. We expressed the candidates as soluble recombinant proteins in HEK293 cells to increase the chance that structurally critical posttranslational modifications were appropriately added. Of the 60 expression plasmids we tested, 39 yielded sufficient protein after purification for vaccination trials (Extended Data Fig. 1a ). For vaccination, we used a prime and two-boost regime that used alum as an adjuvant to bias host responses towards humoral immunity. To reduce any systemic adjuvant-elicited effects on disease progression, we rested the vaccinated mice for a minimum of four weeks following the final boost before parasite challenge (Extended Data Fig. 1b, c ). Trypanosoma vivax loses virulence once removed from donor mice, and so, to avoid confounding effects due to the loss of parasite viability during the infection procedure, we ensured that infections were comparable in control mice challenged before and after the vaccinated mice (Extended Data Fig. 1b ). Fig. 1: Candidate V23 (IFX) induces protective immunity in a mouse model of T. vivax infection. a , Schematic of the genome-led vaccinology approach. b , Summary of mean parasitaemia ( n ≥ 3 mice) quantified by bioluminescence in cohorts of vaccinated mice challenged with T. vivax . Although the V58 candidate had lower mean parasitaemia relative to controls on day 8, it rebounded on day 9 and so was not considered further. c , d , Bioluminescent images of adjuvant-only control (left panels) and mice vaccinated with V31 ( c right) and V23 ( d right); images were taken five (top panels) and eight (bottom panels) days after infection. Source data Full size image We determined the elicited antibody titres to each antigen,<|im_end|> <|im_start|>assistant Scientists have identified a promising vaccine candidate for a parasitic disease that causes a chronic wasting disease in livestock animals across sub Saharan Africa. The disease, called Nagana, threatens the livelihoods of millions of people who depend on animals for milk, food and draft power. It's hoped the research—from the University of York and the Wellcome Sanger Institute—will help alleviate the socioeconomic hardship of people living in some of the most deprived regions in the world. Deadly The disease is caused by trypanosomes: insect-borne parasites that live in the blood which—in humans—are responsible for a deadly disease called African sleeping sickness. Millions of people living in sub-Saharan countries are at risk of trypanosome infections and the economic impact of the livestock disease is vast, with around three million cattle dying every year costing billions of dollars in lost productivity. Trypanosomes have evolved sophisticated protective mechanisms that allow them to thrive in blood and have so far presented a barrier to develop vaccines—which would be an important tool to control these diseases. The researchers identified a vaccine candidate that can elicit sterile immunity to T. vivax—one of the trypanosome parasites responsible for nagana. Parasites Researchers used an approach called "reverse vaccinology" to find new potential vaccines. Professor Gavin Wright from the Department of Biology and the York Biomedical Research Institute said: "Vaccinating against trypanosomes has long been considered a low value option to tackle this awful disease which affects the lives and livelihoods of people living in some of the most deprived regions on the planet. Because of their protective molecular armory, developing a vaccine against these parasites seemed like trying to stop a tank with a peashooter. "Our discovery identifies a vaccine candidate for an important parasitic disease that has constrained the socioeconomic development of sub-Saharan African countries and provides evidence that highly protective vaccines against trypanosome infections can be achieved." Infection The research was in collaboration with Dr. Andrew Jackson at the University of Liverpool. Dr. Jackson said: "Vaccines against parasites are notoriously difficult to produce. For 40 years, researchers have used a trial-and-error approach to look for vaccine candidates that protect against infection, but there are thousands of possibilities. "The real strength of this research is its reverse vaccinology method. It considers all the options and hones in on the protective antigens, taking the luck out of the search. Discovery of this vaccine candidate is a fantastic breakthrough, it removes a long-standing obstacle to progress and will fundamentally change our approach to preventing livestock trypanosomiasis." <|im_end|>

[ 128256, 9125, 198, 2675, 527, 264, 2294, 23672, 13, 14969, 690, 3041, 499, 264, 12624, 5684, 5684, 323, 2610, 499, 311, 3350, 1523, 264, 94800, 1934, 315, 433, 128257, 198, 128256, 882, 198, 16328, 9934, 857, 58375, 527, 18940, 13028, 276, 79383, 430, 5353, 50600, 19338, 11, 2737, 11904, 1456, 857, 437, 316, 3557, 285, 320, 26894, 287, 54950, 8, 304, 12966, 323, 37628, 3444, 304, 47379, 3062, 51876, 220, 16, 1174, 220, 17, 662, 1556, 7524, 25474, 2403, 1456, 857, 58375, 1053, 387, 459, 3062, 2585, 5507, 11, 719, 279, 85573, 706, 28995, 27877, 33119, 454, 4744, 96978, 24717, 76070, 83089, 292, 23851, 220, 18, 2001, 9210, 3118, 459, 14132, 1672, 324, 16966, 481, 22881, 311, 47165, 13, 5810, 584, 1501, 11, 1701, 264, 37538, 33869, 35054, 14027, 258, 2508, 5603, 323, 264, 8814, 1646, 315, 9934, 857, 437, 7942, 18434, 710, 19405, 220, 19, 1174, 430, 29219, 58720, 1207, 3928, 25474, 68937, 729, 649, 387, 11054, 13, 59788, 2617, 449, 264, 3254, 38301, 7006, 519, 13128, 46338, 279, 11741, 65441, 5654, 315, 264, 1615, 2841, 2849, 1355, 10730, 13128, 430, 374, 44589, 311, 279, 5292, 616, 372, 39654, 320, 8370, 584, 4751, 3451, 258, 16349, 5292, 616, 372, 83089, 505, 350, 13, 18434, 710, 18217, 8, 36572, 1317, 65265, 9313, 13, 15695, 2498, 574, 1522, 3210, 23217, 449, 22852, 41529, 11, 323, 38301, 7006, 519, 96157, 12490, 278, 59854, 311, 420, 13128, 1436, 49853, 82743, 9313, 323, 10675, 3892, 24717, 315, 63052, 82076, 40368, 11, 2737, 264, 3682, 3560, 369, 23606, 13, 5751, 18841, 36611, 264, 25474, 9322, 369, 459, 3062, 33403, 49086, 8624, 430, 706, 54852, 80431, 4500, 304, 5961, 304, 1207, 97519, 10384, 220, 20, 1174, 323, 5825, 6029, 430, 7701, 29219, 40300, 2403, 1456, 857, 32554, 30020, 649, 387, 17427, 13, 4802, 11904, 1456, 857, 437, 316, 3557, 285, 374, 459, 50600, 8624, 430, 374, 9057, 555, 88649, 54230, 79383, 315, 279, 64677, 9934, 857, 437, 7942, 1174, 902, 527, 34699, 555, 279, 23556, 315, 459, 29374, 259, 751, 325, 11722, 13, 763, 12966, 11, 1456, 857, 32554, 30020, 5353, 21811, 54950, 25, 264, 25114, 8624, 430, 48926, 279, 6439, 315, 11990, 315, 1274, 889, 3974, 304, 927, 220, 966, 5961, 304, 1207, 97519, 10384, 220, 21, 662, 4427, 9606, 315, 1456, 857, 32554, 1101, 34527, 3062, 51876, 10099, 320, 16564, 36952, 11, 71932, 323, 49910, 8, 323, 5353, 279, 48897, 8624, 37628, 3444, 320, 48999, 11904, 1456, 857, 437, 316, 3557, 285, 705, 902, 22223, 279, 64751, 82, 315, 1274, 889, 17631, 389, 1521, 10099, 369, 14403, 11, 3691, 323, 45196, 3948, 2410, 220, 16, 662, 79904, 2380, 3610, 36952, 2815, 505, 420, 8624, 1475, 1060, 11, 902, 3135, 304, 459, 13240, 2167, 9974, 7100, 2853, 315, 1690, 11758, 315, 11990, 315, 11441, 220, 22, 323, 11105, 264, 3682, 22881, 369, 279, 80431, 50925, 315, 1690, 5961, 304, 10384, 13, 30162, 3444, 374, 15871, 9057, 555, 350, 13, 18434, 710, 323, 9934, 857, 437, 7942, 99898, 337, 1137, 323, 374, 5131, 9152, 449, 11217, 11, 719, 13957, 374, 7859, 220, 23, 662, 30013, 13865, 311, 2274, 1207, 3928, 40300, 2403, 11904, 1456, 857, 32554, 30020, 617, 27463, 279, 27129, 304, 74017, 279, 22852, 77832, 15174, 430, 617, 1027, 28995, 555, 1521, 79383, 311, 7431, 1124, 311, 18167, 304, 3552, 6680, 220, 24, 662, 4314, 15174, 2997, 83089, 292, 23851, 25, 279, 6275, 7645, 315, 459, 44611, 12584, 416, 750, 28544, 3977, 7479, 37807, 38828, 91748, 320, 53, 7939, 705, 323, 279, 11295, 17065, 315, 7479, 50962, 59854, 555, 17055, 22269, 29373, 220, 18, 1174, 220, 605, 662, 1102, 374, 13882, 3463, 430, 279, 650, 7939, 7739, 264, 15320, 10223, 11, 737, 2821, 17820, 481, 7479, 41394, 430, 22562, 2740, 53765, 1023, 7479, 28896, 505, 3552, 59854, 11, 902, 11767, 311, 21249, 30020, 32971, 555, 43524, 1113, 33403, 6388, 22689, 26, 4869, 11, 264, 16994, 6492, 315, 3293, 24693, 2038, 13533, 430, 420, 1646, 1253, 539, 7373, 10552, 279, 29219, 3560, 315, 279, 650, 7939, 82, 220, 806, 662, 1226, 9093, 22601, 83979, 430, 279, 650, 7939, 82, 1253, 1101, 1207, 1653, 5933, 40368, 555, 27252, 279, 24279, 315, 1579, 2442, 49834, 63052, 14847, 311, 29219, 68937, 729, 11, 23377, 430, 95360, 5977, 40334, 4010, 24045, 81846, 3552, 40368, 555, 47165, 1436, 387, 17427, 13, 5810, 584, 1934, 279, 22654, 315, 264, 1615, 2841, 2849, 1355, 10730, 13128, 430, 2345, 9493, 1511, 439, 264, 1207, 3928, 25474, 304, 264, 8814, 1646, 315, 350, 13, 18434, 710, 19405, 55434, 13171, 315, 95360, 5977, 7701, 29219, 40368, 13, 362, 1207, 3928, 25474, 90974, 40368, 311, 350, 13, 18434, 710, 2057, 10765, 1207, 3928, 25474, 11426, 369, 350, 13, 18434, 710, 1174, 584, 9749, 264, 33869, 35054, 14027, 258, 2508, 5603, 1701, 264, 6160, 1152, 1572, 1189, 8814, 1646, 315, 19405, 220, 19, 320, 30035, 13, 220, 16, 64, 7609, 1226, 11075, 430, 11142, 535, 8481, 315, 922, 220, 1041, 79383, 10805, 5389, 7162, 1139, 70245, 33, 2971, 8814, 18939, 19543, 304, 459, 30883, 11, 53823, 79385, 19405, 430, 15480, 16614, 323, 13687, 10484, 2461, 315, 33403, 6388, 22689, 1701, 3177, 6108, 32758, 220, 717, 662, 1226, 4183, 1207, 3928, 25474, 11426, 555, 15389, 279, 350, 13, 18434, 710, 33869, 220, 1032, 369, 21389, 430, 16559, 19698, 2849, 1355, 10730, 323, 6367, 291, 28896, 430, 527, 4461, 311, 387, 15987, 311, 25474, 12, 43723, 1639, 59854, 13, 1226, 4183, 220, 1399, 11426, 1701, 279, 2768, 13186, 25, 320, 16, 8, 814, 1550, 539, 9352, 311, 1370, 32051, 788, 15207, 8689, 320, 998, 30437, 279, 5326, 315, 16003, 90473, 304, 2204, 36041, 10700, 18939, 8, 220, 975, 2652, 320, 17, 8, 13282, 810, 1109, 220, 3101, 42500, 33969, 304, 872, 19698, 11741, 65441, 5654, 320, 438, 779, 527, 4461, 311, 387, 15987, 520, 279, 2849, 7479, 1237, 323, 320, 18, 8, 1047, 6029, 315, 7645, 304, 279, 6680, 18094, 220, 868, 320, 10254, 67082, 6771, 220, 16, 7609, 1226, 92106, 15207, 24630, 11418, 279, 4553, 19698, 11741, 65441, 5654, 11, 323, 55219, 1124, 1139, 264, 36041, 10700, 13128, 7645, 628, 10753, 307, 430, 13282, 459, 506, 53595, 87067, 72249, 323, 94536, 9681, 13, 1226, 13605, 279, 11426, 439, 88045, 38301, 7006, 519, 28896, 304, 11947, 42, 17313, 7917, 311, 5376, 279, 6140, 430, 2080, 43024, 9200, 1772, 1485, 75, 1697, 29882, 1051, 36001, 3779, 13, 5046, 279, 220, 1399, 7645, 628, 10753, 3447, 584, 12793, 11, 220, 2137, 58487, 14343, 13128, 1306, 94536, 369, 47165, 19622, 320, 54290, 2956, 23966, 13, 220, 16, 64, 7609, 1789, 47165, 11, 584, 1511, 264, 10461, 323, 1403, 12, 13297, 17942, 430, 1511, 34060, 439, 459, 1008, 8783, 77282, 311, 15837, 3552, 14847, 7119, 2854, 10020, 40368, 13, 2057, 8108, 904, 46417, 1008, 8783, 77282, 12, 43723, 1639, 6372, 389, 8624, 33824, 11, 584, 66529, 279, 70558, 24548, 369, 264, 8187, 315, 3116, 5672, 2768, 279, 1620, 7916, 1603, 85573, 8815, 320, 54290, 2956, 23966, 13, 220, 16, 65, 11, 272, 7609, 9934, 857, 437, 7942, 18434, 710, 33291, 9043, 59566, 3131, 7108, 505, 35558, 24548, 11, 323, 779, 11, 311, 5766, 2389, 13900, 6372, 4245, 311, 279, 4814, 315, 85573, 68507, 2391, 279, 19405, 10537, 11, 584, 59754, 430, 30020, 1051, 30139, 304, 2585, 24548, 29991, 1603, 323, 1306, 279, 70558, 24548, 320, 54290, 2956, 23966, 13, 220, 16, 65, 7609, 23966, 13, 220, 16, 25, 50683, 650, 1419, 320, 2843, 55, 8, 90974, 29219, 40368, 304, 264, 8814, 1646, 315, 350, 13, 18434, 710, 19405, 13, 264, 1174, 328, 82149, 315, 279, 33869, 35054, 14027, 258, 2508, 5603, 13, 293, 1174, 22241, 315, 3152, 33403, 6388, 22689, 320, 308, 63247, 220, 18, 24548, 8, 10484, 1908, 555, 6160, 1152, 1572, 36634, 304, 90388, 315, 70558, 24548, 29991, 449, 350, 13, 18434, 710, 662, 10541, 279, 650, 2970, 9322, 1047, 4827, 3152, 33403, 6388, 22689, 8844, 311, 11835, 389, 1938, 220, 23, 11, 433, 42632, 291, 389, 1938, 220, 24, 323, 779, 574, 539, 6646, 4726, 13, 272, 1174, 294, 1174, 12371, 1152, 1572, 1189, 5448, 315, 1008, 8783, 77282, 15744, 2585, 320, 2414, 21988, 8, 323, 24548, 70558, 449, 650, 2148, 320, 272, 1314, 8, 323, 650, 1419, 320, 294, 1314, 1237, 5448, 1051, 4529, 4330, 320, 3565, 21988, 8, 323, 8223, 320, 15205, 21988, 8, 2919, 1306, 19405, 13, 8922, 828, 8797, 1404, 2217, 1226, 11075, 279, 95360, 1639, 63052, 8305, 417, 311, 1855, 83089, 11, 128257, 198, 128256, 78191, 198, 72326, 617, 11054, 264, 26455, 25474, 9322, 369, 264, 33403, 49086, 8624, 430, 11384, 264, 21249, 48897, 8624, 304, 51876, 10099, 4028, 1207, 43059, 22026, 10384, 13, 578, 8624, 11, 2663, 30162, 3444, 11, 48926, 279, 64751, 82, 315, 11990, 315, 1274, 889, 6904, 389, 10099, 369, 14403, 11, 3691, 323, 10165, 2410, 13, 1102, 596, 26253, 279, 3495, 88958, 279, 3907, 315, 4356, 323, 279, 8489, 2063, 328, 4091, 10181, 2345, 14724, 1520, 61705, 279, 80431, 67650, 315, 1274, 5496, 304, 1063, 315, 279, 1455, 62683, 13918, 304, 279, 1917, 13, 95937, 578, 8624, 374, 9057, 555, 1456, 857, 58375, 25, 27080, 1481, 17334, 79383, 430, 3974, 304, 279, 6680, 902, 49525, 12966, 83872, 8647, 369, 264, 25114, 8624, 2663, 11904, 21811, 54950, 13, 74418, 315, 1274, 5496, 304, 1207, 97519, 5961, 527, 520, 5326, 315, 1456, 857, 32554, 30020, 323, 279, 7100, 5536, 315, 279, 51876, 8624, 374, 13057, 11, 449, 2212, 2380, 3610, 36952, 23069, 1475, 1060, 54824, 33151, 315, 11441, 304, 5675, 26206, 13, 9934, 857, 58375, 617, 28995, 27877, 29219, 24717, 430, 2187, 1124, 311, 41972, 304, 6680, 323, 617, 779, 3117, 10666, 264, 22881, 311, 2274, 40300, 50004, 1053, 387, 459, 3062, 5507, 311, 2585, 1521, 19338, 13, 578, 12074, 11054, 264, 25474, 9322, 430, 649, 658, 19195, 82743, 40368, 311, 350, 13, 18434, 710, 87671, 315, 279, 1456, 857, 32554, 79383, 8647, 369, 37628, 3444, 13, 94137, 3695, 59250, 1511, 459, 5603, 2663, 330, 26992, 14027, 258, 2508, 1, 311, 1505, 502, 4754, 40300, 13, 17054, 64495, 27839, 505, 279, 6011, 315, 40023, 323, 279, 4356, 12371, 61860, 8483, 10181, 1071, 25, 330, 53, 4575, 16252, 2403, 1456, 857, 58375, 706, 1317, 1027, 6646, 264, 3428, 907, 3072, 311, 22118, 420, 25629, 8624, 902, 22223, 279, 6439, 323, 64751, 82, 315, 1274, 5496, 304, 1063, 315, 279, 1455, 62683, 13918, 389, 279, 11841, 13, 9393, 315, 872, 29219, 31206, 6916, 683, 11, 11469, 264, 25474, 2403, 1521, 79383, 9508, 1093, 4560, 311, 3009, 264, 13192, 449, 264, 1069, 1003, 9945, 13, 330, 8140, 18841, 36611, 264, 25474, 9322, 369, 459, 3062, 33403, 49086, 8624, 430, 706, 54852, 279, 80431, 4500, 315, 1207, 97519, 11904, 5961, 323, 5825, 6029, 430, 7701, 29219, 40300, 2403, 1456, 857, 32554, 30020, 649, 387, 17427, 1210, 763, 13421, 578, 3495, 574, 304, 20632, 449, 2999, 13, 13929, 13972, 520, 279, 3907, 315, 25715, 13, 2999, 13, 13972, 1071, 25, 330, 53, 4575, 1572, 2403, 79383, 527, 73835, 5107, 311, 8356, 13, 1789, 220, 1272, 1667, 11, 12074, 617, 1511, 264, 9269, 9976, 19453, 5603, 311, 1427, 369, 25474, 11426, 430, 6144, 2403, 19405, 11, 719, 1070, 527, 9214, 315, 24525, 13, 330, 791, 1972, 8333, 315, 420, 3495, 374, 1202, 10134, 14027, 258, 2508, 1749, 13, 1102, 32238, 682, 279, 2671, 323, 305, 3233, 304, 389, 279, 29219, 68937, 729, 11, 4737, 279, 15369, 704, 315, 279, 2778, 13, 39193, 315, 420, 25474, 9322, 374, 264, 14964, 42445, 11, 433, 29260, 264, 1317, 56703, 33287, 311, 5208, 323, 690, 43593, 2349, 1057, 5603, 311, 27252, 51876, 1456, 857, 437, 316, 3557, 285, 1210, 220, 128257, 198 ]

1,909