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More recently, it has been proposed as a near-carbon-neutral construction material. Its waterless and less energy-intensive production (in comparison with ordinary cement and regular concrete) makes it a potential alternative for high--emission portland-cement-based materials. Due to improvements in fabrication techniques, it can be produced in high quality and large quantities. Recyclable sulfur concrete sleepers are used in Belgium for the railways infrastructure, and are mass-produced locally. THIOTUBE is the brand name for certified acid-resistant DWF (dry weather flow) discharge pipes used in Belgium.

Metallurgy

Peak copper is the point in time at which the maximum global copper production rate is reached. Since copper is a finite resource, at some point in the future new production from mining will diminish, and at some earlier time production will reach a maximum. When this will occur is a matter of dispute. Unlike fossil fuels, copper is scrapped and reused, and it has been estimated that at least 80% of all copper ever mined is still available (having been repeatedly recycled). Copper is among the most important industrial metals, ranking third after iron and aluminium in terms of quantity used. It is valued for its heat and electrical conductivities, ductility, malleability and resistance to corrosion. Electrical uses account for about three quarters of total copper consumption, including power cables, data cables and electrical equipment. It is also used in cooling and refrigeration tubing, heat exchangers, water pipes and consumer products. Copper has been used by humans for at least 10,000 years. More than 97% of all copper ever mined and smelted has been extracted since 1900. The increased demand for copper due to the growing Indian and Chinese economies since 2006 has led to increased prices and an increase in copper theft.

Metallurgy

Work is progressing on bypassing the conventional route of atomising wrought feedstock or sponge and the inherent cost associated with the traditional Kroll process. Several of these processes, such as the FFC, MER Corporation, OS, Ginatta and BHP Billiton processes rely on the electrolytic reduction of TiO (a cheap and abundant material) to form Ti metal. So far, no material from these processes has been sold commercially on the open market, and cost models have yet to be published, but they offer the possibility of inexpensive titanium powder in the near future. The countries that have such facilities to generate Titanium Sponge are Saudi Arabia, China, Japan, Russia, Kazakhstan, the USA, Ukraine and India. The Titanium Sponge Plant in India is the only one in the world that can undertake all the different activities of manufacturing aerospace grade titanium sponge under one roof.

Metallurgy

This gene encodes an E26 transformation-specific related transcription factor. The encoded protein is primarily expressed in lymphoid cells and can act as both an enhancer and a repressor to regulate transcription of various genes. Alternative splicing results in multiple transcript variants.

Gene expression + Signal Transduction

The mTORC2 signaling pathway is less defined than the mTORC1 signaling pathway. The functions of the components of the mTORC complexes have been studied using knockdowns and knockouts and were found to produce the following phenotypes: * NIP7: Knockdown reduced mTORC2 activity that is indicated by decreased phosphorylation of mTORC2 substrates. * RICTOR: Overexpression leads to metastasis and knockdown inhibits growth factor-induced PKC-phosphorylation. Constitutive deletion of Rictor in mice leads to embryonic lethality, while tissue specific deletion leads to a variety of phenotypes; a common phenotype of Rictor deletion in liver, white adipose tissue, and pancreatic beta cells is systemic glucose intolerance and insulin resistance in one or more tissues. Decreased Rictor expression in mice decreases male, but not female, lifespan. * mTOR: Inhibition of mTORC1 and mTORC2 by PP242 [2-(4-Amino-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol] leads to autophagy or apoptosis; inhibition of mTORC2 alone by PP242 prevents phosphorylation of Ser-473 site on AKT and arrests the cells in G1 phase of the cell cycle. Genetic reduction of mTOR expression in mice significantly increases lifespan. * PDK1: Knockout is lethal; hypomorphic allele results in smaller organ volume and organism size but normal AKT activation. * AKT: Knockout mice experience spontaneous apoptosis (AKT1), severe diabetes (AKT2), small brains (AKT3), and growth deficiency (AKT1/AKT2). Mice heterozygous for AKT1 have increased lifespan. * TOR1, the S. cerevisiae orthologue of mTORC1, is a regulator of both carbon and nitrogen metabolism; TOR1 KO strains regulate response to nitrogen as well as carbon availability, indicating that it is a key nutritional transducer in yeast.

Gene expression + Signal Transduction

Chemokinesis is chemically prompted kinesis, a motile response of unicellular prokaryotic or eukaryotic organisms to chemicals that cause the cell to make some kind of change in their migratory/swimming behaviour. Changes involve an increase or decrease of speed, alterations of amplitude or frequency of motile character, or direction of migration. However, in contrast to chemotaxis, chemokinesis has a random, non-vectorial moiety, in general. <br /> Due to the random character, techniques dedicated to evaluate chemokinesis are partly different from methods used in chemotaxis research. One of the most valuable ways to measure chemokinesis is computer-assisted (see, e.g., Image J) checker-board analysis, which provides data about migration of identical cells, whereas, in Protozoa (e.g., Tetrahymena), techniques based on measurement of opalescence were also developed.

Gene expression + Signal Transduction

The Falcon Continuous (C) centrifugal concentrator is primarily used for the separation of heavy minerals which occur in ore concentrations above 0.1% by weight, such as cassiterite, tantalum and scheelite. It is also used for coal cleaning and pre-concentration of gold bearing ores. The machine generates forces up to 300 times the force of gravity (300 G's) and operates by using a smooth-walled, rotating bowl to stratify the material into heavier and lighter fractions then uses pneumatic valves to control the amount of heavy material that reports to the concentrate collection stream. It does not use any fluidization water and relies entirely on centrifugal force for separation. The Falcon C concentrator is used in various process plants around the world, such as the Tanco mine in Canada, the Sekisovskoye mine in Kazakhstan and the Renison tin mine in Tasmania.

Metallurgy

Structural considerations play an important role in the proper design of copper applications. The primary concern is about thermal effects: movement and stresses related to temperature variations. Thermal effects can be accommodated by preventing movement and resisting cumulative stresses or by allowing movement at predetermined locations, thereby relieving anticipated thermal stresses. Wind resistance is an important structural consideration. Underwriters Laboratories (UL) conducted a series of tests on copper roof systems. A copper standing-seam roof with test panels was subjected to the UL 580, Uplift Resistance Test Protocol. The copper system did not exhibit unusual deformation, the cleats did not loosen from the structural deck, and the system passed UL 580 requirements. UL-90 designation was granted.

Metallurgy

Aluminium smelting is highly energy intensive, and in some countries is economical only if there are inexpensive sources of electricity. In some countries, smelters are given exemptions to energy policy like renewable energy targets. To reduce the energy cost of the smelting process, alternative electrolytes such as Na3AlF6 are being investigated that can operate at a lower temperature. However, changing the electrolyte changes the kinetics of the liberated oxygen from the AlO ore. This change in bubble formation can alter the rate the anode reacts with Oxygen or the electrolyte and effectively change the efficiency of the reduction process. Inert anodes, used in tandem with vertical electrode cells, can also reduce the energy cost of aluminum reduction up to 30% by lowering the voltage needed for reduction to occur. Applying these two technologies at the same times allows the anode-cathode distance to be minimized which decreases restive losses.

Metallurgy

Mars Guy Fontana was a corrosion engineer, professor of Metallurgical Engineering at Ohio State University. He was born April 6, 1910, in Iron Mountain, Michigan, and died February 29, 1988.

Metallurgy

To date there are more than 300 known coregulators. Some examples of these coactivators include: * ARA54 targets androgen receptors * ATXN7L3 targets several members of the nuclear receptor superfamily * BCL3 targets 9-cis retinoic acid receptor (RXR) * CBP targets many transcription factors * CDC25B targets steroid receptors * COPS5 targets several nuclear receptors * DDC targets androgen receptors * EP300 targets many transcription factors * KAT5 targets many nuclear receptors * KDM1A targets androgen receptors * Steroid receptor coactivator (SRC) family ** NCOA1 targets several members of the nuclear receptor superfamily ** NCOA2 targets several members of the nuclear receptor superfamily ** NCOA3 targets several nuclear receptors and transcription factors * YAP targets transcription factors * WWTR1 targets transcription factors

Gene expression + Signal Transduction

Type P (55%Pd/31%Pt/14%Au–65%Au/35%Pd, by weight) thermocouples give a thermoelectric voltage that mimics the type K over the range 500 °C to 1400 °C, however they are constructed purely of noble metals and so shows enhanced corrosion resistance. This combination is also known as Platinel II.

Metallurgy

Tailings deposits tend to be located in rural areas or near marginalized communities, such as indigenous communities. The Global Industry Standard on Tailings Management recommends that "a human rights due diligence process is required to identify and address those that are most at risk from a tailings facility or its potential failure."

Metallurgy

The several RNA polymerases in eukaryotes each have their own means of termination. Pol I is stopped by TTF1 (yeast Nsi1), which recognizes a downstream DNA sequence; the endonuclease is XRN2 (yeast Rat1). Pol III is able to terminate on its on on a stretch of As on the template strand. Finally, Pol II also have poly(A)-independent modes of termination, which is required when it transcribes snRNA and snoRNA genes in yeast. The yeast protein Nrd1 is responsible. Some human mechanism, possibly PCF11, seems to cause premature termination when pol II transcribes HIV genes.

Gene expression + Signal Transduction

The formulation of a coating depends primarily on the function required of the coating and also on aesthetics required such as color and gloss. The four primary ingredients are the resin (or binder), solvent which maybe water (or solventless), pigment(s) and additives. Research is ongoing to remove heavy metals from coating formulations completely. For example on the basis of experimental and epidemiological evidence, it has been classified by the IARC (International Agency for Research on Cancer) as a human carcinogen by inhalation (class I) ([https://www.sicurezza.com/ispesl ISPESL], 2008).

Metallurgy

Signaling pathways are often inactivated by enzymes that reverse the activation state and/or induce the degradation of signaling components. Scaffolds have been proposed to protect activated signaling molecules from inactivation and/or degradation. Mathematical modeling has shown that kinases in a cascade without scaffolds have a higher probability of being dephosphorylated by phosphatases before they are even able to phosphorylate downstream targets. Furthermore, scaffolds have been shown to insulate kinases from substrate- and ATP-competitive inhibitors.

Gene expression + Signal Transduction

Serine/arginine-rich splicing factor 1 (SRSF1) also known as alternative splicing factor 1 (ASF1), pre-mRNA-splicing factor SF2 (SF2) or ASF1/SF2 is a protein that in humans is encoded by the SRSF1 gene. ASF/SF2 is an essential sequence specific splicing factor involved in pre-mRNA splicing. SRSF1 is the gene that codes for ASF/SF2 and is found on chromosome 17. The resulting splicing factor is a protein of approximately 33 kDa. ASF/SF2 is necessary for all splicing reactions to occur, and influences splice site selection in a concentration-dependent manner, resulting in alternative splicing. In addition to being involved in the splicing process, ASF/SF2 also mediates post-splicing activities, such as mRNA nuclear export and translation.

Gene expression + Signal Transduction

Combustion spraying equipment produces an intense flame, which may have a peak temperature more than 3,100 °C and is very bright. Electric arc spraying produces ultra-violet light which may damage delicate body tissues. Plasma also generates quite a lot of UV radiation, easily burning exposed skin and can also cause "flash burn" to the eyes. Spray booths and enclosures should be fitted with ultra-violet absorbent dark glass. Where this is not possible, operators, and others in the vicinity should wear protective goggles containing BS grade 6 green glass. Opaque screens should be placed around spraying areas. The nozzle of an arc pistol should never be viewed directly unless it is certain that no power is available to the equipment.

Metallurgy

In materials science the flow stress, typically denoted as Y (or ), is defined as the instantaneous value of stress required to continue plastically deforming a material - to keep it flowing. It is most commonly, though not exclusively, used in reference to metals. On a stress-strain curve, the flow stress can be found anywhere within the plastic regime; more explicitly, a flow stress can be found for any value of strain between and including yield point () and excluding fracture (): . The flow stress changes as deformation proceeds and usually increases as strain accumulates due to work hardening, although the flow stress could decrease due to any recovery process. In continuum mechanics, the flow stress for a given material will vary with changes in temperature, , strain, , and strain-rate, ; therefore it can be written as some function of those properties: The exact equation to represent flow stress depends on the particular material and plasticity model being used. Hollomon's equation is commonly used to represent the behavior seen in a stress-strain plot during work hardening: Where is flow stress, is a strength coefficient, is the plastic strain, and is the strain hardening exponent. Note that this is an empirical relation and does not model the relation at other temperatures or strain-rates (though the behavior may be similar). Generally, raising the temperature of an alloy above 0.5 T results in the plastic deformation mechanisms being controlled by strain-rate sensitivity, whereas at room temperature metals are generally strain-dependent. Other models may also include the effects of strain gradients. Independent of test conditions, the flow stress is also affected by: chemical composition, purity, crystal structure, phase constitution, microstructure, grain size, and prior strain. The flow stress is an important parameter in the fatigue failure of ductile materials. Fatigue failure is caused by crack propagation in materials under a varying load, typically a cyclically varying load. The rate of crack propagation is inversely proportional to the flow stress of the material.

Metallurgy

Detonation spray coatings are applied using a detonation gun (D-gun) which is composed of a long-water-cooled metal barrel containing inlet valves for introducing gases and powders into the chamber. A preselected amount of the desired protective coating material known as feedstock (in powder form of particle size 5–60μm) is introduced into the chamber (at common powder flow rates of 16–40 g/min). Here oxygen and fuel (generally acetylene) are ignited by a spark plug to create a supersonic shock wave that propels the mixture of melted and/or partially-melted and/or solid feedstock (depending on the type of material used) out of the barrel and onto the subject being sprayed. The barrel is then cleared using a short burst of nitrogen before the D-gun is ready to be fired again. This is an important step because the heat from the residual gases can cause the new fuel mixture to combust which would in turn cause an uncontrollable reaction. Also a small amount of inert nitrogen gas inserted between the two mixtures of fuel and feedstock prior to firing, helps to prevent backfiring. D-guns typically operate at firing rates of between 1–10 Hz. Many different mixtures of coating powders and D-gun settings can be used during detonation gun spraying of a material, all of which influence the final surface characteristics of the sprayed coating. Common powder materials used include but are not limited to: alumina-titania, alumina, tungsten carbide-tungsten-chromium carbide mixture with nickel-chromium alloy binder, chromium carbide, tungsten carbide with cobalt binder. Metallurgists consider the measurements of surface oxygen content, macro and micro-hardness, porosity, bond strength and surface roughness when determining the quality of a thermally sprayed coating.

Metallurgy

Heterotrimeric G protein complexes are composed of three distinct protein subunits named alpha (α), beta (β) and gamma (γ) subunits. The alpha subunits contain the GTP binding/GTPase domain flanked by long regulatory regions, while the beta and gamma subunits form a stable dimeric complex referred to as the beta-gamma complex. When activated, a heterotrimeric G protein dissociates into activated, GTP-bound alpha subunit and separate beta-gamma subunit, each of which can perform distinct signaling roles. The α and γ subunit are modified by lipid anchors to increase their association with the inner leaflet of the plasma membrane. Heterotrimeric G proteins act as the transducers of G protein-coupled receptors, coupling receptor activation to downstream signaling effectors and second messengers. In unstimulated cells, heterotrimeric G proteins are assembled as the GDP bound, inactive trimer (G-GDP-G complex). Upon receptor activation, the activated receptor intracellular domain acts as GEF to release GDP from the G protein complex and to promote binding of GTP in its place. The GTP-bound complex undergoes an activating conformation shift that dissociates it from the receptor and also breaks the complex into its component G protein alpha and beta-gamma subunit components. While these activated G protein subunits are now free to activate their effectors, the active receptor is likewise free to activate additional G proteins – this allows catalytic activation and amplification where one receptor may activate many G proteins. G protein signaling is terminated by hydrolysis of bound GTP to bound GDP. This can occur through the intrinsic GTPase activity of the α subunit, or be accelerated by separate regulatory proteins that act as GTPase-activating proteins (GAPs), such as members of the Regulator of G protein signaling (RGS) family). The speed of the hydrolysis reaction works as an internal clock limiting the length of the signal. Once G is returned to being GDP bound, the two parts of the heterotrimer re-associate to the original, inactive state. The heterotrimeric G proteins can be classified by sequence homology of the α unit and by their functional targets into four families: G family, G family, G family and G family. Each of these G protein families contains multiple members, such that the mammals have 16 distinct -subunit genes. The G and G are likewise composed of many members, increasing heterotrimer structural and functional diversity. Among the target molecules of the specific G proteins are the second messenger-generating enzymes adenylyl cyclase and phospholipase C, as well as various ion channels.

Gene expression + Signal Transduction

The electrolyte for this process is a mixture of lead fluorosilicate ("PbSiF") and hexafluorosilicic acid (HSiF) operating at 45 °C (113 °F). Cathodes are thin sheets of pure lead and anodes are cast from the impure lead to be purified. A potential of 0.5 volts is applied. At the anode, lead dissolves, as do metal impurities that are less noble than lead. Impurities that are more noble than lead, such as silver, gold, and bismuth, flake from the anode as it dissolves and settle to the bottom of the vessel as "anode mud." Pure metallic lead plates onto the cathode, with the less noble metals remaining in solution. Because of its high cost, electrolysis is used only when very pure lead is needed. Otherwise pyrometallurgical methods are preferred, such as the Parkes process followed by the Betterton-Kroll process.

Metallurgy

A reverberatory furnace is a metallurgical or process furnace that isolates the material being processed from contact with the fuel, but not from contact with combustion gases. The term reverberation is used here in a generic sense of rebounding or reflecting, not in the acoustic sense of echoing.

Metallurgy

In these processes, the ore is fed into a tank, where it remains until it is completely reduced. The vessel is then emptied of its pre-reduced ore, and filled with another charge of untreated ore. These processes can therefore be easily extrapolated from laboratory experiments. What's more, their principle, based on batch production, facilitates process control.

Metallurgy

RNA silencing is the mechanism that our cells (and cells from all kingdoms) use to fight RNA viruses and transposons (which originate from our own cells as well as from other vehicles). In the case of RNA viruses, these get destroyed immediately by the mechanism cited above. In the case of transposons, it's a little more indirect. Since transposons are located in different parts of the genome, the different transcriptions from the different promoters produce complementary mRNAs that can hybridize with each other. When this happens, the RNAi machinery goes into action, debilitating the mRNAs of the proteins that would be required to move the transposons themselves.

Gene expression + Signal Transduction

The CKLF-like MARVEL transmembrane domain-containing family (CMTM), previously termed the chemokine-like factor superfamily (CKLFSF), consists of 9 proteins, some of which have various isoforms due to alternative splicing of their respective genes. These proteins along with their isoforms are: *Chemokine-like factor (CKLF), the founding member of this family, has 4 known isoforms, CKLF1 to CKLF4. *CKLF like MARVEL transmembrane domain-containing 1 (CMTM1) has 23 known isoforms, CMTM1-v1 to CMTM1-v23. *CKLF like MARVEL transmembrane domain-containing 2 (CMTM2) has no known isoforms. *CKLF like MARVEL transmembrane domain-containing 3 (CMTM3) has no known isoforms. *CKLF like MARVEL transmembrane domain-containing 4 (CMTM4) has 3 known isoforms, CMTM4-v1 to CMTM4-v3. * CKLF-like MARVEL transmembrane domain-containing 5 (CMTM5) has 6 known isoforms, CMTM5-v1 to CMTM5-v6. * CKLF like MARVEL transmembrane domain containing 6 (CMTM6) has no known isoforms. * CKLF like MARVEL transmembrane domain containing 7 (CMTM7) has 2 isoforms, CMTM7-v1 and CMTM7-v2. * CKLF like MARVEL transmembrane domain-containing 8 (CMTM8) has two isoforms, CMTM8 and CMTM8-v2 (Little is known about the CMTM8-v2 isoform and the CMTM8 isoform is referred to as CMTM8 rather than CMTM8-v1.). All of these proteins have domains (i.e. regions) similar to analogous domains in the chemokine proteins; tetraspanin proteins (also termed transmembrane-4 superfamily proteins); myelin and lymphocyte protein (also termed MAR protein); proteins that direct membrane vesicle trafficking; and other proteins that are embedded in cell membranes. The genes encoding (i.e. directing the production of) these proteins, CKLF, CMTM1, CMTM2, CMTM3, CMTM4, CMTM5, CMTM6, CMTM7, and CMTM8, respectively, also share similar regions that encode the domains just cited for their proteins. (The 8 CMTM genes were formerly termed CKLFSF1, CKLFSF2, CKLFSF3, CKLFSF4, CKLFSF5, CKLFSF6, CKLFSF7, and CKLFSF8.) The CKLF, CMTM1, CMTM2, CTMT3, and CMTM4 genes cluster together in band 22 on the long (i.e. "q") arm of chromosome 16; the CMTM6, CMTM7, and CMTM8 genes form a second cluster in band 22 on the short (i.e. "p") of chromosome 3; and the CMTM5 gene, located in band 11.2 on the q arm of chromosome 14, is not clustered with the other CMTM genes. These structural similarities and clusterings reflect the close relationships of these proteins and genes. Studies suggest that the members of this family may be involved in the development of various cancers autoimmune diseases, cardiovascular diseases, the male reproductive system, and angiogenesis (i.e. development of new blood vessels from pre-existing blood vessels). In most of these cases, however, further studies are needed to determine if these CMTM proteins and/or their corresponding genes and mRNAs will be promising targets to help in the diagnosis, prognosis, and/or treatment of these disorders.

Gene expression + Signal Transduction

Recrystallization kinetics are commonly observed to follow the profile shown. There is an initial nucleation period t where the nuclei form, and then begin to grow at a constant rate consuming the deformed matrix. Although the process does not strictly follow classical nucleation theory it is often found that such mathematical descriptions provide at least a close approximation. For an array of spherical grains the mean radius R at a time t is (Humphreys and Hatherly 2004): where t is the nucleation time and G is the growth rate dR/dt. If N nuclei form in the time increment dt and the grains are assumed to be spherical then the volume fraction will be: This equation is valid in the early stages of recrystallization when f<<1 and the growing grains are not impinging on each other. Once the grains come into contact the rate of growth slows and is related to the fraction of untransformed material (1-f) by the Johnson-Mehl equation: While this equation provides a better description of the process it still assumes that the grains are spherical, the nucleation and growth rates are constant, the nuclei are randomly distributed and the nucleation time t is small. In practice few of these are actually valid and alternate models need to be used. It is generally acknowledged that any useful model must not only account for the initial condition of the material but also the constantly changing relationship between the growing grains, the deformed matrix and any second phases or other microstructural factors. The situation is further complicated in dynamic systems where deformation and recrystallization occur simultaneously. As a result, it has generally proven impossible to produce an accurate predictive model for industrial processes without resorting to extensive empirical testing. Since this may require the use of industrial equipment that has not actually been built there are clear difficulties with this approach.

Metallurgy

According to one vendor, depressants "increase the efficiency of the flotation process by selectively inhibiting the interaction of one mineral with the collector." Thus a typical pulverized ore sample consists of many components, of which only one or a few are targets for the collector. Depressants bind to these other components, lest the collector be wasted by doing so. Depressants are selected for particular ores. Typical depressants are starch, polyphenols, lye, and lime. They are cheap, and oxygen-rich typically.

Metallurgy

Common inspection methods for steel castings are magnetic particle testing and liquid penetrant testing. Common inspection methods for aluminum castings are radiography, ultrasonic testing, and liquid penetrant testing.

Metallurgy

Apoptosis, the process of programmed cell death, involves complex signaling pathways and cascades of molecular events. This process is needed for proper development during embryonic and fetal growth where there is destruction and reconstruction of cellular structures. In adult organisms, apoptosis is needed to maintain differentiated tissue by striking the balance between proliferation and cell death. It is known that intracellular proteases called caspases degrade the cellular contents of the cell by proteolysis upon activation of the death pathway. Mammalian cells have two main pathways that lead to apoptosis. 1. Extrinsic pathway: Initiated by extrinsic ligands binding to death receptors on the surface of the cell. An example of this is the binding of tumour necrosis factor-alpha (TNF-alpha) to TNF-alpha receptor. An example of a TNF receptor is Fas (CD95), which recruits activator caspases like caspase-8 upon binding TNF at the cell surface. The activation of the initiator caspases then initiates a downstream cascade of events that results in the induction of effector caspases that function in apoptosis. 2. Intrinsic pathway: This pathway is initiated by intracellular or environmental stimuli. It is focused on detecting the improper functioning of the mitochondria in the cell and, as a result, activates signaling pathways to commit suicide. The membrane permeability of the mitochondria increases and particular proteins are released into the cytoplasm that facilitates the activation of initiator caspases. The particular protein released from the mitochondria is cytochrome c. Cytochrome c then binds to Apaf-1 in the cytosol and results in the activation of initiator caspase-9. The activation of the initiator caspases then initiates a downstream cascade of events that results in the induction of effector caspases that function in apoptosis. One family of proteins called IAPs plays a role in regulating cell death by inhibiting the process. IAPs like survivin, inhibit apoptosis by physically binding to and inhibiting proper caspase function. The function of IAPs is evolutionarily conserved as Drosophila homologues of IAPs have been shown to be essential for cell survival. IAPs have been implicated in studies to have a regulatory effect on cell division. Yeast cells with knock-outs of certain IAP genes did not show problems associated with cell death, but showed defects in mitosis characterized by improper chromosome segregation or failed cytokinesis. Deletion of particular IAPs does not seem to have a profound effect on the cell-death pathway as there is a redundancy of function by the many IAPs that exist in a cell. They have been implicated, however, to play a role in maintaining an anti-apoptotic environment intracellularly. Changing the expression of particular IAPs has shown an increase in spontaneous cell death induction or increased sensitivity to death stimuli.

Gene expression + Signal Transduction

MVR is thought to affect signal strength in postsynaptic neurons that typically have low receptor occupancy; this number can vary widely throughout the nervous system. This means that for however many receptors are found on a postsynaptic cell in the area of presynaptic cell vesicle release, only a small number of them would typically be occupied by neurotransmitter released from one vesicle (each vesicle can contain up to approximately 10,000 molecules of neurotransmitter). MVR increases the likelihood that an action potential in a presynaptic cell will result in a postsynaptic cell chance in action potential likelihood. This could be either more or fewer action potentials, depending upon if the neurotransmitter / receptor combo is excitatory or inhibitory.

Gene expression + Signal Transduction

Naturally occurring moissanite is found in only minute quantities in certain types of meteorite, corundum deposits, and kimberlite. Virtually all the silicon carbide sold in the world, including moissanite jewels, is synthetic. Natural moissanite was first found in 1893 as a small component of the Canyon Diablo meteorite in Arizona by Ferdinand Henri Moissan, after whom the material was named in 1905. Moissan's discovery of naturally occurring SiC was initially disputed because his sample may have been contaminated by silicon carbide saw blades that were already on the market at that time. While rare on Earth, silicon carbide is remarkably common in space. It is a common form of stardust found around carbon-rich stars, and examples of this stardust have been found in pristine condition in primitive (unaltered) meteorites. The silicon carbide found in space and in meteorites is almost exclusively the beta-polymorph. Analysis of SiC grains found in the Murchison meteorite, a carbonaceous chondrite meteorite, has revealed anomalous isotopic ratios of carbon and silicon, indicating that these grains originated outside the solar system.

Metallurgy

The protein CTCF plays a heavy role in repressing the insulin-like growth factor 2 gene, by binding to the H-19 imprinting control region (ICR) along with differentially-methylated region-1 (DMR1) and MAR3.

Gene expression + Signal Transduction

ASF/SF2 is involved in genomic stability; it is thought that RNA Polymerase recruits ASF/SF2 to nascent RNA transcripts to impede formation of mutagenic DNA:RNA hybrid R-loop structures between the transcript and the template DNA. In this way, ASF/SF2 is protecting cells from the potential deleterious effects of transcription itself. ASF/SF2 is also implicated in cellular mechanisms to hinder exon skipping and to ensure splicing is occurring accurately and correctly.

Gene expression + Signal Transduction

The social, political, and economic stagnation that followed the Roman Empire affected Europe throughout the early medieval period and had a critical impact on technological progress, trade, and social organization. Technological developments that affected the course of metal production were only feasible within a stable political environment, and this was not the case until the 9th century (Martinon-Torres & Rehren in press, a). During the first medieval centuries, the output of metal was in a steady decline with constraints in small-scale activities. Miners adopted methods much less efficient than those of Roman times. Ores were extracted only from shallow depths or from remnants of formerly abandoned mines. The vicinity of the mine to villages or towns was also a determining factor when due to the high cost of material transportation (Martinon-Torres & Rehren in press, b). Only the output of iron diminished less in relation to the other base and precious metals until the 8th century. This fact, correlated with the dramatic decrease in copper production, may indicate a possible displacement of copper and bronze artifacts by iron ones (Forbes 1957, 64; Bayley et al. 2008, 50). By the end of the 9th century, economic, and social conditions dictated a greater need for metal for agriculture, arms, stirrups, and decoration. Consequently, conditions began to favor metallurgy and a slow but steady general progress developed. Starting from the reign of the emperor Otto I in the 960s, smelting sites were multiplied. New mines were discovered and exploited, like the well-known Mines of Rammelsberg, close to the town of Goslar in the Harz Mountains. Open-cast mining and metallurgical activities were mostly concentrated in the Eastern Alps, Saxony, Bohemia, Tuscany, Rhineland, Gaul, and Spain (Nef 1987). It was mainly German miners and metallurgists who were the generators of metal production, but the French and Flemish made contributions to the developments.

Metallurgy

In the Late Bronze Age, Cyprus produced numerous bronze stands that depicted a man carrying an oxhide ingot. The stands were designed to hold vases, and they were cast through the lost-wax process. The ingots show the familiar shape of four protruding handles, and the men carry them over their shoulders. These Cypriot stands were exported to Crete and Sardinia, and both islands created similar stands in local bronze workshops.

Metallurgy

:K = 24 &times; (M / M) where : K is the karat rating of the material, : M is the mass of pure gold in the alloy, and : M is the total mass of the material. 24-karat gold is pure (while 100% purity is very difficult to attain, 24-karat as a designation is permitted in commerce for a minimum of 99.95% purity), 18-karat gold is 18 parts gold, 6 parts another metal (forming an alloy with 75% gold), 12-karat gold is 12 parts gold (12 parts another metal), and so forth. In England, the carat was divisible into four grains, and the grain was divisible into four quarts. For example, a gold alloy of fineness (that is, 99.2% purity) could have been described as being 23-karat, 3-grain, 1-quart gold. The karat fractional system is increasingly being complemented or superseded by the millesimal system, described above for bullion, though jewelry generally tends to still use the karat system. Conversion between percentage of pure gold and karats: * 58.33–62.50% = 14 k (acclaimed 58.33%) * 75.00–79.16% = 18 k (acclaimed 75.00%) * 91.66–95.83% = 22 k (acclaimed 91.66%) * 95.83–99.95% = 23 k (acclaimed 95.83%) * 99.95–100% = 24 k (acclaimed 99.95%)

Metallurgy

Roasting consists of thermal gas–solid reactions, which can include oxidation, reduction, chlorination, sulfation, and pyrohydrolysis. The most common example of roasting is the oxidation of metal sulfide ores. The metal sulfide is heated in the presence of air to a temperature that allows the oxygen in the air to react with the sulfide to form sulfur dioxide gas and solid metal oxide. The solid product from roasting is often called "calcine". In oxidizing roasting, if the temperature and gas conditions are such that the sulfide feed is completely oxidized, the process is known as "dead roasting". Sometimes, as in the case of pre-treating reverberatory or electric smelting furnace feed, the roasting process is performed with less than the required amount of oxygen to fully oxidize the feed. In this case, the process is called "partial roasting" because the sulfur is only partially removed. Finally, if the temperature and gas conditions are controlled such that the sulfides in the feed react to form metal sulfates instead of metal oxides, the process is known as "sulfation roasting". Sometimes, temperature and gas conditions can be maintained such that a mixed sulfide feed (for instance a feed containing both copper sulfide and iron sulfide) reacts such that one metal forms a sulfate and the other forms an oxide, the process is known as "selective roasting" or "selective sulfation".

Metallurgy

Zinc is extracted from the purified zinc sulfate solution by electrowinning, which is a specialized form of electrolysis. The process works by passing an electric current through the solution in a series of cells. This causes the zinc to deposit on the cathodes (aluminium sheets) and oxygen to form at the anodes. Sulfuric acid is also formed in the process and reused in the leaching process. Every 24 to 48 hours, each cell is shut down, the zinc-coated cathodes are removed and rinsed, and the zinc is mechanically stripped from the aluminium plates. Electrolytic zinc smelters contain as many as several hundred cells. A portion of the electrical energy is converted into heat, which increases the temperature of the electrolyte. Electrolytic cells operate at temperature ranges from and at atmospheric pressure. A portion of the electrolyte is continuously circulated through the cooling towers both to cool and concentrate the electrolyte through evaporation of water. The cooled and concentrated electrolyte is then recycled to the cells. This process accounts for approximately one-third of all the energy usage when smelting zinc. There are two common processes for electrowinning the metal: the low current density process, and the Tainton high current density process. The former uses a 10% sulfuric acid solution as the electrolyte, with current density of 270–325 amperes per square meter. The latter uses 22–28% sulfuric acid solution as the electrolyte with a current density of about 1,000 amperes per square metre. The latter gives better purity and has higher production capacity per volume of electrolyte, but has the disadvantage of running hotter and being more corrosive to the vessel in which it is done. In either of the electrolytic processes, each metric ton of zinc production expends about of electric power.

Metallurgy

Though microorganisms are often responsible for corrosion, they can also protect surfaces from corrosion. For example, oxidization is a common cause of corrosion. If a susceptible surface has a biofilm covering it that takes in and uses oxygen, then that surface will be protected from corrosion due to oxidization. Biofilms can also release antimicrobial compounds, which is helpful if the biofilm is not corrosive and can deter microbes that would be. Biofilms provide a barrier between a surface and the ecosystem surrounding it, so as long as the biofilm has no adverse effects, it can serve as protection from corrosion as well. Because biofilms don’t negatively impact the ecosystem, they are potentially one of the best mechanisms for corrosion inhibition. They can also alter the conditions on the surface of a metal so that the metal is less likely to be damaged, preventing corrosion.

Metallurgy

Metastasis is a major cause of cancer deaths, and strategies to prevent or halt invasion are lacking. One study showed that autocrine PDGFR signaling plays an essential role in epithelial-mesenchymal transition (EMT) maintenance in vitro, which is known to correlate well with metastasis in vivo. The authors showed that the metastatic potential of oncogenic mammary epithelial cells required an autocrine PDGF/PDGFR signaling loop, and that cooperation of autocrine PDGFR signaling with oncogenic was required for survival during EMT. Autocrine PDGFR signaling also contributes to maintenance of EMT, possibly through activation of STAT1 and other distinct pathways. In addition, expression of PDGFRα and -β correlated with invasive behavior in human mammary carcinomas. This indicates the numerous pathways through which autocrine signaling can regulate metastatic processes in a tumor.

Gene expression + Signal Transduction

An operon is made up of 3 basic DNA components: * Promoter – a nucleotide sequence that enables a gene to be transcribed. The promoter is recognized by RNA polymerase, which then initiates transcription. In RNA synthesis, promoters indicate which genes should be used for messenger RNA creation – and, by extension, control which proteins the cell produces. * Operator – a segment of DNA to which a repressor binds. It is classically defined in the lac operon as a segment between the promoter and the genes of the operon. The main operator (O1) in the lac operon is located slightly downstream of the promoter; two additional operators, O2 and O3 are located at -82 and +412, respectively. In the case of a repressor, the repressor protein physically obstructs the RNA polymerase from transcribing the genes. * Structural genes – the genes that are co-regulated by the operon. Not always included within the operon, but important in its function is a regulatory gene, a constantly expressed gene which codes for repressor proteins. The regulatory gene does not need to be in, adjacent to, or even near the operon to control it. An inducer (small molecule) can displace a repressor (protein) from the operator site (DNA), resulting in an uninhibited operon. Alternatively, a corepressor can bind to the repressor to allow its binding to the operator site. A good example of this type of regulation is seen for the trp operon.

Gene expression + Signal Transduction

Antitermination in lambda is induced by two quite distinct mechanisms. The first is the result of interaction between lambda N protein and its targets in the early phage transcripts, and the second is the result of an interaction between the lambda Q protein and its target in the late phage promoter. We describe the N mechanism first. Lambda N, a small basic protein of the arginine-rich motif (ARM) family of RNA binding proteins, binds to a 15-nucleotide (nt) stem-loop called BOXB. (We will capitalize the names of sites in RNA and italicize the names of the corresponding DNA sequences; e.g., BOXB and boxB.) boxB is found twice in the lambda chromosome, once in each of the two early operons. It is close to the start point of the P operon transcript and just downstream of the first translated gene of the P operon. Neither the distance between the transcription start site and boxB, nor the nature of the promoter (at least in the case of sigma-70-dependent promoters), nor the nature of the terminator is relevant to N action. Although the boxB sequence is not well conserved in other bacteriophages of the lambda family, most of these phages encode proteins that are analogous to lambda N and have sequences capable of forming BOXB-like structures in their P and P operons. In some cases, it has been shown that these structures are recognized by the cognate N analogs. It is believed that this accounts for the phage specificity of N-mediated antitermination. Processive antitermination requires the complete antitermination complex. The assembly of NusB, S10, and NusG onto the core complex involves nt 2 to 7 of lambda BOXA (CGCUCUUACACA), as well as the carboxyl-terminal region of N, which interacts with RNAP. The role of NusG in the N antitermination reaction is not clear. NusG binds to termination factor Rho and to RNAP. It stimulates the rate of transcription elongation and is required for the activity of certain Rho-dependent terminators. NusG is a component of the complete antitermination complex and enhances N antitermination in vitro. However, alteration of lambda BOXA to a variant called BOXA consensus (CGCUCUUUAACA) allows NusB and S10 to assemble in the absence of NusG. Furthermore, depletion of NusG has no effect on lambda N antitermination in vivo, and unlike nusA, nusB, and nusE, no point mutations in nusG that block N activity have been isolated. A NusG homolog, RfaH, enhances elongation of several transcripts in E. coli and S. typhimurium. The possibility that RfaH and NusG are redundant for N antitermination has not yet been tested, although for several other functions, the two proteins are not interchangeable. Processive antitermination can be mediated by RNA as well as proteins. Coliphage HK022, alone among the known lambdoid phages, does not encode an analog to lambda N. Instead, it promotes antitermination of early phage transcription through the direct action of transcribed sequences called put (for polymerase utilization) sites. There are two closely related put sites, one located in the P operon and the other located in the P operon, roughly corresponding to the positions of the nut sequences in lambda and in other lambda relatives. put sites act in cis to promote readthrough of downstream terminators in the absence of all HK022 proteins. The put transcripts are predicted to form two stem-loops separated by a single unpaired nucleotide. This prediction is supported by mutational studies and the pattern of sensitivity of the two RNAs to cleavage with single- and double-strand-specific endoribonucleases. RNA structure is critical to antitermination because mutations that prevent the formation of base pairs in the stems reduce function, and these mutations can be suppressed by additional mutations that restore base pairing. Like lambda N and Q, the PUT sequences suppress polymerase pausing and promote processive antitermination in a purified in vitro transcription system. In contrast to lambda N, no phage or auxiliary bacterial factors are required. The only mutations known to block PUT-mediated antitermination change highly conserved amino acids located in a cysteine-rich amino-proximal domain of the RNAP beta subunit. Strains carrying these mutations are unable to support lytic growth of HK022 but are normal in all other respects tested, including lytic growth of lambda and other lambda relatives. The phage-restricted phenotypes conferred by these mutations suggest that they alter a domain of RNAP-beta’ that interacts specifically with nascent PUT RNA in the transcription elongation complex, but this idea has not been directly tested. The stability of the putative PUT-RNAP interaction and the nature of the PUT'-induced modification to the elongation complex are unknown. Processive antitermination was first discovered in a bacteriophage, but examples have since been found in bacterial operons. The E. coli rrn operons are regulated by an antitermination mechanism that is dependent on sites that are closely related to lambda boxA and located promoter proximal to the 16S and 23S structural genes in each operon. The sequences of the rrn BOXA sites are more similar to the bacteriophage consensus than is that of lambda, and they bind NusB-S10 more efficiently. Although stem-loop structures analogous to BOXB are found promoter proximal to the BOXA sites, they are not essential for antitermination. An rrn BOXA sequence confers full antitermination activity against Rho-dependent but not against intrinsic terminators. BOXA also increases the rate of transcription elongation by RNAP. Point mutations in BOXA induce premature transcription termination. rrn antitermination requires NusB in vivo, as shown by a NusB depletion experiment. NusA stimulates the elongation rate of rrn RNA chains carrying BOXA. A role for NusA is further suggested by the observation that the nusA10 (Cs) mutation inhibits both antitermination and the rate of transcription elongation in an rrn operon. The role of other Nus factors in rrn regulation in vivo is not clear. In vitro, an antitermination complex that includes NusA, NusB, S10, and NusG forms at the BOXA sequence of rrnG, but these components are not sufficient for antitermination by themselves. An additional factor or factors that can be supplied by a cellular extract are required, but their identities are unknown.

Gene expression + Signal Transduction

In eukaryotes, most of the newly synthesized secretory proteins are transported from the ER to the Golgi apparatus. If these proteins have a particular 4-amino-acid retention sequence for the ERs lumen, KDEL, on their C-terminus, they are retained in the ERs lumen or are routed back to the ER's lumen (in instances where they escape) via interaction with the KDEL receptor in the Golgi apparatus. If the signal is KKXX, the retention mechanism to the ER will be similar but the protein will be transmembranal.

Gene expression + Signal Transduction

siRNAs act in the nucleus and the cytoplasm and are involved in RNAi as well as CDGS. siRNAs come from long dsRNA precursors derived from a variety of single-stranded RNA (ssRNA) precursors, such as sense and antisense RNAs. siRNAs also come from hairpin RNAs derived from transcription of inverted repeat regions. siRNAs may also arise enzymatically from non-coding RNA precursors. The volume of literature on siRNA within the framework of RNAi is extensive. One of the potent applications of siRNAs is the ability to distinguish the target versus non-target sequence with a single-nucleotide difference. This approach has been considered as therapeutically crucial for the silencing dominant gain-of-function (GOF) disorders,where mutant allele causing disease is differed from wt-allele by a single nucleotide (nt). This type of siRNAs with capability to distinguish a single-nt difference are termed as allele-specific siRNAs.

Gene expression + Signal Transduction

Silicon carbide can be used in the production of graphene because of its chemical properties that promote the production of graphene on the surface of SiC nanostructures. When it comes to its production, silicon is used primarily as a substrate to grow the graphene. But there are actually several methods that can be used to grow the graphene on the silicon carbide. The confinement controlled sublimation (CCS) growth method consists of a SiC chip that is heated under vacuum with graphite. Then the vacuum is released very gradually to control the growth of graphene. This method yields the highest quality graphene layers. But other methods have been reported to yield the same product as well. Another way of growing graphene would be thermally decomposing SiC at a high temperature within a vacuum. But this method turns out to yield graphene layers that contain smaller grains within the layers. So there have been efforts to improve the quality and yield of graphene. One such method is to perform ex situ graphitization of silicon terminated SiC in an atmosphere consisting of argon. This method has proved to yield layers of graphene with larger domain sizes than the layer that would be attainable via other methods. This new method can be very viable to make higher quality graphene for a multitude of technological applications. When it comes to understanding how or when to use these methods of graphene production, most of them mainly produce or grow this graphene on the SiC within a growth enabling environment. It is utilized most often at rather higher temperatures (such as 1300 °C) because of SiC thermal properties. However, there have been certain procedures that have been performed and studied that could potentially yield methods that use lower temperatures to help manufacture graphene. More specifically this different approach to graphene growth has been observed to produce graphene within a temperature environment of around 750 °C. This method entails the combination of certain methods like chemical vapor deposition (CVD) and surface segregation. And when it comes to the substrate, the procedure would consist of coating a SiC substrate with thin films of a transition metal. And after the rapid heat treating of this substance, the carbon atoms would then become more abundant at the surface interface of the transition metal film which would then yield graphene. And this process was found to yield graphene layers that were more continuous throughout the substrate surface.

Metallurgy

Aluminium alloys are anodized to increase corrosion resistance and to allow dyeing (colouring), improved lubrication, or improved adhesion. However, anodizing does not increase the strength of the aluminium object. The anodic layer is insulative. When exposed to air at room temperature, or any other gas containing oxygen, pure aluminium self-passivates by forming a surface layer of amorphous aluminium oxide 2 to 3 nm thick, which provides very effective protection against corrosion. Aluminium alloys typically form a thicker oxide layer, 5–15 nm thick, but tend to be more susceptible to corrosion. Aluminium alloy parts are anodized to greatly increase the thickness of this layer for corrosion resistance. The corrosion resistance of aluminium alloys is significantly decreased by certain alloying elements or impurities: copper, iron, and silicon, so 2000-, 4000-, 6000 and 7000-series Al alloys tend to be most susceptible. Although anodizing produces a very regular and uniform coating, microscopic fissures in the coating can lead to corrosion. Further, the coating is susceptible to chemical dissolution in the presence of high- and low-pH chemistry, which results in stripping the coating and corrosion of the substrate. To combat this, various techniques have been developed either to reduce the number of fissures, to insert more chemically stable compounds into the oxide, or both. For instance, sulphuric-anodized articles are normally sealed, either through hydro-thermal sealing or precipitating sealing, to reduce porosity and interstitial pathways that allow corrosive ion exchange between the surface and the substrate. Precipitating seals enhance chemical stability but are less effective in eliminating ionic exchange pathways. Most recently, new techniques to partially convert the amorphous oxide coating into more stable micro-crystalline compounds have been developed that have shown significant improvement based on shorter bond lengths. Some aluminium aircraft parts, architectural materials, and consumer products are anodized. Anodized aluminium can be found on MP3 players, smartphones, multi-tools, flashlights, cookware, cameras, sporting goods, firearms, window frames, roofs, in electrolytic capacitors, and on many other products both for corrosion resistance and the ability to retain dye. Although anodizing only has moderate wear resistance, the deeper pores can better retain a lubricating film than a smooth surface would. Anodized coatings have a much lower thermal conductivity and coefficient of linear expansion than aluminium. As a result, the coating will crack from thermal stress if exposed to temperatures above 80 °C (353 K). The coating can crack, but it will not peel. The melting point of aluminium oxide is 2050°C (2323K), much higher than pure aluminium's 658°C (931K). This and the insulativity of aluminium oxide can make welding more difficult. In typical commercial aluminium anodizing processes, the aluminium oxide is grown down into the surface and out from the surface by equal amounts. Therefore, anodizing will increase the part dimensions on each surface by half the oxide thickness. For example, a coating that is 2 μm thick will increase the part dimensions by 1 μm per surface. If the part is anodized on all sides, then all linear dimensions will increase by the oxide thickness. Anodized aluminium surfaces are harder than aluminium but have low to moderate wear resistance, although this can be improved with thickness and sealing.

Metallurgy

mRNA processing acts as a form of post-transcriptional regulation, which mostly happens in eukaryotes. 3′ cleavage/polyadenylation and 5’ capping increase overall RNA stability, and the presence of 5’ cap allows ribosome binding for translation. RNA splicing allows the expression of various protein variants from the same gene. Specific examples include: * SR proteins * Ribonucleoprotein ** hnRNP ** snRNP

Gene expression + Signal Transduction

In iron and steel metallurgy, ledeburite is a mixture of 4.3% carbon in iron and is a eutectic mixture of austenite and cementite. Ledeburite is not a type of steel as the carbon level is too high although it may occur as a separate constituent in some high carbon steels. It is mostly found with cementite or pearlite in a range of cast irons. It is named after the metallurgist Karl Heinrich Adolf Ledebur (1837–1906). He was the first professor of metallurgy at the Bergakademie Freiberg and discovered ledeburite in 1882. Ledeburite arises when the carbon content is between 2.06% and 6.67%. The eutectic mixture of austenite and cementite is 4.3% carbon, FeC:2Fe, with a melting point of 1147 °C. Ledeburite-II (at ambient temperature) is composed of cementite-I with recrystallized secondary cementite (which separates from austenite as the metal cools) and (with slow cooling) of pearlite. The pearlite results from the eutectoidal decay of the austenite that comes from the ledeburite-I at 723 °C. During more rapid cooling, bainite can develop instead of pearlite, and with very rapid cooling martensite can develop.

Metallurgy

The poly(A) tail acts as the binding site for poly(A)-binding protein. Poly(A)-binding protein promotes export from the nucleus and translation, and inhibits degradation. This protein binds to the poly(A) tail prior to mRNA export from the nucleus and in yeast also recruits poly(A) nuclease, an enzyme that shortens the poly(A) tail and allows the export of the mRNA. Poly(A)-binding protein is exported to the cytoplasm with the RNA. mRNAs that are not exported are degraded by the exosome. Poly(A)-binding protein also can bind to, and thus recruit, several proteins that affect translation, one of these is initiation factor-4G, which in turn recruits the 40S ribosomal subunit. However, a poly(A) tail is not required for the translation of all mRNAs. Further, poly(A) tailing (oligo-adenylation) can determine the fate of RNA molecules that are usually not poly(A)-tailed (such as (small) non-coding (sn)RNAs etc.) and thereby induce their RNA decay.

Gene expression + Signal Transduction

AKT is downstream to PI3K and is inhibited by Ipatasertib. Akt is an AGC-family kinase and a central, integral signaling node of the PAM pathway. There are three Akt isozymes, Akt1, Akt2 and Akt3. Small-molecule inhibitors of Akt1 could be especially useful to target tumors with a high prevalence of Akt1 E17K activating mutations, which is observed in 4–6% of breast cancers and 1–2% of colorectal cancer. Research towards Akt inhibition has focused on inhibition of two distinct binding sites: * the allosteric pocket of the inactive enzyme, and * the ATP binding site. Allosteric Akt inhibitors, highlighted by MK-2206, have been extensively evaluated in a clinical setting; Recently, additional allosteric Akt inhibitors have been identified. ARQ-092, is a potent pan-Akt inhibitor which can inhibit tumor growth preclinically and is currently in Phase I clinical studies.

Gene expression + Signal Transduction

Sepro Agglomeration Drums are specifically designed to prepare feeds with high fines content on Gold and Base Metal heap loading operations. Processes where a Sepro Agglomeration Drum can be utilized include gold, copper, uranium and nickel laterite. The action in the agglomeration drum, combined with small additions of cement or lime, binds the fines into a "pelletised" product, which can be heaped and leached out without "pooling" and "channeling" caused by loss of heap permeability due to blinding by fines. The machine uses flexible rubber liners to prevent build up without the use of lifter bars and is adjustable on a pivotable base frame. Shell supported agglomerators such as the Sepro PTD Agglomeration Drum minimize stress on the shell by spreading the power drive over the full length of the unit.

Metallurgy

At and below, pure tin transforms from the silvery, ductile metallic allotrope of β-form white tin to the brittle, nonmetallic, α-form grey tin with a diamond cubic structure. The transformation is slow to initiate due to a high activation energy but the presence of germanium (or crystal structures of similar form and size) or very low temperatures of roughly −30 °C aids the initiation. There is also a large volume increase of about 27% associated with the phase change to the nonmetallic low temperature allotrope. This frequently makes tin objects (like buttons) decompose into powder during the transformation, hence the name tin pest. The decomposition will catalyze itself, which is why the reaction accelerates once it starts. The mere presence of tin pest leads to tin pest. Tin objects at low temperatures will simply disintegrate.

Metallurgy

Wootz steel originated in the mid-1st millennium BC in India, in present-day Tiruchirappalli, Kodumanal, Erode, Tamil Nadu. There are several ancient Tamil, North Indian, Greek, Chinese and Roman literary references to high-carbon Tamil steel. In later times, wootz steel was also made in Golconda in Telangana, Karnataka and Sri Lanka. The steel was exported as cakes of steely iron that came to be known as "Wootz". The method was to heat black magnetite ore in the presence of carbon in a sealed clay crucible inside a charcoal furnace to completely remove slag. An alternative was to smelt the ore first to give wrought iron, then heat and hammer it to remove slag. The carbon source was bamboo and leaves from plants such as Avārai. Locals in Sri Lanka adopted the production methods of creating wootz steel from the Chera Tamils by the 5th century BC. Joseph Needham in 1971 claimed China produced a similar steel also by the 5th century BCE but more recent research in China (2009) showed that Needham erroneously identified the ancient Chinese steel as hyper-eutectoid and similar to wootz but it was really produced via co-fusion process instead (smelting cast iron and wrought iron together). Genuine wootz in China was mentioned for the first time much later, during the Bei Wei Dynasty (386-534 CE) under the name “Bintie” or “Pin t’ieh” as being produced in India, ingots were initially given by Persian Kings as valuable presents, later the Chinese called "bintie" the various co-fusion hard steels they produced. In Sri Lanka, this early steel-making method employed a unique wind furnace, driven by the monsoon winds. Production sites from antiquity have emerged, in places such as Anuradhapura, Tissamaharama and Samanalawewa, as well as imported artifacts of ancient iron and steel from Kodumanal. Recent archaeological excavations (2018) of the Yodhawewa site (in Mannar District) discovered a lower half-spherical furnace, crucible fragments, and lid fragments related to the crucible steel production through the carburization process. A 200 BC Tamil trade guild in Tissamaharama, in the South East of Sri Lanka, brought with them some of the oldest iron and steel artifacts and production processes to the island from the classical period. Trade between India and Sri Lanka through the Arabian Sea introduced wootz steel to Arabia. The term muhannad مهند or hendeyy هندي in pre-Islamic and early Islamic Arabic refers to sword blades made from Indian steel, which were highly prized, and are attested in Arabic poetry. Further trade spread the technology to the city of Damascus, where an industry developed for making weapons of this steel. This led to the development of Damascus steel. The 12th century Arab traveler Edrisi mentioned the "Hinduwani" or Indian steel as the best in the world. Arab accounts also point to the fame of Teling steel, which can be taken to refer to the region of Telangana. The Golconda region of Telangana clearly being the nodal centre for the export of wootz steel to West Asia. Another sign of its reputation is seen in a Persian phraseto give an "Indian answer", meaning "a cut with an Indian sword". Wootz steel was widely exported and traded throughout ancient Europe and the Arab world, and became particularly famous in the Middle East.

Metallurgy

RNA-dependent RNA polymerase (RdRp) or RNA replicase is an enzyme that catalyzes the replication of RNA from an RNA template. Specifically, it catalyzes synthesis of the RNA strand complementary to a given RNA template. This is in contrast to typical DNA-dependent RNA polymerases, which all organisms use to catalyze the transcription of RNA from a DNA template. RdRp is an essential protein encoded in the genomes of most RNA-containing viruses with no DNA stage including SARS-CoV-2. Some eukaryotes also contain RdRps, which are involved in RNA interference and differ structurally from viral RdRps.

Gene expression + Signal Transduction

The compatibility of two different metals may be predicted by consideration of their anodic index. This parameter is a measure of the electrochemical voltage that will be developed between the metal and gold. To find the relative voltage of a pair of metals it is only required to subtract their anodic indices. To reduce galvanic corrosion for metals stored in normal environments such as storage in warehouses or non-temperature and humidity controlled environments, there should not be more than 0.25V difference in the anodic index of the two metals in contact. For controlled environments in which temperature and humidity are controlled, 0.50V can be tolerated. For harsh environments such as outdoors, high humidity, and salty environments, there should be not more than 0.15V difference in the anodic index. For example: gold and silver have a difference of 0.15V, therefore the two metals will not experience significant corrosion even in a harsh environment. When design considerations require that dissimilar metals come in contact, the difference in anodic index is often managed by finishes and plating. The finishing and plating selected allow the dissimilar materials to be in contact, while protecting the more base materials from corrosion by the more noble. It will always be the metal with the most negative anodic index which will ultimately suffer from corrosion when galvanic incompatibility is in play. This is why sterling silver and stainless steel tableware should never be placed together in a dishwasher at the same time, as the steel items will likely experience corrosion by the end of the cycle (soap and water having served as the chemical electrolyte, and heat having accelerated the process).

Metallurgy

Steel superalloys are of interest because some present creep and oxidation resistance similar to Ni-based superalloys, at far less cost. Gamma (γ): Fe-based alloys feature a matrix phase of austenite iron (FCC). Alloying elements include: Al, B, C, Co, Cr, Mo, Ni, Nb, Si, Ti, W, and Y. Al (oxidation benefits) must be kept at low weight fractions (wt.%) because Al stabilizes a ferritic (BCC) primary phase matrix, which is undesirable, as it is inferior to the high temperature strength exhibited by an austenitic (FCC) primary phase matrix. Gamma-prime (γ): This phase is introduced as precipitates to strengthen the alloy. γ-Ni3Al precipitates can be introduced with the proper balance of Al, Ni, Nb, and Ti additions.

Metallurgy

The Mouse Genome Database collects and curates comprehensive phenotype and functional annotations for mouse genes and alleles. This is an NHGRI-funded project which contributes to the Mouse Genome Informatics database.

Gene expression + Signal Transduction

Ferrosilicon is used as a source of silicon to reduce metals from their oxides and to deoxidize steel and other ferrous alloys. This prevents the loss of carbon from the molten steel (so called blocking the heat); ferromanganese, spiegeleisen, calcium silicides, and many other materials are used for the same purpose. It can be used to make other ferroalloys. Ferrosilicon is also used for manufacture of silicon, corrosion-resistant and high-temperature-resistant ferrous silicon alloys, and silicon steel for electromotors and transformer cores. In the manufacture of cast iron, ferrosilicon is used for inoculation of the iron to accelerate graphitization. In arc welding, ferrosilicon can be found in some electrode coatings. Ferrosilicon is a basis for manufacture of prealloys like magnesium ferrosilicon (MgFeSi), used for production of ductile iron. MgFeSi contains 3–42% magnesium and small amounts of rare-earth metals. Ferrosilicon is also important as an additive to cast irons for controlling the initial content of silicon. Magnesium ferrosilicon is instrumental in the formation of nodules, which give ductile iron its flexible property. Unlike gray cast iron, which forms graphite flakes, ductile iron contains graphite nodules, or pores, which make cracking more difficult. Ferrosilicon is also used in the Pidgeon process to make magnesium from dolomite.

Metallurgy

Chambers isolated by filters are proper tools for accurate determination of chemotactic behavior. The pioneer type of these chambers was constructed by Boyden. The motile cells are placed into the upper chamber, while fluid containing the test substance is filled into the lower one. The size of the motile cells to be investigated determines the pore size of the filter; it is essential to choose a diameter which allows active transmigration. For modelling in vivo conditions, several protocols prefer coverage of filter with molecules of extracellular matrix (collagen, elastin etc.) Efficiency of the measurements was increased by development of multiwell chambers (e.g. NeuroProbe), where 24, 96, 384 samples are evaluated in parallel. Advantage of this variant is that several parallels are assayed in identical conditions.

Gene expression + Signal Transduction

Delivery of DDRNAI DNA constructs is simplified by the existence of several clinically approved and well-characterized gene therapy vectors developed for the purpose. Delivery is a major challenge for RNAi-based therapeutics with new modifications and reagents continually being developed to optimize target cell delivery. Two broad strategies to facilitate the delivery of DNA constructs to the desired cells are available: these use either viral vectors or one of several classes of transfection reagents. In vivo delivery of DDRNAI constructs has been demonstrated using a range of vectors and reagents with different routes of administration (ROA). DDRNAI constructs have also been successfully delivered into host cells ex vivo, and then transplanted back into the host. For example, in phase I clinical trial at the City of Hope National Medical Center, California, US, four HIV-positive patients with non-Hodgkin's lymphoma were successfully treated with autologous hematopoietic progenitor cells pre-transduced ex vivo with DDRNAI constructs using lentiviral vectors. This construct was designed to express three therapeutic RNAs, one of which was a shRNA, thereby combating HIV replication in three different ways: *shRNA, that silences the tat and rev genes of the HIV genome *CCR5 ribozyme, inhibiting viral cell entry *TAR decoy RNA, inhibiting initiation of viral transcription. Ongoing expression of the shRNA has been confirmed in T cells, monocytes, and B cells more than one year after transplantation.

Gene expression + Signal Transduction

MgCu can be prepared by hydrogenation of MgCu or the reaction of magnesium hydride and metallic copper at elevated temperature and pressure: : 2 MgCu + 3 H → 3 MgH + MgCu : MgH + 2 Cu → MgCu + H MgCu can also be prepared by reacting of stoichiometric amounts of metals at about 380 °C in the presence of excess copper.

Metallurgy

miR-324-5p likely regulates cell growth and survival through interaction with multiple pathways. Published research demonstrates that this miRNA interacts with the Hedgehog (HH) signaling pathway via interactions with HH transcription factor Gli1 and HH protein receptor Smo, often contributing to tumorigenesis. miR-324-5p's activating interaction with the protein NfkB also regulates numerous components of cell survival, including cell cycle control, enzyme synthesis, and cell adhesion. In addition, miR-324-5p regulates components of the MAPK pathway, influencing cell growth, proliferation, and survival. Specifically, miR-324-5p downregulates RAF and ERK and is necessary for normal levels of cell growth. Reduced expression leads to increased cell growth and proliferation, and overexpression limits growth, leading to its role in oncogenesis.

Gene expression + Signal Transduction

miR-324-5p is a microRNA that functions in cell growth, apoptosis, cancer, epilepsy, neuronal differentiation, psychiatric conditions, cardiac disease pathology, and more. As a microRNA, it regulates gene expression through targeting mRNAs. Additionally, miR-324-5p is both an intracellular miRNA, meaning it is commonly found within the microenvironment of the cell, and one of several circulating miRNAs found throughout the body. Its presence throughout the body both within and external to cells may contribute to miR-324-5p's wide array of functions and role in numerous disease pathologies – especially cancer – in various organ systems.

Gene expression + Signal Transduction

This large and diverse class of steroids are biosynthesized from isoprenoids and structurally resemble cholesterol. Mammalian steroid hormones can be grouped into five groups by the receptors to which they bind: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestogens.

Gene expression + Signal Transduction

The Condor Dense Medium Separator (DMS) is a multi-stage, high efficiency media separation machine for mineral processing operations at the rougher and scavenger stage. It is typically used in a pre-concentration duty prior to processing or milling to reject barren material. The unit is manufactured with either two or three stages of separation depending on the media with one or two valuable densities resulting, while the unit can produce up to four products from one dense medium vessel altogether. The Condor DMS can take a larger feed particle size compared to a DMS cyclone of the same diameter and capacity, and is capable of handling higher sinks or floats loading without affecting performance. The valuable dense material (or sinks) can be combined or separated at the final stage and is then pumped onto the next process in the circuit. Sepro Mineral Systems Corp. supplies customizable DMS Plants for a wide variety of application requirements. Sepro's standard two product (concentrate, tailings) DMS Plant utilizes a two-stage Condor Separator and single density medium circuit, while the three product (concentrate, middlings, tailings) DMS Plant utilizes a three-stage Condor Separator and two medium circuits at high and low density.

Metallurgy

As sketched above, the ARM domain of β-catenin acts as a platform to which specific linear motifs may bind. Located in structurally diverse partners, the β-catenin binding motifs are typically disordered on their own, and typically adopt a rigid structure upon ARM domain engagement – as seen for short linear motifs. However, β-catenin interacting motifs also have a number of peculiar characteristics. First, they might reach or even surpass the length of 30 amino acids in length, and contact the ARM domain on an excessively large surface area. Another unusual feature of these motifs is their frequently high degree of phosphorylation. Such Ser/Thr phosphorylation events greatly enhance the binding of many β-catenin associating motifs to the ARM domain. The structure of β-catenin in complex with the catenin binding domain of the transcriptional transactivation partner TCF provided the initial structural roadmap of how many binding partners of β-catenin may form interactions. This structure demonstrated how the otherwise disordered N-terminus of TCF adapted what appeared to be a rigid conformation, with the binding motif spanning many beta-catenin repeats. Relatively strong charged interaction "hot spots" were defined (predicted, and later verified, to be conserved for the β-catenin/E-cadherin interaction), as well as hydrophobic regions deemed important in the overall mode of binding and as potential therapeutic small molecule inhibitor targets against certain cancer forms. Furthermore, following studies demonstrated another peculiar characteristic, plasticity in the binding of the TCF N-terminus to beta-catenin. Similarly, we find the familiar E-cadherin, whose cytoplasmatic tail contacts the ARM domain in the same canonical fashion. The scaffold protein axin (two closely related paralogs, axin 1 and axin 2) contains a similar interaction motif on its long, disordered middle segment. Although one molecule of axin only contains a single β-catenin recruitment motif, its partner the adenomatous polyposis coli (APC) protein contains 11 such motifs in tandem arrangement per protomer, thus capable to interact with several β-catenin molecules at once. Since the surface of the ARM domain can typically accommodate only one peptide motif at any given time, all these proteins compete for the same cellular pool of β-catenin molecules. This competition is the key to understand how the Wnt signaling pathway works. However, this "main" binding site on the ARM domain β-catenin is by no means the only one. The first helices of the ARM domain form an additional, special protein-protein interaction pocket: This can accommodate a helix-forming linear motif found in the coactivator BCL9 (or the closely related BCL9L) – an important protein involved in Wnt signaling. Although the precise details are much less clear, it appears that the same site is used by alpha-catenin when β-catenin is localized to the adherens junctions. Because this pocket is distinct from the ARM domain's "main" binding site, there is no competition between alpha-catenin and E-cadherin or between TCF1 and BCL9, respectively. On the other hand, BCL9 and BCL9L must compete with α-catenin to access β-catenin molecules.

Gene expression + Signal Transduction

Spoil tips may be conical in shape, and can appear as conspicuous features of the landscape, or they may be much flatter and eroded, especially if vegetation has established itself. In Loos-en-Gohelle, in the former mining area of Pas-de-Calais, France, are a series of five very perfect cones, of which two rise from the plain.

Metallurgy

Hafnium or zirconium added to niobium–tin increases the maximum current density in a magnetic field. This may allow it to be used at 16 tesla for CERN's planned Future Circular Collider.

Metallurgy

Specific protein complexes, known as histone-modifying complexes catalyze addition or removal of various chemical elements on histones. These enzymatic modifications include acetylation, methylation, phosphorylation, and ubiquitination and primarily occur at N-terminal histone tails. Such modifications affect the binding affinity between histones and DNA, and thus loosening or tightening the condensed DNA wrapped around histones, e.g., Methylation of specific lysine residues in H3 and H4 causes further condensation of DNA around histones, and thereby prevents binding of transcription factors to the DNA that lead to gene repression. On the contrary, histone acetylation relaxes chromatin condensation and exposes DNA for TF binding, leading to increased gene expression.

Gene expression + Signal Transduction

It is carried out in order to: * Manage the inspection of piping. * Identifying piping systems/circuits and assign failure modes. * Capture any changes due to those upgrades or design creep. * Ensure that circuits are identified to indicate inspection points as well as facilitate the implementation of various inspection techniques. * Identify potential damage mechanisms and their locations. Typically, this is performed at the outset of any Mechanical Integrity program i.e. as the facility is built, modified and operated throughout its life. General Requirements of Circuitization: * Use an experienced corrosion/materials engineer to define systems in each unit * Define corrosion circuits within each system based on materials of construction, operating conditions and active damage mechanisms * Circuit identification and naming convention is used for both API RBI and IDMS programs to provide linking and sharing inspection data * Circuit corrosion rates are used in API RBI to calculate circuit risk * Determine the circuit and component next inspection date and inspection effectiveness, including detailed inspection plan * Review or Placement of CML/TML (Condition Monitoring Locations/Thickness Monitoring Locations) recommended by corrosion/materials engineer * CML/TML installed and documented on piping isometric drawings

Metallurgy

In the early 1990s, the market was becoming more familiar with the potential of laser peening to increase fatigue life. In 1991, the U.S. Air Force introduced Battelle and Wagner engineers to GE Aviation to discuss the potential application of laser peening to address a foreign object damage (FOD) problem with fan blades in the General Electric F101 engine powering the Rockwell B-1B Lancer Bomber. The resulting tests showed that laser peened fan blades severely notched after laser peening had the same fatigue life as a new blade. After further development, GE Aviation licensed the laser shock peening technology from Battelle, and in 1995, GE Aviation and the U.S. Air Force made the decision to move forward with production development of the technology. GE Aviation began production laser peening of the F101 fan blades in 1998. The demand for industrial laser systems required for GE Aviation to go into production attracted several of the laser shock peening team at Battelle to start LSP Technologies, Inc. in 1995 as the first commercial supplier of laser peening equipment. Led by founder Jeff Dulaney, LSP Technologies designed and built the laser systems for GE Aviation to perform production laser peening of the F101 fan blades. Through the late 1990s and early 2000s, the U.S. Air Force continued to work with LSP Technologies to mature the laser shock peening production capabilities and implement production manufacturing cells. In the mid 1990s, independent of the laser peening developments ongoing in the United States and France, Yuji Sano of the Toshiba Corporation in Japan initiated the development of a laser peening system capable of laser peening welds in nuclear plant pressure vessels to mitigate stress corrosion cracking in these areas. The system used a low-energy pulsed laser operating at a higher pulse frequency than the higher powered lasers. The laser beam was introduced into the pressure vessels through articulated tubes. Because the pressure vessels were filled with water, the process did not require a water overlay over the irradiated surface. However, the beam had to travel some distance through the water, necessitating using a shorter wavelength beam, 532 nm, to minimize dielectric breakdown of the beam in the water, instead of the 1054 nm beam used in the United States and France. Also, it was impractical to consider using an opaque overlay. This process is now known as Laser Peening without Coating (LPwC). It began to be applied to Japanese boiling water and pressurized water reactors in 1999. Also in the 1990s a significant laser peening research group was formed at the Madrid Polytechnic University by José Ocaña. Their work includes both experimental and theoretical studies using low-energy pulsed lasers both without and with an opaque overlay.

Metallurgy

When microbes were first recognized as the cause of infectious diseases, it was immediately clear that multicellular organisms must be capable of recognizing them when infected and, hence, capable of recognizing molecules unique to microbes. A large body of literature, spanning most of the last century, attests to the search for the key molecules and their receptors. More than 100 years ago, Richard Pfeiffer, a student of Robert Koch, coined the term "endotoxin" to describe a substance produced by Gram-negative bacteria that could provoke fever and shock in experimental animals. In the decades that followed, endotoxin was chemically characterized and identified as a lipopolysaccharide (LPS) produced by most Gram-negative bacteria. This lipopolysaccharide is an integral part of the gram-negative membrane and is released upon destruction of the bacterium. Other molecules (bacterial lipopeptides, flagellin, and unmethylated DNA) were shown in turn to provoke host responses that are normally protective. However, these responses can be detrimental if they are excessively prolonged or intense. It followed logically that there must be receptors for such molecules, capable of alerting the host to the presence of infection, but these remained elusive for many years. Toll-like receptors are now counted among the key molecules that alert the immune system to the presence of microbial infections. The prototypic member of the family, the toll receptor (; Tl) in the fruit fly Drosophila melanogaster, was discovered in 1985 by 1995 Nobel Laureates Christiane Nüsslein-Volhard and Eric Wieschaus and colleagues. It was known for its developmental function in embryogenesis by establishing the dorsal-ventral axis. It was named after Christiane Nüsslein-Volhards 1985 exclamation, "" ("Thats amazing!"), in reference to the underdeveloped ventral portion of a fruit fly larva. It was cloned by the laboratory of Kathryn Anderson in 1988. In 1996, toll was found by Jules A. Hoffmann and his colleagues to have an essential role in the fly's immunity to fungal infection, which it achieved by activating the synthesis of antimicrobial peptides. The first reported human toll-like receptor was described by Nomura and colleagues in 1994, mapped to a chromosome by Taguchi and colleagues in 1996. Because the immune function of toll in Drosophila was not then known, it was assumed that TIL (now known as TLR1) might participate in mammalian development. However, in 1991 (prior to the discovery of TIL) it was observed that a molecule with a clear role in immune function in mammals, the interleukin-1 (IL-1) receptor, also had homology to drosophila toll; the cytoplasmic portions of both molecules were similar. In 1997, Charles Janeway and Ruslan Medzhitov showed that a toll-like receptor now known as TLR4 could, when artificially ligated using antibodies, induce the activation of certain genes necessary for initiating an adaptive immune response. TLR 4 function as an LPS sensing receptor was discovered by Bruce A. Beutler and colleagues. These workers used positional cloning to prove that mice that could not respond to LPS had mutations that abolished the function of TLR4. This identified TLR4 as one of the key components of the receptor for LPS. In turn, the other TLR genes were ablated in mice by gene targeting, largely in the laboratory of Shizuo Akira and colleagues. Each TLR is now believed to detect a discrete collection of molecules – some of microbial origin, and some products of cell damage – and to signal the presence of infections. Plant homologs of toll were discovered by Pamela Ronald in 1995 (rice XA21) and Thomas Boller in 2000 (Arabidopsis FLS2). In 2011, Beutler and Hoffmann were awarded the Nobel Prize in Medicine or Physiology for their work. Hoffmann and Akira received the Canada Gairdner International Award in 2011.

Gene expression + Signal Transduction

The potential for transcription and translation to regulate each other was recognized by the team of Marshall Nirenberg, who discovered that the processes are physically connected through the formation of a DNA-ribosome complex. As part of the efforts of Nirenbergs group to determine the genetic code that underlies protein synthesis, they pioneered the use of cell-free in vitro protein synthesis reactions. Analysis of these reactions revealed that protein synthesis is mRNA-dependent, and that the sequence of the mRNA strictly defines the sequence of the protein product. For this work in breaking in the genetic code, Nirenberg was jointly awarded the Nobel Prize in Physiology or Medicine in 1968. Having established that transcription and translation are linked biochemically (translation depends on the product of transcription), an outstanding question remained whether they were linked physically - whether the newly synthesized mRNA released from the DNA before it is translated, or if can translation occur concurrently with transcription. Electron micrographs of stained cell-free protein synthesis reactions revealed branched assemblies in which strings of ribosomes are linked to a central DNA fibre. DNA isolated from bacterial cells co-sediment with ribosomes, further supporting the conclusion that transcription and translation occur together. Direct contact between ribosomes and RNA polymerase are observable within these early micrographs. The potential for simultaneous regulation of transcription and translation at this junction was noted in Nirenbergs work as early as 1964.

Gene expression + Signal Transduction

The US states of Montana and Wisconsin, the Czech Republic, Hungary, have banned cyanide mining. The European Commission rejected a proposal for such a ban, noting that existing regulations (see below) provide adequate environmental and health protection. Several attempts to ban gold cyanidation in Romania were rejected by the Romanian Parliament. There are currently protests in Romania calling for a ban on the use of cyanide in mining (see 2013 Romanian protests against the Roșia Montană Project). In the EU, industrial use of hazardous chemicals is controlled by the so-called Seveso II Directive (Directive 96/82/EC, which replaced the original Seveso Directive (82/501/EEC brought in after the 1976 dioxin disaster. "Free cyanide and any compound capable of releasing free cyanide in solution" are further controlled by being on List I of the Groundwater Directive (Directive 80/68/EEC) which bans any discharge of a size which might cause deterioration in the quality of the groundwater at the time or in the future. The Groundwater Directive was largely replaced in 2000 by the Water Framework Directive (2000/60/EC). In response to the 2000 Baia Mare cyanide spill, the European Parliament and the Council adopted Directive 2006/21/EC on the management of waste from extractive industries. Article 13(6) requires "the concentration of weak acid dissociable cyanide in the pond is reduced to the lowest possible level using best available techniques", and at most all mines started after 1 May 2008 may not discharge waste containing over 10ppm WAD cyanide, mines built or permitted before that date are allowed no more than 50ppm initially, dropping to 25ppm in 2013 and 10ppm by 2018. Under Article 14, companies must also put in place financial guarantees to ensure clean-up after the mine has finished. This in particular may affect smaller companies wanting to build gold mines in the EU, as they are less likely to have the financial strength to give these kinds of guarantees. The industry has come up with a voluntary "Cyanide Code" that aims to reduce environmental impacts with third party audits of a company's cyanide management.

Metallurgy

*Nitinol can be used to replace conventional actuators (solenoids, servo motors, etc.), such as in the Stiquito, a simple hexapod robot. *Nitinol springs are used in thermal valves for fluidics, where the material both acts as a temperature sensor and an actuator. *It is used as autofocus actuator in action cameras and as an optical image stabilizer in mobile phones. *It is used in pneumatic valves for comfort seating and has become an industry standard. *The 2014 Chevrolet Corvette incorporates nitinol actuators, which replaced heavier motorized actuators to open and close the hatch vent that releases air from the trunk, making it easier to close.

Metallurgy

The binding of CTCF has been shown to have many effects, which are enumerated below. In each case, it is unknown if CTCF directly evokes the outcome or if it does so indirectly (in particular through its looping role).

Gene expression + Signal Transduction

Although Agricola died in 1555, the publication was delayed until the completion of the extensive and detailed woodcuts one year after his death. A German translation was published in 1557 and a second Latin edition appeared in 1561. A version in Spanish, though not a mere translation, was produced by Bernardo Pérez de Vargas in 1569. This was translated into French as Traité singulier de metallique in 1743. In 1912, the first English translation of De Re Metallica was privately published in London by subscription. The translators and editors were Herbert Hoover, a mining engineer (and later President of the United States), and his wife, Lou Henry Hoover, a geologist and Latinist. The translation is notable not only for its clarity of language, but for the extensive footnotes, which detail the classical references to mining and metals, such as the Naturalis Historia of Pliny the Elder, the history of mining law in England, France, and the German states; safety in mines, including historical safety; and known minerals at the time that Agricola wrote De Re Metallica. No expense was spared for this edition: in its typography, fine paper and binding, quality of reproduced images, and vellum covers, the publisher attempted to match the extraordinarily high standards of the sixteenth-century original. As a consequence, copies of this 1912 edition are now both rare and valuable. Fortunately, the translation has been reprinted by Dover Books. Subsequent translations into other languages, including German, owe much to the Hoover translations, as their footnotes detail their difficulties with Agricola's invention of several hundred Latin expressions to cover Medieval German mining and milling terms unknown to classical Latin.

Metallurgy

RNA-seq uses reverse transcriptase to convert the mRNA template to cDNA. During library preparation, the cDNA is fragmented into small pieces, which then serve as the template for sequencing. After sequencing RNA-seq analysis can then be performed.

Gene expression + Signal Transduction

Hot blast refers to the preheating of air blown into a blast furnace or other metallurgical process. As this considerably reduced the fuel consumed, hot blast was one of the most important technologies developed during the Industrial Revolution. Hot blast also allowed higher furnace temperatures, which increased the capacity of furnaces. As first developed, it worked by alternately storing heat from the furnace flue gas in a firebrick-lined vessel with multiple chambers, then blowing combustion air through the hot chamber. This is known as regenerative heating. Hot blast was invented and patented for iron furnaces by James Beaumont Neilson in 1828 at Wilsontown Ironworks in Scotland, but was later applied in other contexts, including late bloomeries. Later the carbon monoxide in the flue gas was burned to provide additional heat.

Metallurgy

An alternate stable form, if it exists, may appear at pressures of at least 50 GPa and temperatures of at least 1,500 K; it has been thought to have an orthorhombic or a double hcp structure. , recent and ongoing experiments are being conducted on high-pressure and superdense carbon allotropes.

Metallurgy

The society awards some 25 awards every year at the annual conference. In addition, the member societies also disburse their own awards, including the Percy Nicholls Award, awarded by SME jointly with American Society of Mechanical Engineers.

Metallurgy

A Rho factor acts on an RNA substrate. Rho's key function is its helicase activity, for which energy is provided by an RNA-dependent ATP hydrolysis. The initial binding site for Rho is an extended (~70 nucleotides, sometimes 80–100 nucleotides) single-stranded region, rich in cytosine and poor in guanine, called the rho utilisation site (rut), in the RNA being synthesised, upstream of the actual terminator sequence. Several rho binding sequences have been discovered. No consensus is found among these, but the different sequences each seem specific, as small mutations in the sequence disrupts its function. Rho binds to RNA and then uses its ATPase activity to provide the energy to translocate along the RNA until it reaches the RNA–DNA helical region, where it unwinds the hybrid duplex structure. RNA polymerase pauses at the termination sequence, which is because there is a specific site around 100 nt away from the Rho binding site called the Rho-sensitive pause site. So, even though the RNA polymerase is about 40 nt per second faster than Rho, it does not pose a problem for the Rho termination mechanism as the RNA polymerase allows Rho factor to catch up. In short, Rho factor acts as an ATP-dependent unwinding enzyme, moving along the newly forming RNA molecule towards its 3′ end and unwinding it from the DNA template as it proceeds.

Gene expression + Signal Transduction

In grain-boundary strengthening, the grain boundaries act as pinning points impeding further dislocation propagation. Since the lattice structure of adjacent grains differs in orientation, it requires more energy for a dislocation to change directions and move into the adjacent grain. The grain boundary is also much more disordered than inside the grain, which also prevents the dislocations from moving in a continuous slip plane. Impeding this dislocation movement will hinder the onset of plasticity and hence increase the yield strength of the material. Under an applied stress, existing dislocations and dislocations generated by Frank–Read sources will move through a crystalline lattice until encountering a grain boundary, where the large atomic mismatch between different grains creates a repulsive stress field to oppose continued dislocation motion. As more dislocations propagate to this boundary, dislocation pile up occurs as a cluster of dislocations are unable to move past the boundary. As dislocations generate repulsive stress fields, each successive dislocation will apply a repulsive force to the dislocation incident with the grain boundary. These repulsive forces act as a driving force to reduce the energetic barrier for diffusion across the boundary, such that additional pile up causes dislocation diffusion across the grain boundary, allowing further deformation in the material. Decreasing grain size decreases the amount of possible pile up at the boundary, increasing the amount of applied stress necessary to move a dislocation across a grain boundary. The higher the applied stress needed to move the dislocation, the higher the yield strength. Thus, there is then an inverse relationship between grain size and yield strength, as demonstrated by the Hall-Petch equation. However, when there is a large direction change in the orientation of the two adjacent grains, the dislocation may not necessarily move from one grain to the other but instead create a new source of dislocation in the adjacent grain. The theory remains the same that more grain boundaries create more opposition to dislocation movement and in turn strengthens the material. Obviously, there is a limit to this mode of strengthening, as infinitely strong materials do not exist. Grain sizes can range from about (large grains) to (small grains). Lower than this, the size of dislocations begins to approach the size of the grains. At a grain size of about , only one or two dislocations can fit inside a grain (see Figure 1 above). This scheme prohibits dislocation pile-up and instead results in grain boundary diffusion. The lattice resolves the applied stress by grain boundary sliding, resulting in a decrease in the material's yield strength. To understand the mechanism of grain boundary strengthening one must understand the nature of dislocation-dislocation interactions. Dislocations create a stress field around them given by: where G is the material's shear modulus, b is the Burgers vector, and r is the distance from the dislocation. If the dislocations are in the right alignment with respect to each other, the local stress fields they create will repel each other. This helps dislocation movement along grains and across grain boundaries. Hence, the more dislocations are present in a grain, the greater the stress field felt by a dislocation near a grain boundary: Interphase boundaries can also contribute to grain boundary strengthening, particularly in composite materials and precipitation-hardened alloys. Coherent IPBs, in particular, can provide additional barriers to dislocation motion, similar to grain boundaries. In contrast, non-coherent IPBs and partially coherent IPBs can act as sources of dislocations, which can lead to localized deformation and affect the mechanical properties of the material.

Metallurgy

Stainless steel is one of the most commonly used metals in many industries. Solid solution strengthening of steel is one of the mechanisms used to enhance the properties of the alloy. Austenitic steels mainly contain chromium, nickel, molybdenum, and manganese. It is being used mostly for cookware, kitchen equipment, and in marine applications for its good corrosion properties in saline environments.

Metallurgy

Iron technology was further advanced by several inventions in medieval Islam, during the Islamic Golden Age. These included a variety of water-powered and wind-powered industrial mills for metal production, including geared gristmills and forges. By the 11th century, every province throughout the Muslim world had these industrial mills in operation, from Islamic Spain and North Africa in the west to the Middle East and Central Asia in the east. There are also 10th-century references to cast iron, as well as archeological evidence of blast furnaces being used in the Ayyubid and Mamluk empires from the 11th century, thus suggesting a diffusion of Chinese metal technology to the Islamic world. Geared gristmills were invented by Muslim engineers, and were used for crushing metallic ores before extraction. Gristmills in the Islamic world were often made from both watermills and windmills. In order to adapt water wheels for gristmilling purposes, cams were used for raising and releasing trip hammers. The first forge driven by a hydropowered water mill rather than manual labour was invented in the 12th century Islamic Spain. One of the most famous steels produced in the medieval Near East was Damascus steel used for swordmaking, and mostly produced in Damascus, Syria, in the period from 900 to 1750. This was produced using the crucible steel method, based on the earlier Indian wootz steel. This process was adopted in the Middle East using locally produced steels. The exact process remains unknown, but it allowed carbides to precipitate out as micro particles arranged in sheets or bands within the body of a blade. Carbides are far harder than the surrounding low carbon steel, so swordsmiths could produce an edge that cut hard materials with the precipitated carbides, while the bands of softer steel let the sword as a whole remain tough and flexible. A team of researchers based at the Technical University of Dresden that uses X-rays and electron microscopy to examine Damascus steel discovered the presence of cementite nanowires and carbon nanotubes. Peter Paufler, a member of the Dresden team, says that these nanostructures give Damascus steel its distinctive properties and are a result of the forging process.

Metallurgy

Although freeze fracture studies have revealed that the nodal axolemma in both the CNS and PNS is enriched in intra-membranous particles (IMPs) compared to the internode, there are some structural differences reflecting their cellular constituents. In the PNS, specialized microvilli project from the outer collar of Schwann cells and come very close to nodal axolemma of large fibers. The projections of the Schwann cells are perpendicular to the node and are radiating from the central axons. However, in the CNS, one or more of the astrocytic processes come in close vicinity of the nodes. Researchers declare that these processes stem from multi-functional astrocytes, as opposed to from a population of astrocytes dedicated to contacting the node. On the other hand, in the PNS, the basal lamina that surrounds the Schwann cells is continuous across the node.

Gene expression + Signal Transduction

Bacterial recombination is a type of genetic recombination in bacteria characterized by DNA transfer from one organism called donor to another organism as recipient. This process occurs in three main ways: * Transformation, the uptake of exogenous DNA from the surrounding environment. * Transduction, the virus-mediated transfer of DNA between bacteria. * Conjugation, the transfer of DNA from one bacterium to another via cell-to-cell contact. The final result of conjugation, transduction, and/or transformation is the production of genetic recombinants, individuals that carry not only the genes they inherited from their parent cells but also the genes introduced to their genomes by conjugation, transduction, and/or transformation. Recombination in bacteria is ordinarily catalyzed by a RecA type of recombinase. These recombinases promote repair of DNA damages by homologous recombination. The ability to undergo natural transformation is present in at least 67 bacterial species. Natural transformation is common among pathogenic bacterial species. In some cases, the DNA repair capability provided by recombination during transformation facilitates survival of the infecting bacterial pathogen. Bacterial transformation is carried out by numerous interacting bacterial gene products.

Gene expression + Signal Transduction

Britannia metal was first produced in 1769 or 1770. James Vickers created it after purchasing the formula from a dying friend. It was originally known as "Vickers White Metal" when made under contract by the Sheffield manufacturers Ebenezer Hancock and Richard Jessop. In 1776 James Vickers took over the manufacturing himself and remained as owner until his death in 1809, when the company passed to his son John and son-in-law Elijah West. In 1836 the company was sold to John Vickers's nephew Ebenezer Stacey (the son of Hannah Vickers and John Stacey). After the development of electroplating with silver in 1846, Britannia metal was widely used as the base metal for silver-plated household goods and cutlery. The abbreviation EPBM on such items denotes "electroplated Britannia metal". Britannia metal was generally used as a cheaper alternative to electroplated nickel silver (EPNS) which is more durable. Until 2016, britannium was used to make the solid core of the Oscar statuettes. The 8½ lb (4 kg) statuettes were Britannia metal plated with gold. The awards have since changed to a bronze core. In his essay "A Nice Cup of Tea", writer George Orwell asserts that "britanniaware" teapots "produce inferior tea" when compared to chinaware.

Metallurgy

Other functions of coatings include: * Anti-fouling coatings * Anti-microbial coatings. * Anti-reflective coatings for example on spectacles. * Coatings that alter or have magnetic, electrical or electronic properties. * Flame retardant coatings. Flame-retardant materials and coatings are being developed that are phosphorus and bio-based. These include coatings with intumescent functionality. * Non-stick PTFE coated cooking pots/pans. * Optical coatings are available that alter optical properties of a material or object. * UV coatings

Metallurgy

The Mountain Pass Rare Earth Mine and Processing Facility, owned by MP Materials, is an open-pit mine of rare-earth elements on the south flank of the Clark Mountain Range in California, southwest of Las Vegas, Nevada. In 2020 the mine supplied 15.8% of the world's rare-earth production. It is the only rare-earth mining and processing facility in the United States. As of 2022, work is ongoing to restore processing capabilities for domestic light rare-earth elements (LREEs) and work has been funded by the United States Department of Defense to restore processing capabilities for heavy rare-earth metals (HREEs) to alleviate supply chain risk.

Metallurgy

There are a number of types of mechanical screening equipment that cause segregation. These types are based on the motion of the machine through its motor drive. *Circle-throw vibrating equipment - This type of equipment has an eccentric shaft that causes the frame of the shaker to lurch at a given angle. This lurching action literally throws the material forward and up. As the machine returns to its base state the material falls by gravity to physically lower level. This type of screening is used also in mining operations for large material with sizes that range from six inches to +20 mesh. *High frequency vibrating equipment - This type of equipment drives the screen cloth only. Unlike above the frame of the equipment is fixed and only the screen vibrates. However, this equipment is similar to the above such that it still throws material off of it and allows the particles to cascade down the screen cloth. These screens are for sizes smaller than 1/8 of an inch to +150 mesh. *Gyratory equipment - This type of equipment differs from the above two such that the machine gyrates in a circular motion at a near level plane at low angles. The drive is an eccentric gear box or eccentric weights. *Trommel screens - Does not require vibration. Instead, material is fed into a horizontal rotating drum with screen panels around the diameter of the drum.

Metallurgy

Let and be two graphs. Graph is a sub-graph of graph (written as ) if and . If and contains all of the edges with , then is an induced sub-graph of . We call and isomorphic (written as ), if there exists a bijection (one-to-one correspondence) with for all . The mapping is called an isomorphism between and . When and there exists an isomorphism between the sub-graph and a graph , this mapping represents an appearance of in . The number of appearances of graph in is called the frequency of in . A graph is called recurrent (or frequent) in when its frequency is above a predefined threshold or cut-off value. We use terms pattern and frequent sub-graph in this review interchangeably. There is an ensemble of random graphs corresponding to the null-model associated to . We should choose random graphs uniformly from and calculate the frequency for a particular frequent sub-graph in . If the frequency of in is higher than its arithmetic mean frequency in random graphs , where , we call this recurrent pattern significant and hence treat as a network motif for . For a small graph , the network , and a set of randomized networks , where , the Z-score of the frequency of is given by where and stand for the mean and standard deviation of the frequency in set , respectively. The larger the , the more significant is the sub-graph as a motif. Alternatively, another measurement in statistical hypothesis testing that can be considered in motif detection is the p-value, given as the probability of (as its null-hypothesis), where indicates the frequency of G in a randomized network. A sub-graph with p-value less than a threshold (commonly 0.01 or 0.05) will be treated as a significant pattern. The p'-value for the frequency of is defined as where indicates the number of randomized networks, is defined over an ensemble of randomized networks, and the Kronecker delta function is one if the condition holds. The concentration of a particular n-size sub-graph in network refers to the ratio of the sub-graph appearance in the network to the total n-size non-isomorphic sub-graphs' frequencies, which is formulated by where index is defined over the set of all non-isomorphic n-size graphs. Another statistical measurement is defined for evaluating network motifs, but it is rarely used in known algorithms. This measurement is introduced by Picard et al. in 2008 and used the Poisson distribution, rather than the Gaussian normal distribution that is implicitly being used above. In addition, three specific concepts of sub-graph frequency have been proposed. As the figure illustrates, the first frequency concept considers all matches of a graph in original network. This definition is similar to what we have introduced above. The second concept is defined as the maximum number of edge-disjoint instances of a given graph in original network. And finally, the frequency concept entails matches with disjoint edges and nodes. Therefore, the two concepts and restrict the usage of elements of the graph, and as can be inferred, the frequency of a sub-graph declines by imposing restrictions on network element usage. As a result, a network motif detection algorithm would pass over more candidate sub-graphs if we insist on frequency concepts and .

Gene expression + Signal Transduction

The following tests are commonly used for geometallurgical modeling: * Bond ball mill work index test * Modified or comparative Bond ball mill index * Bond rod mill work index and Bond low energy impact crushing work index * SAGDesign test * SMC test * JK drop-weight test * Point load index test * Sag Power Index test (SPI(R)) * MFT test * FKT, SKT, and SKT-WS tests

Metallurgy

Leishmania tarentolae (cannot infect mammals) expression systems allow stable and lasting production of proteins at high yield, in chemically defined media. Produced proteins exhibit fully eukaryotic post-translational modifications, including glycosylation and disulfide bond formation.

Gene expression + Signal Transduction

When purifying by electrolysis, an aqueous sulfate solution at 50 to 70 °C is typically used with a lead anode (corrosion products from which will not contaminate the cobalt oxy-hydroxide (CoOOH) electrolyte solution) and a stainless steel cathode which will allow for the easy removal of the deposited cobalt. Electro refining in a chloride or sulfate medium at −0.3 V will make a cathode coating of 99.98% cobalt.

Metallurgy

In canonical notch signaling, ligand proteins bind to the extracellular domain of the notch receptor and induce the cleavage and release of the intracellular domain into the cytoplasm. This subsequently interacts with other proteins, enters the nucleus, and regulates gene expression. In 2006, a non-canonical branch of the notch signaling pathway was discovered. Using cultures of mouse neural stem cells, notch activation was shown to lead to the phosphorylation of several kinases (PI3K, Akt, mTOR) and subsequent phosphorylation of the serine residue of STAT3 in the absence of any detectable phosphorylation of the tyrosine residue of STAT3, a modification that is widely studied in the context of cancer biology. Following this event, Hes3 mRNA was elevated within 30 minutes. Subsequently, the consequences of this pathway were studied.

Gene expression + Signal Transduction

The Wnt signaling pathways are critical in cell-cell signaling during normal development and embryogenesis and required for maintenance of adult tissue, therefore it is not difficult to understand why disruption in Wnt signaling pathways can promote human degenerative disease and cancer. The Wnt signaling pathways are complex, involving many different elements, and therefore have many targets for misregulation. Mutations that cause constitutive activation of the Wnt signaling pathway lead to tumor formation and cancer. Aberrant activation of the Wnt pathway can lead to increase cell proliferation. Current research is focused on the action of the Wnt signaling pathway the regulation of stem cell choice to proliferate and self renew. This action of Wnt signaling in the possible control and maintenance of stem cells, may provide a possible treatment in cancers exhibiting aberrant Wnt signaling.

Gene expression + Signal Transduction

* Borax – for brazing * Beeswax * Citric acid – for soldering copper/electronics * Tallow and lead * Paraffin wax * Palm oil * Zinc chloride ("killed spirits") * Zinc chloride and ammonium chloride * Olive oil and ammonium chloride – for iron * Rosin, tallow, olive oil, and zinc chloride – for aluminium * Cryolite (sodium hexafluoroaluminate) * Cryolite and phosphoric acid * Phosphoric acid and alcohol * Cryolite and barium chloride * Oleic acid * Lithium chloride * Magnesium chloride * Sodium chloride * Potassium chloride * Unslaked lime

Metallurgy

A rusticle is a formation of rust similar to an icicle or stalactite in appearance that occurs deep underwater when iron-loving bacteria attack and oxidize wrought iron and steel. They may be familiar from underwater photographs of shipwrecks, such as the RMS Titanic and the German battleship Bismarck. They have also been found in the #3 turret, 8-inch gun turret on the stern remains in place of the USS Indianapolis. Rusticles are created by microbial organisms that consume iron. The word rusticle is a portmanteau of the words rust and icicle and was coined by Robert Ballard, who first observed them on the wreck of the Titanic in 1986. Rusticles on the Titanic were first investigated in 1996 by Roy Cullimore, based at the University of Regina in Canada. A previously unknown species of bacteria living inside the Titanics rusticles called Halomonas titanicae was discovered in 2010 by Henrietta Mann. Rusticles can form on any submerged steel object and have been seen on other subsea structures such as mooring chains and subsea equipment. They form more rapidly in warmer climates and can form in water with little to no dissolved oxygen.

Metallurgy