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[ "Critics say the tempest is an illustration of all that's wrong with selecting judges in Cook County — where cash and political connections at times carry more weight than temperament and ability. ", "Daley Center judges say traffic court is the best place for a new judge to learn how to manage a courtroom, master a new area of law and do their job in a setting where the possible damage they can inflict is relatively minimal." ]

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[ "Introduction\n============\n\nMembers of the transforming growth factor-β (TGF-β)[\\*](#fn1){ref-type=\"fn\"} superfamily are multifunctional cytokines that regulate growth, differentiation, motility, adhesion, and morphogenesis of various types of cells ([@bib32]; [@bib22]). ", "The TGF-β superfamily includes TGF-βs, activins, bone morphogenetic proteins (BMPs), growth/differentiation factors, and Müllerian inhibiting substance. ", "Cytokines of the TGF-β superfamily bind to two different types of serine/threonine kinase receptors termed types II and I, and transmit intracellular signals by Smad proteins ([@bib13]; [@bib23]; [@bib25]). ", "Of the three different subtypes of Smads, receptor-regulated Smads (R-Smads) are directly phosphorylated by type I serine/threonine kinase receptors, and form oligomeric complexes with common mediator Smads (Co-Smads). ", "The R-Smad--Co-Smad complexes then translocate into the nucleus, where they regulate the transcription of target genes.", "\n\nThe third class of Smads comprises the inhibitory Smads (I-Smads), which include Smad6 and Smad7 in mammals and Daughters against Decapentaplegic in *Drosophila*. ", "Expression of I-Smads is induced by various stimuli, e.g., TGF-β and BMPs ([@bib24]). ", "Smad2 and Smad3, activated by TGF-β, and Smad1 and Smad5, activated by BMPs, bind to the promoter regions and induce the transcription of *Smad7* and *Smad6* genes, respectively ([@bib26]; [@bib4]; [@bib16]). ", "Daughters against Decapentaplegic is also induced by Decapentaplegic signaling ([@bib35]). ", "Thus, I-Smads act as components in negative feedback regulation in the Smad signaling pathways. ", "I-Smads stably bind to activated type I receptors, and compete with R-Smads for receptor activation ([@bib12]; [@bib14]; [@bib27]; [@bib33]). ", "In addition, Smad7, and possibly Smad6, recruit E3 ubiquitin ligases Smurf1 and Smurf2 to type I receptors, leading to ubiquitin-dependent degradation of the TGF-β receptor complexes ([@bib19]; [@bib5]). ", "Smad6 has also been reported to form a complex with Smad1, and to compete with Smad4 for oligomer formation ([@bib11]). ", "Moreover, Smad6 has been shown to bind certain transcription factors and repress transcription in the nucleus ([@bib1]).", "\n\nR-Smads and Co-Smads have highly conserved amino- and carboxy-terminal regions termed Mad homology 1 (MH1) and MH2 domains, respectively, that are linked by linker regions of variable length and sequence. ", "I-Smads have conserved MH2 domains, but their amino-terminal domains (N domains) are highly divergent from the MH1 domains and linker regions of other Smads. ", "Moreover, amino acid sequences of the N domains are only partially conserved between the I-Smads (36.7% between Smad6 and Smad7). ", "Notably, Smad6 and Smad7 have been identified in *Xenopus*, but their N domains are only 51.3 and 67.4% identical to their mammalian homologues, respectively ([@bib29],[@bib30]).", "\n\nAlthough I-Smads inhibit signaling by members of the TGF-β superfamily, significant differences have been observed in their biological activities. ", "BMP signaling is antagonized by both Smad6 and Smad7 ([@bib11]; [@bib7]; [@bib17]), whereas Smad7 is more potent than Smad6 in repressing TGF-β and activin signaling. ", "Thus, Smad7 has been reported to antagonize the growth inhibition, matrix formation, apoptosis induction, and embryonic lung morphogenesis induced by TGF-β or activin ([@bib18]; [@bib17]; [@bib36]). ", "Moreover, bleomycin-induced lung fibrosis, which is mediated by endogenous production of TGF-β, is prevented by the administration of adenovirus containing Smad7, but not Smad6 ([@bib28]).", "\n\nTo elucidate the functional differences between Smad7 and Smad6 in the repression of TGF-β signaling and to determine how Smad7 efficiently inhibits this signaling, we examined the activities of deletion mutants and chimeras of Smad6 and Smad7. ", "Our present findings revealed that the carboxy-terminal MH2 domains of Smad6 and Smad7 are essential for the inhibition of TGF-β and BMP signaling, and the N domain of Smad7 is required for efficient inhibition of TGF-β signaling by Smad7. ", "We also found that the N domains determine the subcellular localization of I-Smads. ", "Physical interaction of Smad7 with TGF-β type I receptor (TβR-I) was found to be one of the most important mechanisms for inhibiting TGF-β signaling. ", "Intriguingly, the isolated N domain of Smad7 physically interacted with the Smad7 MH2 domain, and enhanced the inhibitory activity of the latter through facilitating its interaction with TβR-I.\n\nResults\n=======\n\nSmad7 is more potent than Smad6 in inhibiting TGF-β signaling\n-------------------------------------------------------------\n\nWe examined the inhibition by I-Smads of TGF-β and BMP signaling using transcriptional response assays. ", "We compared the activities of Smad6 and Smad7 using two different promoter--reporter constructs, p3TP--Lux and AR3--Luc, which preferentially respond to TGF-β/activin signaling. ", "Two different types of cells, i.e., R mutant Mv1Lu mink lung epithelial cells and COS7 cells, were used for the transcriptional assays. ", "Smad7 potently inhibited the transcriptional activation of p3TP--Lux induced by a constitutively active form of TβR-I, TβR-I(TD), in both R mutant cells and COS7 cells ([Fig. ", "1](#fig1){ref-type=\"fig\"} A). ", "In contrast, Smad6 was less potent than Smad7 in inhibiting the transcriptional activation induced by TβR-I(TD). ", "Similar results were obtained using the AR3--Luc promoter--reporter construct ([Fig. ", "1](#fig1){ref-type=\"fig\"} B), which contains the promoter region of *Xenopus Mix.2* and responds to TGF-β/activin signaling in the presence of a forkhead transcription factor, FAST1/FoxH3.", "\n\n{#fig1}\n\nTranscriptional repression by I-Smads was determined using 3GC2--Lux activated by a constitutively active BMP type I receptor (BMPR-I), ALK-6(QD). ", "In contrast to their differential effects on the inhibition of TGF-β signaling, both Smad6 and Smad7 inhibited BMP signaling induced by ALK-6(QD). ", "Another BMP-responsive luciferase construct, Tlx2--Lux, was also tested to examine the effects of I-Smads on BMP signaling. ", "Again, Smad6 and Smad7 were nearly equal in their inhibition of BMP signaling induced by ALK-6(QD) ([Fig. ", "1](#fig1){ref-type=\"fig\"} D). ", "Thus, Smad7 is more potent than Smad6 in inhibiting TGF-β signaling, whereas Smad6 and Smad7 were functionally equivalent in inhibiting BMP signaling.", "\n\nThe N domain of Smad7 is important for the inhibition of TGF-β signaling\n------------------------------------------------------------------------\n\nWe next examined which parts of Smad7 are responsible for the inhibition of TGF-β signaling. ", "We prepared deletion mutants of Smad6 and Smad7 ([Fig. ", "2](#fig2){ref-type=\"fig\"} A). ", "Smad6N and Smad7N have only the N domains of Smad6 and Smad7, respectively, whereas Smad6C and Smad7C contain their MH2 domains. ", "We also generated a chimeric molecule containing the N domain of Smad6 and the MH2 domain of Smad7 (Smad6/7), and one containing the Smad7 N domain and the Smad6 MH2 domain (Smad7/6).", "\n\n{#fig2}\n\nThe isolated N domains of Smad6 and Smad7 (Smad6N and Smad7N) were unable to repress TGF-β signaling induced by TβR-I(TD) ([Fig. ", "2](#fig2){ref-type=\"fig\"} B). ", "In contrast, the MH2 domains of Smad6 and Smad7 (Smad6C and Smad7C) repressed the transcriptional activity of TβR-I(TD) to extents similar to that induced by the full-length Smad6, but were less potent than the full-length Smad7. ", "Thus, the MH2 domains of Smad6 and Smad7 are essential for repression of TGF-β signaling, but are not sufficient for the efficient transcriptional repression observed with Smad7.", "\n\nWe also examined the two different Smad6 and Smad7 chimeras, i.e., Smad6/7 and Smad7/6. ", "Smad7/6 was as potent as Smad7, whereas Smad6/7 was functionally similar to Smad6 in the inhibition of TGF-β signaling ([Fig. ", "2](#fig2){ref-type=\"fig\"} B). ", "Thus, the N domain of Smad7 is important for the efficient transcriptional repression induced by Smad7.", "\n\nInhibition by Smad6 and Smad7 of BMP signaling was also studied using the 3GC2--Lux promoter--reporter construct. ", "The N domains of Smad6 and Smad7 were not effective in inhibiting BMP signaling ([Fig. ", "2](#fig2){ref-type=\"fig\"} C). ", "Smad6C and Smad7C were nearly as potent as the full-length Smad6 and Smad7, suggesting that the MH2 domains may be sufficient for repression of BMP signaling. ", "This finding was further confirmed by the observation that the Smad6 and Smad7 chimeras, Smad6/7 and Smad7/6, potently inhibited the signaling activity of the BMPR-I.\n\nMultiple parts of the Smad7 N domain may be responsible for specific inhibition of TGF-β signaling\n--------------------------------------------------------------------------------------------------\n\nTo determine which parts of the N domain of Smad7 are essential for efficient inhibition of TGF-β signaling, we constructed Smad7 chimeras in which the amino-terminal regions were replaced by the corresponding regions of Smad6 ([Fig. ", "3](#fig3){ref-type=\"fig\"} A). ", "In the N domain of Smad7, the most amino-terminal region (amino acids 1--17) and the region adjacent to the MH2 domain (amino acids 192--213) are highly conserved between Smad6 and Smad7, whereas the other regions are less conserved. ", "Functional analyses of the Smad7 chimeras by p3TP--Lux and AR3--Luc assays revealed that depending on the length of the N domain of Smad7 replaced by that of Smad6, the inhibitory activity of Smad7 became gradually less potent ([Fig. ", "3, B and C](#fig3){ref-type=\"fig\"}). ", "A significant difference in the inhibition of TGF-β signaling was observed in AR3--Luc when amino acids 32--90 of Smad7 were replaced by the corresponding region of Smad6. ", "The amino acid sequence of this Smad7 region is divergent from that of Smad6. ", "These findings suggest that multiple parts of the Smad7 N domain may contribute to specific inhibition of TGF-β signaling, and that the region containing amino acids 32--90 is one of the most important regions in the Smad7 N domain for repressing TGF-β signaling.", "\n\n{#fig3}\n\nN domains determine subcellular localization of I-Smads\n-------------------------------------------------------\n\nSmad7 has been reported to be located in the nuclei of COS7 cells ([@bib18]). ", "Moreover, Smad7 is exported to the cytoplasm upon stimulation by TGF-β ([@bib18]), as well as by E3 ubiquitin ligases Smurf1 and Smurf2 ([@bib19]; [@bib5]). ", "We examined which parts of I-Smads determine their subcellular localization. ", "As reported previously ([@bib18]; [@bib19]; [@bib5]), Smad7 was predominantly located in the nuclei of transfected COS7 cells, whereas Smad6 was observed in the nuclei as well as in the cytoplasm ([Fig. ", "4](#fig4){ref-type=\"fig\"} A). ", "The cytoplasmic staining of Smad6 was observed as a dotted pattern. ", "In contrast, Smad6C and Smad7C were detected in the nucleus (unpublished data; see [Fig. ", "8, C and D](#fig8){ref-type=\"fig\"}) . ", "The subcellular localization of the Smad7 chimeras depended on their amino-terminal regions. ", "Thus, S6(31/32)S7 and S6(171/91)S7 were detected in the nucleus, similar to Smad7, whereas S6(225/158)S7 and S6(279/211)S7 were detected as cytoplasmic dotted patterns. ", "These results indicate that the region containing amino acids 91--157 of Smad7 plays an important role in determining the subcellular localization of Smad7 in COS7 cells.", "\n\n###### \n\n**Subcellular localization of I-Smads.** ", "Subcellular localization of Smad6, Smad7, and their chimeras was determined in transfected COS7 (A) or HepG2 cells (B). ", "FLAG-tagged I-Smads were transfected in cells and the subcellular localization of I-Smads was demonstrated by FITC. ", "Nuclear staining was performed by 4,6-diamidino-2-phenylindole (PI).", "\n\n![](", "0106023f4a)\n\n![](", "0106023f4b)\n\n###### \n\n**Physical interaction of Smad7N leads to nuclear export and enhancement of the inhibitory activity of Smad7C.** (A) Enhancement of the inhibitory activity of Smad7C by Smad7N. Effects of Smad6N and Smad7N were examined in the presence of their MH2 domains (Smad6C and Smad7C) by a p3TP--Lux transcription assay induced by TβR-I(TD). ", "+ and ++ are 0.1 and 0.3 μg of DNA, respectively, transfected in R mutant cells. (", "B) Physical interaction between Smad7N and the MH2 domains of Smad7 (7C), Smad3 (3C), and Smad1 (1C). ", "Interaction of Smad7N with the full-length Smad7 (7) was also tested. ", "Interaction was examined by FLAG immunoprecipitation of FLAG--Smads, followed by Myc immunoblotting of Smad7N using transfected COS7 cells (top). ", "Expression levels of transfected proteins were determined and are shown in the lower two panels. (", "C and D) Subcellular localization of Smad7C in the presence and absence of Smad7N was examined in transfected HepG2 (C) or COS7 cells (D) using confocal laser scanning microscopy. ", "FLAG--Smad7C was stained by anti-FLAG antibody in the absence and presence of Smad7N and Smurf1(CA), and its subcellular localization was demonstrated by FITC. ", "In HepG2 cells, 6Myc--Smad7N was stained by rhodamine isothiocyanate (RITC; C, bottom). (", "E) Affinity cross-linking of ^125^I--TGF-β1 was performed using transfected COS7 cells followed by FLAG immunoprecipitation of FLAG--I-Smads (upper). ", "The lower two panels demonstrate the levels of expression of transfected proteins.", "\n\n![](", "0106023f8ab)\n\n![](", "0106023f8cd)\n\n![](", "0106023f8e)\n\nWe also examined the subcellular localization of Smad6, Smad7, and their chimeras in other cell types. ", "In contrast to the findings obtained with COS7 cells, Smad7 was predominantly located in the cytoplasm, whereas Smad6 was detected in both the cytoplasm and the nucleus in HepG2 cells ([Fig. ", "4](#fig4){ref-type=\"fig\"} B). ", "Subcellular localization of the Smad6 and Smad7 chimeras in HepG2 cells also revealed that the localization of I-Smads depended on the amino-terminal region of Smad6 and Smad7, although the chimeras exhibited complicated localization patterns. ", "S6(31/32)S7 and S6(225/158)S7 were detected in the cytoplasm, similar to the full-length Smad7, whereas S6(171/91)S7 and S6(279/211)S7 were in both the nucleus and the cytoplasm. ", "Similar results were obtained when R mutant Mv1Lu cells were used (unpublished data). ", "Thus, the localization of Smad7 in HepG2 and R mutant Mv1Lu cells is different from that in COS7 cells, and multiple parts of the Smad7 N domain appear to determine the subcellular localization of Smad7 in these cells. ", "However, subcellular localization may not primarily determine the potency of Smad7 in inhibiting TGF-β signaling, because the changes in subcellular localization observed with the Smad6 and Smad7 chimeras did not necessarily correlate with the inhibitory activity of Smad7 on TGF-β signaling.", "\n\nSmurf1 induces nuclear export of both Smad6 and Smad7\n-----------------------------------------------------\n\nSmurf1 induces the nuclear export of Smad7 through an interaction with the Smad7 PY motif, and induces ubiquitin-dependent degradation of Smad7 and TβR-I. The nuclear export of Smad7 is not dependent on the enzymatic activity of Smurf1, as an enzymatically inactive form of Smurf1, Smurf1(CA), induces the nuclear export of Smad7 ([@bib5]). ", "We examined whether Smurf1 regulates the subcellular localization of Smad6, Smad7, and their mutants. ", "Smurf1(CA) induced cytoplasmic localization of Smad6 and Smad7 in both COS7 cells and HepG2 cells ([Fig. ", "5, A and B](#fig5){ref-type=\"fig\"}) . ", "However, Smad6C and Smad7C, which lack the PY motif, were not exported to the cytoplasm by Smurf1(CA) ([Fig. ", "5](#fig5){ref-type=\"fig\"} C).", "\n\n###### \n\n**Smurf1 induces nuclear export of Smad6 and Smad7.** (", "A--C) The nuclear export of Smad6, Smad7, and their deletion mutants (Smad6C and Smad7C) induced by Smurf1(CA) was examined in COS7 (A) or HepG2 cells (B and C) as in [Fig. ", "4](#fig4){ref-type=\"fig\"}. (", "D) The effects of Smad7 amino-terminal deletion mutants on p3TP--Lux transcription induced by TβR-I(TD) were examined. ", "+ and ++ are 0.3 and 1.0 μg of DNA, respectively, transfected in R mutant cells. ", "PPPY represents the PY motif.", "\n\n![](", "0106023f5ac)\n\n![](", "0106023f5d)\n\nFunctional importance of the I-Smad PY motif was examined by a p3TP--Lux assay. ", "S7Δ191, which lacks the amino-terminal 191 amino acids of Smad7, is less potent than the full-length Smad7 in inhibiting TGF-β signaling. ", "Further deletion including the PY motif of Smad7 (S7Δ210) resulted in a dramatic decrease in the inhibition of TGF-β signaling ([Fig. ", "5](#fig5){ref-type=\"fig\"} D). ", "In contrast, S6(279/211)S7 was not so weak as S7Δ210 in inhibiting TGF-β signaling ([Fig. ", "3](#fig3){ref-type=\"fig\"} B), probably because S6(279/211)S7 contains the PY motif of Smad6. ", "These findings suggest that in agreement with a previous report ([@bib5]), the PY motif is required for the nuclear export of I-Smads and the degradation of TβR-I, and the absence of the PY motif leads to a decrease in the inhibition of TGF-β signaling by I-Smads. ", "However, because Smurf1 can interact with Smad6 and Smad7, the interaction of I-Smads with Smurf1 may not be responsible for the differential activity of Smad6 and Smad7.", "\n\nRepression of Smad2 phosphorylation by I-Smads correlates with their inhibition of transcription induced by TβR-I(TD)\n---------------------------------------------------------------------------------------------------------------------\n\nThe abilities of the deletion mutants and chimeras of Smad6 and Smad7 to inhibit Smad2 phosphorylation were examined in transfected COS7 cells. ", "Consistent with the results obtained with transcriptional activation assays ([Fig. ", "2](#fig2){ref-type=\"fig\"} B), phosphorylation of Smad2 was abolished by Smad7 and Smad7/6 ([Fig. ", "6](#fig6){ref-type=\"fig\"}) . ", "Smad6, Smad6/7, Smad6C, and Smad7C were less potent in inhibiting Smad2 phosphorylation. ", "As expected, the N domains of Smad6 and Smad7 did not affect the phosphorylation of Smad2. ", "I-Smads have been reported to regulate TGF-β/BMP signaling through various mechanisms, i.e., competition with R-Smads for receptor activation, ubiquitin-dependent degradation of receptors by Smurfs, prevention of complex formation between R-Smads and Co-Smads, and transcriptional repression in the nucleus. ", "Because the levels of Smad2 phosphorylation correlate with the repression of p3TP--Lux transcription by the I-Smad mutants, Smad7 might regulate TGF-β signaling mainly at the receptor level through competition with R-Smads for receptor activation and degradation by Smurfs.", "\n\n{#fig6}\n\nThe N domain of Smad7 determines the affinity of Smad7 for TβR-I\n----------------------------------------------------------------\n\nBecause the interaction between I-Smads and TβR-I appears to be one of the most critical mechanisms in the efficient inhibition of TGF-β signaling, we explored the physical interaction of I-Smads and their mutants with TβR-I. We first examined the interaction between I-Smad constructs with the TβR-I and TβR-II receptor complex cross-linked with ^125^I--TGF-β1. [", "Fig. ", "7](#fig7){ref-type=\"fig\"} A demonstrates that the TβR-II--TβR-I complex was efficiently coimmunoprecipitated by full-length Smad7 and Smad7/6. ", "In contrast, Smad6C and Smad7C weakly interacted with the TGF-β receptor complexes, and the full-length Smad6 and Smad6/7 did so only very weakly. ", "The receptor complexes were not coimmunoprecipitated by the N domains of Smad6 or Smad7. ", "This finding is consistent with those obtained with the transcriptional assays ([Fig. ", "2](#fig2){ref-type=\"fig\"} B), indicating that the direct association of I-Smads with TGF-β receptor complexes is an important mechanism in the inhibition of TGF-β signaling.", "\n\n###### \n\n**Physical interaction of Smads with TGF-**β **receptors.** (", "A) Affinity cross-linking using ^125^I--TGF-β1 followed by immunoprecipitation by anti-FLAG antibody was performed using COS7 cells transfected with the indicated plasmids (top). ", "Levels of expression of I-Smads and their mutants and chimeras were examined by immunoblotting using anti-FLAG antibody (bottom). (", "B) Interaction of I-Smads with TβR-I(TD) was examined by FLAG immunoprecipitation of I-Smads, followed by HA-immunoblotting of TβR-I(TD) using transfected COS7 cells (top). ", "The Smad6 and Smad7 chimeras shown in [Fig. ", "3](#fig3){ref-type=\"fig\"} A were used. ", "6(32), S6(31/32)S7; 6(91), S6(171/91)S7; 6(158), S6(225/158); 6(211), S6(279/211)S7. ", "Note that HA-tagged TβR-I(TD) was comigrated with IgG. Lower panels demonstrate the levels of expression of I-Smads (middle) and TβR-I(TD) (bottom).", "\n\n![](", "0106023f7a)\n\n![](", "0106023f7b)\n\nAs TβR-I acts as a downstream component of TβR-II, we next investigated whether I-Smads and their mutants physically interact with the constitutively active form of TβR-I. Immunoprecipitation of the I-Smad constructs followed by immunoblotting of TβR-I(TD) revealed that the full-length Smad7 and Smad7/6 bound to TβR-I(TD) strongly, whereas Smad6 and Smad6/7 did so only weakly ([Fig. ", "7](#fig7){ref-type=\"fig\"} B). ", "Of the chimeras between Smad6 and Smad7, S6(31/32)S7 bound to TβR-I(TD) strongly. ", "However, the other chimeras bound to TβR-I(TD) less strongly, depending on the lengths of the N domain of Smad7, and their binding affinity correlated with their potency in inhibiting TGF-β signaling, analyzed by transcriptional assays ([Fig. ", "3](#fig3){ref-type=\"fig\"}). ", "When the interaction of the I-Smad chimeras with a constitutively active BMPR-I, ALK-6(QD), was examined by immunoprecipitation followed by immunoblotting, we observed no differences in affinity with ALK-6(QD) among the I-Smad chimeras (unpublished data).", "\n\nThe N domain of Smad7 potentiates the inhibitory activity of its MH2 domain through physical interaction\n--------------------------------------------------------------------------------------------------------\n\nTo elucidate the mechanism by which the N domain of Smad7 represses TGF-β signaling, we cotransfected Smad7N with Smad7C, and examined the inhibition of TGF-β signaling by p3TP--Lux assays. ", "Although Smad7N alone was unable to inhibit TGF-β signaling, cotransfection of Smad7N with Smad7C led to potent inhibition ([Fig. ", "8](#fig8){ref-type=\"fig\"} A). ", "In contrast, cotransfection of Smad6N with Smad6C ([Fig. ", "8](#fig8){ref-type=\"fig\"} A) or Smad7C (unpublished data) did not significantly induce further inhibition of TGF-β signaling compared with transfection of Smad6C alone. ", "When Smad7N was cotransfected with the MH2 domain of Smad3, it did not modulate the transcriptional activity of the latter (unpublished data). ", "These results indicate that the N domain of Smad7 potentiates the inhibitory activity of its MH2 domain in trans.", "\n\nWe next examined whether Smad7N can physically interact with the MH2 domains of Smads. ", "As shown in [Fig. ", "8](#fig8){ref-type=\"fig\"} B, Smad7N was able to interact with Smad7C. Smad7N also interacted with Smad6C (unpublished data), but failed to associate with the MH2 domains of Smad3 or Smad1 ([Fig. ", "8](#fig8){ref-type=\"fig\"} B). ", "We also tested the interaction of Smad6N with the MH2 domains of I-Smads. ", "Smad6N weakly interacted with Smad6C, but not with Smad7C (unpublished data).", "\n\nWe examined the localization of Smad7C in the presence and absence of Smad7N in HepG2 and COS7 cells. ", "In HepG2 cells, Smad7 was detected in the cytoplasm ([Fig. ", "4](#fig4){ref-type=\"fig\"} B), whereas Smad7C was detected in the nucleus ([Fig. ", "8](#fig8){ref-type=\"fig\"} C). ", "However, when Smad7N was cotransfected, Smad7C was observed in the cytoplasm ([Fig. ", "8](#fig8){ref-type=\"fig\"} C). ", "Moreover, Smad7C and Smad7N were colocalized in HepG2 cells, consistent with the observation that they physically interact with each other. ", "In COS7 cells, Smad7 and Smad7C were detected in the nucleus ([Figs. ", "8](#fig8){ref-type=\"fig\"} D and 4 A). ", "Co-transfection of either Smurf1(CA) or Smad7N did not induce the nuclear export of Smad7C. However, Smad7C was detected in the cytoplasm in the presence of both Smad7N and Smurf1(CA) ([Fig. ", "8](#fig8){ref-type=\"fig\"} D).", "\n\nWe then studied the interaction of Smad7C with the TGF-β receptors in the presence and absence of Smad7N by affinity cross-linking, followed by immunoprecipitation of FLAG--Smads. ", "Smad7C weakly interacted with the TGF-β receptor complex, whereas Smad7N alone failed to do so, as shown in [Fig. ", "7](#fig7){ref-type=\"fig\"} A. However, strong interaction between Smad7C and the TGF-β receptor complex was detected in the presence of Smad7N ([Fig. ", "8](#fig8){ref-type=\"fig\"} E). ", "Smurf1 facilitates the interaction of Smad7 with TGF-β receptors by targeting Smad7 to the plasma membrane (unpublished data). ", "In the presence of Smurf1, Smad7C efficiently interacted with TGF-β receptors when cotransfected with Smad7N ([Fig. ", "8](#fig8){ref-type=\"fig\"} E). ", "By immunoprecipitation of Smad7N, the TGF-β receptor complex was weakly coimmunoprecipitated in the presence of Smurf1 and Smad7C, suggesting that Smad7N interacts with these receptors indirectly through Smad7C. These findings suggest that Smad7N physically interacts with Smad7C, leading to an increase in the affinity between Smad7C and the TGF-β receptors.", "\n\nDiscussion\n==========\n\nThe N domain of Smad7 is important for repressing TGF-β signaling\n-----------------------------------------------------------------\n\nWe have shown in the present study that Smad7 is more potent than Smad6 in inhibiting TGF-β signaling, whereas Smad6 and Smad7 are functionally similar in repressing BMP signaling. ", "Analyses by p3TP--Lux and AR3--Luc assays revealed that the N domain of Smad7 plays an important role in efficient inhibition of TGF-β signaling. ", "Although multiple regions of the N domain of Smad7 appeared to contribute to the repression of TGF-β signaling, the transcriptional assay using AR3--Luc and the interaction of the I-Smad chimeras with TβR-I(TD) suggested that the region containing amino acids 31--90 of Smad7 is one of the most important regions for the efficient inhibition of TGF-β signaling.", "\n\nThe N domains of Smad6 and Smad7 have thus far been poorly investigated. ", "The amino acid sequences of the N domains are not highly conserved between Smad6 and Smad7 (36.7%). ", "However, certain regions, e.g., the most amino-terminal part (amino acids 1--17) and a region adjacent to the MH2 domain (amino acids 192--213), are relatively well conserved. ", "The region adjacent to the MH2 domain contains a PY motif that is important for interacting with the E3 ubiquitin-ligases Smurf1 and Smurf2 ([@bib19]; [@bib5]).", "\n\nThe present findings obtained using Smad chimeras appear to be inconsistent with those described in a recent study using *Xenopus* assays ([@bib31]). ", "However, the Smad6/7 chimera used by [@bib31] contains the amino acids 1--154 of Smad6 and 182--382 of Smad7, which is similar to the S6(225/158)S7 chimera in the present study. ", "It will be interesting to examine whether replacing the rest of the N domain of Smad7 with that of Smad6 results in an alteration of the inhibitory activity of Smad6/7 chimeras in *Xenopus* assays.", "\n\nSubcellular localization of I-Smads\n-----------------------------------\n\nLocalization in cells is differentially regulated between Smad6 and Smad7. ", "Smad7 has been reported to be located in the nucleus of transfected COS7 cells ([@bib18]), whereas Smad6 is distributed in both the nucleus and the cytoplasm. ", "Intriguingly, we found that Smad7 was predominantly located in the cytoplasm in HepG2 cells and R mutant Mv1Lu cells, although the reason for the difference in localization of Smad7 between these cell types is unknown. ", "TβR-I(TD) has been shown to induce nuclear export of Smad7 ([@bib18]), but not of Smad6; however, in the present study we were unable to clearly induce the nuclear export of Smad7 by TβR-I(TD) (unpublished data).", "\n\nWe also found that Smurf1 induces nuclear export of Smad6 and Smad7, whereas Smad6C and Smad7C, which lack the ability to interact with Smurf1, were not exported to the cytoplasm even in the presence of Smurf1. ", "These findings suggest that the weak inhibitory activity of Smad6C and Smad7C may be, at least in part, due to their lack of interaction with Smurfs. ", "However, as the PY motif is present in both Smad6 and Smad7, and Smurf1 can interact equally well with both of them ([@bib5]), this region may not solely account for the functional difference between these I-Smads.", "\n\nAnalyses using Smad6 and Smad7 chimeras revealed that various regions of Smad7 play roles in the subcellular localization of Smad7. ", "Intriguingly, Smad7 is differentially located in either the cytoplasm or the nucleus depending on cell type. ", "It is possible that proteins expressed in only certain types of cells may specifically interact with Smad7 through various regions in the N domain, and thereby induce its nuclear export or import. ", "Although subcellular localization differs between S6(171/91)S7 and S6(225/158)S7 in COS7 cells and between S6(171/91)S7, S6(225/158)S7, and S6(279/211)S7 in HepG2 and R mutant Mv1Lu cells, inhibition of TGF-β signaling differed only slightly between these chimeras. ", "Thus, subcellular localization of I-Smads might not be the major determinant of the differential effects on the inhibition of TGF-β signaling, and other mechanisms may also play important roles in their inhibitory signaling.", "\n\nInteraction of I-Smads with TβR-I\n---------------------------------\n\nAs levels of Smad2 phosphorylation correlated very well with the inhibitory activity of the I-Smad chimeras, mechanisms mediated upstream of Smad2 phosphorylation, i.e., interaction of I-Smads with type I receptors and ubiquitin-dependent degradation of these receptors, may play important roles in the specific inhibition of TGF-β signaling. ", "By replacing parts of the N domain of Smad7 with the corresponding regions of Smad6, we found that depending on the lengths of the N domain of Smad7, the I-Smad chimeras interacted with TβR-I less efficiently, and their inhibitory activities became less potent. ", "Intriguingly, a significant decrease in the interaction between the I-Smad chimeras and TβR-I(TD) was observed when amino acids 31--90 of Smad7 were replaced, suggesting that this region may be one of the important regions for efficient inhibition of TGF-β signaling by Smad7.", "\n\nThe L45 loop of type I serine/threonine kinase receptors directly interacts with the L3 loop in the MH2 domains of R-Smads, and determines the specificity of inhibitory signals ([@bib3]; [@bib21]). ", "The L45 loops of TβR-I and activin type IB receptor/ALK-4 interact with and activate Smad2 and Smad3, whereas the BMPR-I L45 loops bind to Smad1 and Smad5. ", "The L45 loop of type I receptors may also interact with the L3 loops of I-Smads. ", "However, the amino acid sequences of the L3 loops of I-Smads are divergent from those of R-Smads. ", "Thus, the L3 loops of Smad6 and Smad7 may have low affinity interactions with TβR-I, and the N domain of Smad7, but not Smad6, is required for efficient interaction. ", "In contrast, interaction of ALK-6 with the MH2 domains of Smad6 and Smad7 might occur with high affinity. ", "Thus, the N domain of Smad6 or Smad7 does not appear to be required for the inhibition of BMP signaling. ", "It will be important to determine the modes of interaction between type I receptors and I-Smads by three-dimensional analysis.", "\n\nPhysical interaction between the N and MH2 domains of Smad7\n-----------------------------------------------------------\n\nInterestingly, Smad7N alone did not inhibit TGF-β signaling, but Smad7N and Smad7C together potently repressed it, as reported by [@bib31]. ", "We showed in the present study that Smad7N physically interacts with its MH2 domain, and suggested that its ability to do so is important for its inhibition of TGF-β signaling. ", "Smad7N induced the nuclear export of Smad7C in HepG2 cells. ", "In COS7 cells, Smad7N required Smurf1 for the nuclear export of Smad7C. Finally, we demonstrated that Smad7N enhances the interaction of Smad7C with the TGF-β receptor complex. ", "Thus, Smad7N has the ability to physically interact with Smad7C, which might result in a conformational change of the MH2 domain and enhancement of its affinity for the receptor complex.", "\n\nThe amino-terminal MH1 domains of R-Smads have been shown to physically interact with their MH2 domains ([@bib10]). ", "However, the MH1 domains of R-Smads repress the activity of their MH2 domains through physical interaction, and this interaction is released upon receptor activation and phosphorylation of R-Smads. ", "In contrast, the N domain of Smad7 physically interacts with the MH2 domain, resulting in enhancement of the inhibitory activity of Smad7 through facilitation of the interaction with TGF-β receptors ([Fig. ", "9](#fig9){ref-type=\"fig\"}) . ", "Our present study also revealed that Smad7N specifically interacts with the MH2 domains of I-Smads, but not with those of R-Smads. ", "Thus, the present findings suggest a new mode of action for the Smad7 N domain in supporting the inhibitory activity of the MH2 domain in TGF-β signaling.", "\n\n{#fig9}\n\nMaterials and methods\n=====================\n\nConstruction of plasmids\n------------------------\n\nThe original constructions of constitutively active forms of TβR-I and ALK-6 (TβR-I\\[TD\\] and ALK-6\\[QD\\], respectively), TβR-II, BMPR-II, Smad1, Smad2, Smad3, Smad6, Smad7, Smurf1(CA), and FAST1/FoxH3 cDNAs were created as previously described ([@bib14]; [@bib20]; [@bib9]; [@bib5]). ", "FLAG--pcDNA3, 6Myc--pcDNA3, and pcDNA3--HA were created as described previously ([@bib15]; [@bib20]). ", "Deletion mutants and chimeras of Smad6 and Smad7 were prepared by a PCR-based approach. ", "To obtain efficient levels of protein expression, some constructs, including all the FLAG-tagged Smad constructs, were subcloned into pcDEF3 ([@bib8]). ", "Expression levels of transfected Smad proteins were similar when they were examined by immunoblotting. ", "All of the PCR products were sequenced before use.", "\n\nCell culture and cDNA transfection\n----------------------------------\n\nR mutant Mv1Lu mink lung epithelial cells (gift of J. Massagué, Memorial Sloan-Kettering Cancer Center, New York, NY, and M. Laiho, Haartman Institute, University of Helsinki, Finland), COS7 cells, HepG2 cells (American Type Culture Collection accession number HB-8065), and P19 embryonal carcinoma cells (gift of T. Momoi, National Institute of Neuroscience, Kodaira, Tokyo, Japan) were cultured in DME containing 10% fetal bovine serum and antibiotics. ", "Cells were transiently transfected using FuGENE6 (Roche Diagnostics) following the manufacturer\\'s recommendations.", "\n\nLuciferase assay\n----------------\n\nR mutant mink lung epithelial cells, COS7 cells, or P19 embryonal carcinoma cells were transiently transfected with an appropriate combination of p3TP--lux ([@bib2]), AR3--Luc ([@bib12]), 3GC2--Lux ([@bib16]), or Tlx2--Lux ([@bib34]) promoter--reporter constructs, expression plasmids, and pcDNA3. ", "Total amounts of transfected DNAs were the same in each experiment, and values were normalized using Renilla luciferase activity. ", "All the Smad constructs used in luciferase assays were subcloned in pcDEF3, and their protein expression levels were verified by immunoblotting before use or in parallel with luciferase assays.", "\n\nImmunoprecipitation and immunoblotting\n--------------------------------------\n\nCOS7 cells, transfected with expression constructs, were solubilized in a buffer containing 20 mM Tris-HCl, pH 7.5, 150 mM NaCl, 1% Nonidet P-40, 1% aprotinin, and 1 mM phenylmethyl sulfonyl fluoride. ", "The cell lysates were precipitated by centrifugation and the supernatants were incubated with anti-FLAG M2 (Eastman Kodak Co.) antibody for 1 h, followed by incubation with protein A-- or G--Sepharose beads. ", "The beads were washed four times with the buffer used for cell solubilization. ", "The immune complexes were then eluted by boiling for 3 min in SDS sample buffer (100 mM Tris-HCl, pH 8.8, 0.01% bromophenol blue, 36% glycerol, 4% SDS, 10 mM DTT) and applied to SDS-PAGE. ", "Aliquots of the cell lysates were directly subjected to SDS-PAGE without immunoprecipitation. ", "Proteins were electrotransferred to ProBlott membranes (Applied Biosystems) and immunoblotted with anti-HA 3F10 (Boehringer), anti-phosphoserine (Zymed Laboratories), anti-FLAG M2, or anti-myc 9E10 (PharMingen) antibodies and detected using an ECL detection system (Amersham Pharmacia Biotech). ", "For reblotting, the membranes were stripped in accordance with the manufacturer\\'s protocol.", "\n\nAffinity cross-linking analysis\n-------------------------------\n\nRecombinant TGF-β1 (R&D Systems) was iodinated using the chloramine T method ([@bib6]). ", "COS7 cells were transfected with expression vectors, and affinity cross-linked using ^125^I--TGF-β1. ", "Subsequent immunoprecipitation and analysis by SDS-PAGE were performed as previously described ([@bib14]).", "\n\nImmunofluorescence labeling\n---------------------------\n\nImmunohistochemical staining of Smad6 and Smad7 was performed using transfected COS7, HepG2, or R mutant cells. ", "Eight-well Lab-Tek chamber slides (Nalge Nunc International) were treated with 0.03 mg/ml Cellmatrix type IV (Nitta Gelatin Co., Ltd.) at 37°C for 30 min. ", "Cells were seeded in the chambers, transfected with indicated cDNAs, and incubated for an additional 24 h. Cells were then fixed and treated with mouse anti-FLAG antibody and biotinylated horse anti--mouse IgG (affinity purified IgG \\[H+L\\]; Vector Laboratories), followed by incubation with FITC-labeled Avidin DCS (Vector Laboratories). ", "For double staining of FLAG- and 6Myc-tagged Smads, 6Myc--Smads were stained using rabbit anti-Myc antibody (gift of C.-H. Heldin, Ludwig Institute for Cancer Research, Uppsala, Sweden), followed by incubation with rhodamine isothiocyanate--labeled goat anti--rabbit IgG (Cappel). ", "The nuclei were stained by 4,6-diamidino-2-phenylindole. ", "Intracellular localization was determined by confocal laser scanning microscopy.", "\n\nWe are grateful to Y. Inada and A. Nishitoh-Sakai for technical help.", "\n\nThis study was supported by Grants-in-Aid for Scientific Research and Special Coordination Funds for Promoting Science and Technology of the Ministry of Education, Culture, Sport, Science, and Technology of Japan. ", "This study was also supported by a Ludwig Institute for Cancer Research Fund.", "\n\nAbbreviations used in this paper: BMP, bone morphogenetic protein; BMPR-I, BMP type I receptor; Co-Smad, common mediator Smad; I-Smad, inhibitory Smad; MH, Mad homology; R-Smad, receptor-regulated Smad; TβR-I, TGF-β type I receptor; TGF-β, transforming growth factor-β.", "\n\n[^1]: Address correspondence to Kohei Miyazono, Department of Biochemistry, The JFCR Cancer Institute, 1-37-1 Kami-ikebukuro, Toshima-ku, Tokyo 170-8455, Japan. ", "Tel.: ", "81-35-394-3866. ", "Fax: 81-33-918-0342. ", "E-mail: <miyazono-ind@umin.ac.jp>\n" ]

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[ "I was happy to offer reluctant praise for the content-loaded Crash Bandicoot N. Sane Trilogy earlier this month, but I am admittedly not a Bandi-cologist. ", "I have been watching how more hardcore fans, such as speedrunners, might react to this anthology, which required a full code rewrite, and eagle-eyed fans caught some issues that I didn't.", "\n\nThe anthology's developers at Vicarious Visions took to their official blog on Monday to confirm the issue: yep, you're not imagining things.", "\n\n\"Our game engine features a different collision system than the original game, and combined with the addition of physics, certain jumps require more precision than the originals,\" the Monday blog post reads. ", "This admission joins a longer description of how the jumps in each of the anthology's original PS1 games had different animation speeds and tunings, which VV only preserved to a certain extent. ", "All three games' basic handling systems are now derived from the Crash 3 model, VV says, and \"jump tunings\" have been attached to the updated Crash 1 and Crash 2 to make them feel a little more like the originals.", "\n\nWell, with one exception: now, in Crash 1, \"you fall more quickly upon release of the X button than you did in the original first game,\" the company writes.", "\n\nThis lack of definitive game-by-game emulation contrasts sharply with Vicarious' statements to Ars Technica in an E3 interview. ", "At that time, Vicarious designer Dan Tanguay stressed specific game-by-game elements that were examined and addressed (again, all from scratch) in an effort to \"earn speedrunner love.\" ", "When Tanguay spoke at length about how the series' crates break and affect momentum differently in each game and how his team made sure to address those concerns, I didn't even think to ask if the jumps would feel different on a game-by-game basis.", "\n\nVV's blog admission may show one reason that the anthology launched at a reasonable $40 price point. ", "As this week's blog post states, the Crash 3 handling model may very well \"unify the design\" and provide \"a cohesive experience across all three games.\" ", "But it also saves the developer the legwork of creating distinct animation and physics systems for three games; instead, one engine could do the trick, with \"jump tunings\" used to more simply fake the accuracy of the other games. ", "That guess is offered entirely as speculation, as opposed to being based on anything VV said in its blog post. ", "But remember, this is a creative industry that very recently tried to convince its fans that modeling and animating a female character was too much work.", "\n\nClearly, VV's work in eyeballing and video-analysis was ample enough to reveal the exact tunings that fueled each of the first three Crash games, as evidenced by this lengthy post. ", "The team's ability to preserve the original games' mechanics was not hindered by data discovery. ", "For a game that relies so much on agonizingly difficult and frame-perfect jumps, any admission that players need to bring more precision and more careful jump timings to the experience is not a good one. ", "But after reading the blog post, which describes all of these changes as efforts toward design \"unity,\" it stands to reason that the anthology will not be patched or updated to make the anthology a more accurate representation of its source material." ]

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[ "\nVietnam managed to keep its Covid-19 death toll “at zero” - finphil\nhttps://www.cnn.com/2020/05/29/asia/coronavirus-vietnam-intl-hnk/index.html\n======\ncmurf\nAmericans even lack the capacity to be humiliated about the facts: free market\nunpreparedness, and slow to react; government unpreparedness, slow to react\nand frequently in denial; the death toll itself. ", "Are Americans just\noverwhelmed with the obvious extent of the incompetency? ", "Or is it cognitive\ndissonance?", "\n\nWhile Italy was at it's peak, Americans seemed to be \"won't happen here, we're\njust better at this.\" ", "At every turn there's goal post shifting. ", "Oh well,\nthey're just old people. ", "Oh well, they just have pre-existing conditions. ", "Oh\nwell, whataboutism traffic accidents. ", "Oh well, the economy matters more.", "\n\nOf all the things America seems to have lost, it's honesty. ", "It can't even\nself-assess, let alone self-correct. ", "For anything.", "\n\n" ]

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[ "---\ntitle: গো (Go) ডেভেলপারদের জন্য ইথেরিয়াম\ndescription: শিখুন কিভাবে গো-ভিত্তিক প্রজেক্ট ও টুল ব্যবহার করে ইথেরিয়ামের জন্য ডেভেলপ করা যায়\nlang: bn\nsidebar: true\n---\n\n# গো (Go) ডেভেলপারদের জন্য ইথেরিয়াম {#ethereum-for-go-devs}\n\n<div class=\"featured\">শিখুন কিভাবে গো-ভিত্তিক প্রজেক্ট ও টুল ব্যবহার করে ইথেরিয়ামের জন্য ডেভেলপ করা যায়</div><br/>\n\nইথেরিয়াম ব্যবহার করে বিকেন্দ্রীভূত অ্যাপ্লিকেশন (বা \"ড্যাপস\") তৈরি করুন যেগুলো ক্রিপ্টোকারেন্সি এবং ব্লকচেইন প্রযুক্তির সুবিধাগুলোকে কাজে লাগায়। ", "এই ড্যাপগুলো বিশ্বাসযোগ্য হতে পারে, অর্থাৎ এগুলোকে একবার ইথেরিয়ামে প্রয়োগ করা হয়ে গেলে, এগুলো সবসময় প্রোগ্রামড হিসেবে চলতে থাকবে। ", "নতুন ধরণের আর্থিক অ্যাপ্লিকেশন তৈরি করার জন্য এগুলো ডিজিটাল সম্পদকে নিয়ন্ত্রণ করতে পারে। ", "এগুলো বিকেন্দ্রীভূত হতে পারে, যার মানে কোনো একক সত্ত্বা বা ব্যক্তি এগুলোকে নিয়ন্ত্রণ করে না এবং এগুলোকে সেন্সর করা প্রায় অসম্ভব।", "\n\n<img src=\"https://i.imgur.com/MFg8Nop.png\" width=\"100%\" />\n\n## স্মার্ট কন্ট্র্যাক্টস এবং সলিডিটি ল্যাঙ্গুয়েজ দিয়ে শুরু করা {#getting-started-with-smart-contracts-and-solidity}\n\n**গো-এর সাথে ইথেরিয়ামকে একীভূত করার জন্য প্রথম পদক্ষেপ নিন**\n\nএকদম প্রথম থেকে শুরু করতে চান ? [", "ethereum.org/learn](/bn/learn/) বা [ethereum.org/developers](/bn/developers/) দেখুন।", "\n\n- [ব্লকচেইনের ব্যাখ্যা](https://kauri.io/article/d55684513211466da7f8cc03987607d5/blockchain-explained)\n- [স্মার্ট কন্ট্র্যাক্টস সম্বন্ধে বোঝা](https://kauri.io/article/e4f66c6079e74a4a9b532148d3158188/ethereum-101-part-5-the-smart-contract)\n- [নিজের প্রথম স্মার্ট কন্ট্র্যাক্ট লিখুন](https://kauri.io/article/124b7db1d0cf4f47b414f8b13c9d66e2/remix-ide-your-first-smart-contract)\n- [শিখুন কীভাবে সলিডিটি কম্পাইল ও ডেপ্লয় করতে হয়](https://kauri.io/article/973c5f54c4434bb1b0160cff8c695369/understanding-smart-contract-compilation-and-deployment)\n- [কন্ট্র্যাক্টের প্রশিক্ষণ](https://github.com/ethereum/go-ethereum/wiki/Contract-Tutorial)\n\n## শিক্ষানবিশের জন্য প্রবন্ধ ও বই {#beginner-articles-and-books}\n\n- [একটি ইথেরিয়াম ক্লায়েন্ট বেছে নেওয়া](https://www.trufflesuite.com/docs/truffle/reference/choosing-an-ethereum-client)\n- [Geth দিয়ে শুরু করা](https://medium.com/@tzhenghao/getting-started-with-geth-c1a30b8d6458)\n- [ইথেরিয়ামের সঙ্গে সংযুক্ত করার জন্য Golang ব্যবহার করা](https://www.youtube.com/watch?v=-7uChuO_VzM)\n- [Golang ব্যবহার করে ইথেরিয়াম স্মার্ট কন্ট্র্যাক্টস ডেপ্লয় করা](https://www.youtube.com/watch?v=pytGqQmDslE)\n- [গো-তে ইথেরিয়াম স্মার্ট কন্ট্র্যাক্টস টেস্ট ও ডেপ্লয় করার জন্য একটি ধাপে ধাপে নির্দেশিকা](https://hackernoon.com/a-step-by-step-guide-to-testing-and-deploying-ethereum-smart-contracts-in-go-9fc34b178d78)\n- [ইবুক: গো-এর সঙ্গে ইথেরিয়াম অ্যাপ্লিকেশন](https://goethereumbook.org/) - _ তৈরি করার জন্য গো-এর সঙ্গে ইথেরিয়াম ডেভেলপমেন্ট_\n\n## মধ্যবর্তী প্রবন্ধ ও নথিপত্র {#intermediate-articles-and-docs}\n\n- [গো ইথেরিয়াম ডকুমেন্টেশন](https://geth.ethereum.org/docs/) - _আধিকারিক ইথেরিয়াম Golang এর জন্য ডকুমেন্টেশন_\n- [গো ইথেরিয়াম গোডক (GoDoc)](https://godoc.org/github.com/ethereum/go-ethereum)\n- [Geth এর সাথে গো-তে একটি ড্যাপ (DApp) তৈরি করা](https://kauri.io/article/60a36c1b17d645939f63415218dc24f9/creating-a-dapp-in-go-with-geth)\n- [Golang ও Geth এর সাথে ইথেরিয়াম প্রাইভেট নেটওয়ার্কের সঙ্গে কাজ করা](https://myhsts.org/tutorial-learn-how-to-work-with-ethereum-private-network-with-golang-with-geth.php)\n- [গো-এর সাথে ইথেরিয়ামে সলিডিটি কন্ট্র্যাক্টগুলোর ইউনিট টেস্টিং](https://medium.com/coinmonks/unit-testing-solidity-contracts-on-ethereum-with-go-3cc924091281)\n\n## উন্নত ইউজ প্যাটার্ন {#advanced-use-patterns}\n\n- [GETH ্সিমুলেটেড ব্যাকএন্ড](https://kauri.io/article/6285c9692883411aa041b6b970405a17/v1/the-geth-simulated-backend)\n- [ইথেরিয়াম ও কোরাম (Quorum) ব্যবহারকারী পরিষেবা-হিসেবে-ব্লকচেইন অ্যাপগুলো](https://blockchain.dcwebmakers.com/blockchain-as-a-service-apps-using-ethereum-and-quorum.html)\n- [ইথেরিয়াম ব্লকচেইন অ্যাপ্লিকেশনগুলোতে ডিস্ট্রিবিউটেড স্টোরেজ IPFS ও সোয়ার্ম ইন](https://blockchain.dcwebmakers.com/work-with-distributed-storage-ipfs-and-swarm-in-ethereum.html)\n- [মোবাইল ক্লায়েন্ট: লাইব্রেরি ও Inproc ইথেরিয়াম নোড](https://github.com/ethereum/go-ethereum/wiki/Mobile-Clients:-Libraries-and-Inproc-Ethereum-Nodes)\n- [নেটিভ ড্যাপ: ইথেরিয়াম কন্ট্র্যাক্টের সঙ্গে গো বাইন্ডিং](https://github.com/ethereum/go-ethereum/wiki/Native-DApps:-Go-bindings-to-Ethereum-contracts)\n\n## গো প্রোজেক্ট ও টুল {#go-projects-and-tools}\n\n- [Geth / গো ইথেরিয়াম](https://github.com/ethereum/go-ethereum) - _ইথেরিয়াম প্রোটোকলের আধিকারিক গো প্রয়োগ_\n- [গো ইথেরিয়াম কোড বিশ্লেষণ](https://github.com/ZtesoftCS/go-ethereum-code-analysis) - _গো ইথেরিয়াম সোর্স কোডের পর্যালোচনা ও বিশ্লেষণ_\n- [Golem](https://github.com/golemfactory/golem) - _Golem কম্পিউটিং ক্ষমতার জন্য একটি বিশ্বজনীন বাজার তৈরি করছে_\n- [কোরাম](https://github.com/jpmorganchase/quorum) - _ইথেরিয়ামের একটি অনুমোদিত বাস্তবায়ন যা তথ্যের গোপনীয়তাকে সমর্থন করে_\n- [Prysm](https://github.com/prysmaticlabs/prysm) - _ইথেরিয়াম 'Serenity' 2.0 গো এর বাস্তবায়ন_\n- [Eth Tweet](https://github.com/yep/eth-tweet) - _বিকেন্দ্রীভূত টুইটার: ইথেরিয়াম ব্লকচেইনে চলে এমন একটি মাইক্রোব্লগিং পরিষেবা_\n- [প্লাজমা MVP Golang](https://github.com/kyokan/plasma) — _মিনিমাম ভায়াবল প্লাজমা বৈশিষ্ট্যের Golang বাস্তবায়ন ও প্রসারণ_\n- [ওপেন ইথেরিয়াম মাইনিং পুল](https://github.com/sammy007/open-ethereum-pool) - _একটি ওপেন সোর্স ইথেরিয়াম মাইনিং পুল_\n- [ইথেরিয়াম HD ওয়ালেট](https://github.com/miguelmota/go-ethereum-hdwallet) - _গো-তে ইথেরিয়াম HD ওয়ালেট ডেরিভেশন_\n- [মাল্টি Geth](https://github.com/multi-geth/multi-geth) - _ইথেরিয়াম নেটওয়ার্কগুলির অনেক প্রজাতির জন্য সহায়তা_\n- [Geth লাইট ক্লায়েন্ট](https://github.com/zsfelfoldi/go-ethereum/wiki/Geth-Light-Client) - _হালকা ইথেরিয়াম সাবপ্রোটোকলের Geth প্রয়োগ_\n\nআরও সংস্থান খুঁজছেন? [", "ethereum.org/developers](/bn/developers/) দেখুন\n\n## গো কমিউনিটিতে অবদান প্রদানকারী {#go-community-contributors}\n\n- [Geth ডিসকর্ড](https://discordapp.com/invite/nthXNEv)\n- [Geth জিস্ট](https://gitter.im/ethereum/go-ethereum)\n- [গোফার্স স্ল্যাক](https://invite.slack.golangbridge.org/) - [#ethereum চ্যানেল](https://https:/gophers.slack.com/messages/C9HP1S9V2)\n- [স্ট্যাকএক্সচেঞ্জ- ইথেরিয়াম](https://ethereum.stackexchange.com/)\n- [মাল্টি Geth গিটার](https://gitter.im/ethoxy/multi-geth)\n- [ইথেরিয়াম গিটার](https://gitter.im/ethereum/home)\n- [Geth হালকা ক্লায়েন্ট গিটার](https://gitter.im/ethereum/light-client)\n\n## অন্যান্য সমষ্টীভূত তালিকা {#other-aggregated-lists}\n\n- [চমৎকার ইথেরিয়াম](https://github.com/btomashvili/awesome-ethereum)\n- [কনসেনসিস: ইথেরিয়াম ডেভেলপার টুলগুলোর একটি সুনির্দিষ্ট তালিকা](https://media.consensys.net/an-definitive-list-of-ethereum-developer-tools-2159ce865974)। [", "GitHub উৎস](https://github.com/ConsenSys/ethereum-developer-tools-list)\n" ]

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[ "<?xml version=\"1.0\" encoding=\"utf-8\" ?", ">\n<ApplicationInsights xmlns=\"http://schemas.microsoft.com/ApplicationInsights/2013/Settings\">\n</ApplicationInsights>\n" ]

{ "pile_set_name": "Github" }

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[ "package org.zstack.kvm;\n\nimport org.springframework.http.", "HttpMethod;\nimport org.zstack.header.host.", "APIAddHostEvent;\nimport org.zstack.header.host.", "APIAddHostMsg;\nimport org.zstack.header.host.", "HostVO;\nimport org.zstack.header.log.", "HasSensitiveInfo;\nimport org.zstack.header.message.", "APIParam;\nimport org.zstack.header.log.", "NoLogging;\nimport org.zstack.header.message.", "DefaultTimeout;\nimport org.zstack.header.rest.", "RestRequest;\nimport org.zstack.header.tag.", "TagResourceType;\n\nimport java.util.concurrent.", "TimeUnit;\n\n/**\n * @api\n *\n * add a kvm host\n *\n * @category kvm\n *\n * @since 0.1.0\n *\n * @cli\n *\n * @httpMsg\n * {\n\"org.zstack.kvm.", "APIAddKVMHostMsg\": {\n\"username\": \"user\",\n\"password\": \"password\",\n\"port\": \"port\",\n\"name\": \"host1\",\n\"managementIp\": \"localhost\",\n\"clusterUuid\": \"0f8b6a4702a840bfaf928f04ff0a5da4\",\n\"session\": {\n\"uuid\": \"0a1b3dd187af40b5871e5ab12b0d7875\"\n}\n}\n}\n *\n * @msg\n * {\n\"org.zstack.kvm.", "APIAddKVMHostMsg\": {\n\"username\": \"user\",\n\"password\": \"password\",\n\"port\": \"port\",\n\"name\": \"host1\",\n\"managementIp\": \"localhost\",\n\"clusterUuid\": \"0f8b6a4702a840bfaf928f04ff0a5da4\",\n\"session\": {\n\"uuid\": \"0a1b3dd187af40b5871e5ab12b0d7875\"\n},\n\"timeout\": 1800000,\n\"id\": \"9fca21a7aedb43669a146b0a4c7b9146\",\n\"serviceId\": \"api.portal\"\n}\n}\n *\n * @result\n *\n * see :ref:`APIAddHostEvent`\n */\n@TagResourceType(HostVO.class)\n@RestRequest(\n path = \"/hosts/kvm\",\n method = HttpMethod.", "POST,\n parameterName = \"params\",\n responseClass = APIAddHostEvent.class\n)\n@DefaultTimeout(timeunit = TimeUnit.", "HOURS, value = 3)\npublic class APIAddKVMHostMsg extends APIAddHostMsg implements AddKVMHostMessage, HasSensitiveInfo {\n /**\n * @desc user name used for ssh login.", "\n * Max length of 255 characters\n */\n @APIParam(maxLength = 255)\n private String username;\n /**\n * @desc password for ssh login\n * Max length of 255 characters\n */\n @APIParam(maxLength = 255, password = true)\n @NoLogging\n private String password;\n\n\n /**\n * @desc ssh port for login\n * port range (1,65535)\n */\n @APIParam(numberRange = {1, 65535}, required = false)\n private int sshPort = 22;\n\n @Override\n public String getUsername() {\n return username;\n }\n\n public void setUsername(String username) {\n this.username = username;\n }\n\n @Override\n public String getPassword() {\n return password;\n }\n\n public void setPassword(String password) {\n this.password = password;\n }\n\n @Override\n public int getSshPort() {\n return sshPort;\n }\n\n public void setSshPort(int sshPort) {\n this.sshPort = sshPort;\n }\n \n public static APIAddKVMHostMsg __example__() {\n APIAddKVMHostMsg msg = new APIAddKVMHostMsg();\n msg.setUsername(\"userName\");\n msg.setPassword(\"password\");\n msg.setSshPort(22);\n msg.setClusterUuid(uuid());\n msg.setName(\"newHost\");\n msg.setManagementIp(\"127.0.0.1\");\n return msg;\n }\n\n}\n" ]

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[ "Nobody sets out to be biased, but it's harder to avoid than you would think. ", "Wikipedia lists over 100 documented biases from authority bias and confirmation bias to the Semmelweis effect, we have an enormous tendency to let things other than the facts to affect our judgments. ", "We all, as much as we hate to admit it, are vulnerable.", "\n\nMachines, even virtual ones, have biases too. ", "They are designed, necessarily, to favor some kinds of data over others. ", "Unfortunately, we rarely question the judgments of mathematical models and, in many cases, their biases can pervade and distort operational reality, creating unintended consequences that are hard to undo.", "\n\nYet the biggest problem with data bias is that we are mostly unaware of it, because we assume that data and analytics are objective. ", "That's almost never the case. ", "Our machines are, for better or worse, extensions of ourselves and inherit our subjective judgments. ", "As data and analytics increasingly become a core component of our decision making, we need to be far more careful.", "\n\nOverfitting The Past\n\nImagine you're running a business that hires 100 people a year and you want to build a predictive model that would tell you what colleges you should focus our recruiting efforts on. ", "A seemingly reasonable approach would be to examine where you've recruited people in the past and how they performed. ", "Then you could focus recruiting from the best performing schools.", "\n\nOn the surface, that would seem to make sense, but if you take a closer look it is inherently flawed. ", "First of all, 100 students spread across perhaps a dozen colleges is far from statistically significant. ", "Second. ", "It's not hard to see how a one or two standouts or dullards from a particular school would skew the results massively.", "\n\nA related problem is what statisticians call overfitting, which basically means that because there is an element of bias in every data set, the more specifically we tailor a predictive model to the past the less likely it is to reflect the future. ", "In other words, the more detailed you make your model to fit the data, the worse the predictions are likely to get.", "\n\nThat may seem counterintuitive, and it is, which is why overfitting is so common. ", "People who sell predictive software love to be able to say things like, \"our model has been proven to be 99.8% accurate,\" even if that is often an indication that their product is actually less reliable than one that is, say, 80% accurate, but far simpler and more robust.", "\n\nBias In The Learning Corpus\n\nWith humans, we are careful to construct learning environments thoughtfully. ", "We design curriculums, carefully selecting materials, instructors and students to try and get the right mix of information and social dynamics. ", "We go to all this trouble because we understand that the environment we create greatly influences the learning experience.", "\n\nMachines also have a learning environment called a \"corpus.\" ", "If, for example, you want to teach an algorithm to recognize cats, you expose it to thousands of pictures of cats. ", "Eventually, it figures out how to tell the difference between, say, a cat and a dog. ", "Much like with human beings, it is through learning from these experiences that algorithms become useful.", "\n\nHowever, the process can go horribly awry, as in the case of Microsoft's Tay, a Twitter bot that the company unleashed on the microblogging platform. ", "In under a day, Tay went from being friendly and casual (\"humans are super cool\") to downright scary, (\"Hitler was right and I hate Jews\"). ", "It was profoundly disturbing.", "\n\nBias in the learning corpus is far more common than we often realize. ", "Do an image search for word \"Grandma\" and you will get almost exclusively white faces. ", "The same goes for prestigious titles, like doctor, lawyer and scientist. ", "When we query machines, all too often we find our own biases baked in.", "\n\nPerpetuating Bias\n\nFor over a century, the intelligence quotient (IQ) has been the standard method to test intelligence and has been shown to be strongly correlated with educational, professional and economic outcomes. ", "However, a strong correlation is not a perfect correlation and researchers have consistently found a number of sources of bias in the testing that can affect scores.", "\n\nThe flaws of IQ tests are well known and educators are generally aware of them, so are well placed to mitigate the problems that bias creates, but still test results help shape the educational experience. ", "Students that test well are placed in different classrooms, get different curriculums and are treated differently by teachers.", "\n\nOnce you get on the wrong side of an algorithm, your life immediately becomes more difficult. ", "Unable to get into a good school or to get a job, you earn less money and live in a worse neighborhood. ", "Those facts get fed into new algorithms and your situation degrades even further. ", "Each step of your humiliating descent is documented, measured and evaluated.", "\n\nCorrecting For Bias\n\nAs Daniel Kahneman explains in Thinking Fast, Thinking Slow, humans can overcome their biases. ", "He describes our brains as two systems. ", "The first is quick to judgement, but the second is slower and weighs data more carefully. ", "With training and experience, we can learn to disengage our system 1 and replace it with system 2.", "\n\nYet we rarely do the same with machines. ", "We don't ask our algorithms to \"sleep on it\" or to get a second opinion. ", "Often, we don't even stop to question their judgments. ", "If a human told us to make a decision in a certain way, we would want to know why, but when a mathematical model does it, we usually just accept it and move on.", "\n\nWe shouldn't. ", "Our data systems are designed by people and inherit many of our human flaws. ", "We need to hold them to higher standards. ", "Good systems, like good people, need to be transparent and accountable. ", "We should know what information is being used, how factors are weighted and how decisions are made." ]

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[ "The invention relates to piperidine derivatives as N-Methyl-D-Aspartate (NMDA) antagonists useful in the treatment of diseases and disorders responsive to antagonism of NMDA receptors.", "\nMany of the physiological and pathophysiological effects of the endogenous excitatory neurotransmitter glutamate are mediated via actions at N-Methyl-D-Asparate (NMDA) receptors. ", "Over-excitation of the NMDA receptors on postsynaptic cells-mediated by excessive release of glutamate from nerve endings or glial cells-results in a massive calcium ion influx through a calcium ion channel into neuronal cells, leading to neuronal cell death. ", "These events occur under ischemic or hypoxic conditions such as, for example, stroke, hypoglycemia, cardiac arrest, or acute physical trauma.", "\nNMDA receptors in vivo form an NMDA receptor channel complex in cell walls comprising at least three binding domains, including a glutamic acid (or NMDA) recognition site, a channel blocking binding site, and a strychnine-insensitive glycine binding site. ", "Physiologically, a blockade of at least one of these sites terminates the channel opening of the NMDA receptor, thereby preventing calcium ion influx into cells. ", "Accordingly, an NMDA receptor antagonist is therapeutically useful because it minimizes damage to the central nervous system induced by calcium ion influx under ischemic or hypoxic conditions.", "\nA functional NMDA receptor is comprised of the combination of at least one subunit termed xe2x80x9cNR1xe2x80x9d, which has 8 splice variants including NR1A, and one (or more) subunit termed xe2x80x9cNR2Axe2x80x9d, xe2x80x9cNR2Bxe2x80x9d, xe2x80x9cNR2Cxe2x80x9d, and xe2x80x9cNR2Dxe2x80x9d. ", "The combinations are designated NR1/2A, NR1/2B, NR1/2C and NR1/2D, respectively. ", "The different NR2 subunits have distinct developmental and anatomical distributions. ", "This suggests that agents that selectively antagonize one NR1/NR2 combination would have therapeutic actions without the psychotomimetic or dysphoric side effects associated with antagonists which block multiple NR1/NR2 combinations.", "\nA subtype-selective NMDA receptor antagonist may be identified by methods well known in the pharmaceutical arts, such as, for example, screening compounds in an electrophysiology assay. ", "In one such electrophysiology assay, different subunit combinations of recombinant NR1 and NR2 receptors are expressed in Xenopus oocytes, and a potential agent is administered at different concentrations. ", "NMDA-based electrical currents are activated by co-administration of fixed concentrations of an excitatory amino acid such as, for example, glutamic acid or glycine. ", "The ability of an agent to antagonize the activation of the electrical current by an excitatory amino acid is measured by recording the change in the current versus the change in the concentration of the agent.", "\nScreening of compounds in recent years have identified a number of NMDA receptor antagonists that have been used in animal and clinical human studies to demonstrate proof of concept for use of such an antagonist in the treatment of a variety of disorders. ", "Disorders known to be responsive to blockade of NMDA receptors include acute cerebral ischemia (stroke or cerebral trauma, for example), muscular spasm, convulsive disorders, pain, including chronic and neuropathic pain, anxiety, and chronic neurodegenerative disorders such as Parkinson\"\"s disease. ", "NMDA receptor antagonists may also be used to prevent tolerance to opiate analgesia or to help control symptoms of withdrawal from addictive drugs. ", "In fact, excessive excitation by neurotransmitters may be responsible for the loss of neurons in a wide variety of conditions. ", "Additional conditions include cerebral vascular disorders such as cerebral ischemia or cerebral infarction resulting in a range of conditions such as thromboembolic or hemorrhagic stroke, cerebral vasospasm, hypoglycemia, cardiac arrest, status epilepticus, perinatal, asphyxia anoxia, such as from near drowning, pulmonary surgery and cerebral trauma, as well as lathyrism, Alzheimer\"\"s disease, and Huntington\"\"s disease. ", "Other conditions amendable to treatment with an subtype-selective NMDA receptor antagonist include amyotrophic lateral sclerosis (ALS), epilepsy, and schizophrenia.", "\nFor example, studies have demonstrated that compounds that act as antagonists at NMDA receptors have beneficial pharmacological effects on patients suffering from Parkinson\"\"s disease. ", "In Parkinson\"\"s disease, there is a loss of dopamine neurons in the substantia nigra. ", "Secondary to this dopamine loss is a hyperactivity of specific brain glutamatergic pathways. ", "This glutamatergic hyperactivity is thought to mediate some of the pathophysiological aspects of Parkinson\"\"s disease, as well as some of the side effects associated with the long term treatment of the disease by dopamine agonists, such as L-DOPA, pergolide, ropinirole or pramipexole. ", "Clinical studies in humans have demonstrated that antagonists at NMDA receptors have beneficial effects in Parkinson\"\"s disease or in treating the side effects associated with the treatment of Parkinson\"\"s disease with dopamine agonists.", "\nPain is another example of a condition shown to be responsive to NMDA receptor antagonism. ", "For example in previous studies, stimulation of NMDA receptors by afferent nerves transmitting painful stimuli has been demonstrated to be involved in hyperalgesic and neuropathic pain states. ", "Animal studies have demonstrated that compounds that act as antagonists at NMDA receptors have beneficial effects in treating hyperalgesic and neuropathic pain states.", "\nHowever, while NMDA antagonists have been successfully used to demonstrate the proof of concept mentioned above, very few, if any, of these antagonists have shown a suitable drug profile in clinical studies. ", "This is so even though numerous NMDA receptor antagonists have been synthesized and tested. ", "For example, U.S. Pat. ", "Nos. ", "5,714,502; 6,124,317; 6,124,323; and 6,130,234 describes the piperidine-based NMDA receptor antagonists shown below.", "\nU.S. Pat. ", "No. ", "5,714,502 provides piperidines of formula \nin which\nR1 and R2 in each case independently of one another are unsubstituted or mono- to disubstituted phenyl radicals whose substituents can be A, OA, aryloxy having 6 to 10 C atoms, aralkyloxy having 7 to 11 C atoms, xe2x80x94Oxe2x80x94(CH2)nxe2x80x94Oxe2x80x94(bonded in directly adjacent positions or in the meta- or para-position to one another on the phenyl ring), xe2x80x94Oxe2x80x94(CH2)nxe2x80x94OH, Hal, CF3, OH, NO2, NH2, NHA, NA2, NHR3, NAR3, SO2NH2, SO2NHA, SO2NA2, SO2NHR3 (excluding R3xe2x95x90SO2A), SO2N(R3)2 (excluding R3xe2x95x90SO2A) or R3,\nR3 is COH, CO-alkyl having 1 to 7 C atoms in the alkyl portion, CO-alkyl-aryl having 8 to 12 C atoms in the alkyl and aryl portions, CO-aryl having 7 to 13 C atoms in the aryl portion, or SO2A\nA is an alkyl radical having 1 to 6 C atoms\nn is 1 or 2\nHal is F, Cl, Br, or I,\nand their physiologically acceptable salts. ", "The invention also relates to the preparation of these novel compounds and their use as psychopharmacologically active substances.", "\nU.S. Pat. ", "No. ", "6,124,317 provides 2-substituted piperidine NMDA receptor antagonists of formula \nor a pharmaceutically acceptable salt thereof wherein\nAr1 and Ar2 are independently aryl or a heteroaryl group, either of which may be independently substituted by hydrogen, hydroxy, alkyl, a halogenated alkyl group, halogen, nitro, aryl, aralkyl, amino, a lower alkyl amino group or a lower alkoxy group;\neach R1 is independently hydrogen, alkyl or hydroxy;\neach R2 is independently hydrogen, alkyl or hydroxy;\nX is xe2x80x94CH2xe2x80x94, O, S, or NR3, wherein R3 is hydrogen or a lower alkyl group having 1 to 6 carbon atoms;\nY is xe2x80x94CH2xe2x80x94, xe2x80x94CHxe2x95x90CHxe2x80x94, xe2x80x94Cxe2x89xa1Cxe2x80x94, O, S or NR3;\nm is 0, 1 or 2; and\nn is 0, 1, 2, 3, 4 or 5,\nprovided that when m is 0 and X is xe2x80x94CH2xe2x80x94, or m is 1, R1 is H and X is xe2x80x94CH2xe2x80x94 that either Y is not xe2x80x94CH2xe2x80x94 or at least one of R2 is not hydrogen and further provided that when Y is xe2x80x94Cxe2x95x90Cxe2x80x94 then X is not O.\nU.S. Pat. ", "No. ", "6,124,323 provides 4-substituted piperidine-based NMDA receptor antagonists of formula \nor a pharmaceutically acceptable salt thereof wherein\nAr1 and Ar2 are independently aryl or a heteroaryl group, either of which may be independently substituted by hydrogen, hydroxy, alkyl, halogen, nitro, cyano, carboxaldehyde, aldehyde oxime, lower alkoxy carbonylmethyl, hydroxy lower alkyl, amino carbonylmethyl, hydrazinocarbonylmethyl, acetamido, aryl, aralkyl, amino, a halogenated alkyl group, a lower alkyl amino group or a lower alkoxy group;\nz is a single or double bond;\nX is xe2x80x94(CHR3)mxe2x80x94, O, S or NR4, wherein each R3 is independently hydrogen, hydroxy or a lower alkyl group having 1 to 6 carbon atoms, R4 is hydrogen or a lower alkyl group having 1 to 6 carbon atoms and m is 0, 1 or 2, provided that when z is a double bond then X is not O or NR4;\nR1 is hydrogen or hydroxy;\neach R2 is independently hydrogen, hydroxy or a lower alkyl group having 1 to 6 carbon atoms;\nn is 0, 1, 2, 3 or 4;\nY is O, S, NR4 or a single bond; and\nR5 is hydrogen or hydroxy when z is a single bond preferably provided that:\n(i) R2 cannot be hydroxy in a position alpha to Ar2; (ii) if X is a single bond, z is a double bond or R5 is hydroxy and Ar2 is phenyl then Y cannot be O; (iii) if Y is O, n is 3 or 4, R2 is exclusively hydrogen, z is a single bond, R1 and R5 are hydrogen and Ar2 is phenyl, or halogen, methoxy, or trifluoromethyl substituted phenyl then X cannot be methylene or ethylene; (iv) if X is xe2x80x94(CHR3)mxe2x80x94, m is 2 and R3 is exclusively hydrogen then Ar1 cannot be imidazolyl substituted; (v) if Y is O, n is 2, 3 or 4, R2 is hydrogen or hydroxy, z is a single bond, R1 and R5 are hydrogen, and Ar2 is phenyl, or NO2, CN, 1-imidazoyl, or 1,2,4-triazol-1-yl substituted phenyl then X cannot be methylene, hydroxymethylene, or O; (vi) if Y is O or S, R1 and R5 are hydrogen and R2 is hydroxy then X is not methylene or a single bond; or (vii) if Y is a single bond, R2 is exclusively hydrogen and Ar2 is phenyl, then either R1 or R5 must be hydroxy.", "\nU.S. Pat. ", "No. ", "6,130,234 provides piperidine-based NMDA receptor antagonists of formula \nor a pharmaceutically acceptable salt thereof wherein\nAr1 and Ar2 are independently aryl or a heteroaryl group, either of which may be independently substituted by hydrogen, hydroxy, alkyl, halogen, nitro, aryl, aralkyl, amino, a halogenated alkyl group, xe2x80x94NHAc, xe2x80x94NHSO2Me, xe2x80x94N(SO2Me)2, xe2x80x94CONHalkyl, xe2x80x94SO2NH2, an alkylguanidine group, a lower alkyl amino group or a lower alkoxy group;\nz is a single or double bond;\nX is xe2x80x94(CHR2)mxe2x80x94, O, S or NR3, wherein each R2 is independently hydrogen, hydroxy, lower alkoxy or a lower alkyl group having 1 to 6 carbon atoms and m is 0, 1 or 2, and R3 is hydrogen or a lower alkyl group having 1 to 6 carbon atoms, provided that when z is a double bond then X is not O, S or NR3;\nR1 is hydrogen or hydroxy;\nn is 0, 1 or 2;\nQ is xe2x80x94CHxe2x95x90CHxe2x80x94 or xe2x80x94Cxe2x89xa1xe2x80x94Cxe2x80x94; and\nR4 is hydrogen or hydroxy when z is a single bond provided that: (i) when n is 0, then z is a double bond and R4 is not present; (ii) when n is 1 or 2 and Q is xe2x80x94Cxe2x89xa1Cxe2x80x94 and z is a double bond or R4 is hydroxy, then Ar1 is aryl substituted by halogen; and (iii) when R4 is hydroxy then R2 is not hydroxy or lower alkoxy.", "\nThe difficulty referenced above with demonstrating clinical utility of NMDA receptor antagonists has been the antagonists\"\" lack of NMDA receptor subtype selectivity and/or biological activity when dosed orally. ", "Before the present invention, many of the drugs of the NMDA receptor antagonist class were nonselective antagonists of NMDA receptor subtypes that were administered intravenously (IV), which accounts for their undesired side effects and lack of efficacy, respectively. ", "Given that the need for medicinal agents that treat diseases responsive to antagonism of NMDA receptors remains unmet, the search for NMDA receptor antagonists that are subtype-selective and orally efficacious continues.", "\nA series of novel piperidines have been discovered that are subtype-selective NMDA receptor antagonists and are efficacious in vivo when dosed orally. ", "All that is needed to practice the invention is to administer from 1 to 6 times daily to a patient in need thereof, a therapeutically effective amount of a compound of the invention. ", "As is discussed below, determination of dosage forms and amounts of the invention compounds, routes of administration, and identification of patients in need of treatment, is within the average skill in the pharmaceutical and medical arts.", "\nDescribed are piperidines of Formula I \nand pharmaceutically acceptable salts thereof wherein:\nR1 is independently selected from alky, substituted alkyl, alkenyl, substituted alkenyl, alkoxy, substituted alkoxy, alkylaminoalkyl, hydroxyalkyl, (aminocarbonyl)-alkyl, (alkylthio)-alkyl, carboxyalkyl, haloalkyl, and halogen;\ng is an integer of from 0 to 3;\nZ is (CH2)h, Cxe2x95x90O, O, S, SO, SO2, CHOH, or C(Me)OH;\nh is an integer of from 0 or 1;\nR2 is hydrogen, OH, alkoxy, or substituted alkoxy;\nR3 is hydrogen, OH, alkoxy, or substituted alkoxy;\nV is (CH2)n or (CH2)mxe2x80x94Cxe2x95x90O, wherein n is an integer of from 1 to 4, and m is an integer of from 0 to 4;\nB is a 4-, 5-, or 6-membered, carbon-linked, substituted or unsubstituted, heterocyclene, containing from 1 to 3 heteroatoms, which are N, O, or S, selected from the group consisting of:\n(i) 1-aza-2-cyclobutanon-3,4-diyl of formula \n(ii) a 5-membered aromatic, nonaromatic dihydro, or nonaromatic tetrahydro diradical heterocyclic ring having carbon atoms and from 1 to 3 heteroatoms selected from N, O, and S;\n(iii) a 5-membered oxo-substituted, nonaromatic tetrahydro, diradical heterocyclic ring having carbon atoms and 1 or 2 heteroatoms selected from N, O, and S;\n(iv) a 6-membered aromatic, nonaromatic tetrahydro, or nonaromatic hexahydro diradical heterocyclic ring having carbon atoms and 1 or 2 heteroatoms, which heteroatoms are nitrogen, and\n(v) a 6-membered nonaromatic oxo-substituted hexahydro diradical heterocyclic ring having carbon atoms and 1 or 2 heteroatoms which are nitrogen and 0 or 1 heteroatom which is oxygen\nwherein the atoms of the heterocyclene ring that are bonded to the group V and the phenyl bearing the group (X1)d are carbon atoms, and further wherein when B is a nonaromatic heterocycle containing sulfur, said sulfur may further comprise \nX1 is alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkoxy, substituted alkoxy, aralkyl, substituted aralkyl, halogen, haloalkyl, cyano, nitro, amino, aminoalkyl, alkylaminoalkyl, hydroxyalkyl, carboxyalkyl, (aminocarbonyl)-alkyl, (alkylthio)-alkyl, or C(O)-alkyl;\nd is an integer of from 0 to 2;\nE is hydrogen; and\nY is OH; or\nE and Y may be taken together with the phenylene to which they are attached to form a fused 9- or 10-membered bicyclic ring, containing from 0 to 3 heteroatoms in E to Y selected from N, O, and S, wherein\nE is a linker group containing 2 or 3 atoms of the bicyclic ring, and\nY is a hydrogen bond donor group containing 1 atom of the bicyclic ring.", "\nPreferred is a compound of Formula I wherein:\nB is a heterocyclene selected from the group consisting of: \nxe2x80x83wherein X is selected from O, S, and Nxe2x80x94R, wherein R is hydrogen or alkyl;\nX1 is alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkoxy, substituted alkoxy, aralkyl, halogen, haloalkyl, cyano, nitro, amino, aminoalkyl, alkylaminoalkyl, hydroxyalkyl, carboxyalkyl, (aminocarbonyl)-alkyl, (alkylthio)-alkyl, or C(O)CH3, and one X1 is ortho to V and para to E; and\nR2 is hydrogen or OH;\nR3 is hydrogen or OH;\nV is CH2 or Cxe2x95x90O;\nZ is (CH2)h; and\nh is 1.", "\nPreferred is a compound of Formula II \nand pharmaceutically acceptable salts thereof wherein R1, g, Z, h, R2, R3, V, B, X1, and d are as defmed above for Formula I; and wherein when B is a 5-membered, oxo-substituted, nonaromatic tetrahydro, diradical heterocyclic ring having carbon atoms and 1 or 2 heteroatoms selected from N, O, and S which is an oxazolidinone, the oxazolidinone is selected from: \nAlso preferred is a compound of Formula III \nand pharmaceutically acceptable salts thereof wherein R1, g, Z, h, R2, R3, V, B, X1, and d are as defined above for Formula I; and\nE and Y together with the phenylene to which they are attached form a 9- or 10-membered bicyclic ring, containing from 0 to 3 heteroatoms selected from N, O, and S wherein\nE is a linker group containing 2 or 3 atoms of the bicyclic ring; and\nY is a hydrogen bond donor group containing 1 atom of the bicyclic ring.", "\nMore preferred is a compound of Formula III wherein\nY is selected from xe2x80x94N(H)xe2x80x94, xe2x80x94CH(OH)xe2x80x94, and xe2x80x94N(OH)xe2x80x94, and\nE is selected from xe2x80x94CHxe2x95x90CHxe2x80x94, xe2x80x94CH2xe2x80x94CH2xe2x80x94, xe2x80x94CHxe2x95x90Nxe2x80x94, xe2x80x94C(O)xe2x80x94CH2xe2x80x94, xe2x80x94CH2xe2x80x94C(O)xe2x80x94, xe2x80x94CH2xe2x80x94S(O)xe2x80x94, xe2x80x94CH2xe2x80x94S(O)2xe2x80x94, xe2x80x94Nxe2x95x90C(H)xe2x80x94, xe2x80x94N(H)xe2x80x94C(O)xe2x80x94, xe2x80x94Oxe2x80x94C(O)xe2x80x94, xe2x80x94Sxe2x80x94C(O)xe2x80x94, xe2x80x94Nxe2x95x90Nxe2x80x94, xe2x80x94CHxe2x95x90CHxe2x80x94C(H)xe2x80x94, xe2x80x94CH2xe2x80x94CH2xe2x80x94CH2xe2x80x94, xe2x80x94CH2xe2x80x94CH2xe2x80x94C(O)xe2x80x94, xe2x80x94CH2xe2x80x94CH2xe2x80x94S(O)xe2x80x94, xe2x80x94CH2xe2x80x94CH2xe2x80x94S(O)2xe2x80x94, xe2x80x94CHxe2x95x90CHxe2x80x94C(O)xe2x80x94, xe2x80x94Nxe2x95x90CHxe2x80x94C(O)xe2x80x94, xe2x80x94Oxe2x80x94CH2xe2x80x94C(O)xe2x80x94, xe2x80x94Sxe2x80x94CH2xe2x80x94C(O)xe2x80x94, and xe2x80x94N(H)xe2x80x94C(O)xe2x80x94C(O)xe2x80x94; or\nY is selected from xe2x95x90C(OH)xe2x80x94; and\nE is selected from xe2x80x94CHxe2x95x90CHxe2x80x94C(H)xe2x95x90, xe2x80x94C(O)xe2x80x94C(H)xe2x95x90, xe2x80x94C(O)xe2x80x94Nxe2x95x90, xe2x80x94Oxe2x80x94Nxe2x95x90, xe2x80x94Sxe2x80x94Nxe2x95x90, xe2x80x94C(O)xe2x80x94N(H)xe2x80x94Nxe2x95x90, xe2x80x94CHxe2x95x90Nxe2x80x94Nxe2x95x90, xe2x80x94CHxe2x95x90N(O)xe2x80x94Nxe2x95x90, and xe2x80x94N(H)xe2x80x94C(O)xe2x80x94Nxe2x95x90.", "\nMore preferred is a compound of Formula III wherein:\nxe2x80x94Exe2x80x94Yxe2x80x94 is selected from the group consisting of\nxe2x80x94CHxe2x95x90CHxe2x80x94N(H)xe2x80x94,\nxe2x80x94(CH2)2xe2x80x94N(H)xe2x80x94,\nxe2x80x94CHxe2x95x90Nxe2x80x94N(H)xe2x80x94,\nxe2x80x94C(O)xe2x80x94CH2xe2x80x94N(H)xe2x80x94,\nxe2x80x94CH2xe2x80x94C(O)xe2x80x94N(H)xe2x80x94,\nxe2x80x94CH2xe2x80x94S(O)xe2x80x94N(H)xe2x80x94,\nxe2x80x94CH2xe2x80x94S(O)2xe2x80x94N(H)xe2x80x94,\nxe2x80x94CHxe2x95x90CHxe2x80x94CH(OH)xe2x80x94,\nxe2x80x94(CH2)2xe2x80x94CH(OH)xe2x80x94,\nxe2x80x94C(O)xe2x80x94C(H)xe2x95x90C(OH)xe2x80x94,\nxe2x80x94C(O)xe2x80x94Nxe2x95x90C(OH)xe2x80x94,\nxe2x80x94Nxe2x95x90CHxe2x80x94N(H)xe2x80x94,\nxe2x80x94N(H)xe2x80x94C(O)xe2x80x94N(H)xe2x80x94,\nxe2x80x94Oxe2x80x94C(O)xe2x80x94NHxe2x80x94,\nxe2x80x94Sxe2x80x94C(O)xe2x80x94NHxe2x80x94,\nxe2x80x94Oxe2x80x94Nxe2x95x90CH(OH)xe2x80x94,\nxe2x80x94Sxe2x80x94Nxe2x95x90CH(OH)xe2x80x94,\nxe2x80x94Nxe2x95x90Nxe2x80x94N(H)xe2x80x94,\nxe2x80x94Nxe2x95x90Nxe2x80x94N(OH)xe2x80x94,\nxe2x80x94CHxe2x95x90CHxe2x80x94CHxe2x95x90C(OH)xe2x80x94,\nxe2x80x94(CH2)3xe2x80x94CH(OH)xe2x80x94,\nxe2x80x94(CH2)2xe2x80x94C(O)xe2x80x94N(H)xe2x80x94,\nxe2x80x94(CH2)2xe2x80x94S(O)xe2x80x94N(H)xe2x80x94,\nxe2x80x94(CH2)2xe2x80x94S(O)2xe2x80x94N(H)xe2x80x94,\nxe2x80x94CHxe2x95x90CHxe2x80x94C(O)xe2x80x94N(H)xe2x80x94,\nxe2x80x94C(O)xe2x80x94NHxe2x80x94Nxe2x95x90C(OH)xe2x80x94,\nxe2x80x94CHxe2x95x90Nxe2x80x94Nxe2x95x90C(OH)xe2x80x94,\nxe2x80x94CHxe2x95x90N(O)xe2x80x94Nxe2x95x90C(OH)xe2x80x94,\nxe2x80x94N(H)xe2x80x94C(O)xe2x80x94Nxe2x95x90C(OH)xe2x80x94,\nxe2x80x94Nxe2x95x90CHxe2x80x94C(O)xe2x80x94NHxe2x80x94,\nxe2x80x94Oxe2x80x94CH2xe2x80x94C(O)xe2x80x94NHxe2x80x94,\nxe2x80x94Sxe2x80x94CH2xe2x80x94C(O)xe2x80x94NHxe2x80x94, and\nxe2x80x94N(H)xe2x80x94C(O)xe2x80x94C(O)xe2x80x94N(H)xe2x80x94.", "\nAlso preferred is a compound of Formula IV \nand pharmaceutically acceptable salts thereof wherein R1, g, h, R2, V, B, X1, and d are as defined above for Formula I; and\nX2 is selected from O, S, NH, and CH2; and\nB is selected from the group consisting of: \nwherein X is selected from O, S, and Nxe2x80x94R, wherein R is hydrogen or alkyl, and wherein Z is selected from O or S.\nMore preferred is a compound of Formula IV selected from the group consisting of:\n6-[5-(4-Benzylpiperidin-1-ylmethyl)-4,5-dihydroisoxazol-3-yl]-3H-benzoxazol-2-one;\n6-[5-(4-Benzylpiperidin-1-ylmethyl)-3-methylisoxazol-4-yl]-3H-benzoxazol-2-one;\n6-{5-[4-(4-fluorobenzyl)piperidin-1-ylmethyl]-4,5-dihydroisoxazol-3-yl}-3H-benzoxazol-2-one hydrochloride;\n(+)-6-{5-[4-(4-fluorobenzyl)piperidin-1-ylmethyl]-4,5-dihydroisoxazol-3-yl}-3H-benzoxazol-2-one;\n(xe2x88x92)-6-{5-[4-(4-fluorobenzyl)piperidin-1-ylmethyl]-4,5-dihydroisoxazol-3-yl}-3H-benzoxazol-2-one;\n6-{3-[4-(4-Fluorobenzyl)piperidin-1-ylmethyl]-4,5-dihydroisoxazol-5-yl}-3H-benzoxazol-2-one;\n6-{2-[4-(4-Fluorobenzyl)piperidin-1-ylmethyl]thiazol-5-yl}-3H-benzoxazol-2-one;\n6-{2-[4-(4-fluorobenzyl)piperidin-1-ylmethyl]thiazol-5-yl}-3H-benzothiazol-2-one;\n5-[2-(4-Benzylpiperidin-1-ylmethyl)thiazol-5-yl]-1,3-dihydrobenzimidazole-2-thione;\n6-{2-[4-(4-Fluorobenzyl)piperidin-1-ylmethyl]oxazol-5-yl}-3H-benzothiazol-2-one;\n6-[2-(4-Benzylpiperidin-1-ylmethyl)oxazol-5-yl]-3H-benzoxazol-2-one;\n5-[2-(4-Benzylpiperidin-1-ylmethyl)oxazol-5-yl]-1,3-dihydroindol-2-one;\n6-{5-[4-(4-Fluorobenzyl)piperidin-1-ylmethyl]-4,5-dihydrothiazol-2-yl}-3H-benzoxazol-2-one;\n6-[5-(4-Benzylpiperidin-1-ylmethyl)-4,5-dihydrothiazol-2-yl]-3H-benzoxazol-2-one;\n6-[2-(4-Benzylpiperidin-1-ylmethyl)-4,5-dihydrothiazol-5-yl]-3H-benzoxazol-2-one;\n6-{5-[4-(4-Fluorobenzyl)piperidin-1-ylmethyl]isoxazol-3-yl}-3H-benzoxazol-2-one;\n6-{5-[4-(4-Fluorobenzyl)piperidin-1-yl]methyl}-4,5-dihydroisoxazol-3-yl}-3H-benzothiazol-2-one;\n6-[5-(4-Benzyl-4-hydroxypiperidin-1-ylmethyl)-4,5-dihydroisoxazol-3-yl]-3H-benzoxazol-2-one;\n6-{5-[4-(4-Fluorobenzyl)piperidine-1-carbonyl]-4,5-dihydroisoxazol-3-yl}-3H-benzoxazol-2-one;\n6-(5-{2-[4-(4-Fluorobenzyl)piperidin-1-yl]ethyl}-4,5-dihydroisoxazol-3-yl)-3H-benzoxazol-2-one;\n6-{5-[4-(4-Fluorobenzyl)-4-hydroxypiperidin-1-ylmethyl]-4,5-dihydroisoxazol-3-yl}-3H-benzoxazol-2-one;\n6-{5-[4-(4-Fluorobenzyl)piperidin-1-ylmethyl]-5-methyl-4,5-dihydroisoxazol-3-yl}-3H-benzoxazol-2-one;\n5-[4-(4-Fluorobenzyl)piperidin-1-ylmethyl]-3-(2-oxo-2,3-dihydrobenzoxazol-6-yl)-4,5-dihydroisoxazole-5-carboxylic acid;\n5-[4-(4-Fluorobenzyl)piperidin-1-ylmethyl]-3-(2-oxo-2,3-dihydrobenzoxazol-6-yl)-4,5-dihydroisoxazole-5-carboxylic acid methyl ester;\n4-(4-Fluorobenzyl)-1-[3-(2-oxo-2,3-dihydrobenzoxazol-6-yl)-4,5-dihydroisoxazol-5-ylmethyl]piperidine-4-carboxylic acid ethyl ester;\n4-(4-Fluorobenzyl)-1-[3-(2-oxo-2,3-dihydrobenzoxazol-6-yl)-4,5-dihydroisoxazol-5-ylmethyl]piperidine-4-carboxylic acid;\n6-{5-[4-(4-Fluorobenzyl)-3-hydroxypiperidin-1-ylmethyl]-4,5-dihydroisoxazol-3-yl }-3H-benzoxazol-2-one;\n6-{5-[4-(4-Fluorophenoxy)piperidin-1-ylmethyl]-4,5-dihydroisoxazol-3-yl}-3H-benzoxazol-2-one;\n6-{5-[4-(4-Fluorophenylsulfanyl)piperidin-1-ylmethyl]-4,5-dihydroisoxazol-3-yl}-3H-benzoxazol-2-one;\n6-{5-[4-(4-Fluorobenzenesulfinyl)piperidin-1-ylmethyl]-4,5-dihydroisoxazol-3-yl}-3H-benzoxazol-2-one;\n6-{5-[4-(4-Fluorobenzoyl)piperidin-1-ylmethyl]-4,5-dihydroisoxazol-3-yl}-3H-benzoxazol-2-one;\n6-(5-{4-[(4-Fluorophenyl)hydroxymethyl]piperidin-1-ylmethyl}-4,5-dihydroisoxazol-3-yl)-3H-benzoxazol-2-one;\n4-Chloro-6-{5-[4-(4-fluorobenzyl)piperidin-1-ylmethyl]-4,5-dihydroisoxazol-3-yl}-5-methyl-3H-benzoxazol-2-one;\n-{5-[4-(4-Fluorophenyl)piperidin-1-ylmethyl]-4,5-dihydroisoxazol-3-yl}-3H-benzoxazol-2-one;\n6-[5-(4-Phenyl-4-hydroxy)piperidin-1-ylmethyl)-4,5-dihydroisoxazol-3-yl]-3H-benzoxazol-2-one; and\n6-(5-{2-[4-(4-Fluorophenyl)piperidin-1-yl]ethyl }-4,5-dihydroisoxazol-3-yl)-3H-benzoxazol-2-one.", "\nMore preferred is a compound of Formula IV named (xe2x88x92)-6-{5-[4-(4-fluorobenzyl)piperidin-1-ylmethyl]-4,5-dihydroisoxazol-3-yl}-3H-benzoxazol-3-one.", "\nStill more preferred is a compound of Formula IV named (+)-6-{5-[4-(4-fluorobenzyl)piperidin-1-ylmethyl]-4,5-dihydroisoxazol-3-yl}-3H-benzoxazol-3-one.", "\nPreferred is a compound of Formula V \nand pharmaceutically acceptable salts thereof wherein R1, g, Z, h, R2, R3, V, X1, d, E, and Y are as defined above for Formula I;\nX is O, S, or Nxe2x80x94R, wherein R is hydrogen or alkyl; and\n* means a chiral center designated R, S, or mixtures thereof.", "\nPreferred is a compound of Formula VI \nand pharmaceutically acceptable salts thereof wherein R1, g, Z, h, R2, R3, V, X1, d, E, and Y are as defined above for Formula I;\nX is O, S, or Nxe2x80x94R, wherein R is hydrogen or alkyl; and\n* means a chiral center designated R, S, or mixtures thereof.", "\nPreferred is a compound of Formula VII \nand pharmaceutically acceptable salts thereof wherein R1, g, Z, h, R2, R3, V, X1, d, E, and Y are as defined above for Formula I; and\nX is O, S, or Nxe2x80x94R, wherein R is hydrogen or alkyl.", "\nPreferred is a compound of Formula VIII \nand pharmaceutically acceptable salts thereof wherein R1, g, Z, h, R2, R3, V, X1, d, E, and Y are as defined above for Formula I; and\nX is O, S, or Nxe2x80x94R, wherein R is independently hydrogen or alkyl.", "\nPreferred is a compound of Formula IX \nand pharmaceutically acceptable salts thereof wherein R1, g, Z, h, R2, R3, V, X1, d, E, and Y are as defined above for Formula I; and\nX is O, S, or Nxe2x80x94R, wherein R is hydrogen or alkyl.", "\nPreferred is a compound of Formula X \nand pharmaceutically acceptable salts thereof wherein R1, g, Z, h, R2, R3, V, X1, d, E, and Y are as defined above for Formula I;\nX is O, S, or Nxe2x80x94R, wherein R is hydrogen or alkyl; and\n* means a chiral center designated R, S, or mixtures thereof.", "\nPreferred is a compound of Formula XI \nand pharmaceutically acceptable salts thereof wherein R1, g, Z, h, R2, R3, V, X1, d, E, and Y are as defined above for Formula I;\nX is O, S, or Nxe2x80x94R, wherein R is hydrogen or alkyl; and\n* means a chiral center designated R, S, or mixtures thereof.", "\nPreferred is a compound of Formula XII \nand pharmaceutically acceptable salts thereof wherein R1, g, Z, h, R2, R3, V, X1, d, E, and Y are as defined above for Formula I.\nPreferred is a compound of Formula XIII \nand pharmaceutically acceptable salts thereof wherein R1, g, Z, h, R2, R3, V, X1, d, E, and Y are as defined above for Formula I.\nPreferred is a compound of Formula XIV \nand pharmaceutically acceptable salts thereof wherein R1, g, Z, h, R2, R3, V, X1, d, E, and Y are as defined above for Formula I;\nR is hydrogen or alkyl; and\n* means a chiral center designated R, S, or mixtures thereof.", "\nPreferred is a compound of Formula XV \nand pharmaceutically acceptable salts thereof wherein R1, g, Z, h, R2, R3, V, X1, d, E, and Y are as defined above for Formula I;\nR is hydrogen, alkyl, or substituted alkyl; and\n* means a chiral center designated R, S, or mixtures thereof.", "\nThe invention also provides a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula I, or a pharmaceutically acceptable salt thereof, together with a diluent, carrier, or excipient.", "\nIn a preferred embodiment, the invention provides a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula II or Formula IV together with a diluent, carrier, or excipient.", "\nIn a more preferred embodiment, the invention provides a pharmaceutical composition comprising a therapeutically effective amount of a compound selected from the group consisting of:\n(+)-6-{5-[4-(4-Fluorobenzyl)piperidin-1-ylmethyl]-4,5-dihydroisoxazol-3-yl}-3H-benzoxazol-3-one;\n(xe2x88x92)-6-{5-[4-(4-Fluorobenzyl)piperidin-1-ylmethyl]-4,5-dihydroisoxazol-3-yl}-3H-benzoxazol-3-one, or\na pharmaceutically acceptable salt thereof., ", "together with a diluent, carrier, or excipient.", "\nThe invention also provides a method of treating disorders responsive to the selective blockade of the N-methyl-D-aspartate receptor subtypes in a mammal, including a human, suffering therefrom which comprises administering a compound of Formula I or a pharmaceutically acceptable salt thereof.", "\nIn a preferred embodiment, the invention provides a method of treating disorders responsive to the selective blockade of the N-methyl-D-aspartate receptor subtypes in a mammal, including a human, suffering therefrom comprising administering a compound of Formula I or a pharmaceutically acceptable salt thereof, wherein the disorders are selected from stroke, cerebral ischemia, central nervous system disorders, depression, trauma, hypoglycemia, neurodegenerative disorders, anxiety, migraine headache, convulsions, aminoglycoside antibiotics-induced hearing loss, psychosis, glaucoma, CMV retinitis, opioid tolerance or withdrawal, pain, including chronic pain, neuropathic pain, or surgical pain, and urinary incontinence.", "\nIn a more preferred embodiment, the invention provides a method of treating disorders responsive to the selective blockade of the N-methyl-D-aspartate receptor subtypes in a mammal, including a human, suffering therefrom comprising administering a compound of Formula I or a pharmaceutically acceptable salt thereof, wherein the disorder is pain.", "\nIn another more preferred embodiment, the invention provides a method of treating disorders responsive to the selective blockade of the N-methyl-D-aspartate receptor subtypes in a mammal, including a human, suffering therefrom comprising administering a compound of Formula I or a pharmaceutically acceptable salt thereof, wherein the disorder is Parkinson\"\"s disease.", "\nIn a still more preferred embodiment, the invention provides a method of treating disorders responsive to the selective blockade of the N-methyl-D-aspartate receptor subtypes in a mammal, including a human, suffering therefrom comprising administering a compound of Formula II or Formula IV.", "\nIn a still more preferred embodiment, the invention provides a method of treating disorders responsive to the selective blockade of the N-methyl-D-aspartate receptor subtypes in a mammal, including a human, suffering therefrom comprising administering a compound selected from the group consisting of:\n(+)-6-{5-[4-(4-Fluorobenzyl)piperidin-1-ylmethyl]-4,5-dihydroisoxazol-3-yl}-3H-benzoxazol-3-one;\n(xe2x88x92)-6-{5-[4-(4-Fluorobenzyl)piperidin-1-ylmethyl]-4,5-dihydroisoxazol-3-yl}-3H-benzoxazol-3-one, or\na pharmaceutically acceptable salt thereof.", "\nIn another more preferred embodiment, the invention provides a method of treating disorders responsive to the selective blockade of the N-methyl-D-aspartate receptor subtypes in a mammal, including a human, suffering therefrom comprising administering a compound of Formula I or a pharmaceutically acceptable salt thereof, further comprising administering a dopamine agonist.", "\nIn another more preferred embodiment, the invention provides a method of treating disorders responsive to the selective blockade of the N-methyl-D-aspartate receptor subtypes in a mammal, including a human, suffering therefrom comprising administering a compound of Formula I or a pharmaceutically acceptable salt thereof, further comprising administering a dopamine agonist wherein said dopamine agonist is L-DOPA.", "\nIn another preferred embodiment, the invention provides a method of treating disorders comprising administering a compound of Formula I or a pharmaceutically acceptable salt thereof in unit dosage form.", "\nAlso, the invention provides a compound selected from the group consisting of:\n6-(2-Azido-1-hydroxyethyl)-3H-benzoxazol-2-one;\n6-[2-Azido-1-(tert-butyldimethylsilanyloxy)ethyl]-3H-benzoxazol-2-one;\n6-[2-Amino-1-(tert-butyldimethylsilanyloxy)ethyl]-3H-benzoxazol-2-one;\n2-(4-Benzylpiperidin-1-yl)-N-[2-(tert-butyldimethylsilanyloxy)-2-(2-oxo-2,3-dihydrobenzoxazol-6-yl)ethyl]acetamide;\n2-(4-Benzylpiperidin-1-yl)-N-[2-(tert-butyldimethylsilanyloxy)-2-(2-oxo-2,3-dihydrobenzoxazol-6-yl)ethyl]thioacetamide;\n2-(4-Benzylpiperidin-1-yl)-N-[2-hydroxy-2-(2-oxo-2,3-dihydrobenzoxazol-6-yl)ethyl]thioacetamide;\n1-Chloro-3-[4-(4-fluorobenzyl)piperidin-1-yl]propan-2-ol;\n1-Chloro-3-(4-benzylpiperidin-1-yl)propan-2-ol;\n2-{3-[4-(4-Fluorobenzyl)piperidin-1-yl]-2-hydroxypropyl}isoindole-1,3-dione;\n2-[3-(4-Benzylpiperidin-1-yl)-2-hydroxypropyl]isoindole-1,3-dione;\n1-Amino-3-[4-(4-fluorobenzyl)piperidin-1-yl]propan-2-ol bis-hydrochloride salt;\n1-Amino-3-[4-benzylpiperidin-1-yl]propan-2-ol bis-hydrochloride salt;\n{3-[4-(4-Fluorobenzyl)piperidin-1-yl]-2-hydroxypropyl}carbamic acid benzyl ester;\n[3-(4-Benzylpiperidin-1-yl)-2-hydroxypropyl]carbamic acid benzyl ester;\n{2-(tert-Butyldimethylsilanyloxy)-3-[4-(4-fluorobenzyl)piperidin-1-yl]propyl}carbamic acid benzyl ester;\n{2-(tert-Butyldimethylsilanyloxy)-3-[4-benzylpiperidin-1-yl]propyl}carbamic acid benzyl ester;\n{2-(tert-Butyldimethylsilanyloxy)-3-[4-(4-fluorobenzyl)piperidin-1-yl]propylamine;\nMethyl 2-oxo-2,3-dihydrobenzoxazole-6-carboxylate;\n2-Oxo-2,3-dihydrobenzoxazole-6-carboxylic acid;\n2-Oxo-2,3-dihydrobenzoxazole-6-carboxylic acid [3-(4-benzylpiperidin-1-yl)-2-(tert-butyldimethylsilanyloxy)propyl]amide;\n2-Oxo-2,3-dihydrobenzoxazole-6-carboxylic acid [3-(4-(4-fluorobenzyl)piperidin-1-yl)-2-(tert-butylimethylsilanyloxy)propyl]amide;\n2-Oxo-2,3-dihydrobenzoxazole-6-carbothioic acid [3-(4-benzylpiperidin-1-yl)-2-(tert-butyldimethylsilanyloxy)propyl]amide;\n2-Oxo-2,3-dihydrobenzooxazole-6-carbothioic acid [3-(4-benzylpiperidin-1-yl)-2-hydroxypropyl]amide;\n6-(2-Azido-1-hydroxyethyl)-3H-benzoxazol-2-one;\n6-[2-Azido-1-(tert-butyldimethylsilanyloxy)ethyl]-3H-benzoxazol-2-one;\n6-[2-Amino-1-(tert-butyldimethylsilanyloxy)ethyl]-3H-benzoxazol-2-one;\n2-(4-Benzylpiperidin-1-yl)-N-[2-(tert-butyldimethylsilanyloxy)-2-(2-oxo-2,3-dihydrobenzoxazol-6-yl)ethyl]acetamide;\n2-(4-Benzylpiperidin-1-yl)-N-[2-(tert-butyldimethylsilanyloxy)-2-(2-oxo-2,3-dihydrobenzoxazol-6-yl)ethyl]thioacetamide; and\n2-(4-Benzylpiperidin-1-yl)-N-[2-hydroxy-2-(2-oxo-2,3-dihydrobenzoxazol-6-yl)ethyl]thioacetamide.", "\nAlso, the invention provides a process for preparing the compound of Formula I and pharmaceutically acceptable salts thereof comprising the steps of:\n1) aminating a precursor alkyl halide;\n2) cyclizing the product of Step 1;\n3) recovering the desired compound of Formula I; and\n4) converting, if desired, to a pharmaceutically acceptable salt.", "\nAlso, the invention provides a process for preparing the compound of Formula I and pharmaceutically acceptable salts thereof comprising the steps of:\n1) halogenating an unsaturated side chain of a precursor to the compound;\n2) cyclizing the product of Step. ", "1;\n3) recovering the desired compound of Formula I; and\n4) converting, if desired, to a pharmaceutically acceptable salt.", "\nAs recited above, one aspect of the present invention is a compound of Formula I \nand a pharmaceutically acceptable salt thereof, wherein R1, g, Z, h, R2, R3, V, B, X1, d, E, and Y are as defined above.", "\nAll of the references cited herein, including patents, are incorporated herein by reference.", "\nThe following definitions apply to terms used in this specification and claims.", "\nThe term xe2x80x9cpatientxe2x80x9d means a mammal, including a human.", "\nPreferred patients are humans, cats, and dogs.", "\nThe term xe2x80x9cIC50xe2x80x9d means the concentration of test compound required to inhibit activity of a receptor or enzyme by 50%.", "\nThe term xe2x80x9cL-DOPAxe2x80x9d means 3-hydroxy-L-tyrosine.", "\nThe term xe2x80x9c(X1)dxe2x80x9d wherein d is an integer of from 0 to 2 means the group X1 is present 0 to 2 times on the phenylene to which it is attached. ", "The groups X1 are independently the same or different. ", "Illustrative examples of substituted phenylenes are drawn below.", "\nd is 0: \nd is 1: \nd is 2: \nLikewise the term xe2x80x9c(R1)gxe2x80x9d wherein g is an integer of from 0 to 3 means the group R1 is present 0 to 3 times on the phenyl to which it is attached. ", "The groups R1 are independently the same or different. ", "Illustrative examples of substituted phenyls are drawn below.", "\ng is 0: \ng is 1: \ng is 2: \ng is 3: \nThe term xe2x80x9ccomprisingxe2x80x9d, which is synonymous with the terms xe2x80x9cincludingxe2x80x9d, xe2x80x9ccontainingxe2x80x9d, or xe2x80x9ccharacterized byxe2x80x9d, is inclusive or open-ended and does not exclude additional, unrecited elements or method steps from the scope of the invention that follows.", "\nThe phrase xe2x80x9cconsisting ofxe2x80x9d, is closed-ended and excludes any element, step, or ingredient not specified in the description of the invention that follows.", "\nThe phrase xe2x80x9cconsisting essentially ofxe2x80x9d limits the scope of the invention that follows to the specified elements or steps and those further elements or steps that do not materially affect the basic and novel characteristics of the invention.", "\nThe phrase xe2x80x9cfilter aidxe2x80x9d means a filter medium comprising small particulates. ", "Illustrative examples of filter aids include kieselguhr and CELITE (Celite Corporation, Lompoc, Calif.), a diatomaceous earth filter aid.", "\nThe term xe2x80x9calkylxe2x80x9d means a straight or branched, unsubstituted or substituted, hydrocarbon group having from 1 to 12 carbon atoms. ", "Preferred alkyl groups are C1-C6 alkyl. ", "Typical examples of unsubstituted alkyl groups include methyl (i.e., CH3xe2x80x94), ethyl, 1-propyl, and 2-propyl, 1-butyl, 2-butyl, 2-methyl-1-propyl, 1,1-dimethylethyl, 1-pentyl, 2-pentyl, 3-pentyl, 2,2-dimethylpropyl, 1-hexyl, 2-hexyl, 3-hexyl, 4-methyl-1-pentyl, 1-heptyl, 2-heptyl, 3-heptyl, 4-heptyl, 5-methyl-1-hexyl, 1-octyl, 2-octyl, 3-octyl, 4-octyl, 6-methyl-1-heptyl, 5,5-dimethylhexyl, 1-nonyl, 2-nonyl, 1-decyl, 2-decyl, 1-undecyl, 2-undecyl, 1-dodecyl, and 5-dodecyl. ", "Substituted alkyl groups are described below.", "\nThe term xe2x80x9calkenylxe2x80x9d means a straight or branched, unsubstituted or substituted, hydrocarbon group having from 2 to 12 carbon atoms and 1 or 2 sites of unsaturation. ", "Preferred groups are C2-C6 alkenyl. ", "Illustrative examples of unsubstituted alkenyl groups include ethenyl [i.e., CH2xe2x95x90C(H)xe2x80x94], 1-propenyl, 2-propenyl, 1-buten-1-yl, 2-buten-1-yl, 1-penten-1-yl, 2-penten-1-yl, 1-penten-3-yl, 1-penten-5-yl, 1-hexen-1-yl, 1-hexen-4-yl, 2-hexen-1-yl, 3-hexen-1-yl, 2-octen-3-yl, 5-nonen-2-yl, 4-undecen-4-yl, and 5-dodecen-2-yl. ", "Substituted alkenyl groups are defined below.", "\nThe term xe2x80x9calkoxyxe2x80x9d means a straight or branched, substituted or unsubstituted, alkyl group of from 1 to 12 carbon atoms linked through an oxygen atom. ", "Preferred is C1-C6 alkoxy. ", "Illustrative examples of unsubstituted alkoxy groups include methoxy (i.e., CH3xe2x80x94Oxe2x80x94), ethoxy, isopropoxy, tert-butoxy, iso-pentoxy, octyloxy, and 7,7-dimethyloctyloxy. ", "Substituted alkoxy groups are defined below.", "\nThe term xe2x80x9carylxe2x80x9d means an unsubstituted or substituted aromatic carbocyclic ring having 6 or 10 carbon atoms. ", "Illustrative examples of unsubstituted aryl groups include phenyl (i.e., C6H5xe2x80x94), 1-naphthyl, and 2-naphthyl. ", "Substituted aryl groups are defined below.", "\nThe term xe2x80x9caralkylxe2x80x9d means an unsubstituted or substituted aromatic carbocyclic ring having 6 or 10 carbon atoms (i.e., an aryl group) linked through an alkylene group, wherein alkylene is as defined below. ", "Illustrative examples of unsubstituted aralkyl groups include benzyl, 2-phenylethyl, 3-phenylpropyl, 4-phenylbutyl, 3-methyl-3-phenylpropyl, 1-naphthylmethyl, 1-naphthylethyl, 3-(1-naphthyl)-propyl, 4-(1-naphthyl)-butyl, 4-(2-naphthyl)-butyl, 4-phenylheptyl, and 12-(2-hydroxyphenyl)-dodec-3-yl. ", "Substituted aralkyl groups are defined below.", "\nThe term xe2x80x9calkylenexe2x80x9d means a straight or branched hydrocarbon chain diradical of from 1 to 12 carbon atoms. ", "Preferred groups are C1-C6 alkylene. ", "Illustrative examples of alkylene groups include methylene (i.e., xe2x80x94CH2xe2x80x94), 1,2-ethylene, 1,2-propylene, 1,3-propylene, 2,2-dimethyl-hexane-1,6-diyl, and dodecan-1,12-diyl.", "\nThe term xe2x80x9ccycloalkylxe2x80x9d means an unsubstituted or substituted, saturated carbocyclic ring having from 3 to 7 carbon atoms. ", "Illustrative examples of unsubstituted cycloalkyl groups include cyclopentyl, cyclopropyl, cyclohexyl or cycloheptyl. ", "Substituted cycloalkyl is defined below.", "\nAs discussed above, the groups alkyl, alkenyl, alkoxy, aryl, aralkyl, and cycloalkyl may be substituted. ", "These substituted groups are respectively termed: xe2x80x9csubstituted alkylxe2x80x9d, xe2x80x9csubstituted alkenylxe2x80x9d, xe2x80x9csubstituted alkoxyxe2x80x9d, xe2x80x9csubstituted arylxe2x80x9d, xe2x80x9csubstituted aralkylxe2x80x9d, and xe2x80x9csubstituted cycloalkylxe2x80x9d.", "\nThe groups can be substituted with from 1 to 3 substituents independently selected from halogen, OH, Oxe2x80x94(C1-C6 alkyl), OC(O)xe2x80x94(C1-C6 alkyl), xe2x80x94(C1-C6 alkylene)-OH, xe2x80x94(C1-C6 alkylene)-Oxe2x80x94(C1-C6 alkyl), NH2, N(H)xe2x80x94(C1C6 alkyl), Nxe2x80x94(C1-C6 alkyl)2, NHC(O)xe2x80x94(C1-C6 alkyl), xe2x80x94(C1-C6 alkylene)-NH2, xe2x80x94(C1-C6 alkylene)-N(H)xe2x80x94(C1-C6 alkyl), xe2x80x94(C1-C6 alkylene)-Nxe2x80x94(C1-C6 alkyl)2, SH, Sxe2x80x94(C1-C6 alkyl), Sxe2x80x94C(O)xe2x80x94(C1-C6 alkyl), xe2x80x94(C1-C6 alkylene)-SH, xe2x80x94(C1-C6 alkylene)-Sxe2x80x94(C1-C6 alkyl), unsubstituted cycloalkyl, C(O)xe2x80x94(C1-C6 alkyl), CO2H, CO2xe2x80x94(C1-C6 alkyl), C(O)NH2, C(O)NHxe2x80x94(C1-C6 alkyl), and C(O)Nxe2x80x94(C1-C6 alkyl)2, wherein (C1-C6 alkyl) means a straight or branched hydrocarbon radical having from 1 to 6 carbon atoms, (C1-C6 alkylene) means a straight or branched hydrocarbon chain diradical of from 1 to 6 carbon atoms, and unsubstituted cycloalkyl is as defined above. ", "Further, 1 of the 3 substituents in substituted alkyl, substituted alkenyl (on saturated carbons only), substituted alkoxy, substituted aralkyl (on saturated carbon atoms only) and substituted cycloalkyl may be oxo. ", "Examples of these substituted groups are provided below.", "\nIllustrative examples of substituted alkyl groups include HOCH2, CF3, (CH2)4SCH3, (CH2)8NH2, C(CH3)2CH[CO2C(CH3)3]CH3, CF2OH, and CH(CO2H)CH2CH2C(O)NMe2.", "\nIllustrative examples of substituted alkenyl groups include 2-fluoro-ethen-1-yl [i.e., CH(F)xe2x95x90C(H)xe2x80x94], methyl propenoate-2-yl, and 5-iso-butoxy-1-penten-5-yl.", "\nIllustrative examples of substituted alkoxy groups include fluoromethoxy (i.e., FCH2xe2x80x94Oxe2x80x94), 2-ethoxycarbonyl-ethoxy, 4-aminocarbonyl-oxybutyl, and 8-thio-nonyloxy [i.e., CH3CH(SH)xe2x80x94(CH2)7xe2x80x94Oxe2x80x94].", "\nIllustrative examples of substituted aryl groups include 2-fluorophenyl, 2,4,6-trimethoxyphenyl, 4-chloro-2-methylphenyl, 5,6-dichloro-naphth-1-yl, and 8-(dimethylaminomethyl)-naphth-2-yl.", "\nIllustrative examples of substituted aralkyl groups include 4-fluorophenylmethyl, 2-(2,4,6-trimethoxyphenyl)-ethyl, 3-(2-carboxyphenyl)-propyl, 4-phenyl-4-hydroxy-butyl, 4-(2-dimethylaminomethyl-naphth-1-yl)-butyl, and 12-(2-hydroxyphenyl)-dodec-3-yl.", "\nIllustrative examples of substituted cycloalkyl groups include 3-methyl-cyclopentyl, 4-hydroxy-cyclohexyl, and 1-methoxy-cycloheptyl.", "\nThe term xe2x80x9cheteroatomxe2x80x9d includes nitrogen, oxygen, and sulfur. ", "When the heteroatom is incorporated in a nonaromatic ring, the heteroatom further includes \nThe term xe2x80x9coxoxe2x80x9d means xe2x95x90O.\nThe term xe2x80x9coxo-substitutedxe2x80x9d means any group which contains a carbon atom that is substituted with an oxo group (i.e., xe2x95x90O). ", "A carbon atom substituted with an oxo group forms a carbonyl group of formula Cxe2x95x90O.\nThe phrase xe2x80x9cfused 9- or 10-membered bicyclic ring containing from 0 to 3 heteroatomsxe2x80x9d means a group wherein 2 ring systems share 2 and only 2 atoms. ", "Illustrative examples of a fused bicyclic group containing 0 heteroatoms include \nThe term xe2x80x9chalogenxe2x80x9d means bromine, chlorine, fluorine, or iodine.", "\nThe term xe2x80x9caminoalkylxe2x80x9d means a H2N group linked through an alkylene group, wherein alkylene has the meaning as defined above. ", "Illustrative examples of aminoalkyl groups include aminomethyl (i.e., H2Nxe2x80x94CH2xe2x80x94), 3-aminopropyl, and 1-amino-1,1-dimethylethyl.", "\nThe term xe2x80x9calkylaminoalkylxe2x80x9d means an alkyl group, linked through an N(H) group, which in turn is linked through an alkylene group, wherein alkyl and alkylene are as defined above. ", "Illustrative examples of alkylaminoalkyl groups include methylaminomethyl (i.e., CH3NHCH2xe2x80x94), 3-(tert-butylamino)-propyl, and 6-(hexylamino)-hexyl.", "\nThe term xe2x80x9chydroxyalkylxe2x80x9d means an OH group linked through an alkylene group, wherein alkylene has the meaning defined above. ", "Illustrative examples of hydroxyalkyl groups include hydroxymethyl, 2-hydroxyethyl, and 2-hydroxy-1,1-dimethylethyl.", "\nThe term xe2x80x9c(aminocarbonyl)-alkylxe2x80x9d means an C(O)NH2 group linked through an alkylene group, wherein alkylene has the meaning defined above. ", "Illustrative examples of (aminocarbonyl)-alkyl groups include H2NC(O)xe2x80x94CH2xe2x80x94 and H2NC(O)xe2x80x94C(CH3)3.", "\nThe term xe2x80x9c(alkylthio)-alkyl-xe2x80x9d means an alkyl group linked through a sulfur atom, which in turn is linked through an alkylene group, wherein alkyl and alkylene have the meanings defined above. ", "Illustrative examples of (alkylthio)-alkyl groups include CH3xe2x80x94Sxe2x80x94CH2xe2x80x94, CH3CH2xe2x80x94Sxe2x80x94(CH2)2xe2x80x94, and CH3CH(CH3)CH2C(CH3)2xe2x80x94Sxe2x80x94C(CH3)2CH2xe2x80x94.", "\nThe term xe2x80x9ccarboxyalkylxe2x80x9d means a CO2H group linked through an alkylene group, wherein alkylene has the meaning defined above. ", "Illustrative examples of carboxyalkyl groups include carboxymethyl, 2-carboxyethyl, and 2-carboxy-1,1-dimethylethyl.", "\nThe term xe2x80x9caminoxe2x80x9d means the xe2x80x94NH2 group.", "\nThe term xe2x80x9chaloalkylxe2x80x9d means a halogen linked through an alkylene group, wherein halogen and alkylene are as defined above. ", "Illustrative examples of haloalkyl include trifluoromethyl, difluoromethyl, fluoromethyl, and 2,2,2-trichloroethyl.", "\nThe term xe2x80x9cC(O)-alkylxe2x80x9d means an alkyl group as defined above linked through a carbonyl carbon atom. ", "Illustrative examples of C(O)-alkyl groups include acetyl (i.e., C(O)CH3), 2,2-dimethylpropionyl, and dodecanoyl.", "\nThe term xe2x80x9cheterocyclenexe2x80x9d means a 4-, 5-, or 6-membered, carbon-linked, unsubstituted or substituted with, for example, alkyl, carboxylic acid, or ester, heterocyclic diradical ring, containing from 1 to 3 heteroatoms which are N, O, or S, selected from the group consisting of:\n(i) 1-aza-2-cyclobutanon-3,4-diyl of formula \n(ii) a 5-membered aromatic, nonaromatic dihydro, or nonaromatic tetrahydro ring having carbon atoms and from 1 to 3 heteroatoms selected from N, O, and S;\n(iii) a 5-membered oxo-substituted nonaromatic tetrahydro ring having carbon atoms and 1 or 2 heteroatoms selected from N, O, and S;\n(iv) a 6-membered aromatic, nonaromatic tetrahydro, or nonaromatic hexahydro ring having carbon atoms and 1 or 2 heteroatoms, which heteroatoms are nitrogen, and\n(v) a 6-membered nonaromatic oxo-substituted hexahydro ring having carbon atoms and 1 or 2 heteroatoms which are nitrogen and 0 or 1 heteroatom which is oxygen;\nwherein the radical atoms of the heterocyclene are carbon atoms, and further wherein when B is a nonaromatic heterocyclene containing sulfur, said sulfur may further comprise \nIllustrative examples of 5- and 6-membered heterocyclenes include:\n1) A 5-membered heterocyclic ring having one heteroatom such as, for example, the following rings: \nxe2x80x83wherein X is O, S, or Nxe2x80x94R wherein R is H or alkyl.", "\n2) A 5-membered, substituted or unsubstituted, wherein xe2x80x9csubstitutedxe2x80x9d is defined as above, heterocyclic ring having 2 heteroatoms such as, for example, the following rings: \nxe2x80x83wherein X and R are as defined above.", "\n3) A 5-membered heterocyclic ring having 3 heteroatoms such as, for example, the following rings: \nxe2x80x83wherein X and R are as defined above.", "\n4) A 6-membered aromatic heterocyclic ring having 1 to 3 nitrogen atoms such as, for example, following rings: \n5) A 6-membered nonaromatic tetrahydro heterocyclic ring having 1 or 2 nitrogen atoms such as, for example, the following rings: \nxe2x80x83wherein R is independently hydrogen or alkyl;\n6) A 6-membered nonaromatic hexahydro heterocyclic ring having 1 or 2 nitrogen atoms such as, for example, the following rings: \nxe2x80x83wherein R is independently hydrogen or alkyl;\n7) A 5-membered oxo-substituted heterocyclic nonaromatic tetrahydro ring having 1 or 2 heteroatoms O, S, or Nxe2x80x94R such as, for example, the following rings: \nxe2x80x83wherein X and R are as defined above.", "\n8) A 6-membered oxo-substituted hexahydro nonaromatic heterocyclic rings having 1 or 2 nitrogen atoms, and 0 or 1 heteroatoms selected from O and S, such as, for example, the following rings: \nxe2x80x83wherein R and X are as defined above.", "\nIt is to be appreciated that the above rings do not represent all possible isomers or rings that are described above by the term xe2x80x9cheterocyclenexe2x80x9d.", "\nIt is also to be appreciated that the compounds of Formula I may have chiral centers, in which case all stereoisomers thereof, both separately and as racemic and/or diastereoisomeric mixtures, are included.", "\nSome of the compounds of Formula I are capable of further forming nontoxic pharmaceutically acceptable acid-addition and/or base salts. ", "All of these forms are within the scope of the present invention.", "\nFor example, pharmaceutically acceptable acid addition salts of the compounds of Formula I include salts derived from inorganic acids such as hydrochloric, nitric, phosphoric, sulfuric, hydrobromic, hydriodic, hydrofluoric, phosphorous, and the like, as well as the salts derived from organic acids, such as aliphatic mono- and dicarboxylic acids, phenyl-substituted alkanoic acids, hydroxy alkanoic acids, alkanedioic acids, aromatic acids, aliphatic and aromatic sulfonic acids, etc. ", "Such salts thus include sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, nitrate, phosphate, monohydrogenphosphate, dihyrogenphosphate, metaphosphate, pyrophosphate, chloride, bromide, iodide, acetate, trifluoroacetate, propionate, caprylate, isobutyrate, oxalate, malonate, succinates suberate, sebacate, fumarate, maleate, mandelate, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, phthalate, benzenesulfonate, toluenesulfonate, phenylacetate, citrate, lactate, malate, tartrate, methanesulfonate, and the like. ", "Also contemplated are salts of amino acids such as arginate and the like and gluconate, galacturonate (see, for example, Berge S. M., et al., ", "xe2x80x9cPharmaceutical Salts,xe2x80x9d Journal of Pharmaceutical Science, 1977;66:1-19.", "\nThe acid addition salts of basic invention compounds are prepared by contacting the free base form of the invention compounds with a sufficient amount of the desired acid to produce the salt in the conventional manner.", "\nPharmaceutically acceptable base salts are formed with metals or amines, such as alkali and alkaline earth metals or organic amines. ", "Examples of metals used as cations are sodium, potassium, magnesium, calcium, and the like. ", "Examples of suitable amines are N,N-dibenzylethylenediamine, chloroprocaine, choline, diethanolamine, dicyclohexylamine, ethylenediamine, N-methylglucamine, and procaine (see, for example, Berge, supra., ", "1977).", "\nBase salts of acidic invention compounds are prepared by contacting the free acid form of the invention compounds with a sufficient amount of the desired base to produce a salt in the conventional manner.", "\nCertain of the compounds of the present invention can exist in unsolvated forms as well as solvated forms, including hydrated forms. ", "In general, the solvated forms, including hydrated forms, are equivalent to unsolvated forms and are intended to be encompassed within the scope of the present invention.", "\nThe compounds of the invention may be prepared by a number of methods well known to a person of average skill in the arts of organic and medicinal chemistries.", "\nIt should be appreciated that the organic and medicinal chemistry arts provide the skilled artisan with electronically searchable literature, reaction, and reagent databases and a wide variety of commercially available starting materials. ", "For example, see the databases of the Chemical Abstracts service (Columbus, Ohio); Katritzky, Alan R., Handbook of Heterocyclic Chemistry, Pergamon Press, Ltd., 1985, Volumes 4 and 5; and The Aldrich Catalog (Sigma-Aldrich Corporation, St. Louis, Mo.).", "\nFor examples of the preparation of optically pure xcex942-isoxazolines (i.e., chiral xcex942-isoxazolines that consist of only one enantiomer, or substantially one enantiomer), see Yang, K-S, et al., ", "Tetrahedron Letters, 2000;41:1453-1456 or Shimizu, M. et al., ", "Chemistry Letters, 1996:455-456.", "\nAs described above, some of the invention compounds possess chiral centers. ", "It should be appreciated that a person skilled in the medicinal and organic chemistry arts is able to prepare chiral invention compounds by classical resolution techniques and/or asymmetric synthesis.", "\nIt should also be appreciated for purposes of synthesizing the compounds of the invention that reactive functional groups present in starting materials, reaction intermediates, or reaction products may be protected during chemical reactions using protecting groups which render the reactive functional groups substantially inert to the reaction conditions (see for example, Protective Groups in Organic Synthesis, 2nd ed., ", "Green T W and Wuts P G, John Wiley and Sons, New York, N.Y. 1991). ", "Thus, for example, protecting groups such as the following may be utilized to protect suitable amino, hydroxyl, and other groups of related reactivity: carboxylic acyl groups, such as formyl, acetyl, trifluoroacetyl; alkoxycarbonyl groups, such as ethoxycarbonyl, t-butoxycarbonyl (BOC), xcex2,xcex2,xcex2-trichloroethoxycarbonyl (TCEC), xcex2-iodoethoxycarbonyl; aryloxycarbonyl groups, such as benzyloxycarbonyl (CBZ), p-methoxybenzyloxycarbonyl, phenoxycarbonyl; trialkyl silyl groups, such as trimethylsilyl and t-butyldimethylsilyl (TBDMS); and groups such as trityl, tetrahydropyranyl, vinyloxycarbonyl, o-nitrophenylsulfenyl, diphenylphosphinyl, p-toluenesulfonyl, and benzyl may all be utilized. ", "The protecting group may be removed, after completion of the synthetic reaction of interest, by procedures known to those skilled in the art. ", "For example, a BOC group may be removed by acidolysis, a trityl group by hydrogenolysis, TBDMS by treatment with fluoride ions, and TCEC by treatment with zinc. ", "Use of protecting groups in organic synthesis is well within the skill of the average artisan.", "\nIt should be appreciated that reagents, solvents, and starting materials necessary for the preparation of the compounds of the invention may be purchased from a number of commercial sources or may be readily prepared by a number of methods well known to one of average skill in the art of organic chemistry. ", "Further, reactions used to prepare the invention compounds can be carried out under a wide variety of conditions comprising solvents, reagents, catalysts, temperatures, time, atmosphere, and pressure.", "\nMany different methods may be used to prepare the invention compounds. ", "However for purposes of practicing the invention, which comprises compounds, pharmaceutical compositions, and methods of treating certain disorders and diseases, it does not matter how the compounds are made. ", "Nevertheless, novel methods of preparing the invention compounds are valuable as they may afford improvements in ease of synthesis or purification, cost of preparation, or process time. ", "As discussed above, the invention provides novel methods of making the invention compounds.", "\nFor example, one method of preparing the compounds of the invention is described below in Scheme 1. ", "\nwherein R1, g, Z, h, R2, R3, V, B, X1, d, E, and Y are as defined above and L is a leaving group such that when V is (CH2)n or (CH2)mxe2x80x94Cxe2x95x90O, wherein m is not 0, L is, for example, halogen, CH3CO2xe2x80x94, CF3CO2xe2x80x94, CF3SO3xe2x80x94, p-toluyl-SO3xe2x80x94, and the like; and when V is Cxe2x95x90O, L is, for example, halogen, hydroxy, which can form intermediates activated for displacement by a compound of formula A by reaction with coupling agents such as, for example, carbonyldiimidazole (CDI), N,Nxe2x80x2-dicyclohexylcarbodiimide (DCC), and the like, benzotriazol-1-yl, imidazol-1-yl, CH3CO2xe2x80x94, and the like.", "\nIn Scheme 1, a compound of formula A, wherein R1, g, and R2 are as defined above, is allowed to react with a compound of formula B, wherein L is a leaving group which is displaced by a compound of formula A, to provide a compound of Formula I. In a preferred procedure, a compound of formula A is dissolved or suspended in an aprotic, polar solvent such as, for example, N,N-dimethylformamide (DMF), ethyl acetate, dimethylsulfoxide (DMSO), acetonitrile, nitromethane, acetone, and the like, and optionally a 1 to 2 molar equivalents of a non-nucleophilic base such as, for example, triethylamine, diisopropylethylamine, sodium hydride, and the like is added, followed by addition of a compound of formula B as a neat material (i.e., only the material itself in solid or liquid form) or in a solution of an aprotic, polar solvent such as, for example, the aprotic, polar solvents recited above, at an addition rate that maintains a desired reaction temperature, and the mixture is stirred in air or under an inert atmosphere such as, for example, nitrogen or argon, to give a compound of Formula I. In another preferred procedure, a compound of formula A is dissolved or suspended in an aprotic, nonpolar solvent such as, for example, tetrahydrofuran (THF), diethylether, hexanes, and the like, and about one molar equivalent of a strong base such as, for example, n-butyl lithium, sec-butyl lithium, tert-butyl lithium, potassium hexamethyldisilazide (KHMDS), and the like is added, followed by addition of a compound of formula B as a neat material or in a solution of a nonpolar, aprotic solvent such as, for example, the nonpolar, aprotic solvents recited above, at an addition rate that maintains a desired reaction temperature, and the mixture is stirred to give a compound of Formula I. In still another preferred procedure, a compound of formula B, wherein Lxe2x80x94Vxe2x80x94 is HOxe2x80x94C(O)xe2x80x94, is dissolved or suspended in an aprotic solvent such as, for example, THF, DMF, ethyl acetate, and the like, and about 1 molar equivalent of a coupling agent such as, for example, CDI, DCC, bis(2-oxo-3-oxazolidinyl)phosphinic chloride (BOPxe2x80x94Cl), and the like, followed by addition of a compound of formula A as a neat material or in a solution of an aprotic solvent such as, for example, the aprotic solvents recited above, at an addition rate that maintains a desired reaction temperature, and the mixture is stirred to give a compound of Formula I. In Scheme 1, the preferred molar ratio of a compound of formula A to a compound of formula B is about 1:1.", "\nAnother method of preparing the compounds of the invention is described below in Scheme 2. ", "\nwherein Rl, g, Z, h, R2, R3, V, B, X1, d, E, and Y are as defined above, and PG1 and PG2 are protecting groups which may be deprotected to provide the groups E and Y, respectively, of compounds of Formula I. Illustrative examples of PG1 are hydrogen (when E is H), xe2x80x94O-benzyl, xe2x80x94S-benzyl, xe2x80x94NH-benzyl, xe2x80x94NH-(4-methoxybenzyl), xe2x80x94NHxe2x80x94BOC, xe2x80x94NHxe2x80x94CBZ, xe2x80x94Oxe2x80x94TBDMS, xe2x80x94CH2-halo, C(O)xe2x80x94CH2-halo, xe2x80x94CO2Me, C(Oxe2x80x94CH2)2, CH2CH2CO2Me, and the like. ", "Illustrative examples of PG2 are xe2x80x94NH-benzyl, xe2x80x94NH-(4-methoxybenzyl), xe2x80x94NHxe2x80x94BOC, xe2x80x94NHxe2x80x94CBZ, CO2Me, xe2x80x94O-benzyl, xe2x80x94Oxe2x80x94TBDMS, and the like.", "\nIn Scheme 2, a compound of formula C is deprotected to give a compound of Formula I. In a preferred procedure, a compound of formula C, wherein PG1 and/or PG2 is xe2x80x94O-benzyl, xe2x80x94S-benzyl, xe2x80x94NH-benzyl, xe2x80x94NHxe2x80x94CBZ, and the like, is dissolved or suspended in a suitable solvent such as, for example, acetic acid, ethanol, THF, dichloromethane, and the like, and allowed to react with a deprotecting reagent such as, for example, a mixture of hydrogen gas and a suitable hydrogenation catalyst such as, for example, palladium on carbon, palladium on barium sulfate, platinum on carbon, sponge nickel, and the like, under pressure, phosphorous tribromide, hydrochloric acid, titanium tetrachloride, and the like, at an addition rate that maintains a desired reaction temperature, to give a compound of Formula I. Examples 1, 3, 4a, 4b, 5, and 9 are representative of the chemistry described in Scheme 2.", "\nAnother method of preparing the compounds of the invention is described below in Scheme 3. ", "\nwherein R1, g, Z, h, R2, R3, V, B, X1, d, E, and Y are as defined above, and U is xe2x80x94C(H)xe2x95x90C(H)xe2x80x94 or xe2x80x94Cxe2x89xa1Cxe2x80x94.", "\nIn Scheme 3, a compound of formula D is allowed to react with a 3- or 4-membered cyclization reagent to give a compound of Formula I, wherein B is a 5- or 6-membered heterocyclene, respectively. ", "In a preferred procedure, a compound of formula D is dissolved or suspended in an aprotic solvent such as, for example, THF, dichloromethane, acetone, DMF, and the like, and allowed to react with a 3-membered cyclizing reagent such as, for example, an alkylazide, alkyldiazomethane, acetonitrile oxide, prepared by reaction of an aldoxime such as, for example, acetaldoxime [i.e., CH3C(H)xe2x95x90Nxe2x80x94OH] with a radical generating agent such as, N-bromosuccinimide (NBS), N-chlorosuccinimde (NCS), and the like, or a 4-membered cyclizing reagent such as, for example, H2Cxe2x95x90C(H)xe2x80x94C(H)xe2x95x90Nxe2x80x94EDG, wherein EDG is an electron donating group such as, for example, xe2x80x94N(CH3)2, xe2x80x94OMe, and the like, to give a compound of Formula I. Example 2 is representative of the chemistry described in Scheme 3.", "\nAnother method of preparing the compounds of the invention is described below in Scheme 4. ", "\nwherein R1, g, Z, h, R2, R3, V, X1, d, E, and Y are as defined above, B is oxazole, dihydrooxazole, thiazole, or dihydrothiazole, and T is Cxe2x95x90O or C(H)OH.", "\nIn Scheme 4, a compound of formula E is allowed to react with a reagent and/or catalyst under cyclizing conditions to provide a compound of Formula I. In a preferred procedure, a compound of formula D is dissolved in an aprotic solvent such as, for example, THF, ethyl acetate, DMF, DMSO, and the like, and a dehyrdating reagent such as, for example, anhydrous magnesium sulfate, anhydrous calcium chloride, activated 3 angstrom molecular sieves, trimethoxymethane, oxalyl chloride, PCl5, phosphorous pentoxide and the like, is added and optionally an acid catalyst such as, for example, trifluoroacetic acid, para-toluenesulfonic acid, and the like, is added, and the mixture is stirred to provide a compound of Formula I, wherein B is oxazole or dihydrooxazole. ", "In another preferred procedure, a compound of formula D is dissolved in an aprotic solvent such as, for example, THF, ethyl acetate, DMF, DMSO, and the like, and a sulfurating reagent (i.e., a reagent that introduces a sulfur atom) such as, for example, P2S5, [2,4-bis(4-methoxyphenyl)-1,3-dithian-2,4-diphosphetane-2,4-disulfide] (i.e., Lawesson\"\"s reagent), and the like, is added, and the mixture is stirred to provide a compound of Formula I, wherein B is thiazole or dihydrothiazole. ", "Examples 6(a)-6(f) and 8 are representative of the chemistry described in Scheme 4.", "\nAnother method of preparing the compounds of the invention is described below in Scheme 5. ", "\nwherein R1, g, Z, h, R2, R3, V, X1, d, E, and Y are as defined above, B is oxazole, dihydrooxazole, thiazole, or dihydrothiazole, and T is Cxe2x95x90O or C(H)OH.", "\nIn Scheme 5, a compound of Formula F is allowed to react with a reagent and/or catalyst under cyclizing conditions to provide a compound of Formula I. Preferred procedures are as described above in Scheme 4. ", "Examples 7(a) and 7(b) are representative of the chemistry described in Scheme 5.", "\nAnother method of preparing the compounds of the invention is described below in Scheme 6. ", "\nwherein R1, g, Z, h, R2, R3, V, B, X1, d, E, and Y are as defined above.", "\nIn Scheme 6, a compound of Formula I is allowed to react with a reagent to provide a different compound of Formula I. In a preferred procedure, a compound of Formula I wherein V is (CH2)mCxe2x95x90O is dissolved or suspended in a suitable aprotic, nonpolar solvent such as, for example, THF, methyl-tert-butylether (MTBE), hexanes, and the like, and a reducing agent such as, for example, lithium aluminum hydride, sodium borohydride, sodium triacetoxyborohydride, diisobutylaluminum hydride (DIBAL), and the like, is added at an addition rate that maintains a desired reaction temperature, and the mixture is stirred to give a compound of Formula I wherein V is (CH2)n.", "\nAnother method of preparing the compounds of the invention is described below in Scheme 7. ", "\nwherein R1, g, Z, h, R2, R3, V, X1, d, E, and Y are as defined above, B is isoxazole, dihydroisoxazole (i.e., isoxazoline), dihydrothiazoline, or oxazole; J is C(H)xe2x95x90CH2 or Cxe2x89xa1Cxe2x80x94H, and K is C(Cl)xe2x95x90Nxe2x80x94OH.", "\nIn Scheme 7, a compound of formula G is allowed to react with a compound of formula H under [3+2] cyclization conditions to provide a compound of formula I. In a preferred procedure, a compound of formula G and a compound of formula H are dissolved or suspended in a solvent such as, for example, methanol, ethanol, THF, ethyl acetate, toluene, dichloromethane, and the like, and optionally a non-nucleophilic base such as, for example, triethylamine, diisopropylethylamine, sodium hydride, and the like is added, and the mixture is stirred to provide a compound of Formula I. Examples 10 to 16 are representative of the chemistry described in Scheme 7.", "\nExamples of the preparation of the invention compounds are described below." ]

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[ "TobyMac - Me Without You\n\nTobyMac has released his brand new music video for the 2012 radio single, ‘Me Without You’. ", "With the video featuring a special appearance from his son Truett, you can check out the video below. ", "What do you think of the music video and song?" ]

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[ "Neculăieuca\n\nNeculăieuca is a village in Orhei District, Moldova.", "\n\nReferences\n\nCategory:Villages of Orhei District\nCategory:Shtetls\nCategory:Former Jewish agricultural colonies of Bessarabia" ]

{ "pile_set_name": "Wikipedia (en)" }

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[ "Left Foot Forward Left Foot Forward Building a left strong enough to finally send the zombie of neoliberalism to its grave, while holding off Trumpism with the other hand, is a daunting task. ", "But it’s in the struggle that we know we’re the ones still living. ", "Rep. Keith Ellison meets labor organizers at a forum in Minneapolis, February 9, 2016 (Department of Labor / Flickr)\n\nTwenty years ago, in an essay called “Why Fascism is the Wave of the Future,” Edward Luttwak wrote that globalization was accelerating change to an untenable pace. “", "When the sons and daughters of U.S. steelworkers, British miners or German welders must become software-writers, teachers, lawyers, or for that matter shop attendants, because the respective paternal industries offer less and less employment, few of them have reason to complain,” he wrote. “", "But when the same mechanisms of change work so fast that steelworkers, coalminers or welders must themselves abandon lifetime proclivities, self-images and workplace companions to acquire demanding new skills—on penalty of chronic unemployment or unskilled low-wage labour—failure and frustration are the likely results.” ", "Today, one of the most prominent critics of this unfettered globalization—he’s called the Republicans “the Party of Davos donors” and refers to “crony capitalism”—is Steve Bannon, white supremacist senior counselor to president-elect Donald Trump and former executive chairman of Breitbart News.", "\n\nNow that our enemies are in power, what comes next? ", "For starters, if the Democrats stand a chance in the near future, Republicans have conveniently demonstrated for them what they did not believe coming from the left: economic populism works. ", "The DNC chairmanship is up for grabs, and Keith Ellison, a consistently left-wing voice in the Democratic Party and former organizer hailing from Minnesota, is in the race against party stalwarts like South Carolina Democratic Party chairman Jaime Harrison. ", "He’s backed by consistent lefties like Raúl Grijalva and party heavyweights like Chuck Schumer, and enjoys the blessing of Bernie Sanders. ", "The DNC deploys substantial resources, election year or no, and we should be happy to have them in the hands of someone like Ellison.", "\n\nWhen it comes time to legislate, Democrats would do well to drive a wedge between the promised economic populism of Trump, and the budget-cutting priorities of the Paul Ryan camp, by insisting on massive infrastructure spending that isn’t structured as federal tax credits for companies that pledge to build, and by going after Wall Street, a representation of capital that Americans still love to hate. ", "One of Bannon’s trademark targets? ", "The bank bailouts following the 2008 crash. ", "And popular members of the left wing of the Democratic Party—including Sanders and Elizabeth Warren—have shown that left-wing ideas must be delivered by people who hold in common with average Americans a true contempt for the people who have made a mockery of American livelihoods and democracy for about forty years.", "\n\nOn the left, we have our work cut out for us. ", "There are people under immediate threat from a Trump presidency, notably immigrants on the DACA list that protects those brought over illegally as children. ", "Trump is receiving a database of about 800,000 names, and he has promised to deport undocumented immigrants “so fast.” ", "Students and academics are already pushing to turn their schools into sanctuaries for immigrants, and some churches are carrying on their own sanctuary traditions. ", "We must take guidance from the relentlessly brave immigration movement in the days ahead. ", "Similarly, Muslims fear everything from street violence to being registered with the government in a terrifying recapitulation of internment-era policies. ", "There are many organizations working to protect the rights of Muslims in America, from DRUM to the ACLU, that need support. ", "A populist economics means nothing if it is not fused with radical antiracism.", "\n\nThe list of issues goes on, and we have no party, no central structure to fuse them all together. ", "Neoliberalism as an idea is dead, but it’s a zombie walking still. ", "Building a left strong enough to finally send it to its grave, while holding off Trumpism with the other hand, is a daunting task. ", "But it’s in the struggle that we know we’re the ones still living.", "\n\nSarah Leonard is a senior editor at the Nation and editor-at-large at Dissent." ]

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[ "\r\n1. ", "PUT/POST without a known auth to use (possibly no auth required):\r\n\r\n (When explicitly set to use a multi-pass auth when doing a POST/PUT,\r\n libcurl should immediately go the Content-Length: 0 bytes route to avoid\r\n the first send all data phase, step 2. ", "If told to use a single-pass auth,\r\n goto step 3.)", "\r\n\r\n Issue the proper PUT/POST request immediately, with the correct\r\n Content-Length and Expect: headers.", "\r\n\r\n If a 100 response is received or the wait for one times out, start sending\r\n the request-body.", "\r\n\r\n If a 401 (or 407 when talking through a proxy) is received, then:\r\n\r\n If we have \"more than just a little\" data left to send, close the\r\n connection. ", "Exactly what \"more than just a little\" means will have to be\r\n determined. ", "Possibly the current transfer speed should be taken into\r\n account as well.", "\r\n\r\n NOTE: if the size of the POST data is less than MAX_INITIAL_POST_SIZE (when\r\n CURLOPT_POSTFIELDS is used), libcurl will send everything in one single\r\n write() (all request-headers and request-body) and thus it will\r\n unconditionally send the full post data here.", "\r\n\r\n2. ", "PUT/POST with multi-pass auth but not yet completely negotiated:\r\n\r\n Send a PUT/POST request, we know that it will be rejected and thus we claim\r\n Content-Length zero to avoid having to send the request-body. (", "This seems\r\n to be what IE does.)", "\r\n\r\n3. ", "PUT/POST as the last step in the auth negotiation, that is when we have\r\n what we believe is a completed negotiation:\r\n\r\n Send a full and proper PUT/POST request (again) with the proper\r\n Content-Length and a following request-body.", "\r\n\r\n NOTE: this may very well be the second (or even third) time the whole or at\r\n least parts of the request body is sent to the server. ", "Since the data may\r\n be provided to libcurl with a callback, we need a way to tell the app that\r\n the upload is to be restarted so that the callback will provide data from\r\n the start again. ", " This requires an API method/mechanism that libcurl\r\n doesn't have today. ", "See below.", "\r\n\r\nData Rewind\r\n\r\n It will be troublesome for some apps to deal with a rewind like this in all\r\n circumstances. ", "I'm thinking for example when using 'curl' to upload data\r\n from stdin. ", "If libcurl ends up having to rewind the reading for a request\r\n to succeed, of course a lack of this callback or if it returns failure, will\r\n cause the request to fail completely.", "\r\n\r\n The new callback is set with CURLOPT_IOCTLFUNCTION (in an attempt to add a\r\n more generic function that might be used for other IO-related controls in\r\n the future):\r\n\r\n curlioerr curl_ioctl(CURL *handle, curliocmd cmd, void *clientp);\r\n\r\n And in the case where the read is to be rewinded, it would be called with a\r\n cmd named CURLIOCMD_RESTARTREAD. ", "The callback would then return CURLIOE_OK,\r\n if things are fine, or CURLIOE_FAILRESTART if not.", "\r\n\r\nBackwards Compatibility\r\n\r\n The approach used until now, that issues a HEAD on the given URL to trigger\r\n the auth negotiation could still be supported and encouraged, but it would\r\n be up to the app to first fetch a URL with GET/HEAD to negotiate on, since\r\n then a following PUT/POST wouldn't need to negotiate authentication and\r\n thus avoid double-sending data.", "\r\n\r\n Optionally, we keep the current approach if some option is set\r\n (CURLOPT_HEADBEFOREAUTH or similar), since it seems to work fairly well for\r\n POST on most servers.", "\r\n" ]

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[ "Q&A: Stockbox Grocers\n\nWal-Mart, Supervalu and ShopRite are just a few of the many national and regional supermarkets that have committed to bringing fresh, healthful foods back to neighborhoods where the nearest store is measured in impossible miles. ", "The campaign to repair the nation’s food deserts is well underway, but good intentions can take time as store-building projects wend their way through the siting, zoning and construction process. ", "In the meantime, nimble startups like Stockbox Grocers in Seattle are worth watching for the unique ideas they bring to these underserved areas. ", "Chief among them: Why not sell it all out of a shipping container? ", "Co-founder Carrie Ferrence explains.", "\n\nStockbox Grocery’s pilot store operated out of a shipping container placed in the parking lot of a housing project. ", "Why?", "\n\nWe were really looking for ways to minimize our setup and operating costs. ", "That’s really one of the bigger reasons why grocery stores and convenience store aren’t serving these communities with good food. ", "By directly addressing the limitations of competitors, we were able to put a bigger focus on the food itself, to focus on the food that isn’t being provided like produce and healthy grocery staples.", "\n\nSo apples, oranges, and other produce items mostly?", "\n\nWe’re not just focusing on produce. ", "We’re focusing on fresh food and the food that people purchase most frequently in between large grocery trips. ", "We can’t replace a 40,000 square foot store, but what we can do is provide the items that people run out of most frequently to get them in between the larger trips\n\nWhat was the demand like during the three-month trial?", "\n\nWe were surprised by the demand for produce. ", "I think sometimes food desert communities it’s assumed they aren’t looking for fresh and healthy food, and we learned that there is a lot of pent-up demand for it.", "\n\nWere people hesitant at all? ", "What did they think when they suddenly saw this shipping container full of food?", "\n\nWe would often find people standing 20 feet away from the store, just staring at it. ", "We would have to literally invite them into the space. ", "I think that’s just something that, when you’re promoting a different concept like that, you have to put that much more effort into creating a bridge.", "\n\nWill outreach be a bigger part of the business plan going forward?", "\n\nWe had been building relationships with community groups prior to opening the prototype store, but we are expanding our work with other nonprofits to expand education. ", "We also want to get the word out to more diverse communities, as well. ", "So we’re expanding our ability to communicate in different languages and use different messages.", "\n\nWhat’s the rollout plan for this year?", "\n\nWe are hoping to get the first store off the ground in May, and then get a second store off the ground later in the year. ", "So the goal is for two stores in 2012. ", "We are still finalizing the financing and the location, but we have most of our suppliers in line. ", "We can roll a store out pretty quickly once we get the financing in line.", "\n\nHow many products will the stores carry?", "\n\nThe prototype we had 300 unique SKUs. ", "We will probably have a little bit more in our permanent stores once we get the first one off the ground. ", "We’ll probably have closer to 400 SKUs.", "\n\nSo why start a supermarket like this and not a mobile market, as so many others are doing in food deserts?", "\n\nStockbox initially started as a mobile market. ", "But we quickly changed it to be a more permanent model based on the analysis we did of existing mobile markets. ", "Several of them have failed and several have only stayed in existence as a nonprofit model. ", "When we looked into why, we discovered the reason is communities couldn’t depend on them. ", "If you run out of milk or you run out of produce and the truck doesn’t come by for a couple days, it’s not really responding to the fundamental need for access. ", "So we wanted to make something really dependable and really accessible in the community\n\nI read you’ve been getting calls from people interested in franchising?", "\n\nWe’re surprised to see how much support there has been for this idea. ", "I think we see people all over the country seeing an opportunity for this to work. ", "Everyone has parking lots, everyone has shipping containers. ", "These are resources that can be adapted to work in most urban environments." ]

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[ ". ", "What is x(o)?", "\n3\nLet f(q) be the third derivative of q**5/6 + q**4/24 - q**3/6 - 3087*q**2. ", "Let n be 4/(-6)*(-3)/2. ", "Calculate f(n).", "\n10\nLet f = -6 - -8. ", "Let r(s) = -s**f + 5*s**2 - 4*s**2 - s**2 - s. Let v be (5/(-3) - 1) + 32/48. ", "Calculate r(v).", "\n-2\nLet p(f) = -f**3 + f**2 + 2*f - 12. ", "Let n be (-140)/(-44) + 44/(-242). ", "Let c be n*18/(-297) - 8/(-44). ", "Give p(c).", "\n-12\nLet k(i) be the second derivative of i**4/12 + 4*i**3/3 + 9*i**2/2 - 17*i + 6. ", "Let z be (-3)/(-2)*14/21. ", "Suppose 0 = -5*o, -5 = s + 2*o + z. Calculate k(s).", "\n-3\nLet j be ((-52)/12 + 3)*-6. ", "Suppose -j = -5*b + 2. ", "Let y(n) = 5 - 8*n + 2 + n**b + 1 - 10. ", "Give y(8).", "\n-2\nLet j(k) be the third derivative of k**4/24 + 23*k**3/6 - 551*k**2. ", "Give j(-11).", "\n12\nLet u = -25849 + 25849. ", "Let k(o) be the second derivative of 33*o - 1/3*o**3 + u + o**2. ", "Calculate k(-5).", "\n12\nLet d(w) be the second derivative of -w**5/10 - 7*w**4/12 + w**3/6 + w**2 - 2672*w + 2. ", "Give d(-3).", "\n-10\nLet a(v) = v**3 - 15*v**2 + 24*v + 47. ", "Suppose 5*o - 5*h - 80 = 0, 411*o = 407*o + h + 55. ", "Give a(o).", "\n21\nLet q(b) = 57*b**2 - b**3 + 306*b - 50*b**2 - 311*b. ", "What is q(5)?", "\n25\nLet a be 4*14*(21/132 - (-50)/550). ", "Let q(n) be the third derivative of n**6/120 - 7*n**5/30 + n**4/24 - 5*n**3/6 + n**2. ", "What is q(a)?", "\n9\nLet v(j) = j + 1. ", "Let c(g) = -4*g + 1. ", "Let k(w) = 6*c(w) + 7*v(w). ", "What is k(-2)?", "\n47\nSuppose 2*a + 3*p = 5, 0 = 5*p + 157 - 162. ", "Let j(k) = -4*k + 7. ", "What is j(a)?", "\n3\nLet d(p) = -p**3 - 5*p**2 + 7*p + 1. ", "Let q be d(-6). ", "Let y(z) = -3*z**2 + 5*z. ", "Let h(b) = 2 - 1 + 9*b**2 - 10*b - 2*b**2. ", "Let a(u) = 4*h(u) + 9*y(u). ", "Give a(q).", "\n4\nSuppose 6*g - 7 = u + 4*g, 0 = -2*u - 5*g + 4. ", "Let r(n) = -n**2 - 6*n - 5. ", "Give r(u).", "\n4\nLet r(u) = -u**2 - 7*u + 9. ", "Let b(y) = 22*y + 234. ", "Let s be b(-11). ", "Determine r(s).", "\n1\nLet j be 13/(-390)*(-6 - -1). ", "Let l(b) be the third derivative of 0*b - j*b**4 + 1/3*b**3 + 10*b**2 + 1/20*b**5 + 0. ", "Calculate l(2).", "\n6\nLet v = 8 - 16. ", "Let s(d) be the first derivative of d**4/4 + 3*d**3 + 5*d**2 + 8*d - 25258. ", "Give s(v).", "\n-8\nLet p(a) be the second derivative of -7*a**3/6 - a**2/2 - 20*a. ", "Suppose -3*h + 447 = -5*d - 0*h, -h - 1 = 0. ", "Let u = d - -91. ", "Determine p(u).", "\n-8\nLet q(w) = -14*w + 14. ", "Let l be q(9). ", "Let j = -161 - l. Let h = j + 44. ", "Let g(u) = u**2 + 7*u + 3. ", "Give g(h).", "\n-7\nLet m(u) = -2*u + 7*u + u - 14 - 5*u. ", "Let s be (-1 + 52/(-28))*21/(-6). ", "What is m(s)?", "\n-4\nLet t(n) = -n**3 + 5*n**2 - 5*n + n - 7 + n. Let k be 2/10 + 2/(-10)*-24. ", "Suppose k*h - 8 = 17. ", "What is t(h)?", "\n-22\nLet r(o) be the third derivative of -o**5/30 + 7*o**4/12 + o**3/3 + 740*o**2. ", "Determine r(10).", "\n-58\nLet a(i) be the first derivative of i**2 - 39*i - 961. ", "Determine a(18).", "\n-3\nLet l(p) be the first derivative of p**4/4 + 2*p**3/3 - 3*p**2/2 + 4*p - 15. ", "Let n = 697 - 700. ", "What is l(n)?", "\n4\nLet v(t) be the second derivative of t**5/10 - t**4/6 + t**3/3 - 2*t. ", "Let q = -167 + 168. ", "Let n be -1 + -2 + (q - (-4)/1). ", "Give v(n).", "\n12\nLet a(w) = -w**2 + 2*w + 2. ", "Let n = 325 - 664. ", "Let h = 344 + n. What is a(h)?", "\n-13\nLet r(t) = t - 28. ", "Let a be r(39). ", "Suppose 0 = -6*p + 53 - a. Let q(k) = k**2 - 5*k - 12. ", "Calculate q(p).", "\n2\nLet r(v) be the third derivative of -v**5/20 - v**4 - v**3/2 + 3714*v**2. ", "What is r(-8)?", "\n-3\nLet k(n) be the first derivative of -n**6/60 - n**5/30 + n**4/24 - n**3/6 + 13*n**2 - 73. ", "Let l(m) be the second derivative of k(m). ", "Calculate l(-2).", "\n5\nLet h(n) = 4*n - 20. ", "Let s(q) = -q**2 - 45*q - 499. ", "Let u be s(-22). ", "Give h(u).", "\n8\nLet d(k) = k**3 + 3*k - 1. ", "Suppose -21 = -48*t + 53*t + 2*w, 4*w = -5*t - 27. ", "Calculate d(t).", "\n-37\nLet s = -35472 - -35463. ", "Let y(a) = a**3 + 10*a**2 + 8*a - 3. ", "Give y(s).", "\n6\nSuppose 5*t = 20, 6 = 4*b - 3*t + 2. ", "Let d(g) = g + 10. ", "Let m(f) = f + 7. ", "Let n(p) = 3*d(p) - 4*m(p). ", "Calculate n(b).", "\n-2\nLet d = 58 + -90. ", "Suppose -146 = -10*y - 226. ", "Let o be (48/d)/(6/y). ", "Let b(g) = 3*g**2 - g - 2. ", "Determine b(o).", "\n8\nLet a(z) = 18*z - 1. ", "Let m(p) = -55*p + 4. ", "Suppose -7 = -3*j - 1. ", "Let g(u) = j*m(u) + 7*a(u). ", "Let f(n) = -n**3 + 18*n**2 - 14*n - 52. ", "Let h be f(17). ", "Give g(h).", "\n-15\nLet f(j) = -44*j - 219. ", "Let b be f(-5). ", "Let a(z) = z. Determine a(b).", "\n1\nLet m(g) = -272*g**3 + 11*g**2 + 7*g. ", "Let q(w) = -147*w**3 + 6*w**2 + 4*w. ", "Let s(p) = 6*m(p) - 11*q(p). ", "Give s(-2).", "\n124\nLet s(d) = -d**3 + 10*d**2 + 11*d - 1. ", "Let v(k) = k**3 + 8*k**2 + 14*k + 6. ", "Suppose -3*m + 26 = 41. ", "Let l be v(m). ", "Calculate s(l).", "\n-1\nLet f(k) be the first derivative of -k**4/4 + 2*k**3/3 + 3*k**2/2 + k + 18. ", "Let d be f(3). ", "Let h be 21/(-14)*(1 + d). ", "Let b(n) = -n - 1. ", "Calculate b(h).", "\n2\nLet b(h) = h + 2. ", "Suppose 14 + 16 = -5*s. ", "Suppose -4*j = 12 + 12. ", "Let p be 3 + s - (2 - 1)*j. ", "Determine b(p).", "\n5\nLet y(j) = j**2 - j - 3. ", "Let x(s) = 8*s**2 - 5*s - 4. ", "Let w(n) = -14*n**2 + 9*n + 8. ", "Let g(v) = 3*w(v) + 5*x(v). ", "Let u(a) = 2*g(a) + 3*y(a). ", "What is u(1)?", "\n-1\nLet a be 76/57 - ((-10)/6 - -1). ", "Let q(n) = 2*n**2 - 5*n + 4. ", "Let g be q(a). ", "Let b(u) = 5*u**2 + u + 11*u**2 - g*u**2. ", "Give b(1).", "\n15\nLet p be ((-165)/(-10))/(27/18). ", "Let o(s) = s**3 - 10*s**2 - 14*s + 4. ", "Determine o(p).", "\n-29\nLet h(c) be the third derivative of c**5/60 + c**4/3 - 5*c**3/6 + 9*c**2 + 10*c. ", "What is h(-7)?", "\n-12\nLet f(p) = p**3 - 6*p**2 + 4*p + 3. ", "Suppose -4*c - 39 = -147. ", "Let v(g) = -g**3 + 17*g**2 + 4*g - 36. ", "Let z be v(17). ", "Let y = z - c. What is f(y)?", "\n-2\nLet a(p) = 15*p**3 - 2*p**2 + 1. ", "Let i(r) = r**3 + 36*r**2 + 39*r + 141. ", "Let l be i(-35). ", "Calculate a(l).", "\n14\nLet q(o) = -o**2 + 6*o + 9. ", "Suppose -c + 14 = 2*k, -6*k - 17 = -4*c - k. Calculate q(c).", "\n-7\nLet l(u) = -u**2 - 10*u - 19. ", "Suppose -2*k - 35 = 8*m - 3*m, -3*m = 2*k + 17. ", "Give l(m).", "\n-10\nLet u(m) = m**2 - 5*m - 3. ", "Suppose 4*g - l = 107, -4*g - 3*l + 38 + 73 = 0. ", "Suppose 5*b = 18*q - 23*q, -4*q - g = -5*b. ", "Calculate u(b).", "\n-9\nLet n(k) = -6*k + 2*k**2 + 0*k - 5*k**2. ", "Let t(g) = -g**3 + 24*g**2 + 100*g - 517. ", "Let b be t(27). ", "What is n(b)?", "\n-24\nLet h be ((-6)/(-240)*-2)/((-66)/55). ", "Let r(l) be the third derivative of 0 - 9*l**2 + 0*l - 5/3*l**3 - h*l**4. ", "What is r(-7)?", "\n-3\nLet s(w) be the second derivative of -w**5/10 + 8*w**4/3 - w**3/2 + 18*w**2 - 10279*w. ", "What is s(16)?", "\n-12\nLet k = -19173 + 57521/3. ", "Let w(v) be the first derivative of v + k*v**3 + 11 + 2*v**2. ", "Give w(-4).", "\n17\nLet i(q) be the third derivative of q**7/5040 - q**5/20 - 2*q**2. ", "Let h(o) be the third derivative of i(o). ", "Suppose 26 = -2*v - 5*x, -x + 16 = -5*x. ", "Give h(v).", "\n-3\nLet u be (-180)/(95 + -59) - (0 - -7 - 0). ", "Let t(o) = o**3 + 11*o**2 - 6*o - 7. ", "Determine t(u).", "\n-79\nSuppose 3*d = -4*f - 116, -f + 0*f = 5*d + 199. ", "Let b = d + 46. ", "Let n(z) = -b*z**3 - 7 - 5*z + 7*z**3 + 4*z**2 + 0*z. ", "What is n(-5)?", "\n-7\nLet y be (-30)/315 + (-1640)/(-21). ", "Suppose 8*p + 126 - y = 0. ", "Let a(o) = 2*o + 3. ", "Determine a(p).", "\n-9\nLet y = -199 - -202. ", "Let p(b) = 0*b**y - 5 + 9 + 6*b - b**3 - 4*b**2. ", "Determine p(-5).", "\n-1\nLet f(o) = o + 5 + 15 + o - 6*o**2 - 8 + o**3. ", "Let x be f(5). ", "Let k(s) = s**3 + 2*s**2 - 4*s - 2. ", "Give k(x).", "\n1\nLet f(q) = -q**3 - 4*q**2 + 2*q - 12. ", "Suppose -3*o - n = -3, -2*o = 2*o + 3*n - 9. ", "Suppose -7*b - b - 40 = o. Determine f(b).", "\n3\nSuppose -16*m + 6*m = 250. ", "Let f be (m - -17)*6/8. ", "Let w(d) = -d**3 - 5*d**2 + 7*d + 5. ", "What is w(f)?", "\n-1\nLet k(l) = l + 22. ", "Suppose -113 = 3*b - 5*y - 30, -2 = y. Give k(b).", "\n-9\nLet l(t) = 3*t - 17207*t**2 - 9 + 17208*t**2 - 1 - 3*t. ", "What is l(3)?", "\n-1\nLet v(b) = b**2 - 11*b - 12. ", "Suppose 2*c + 16 = 3*p, -4*c + 8 = p - 2*c. ", "Suppose p*r - 19*r - 2691 = 0. ", "Let m be r/(-18) - 2/4. ", "Give v(m).", "\n-12\nSuppose 0 = -4*s, 3*s = -b + 3*s + 5*s - 15. ", "Let j(h) = -6*h - 82. ", "What is j(b)?", "\n8\nLet p(j) = 4*j**2 - 4 - 53*j + 57*j - j**3 - 2*j**2 - 3. ", "Let l be p(3). ", "Let q(t) = -2*t - 2. ", "Calculate q(l).", "\n6\nLet u(t) = 2*t + 0*t**2 + 3*t**3 - 2*t**3 + t**2 - 2*t**2 + 4. ", "Suppose 0 = 4*b - 5*b - 9*v - 9, 2*v + 2 = -3*b. ", "Give u(b).", "\n4\nSuppose 4*i - 4 = 2*s, 4*s - 4*i + 4 = -4. ", "Let x(y) = -2*y**3 - 4*y**2 - 4*y - 2. ", "Calculate x(s).", "\n6\nLet o be (-11)/(-3) + -1 + (-130)/(-39). ", "Let t(k) = 29*k - 175. ", "Calculate t(o).", "\n-1\nLet z(s) = s**2 + 6*s - 2. ", "Let l = 51 - 45. ", "Let m = l - 52. ", "Let a = 41 + m. Determine z(a).", "\n-7\nLet i(h) be the first derivative of -h**2 - 1/4*h**4 - 3 - 5/3*h**3 + h. Let c be i(-4). ", "Let j(x) = -2*x - 7. ", "Calculate j(c).", "\n7\nSuppose -2646 = -109*g - 121*g + 41*g. ", "Let u(z) = -10*z + 140. ", "Calculate u(g).", "\n0\nLet w = -301 - -304. ", "Let b(x) = -5*x**3 + 3*x**2 + 18*x**w - 2 - 3*x - 4*x**3 - 8*x**3. ", "Calc" ]

{ "pile_set_name": "DM Mathematics" }

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[ "Plain English summary {#Sec1}\n=====================\n\nMistreatment during childbirth remains a well-documented worldwide challenge, especially among poorer, younger and less educated women. ", "In Ghana, the most vulnerable groups include adolescents, who also happen to bear a disproportionately high risk of maternal mortality. ", "Despite the increasing rates of facility-based births which are attended to by trained obstetric professionals, maternal mortality persists as a public health challenge in Ghana and sub-Saharan Africa in general. ", "Following landscape studies which suggest that mistreatment during delivery may be a strong predictor for poor birth outcomes, the WHO has recommended that this issue be addressed with respectful maternity care. ", "This study, therefore, aims to determine the effectiveness of a training intervention for health providers targeted at reducing mistreatment of adolescents during childbirth. ", "This will contribute to knowledge and inform programming and policy on improving maternal healthcare and reducing maternal mortality and morbidity, especially among adolescents.", "\n\nBackground {#Sec2}\n==========\n\nMistreatment suffered by women who deliver within health facilities is an extensively documented phenomenon \\[[@CR1]--[@CR3]\\]. ", "The most reported forms of facility-based mistreatment which often occur in a continuum are categorized as physical abuse, non-consented care, non-confidential care, non-dignified care, discrimination based on specific patient attributes, abandonment of care, and detention in facilities \\[[@CR4]\\]. ", "Whilst intrapartum mistreatment traverses geographical boundaries and socio-economic levels, \\[[@CR1], [@CR2], [@CR5]--[@CR7]\\] certain factions of women appear to bear a markedly high burden of the phenomenon \\[[@CR8]--[@CR10]\\]. ", "As a group of interest, adolescent women appear disproportionately predisposed to disrespectful treatment attributable to their young age, lower educational attainment, lower socio-economic status, lack of autonomy, as well as provider and social prejudices about their engagement in pre-marital and early sex \\[[@CR11]--[@CR15]\\]. ", "Mistreatment in service provision for pregnant adolescents is problematic as it compounds the already existing burden of social and health risks \\[[@CR11], [@CR16]--[@CR18]\\]. ", "Currently, maternal mortality remains one of the leading global causes of death among adolescents, especially in sub-Saharan Africa and is considered a pressing public health challenge \\[[@CR19]\\]. ", "Approximately 11% of births worldwide occur among adolescent girls aged between 15 and 19 years old, majority of which occur in low to middle income countries \\[[@CR20]\\]. ", "In Ghana, this proportion of 14% is approximately a third higher than the global average \\[[@CR21], [@CR22]\\]. ", "Despite the absence of nationally representative data on what proportion of maternal deaths are adolescents, research suggests adolescents may constitute a larger proportion of maternal mortality and morbidity figures since they bear a higher risk of pregnancy-related complications than their older counterparts \\[[@CR23]\\]. ", "A WHO Multi-country Survey on Maternal and Newborn Health revealed that adolescents 19 years and below were twice as likely to develop eclampsia than women over 20 years of age \\[[@CR24]\\]. ", "The same study reported a 50% higher probability of systemic infections among adolescents and a 13% higher likelihood of severe maternal outcomes as compared to women over the age of 20 years. ", "Studies investigating efficacious strategies which may successfully alleviate this burden have identified appropriately-timed intrapartum interventions to be the most beneficial means of reducing maternal mortality and morbidity compared to antenatal and postpartum interventions \\[[@CR25]--[@CR27]\\]. ", "These include promoting facility-based births and as a corollary, increasing skilled birth attendance to enable early identification and management of complications \\[[@CR27], [@CR28]\\]. ", "Accordingly, interventions in Ghana have targeted overcoming barriers to facility access especially geographic and financial factors. ", "Financial access has been improved by waiving antenatal care and delivery fees whilst the establishment of Community-Based Health Planning Service Compounds (CHPS-Compound) has improved provision of maternal care to the last mile within communities \\[[@CR29]--[@CR31]\\]. ", "Nonetheless, the proportion of facility-based births in Ghana at 78% is currently less than the global average of 81% \\[[@CR22]\\]. ", "Additionally, the national maternal mortality rate of 308 per 1000 births is still markedly higher than the global average of 211 per 1000 births and far short of the SDG target of 70 per 1000 births \\[[@CR21]\\]. ", "Within the five years preceding the 2017 Ghana Maternal and Health Survey, only 71% of pregnant adolescents utilized facility-based deliveries \\[[@CR22]\\]. ", "This has been linked to the mistreatment parturients face during facility-based births \\[[@CR32], [@CR33]\\]. ", "This data suggests that attempts to improve maternal mortality and morbidity may be hindered by the mistreatment of adolescents during childbirth.", "\n\nConsequently, the Human Reproduction Programme of the World Health Organization (WHO-HRP), has prescribed recommendations on addressing mistreatment of women during childbirth with respectful maternity care \\[[@CR34]\\]. ", "Respectful Maternity Care (RMC) refers to the organization and management of health systems in a manner that ensures respect for women's sexual and reproductive health and human rights \\[[@CR34]\\]. ", "Indeed, the absence of RMC has been identified as a key disincentive to accessing facility-based births; even in contexts where financial and physical access are not necessarily problematic \\[[@CR14], [@CR32], [@CR35]\\]. ", "Studies have also reported adverse clinical outcomes like prolonged labour, unnecessary pain, haemorrhage, mental distress and in extreme cases, death \\[[@CR36]--[@CR39]\\] during facility based births where RMC is not practiced. ", "This underscores the need for RMC not only to promote uptake of facility-based deliveries, but also to improve birth outcomes and reduce complications.", "\n\nConsidering that the sexual reproductive health and rights (SRHR) of Ghanaian adolescents are constitutionally entrenched \\[[@CR40]\\], backed by research-based policy \\[[@CR41]\\] and heavily invested in by the government of Ghana and other development partners, improving the quality of maternity care for adolescents should be a national priority. ", "Moreover, whilst studies have strongly linked mistreatment to poor outcomes, there is relatively little insight on specific interventions that successfully promote RMC for adolescents. ", "Against this background of limited information and knowledge about adolescents' experiences and outcomes with mistreatment during childbirth, this study seeks to characterize the experiences and outcomes of adolescents who face mistreatment during facility-based births. ", "The study seeks to test the outcome of the proposed intervention in promoting RMC during facility-based deliveries for parturient adolescents. ", "This study also presents an opportunity in addressing some existing gaps in knowledge and information for policy and programming for adolescent maternal health and SRHR.", "\n\nStudy aim {#Sec3}\n---------\n\nThe overall aim of the study is to determine the effectiveness of a training intervention in promoting respectful maternity care for adolescents during facility-based delivery.", "\n\nSpecific objectives {#Sec4}\n-------------------\n\nThe specific objectives of this study are to. ", "Synthesise the available evidence relating to the mistreatment and the provision of respectful maternity care for adolescents during facility-based childbirth using a systematic review approach.", "Estimate the prevalence of mistreatment during facility-based childbirth among adolescents.", "Identify the risk factors and outcomes of intra-partum mistreatment during facility-based childbirth among adolescents.", "Document and characterize the experiences of adolescents who suffer mistreatment during facility-based childbirth.", "Determine the most and least common forms of Respectful Maternity Care offered to adolescent parturients.", "Determine the effectiveness of an intervention in promoting respectful maternity care and increasing satisfaction with facility-based births and skilled birth attendance for parturient adolescents.", "\n\nConceptual framework {#Sec5}\n--------------------\n\nThe proposed study is diagrammatically represented in Fig.", " [1](#Fig1){ref-type=\"fig\"}. ", "The conceptual framework is theoretically based and developed from the review of existent literature on intrapartum mistreatment and RMC. ", "Fig. ", "1Conceptual Framework\n\nMethods {#Sec6}\n=======\n\nStudy settings {#Sec7}\n--------------\n\nThe study intervention will be sited in three regions in Ghana: Eastern, Central and Greater-Accra regions. ", "The intervention sites are public health facilities in the Lower Manya Krobo, Upper Manya Krobo district, and the Awutu-Senya East Municipality. ", "The control sites will be in the Ada East, Shai-Osudoku and Effutu Districts. ", "These districts have an average of 11% of their population being adolescent females \\[[@CR42]\\] and reported adolescent pregnancy rates higher than the national average of 14% \\[[@CR22]\\] . ", "The intervention and control sites are selected health facilities which are matched on the type of facilities being district health centres and district hospitals. ", "For each of the intervention sites, a senior member of the district quality of care team will be included as a resource person in the RMC trainings.", "\n\nStudy design {#Sec8}\n------------\n\nThe study is a non-equivalence pre-test post-test quasi-experimental study. ", "Both qualitative and quantitative methods will be used in data collection.", "\n\nQuantitative study population {#Sec9}\n-----------------------------\n\nStudy participants in the quantitative phase will be adolescent females between the ages of 10 and 19 years old who deliver at the participating facilities.", "\n\nQualitative study population {#Sec10}\n----------------------------\n\nThe first group of participants in the qualitative phase of this study are adolescent females between the ages of 10 and 19 years old who deliver at the participating study sites. ", "The second group of participants are health providers in full time employment at the study sites. ", "Adolescents and health professionals alike will be invited to participate in the study based on the study inclusion criteria and will be enrolled based on their consent to participate. ", "Adolescents will be invited to participate in In-Depth Interviews (IDIs) and the professionals will participate in Key Informant Interviews (KIIs).", "\n\nInclusion criteria {#Sec11}\n------------------\n\nAdolescents will be deemed eligible for participation if they satisfy the following criteria. ", "i.Between the ages of 10 and 19 years.ii.", "Present at any of the selected health facilities for delivery, antenatal care within their third trimester or post-natal care within two weeks of delivery.iii.", "Consent to participate in the study.", "\n\nEligibility criteria for health professionals are. ", "i.Health providers including midwives and administrators who are in full time employment at the selected health facilities.ii.", "Consent to participate in the study.", "\n\nExclusion criteria {#Sec12}\n------------------\n\nHealth professionals and adolescents will be excluded based on the following criteria i.Decline to participateii.", "Are physically or mentally ill or indisposediii.", "Did not deliver at the facilities in the study if they are adolescents or are not obstetric care providers or administrative staff of the facilities\n\nSample size determination {#Sec13}\n-------------------------\n\nThe minimum sample size for adolescents is obtained observing the assumptions that the estimated proportion of women who encounter mistreatment during childbirth is 18% \\[[@CR43]\\] and the proposed intervention may reduce this by 10 percentage points. ", "Additionally, a 5% margin of error, a 95% significance level and 80% power are estimated. ", "N = estimated sample size for one arm.", "Za = Critical value at confidence interval of 95% (1.96).Zb = Critical value at power of 80% (0.842).d = Actual difference in proportion between control and intervention groups (0.1).P = Average of difference in proportion of both groups\n\n$$\\documentclass[12pt]{minimal}\n \\usepackage{amsmath}\n \\usepackage{wasysym} \n \\usepackage{amsfonts} \n \\usepackage{amssymb} \n \\usepackage{amsbsy}\n \\usepackage{mathrsfs}\n \\usepackage{upgreek}\n \\setlength{\\oddsidemargin}{-69pt}\n \\begin{document}$$ \\mathrm{N}=2\\times \\frac{{\\left( Z\\alpha + Z\\beta \\right)}^2}{d^2}\\times p\\left(1-p\\right) $$\\end{document}$$\n\nAn intra-cluster design effect of 1.11 and a non-response adjustment of 10% is factored to obtain a minimum sample size of 392.", "\n\nA minimum of 10 healthcare participants and 10 adolescents will be included in qualitative Key Informant Interviews It is anticipated that the number of interviews will allow a sample size large enough to allow data saturation to understand the phenomenon of mistreatment from both provider and client perspectives.", "\n\nSampling procedure {#Sec14}\n------------------\n\nMultistage, stratified and systematic sampling will be used to recruit study participants from the facilities where they attend. ", "Using data available from the 2010 Population and Housing Census, three out of the formerly ten regions in Ghana with adolescent pregnancy rates higher than the national average (14%) were randomly selected. ", "Subsequently, six districts were purposefully selected from these regions considering appropriateness for the intervention, available resources, and geographical non-proximity between intervention and control facilities. ", "Facilities in the intervention and control arms of the study were matched based on the number of adolescent pregnancies delivered annually using the Ghana Health Service District Health Information Management System (GHS-DHIMS) data from 2018 as a guide.", "\n\nAll eligible adolescent participants who attend the participating intervention and control facilities for antenatal care in their third trimester and delivery will be invited to enrol in the study by a trained research assistant. ", "The nature of the study and all ethical concerns will be explained to the candidate prior to their enrolment. ", "Enrolment will be run on a cumulative bases until the minimum sample size is satisfied. ", "Some adolescents will be purposively selected to participate in the adolescent IDIs based on their characteristics which is aimed at achieving maximum variability of participants. ", "Each district will have a health professional who works in administrative capacity and in a caregiving capacity invited to participate in the Key Informant Interviews.", "\n\nMeasurement tools {#Sec15}\n-----------------\n\nQuantitative data will be collected with the aid of an electronically-based structured questionnaire adapted from Bohren and colleagues' study \\[[@CR44]\\] which has been modified to suit the local context. ", "The tool is designed to collect data on the socio-demographic characteristics of adolescents and their knowledge on health and sexual reproductive rights. ", "The tool will additionally collect data on the labour experience including the provider-patient encounter and relationships, encounters of mistreatment and RMC, and health facility factors.", "\n\nQualitative data collection will be done with the aid of interview guides adapted from the studies by Bohren et al. ", "\\[[@CR44]\\] and Afulani and colleagues \\[[@CR45]\\]. ", "The tool is specifically developed to collect data on the varying forms of mistreatment within the local context. ", "Sections of the guide probe for an in-depth discussion on the themes of knowledge on health and sexual reproductive rights, provider-patient interactions, encounters of mistreatment and RMC and health facility factors. ", "For professionals, the interview will probe for the role of healthcare providers in the labour experience especially in the administration of RMC.", "\n\nData collection procedure {#Sec16}\n-------------------------\n\nThe quantitative interviews will be administered by trained research assistants. ", "Interviews will be administered both at baseline and endline (from day 1 following the intervention). ", "They are estimated to last between 30 and 45 min per participant and will be held at the home of the participant or a convenient private venue outside the health facility within two weeks after delivery. ", "This venue arrangement is considered important to create an enabling environment which allows free and candid dialogue with the participant which may not be possible at the health facility due to fear of retaliation from providers. ", "This time interval between delivery and the interview is also considered adequate for the parturient to recuperate without introducing significant recall bias. ", "Interviews with adolescent participants will be in the most commonly spoken languages in the district which are English, Twi, Dangme or Krobo, based on the preference of the participant. ", "This will allow the participants to express themselves freely in the language they are most comfortable with.", "\n\nQualitative IDIs will be conducted with selected adolescent participants and KIIs with health professionals. ", "Interviews will be audio-taped, with prior permission from the participant. ", "Additionally, notes will be taken to capture non-verbal nuances and expressions which may aid in better analysis and interpretation of the audio information. ", "The number of interviews will continue until a saturation of information is reached. ", "Each interview is estimated to last between 45 and 60 min. ", "For adolescents, IDIs will take place at a location convenient to the participant outside the facility within two weeks after delivery. ", "Similar to the quantitative interviews, the qualitative interviews will be conducted within a post-recovery timeframe which mitigates the probability of recall bias. ", "Based on the preference of the participant, IDIs will be conducted in English, Twi, Ga-Dangme or Krobo as done in the quantitative interviews. ", "The KIIs will be conducted within the facilities where the staff work and will be conducted in English.", "\n\nData quality assurance activities {#Sec17}\n---------------------------------\n\nThe quality of the study and data collected will be assured via the following means Intervention-Control Allocation: The intervention and control facilities are selected based on the similarity of their characteristics. ", "This includes the type of facility, proportion of adolescent deliveries per year and the socio-demographic characteristics of the community. ", "The geographic non-proximity of the facilities was also highly considered to avoid contamination of the control communities.", "Research Assistants Recruitment, Training & Monitoring: Research assistants will be selected based on the following criteria Sex: femaleAge: 18 to 25 yearsAcademic qualification: minimum of a secondary school certificateTechnical proficiency: smartphone literacyLanguage proficiency: at least one of the languages (Ga-Dangme/ Krobo/Twi)The age group and sex of the assistants will help establish rapport between the assistants and participants. ", "This will also help minimize response desirability bias on the side of participants. ", "The educational and technical criterion are necessary to ensure that the assistants understand and effectively carry out their roles in the study to collect quality data. ", "The assistants will undergo a two-day training on the theoretical background of the study, enrolment and obtaining consent from participants, administration of questionnaires and facilitation of interviews, as well as ethical issues. ", "The principal investigator will always closely supervise the research assistants to ensure their observance of study protocols and ethical codesData Collection Instruments: The data collection instruments are adapted from a previous multi-country study (which included Ghana) which included parturient women of all ages \\[[@CR46]\\] instruments will be adapted for use with adolescents. ", "The tools will be pretested on 5% of the sample size in a pilot facility in the Kpone-Katamanso district and modified accordingly based on findings from the pilot. ", "The pilot district was selected based on its similarity to study sites in having an adolescent birth rate of greater than 11%.Data Collection Timing and Location: Data collection at baseline will be over a 3-month period. ", "Endline data collection will start from day 1 after the intervention until three-months post-intervention. ", "The venue and time interval between delivery and the adolescent surveys will allow participants express themselves freely without fear of victimization by health providers. ", "This will also allow the participants enough recovery time from childbirth with minimal recall bias.", "Data Monitoring: Data collection will be conducted in real time electronically. ", "The data will be monitored daily to allow early detection of discrepancies and resultant remedial action. ", "Transcripts from audio interviews will be reviewed by an independent listener who is fluent in the language and did not conduct or transcribe the interview to audit for accuracy and completeness.", "\n\nData processing and statistical analysis {#Sec18}\n----------------------------------------\n\nBoth baseline and endline data will be reviewed and edited for completeness and consistency daily. ", "The primary outcome variable of interest is defined as disrespectful intrapartum care which is measured as a response of \"Yes\" to any of the nine mistreatment questions. ", "The explanatory variables of interest include socio-economic status, educational level, marital status and knowledge of health rights. ", "Data will be collected on the KoBoCollect platform, synced onto a web server and downloaded in Ms-Excel format to the principal investigator's computer. ", "The data will be exported in STATA version 16 for cleaning and analyses. ", "Descriptive statistics as well as binary and multiple logistic regressions will be computed. ", "Additionally, Difference in Differences (DID) will be calculated to determine the net RMC training intervention effect on mistreatment and RMC. ", "Finally, statistical significance of the RMC training intervention effect will be evaluated using adjusted prevalence ratio, adjusted odds/risk ratio at 95% confidence interval (CI) and *P*-Value of less than 0.05.", "\n\nAudiotapes from qualitative interviews will be translated and transcribed verbatim into Ms-Word format in English. ", "Themes will be identified and coded in Ms-Excel and exported into NVivo for analyses. ", "Quotes will be narrated and cited in participant codes.", "\n\nData analysis for qualitative and quantitative data will be conducted separately. ", "Subsequently, inferences from both qualitative and quantitative results will be jointly used to draw conclusions.", "\n\nIntervention {#Sec19}\n------------\n\nThe proposed intervention aims to educate and inform midwives about the concepts of mistreatment and RMC. ", "The training additionally seeks to help participants explore and shift their current values and beliefs about mistreatment of adolescent parturients towards more positive behaviours. ", "It also aims to encourage the practice of RMC by promoting adherence to positive professional codes of conduct, ethics, roles, values and attitudes. ", "The proposed intervention is a training module facilitated with the aid of a resource package adapted from the White Ribbon Alliance/ USAID \"Respectful Maternity Care for Healthcare Workers: Tackling Disrespect & Abuse During Facility-Based Childbirth\" project \\[[@CR47]\\]. ", "Additionally, the structure and content of the module is influenced by evidence from previous studies and systematic reviews on mistreatment and RMC \\[[@CR48]--[@CR54]\\]. ", "This course will be presented in the format of presentations, case studies, role plays, discussions and evaluations. ", "The content will cover the adolescent and their reproductive health rights, the Ghana Health Service (GHS) code of professional ethics, Nurses and Midwives Code of Conduct, definitions and typologies of mistreatment and RMC as well as their outcomes to the woman, neonate, professional and health system. ", "The content will also cover the professionals' role in the delivery of RMC. ", "The training workshops will be implemented by the principal investigator supported by a facilitator who is member of the District Quality of Care team. ", "Each workshop will be a two-day event. ", "The first day will cover a theoretical introduction of the concepts of mistreatment and RMC and the role of the obstetric professional. ", "The second day will be a series of case studies and role plays to apply the theoretical basis from day 1. ", "The facilities will additionally be provided with visible posters and materials as a constant reminder of the contents of the training programme.", "\n\nThere will be no intervention conducted in the control facilities.", "\n\nExpected outcomes {#Sec20}\n-----------------\n\nIt is anticipated that at the end of this proposed study, the following outcomes will be achieved per each objective as summarised in Table [1](#Tab1){ref-type=\"table\"}. ", "Table 1Expected Outcomes of the StudySpecific Objective 1: Synthesise the available evidence relating to the mistreatment and the provision of respectful maternity care for adolescents during childbirth using a systematic review approachConduct a review of the existing published and grey literature on mistreatment and RMC globally for adolescents.", "Identify the reported prevalence and associated factors of mistreatmentIdentify interventions that address mistreatment and promote RMCSpecific Objective 2:Estimate the prevalence of mistreatment during childbirth among adolescentsConduct a baseline assessment of mistreatment across adolescent participants in intervention and control facilities.", "Specific Objective 3: Identify the risk factors and outcomes of intra-partum mistreatment among a cross-section of adolescentsInterview health professionals to explore their perceptions on the associated risk factors of mistreatment and its outcomes on adolescents, health professionals and the national health system.", "Specific Objective 4: Document and characterize the experiences of a group of adolescents who suffer mistreatment during childbirthInterview adolescents on their detailed perceptions and personal experiences with intrapartum mistreatmentSpecific Objective 5: Determine the most and least common forms of Respectful Maternity Care offered to adolescent parturientsConduct an evaluation of the most and least commonly occurring RMC practices offered in the selected intervention and control facilitiesSpecific Objective 6: Determine the effectiveness of an intervention in promoting respectful maternity care and increasing satisfaction with facility-based births and skilled birth attendance for parturient adolescentsImplement an RMC training intervention across the selected intervention communitiesConduct an endline assessment across intervention and control facilities to determine the prevalence of mistreatmentCompute the differences in mistreatment and RMC between intervention and control facilities at baseline and endline.", "\n\nDiscussion {#Sec21}\n==========\n\nThis study will firstly establish the prevalence of mistreatment among parturient adolescents. ", "Several studies worldwide have reported the prevalence of mistreatment among women in general \\[[@CR3], [@CR55]--[@CR58]\\]. ", "This proposed study, however, is among the first of its type to focus exclusively on the mistreatment of adolescents. ", "Furthermore, the study will determine the effectiveness of an intervention in promoting RMC in Ghana and reducing mistreatment. ", "Previous studies have employed interventions that target facility users such as holding maternity open birth days and community workshops to improve public awareness about mistreatment \\[[@CR6], [@CR43]\\]. ", "Mediation and resolution of past incidences of mistreatment whilst preventing future events has also been managed by educating communities on their SRHR whilst providing a means of legal redress \\[[@CR59]\\]. ", "Whilst these interventions may be helpful for older women, they may not be ideal for younger adolescents as they may not possess the autonomy required to properly exercise these facilities. ", "Some interventions have also targeted providers with evidence-based information by providing access to the World Health Organization Reproductive Health Library (RHL) \\[[@CR60]\\] and promoting advocacy for birth companions \\[[@CR61]\\]. ", "A study by Abuya and colleagues in Kenya recorded a 7% reduction in mistreatment following the implementation of a multi-component intervention at the policy, facility and community levels \\[[@CR43]\\]. ", "However, there was no special focus in these studies on adolescent sub-groups and their peculiar experiences or needs. ", "This study therefore seeks to provide insight on interventions that may better address the peculiar maternal care needs of adolescent parturients.", "\n\nLimitations {#Sec22}\n-----------\n\nThere are a few limitations in this study which measures have been taken to address. ", "Firstly, it was not possible to randomly assign the study sites due to geographical and health system constraints. ", "It is therefore possible that there will be observed and unobserved differences in the baseline measures of the intervention and comparison groups that may account for differences in outcomes. ", "However, the study sites were selected based on their similarities in characteristics such as type of facility and socio-geographic factors. ", "Furthermore, the use of difference-in-differences analytic methods in the analyses of data will allow the account of both observed and unobserved confounders. ", "Another limitation that may be faced is the employment of new staff into intervention facilities after the intervention has been conducted. ", "To mitigate this limitation, we shall take note of new staff and encourage the training module to be shared during their staff orientation.", "\n\nDissemination {#Sec23}\n-------------\n\nDissemination strategies have been drawn for results emanating from this study. ", "Oral and poster presentations of the results will be made to the participating facilities as well as district and regional directorates of the Ghana Health Service. ", "Furthermore, the results of the specific objectives in this proposal will be published in peer review journals. ", "The data management procedures, study materials including questionnaires and implementation frameworks of the study will be made upon reasonable request to the corresponding author.", "\n\nASRHR\n\n: Adolescent Sexual Reproductive Health & Rights\n\nCHPS\n\n: Community-based Health Planning & Services\n\nDHIMS\n\n: District Health Information Management Systems\n\nFBD\n\n: Facility-Based Delivery\n\nGDHS\n\n: Ghana Demographic & Health Survey\n\nGHS\n\n: Ghana Health Service\n\nGMHS\n\n: Ghana Maternal Health Survey\n\nHRP\n\n: Human Reproduction Programme\n\nIDI\n\n: In-Depth Interview\n\nKII\n\n: Key Informant Interview\n\nRMC\n\n: Respectful Maternity Care\n\nSBA\n\n: Skilled Birth Attendance\n\nSDG\n\n: Sustainable Development Goals\n\nSRHR\n\n: Sexual Reproductive Health & Rights\n\nWHO\n\n: World Health Organization\n\n**Publisher's Note**\n\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.", "\n\nThe authors acknowledge the support of the WHO/HRP Alliance and its Regional hub at the University of Ghana School of Public Health.", "\n\nHH conceived the study and KT, EM and AA made substantial contributions to its design. ", "The initial version of this manuscript was drafted by HH and it was revised thoroughly by KT, EM and AA. ", "All authors read and approved the final manuscript.", "\n\nThis proposed study will be funded by the HRP Alliance, part of the UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), a cosponsored programme executed by the World Health Organization (WHO). ", "This article represents the views of the named authors only and does not represent the views of the World Health Organization.", "\n\nThe data management procedures, study materials including questionnaires and implementation frameworks of the study will be made upon reasonable request to the corresponding author.", "\n\nEthical approval for this study has been obtained from Ghana Health Service Ethics Review Committee with registration code (GHS-ERC009/03/20). ", "Familiarisation meetings have been held with the district and facility authorities about the project to obtain their consent and support for the research study. ", "Informed consent will be obtained from all participants after explaining to them the direct risks and benefits of their participation as well as their freedom to withdraw their participation at any time in the study.", "\n\nN/A\n\nThe authors declare no competing interests.", "\n" ]

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[ "Q:\n\nIs this my Bee Balm or just a weed?", "\n\nI have a large open area in my backyard that is sloped where i dont want grass because it would be dangerous to mow. ", "A couple years ago i went to a local gardening shop and asked for recommendations on a variety of flowering plants that will spread over time and take over the area. ", "I was looking to attract butterflys, bees, and hummingbirds.", "\nFast forward a baby and an injured wife later, I simply didnt have the time to devote to weeding one year and it was overtaken in short order. ", "Half of the plants have been choked out but I found the time recently to clean it up.", "\nI have some Bee Balms like below:\n\nI am not sure though if it is spreading very much, however there is this one plant that looks incredibly similar to me that spreads like crazy and comes back with a vengeance when i pull it. ", "My wife told me to stop pulling these because she says it is the Bee Balm trying to spread but there are a few minor differences.", "\nWhere I planted the Bee Balm it has these beautiful red flowers however this spreading plant below does not seem to flower. ", "The leaves and stems are very very similar but I am just not sure.", "\n\nAre these the same plant? ", "If not what kind of virulent weed is this?", "\n\nA:\n\nI can tell you that it isn't Monarda (bee balm) - if you look closely at the images you've posted, you will see tiny flowers in the leaf axils. ", "Those rule out Monarda - but I cannot tell you what it actually is because I don't recognise it. ", "If you did not plant anything else in that area, the likelihood is its a weed, but remember, the definition of a weed is simply a plant growing in the wrong place. ", "If you do not have the time to weed out thoroughly, nor have ideas for what to plant instead, its probably best to leave them in situ until you do have time. ", "Many plants considered to be weeds are attractive to insects, usually because they are native plants, or wild flowers.", "\nSome sort of ground cover plant that you do like would be useful, if its a large area - relying on taller perennials to spread and fill such an area will take years. ", "It depends where you are and the aspect in regard to what plants would suit the situation, but a combination of taller, insect friendly plants and something that covers the ground to keep out weeds would be best if the area is very large.", "\nUPDATE - Having checked, you appear to be in USDA zone 6b - some information here on ground cover plants for your area https://www.gardeningknowhow.com/garden-how-to/gardening-by-zone/zone-6/zone-6-ground-covers.htm. ", "Those which flower will attract insects, particularly pollinating ones like bees.", "\n\nA:\n\nIt appears to be False Nettle (Boehmeria cylindrica), as Bamboo says not Monarda; yes it comes back rapidly and weedily but it pulls easily, despite being a nettle it does not sting, and makes good compost. ", "Check this page for a good description - here is a wiki page. ", "Focus on the flower differences.", "\n\n" ]

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[ "Q:\n\nWP8 Task DownloadString\n\nI want to use this class to download JSON data from rest WebServices :\npublic static class Extensions\n {\n public static Task<string> DownloadStringTask(Uri uri)\n {\n WebClient webClient = new WebClient();\n var tcs = new TaskCompletionSource<string>();\n\n webClient.", "DownloadStringCompleted += (s, e) =>\n {\n if (e.Error !", "= null)\n {\n tcs.", "SetException(e.", "Error);\n }\n else\n {\n tcs.", "SetResult(e.", "Result);\n }\n };\n\n webClient.", "DownloadStringAsync(uri);\n\n return tcs.", "Task;\n }\n }\n\nBut i dont know how to call this function.", "\nIs there an other function used to download JSON data ?", "\n\nA:\n\nIt can be as simple as:\nvar uri = new Uri(\"example.org\");\nvar dl = Extensions.", "DownloadStringAsync(uri); -- starts download\n// .. do something in the meantime\nConsole.", "WriteLine(dl.", "Result); --- wait for the download to complete\n\nYou can also use the async and await c# keywords:\npublic static async void DoDownload() \n{\n var uri = new Uri(\"example.org\");\n Console.", "WriteLine(await Extensions.", "DownloadStringAsync(uri)); \n}\n\n" ]

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[ "The Best Turntable\n\nAudio-Technica AT-LP120-USB Review Music and technology move on at a very fast pace these days, basically much like any technological advancement; if you stand still, you’re lost! ", "The problem with that whole situation is that the things you enjoy about the way things were, can often become lost too, or even obsolete. ", "For instance, you…" ]

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[ "Calculators\n\nEquipment Loans\n\nAt the root of every remarkable endeavor is a dream. ", "Fund your dreams.", "Get Started\n\nMeet your team.", "\n\nYou work hard, and our ag lending team works hard for you. ", "At Dakota MAC, a division of First Dakota National Bank, our ag loan team offers you the personal, hometown bank service you expect. ", "Our goal is always to listen to your needs, while providing ag loan solutions that truly fit your operation.", "\nMeet our loan team, and reach out anytime if you have questions or would like to begin applying for an ag loan." ]

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[ "Louisiana Heat Ch. ", "03\n\nThis is a ten chapter romantic Crime thriller with consenting erotic and romantic sex, male on male violence and a lot of exciting cliff hangers at the endings of each chapter.", "\n\nAs is usual in my stories there are a large selection of colourful characters and not all of the people in my stories have happy endings.", "\n\nYou have been warned -- so if you like the kind of story that combines sex, violence, complicated and interweaving story lines, and that you can sit back each day and read a new chapter -- read on.", "\n\n*\n\nThe Mayor stood on the front porch of Abigail house straightening his tie, checking himself out making sure his suit was brushed down and then wiping his face with his handkerchief, clearing the sheen of sweat off of the round overweight jowls and cheeks. ", "Raising his hand he knocked on the door and waited for the door to open. ", "Earlier in his office he had picked up signs that he thought was Abigail flirting with him, but he was unsure. ", "She seemed to be subtly coming on to him, but he knew she was having an affair with Rory, and he was also aware that she had played that sucker Jake before that, and now she seemed to be coming on to himself.", "\n\nMaybe she thought she could play him, but he knew that his Mama didn't raise a stupid man, no Sir. ", "Mama Gaudet had raised a canny man, a clever and careful man who knew how to manipulate and get what he wanted.", "\n\nA winner.", "\n\nAnd what he wanted was a good poke in Miss Abigail, and see what she was up to at the same time. ", "Because he had an inkling that the young woman was up to something and he would play along if it would get him what he wanted.", "\n\nThe door opened and the sweet smell of roses wafted out along with the sound of the radio playing Cole Porters 'Night and Day'. ", "Abigail was dressed in a light summer blue dress, her arms bare, and the beginnings of the swell of her breasts visible in the scoop neck of the light cotton bodice. ", "Claude stepped over the threshold and through the door, removing his hat and murmured, \"Miss Abigail.\"", "\n\nStepping back she smiled and replied, \"Thank you for coming.......would you like an iced tea?\"", "\n\n\"Sounds fine......\" and he walked further into the hall and followed Abigail into a light and bright front room where a large wooden ceiling fan moved the warm air around and large vases of blood red roses gave off their sweet smelling scent into the room.", "\n\n\"What was it you wanted to discuss Miss Abigail.....what is it that's troublin' you?\"", "\n\nTurning her head to look provocatively over her shoulder as she poured the iced tea from the pre prepared jug, she asked him, \"Claude.....I can call you Claude?\"", "\n\n\"Yes Missy....Claude's just fine.\"", "\n\nTurning she handed him the tall glass of drink. \"", "Claude, why don't you take off your jacket and get comfortable. ", "It sure is hot today. ", "Sit down and make yourself comfortable.....\" and she took her own glass and sat down on the chair opposite where the Mayor sat, who after placing his glass on the table, and placing his now removed jacket on the easy chairs back, pulled out a cigar from his vest pocket and started the process of lighting it.", "\n\n\"Claude......I have always admired you.......you're a powerful man.......a clever and commanding man. ", "I'm kind of in a difficult position and I need to be able to ask for your help......\"\n\nPulling on his cigar, great clouds of smoke rising up to join the wooden fan swirling around attached to the ceiling he sat back and relaxing raised on eyebrow, inviting her to carry on.", "\n\n\"It's Rory.....\"\n\nRaising his other eyebrow he waited.", "\n\n\"Well......\" and she took a sip of her drink then placed it down on the coffee table alongside his, \"I'm worried......\"\n\nIn the protracted silence that the Mayor deliberately gave her she continued, \"As you know, Rory and I have been....close.......very close......and he has confided in me some things......things I think you would be at an advantage to know.\"", "\n\nGetting up and going around the table to stand next to the Mayor, she then sat down on the edge of the coffee table in front of him, as if she was about to tell a secret and didn't want anyone else to hear. ", "Leaning forward she placed her hand on his knee, the scoop of her bodice falling forward allowing Claude a deeper view of her breasts. \"", "I'm scared......no one realises the truth about Rory.....his temper......his drinking......I thought he was different than he turned out to be......he's so brash.....talks too much.....is rough......not like you......I feel I could trust you.....a man like you that everyone looks up to.....so cultured....a real gentleman.\" ", "And her hand squeezed his thigh gently.", "\n\nClaude felt himself harden, his cock twitching behind the material of his flies.", "\n\n\"When he drinks he says things......like about what he has done on behalf of yourself and how you framed Jake.\"", "\n\nThe Mayor cleared his throat. \"", "Seems to me you were a little bitty tied up with what we all did to Jake......you're no innocent Miss Abigail.\"", "\n\nSliding down onto her knees between the Mayors legs she slid her hands up both his thighs. \"", "No Claude....not a complete innocent....but you know I like a man with power.....a man with style....a man with experience......Rory is young and stupid......he's talking too much.....has plans to rise higher in this town.....but he's no competition for you.....\"\n\nHer fingers started to unbutton his flies and Claude's arms spread out each side of himself along the arms of the chair, and as her eyes bore into his, the cigar between his fat fingers now forgotten, \"I need protection of a man like you from Rory......I need a man that can fulfil me and what I want.......I can give you sweet release, tell you what Rory is up to.....what he is saying and to whom......\" and she lowered her head down into his crotch and with her small hand lifted his now hard cock to her mouth.", "\n\nClaude's head dropped back, eyes rolling in his head with pleasure as her hot wet mouth slid up and down his rock hard rod, her tongue swirling over him, and the suction in her mouth pulling him further into the perfect cavern of her warm wet mouth giving him a blow job better than he'd ever had. ", "Better than the ones the cheap whores over in the next Parish gave him on the odd times he went over there away from prying eyes, or the non existent ones his dried up wife of twenty years never gave him, or ever had or would.", "\n\nThe exquisite pleasure peaked and he shot his wad into her mouth, then sat there knowing that this was going to be the start of a new partnership.......one in which he would have to watch her carefully if he was going to get everything he wanted out of her and walk away unscathed.", "\n\nTaking a long pull on his cigar and blowing out the smoke he smiled a calculating smile and asked, \"So Missy......what is it that Rory is sayin' 'bout me that I need to be so damn careful about?\"", "\n\nDoing up his flies Abigail smiled up at the Mayor through her eyelashes, \"He says he has kept proof of what you've been up to.....proof about forcing the farmers to sell up at greatly reduced prices, and selling on the land, proof about the framing of Jake, and where all the skeletons, figuratively speaking is buried.\"", "\n\n\"Did he now?\"", "\n\n\"He trusts me.....he thinks he can control me.....but I know that my future is safer in the sure hands of someone that has so much more experience.....if you know what I mean?\"", "\n\n\"I know what you mean.......so do you know where he keeps this information?\"", "\n\n\"No......but if you would take me under your wing, so to speak......make it worth my while.....maybe a little present.....a nice amount of cash.....I can find out where......I can give you what you want.....whatever you want.\"", "\n\n\"Whatever I want?\"", "\n\n\"Whatever.....\"\n\n\"That Ma Cher would be a very interestin' prospect.......\"\n\nAnd the deal was discussed and then struck between the two people, each believing they could play the other for whatever they could get.....neither really trusting the other.", "\n\n*\n\nThe truck was loaded with the now picked produce, eggs harvested and fruit in tins and baskets, vegetables in crates in the flat back of the vehicle. ", "Climbing up behind the wheel Frank looked down at Hannah as she stood swaying slightly in exhaustion, and he told her, \"Forgit sortin' out horses, I'll do it whennin I get back'n from deliverin' this to town......wash up.....lay down an' rest....later'll be soon 'nough to do chores.\"", "\n\nHannah looked up at her old and faithful farmhand and gave a weak smile, \"Who's the boss here Frank. ", "You just be careful in town.....do the delivery and bring back those supplies.....I'll see you then.\" ", "Closing the trucks door she waved as he set off down the dirt road in the direction of the town, and then turned around and walked wearily to the door of the house. ", "A nice long soak in the bath sounded good about now.......and then a small rest before she completed the rest of the never ending chores around the farm.", "\n\nEntering the bathroom she turned on the faucets and listened as the old plumbing made its usual cranks and wheezing sounds before the water sputtered out, precious water that came from the water tower and tanks now only half full compared to how they used to be before the levees were put in the rivers, lowering the water table and drying up her rice fields, once the main produce and life blood of the small farm.", "\n\nStripping off her loose cotton blouse and baggy worn denim dungarees she stepped out of her panties and bra and stepped into the tepid water before blissfully laying back to cool off, and then picking up the worn old sponge and plain bar of soap she washed the sweat from working all day in the fields off of her skin before sinking back and lowering her face down under the water to wash her soft brown hair.", "\n\n*\n\nThe woods were now turning into swamp with soft earth underfoot becoming squishy, small trickling bayou's and lots of tangled undergrowth under foot. ", "Gripping his side which was a continual burning throb where the bullet had cut out a furrow of his flesh, and stumbling along lost, Jake made his way slowly forward, every so often looking over his shoulder or stopping to listen to see if he was being followed.", "\n\nStopping and falling to his knees beside one of the slow moving bayou's running through the pungent earth he bent and scooped up water to drink and then sluice some over his head and shoulders to cool himself down. ", "Sitting, legs crossed he looked at the wound in his side and noticed it had stopped bleeding but there was a definite swollen puffy redness around the wound.", "\n\nInfection was setting in. ", "He needed to get to medical supplies and fast.", "\n\nScooping up in his cupped hand some more water he carefully washed the wound as best he could before getting to his feet and crossing the water and carried on his way deeper into the swamp ahead.", "\n\n*\n\nBack at the compound Broussard who had made it finally back there, reported that they had been attacked by five of the convicts and that they had killed the other guard and the sixth prisoner, Granger, before escaping. ", "He claimed that the ringleader was Jake Bailey and that he had tried to save the other prisoners from killing Granger but had been overpowered.", "\n\nA posse was arranged and climbing into a car, four men including an injured Broussard went back towards the clearing where the two bodies still lay. ", "Standing looking down at the corpses and then picking up the discarded prison jacket laying on the ground where Jake had dropped it, it was decided to contact the main prison and get a couple of bloodhounds to get the scent off of the jacket and then follow the dogs as they tracked the missing men.", "\n\nScooping up the dead bodies and placing them in the trunk of the car the posse drove back to the compound to get more organised for the chase and capture of the six missing members of the chain gang.", "\n\n*\n\nDarkness had begun to fall and utter exhaustion fell over Jake so that he was hardly making any progress. ", "Looking around he decided climb up into a large tree to relative safety and get some rest.", "\n\nOnce he was wedged into a high up area of the tree and had lain back, he closed his eyes and was out like a light. ", "Sleep and exhaustion had taken over his body, so that as the night animals took over the area and came out looking for food below him he never noticed.", "\n\n*\n\nRory walked into his home, slammed the front door and strode past his wife as she stood there, babe in arms, totally ignoring her. ", "Striding up the stairs he flung off his jacket and suit vest and put the package of bubble bath down on the dresser, and then sat down on the end of the bed to remove his shoes.", "\n\nHis wife had followed him up and now stood timidly in the doorway, a sad and mournful look on her thin face, her tearful grey eyes following him as he undressed ready to have a shower. \"", "You're going out to her aren't you?......that woman?\"", "\n\nHe ignored her comment, continuing to remove his shirt, \"You're going to meet her.....why don't you stay at home?.....what's happening to us Rory....we used to be so happy?\"", "\n\nHe gave a long hard look, derision in his eyes, \"Happy?......I wasn't happy.....we were just existing?\"", "\n\n\"But......\"\n\nHe cut her off, his voice harsh, \"But what!......look at yourself.....just look at yourself.....since the baby was born you've become a nothing......you're just a shadow of what a woman should be.....carrying around that crying brat......that look of 'oh so hurt martyrdom' on your face......a man needs a woman....a real woman....not someone like you.\"", "\n\n\"You didn't used to think so.\"", "\n\n\"I didn't have much option before....I wanted to fuck...you wanted to get married....now I want to fuck someone else.....get it?\"", "\n\nTears ran down her cheeks and she held the baby close to her, rocking in the doorway, \"Please don't go out...stay here....I promise.....\"\n\n\"SHUT UP......just shut up and get out of my sight.\"", "\n\n\"But.......\"\n\n\"SHUT UP......\"\n\n\"Please....\"\n\nRushing over to her, his face just inches from hers he screamed at her, his face red with rage, \"JUST SHUT THE FUCK UP AND GET OUT OF MY SIGHT.......\"\n\nJerking her face back as if she had been slapped, his wife stared at him, not recognising the man she had fallen in love with. ", "It was as if someone had taken over Rory's body, someone that she didn't recognise, the complete opposite of the person she once had known. ", "Turning on her heels she left the bedroom and went downstairs, laying the child down on the sofa where she sat crying her heart out as her husband carried on getting changed upstairs, making himself ready to go over to Abigail, the other woman in his life, and the focus of his obsession.", "\n\n*\n\nThe Mayor walked into his house, kissed the cheek of his wife and sat down content. ", "Soon the last farm would be his to sell on for a high profit to the county, he would have any incriminating proof of his crooked deals that Rory had, a wife that was respected throughout the county for her good deeds, he had high position and power in the town, money in the bank and his eye on the Governorship. ", "And now he had a young mistress to see to his needs.", "\n\nHe was indeed feeling a contented man.", "\n\nLeaning back he undid the buttons on his straining vest where it pulled across his round paunch, kicked out his legs and smiled to himself.", "\n\n*\n\nThe Sheriff peered through the window of the old farmhouse, letting the shadows of the night hide him as he watched Hannah move about the room inside, her pink worn Chenille bathrobe pulled loosely around her slim long body.", "\n\nLicking his lips he watched as she sat down, the mug of coffee in her hands, as the robe gaped slightly and her long naked legs bent as she pulled them up onto the couch exposing her knees and thighs to his sight. ", "The sounds of the countryside night surrounded him and he placed a hand against the wooden wall of the old house as he leaned forward, squinting through the gap that the curtains made as they covered the inside of the window glass.", "\n\nHer hair was still wet from the bath, the ends curling gently around her face and falling on her shoulders, and he yearned to be able to knock at the front door and then enter into the room, take her in his arms and kiss her like he wanted to, like he had dreamed of all these years.", "\n\nBut his insides were in knots and he slowly moved away from the window and walked quietly back through the fields to where he had left the car, far enough away so that it couldn't be heard by Hannah when he started it up and drove away.", "\n\nThe Mayor wanted him to burn down her fields, but he knew he couldn't do that.", "\n\nNot to Hannah.", "\n\nHe needed to make her sell up and come to him. ", "He could look after her once she sold the farm. ", "He'd earnt enough money as Sheriff, and he loved her." ]

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[ ".TH OVF2OVP 1 \"14 April 2016\" \"Web2C @VERSION@\"\n.PP \n.SH \"NAME\" \novf2ovp \\- convert virtual font file and associated font metrics to property-list format\n.PP \n.SH \"SYNOPSIS\" \n.PP \n.B ovf2ovp\n.RI [ options ]\n.IR ovfname [ \\fB.ovf\\fP ]\n.RI [ ofmname [ \\fB.ofm\\fP ]\n.RI [ ovpfile [ \\fB.ovp\\fP ]]]\n.PP \n.SH \"DESCRIPTION\" \n.PP \n\\fBovf2ovp\\fP translates a virtual font (OVF) file, \\fIovfname\\fP,\nand its companion font metric (OFM) file, \\fIofmname\\fP, into a\nhuman-readable property-list format\\&. ", " The program writes to standard\noutput (by default) or to a file specified as \\fIovpname\\fP\\&.", "\n.PP \nThe program also works with TeX VF and TFM files, producing TeX VPL\nfiles\\&.", "\n.PP \n.SH \"OPTIONS\" \n.PP\n(Same as \\fBofm2opl\\fP).", "\n.IP\n.IP \"\\fB-charcode-format=\\fP\\fItype\\fP\" \noutput character codes according to \\fItype\\fP,\neither `hex\\&', `octal\\&' or `ascii\\&'\\&. ", " Default is\n`hex\\&'\\&; `ascii' says to use\nASCII for letters and digits, hex for all else\\&.", "\n.IP \"\\fB-char-format=\\fP\\fIstype\\fP\"\noutput character codes according to \\fIstype\\fP,\neither `num\\&' or `ascii\\&'\\&. ", "Default is `num'; `ascii' as in\n-charcode-format. ", " (These two redundant options both exist only for\nhistorical compatibility.)", "\n.IP \"\\fB-num-format=\\fP\\fIntype\\fP\"\noutput numbers according to \\fIntype\\fP,\neither `hex' or `octal'; default is hex.", "\n.IP \"\\fB-text-format=\\fP\\fIttype\\fP\"\noutput coding scheme and family according to \\fIttype\\fP,\neither `mixed' or `upper' case; default is mixed.", "\n.IP \"\\fB-help\\fP\" \ndisplay a brief summary of syntax and options \n.IP \"\\fB-verbose\\fP\" \ndisplay progress reports\n.IP \"\\fB-version\\fP\" \noutput version information and exit\n.IP \n.PP \n.SH \"FILES\" \n.PP \n.IP \"\\fIovpfile\\fP\" \nOmega Virtual Property List file\n.IP \"\\fIofmname\\fP\" \nOmega Font Metric file\n.IP \"\\fIovfname\\fP\" \nOmega Virtual Font file\n.PP \n.SH \"BUGS\" \n.PP \nSend bug reports to <http://lists.tug.org/tex-k>\n(mailing list); may also check if the same bug is present in\n\\fBvftovp\\fP(1)\\&. ", " General discussion of Omega (and Aleph) can take place\non the <http://lists.tug.org/omega> mailing list.", "\n.PP \n.SH \"SEE ALSO\" \n.PP \n\\fBomega\\fP(1), \\fBaleph\\fP(1), \\fBofm2opl\\fP(1), \\fBovp2ovf\\fP(1),\n\\fBpltotf\\fP(1), \\fBtftopl\\fP(1), \\fBvftovp\\fP(1),\n\\fBvptovf\\fP(1)\n.PP \n.SH \"AUTHOR\" \n.PP \nAccording to the WEB documentation:\n.PP \n.RS \n\\fBVFtoVP\\fP is an extended version of the program \\fBTFtoPL\\fP,\nwhich is part of the standard TeXware library\\&. ", " The idea of a\nvirtual font was inspired by the work of David R\\&. ", "Fuchs who designed a\nsimilar set of conventions in 1984 while developing a device driver\nfor ArborText, Inc\\&. ", " He wrote a somewhat similar program called\n\\fBAMFtoXPL\\fP\\&.", "\n.RE \n.PP\nThus, \\fBovf2ovp\\fP is based on the WEB source code for \\fBvftovp\\fP(1),\nalthough nowadays it is a link to \\fBomfonts\\fP, implemented entirely in\nC.\n.PP \nThe primary authors of Omega are John Plaice and Yannis Haralambous.", "\nOmega (and Aleph) are now maintained as part of TeX Live.", "\n.PP \nThis manual page was written by C\\&.M\\&. ", "Connelly\n<cmc@debian\\&.org>, for\nthe Debian GNU/Linux system\\&. ", " It may be used by other distributions\nwithout contacting the author\\&. ", " Any mistakes or omissions in the\nmanual page are my fault; inquiries about or corrections to this\nmanual page should be directed to me (and not to the primary author)\\&.", "\n" ]

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[ "Analysis of Passivation Techniques in InP HEMTs and Implementation of an Analytical Model of fT Based on the Small Signal Equivalent Circuit.", "\nThis paper analyses, the influence of Si₃N₄-PECVD and Al₂O₃-ALD surface passivation on the DC and RF characteristics of InP HEMTs with different gate lengths 0.08 μm, 0.1 μm, 0.12 μm, and 0.15 μm. ", "A significant improvement in maximum drain current IDS, MAX, transconductance gm, MAX and oscillation frequency fmax, MAX is obtained by scaling the thickness of the passivation layers An increase in gm, MAX and fmax, MAX, fT, MAX is observed by reducing parasitic capacitance w.r.t. ", "the decrease in gate length. ", "In addition, an analytical model of fT based on a small-signal equivalent circuit is developed, which consist of extrinsic parameters Rs, Rd, Cgs_ext and Cgd_ext and intrinsic parameters Cgsi, Cgdi, gmi and goi. ", "The carrier transport is improved by increasing gmi, thus the transit time τt , the parasitic charging delay τext and the τpar are reduced by lowering the extrinsic capacitances. ", "An excellent fitting between measured and simulated fT is achieved, which inturn leads a realistic way for further improvement in fT." ]

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[ "Palo Alto Networks News of the Week – January 16\n\nIt’s been a busy week for Unit 42, our threat intelligence team. ", "Learn more about what they found after they took a closer look at recent holiday season-themed attacks. ", "They also found over 90,000 websites compromised, leading them to believe Angler Exploit Kit is continuing to evade detection. ", "And Josh Grunzweig continued the series “How to Use IDAPython to Make Your Life Easier” with part 5. (", "Check out part 1, part 2, part 3, part 4)." ]

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[ "Norbury railway station\n\nNorbury railway station is in the London Borough of Croydon in south London, down the line from . ", "The station is operated by Southern, who also provide the majority of services (the only exceptions being two early morning departures operated by Thameslink) and is in Travelcard Zone 3. ", "Ticket barriers are in operation at this station.", "\n\nHistory \nThe Balham Hill and East Croydon line was constructed by the London Brighton and South Coast Railway (LB&SCR) as a short-cut on the Brighton Main Line to London Victoria, avoiding Crystal Palace and Norwood Junction. ", "It was opened on 1 December 1862. ", "However, Norbury station was not opened until January 1878, as the surrounding area was very rural. ", "The station was rebuilt in 1903 when the lines were quadrupled. ", "In 1925 the lines were electrified.", "\n\nTicket gates were installed in 2009.", "\n\nA nearby Victorian race track, dating from 1868, was situated in fields forming part of Lonesome Farm, which later became the sports ground of the National Westminster Bank (NatWest Bank). ", "The course, which included a water jump across the River Graveney, hosted the 'Streatham Races'. ", "Race meetings attracted huge crowds of racegoers, bookies and other notorious characters, who flocked to the course by train. ", "This exciting but disreputable period of history came to an end in 1879 when the Racecourse Licensing Act banned racecourses within a radius of of London.", "\n\nService \n\nThe typical off-peak service in trains per hour (tph) is: \n\n 4 tph to London Victoria\n 2 tph to London Bridge via Peckham Rye\n 2 tph to Sutton\n 2 tph to Epsom Downs\n 2 tph to Caterham\n 1 tph to East Croydon\n 1 tph to Milton Keynes Central\n\nConnections\nLondon Buses routes 50, 109 and 255 and night route N109 serve the station.", "\n\nReferences\n\nExternal links \n\nCategory:Railway stations in the London Borough of Croydon\nCategory:Former London, Brighton and South Coast Railway stations\nCategory:Railway stations opened in 1878\nCategory:Railway stations served by Southern\nCategory:1878 establishments in England" ]

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[ "In a statement, Redskins owner Dan Snyder said, \"I am THRILLED! ", "Hail to the Redskins,\" after the Supreme Court ruled it can't refuse to register trademarks it deems offensive." ]

{ "pile_set_name": "OpenWebText2" }

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[ "Betty Friedan goes beyond gender limits\n\nWhen Betty Friedan's \"inner Geiger counter\" began ticking loudly in the early 1960s, she wrote \"The Feminine Mystique\" and touched a spark to the repressed ambition and anger of millions of dissatisfied women. ", "The movement those women created proceeded to challenge the status quo of gender roles and responsibilities and turn conventional wisdom upside down.", "\n\nFriedan's Geiger counter is ticking again. ", "This time, her attention is homed on difficulties created in part by the successes of the feminist movement.", "\n\nAs more women work out of the home - whether from economic necessity or from professional aspirations or a mixture of both - there is less time for families, for community, for nourishing the ties that bind women, men and children into healthy families. ", "Meanwhile, both women and men are feeling the sting of corporate downsizing, mandatory overtime and stagnant wages.", "\n\nWhat to do? ", "Friedan's latest tract, \"Beyond Gender: The New Politics of Work and Gender,\" attempts to address those issues by searching for a new paradigm - ways to restructure the economy so that all workers can better balance obligations to their employers, their families and to the larger community.", "\n\n\"Beyond Gender\" is largely a narrative history of Friedan's own thinking about these issues, amplified by conversations with friends and participants in seminars she has run at the Woodrow Wilson Center and other places. ", "The topics are familiar to anyone concerned about family issues: the increasing polarization between the wealthy and the poor; the effect of downsizing on the families of laid-off workers, as well as on those of the over-taxed employees who retain their jobs; the impact of welfare reform; the time pressures that strain working parents everywhere; and so on.", "\n\nFriedan notes that these discussions can still spark divisions among feminists, with some arguing that the women's movement should focus primarily on women, not on economic issues that affect both women and men. ", "Friedan is frank about her discomfort with this kind of thinking, arguing that it is both divisive and destructive since it encourages a backlash against women's success.", "\n\nFriedan's quest is for a \"new paradigm\" that goes beyond the old sexual politics pitting men against women. ", "Instead of dividing people into special interests, the new paradigm would instead create ways for both women and men to find fulfillment and decent wages in work, while also having the time and energy for a healthy home life and participation in the larger community.", "\n\nMuch of \"Beyond Gender\" is devoted to discussion of such possibilities. ", "Flex-time, shorter work weeks, pro-rated benefits for part-timers and other good ideas get prominent attention. ", "But neither Friedan nor the participants in her seminars seem to have a clear notion of how best to move these proposals from theory to reality, or even much optimism that it can be done. ", "After all, who can now imagine Congress legislating a 32-hour work week?", "\n\nPlenty of readers will agree with Friedan that we need a new paradigm of work and family. ", "But what they find here will be more food for thought than a road map for getting there.", "\n\nSara Engram is deputy editorial page editor at The Sun. ", "She is author of Mortal Matters: When a loved one dies (1990)." ]

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[ "Their\nshriveled swords are red with rust,Their\nplumed heads are bowed,Their\nhaughty banner, trailed in dust,Is\nnow their martial shroud.", "And\nplenteous funeral tears have washedThe\nred stains from each brow,And\nthe proud forms, by battle gashedAre\nfree from anguish now.", "\n\nLike\nthe fierce Northern hurricaneThat\nsweeps the great plateau,Flushed\nwith triumph, yet to gain,Come\ndown the serried foe,Who\nheard the thunder of the frayBreak\no'er the field beneath,Knew\nthe watchword of the dayWas\n\"Victory or death!\"", "\n\nLong\nhad the doubtful conflict ragedO'er\nall that stricken plain,For\nnever fiercer fight had wagedThe\nvengeful blood of Spain;And\nstill the storm of battle blew,Still\nswelled the glory tide;Not\nlong, our stout old Chieftain knew,Such\nodds his strength could bide.", "\n\nTwas\nin that hour his stern commandCalled\nto a martyr's graveThe\nflower of his beloved land,The\nnation's flag to save.", "By\nrivers of their father's goreHis\nfirst-born laurels grew,And\nwell he deemed the sons would pourTheir\nlives for glory too.", "\n\nFor\nmany a mother's breath has sweptO'er\nAngostura's plain --And\nlong the pitying sky has weptAbove\nits moldered slain.", "The\nraven's scream, or eagle's flight,Or\nshepherd's pensive lay,Alone\nawakes each sullen heightThat\nfrowned o'er that dread fray.", "\n\nSons\nof the Dark and Bloody GroundYe\nmust not slumber there,Where\nstranger steps and tongues resoundAlong\nthe heedless air.", "Your\nown proud land's heroic soilShall\nbe your fitter grave;She\nclaims from war his richest spoil --The\nashes of her brave.", "\n\nThus\n'neath their parent turf they rest,Far\nfrom the gory field,Borne\nto a Spartan mother's breastOn\nmany a bloody shield;The\nsunshine of their native skySmiles\nsadly on them here,And\nkindred eyes and hearts watch byThe\nheroes sepulcher." ]

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[ "tor of (-254)/4*2/6 and (h - (-166)/60)*(-50)/(-4).", "\n12\nLet m = 41 - -43. ", "What is the common denominator of (m/(-54))/(-1) + 3 and 43/3?", "\n9\nLet w = -805/243 - -792743/240327. ", "Let t = w + -83449/43516. ", "Calculate the common denominator of t and -3.", "\n44\nSuppose -5283*c = -5284*c + 44. ", "Calculate the least common multiple of c and 84.", "\n924\nLet v be ((-6)/4 + 0)*1460/(-12). ", "Let w = -197 + v. What is the common denominator of w and 2/(-36)*(-1 + -6)?", "\n18\nLet z = 132 - 130. ", "Let s = 3 - -5. ", "What is the least common multiple of z and s?", "\n8\nSuppose 28*h = 30*h - 24. ", "What is the smallest common multiple of h and 72?", "\n72\nLet g = -17 - -18. ", "Suppose 2*c - 60 = -c. ", "Calculate the lowest common multiple of c and 1 - (-12 + -4 + g).", "\n80\nLet o = -4064 - -1076962/265. ", "Calculate the common denominator of -109/6 and o.\n1590\nFind the common denominator of 23/28 and -6 - (1341/126)/(-1).", "\n28\nLet m(y) = -y**2 + 6*y - 2. ", "Let u be m(5). ", "Suppose 2*q - 20 = u*v - 7*v, -3*q = -5*v + 14. ", "What is the least common multiple of 8 and q?", "\n8\nWhat is the common denominator of ((-300)/(-160))/((-81)/(-12)) and 7/27?", "\n54\nWhat is the common denominator of -11/39 and 15 - (-51919)/(-3528) - 2/(-7)?", "\n936\nWhat is the common denominator of -49/48 and (-23)/(-92) - (-411)/(-84)?", "\n336\nLet d be 41918/44 + 6/(-33). ", "Let t = d - 19113/20. ", "What is the common denominator of t and 1/(70/153) - (-146)/(-511)?", "\n20\nSuppose 7*q = 4*q + 9. ", "Let a be (-1390)/(q/(9/2)). ", "Find the common denominator of ((-2)/15)/((-36)/a) and 121/20.", "\n180\nLet q = 207 - 141. ", "Calculate the lowest common multiple of q and 6.", "\n66\nSuppose 0*p = -3*p - 6, 4*i + 4*p = 364. ", "Calculate the common denominator of ((-12)/(-9))/(18/i) and 2/11.", "\n99\nLet g be (16/(-24))/(2/(-129)). ", "Let s = 46 - g. Let x(w) = -w - 4. ", "Calculate the smallest common multiple of s and x(-5).", "\n3\nLet v(m) = 6*m - 88. ", "Calculate the lowest common multiple of 74 and v(16).", "\n296\nSuppose 23*v + 29*v - 364 = 0. ", "What is the lowest common multiple of 217 and v?", "\n217\nLet r = -423 - -433. ", "What is the smallest common multiple of 6 and r?", "\n30\nLet y = -76 - -209/3. ", "Let m(f) be the second derivative of f**4/12 + f**3/2 + 11*f**2/2 + 4*f. ", "What is the common denominator of y and m(-7)?", "\n3\nLet x = 34 + -6. ", "Suppose 0*d + x = 4*d. ", "Calculate the lowest common multiple of 60/(-21)*d/(-2) and 2.", "\n10\nLet f = -4232/3 - -42581/30. ", "What is the common denominator of (10/(-40))/(2/(-8))*34 and f?", "\n10\nLet i be (-3)/(-12) + (-279115)/(-44). ", "Suppose -3*g + 6*g - 19026 = 0. ", "Let q = i - g. Calculate the common denominator of q and -29/22.", "\n22\nLet u(g) = 10*g - 2. ", "Calculate the smallest common multiple of u(2) and 24.", "\n72\nLet o(j) be the first derivative of j**3/3 + 3*j**2/2 - 7. ", "Let m be o(-2). ", "What is the common denominator of -107/30 and (-39)/60 + m/(-2)?", "\n60\nLet u = -858097194 - -602384129267/702. ", "Let i = 1834/13 + u. Calculate the common denominator of 35/8 and i.\n216\nLet b = -1/697 + -29959/8364. ", "Calculate the common denominator of -113/30 and b.\n60\nLet p = 3/364 - 1199/364. ", "Find the common denominator of p and ((-34)/3)/(20/(-3)).", "\n70\nSuppose -867*g + 864*g + 9 = 0. ", "What is the least common multiple of g and 12?", "\n12\nSuppose 83 = -5*p + 4*v, p + 0*v - 5*v = -25. ", "Calculate the smallest common multiple of 2 and ((-40)/(-6))/((-10)/p).", "\n10\nFind the common denominator of 48/561*19/(-38) and -8/51.", "\n561\nLet c = 10248 + -25528. ", "Let w = -134229/40 + -4294999/360. ", "Let m = c - w. What is the common denominator of 17/3 and m?", "\n18\nSuppose -28 = -8*x + 3*x + 3*l, -4 = 4*l. ", "What is the least common multiple of 20 and x?", "\n20\nSuppose -l - 2*r + 7*r + 16 = 0, 5*r = -3*l + 68. ", "What is the least common multiple of l and 30?", "\n210\nLet w = -92817/19558 - 24/889. ", "Suppose 170 + 140 = 5*i. ", "Find the common denominator of w and 3/(2*14/i).", "\n154\nLet j be (-69)/(-36)*(-135)/(-5). ", "Let i = j + -415/12. ", "Calculate the common denominator of 75/4 and i.\n12\nLet j = -2/1173 - 7411/10557. ", "What is the common denominator of 149/156 and j?", "\n1404\nWhat is the common denominator of 27459/(-8424)*8/18 and -29/6?", "\n78\nSuppose 8 = -2*m, m = c - 1 - 5. ", "Let i(k) = -k**2 - 7*k - 5. ", "Let s be i(-6). ", "Let q = 2 - s. Calculate the lowest common multiple of c and q.\n2\nLet m = -1/5775 + -67363/69300. ", "What is the common denominator of m and 115/28?", "\n252\nLet n = -700 + 1247. ", "Suppose 0 = -4*r + 2*g - 131 + n, -2*g - 212 = -2*r. ", "Find the common denominator of -151/12 and r/(-15) - -2 - 2.", "\n60\nLet n(o) = 15*o - 6. ", "Let j be n(-1). ", "Suppose -33 = 4*f - 9. ", "Calculate the smallest common multiple of j*(-2)/f*-1 and 7.", "\n7\nLet x = -1/10717 - -439477/857360. ", "Calculate the common denominator of x and -17/10.", "\n80\nCalculate the smallest common multiple of (1/((-2)/(-16)))/(81/162) and 1618.", "\n12944\nLet b = -638 + 734. ", "What is the smallest common multiple of 90 and b?", "\n1440\nLet d(w) = 2*w**2 - 8*w + 25. ", "What is the lowest common multiple of d(3) and 2?", "\n38\nLet m = -86 - -134. ", "Suppose d = -4*i + 4*d + 48, -2*d - m = -4*i. ", "What is the least common multiple of i and 15?", "\n60\nLet h be ((-3711)/(-40))/((-48)/(-1376)). ", "Let w = h - 2662. ", "What is the common denominator of w and 53/48?", "\n240\nFind the common denominator of 210/891 - (27 + -27) and 19/264.", "\n2376\nLet t = 7264/9 + -71587/90. ", "Suppose 2*h + 261 = -4*g + 1085, 1037 = 5*g - h. Calculate the common denominator of t and 0 + 1 + g/12.", "\n20\nLet s be (44277/10)/((-6)/(-5)). ", "Let d = -3708 + s. What is the common denominator of 9/((-54)/(-30)) - 232/(-12) and d?", "\n12\nLet s be (-5)/(-50)*12657/(-14). ", "Let p = -454/5 - s. Find the common denominator of -111/10 and p.\n140\nLet t = -3 + 12. ", "Suppose 16*g = -466 + 498. ", "Calculate the least common multiple of 6/t - (-128)/6 and g.\n22\nLet g(x) = x**2 + 4 - 2 - 3*x**2 - x**3 - x**2 + 6*x. ", "Let r be g(-4). ", "Let y(u) = u**3 + 5*u**2 - 9*u - 6. ", "Calculate the least common multiple of y(r) and 20.", "\n60\nSuppose -20 = 4*f, -3*n + 4*n + 13 = 5*f. ", "Let g = n + 92. ", "What is the least common multiple of 3 and g?", "\n54\nLet n be (3 + -7)*(5 - 3). ", "Find the common denominator of 65/9 and 2 - (2/n + (-70)/(-28)).", "\n36\nSuppose 15*f - 9*f = 414. ", "Let k = f + -49. ", "Calculate the lowest common multiple of k and 268.", "\n1340\nLet f = 93 + -75. ", "What is the lowest common multiple of f and 18?", "\n18\nLet l = -770 + 780. ", "Calculate the smallest common multiple of l and 11.", "\n110\nLet b = 4 + -6. ", "Let g be (-4)/(b + 3) + -2. ", "Find the common denominator of (-52)/g*12/(-112) and 11/6.", "\n42\nLet m = -35837/2829 - -1/943. ", "What is the common denominator of m and 780/(-65) - 50/(-3)?", "\n3\nLet a = 2377 - 2277. ", "Calculate the lowest common multiple of 60 and a.\n300\nSuppose 3*x - 3*t - 102 = 0, -2*x - 3*t = 3*x - 178. ", "Let r = 43 - x. What is the least common multiple of 4 and r?", "\n8\nLet s = 2425/6 - 3193/8. ", "What is the common denominator of s and 137/12?", "\n24\nLet x = 15845 + -46870/3. ", "Let y = -7231/33 + x. What is the common denominator of -6*94/40 + 3 and y?", "\n110\nLet v be 9/2*4/(-6). ", "Let l = -108 + 126. ", "What is the least common multiple of v*1 + 3 + 6 and l?", "\n18\nLet p(l) = -l**2 - 8*l + 15. ", "Suppose -9*z - 74 - 7 = 0. ", "Calculate the least common multiple of p(z) and 21.", "\n42\nLet k be 7*15/(-42)*-2. ", "Let n(j) = j**3 - 4*j**2. ", "Let o be n(k). ", "Suppose -d + 4*d = x + o, -2*d + 3*x = -26. ", "Calculate the least common multiple of 3 and d.\n21\nLet v be (-487068)/(-8)*38/(-90). ", "Let z = 25709 + v. Calculate the common denominator of 67/45 and z.\n90\nLet y = -818522668948/54871 + 14917218. ", "Let b = y + -1605389/548710. ", "Let k = b - -1/37. ", "Find the common denominator of k and -25/22.", "\n110\nLet m = 31 - 26. ", "Suppose -5*u - 20 = -m*c, 6*u - 2*u - 12 = -3*c. ", "Calculate the common denominator of (u - -14)/(30/(-35)) and -18/5.", "\n15\nWhat is the common denominator of (-1 - (-142)/(-132)) + (-5 - -7) and 62/9?", "\n198\nLet k be -6*(20/(-8) - -2). ", "Let m = 7 - k. Calculate the least common multiple of 3*-2 + m - -4 and 22.", "\n22\nSuppose 10*c + 687 = 11*c. ", "Let k = -5551/8 + c. Let t = 643 - 3827/6. ", "Find the common denominator of k and t.\n24\nLet a(o) = o - 1. ", "Let c be a(5). ", "Suppose -4 = k + 3*v + 6, 0 = -2*k + c*v + 30. ", "Let m(w) = 3*w - 1. ", "Calculate the lowest common multiple of 4 and m(k).", "\n28\nLet o(d) = -1 + 4*d + 0*d - 8*d - 4*d - 3*d**2. ", "Let x be o(-6). ", "Calculate the least common multiple of (-14)/(-49) - x/7 and 4.", "\n36\nLet c = 75 + -76. ", "Let d(z) = -36*z - 3. ", "Calculate the smallest common multiple of d(c) and 24.", "\n264\nLet u = -61 - -156. ", "Let z = u" ]

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[ "Canonical Wnt Signaling Modulates the Expression of Pre- and Postsynaptic Components in Different Temporal Patterns.", "\nWnt ligands play critical roles in neuronal development, synapse formation, synaptic activity, and plasticity. ", "Synaptic plasticity requires molecular remodeling of synapses, implying the expression of key synaptic components. ", "Some studies have linked Wnt signaling activity to changes in synaptic protein levels. ", "However, the presynaptic and postsynaptic gene expression profiles of hippocampal neurons exposed to Wnt proteins have not been studied. ", "Hence, we treated rat cultured hippocampal neurons with recombinant Wnt3a, lithium, and the Wnt inhibitor Dkk-1 for different treatment durations and measured the mRNA and protein levels of pre- and postsynaptic components. ", "The ligand Wnt3a promoted the differential temporal expression of genes encoding presynaptic and postsynaptic proteins. ", "Gene expression of the presynaptic proteins Rim1, piccolo (Pclo), Erc2, Ctbp1 and Rimbp2 increased in a specific temporal pattern. ", "Simultaneously, the mRNA and protein levels of postsynaptic components showed a different temporal expression pattern, e.g., the mRNAs for postsynaptic scaffolding components such as postsynaptic density protein-95 (PSD-95/Dlg4), Homer1 and Shank1 were temporally regulated by both Wnt3a and lithium. ", "On the other hand, the mRNA levels of the gene encoding the protein calcium/calmodulin-dependent protein kinase IV (Camk4), canonically upregulated by Wnt, were increased. ", "Our results suggest that Wnt signaling orchestrates expressional changes in genes encoding presynaptic and postsynaptic components, probably as part of a synaptic plasticity mechanism in neurons." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "Welcome! ", "This blog documented my my thoughts and insights as I progressed through the 4 year naturopathic medicine program in Canada and now provides some highlights of an ND's private practice. ", "It includes links for those interested in becoming a Naturopathic Doctor as well as resources for students and patients interested in the field. ", "My clinic is located in Airdrie Alberta.", "\n\nTuesday, April 29, 2008\n\nThis is a very, very brief summary. ", "Please read the book Nature Doctors by Friedhelm Kirchfeld & Wade Boyle to get a good understanding of where naturopathy came from.", "\n\nThe term naturopathy (a hybridization of the Latin-natura and the Greek-pathy) was first coined in 1892 by John Scheel, a MD in New York. ", "Benedict Lust, a German immigrant who had been helped by Father Sebastian Kneipp's water cure, came to America in 1896 to teach Kneipp's hydrotherapy methods. ", "Benedict Lust purchased the term, \"naturopathy\" from Dr. Scheel in 1902. ", "Lust was looking for a term that was not persecuted by the Medical Doctors of the time and used it to describe the methods of healing taught at his school. ", "In 1956, Joseph Boucher (who was born in Edmonton) was joined by John Bastyr to open National College of Naturopathic Medicine (initially in Seattle before moving to Portland). ", "Boucher was said to be a key figure in keeping naturopathic medicine alive during the tremendous hardships endured by Naturopaths in the 50's, 60's and 70's.", "\n\nThis is a very brief overview the beginnings in North America, however, the roots of naturopathy are in Europe where nature cure (water, sunlight, exercise, diet) began and can even be traced all the way back to ancient Egyptian, Greek, Roman and Chinese civilizations. (", "Click here for an article on Medicine in the Ancient World)\n\nFurthermore, there are now many more therapies that are offered by some Naturopaths including IV therapy, chelation therapy, Bowen, etc. ", "Therefore, Naturopathy is an umbrella term used to describe many methods by which a person can maintain or regain health." ]

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[ "Q:\n\nChange color in tree view odoo 9\n\nIs it possible change color in tree view, for example if field total_time (float time widget) <= 00:00 put red color.", "\nI'm try below exampke but not working!", "\ncolors=\"red:total_time<='00:00'\"\n\nA:\n\nYou can do it using following method.", "\ncolors=\"red:total_time&lt;='00:00'\"\n\nYou must escaped special characters in XML.", "\nEx: \nless than (<) is escaped to &lt;\n\ngreater than (>) is escaped to &gt;\n\nThis may help you.", "\n\n" ]

{ "pile_set_name": "StackExchange" }

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[ "Maybe he forgot to get his flu shot this season. ", "Considering Neil Young has had a career spanning 38 years if you count Buffalo Springfield, CSNY and Crazy Horse, that comes to roughly 28 solo albums, not counting movie soundtracks, live albums and compilations.", "\n\nIt seems bizarre only 8 years and 16 songs are represented on this new greatest hits collection. ", "This means, if you break it down song by song, according to albums, only 2 percent of his entire repertoire is used.", "\n\nAccording to the disclaimer on the back cover of the CD, allegedly written by Young himself, \"Greatest hits inclusion based on original record sales, airplay and known download history.\" ", "No doubt his record label (Reprise) is trying to recoup from the sales of last year's abysmal concept record \"Greendale\" and its accompanying DVD.", "\n\nThere is virtually nothing from Young's weird, confused, drugged-out period from the mid '70s, when he released albums such as \"Time Fades Away\" (1973), \"On The Beach\" (1974), \"Zuma\" and \"Tonight's the Night\" (both from 1975). ", "The latter contained possibly his darkest and most distorted but most brilliant compositions.", "\n\nSince this assortment of tunes was released on the Reprise label, you can forget about Young's \"lost years\" in the '80s, when he supposedly was releasing crappy albums to get out of his record contract with Geffen. ", "This means there is zilch from \"Trans\" (1982), \"Everybody's Rockin'\" (1983), \"Old Ways\" (1985), etc. ", "This leaves a big gap in his career, because it makes the jump from 1978 to 1991.", "\n\nIn fact, only one song from the '80s (\"Rockin In The Free World\") and one song from the '90s (\"Harvest Moon\") is represented here.", "\n\nThis greatest hits package is a compromise, playing it safe, playing by the rules, which is the antithesis of what Neil Young \"the artist\" is all about. ", "Young always has been difficult and never was out to please anybody but himself.", "\n\nDon't get me wrong. ", "These are great songs, but I seriously doubt Young himself had anything to do with it. ", "In the meantime, a more comprehensive representation and a more cost-effective investment of Young's work would still have to be 1977's \"Decade.\" ", "Rust never sleeps!" ]

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[ "Lipoic acid and dihydrolipoic acid. ", "A comprehensive theoretical study of their antioxidant activity supported by available experimental kinetic data.", "\nThe free radical scavenging activity of lipoic acid (LA) and dihydrolipoic acid (DHLA) has been studied in nonpolar and aqueous solutions, using the density functional theory and several oxygen centered radicals. ", "It was found that lipoic acid is capable of scavenging only very reactive radicals, while the dehydrogenated form is an excellent scavenger via a hydrogen transfer mechanism. ", "The environment plays an important role in the free radical scavenging activity of DHLA because in water it is deprotonated, and this enhances its activity. ", "In particular, the reaction rate constant of DHLA in water with an HOO(•) radical is close to the diffusion limit. ", "This has been explained on the basis of the strong H-bonding interactions found in the transition state, which involve the carboxylate moiety, and it might have implications for other biological systems in which this group is present." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "Q:\n\nValidating AMP page issue\n\nI am adding amp-html to our business website. ", "I keep getting the error below,\nThe mandatory text (CDATA) inside tag 'head > style : boilerplate' is missing or incorrect.", "\n\nI am following https://www.ampproject.org/docs/reference/spec.html#required-markup but I can't seem to find this last issue in the page can someone tell me what I am missing? ", "\nThis is the link I am testing it with right now http://purencool.com.au/brand-derived-from-who-you-are/amp#development=1 and the attached image is the error that is showing\n\nA:\n\nYou need the AMP Boilerplate code somewhere in the <head> of your document.", "\n\n" ]

{ "pile_set_name": "StackExchange" }

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[ "If this is your first visit, be sure to\ncheck out the FAQ by clicking the\nlink above. ", "You may have to register\nbefore you can post: click the register link above to proceed. ", "To start viewing messages,\nselect the forum that you want to visit from the selection below.", "\n\nhelp with javascript Calculations radio box\n\nCan anyone help me\nI trying to do a piece of coding which has two groups of radio button in them one that selects the water system and the time it take and the other one selects which soil type and how many time to water the soil for. ", "I al so have a checked box if there are large plants to be watered which added and extra 1.5 time on\nI need to validate also if the radio button have been checked or not.", "\nI am have problems working on the calculation being a newbie at all this JavaScript thing" ]

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[ "FCA Mission: To present to coaches and athletes, and all whom they influence, the challenge and adventure of receiving Jesus Christ as Savior and Lord, serving Him in their relationships and in the fellowship of the church.", "\n\nMission StatementCentral Valley Public Schools mission is to provide academic and social opportunities for all individualsto experience, explore, and expand to become successful citizens." ]

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[ "Q:\n\nCalculate the co occurrence in file text\n\nI have one list, one file text and one string\nlist1 = ['man', 'girl', 'woman']\nstr = \"work\"\ntext_file\n\nWhat needed is to calculate the co occurrence of the string \"work\" with every item in the list1, when both of them occur in the same line in the text_file.", "\nI tried this\nn_occurrence = 0\nfor line in text_file:\n for item in list1:\n if item in line and str in line:\n n_occurrence +=1\n\nThis code calculates the co occurrence of str with all the elements of the list, but I want the co occurrence of str separately with each item in the list. ", "\nCan someone help?", "\n\nA:\n\nTry this\nfrom collections import defaultdict\nn_occurence = defaultdict(lambda:0)\nfor line in text_file:\n for item in list1:\n if item in line and str in line:\n n_occurence[item] +=1\n\n" ]

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[ "Q:\n\npopulating display tag in a popup using javascript\n\nIn my application,i am using jQuery-Ajax to get the list to be populated in a popup. ", "I am getting a list in the javascript code, like [[\"1\",\"abc\"],[\"2\",\"bcd\"]].. I am using a display tag in the popup section to display the popup.", "\nMy javascript function is like\nfunction getData()\n{\n $.ajax({\n url: 'getLists.jav',\n type: 'GET',\n success: function(data){\n $.each(data, function(key, value){\n alert(\"Success\"+value);\n });\n },\n error: function(data){\n alert(\"Error\");\n }\n });\n}\n\nI need my display tag to populate with that data using javascript. ", "Is it posible?", "\n\nA:\n\nIf you are populating dropdowns are smaller tables doing this in javascript is fine. ", "but if the table table more number of columns then its little difficult. ", "In the below case, in function(index, value) value is the domail object which has attributes of code, value, codeValue and its getters and setters. ", "i used to refresh the table of contents by rendering JSp since it has more number of columns. ", "Let me know your other technologies(Java/Struts/.Net) so that i can help you in that.", "\n$.ajax({\n type :\"POST\",\n url :methodArguments[1]+value,\n data :\"&random=\"\n + Math.random(),\n dataType: \"json\",\n success : function(data) {\n $.each(data.lstJSONValues, function(index, value){\n $(\"#\"+methodArguments[2]).append($(\"<option/>\").attr(\"value\", value.code).text(value.valueCode)); \n });\n },\n error:function(data)\n {\n alert(data);\n }\n });\n\n" ]

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[ "/****************************************************************************\n**\n** Copyright (C) 2009 Nokia Corporation and/or its subsidiary(-ies).", "\n** All rights reserved.", "\n** Contact: Nokia Corporation (qt-info@nokia.com)\n**\n** This file is part of the examples of the Qt Toolkit.", "\n**\n** $QT_BEGIN_LICENSE:LGPL$\n** Commercial Usage\n** Licensees holding valid Qt Commercial licenses may use this file in\n** accordance with the Qt Commercial License Agreement provided with the\n** Software or, alternatively, in accordance with the terms contained in\n** a written agreement between you and Nokia.", "\n**\n** GNU Lesser General Public License Usage\n** Alternatively, this file may be used under the terms of the GNU Lesser\n** General Public License version 2.1 as published by the Free Software\n** Foundation and appearing in the file LICENSE.LGPL included in the\n** packaging of this file. ", " Please review the following information to\n** ensure the GNU Lesser General Public License version 2.1 requirements\n** will be met: http://www.gnu.org/licenses/old-licenses/lgpl-2.1.html.", "\n**\n** In addition, as a special exception, Nokia gives you certain additional\n** rights. ", " These rights are described in the Nokia Qt LGPL Exception\n** version 1.1, included in the file LGPL_EXCEPTION.txt in this package.", "\n**\n** GNU General Public License Usage\n** Alternatively, this file may be used under the terms of the GNU\n** General Public License version 3.0 as published by the Free Software\n** Foundation and appearing in the file LICENSE.GPL included in the\n** packaging of this file. ", " Please review the following information to\n** ensure the GNU General Public License version 3.0 requirements will be\n** met: http://www.gnu.org/copyleft/gpl.html.", "\n**\n** If you have questions regarding the use of this file, please contact\n** Nokia at qt-info@nokia.com.", "\n** $QT_END_LICENSE$\n**\n****************************************************************************/\n\n#include <QDebug>\n#include \"hello.h\"\n\nMyPushButton::MyPushButton(const QString &text)\n : QPushButton(text)\n{\n setObjectName(\"mypushbutton\");\n qDebug() << \"My PushButton has been constructed\";\n}\n" ]

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[ "The present invention relates to optical communications. ", "More particularly, the present invention relates to a tunable filter for use in conjunction with optical communications systems.", "\nFIG. ", "1a depicts a simplified schematic diagram of atypical WDM network 100 in the prior art. ", "WDM network 100 includes a plurality of transmitters TX-1 through TX-n. Each of the transmitters includes an optical source for generating an optical signal xcex-i, i=1, n. Each optical signal xcex-i is characterized by a unique peak wavelength onto which information may be modulated in well-known fashion. ", "The plurality of optical signals xcex-1 through xcex-n are combined into a single xe2x80x9cmultiplexedxe2x80x9d signal m-xcex by wavelength multiplexer 102, and the multiplexed signal m-xcex is then launched into optical fiber 104.", "\nA plurality of subscriber terminals (e.g., 106-S1, 106-S2 and 108-S1 through 108-Sn) are in optical communication with network 100. ", "Each such subscriber terminal includes a receiver(s) (not shown) for receiving information that is carried over network 100 via multiplexed signal m-xcex. ", "An individual subscriber terminal may subscribe to the information contained on only a single channel (i.e., on a single optical signal xcex-i) of multiplexed signal m-xcex.", "\nSubscriber terminals 108-S1 through 108-Sn located at end terminal 108 require, collectively, most or all of the individual channels xcex-1 through xcex-n multiplexed signal m-xcex. ", "To provide such channels to subscriber terminals 108-S1 through 108-Sn, multiplexed signal m-xcex is typically demultiplexed, fully resolving it into its constituent channels. ", "Demultiplexer 110 is used for that purpose.", "\nSubscriber terminals 106-S1 and 106-S2 are located at xe2x80x9csmallxe2x80x9d intermediate node 106. ", "Node 106 requires only a few of the channels of multiplexed signal m-xcex (ie., ", "terminal 106-S1 receives only channel xcex-1 and terminal 106-S2 receives only channel xcex-3). ", "As a consequence, rather than fully demultiplexing multiplexed signal m-xcex at node 106, only the required channels are dropped (i.e., removed or separated) from multiplexed signal m-xcex and delivered to the appropriate subscriber terminal. ", "One or more xe2x80x9cwavelength xe2x80x9c(add)/dropxe2x80x9d filters (i.e., filters 106-WAD1, 106-WAD2), which are operable to drop a single channel, are advantageously used for this purpose.", "\nFor example, in network 100 at node 106, add-drop filter 106-WAD1 separates and drops channel xcex-1 from multiplexed signal m-xcex. ", "Channel xcex-1 is then transmitted to subscriber terminal 106-S1. ", "Also, add-drop filter 106-WAD2 separates and drops channel xcex-3, which is then transmitted to subscriber terminal 106-S2. ", "As the name implies, in at least some embodiments, wavelength add-drop filters are operable to add a single channel having the same characteristic wavelength as the drop channel. ", "For example, in network 100, transmitter 106-T1 generates signal xcex-1 that is added to multiplexed signal m-xcex via 106-WAD1. ", "Alternatively, such a channel may be added to the multiplexed signal elsewhere in network 100.", "\nIt will be clear to those skilled in the art that a typical WDM optical communications network will have many more nodes and typically includes many other elements (e.g., amplifiers for maintaining signal strength, etc.) ", "than are depicted in FIG. ", "1a. ", "These other nodes and other elements are not shown so that attention can be focused on those elements that are germane to an understanding of the present invention.", "\nFIG. ", "1b depicts a known wavelength add-drop filter. ", "The particular filter depicted in FIG. ", "1b is a Fabry-Perot etalon filter, well known in the art. ", "Etalon filter 150 consists of a pair of highly reflective dielectric mirrors M1 and M2 that are separated by a precisely defined gap G. An optical cavity OC is defined between opposed surfaces SM1 and SM2 of the final dielectric layer of each mirror.", "\nA multiple-wavelength signal MWS-IN from input waveguide (e.g., an optical fiber) F-IN is collimated by lens L1 and illuminates the mirrors M1 and M2. ", "Most of wavelengths of signal MWS-IN are reflected from the filter and couple into output waveguide F-OUT. ", "Signals Dxcex1-Dxcexj having a wavelength within a very narrow range or xe2x80x9cpassbandxe2x80x9d are, however, transmitted through the mirrors, pass through lens L2, and couple into drop waveguide F-D. Any signals Axcex having a wavelength within the narrow pass band of the filter can be delivered to filter 150 from xe2x80x9caddxe2x80x9d waveguide F-A and coupled into output waveguide F-OUT.", "\nPerformance parameters of the etalon filter 150, such as reflectivity/transmissibility, passband, center transmission wavelength of the passband and finesse are readily calculable and are dependent on properties of the optical cavity OC (i.e., gap G) and mirror reflectivity and the coupling efficiency into output waveguides.", "\nReturning to illustrative network 100, to xe2x80x9cdropxe2x80x9d two channels (e.g., xcex-1 and xcex-3) from multiplexed signal m-xcex, two add-drop switches (e.g., implemented as described above) can be used. ", "Alternatively, it is possible to drop the same two channels using a single xe2x80x9ctunablexe2x80x9d etalon filter having an adjustable passband xe2x80x9ccenterxe2x80x9d wavelength. ", "The xe2x80x9ccenterxe2x80x9d wavelength is the predominant wavelength of the passband (hereinafter xe2x80x9ccenter transmission wavelengthxe2x80x9d).", "\nIn such tunable etalon filters, one of the two mirrors is typically placed on a translation actuator (e.g., a piezoelectric transducer) that is under electrical control. ", "Moving the actuator changes the size of the gap between the mirrors. ", "Since the gap (size) controls the center transmission wavelength of the filter, moving the actuator changes that center transmission wavelength.", "\nA problem exists, however, with existing tunable filters. ", "As explained above, to change the center transmission wavelength, the size of the gap between the two mirrors is altered. ", "In doing so, the gap will assume a number of intermediate sizes until the desired size is attained. ", "At such intermediate gap sizes, the optical cavity will tune to channels or signals having intervening wavelengths (hereinafter xe2x80x9cintervening channelsxe2x80x9d or xe2x80x9cintervening signalsxe2x80x9d). ", "Such intervening signals will be transmitted by the filter, delivered to the drop fiber and passed to the subscriber terminal rather than to the intended destination. ", "To prevent intervening signals from being delivered to a subscriber terminal in this manner, those signals must be disadvantageously temporarily interrupted while tuning the filter to a new center transmission wavelength.", "\nThe art would therefore benefit from a tunable filter that, during tuning, does not disrupt intervening channels.", "\nSome embodiments of the present invention provide a tunable filter without some of the disadvantages of the prior art. ", "In particular, the illustrative embodiment of the present invention is a tunable filter that does not interrupt intervening channels during tuning.", "\nIn accordance with the illustrative embodiment of the present invention, a tunable filter includes an optical cavity, a tuning device and a filter-disabling device. ", "The length of the optical cavity defines the center transmission wavelength of the filter. ", "Other attributes of the optical cavity and the mirrors define the finesse of the filter.", "\nAs used herein, the term xe2x80x9cpassbandxe2x80x9d refers to the range of wavelengths that are transmitted or passed by a filter, the term xe2x80x9ccenter transmission wavelengthxe2x80x9d refers to the predominant or peak wavelength in the passband, and the term xe2x80x9cfinessexe2x80x9d refers to the transmissibility of the filter. ", "The term xe2x80x9cfinessexe2x80x9d is also properly considered to be a measure of the xe2x80x9csharpnessxe2x80x9d of the transmission peak of the filter. ", "And, as will be appreciated by those skilled in the art, the term xe2x80x9cfinessexe2x80x9d also has mathematical definitions (e.g., assuming equal reflectivity mirrors: finesse=4r/(1xe2x88x92r2), where xe2x80x9crxe2x80x9d is the reflectivity of the mirrors). ", "In the context of the present invention, the term xe2x80x9cfinessexe2x80x9d is intended to refer to the transmissibility of the filter, as will become clear later in this Specification.", "\nThe tuning device is operable to change the center transmission wavelength of the tunable filter. ", "The filter-disabling device is operable to temporarily disrupt the finesse or otherwise substantially lower the transmissibility of the optical cavity, thereby preventing the transmission of any wavelengths through the tunable filter. ", "In some embodiments, filter transmissibility is lowered by disrupting the reflectivity (along the optical axis) of at least one of the two mirrors defining an optical cavity.", "\nIn accordance with the present teachings, before changing the center transmission wavelength, the filter-disabling device is enabled. ", "Doing so disrupts the finesse of the optical cavity thereby substantially preventing the transmission of any optical signals through the filter. ", "The tuning device is then used to change the center transmission wavelength. ", "Even though the tuning device will tune to undesired intervening channels during the tuning process, the filter will not transmit such intervening channels since the finesse of the optical cavity is disrupted (i.e., the transmissibility of the filter is low). ", "After tuning is complete, the filter-disabling device is defeated and the filter exhibits its desired transmission characteristic (i.e., transmits the desired channel through the filter).", "\nThe inventive concept may be implemented in a variety of ways. ", "Several illustrative embodiments are summarized below and described in more detail later in this Specification.", "\nIn some embodiments, the optical cavity comprises two spaced-apart mirrors. ", "In a few of those embodiments, one of the mirrors is movable and functions as the tuning device. ", "In particular, moving the movable mirror changes the length of the optical cavity thereby changing the center transmission wavelength of the filter. ", "The movable mirror can be readily implemented using well-known surface micromachining techniques (e.g., micro-electromechanical systems xe2x80x9cMEMSxe2x80x9d).", "\nIn one embodiment, filter-disabling device comprises an arrangement for tilting or rotating one of the mirrors. ", "Tilting a mirror disrupts the finesse of the optical cavity such that the filter becomes reflective of all wavelengths of light.", "\nIn other embodiments, the optical cavity is modified wherein one of the two mirrors is xe2x80x9csplitxe2x80x9d into two groups of layers of dielectric material that are separated by a gap. ", "Thus, the filter has two xe2x80x9cgaps,xe2x80x9d a primary gap between the first and the second mirror (tuning device), and an auxiliary gap (filter-disabling device) that divides the layers of the xe2x80x9csplitxe2x80x9d mirror. ", "Both the primary gap and the auxiliary gap are variable. ", "When the auxiliary gap is at a (readily) predetermined size, the finesse of the filter is at a maximum. ", "By appropriately changing the auxiliary gap, the finesse of the filter is disrupted and the filtering function is defeated.", "\nIn other embodiments, the filter-disabling device comprises an electrically-switched absorbing, scattering or depolarizing media that is disposed in the optical cavity. ", "By applying a voltage, the optical characteristic of the media can be changed from non-transmissible to transmissible (or visa-versa). ", "The cavity is tuned (i.e., the center transmission wavelength is changed) by changing the length of the optical cavity.", "\nIn still other embodiments, an optical cavity incorporates a semiconductor optical amplifier that provides either a zero-loss or highly lossy roundtrip as a function of whether current is flowing through the optical amplifier." ]

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[ "Check out our new site Makeup Addiction\n\nadd your own caption\n\nadd your own caption\n\nadd your own caption\n\nadd your own caption\n\nadd your own caption\n\nadd your own caption\n\nadd your own caption\n\nadd your own caption\n\nadd your own caption\n\nadd your own caption\n\nadd your own caption\n\nI wish I owned a cat So I could get upvotes too" ]

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[ "Dacology\n\nDacology is a branch of Thracology which focuses on the scientific study of Dacia and Dacian antiquities and is a regional and thematic branch of the larger disciplines of ancient history and archaeology. ", "A practitioner of the discipline is a Dacologist. ", "Dacology investigates the range of ancient Dacian culture (language, literature, history, religion, art, economics, and ethics) from c. 1000 BC up to the end of Roman rule in the 4th-7th centuries. ", "It is directly subordinated to Thracology, since Dacians are considered a branch of the Thracians by most mainstream research and historical sources. ", "Other theories sustain that the Daco-Thracian relation is not as strong as originally thought and as such Dacology has the potential to evolve as an independent discipline from Thracology.", "\n\nHistory \nOne of the first mentions of the term Dacology was made by the historian Radu Vulpe at the 2nd International Congress of Thracology in September 1976 in connection with the Romanian historians Bogdan Petriceicu Hasdeu and Ion I. Russu. ", "The Romanian Thracology Institute I.G Bibicescu, part of Romanian Academy, was founded in Bucharest in the same year. ", "One of his first directors was the thracologist Dumitru Berciu (1907–1998).", "\n\nThe related term Thraco-Dacology also exists, alluding to Thraco-Dacian, and one of the first uses is also from around 1980, in the Romanian government archive.", "\n\nThe term Dacologist has been negatively affected by the association with Protochronism. ", "Some researchers prefer to call themselves Thracologists instead of Dacologists. ", "This choice of title is made in the context of their research being focused on the Dacians and without necessarily promoting a strong connection between the Thracians and Dacians.", "\n\nDacologists \nResearchers who have been noted in the field of Dacology include:\n Bogdan Petriceicu Hasdeu\n Ion I. Russu\n Radu Vulpe\n Andrei Vartic\n\nInternational Congress of Dacology \nThere have been 11 editions of the International Congress of Dacology organized so far. ", "However, they have been organized by the controversial Dacomanic group around Napoleon Săvescu, thus making the term Dacology synonymous with Protochronism in this ambiance.", "\n\nSee also \n Dacia\n Thracology\n Dacian language\n Thracian language\n Protochronism\n\nNotes\n\nReferences\n\nExternal links \n\n Nationalism and the Representation of Society in Romanian Archaeology\n La plecarea lui Andrei Vartic\n\n \nCategory:Historiography of Dacia\nCategory:Archaeology of Romania\nCategory:Dacian archaeology" ]

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[ "•As a result of our successful fundraiser and summer workshop series, I’m happy to announce that we’re hiring two additional full-time researchers later in 2015: Mihaly Barasz and Scott Garrabrant!", "\nGeneral updates\n\n•We’ve wrapped up our largest fundraiser ever: 256 donors brought in a total of $617,678! ", "Thanks to you, we’ve hit our first two fundraising goals and received $117,678 that will go toward our third goal: Taking MIRI to the Next Level. (", "These number may increase over the next week as we add any donations we receive that were initiated before the end of the fundraiser.)", "\n\n•“If you agree AI matters, why MIRI?” ", "Two new replies to this question: Assessing Our Past and Potential Impact and What Sets MIRI Apart?", "\n\n•We’re moving to a larger office in the same building this October. ", "If you have experience in office planning or access control systems and would like to help out with our plans, shoot Malo an email at malo@intelligence.org.", "\n\nNews and links •GiveWell publishes its initial review of potential risks from advanced artificial intelligence, as well as a new article on the long-term significance of reducing global catastrophic risks.", "\n\n•Stuart Russell explains the AI alignment problem in a San Francisco talk and in a (paywalled) interview in Science.", "\n\n•A much earlier discusion of the AI control problem in a 1960 Science article." ]

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[ "Intravascular ultrasound to assess anastomotic patency after lung transplantation.", "\nPulmonary arterial anastomotic stenosis is an unusual complication after single-lung transplantation. ", "Intravascular ultrasound, performed at the bedside with an introducer sheath and guidewire, is a new technique that provides high-resolution tomographic images of the anastomotic site. ", "This modality was used early in the postoperative course of a 58-year-old man to exclude significant pulmonary arterial anastomotic narrowing after right single-lung transplantation for primary pulmonary hypertension." ]

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[ "Wednesday, December 6, 2017\n\nYamaha PSRE253 61-Key Portable Keyboard $69.99 + Free Shipping & More\n\n61 full-sized keys are great for learning and developing keyboard playing\ntechnique.", "\n\nDuo mode splits the keyboard into two halves, each with their own\n\"middle C\" for practicing with a partner\n\nThe Aux Line Input allows you to\nconnect any music device with a headphone output, such as an MP3 player, a\ncomputer, a mixer or even another keyboard, and hear it through the internal\nspeakers. ", "The Portable Grand button and instantly resets the keyboard to the\ngrand piano Voice\n\n32-note polyphony allows for the performance of beginner to\nadvanced level pieces, allowing for sustained notes to ring through without\nbeing cut off.", "\n\nThe PSRE253 operates on batteries or with a power adapter.", "\nNOTE - Power Adapter is sold separately (Available here for $10.96)." ]

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[ "Arabidopsis Firsts\n\nStatus message\n\nNew Feature: Guest Login function added to facilitate site exploration without registering. ", "Try it out!", "\n\nThis topic captures responses to the question posed to the Newsgroup recently: \"What are some seminal contributions to plant biology and to science in general coming first from Arabidopsis?\" ", "Comments and additions are welcome.", "\n\nTo me, I think of circadian clock components that were relevant to the animal literature, that were found first in Arabidopsis. ", "Even cry1 receptors are important in animals with a minor role in plants (at best).", "\n\nMy research discovered an Arabidopsis-specific orphan gene that functions in regulating carbon allocation-- the first research to discover a function of an orphan gene in plant metabolism. ", "The gene name is Qua Quine Starch.", "\n\nThe Arabidopsis Information Portal is funded by a grant from the National\nScience Foundation (#DBI-1262414)\nand co-funded by a grant from the Biotechnology and Biological Sciences\nResearch Council (BB/L027151/1)" ]

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[ "New website and Newsletter\n\nThe new website of the library of the Peace Palace is now live! ", "With this renewed website we strive to improve our (online) library services and optimize the accessibility of our resources. ", "The main menu at the top of the webpage displays an overview of our collection and webservices. ", "The completely renewed design and interface displays our services as clear, attractive and user friendly as possible. ", "We hope you will benefit a lot from these improvements.", "\n\nHelp us improve our new website\n\nWe realize there are some loose ends, even undetected loose ends. ", "Until the moment we have removed these irregularities, we can call this a beta-release of the website. ", "We ask you, our user, to browse our new website to get a taste of it. ", "See how it works and then let us know what you think about it. ", "So, give us feedback and / or fill in our questionnaire. ", "This way it will be a lot easier for us to provide you with the most relevant and needed information. ", "Remember, what we offer now is just a starting point! ", "In the near future our research guides and other services will continue to develop, the information landscape will be continuously adapted and updated. ", "We hope that this new approach will be most beneficial to you!", "\n\nResearch guides: a new way of presenting our resources\n\nRearranging the way in which libraries usually profile themselves on the web, is a hard thing to do. ", "Libraries intend to express what they can provide: lots of books and journals, nowadays also e-books and e-journals. ", "And that there is a library system to be used for searching or detecting what you want.", "\nHowever, we decided to change course about one year ago. ", "We will not state any more that we have tons and tons of publications in whatever form, although this is really the case, but we will try to focus on a selection of important subjects in the domain of international law. ", "Therefore, we developed so called research guides, each having an introduction, an up to date bibliography, the most important reference works, related keywords and so on. ", "Explore our new Research guides »\n\nAsk our librarians or share your expertise\n\nThose responsible for creating and maintaining the research guides are experts in their fields. ", "If you have any questions about a research guide or you need custom advise, ask our librarians.", "\nBesides that we strongly invite you to express your meaning or give extra information using the contact form presented with each research guide or by commenting on blogs and library news items.", "\n\nPeace Palace Library Newsletter\n\nThe Library starts this year with a new service: the Peace Palace Library Newsletter. ", "With this service we keep you up to date with news about your Library and information about topics and resources on international law. ", "Our relations receive the first newsletter in January 2012. ", "If you did not yet receive the newsletter and you are interested in receiving it, use the subscription form on our website to sign up. ", "The newsletter will appear approximately once every two months.", "\n\nExplore our Research guides\n\nEuropean Union\n\nIn 2012, the European Union (EU) received the Nobel Peace Prize for its decades-long contribution to the advancement of peace and reconciliation, democracy and human rights in Europe. ", "When the first steps towards supranational cooperation were made in the aftermath of World War II, primarily targeted at preventing the rearmament of Germany, the Founding Fathers of the European integration could never have imagined this outcome in their wildest dreams." ]

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[ "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE \\[[@pone.0212662.ref085]\\] partner repository with the dataset identifier PXD012720).", "\n\nIntroduction {#sec001}\n============\n\nAnterior cruciate ligament (ACL) injuries are has been linked to increased risk of posttraumatic osteoarthritis (OA) in humans and animal models \\[[@pone.0212662.ref001]--[@pone.0212662.ref003]\\]. ", "Synovial fluid has been an attractive source to identify new biomarkers for monitoring joint health and a better understanding of the disease pathophysiology. ", "This attraction is primarily due to the fact the synovial fluid bathes all the intrinsic structures of diarthrodial joints, including articular cartilage and synovium, both of which have shown to be actively involved in OA development \\[[@pone.0212662.ref004], [@pone.0212662.ref005]\\]. ", "Additionally, alterations in these structures due to OA may be directly reflected in the composition of synovial fluid, which could be correlated to disease severity and progression. ", "Recent advances in high-throughput and sensitive mass spectrometry (MS)-based approaches have facilitated protein profiling of complex biological fluids including synovial fluid. ", "As such, this technology has emerged as a powerful and reproducible technique to identify proteins involved in disease etiology and pathogenesis, as well as potential biomarkers for a range of diseases, including arthritis \\[[@pone.0212662.ref006]--[@pone.0212662.ref011]\\].", "\n\nRecently, a biologically augmented ACL repair procedure, bridge-enhanced ACL repair, has shown to be successful in reducing macroscopic evidence of posttraumatic OA following ACL injury in porcine knees \\[[@pone.0212662.ref012]\\]. ", "This new surgical technique uses a combination of a novel extracellular matrix-based scaffold to augment a suture repair of the torn ACL \\[[@pone.0212662.ref013]\\]. ", "Using the porcine ACL transection model, where the untreated knee progresses to posttraumatic OA and the repaired knee promotes cartilage preservation, allows us to compare these two different consequences of an identical surgical injury and potentially identify mechanisms and biomarkers for posttraumatic OA development.", "\n\nCompared to other animal models, the porcine knee has been shown to be closest to the human based on its size, anatomy and functional dependency on the ACL \\[[@pone.0212662.ref014]\\]. ", "Furthermore, porcine knee develops posttraumatic OA following ACL transection in a pattern similar to that reported in humans, but at a faster rate, with the joint changes at 1 year reflective of those seen at 10--15 years after ACL reconstruction in humans \\[[@pone.0212662.ref012]\\]. ", "This faster onset of post-traumatic OA allows for more rapid assessment of factors that may influence the development of posttraumatic OA following ACL injury and treatment. ", "The high degree of similarity between human and porcine synovial fluid \\[[@pone.0212662.ref015]\\]. ", "further justifies the porcine knee as a suitable model to study the biology of OA.", "\n\nIn the current work, we used an isotopically labeled high resolution LC MS/MS-based proteomics approach to analyze the protein profile of synovial fluid at 6 and 12 months after ACL transection in untreated and repaired porcine knees. ", "Our primary aim was to determine how the synovial fluid proteome differs between the two groups in an effort to identify candidate proteins that may be associated with the development of posttraumatic OA. ", "We hypothesized that the development of macroscopic cartilage damage following surgical ACL transection would be accompanied by differential changes in synovial fluid proteome in untreated knees compared to repaired joints.", "\n\nMaterials and methods {#sec002}\n=====================\n\nStudy design {#sec003}\n------------\n\nThis study was approved by the Institutional Animal Care and Use Committee at Boston Children\\'s Hospital. ", "The study was designed as a randomized controlled large animal trial with cross-sectional outcome assessments at two post-injury time points. ", "The study was designed as a randomized controlled large animal trial with cross-sectional outcome assessments at two post-injury time points. ", "A total of 30 adolescent Yucatan mini-pigs (ages 14--16 months) underwent unilateral ACL transection and were randomly treated with bridge-enhanced ACL repair (BEAR, n = 16) or left untreated (ACLT, n = 14). ", "Animals were obtained from LoneStar Laboratory Swine (Sioux Center, IA, USA). ", "A computer based random permutation of the complete set of animal identifiers was used to randomize treatment allocation and side of unilateral surgery. ", "Half of the animals within each treatment group were euthanized at 6 months, while the other half was followed up to 12 months post-injury. ", "The histological, biomechanical and OA-related outcomes for these animals have been previously reported by our group \\[[@pone.0212662.ref012], [@pone.0212662.ref016]\\]. ", "For the current study, synovial fluid from an additional 6 healthy intact age-matched adolescent Yucatan minipigs was also used as a control.", "\n\nSurgical procedure {#sec004}\n------------------\n\nAll animals were acclimated to the animal care facility environment for a minimum of 7 days prior to any surgical procedures. ", "Animals allocated to ACLT or BEAR groups underwent ACL surgery under general anesthesia and postoperative housing as previously reported \\[[@pone.0212662.ref012], [@pone.0212662.ref016]\\]. ", "In brief, the ACL was transected surgically and for the animals assigned to BEAR group, the torn ACL was repaired using an extracellular matrix--based scaffold soaked with autologous blood as previously described \\[[@pone.0212662.ref017]\\]. ", "After surgery, all animals were housed in individualized pens and checked multiple times a day for 4 weeks. ", "They were then shipped to a farm for long-term care (Coyote Consulting Corp Inc, Douglas, Massachusetts). ", "Full weightbearing status was achieved within 48 to 72 hours and the animals were allowed ad libitum activity. ", "Two animals (both in the ACLT group) developed subcutaneous abscesses near the jaw that were treated with short-term oral antibiotics. ", "These animals were included in the study as there was no visual evidence of joint synovitis at the time of dissection. ", "In the BEAR group, one animal (12 months) was shipped to the external holding facility at 2 weeks rather than 4 weeks postoperatively, a deviation in the postoperative rehabilitation, thus it was excluded from the analysis. ", "Also, one BEAR animal (6 months) had a missing synovial fluid sample, thus was excluded from this study. ", "The total number of animals, analyzed in this study, was 7 in each group at each time point.", "\n\nAfter 6 and 12 months, synovial fluid was aspirated from the injured knee joints under anesthesia. ", "For control animals, synovial fluid was obtained under anesthesia within 1 week of arrival to the animal care facility. ", "Samples were centrifuged at 3,000g at room temperature for 10 min and the supernatant stored at −80°C. ", "Following aspiration, animals were euthanized and the knees were harvested and stored at -20°C.", "\n\nProteomics analysis {#sec005}\n-------------------\n\n### Sample preparation {#sec006}\n\nA multiplexed Isobaric Tag for Relative and Absolute Quantitation (iTRAQ) \\[[@pone.0212662.ref018]\\] coupled with liquid chromatography with tandem mass spectrometry (LC-MS/MS) was used to identify the changes in synovial fluid protein levels. ", "iTRAQ is a chemical labeling method, which uses multiplexed isobaric tagging reagent to label peptide mixtures which allows post label mixing of the samples (after enzymatic digestion) without adding complexity to the MS analysis \\[[@pone.0212662.ref019]\\]. ", "This will help minimizing the quantitation variability during sample preparation prior to LC MS/MS data collection. ", "The iTRAQ-based quantitative proteomics approach has been widely used to identify biomarkers for several diseases including end stage OA and rheumatoid arthritis \\[[@pone.0212662.ref007], [@pone.0212662.ref008], [@pone.0212662.ref011]\\].", "\n\nComparison of the peak areas and resultant peak ratios for MS/MS reporter ions was used to measure the relative abundance of proteins. ", "Synovial fluid from each individual sample was reduced with DTT, alkylated with iodoacetamide, and digested with trypsin at 37°C overnight. ", "Digested samples were separated across five different sets for comparison with each set consisting of seven unique samples ([S1 Table](#pone.0212662.s001){ref-type=\"supplementary-material\"}). ", "A pooled sample consisting of equal amount of proteins from all 35 total samples was made to serve as a common eighth sample across the five different sets of comparison. ", "Per each comparison set, equal amounts of total peptides were aliquoted and labeled with the 8-plex iTRAQ reagents (iTRAQ Reagents Multiplex kit, Applied Biosystems, CA), then pooled, dried and stored until analyzed by mass spectrometry. ", "Total digested peptides in each sample were quantified by Amino Acid Analysis (AAA; Hitachi Model L-8900) prior to iTRAQ labeling to ensure equal amounts of total peptides for each sample.", "\n\n### LC-MS/MS analysis {#sec007}\n\nLC-MS/MS analysis of the iTRAQ labeled samples peptides were carried out using AB SCIEX TripleTOF 5600 mass spectrometer (SCIEX, Framingham, MA) coupled to a NanoACQUITY UPLC system (Waters Inc., Milford, MA). ", "The dried peptide samples were dissolved in 70% formic acid/water, diluted with 13 μl 0.1% trifluoroacetic acid (TFA) and quantitated at A280 absorption on a Nanodrop (ThermoFisher Scientific, Wilmington, DE). ", "Peptides were loaded on a NanoACQUITY Symmetry C18 UPLC Trap column, washed in 9% Buffer A (0.1% formic acid in water) then run for 160 minutes over a linear gradient 99%A to 65% A at 500 nL/min. ", "The parameters utilized on the 5600 Triple-TOF were: 2300 V IonSpray Voltage Floating, Ion Source Gas 1 of 10, Curtain Gas of 20, Interface Heater Temperature 120, with a declustering potential of 60. ", "MS cycle time was 250 milliseconds, with a maximum 20 MS/MS spectra taken each with a 100-millisecond accumulation time, and collision energy adjusted for iTRAQ reagents.", "\n\n### Protein abundance level calculation and analysis {#sec008}\n\nThe ProteinPilot peptide summary was filtered to only include peptides with zero mis-cleavages, high confidence peptide identifications, and two or more iTRAQ reporter ion ratios measured. ", "We then performed a cyclic Lowess normalization \\[[@pone.0212662.ref020]\\] on the remaining peptides to compensate for any differences between iTRAQ labels. ", "All peptides across the 5 sets were merged and normalized to the common pooled sample. ", "This was done by subtracting the common pooled sample, replicated in each set, from the other 7 samples in each set. ", "The purpose of this adjustment is to remove set-specific effects to facilitate comparisons between the experimental groups (i.e. Intact, ACLT and BEAR) and time points (i.e. 6 and 12 months) across all the sets. ", "A linear mixed effect model was used to compare the normalized protein abundance levels between the groups at each time point (limma package in R v3.3.1, The R Foundation for Statistical Computing) \\[[@pone.0212662.ref021]\\]. ", "Benjamini and Hochberg method was used to adjust the p-values to control the false discovery rate \\[[@pone.0212662.ref022]\\]. ", "P≤0.05 considered statistically significant and used to select differentially abundant proteins between the groups (i.e. Intact, ACLT 6 months, ACLT 12 months, BEAR 6 months and BEAR 12 months). ", "Bivariate linear regression analyses were used to assess the correlations between the macroscopic cartilage damage (total lesion area assessed at 6 or 12 months after ACLT and BEAR) and normalized abundance levels of each identified secreted proteins.", "\n\n### Pathway enrichment analysis {#sec009}\n\nThe differentially abundant proteins were used to analyze the enrichment of specific pathways using the Process Networks ontology in the MetaCore bioinformatics suite (Thomson Reuters) \\[[@pone.0212662.ref023]\\]. ", "Sus scrufa Ensembl identifiers and, if not recognized, gene symbols of the corresponding gene for each protein were used for as input for the analysis. ", "Pathways were considered significantly enriched when they contain at least 2 unique proteins and adjusted P values (false discovery rate; FDR) were less than 0.05.", "\n\nResults {#sec010}\n=======\n\nAs previously reported, macroscopic cartilage damage was observed in the ACLT knees, primarily across the medial femoral condyle \\[[@pone.0212662.ref012]\\]. ", "While at 6 months no difference in total cartilage lesion area was observed between ACLT and BEAR knees, ACLT knees had a significantly larger total lesion area at 12 months compared to the BEAR knees ([Fig 1](#pone.0212662.g001){ref-type=\"fig\"}) \\[[@pone.0212662.ref012]\\].", "\n\n![", "Development of macroscopic cartilage damage following ACL transection.\\\nTotal cartilage lesion area at 6 and 12 months after untreated ACL injury (ACLT) and bridge-enhanced ACL repair (BEAR). ", "Data is presented as Mean ± SD. ", "P value is derived from a one-way ANOVA with posthoc Bonferroni correction for multiple comparisons (adopted and modified with permission from Murray MM and Fleming BC, Am J Sports Med 2013 \\[[@pone.0212662.ref012]\\]) Macroscopic cartilage damage was assessed by measuring the cartilage lesions across the femoral condyles and tibial plateau in medial and lateral compartments using India ink staining and calipers \\[[@pone.0212662.ref012]\\].](pone.0212662.g001){#pone.0212662.g001}\n\nMost abundant secreted proteins found in the synovial fluid after ACL transection {#sec011}\n---------------------------------------------------------------------------------\n\nA total of 1,340 unique peptides corresponding to 232 proteins were identified across all 34 samples ([S2 Table](#pone.0212662.s002){ref-type=\"supplementary-material\"}). ", "Of the 232 detected proteins, 80 (34%) were secreted extracellular proteins. ", "The subcellular localization patterns of the identified proteins were similar to those reported in knee synovial fluid proteins of humans with knee OA \\[[@pone.0212662.ref024]\\]. ", "The top 20 most abundant secreted proteins in the synovial fluid of each surgical group are listed in [Table 1](#pone.0212662.t001){ref-type=\"table\"}. ", "Of the 232 detected proteins, 65 (28%) were significantly differentially abundant in at least one of the comparisons between the experimental groups (i.e. ACLT, BEAR and Intact) and / or between the time points ([S3 Table](#pone.0212662.s003){ref-type=\"supplementary-material\"}), and 33 (51%) of these were secreted extracellular proteins.", "\n\n10.1371/journal.pone.0212662.t001\n\n###### Top 20 most abundant secreted proteins detected in the synovial fluid in each surgical group.", "\n\nThe uniquely abundant proteins in each group are highlighted in bold.", "\n\n![](", "pone.0212662.t001){#pone.0212662.t001g}\n\n ------------------------------------------------------ -------------------------------------------------------- ---------------- ---------- ---------------------------------------------- ----------------\n **Abundant Proteins in the ACLT Group at 6 Months** \n **Rank** **Protein** **Gene** **Rank** **Protein** **Gene**\n 1 Peptidylprolyl isomerase A *PPIA* 11 Serotransferrin *TF*\n 2 Vitamin K-dependent protein C *PROC* 12 **Aggrecan core protein** ***ACAN***\n 3 Lactadherin *MFGE8* 13 Corticosteroid-binding globulin *SERPINA6*\n 4 Cartilage intermediate layer protein 1 *CILP* 14 Alpha-2-HS-glycoprotein *AHSG*\n 5 Coagulation Factor 12 *F12* 15 Protein AMBP *AMBP*\n 6 Glucose-6-phosphate isomerase *GPI* 16 Hemopexin *HPX*\n 7 Alpha-1-antitrypsin *SERPINA1* 17 Complement component C7 *C7*\n 8 **Pituitary adenylate cyclase-activating polypeptide** ***ADCYAP1*** 18 Serum albumin *ALB*\n 9 **Haptoglobin** ***HP*** 19 Apolipoprotein E *APOE*\n 10 Inhibitor of carbonic anhydrase *ICA* 20 Clusterin *CLU*\n **Abundant Proteins in the BEAR Group at 6 Months** \n **Rank** **Protein** ***Gene*** **Rank** **Protein** **Gene**\n 1 Peptidylprolyl isomerase A *PPIA* 11 Serotransferrin *TF*\n 2 Vitamin K-dependent protein C *PROC* 12 Complement component C7 *C7*\n 3 **Plasminogen activator inhibitor 1** ***SERPINE1*** 13 **Apolipoprotein C3** ***APOC3***\n 4 Cartilage intermediate layer protein 1 *CILP* 14 Apolipoprotein E *APOE*\n 5 Lactadherin *MFGE8* 15 Inhibitor of carbonic anhydrase *ICA*\n 6 Glucose-6-phosphate isomerase *GPI* 16 Serum albumin *ALB*\n 7 Coagulation Factor 12 *F12* 17 Protein AMBP *AMBP*\n 8 Corticosteroid-binding globulin *SERPINA6* 18 Hemopexin *HPX*\n 9 Alpha-1-antitrypsin *SERPINA1* 19 Alpha-2-HS-glycoprotein *AHSG*\n 10 **Elafin** ***PI3*** 20 Clusterin *CLU*\n **Abundant Proteins in the ACLT Group at 12 Months** \n **Rank** **Protein** **Gene** **Rank** **Protein** **Gene**\n 1 Cystatin-B *CSTB* 11 Hyaluronan and proteoglycan link protein 1 *HAPLN1*\n 2 Protein S100-A12 *S100A12* 12 **Peptidylprolyl isomerase A** ***PPIA***\n 3 Complement C5 *C5* 13 Aggrecan core protein *ACAN*\n 4 Lactotransferrin *LTF* 14 Alpha-1-antitrypsin *SERPINA1*\n 5 von Willebrand factor *VWF* 15 Cathepsin D *CTSD*\n 6 **Vitamin K-dependent protein C** ***PROC*** 16 **Prothrombin** ***F2***\n 7 **Prophenin-2** 17 Complement factor D *CFD*\n 8 Insulin-like growth factor-binding protein 2 *IGFBP2* 18 Prophenin-1 \n 9 Complement C1q subcomponent subunit A *C1QA* 19 **Decorin** ***DCN***\n 10 **Chitinase-3-like protein 1** ***CHI3L1*** 20 **Thyroxine-binding globulin** ***SERPINA7***\n **Abundant Proteins in the BEAR Group at 12 Months** \n **Rank** **Protein** **Gene** **Rank** **Protein** **Gene**\n 1 Hyaluronan and proteoglycan link protein 1 *HAPLN1* 11 Protein S100-A12 *S100A12*\n 2 Cystatin-B *CSTB* 12 Complement C1q subcomponent subunit A *C1QA*\n 3 **Cartilage intermediate layer protein 1** ***CILP*** 13 Complement factor D *CFD*\n 4 von Willebrand factor *VWF* 14 **Apolipoprotein A4** ***APOA4***\n 5 **Annexin A2** ***ANXA2*** 15 Insulin-like growth factor-binding protein 2 *IGFBP2*\n 6 Complement C5 *C5* 16 **Clusterin** ***CLU***\n 7 Cathepsin D *CTSD* 17 **Alpha-2-HS-glycoprotein** ***AHSG***\n 8 **Apolipoprotein M** ***APOM*** 18 Prophenin-1 \n 9 **Annexin A1** ***ANXA1*** 19 Alpha-1-antitrypsin *SERPINA1*\n 10 Aggrecan core protein *ACAN* 20 Lactotransferrin *LTF*\n ------------------------------------------------------ -------------------------------------------------------- ---------------- ---------- ---------------------------------------------- ----------------\n\nTreatment related changes in synovial fluid proteome {#sec012}\n----------------------------------------------------\n\nAt 6 months, a total of 27 secreted proteins were significantly differentially abundant between intact group and surgical groups (ACLT and/or BEAR; [Table 2](#pone.0212662.t002){ref-type=\"table\"}). ", "There were no significant differences in the normalized abundance levels of the detected secreted proteins between the ACLT and BEAR groups at 6 months.", "\n\n10.1371/journal.pone.0212662.t002\n\n###### Secreted proteins that are significantly different in abundance in ACLT and/or BEAR knees compared to intact group at 6 months.", "\n\nFold change values represent the ratio of detection in the ACLT or BEAR group versus intact group; thus a fold change greater than 1 reflects higher protein abundance in the synovial fluid of the ACLT or BEAR group and a fold change less than 1 reflects higher protein abundance in the synovial fluid of the intact group.", "\n\n![](", "pone.0212662.t002){#pone.0212662.t002g}\n\n Protein Gene ACLT / Intact BEAR / Intact \n -------------------------------------------------------------------------------------- ------------ --------------- --------------- ------- ----------\n **Differentially Abundant Proteins in both ACLT and BEAR Groups Compared to Intact** \n Vitamin K-dependent protein C *PROC* 6 1.03E-06 7.35 6.91E-08\n Cartilage intermediate layer protein 1 *CILP* 3.82 5.51E-03 5.35 8.34E-04\n Coagulation Factor XII *F12* 2.71 2.74E-04 2.67 3.34E-04\n Alpha-1-antitrypsin *SERPINA1* 1.62 8.92E-04 1.56 1.80E-03\n Clusterin *CLU* 1.6 6.52E-05 1.65 2.66E-05\n Inhibitor of carbonic anhydrase *ICA* 1.6 1.02E-04 1.47 8.87E-04\n Hemopexin *HPX* 1.59 2.16E-04 1.52 6.56E-04\n Serotransferrin *TF* 1.42 6.18E-05 1.5 7.23E-06\n Apolipoprotein A4  *APOA4* 1.38 2.59E-02 1.63 1.22E-03\n Protein AMBP *AMBP* 1.37 1.23E-02 1.31 2.99E-02\n Serum albumin *ALB* 1.13 3.68E-02 1.18 4.55E-03\n Transthyretin *TTR* 0.83 2.77E-02 0.79 8.35E-03\n Inter-α trypsin inhibitor heavy chain 2 *ITIH2* 0.8 1.99E-02 0.76 5.95E-03\n Complement factor B *CFB* 0.69 3.64E-02 0.72 4.43E-02\n Ig lambda-1 chain C regions *IGLC1* 0.59 2.36E-03 0.59 2.16E-03\n Complement factor D *CFD* 0.58 3.05E-04 0.61 1.17E-03\n Ficolin-2 *FCN2* 0.39 5.27E-03 0.54 3.98E-02\n **Differentially Abundant Proteins in ACLT Compared to Intact** \n Haptoglobin *HP* 3.21 8.33E-04 \n Coagulation factor V *F5* 0.09 4.33E-02 \n **Differentially Abundant Proteins in BEAR Compared to Intact** \n Peptidylprolyl isomerase A *PPIA* 11.53 1.74E-02\n Apolipoprotein C3 *APOC3* 1.75 4.57E-03\n Apolipoprotein E *APOE* 1.37 2.13E-02\n Apolipoprotein A1 *APOA1* 1.33 2.08E-02\n Prothrombin *F2* 0.73 1.13E-02\n Vitronectin *VTN* 0.71 5.80E-03\n\nAt 12 months, a total of 16 secreted proteins were significantly differentially abundant between intact group and surgical groups (ACLT and/or BEAR; [Table 3](#pone.0212662.t003){ref-type=\"table\"}). ", "Compared to the BEAR group, the ACLT group had higher normalized abundance levels of vitamin K-dependent protein C (by 2.4 fold, P = 0.00126) along with lower normalized abundance levels of apolipoprotein A4 (by 0.7 fold, P = 0.0213) and cartilage intermediate layer protein (by 0.35 fold, P = 0.049).", "\n\n10.1371/journal.pone.0212662.t003\n\n###### Secreted proteins that are significantly different in abundance in ACLT and/or BEAR knees compared to intact group at 12 months.", "\n\nFold change values represent the ratio of detection in the ACLT or BEAR group versus intact group; thus a fold change greater than 1 reflects higher protein abundance in the synovial fluid of the ACLT or BEAR group and a fold change less than 1 reflects higher protein abundance in the synovial fluid of the intact group.", "\n\n![](", "pone.0212662.t003){#pone.0212662.t003g}\n\n Protein Gene ACLT / Intact BEAR / Intact \n -------------------------------------------------------------------------------------- --------- --------------- --------------- ------ ----------\n **Differentially Abundant Proteins in both ACLT and BEAR Groups Compared to Intact** \n Trypsin-1 *PRSS1* 2.23 1.06E-02 2.24 8.52E-03\n Haptoglobin *HP* 1.96 4.03E-02 1.91 4.32E-02\n Actin beta *ACTB* 1.52 1.58E-02 1.65 3.55E-03\n Clusterin *CLU* 1.43 1.28E-03 1.7 7.33E-06\n Apolipoprotein A4  *APOA4* 1.36 3.17E-02 1.86 5.79E-05\n Apolipoprotein A1 *APOA1* 1.29 3.71E-02 1.43 3.90E-03\n Vitronectin *VTN* 0.77 3.28E-02 0.64 4.63E-04\n Inter-α trypsin inhibitor heavy chain family member 4 *ITIH4* 0.63 6.81E-03 0.55 6.32E-04\n **Differentially Abundant Proteins in ACLT Compared to Intact** \n Serotransferrin *TF* 1.2 2.14E-02 \n **Differentially Abundant Proteins in BEAR Compared to Intact** \n Cartilage intermediate layer protein *CILP* 2.83 5.01E-02\n Annexin A1 *ANXA1* 2.48 4.36E-02\n Plasminogen *PLG* 0.84 4.88E-02\n Inter-α trypsin inhibitor heavy chain 1 *ITIH1* 0.8 1.69E-02\n Inter-α trypsin inhibitor heavy chain 2 *ITIH2* 0.8 1.67E-02\n Ig lambda-1 chain C regions *IGLC1* 0.68 1.73E-02\n Vitamin K-dependent protein C *PROC* 0.44 1.99E-03\n\nThere were 20 secreted synovial fluid proteins with significant fold changes between the 6 to 12-month time points in ACLT and/or BEAR knees ([Table 4](#pone.0212662.t004){ref-type=\"table\"}). ", "Nine proteins had significant fold changes from 6 to 12 months after surgery in both groups. ", "Five proteins had a significant fold change from 6 to 12 months only after untreated ACL transection. ", "Six proteins had a significant fold change from 6 to 12 months only after bridge-enhanced ACL repair.", "\n\n10.1371/journal.pone.0212662.t004\n\n###### Secreted proteins that are significantly different in abundance between 6 and 12 months after surgery.", "\n\n![](", "pone.0212662.t004){#pone.0212662.t004g}\n\n --------------------------------------------------- --------------- -------------------------- -------------------------- -------------------------- ----------\n **Differentially abundant in both ACLT and BEAR** \n **Protein** **Gene** **ACLT (12 / 6 months)** **BEAR (12 / 6 months)** \n **Fold Change** ***P*-Value** **Fold Change** ***P*-Value** \n **Increased from 6 months to 12 months** \n Complement factor D *CFD* 1.80 8.97E-05 1.81 4.98E-05\n Transthyretin *TTR* 1.29 3.36E-03 1.37 2.69E-04\n **Decreased from 6 months to 12 months** \n Serotransferrin *TF* 0.85 2.93E-02 0.72 5.78E-05\n Serum albumin *ALB* 0.85 4.13E-03 0.76 1.05E-05\n Inhibitor of carbonic anhydrase *ICA* 0.74 5.26E-03 0.77 1.09E-02\n Apolipoprotein E *APOE* 0.73 1.61E-02 0.68 3.14E-03\n Protein AMBP *AMBP* 0.73 9.04E-03 0.69 2.07E-03\n Coagulation Factor 12 *F12* 0.60 3.46E-02 0.55 1.18E-02\n Vitamin K-dependent Protein C *PROC* 0.17 1.47E-06 0.06 8.04E-10\n **Differentially abundant only in ACLT** \n **Protein** **Gene** **ACLT (12 / 6 months)** \n **Fold Change** ***P*-Value** \n **Increased from 6 months to 12 months** \n Insulin-like growth factor-binding protein 2 *IGFBP2* 1.80 2.63E-02 \n Ig lambda-1 chain C regions *IGLC1* 1.45 2.20E-02 \n Thyroxine-binding globulin *SERPINA7* 1.45 1.24E-02 \n **Decreased from 6 months to 12 months** \n Hemopexin *HPX* 0.72 4.98E-03 \n Cartilage intermediate layer protein 1 *CILP* 0.26 5.46E-03 \n **Differentially abundant only in BEAR** \n **Protein** **Gene** **BEAR (12 / 6 months)** \n **Fold Change** ***P*-Value** \n **Increased from 6 months to 12 months** \n Annexin A1 *ANXA1* 3.82 2.81E-03\n **Decreased from 6 months to 12 months** \n Alpha-1-antitrypsin *SERPINA1* 0.73 1.51E-02\n Complement component C7 *C7* 0.58 2.73E-02\n Apolipoprotein C3 *APOC3* 0.56 1.87E-03\n Leukocyte elastase inhibitor *SERPINB1* 0.42 3.84E-02\n Peptidylprolyl isomerase A *PPIA* 0.07 6.66E-03\n --------------------------------------------------- --------------- -------------------------- -------------------------- -------------------------- ----------\n\nDifferentially abundant proteins enriched 7 biological pathways (Process Network ontology) including terms related to blood coagulation, proteolysis, inflammation and cell adhesion ([Table 5](#pone.0212662.t005){ref-type=\"table\"}).", "\n\n10.1371/journal.pone.0212662.t005\n\n###### Biological pathways enriched by differentially abundant proteins at 6 months.", "\n\n![](", "pone.0212662.t005){#pone.0212662.t005g}\n\n -----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------\n Pathway FDR Proteins\n ------------------------------------------------------------- ---------- ----------------------------------------------------------------------------------------------------------------------------\n Blood Coagulation 1.18E-04 Vitamin K-dependent protein C, Prothrombin, Plasminogen, Coagulation Factor V, Coagulation Factor XII, Alpha-1-antitrypsin\n\n Proteolysis (ECM Remodeling) 3.50E-04 Plasminogen, Prothrombin, Vitronectin, Coagulation Factor XII, Trypsin I, Clusterin, Alpha-1-antitrypsin\n\n Inflammation (Kallikrein-Kinin System) 7.63E-04 Inter-α trypsin inhibitor heavy chain\\\n family member 4, Prothrombin, Plasminogen, Coagulation Factor V, Coagulation Factor XII, Alpha-1-antitrypsin\n\n Inflammation (Protein C Signaling) 7.63E-04 Vitamin K-dependent protein C, Actin Beta, Prothrombin, Plasminogen, Coagulation Factor V\n\n Inflammation (Complement System) 7.63E-04 Complement Component C7, Ficolin, Clusterin, Complement Factor B, Complement Factor D\n\n Cell Adhesion (Platelet-Endothelium-Leucocyte Interactions) 1.79E-03 Vitamin K-dependent protein C, Prothrombin, Plasminogen, Coagulation Factor V, Vitronectin, Coagulation Factor XII\n\n Proteolysis (Connective Tissue Degradation) 4.51E-02 Plasminogen, Vitronectin, Trypsin 1, Alpha-1-antitrypsin\n -----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------\n\nAssociations between protein levels and total area of macroscopic articular cartilage damage {#sec013}\n--------------------------------------------------------------------------------------------\n\nAmong all the identified secreted proteins, notable associations (R^2^ ≥ 0.1) were only found between the total area of the macroscopic cartilage damage across the femoral condyles and tibial plateau and the normalized abundance levels of Ig lambda-1 chain C regions (r = 0.52), Hemopexin (r = -0.40), Clusterin (r = -0.35), Coagulation factor 12 (r = -0.32) and Cartilage intermediate layer protein 1 (r = -0.33); [Fig 2](#pone.0212662.g002){ref-type=\"fig\"}.", "\n\n{#pone.0212662.g002}\n\nDiscussion {#sec014}\n==========\n\nThe results of this study support our hypothesis that development of macroscopic cartilage damage following an ACL injury and subsequent surgery are accompanied with changes in synovial fluid proteome with different responses in untreated knees compared to repaired joints. ", "There was no significant difference in cartilage lesion area or quantitative protein abundance levels between the two treatment groups at 6 months. ", "However, by 12 months after surgery, there was significantly greater cartilage damage in the knees with an untreated ACL transection than in those knees that underwent bridge-enhanced ACL repair ([Fig 1](#pone.0212662.g001){ref-type=\"fig\"}). ", "This damage was accompanied by differences in the proteome between the groups at 12 months, with the ACLT group having a higher concentration of Vitamin K-dependent Protein C (2.4 fold), and a decreased content of Apolipoprotein A4 (0.7 fold) and Cartilage intermediate layer protein 1 (0.35 fold) when compared to the BEAR knees. ", "In addition, there was also a difference in the proteins which significantly changed in abundance between 6 and 12 months ([Table 4](#pone.0212662.t004){ref-type=\"table\"}), with Insulin-like growth factor-binding protein 2 (IGFBP2), Ig lambda-1 chain C regions (IGLC1), Hemopexin and CILP changing in the ACLT group, and significant changes in Annexin A1, alpha-1 antitrypsin, Complement C7, Apolipoprotein C3, Leukocyte elastase inhibitor and Peptidylprolyl isomerase A (PPIA) found in the BEAR group. ", "Increased levels of IGLC1 and decreased levels of Hemopexin, Clusterin, Coagulation factor 12 and CILP were also found to correlate with greater cartilage lesion area when the knees from both groups were pooled ([Fig 2](#pone.0212662.g002){ref-type=\"fig\"}).", "\n\nWhile there were no statistically significant differences in protein abundance between the surgical groups at 6 months after surgery, the makeup of the synovial fluid proteome, and specifically the top 20 most abundant proteins in the fluid, were similar but not identical in the two surgical groups. ", "Seventeen of the 20 most abundant secreted proteins ([Table 1](#pone.0212662.t001){ref-type=\"table\"}) were the same in ACLT and BEAR groups, 15 of which have been previously reported to be abundant in synovial fluid of human knees with OA \\[[@pone.0212662.ref008], [@pone.0212662.ref011], [@pone.0212662.ref024]\\]. ", "For the six differences (three in each group) in the top 20 secreted proteins, the ACLT knees had 2 additional pro-inflammatory proteins (Haptoglobin and Pituitary adenylate cyclase-activating polypeptide) while the BEAR group had two protease inhibitors at 6 months (Plasminogen activator inhibitor 1 and Elafin). ", "The pro-inflammatory role of Haptoglobin, Pituitary adenylate cyclase-activating polypeptide (PACAP), Plasminogen activation and Elastase are well documented \\[[@pone.0212662.ref025]--[@pone.0212662.ref028]\\]. ", "High synovial fluid concentrations of Haptoglobin, Plasminogen (or Plasmin) and Elastase have been reported in arthritic knees \\[[@pone.0212662.ref011], [@pone.0212662.ref024], [@pone.0212662.ref029]--[@pone.0212662.ref031]\\]. ", "PACAP-deficiency in mice has shown to result in lower inflammation in early arthritis followed by increased immune cell function and bone formation (e.g. osteophytes) in late arthritis \\[[@pone.0212662.ref032]\\]. ", "The presence of Haptoglobin and PACAP among the most abundant proteins in the ACLT group in addition to the presence of Plasminogen activator inhibitor 1 and Elafin among the most abundant proteins in the BEAR group at 6 months might be indicative of a more pro-inflammatory environment in ACLT knees at early stages of the disease. ", "Further studies would be needed to validate this hypothesis.", "\n\nIn addition to proteases and protease inhibitors, Apolipoprotein C3 and Aggrecan core protein (Aggrecan) were the other two secreted proteins which were uniquely present in the BEAR or ACLT top 20 abundance lists, respectively, at 6 months ([Table 1](#pone.0212662.t001){ref-type=\"table\"}). ", "Apolipoprotein C3 has previously been identified in the synovial fluid of human knees with OA \\[[@pone.0212662.ref024]\\], and its plasma levels have been found to be elevated in patients with non-progressing radiographic knee OA compared to those who progress \\[[@pone.0212662.ref033]\\]. ", "This is reflected by our finding of Apolipoprotein C3 among the most abundant proteins in the non-progressive BEAR group and not in the progressive ACLT group at 6 months ([Table 1](#pone.0212662.t001){ref-type=\"table\"}). ", "Aggrecan has also been previously detected in synovial fluid of knees with OA \\[[@pone.0212662.ref011], [@pone.0212662.ref024]\\]; however, in this case, increased Aggrecan in the synovial fluid has been associated with greater cartilage damage in osteoarthritic joints \\[[@pone.0212662.ref034]--[@pone.0212662.ref037]\\]. ", "This is reflected in our study where Aggrecan was among the most abundant proteins in the ACLT group and not in BEAR or intact groups ([Table 1](#pone.0212662.t001){ref-type=\"table\"}).", "\n\nAt 12 months after surgery, there were significant differences in protein abundance levels between the BEAR and ACLT groups, with an increase in Vitamin K-dependent protein C and decreases in Apolipoprotein A4 and CILP seen in the ACLT group. ", "Vitamin K-dependent protein C is an activator of several matrix metalloproteinases (MMPs), including MMP2, 9 and 13, and has shown to be significantly elevated in the synovium and synovial fluid of patients with rheumatoid arthritis (RA) and OA \\[[@pone.0212662.ref038]\\]. ", "While Apolipoprotein A4 has been detected in the synovial fluid of human knees with OA \\[[@pone.0212662.ref008], [@pone.0212662.ref024]\\], their role in OA pathogenesis is not well understood and warrants further studies. ", "Considering recent reports on the role of lipid metabolism in the OA development \\[[@pone.0212662.ref039], [@pone.0212662.ref040]\\], it is possible that apolipoprotein proteins affects knee OA progression by regulating the lipid metabolism and efflux. ", "CILP is a large secreted glycoprotein with major role in cartilage scaffolding and new cartilage formation \\[[@pone.0212662.ref041]\\]. ", "Increased CILP synthesis by chondrocytes has also been reported in early-stage OA \\[[@pone.0212662.ref042], [@pone.0212662.ref043]\\]. ", "which can be indicative of joint response to repair damaged cartilage \\[[@pone.0212662.ref044]\\]. ", "The consistently higher abundance of CILP in BEAR knees compared to intact (at 6 and 12 months) and ACLT (at 12 months) knees may suggest a more chondroprotective environment in repaired knees (Tables [2](#pone.0212662.t002){ref-type=\"table\"} & [3](#pone.0212662.t003){ref-type=\"table\"}).", "\n\nIn addition, at 12 months, the top 20 most abundant proteins in the ACLT knees had 5 additional pro-inflammatory proteins (Vitamin K-dependent protein C, Prothrombin, PPIA and Chitinase-3-like protein 1) and 3 fewer anti-inflammatory proteins (Clusterin, Alpha-2-HS glycoprotein and Annexin A1; [Table 1](#pone.0212662.t001){ref-type=\"table\"}). ", "The pro-inflammatory role of Vitamin K-dependent protein C, Prothrombin, PPIA and Chitinase-3-like protein 1, as well as anti-inflammatory role of Clusterin, Alpha-2-HS glycoprotein (Fetuin-A) and Annexin A1 in arthritic joints are well documented \\[[@pone.0212662.ref025]--[@pone.0212662.ref028], [@pone.0212662.ref045]--[@pone.0212662.ref061]\\]. ", "Elevated levels of these pro-inflammatory proteins have been reported in serum and synovial fluid of patients with RA and OA \\[[@pone.0212662.ref008], [@pone.0212662.ref024], [@pone.0212662.ref049], [@pone.0212662.ref062]--[@pone.0212662.ref065]\\]. ", "Prophenin-2 is a porcine specific Cathelicidin antimicrobial peptide, with similar pro-inflammatory properties as LL-37 (the only identified Cathelicidin antimicrobial peptide in humans), which is regulated by macrophages, polymorphonuclear leukocytes, and keratinocytes \\[[@pone.0212662.ref066]\\]. ", "A recent study has shown strong overexpression of Cathelicidin in joints of patients with RA and rats with pristane-induced arthritis \\[[@pone.0212662.ref067]\\]. ", "A recent proteomic analysis has also reported LL-37 among identified synovial fluid proteins in the patients with knee OA \\[[@pone.0212662.ref024]\\]. ", "The presence of pro-inflammatory proteins among the most abundant proteins in the ACLT group and the anti-inflammatory proteins among the most abundant proteins in the BEAR group at 12 months suggests there may be a greater pro-inflammatory environment in ACLT knees at a later stage of the disease. ", "This is further supported by the observed significantly lower abundance of the Vitamin K-dependent protein C in BEAR knees compared to ACLT and intact groups as well as higher abundance of Annexin A1 in the BEAR knees compared to intact group.", "\n\nIn comparing the proteomes at 6 and 12 months after surgery ([Table 4](#pone.0212662.t004){ref-type=\"table\"}), there were significant increases in IGFBP2 and IGLC1 levels, as well as significant decreases in CILP and Hemopexin levels in the synovial fluid of ACLT knees from 6 to 12 months. ", "IGFP2 is synthesized by synoviocytes and chondrocytes and regulates Insulin-like growth factor (IGF) \\[[@pone.0212662.ref068], [@pone.0212662.ref069]\\], a key promoter of cartilage growth \\[[@pone.0212662.ref070], [@pone.0212662.ref071]\\]. ", "Increased levels of IGFBPs have been reported in the synovial fluid of arthritic joints \\[[@pone.0212662.ref072], [@pone.0212662.ref073]\\], and serum concentration has been correlated with RA disease severity \\[[@pone.0212662.ref074]--[@pone.0212662.ref076]\\]. ", "Hemopexin has a negative modulatory function on T-cell differentiation \\[[@pone.0212662.ref077], [@pone.0212662.ref078]\\], and exogenous administration of Hemopexin has recently been shown to result in increased glycosaminoglycan deposition \\[[@pone.0212662.ref079]\\]. ", "In contrast to increased synovial concentrations of pro-inflammatory proteins (IGFBP2 and IGLC1) in the ACLT knees, there were significant decreases in the synovial concentrations of two pro-inflammatory proteins (PPIA and complement C7) in the BEAR knees from 6 to 12 months.", "\n\nBiological pathways enriched by the changes in synovial fluid protein content were related to blood coagulation, proteolysis, inflammation and cell adhesion ([Table 5](#pone.0212662.t005){ref-type=\"table\"}). ", "Among those, proteolysis (ECM remodeling) and inflammation (complement pathway) pathways have consistently shown to play an active role in OA pathophysiology \\[[@pone.0212662.ref008], [@pone.0212662.ref080]--[@pone.0212662.ref083]\\]. ", "The role of remaining 5 enriched pathways in the development of OA is less studied. ", "Recent comparative analysis of synovial fluid in patients with healthy knees with those with knee OA (both early and late stages) have shown significant enrichment of blood coagulation pathway by differentially abundant proteins between the groups \\[[@pone.0212662.ref008]\\]. ", "Our group has also shown enrichment of cell adhesion (platelet-endothelium-leucocyte interactions) and proteolysis (connective tissue degradation) pathways by differentially expressed genes in the synovium and cartilage within 2 weeks after ACL injury in a minipig model of posttraumatic OA \\[[@pone.0212662.ref080], [@pone.0212662.ref081]\\]. ", "These findings, in addition to abovementioned evidence supporting the involvement of the proteins / genes, which enriched these pathways, in OA pathophysiology underscore their importance as potential targets to mediate the biologic joint response to injury in an effort to lower the risk of posttraumatic OA.", "\n\nLimitations {#sec015}\n-----------\n\nUnbiased LC MS/MS proteomics techniques are primarily limited to detection of more highly abundant proteins within a complex biological matrix. ", "Antibody-based depletion methods could have been used to improved our ability to quantify lower abundance level proteins by removing the top abundance level proteins. ", "However, they can also result in removal of lower abundance level proteins and ultimately pose challenges in accurate quantification of protein contents \\[[@pone.0212662.ref084]\\]. ", "In our discovery workflow, we wanted to capture a \"global\" representation of proteins in the synovial fluid, as such chose to avoid antibody-based depletion. ", "To better compensate and delve deeper into the synovial fluid proteome, additional in-depth and/or targeted approaches are required to further study less abundant proteins that are likely present but not detectable or quantifiable using this technique (i.e. Lubricin, matrix metalloproteinases and cytokines). ", "We have previously used similar MS-based proteomics approach to study the synovial fluid proteome of healthy porcine knees \\[[@pone.0212662.ref015]\\]. ", "The substantial overlap between those findings and identified proteins here is reassuring and supports our MS-based protein discovery approach. ", "However, further efforts are essential for orthogonal validation of the identified proteins in individual samples compared to the pooled samples in independent cohorts. ", "Another limitation is the cross-sectional nature of the study. ", "While the cross-sectional time points have enabled us to macroscopically assess the cartilage health, longitudinal analyses are required to better characterize the changes in synovial fluid proteome in response to joint degeneration over time. ", "Finally, the current results only support associations between cartilage damage and certain synovial fluid proteins in early posttraumatic OA. ", "Further functional studies are required to investigate the mechanistic nature of these associations and to determine the potential application of suggested targets as biomarkers for OA progression or as disease modifiers for development of novel therapeutics.", "\n\nConclusions {#sec016}\n===========\n\nKnees treated with a surgical procedure that results in posttraumatic OA (ACLT group) had higher concentrations of pro-inflammatory proteins and lower concentrations of anti-inflammatory proteins than knees treated with a surgical procedure that does not result in post-traumatic OA (bridge-enhanced ACL repair). ", "In addition, the group developing posttraumatic OA had a lower and declining synovial concentrations of CILP, in contrast to a consistently high abundance of CILP in repaired knees. ", "These differences suggest that the knees treated with bridge-enhanced ACL repair may be maintaining an environment that is more protective of the extracellular matrix, a function which is not seen in the ACLT knees.", "\n\nSupporting information {#sec017}\n======================\n\n###### iTRAQ labeling of the synovial fluid samples.", "\n\n(XLSX)\n\n###### \n\nClick here for additional data file.", "\n\n###### Detected synovial fluid proteins.", "\n\n(XLSX)\n\n###### \n\nClick here for additional data file.", "\n\n###### Significant differentially abundant proteins between groups.", "\n\n(XLSX)\n\n###### \n\nClick here for additional data file.", "\n\n###### ARRIVE guidelines checklist.", "\n\n(PDF)\n\n###### \n\nClick here for additional data file.", "\n\nAuthors would like to thank: Patrick Vavken (Boston Children\\'s Hospital) for helping with surgical procedures, and Edward Voss and Jean Kanyo (MS & Proteomics Resource within the Keck Biotechnology Resource Laboratory at Yale University) for proteomics sample preparation and collecting the mass spectrometric proteomics data, respectively.", "\n\n[^1]: **Competing Interests:**The authors have no competing interests directly related to this study. ", "However, it should be noted that Dr. Murray holds several patents related to the BEAR surgical procedure, and that Drs. ", "Murray and Fleming recently founded a company (Miach Orthopaedics Inc) to translate the BEAR surgical procedure to clinical use. ", "This does not alter our adherence to PLOS ONE policies on sharing data and materials. ", "Patents: - Biologic replacement for fibrin clot (EP US WO Application US20040059416A1 & US WO Application US20020123805A1) - Device for mixing and delivering fluids for tissue repair (CA EP JP US WO Grant US8308681B2) - Methods and procedures for ligament repair (CA EP JP US WO Application WO2007087353A2) - Activation and delivery devices for therapeutic compositions(US Application US20120116300A1) - Methods and collagen products for tissue repair (US EP JP CA WO Application WO2008060361A2) - Biologic replacement for fibrin clot for intra-articular use (WO Application WO2000078370A1 & EP CA Application CA2377595A1) - Indirect method of articular tissue repair (CA WO Application CA3024196A1)\n" ]

{ "pile_set_name": "PubMed Central" }

[ 0.010471204188481676, 0.012711864406779662, 0, 0.006968641114982578, 0, 0, 0.0072992700729927005, 0.012875536480686695, 0.006060606060606061, 0, 0.005376344086021506, 0.0034965034965034965, 0, 0.010101010101010102, 0, 0, 0, 0, 0.009950248756218905, 0, 0, 0.009615384615384616, 0.01282051282051282, 0, 0, 0.011834319526627219, 0, 0, 0.026455026455026454, 0.016597510373443983, 0, 0.009433962264150943, 0, 0.007407407407407408, 0, 0.004464285714285714, 0.009523809523809525, 0, 0.009900990099009901, 0, 0.009708737864077669, 0.010526315789473684, 0.006042296072507553, 0.007751937984496124, 0.008620689655172414, 0.012658227848101266, 0.0072992700729927005, 0.007142857142857143, 0, 0, 0.008403361344537815, 0.015957446808510637, 0.02857142857142857, 0.004761904761904762, 0.01020408163265306, 0.009950248756218905, 0.011764705882352941, 0.00392156862745098, 0.006369426751592357, 0, 0, 0.009433962264150943, 0.008849557522123894, 0.007936507936507936, 0.015384615384615385, 0.00796812749003984, 0.007751937984496124, 0, 0.006134969325153374, 0.010752688172043012, 0.01824817518248175, 0, 0.015625, 0, 0.008443908323281062, 0, 0.00558659217877095, 0, 0.008849557522123894, 0, 0, 0, 0.004024342363564979, 0.013157894736842105, 0.011695906432748537, 0.01238390092879257, 0, 0.004021164021164021, 0.009966777408637873, 0.011627906976744186, 0.01238390092879257, 0, 0.003350593968930856, 0, 0.00980392156862745, 0.009900990099009901, 0, 0, 0.0019877422560874605, 0, 0, 0.014380530973451327, 0, 0.0041841004184100415, 0, 0, 0.006042296072507553, 0.015904572564612324, 0.01556420233463035, 0, 0.015873015873015872, 0.015873015873015872, 0.014285714285714285, 0.02643171806167401, 0.004694835680751174, 0.018018018018018018, 0, 0.010238907849829351, 0.010416666666666666, 0.013513513513513514, 0.012461059190031152, 0.010869565217391304, 0.012244897959183673, 0.01098901098901099, 0.013513513513513514, 0.007936507936507936, 0.014814814814814815, 0.014925373134328358, 0.01020408163265306, 0.010416666666666666, 0.01440922190201729, 0.020114942528735632, 0.020080321285140562, 0.006688963210702341, 0.012345679012345678, 0.006666666666666667, 0.01, 0.01646090534979424, 0.017064846416382253, 0.025, 0.019157088122605363, 0.01858736059479554, 0.010869565217391304, 0, 0.017094017094017096, 0, 0.0036231884057971015, 0.0058309037900874635, 0, 0.0055248618784530384, 0, 0.0055248618784530384, 0, 0.0032258064516129032, 0.013245033112582781, 0.006944444444444444, 0, 0, 0, 0, 0, 0.005714285714285714, 0.005494505494505495, 0.004651162790697674, 0, 0, 0, 0, 0, 0, 0, 0.018518518518518517, 0.02040816326530612, 0, 0.016666666666666666, 0.023255813953488372, 0, 0.008571428571428572 ]

[ "Q:\n\nCloudgraph service throws Number format exception under high load conditions\n\nCloudgraph service throws Number format exception under high load conditions.", "\nWe randomly see the following exception under high load.", "\n Caused by: java.lang.", "NumberFormatException: For input string: \"\"\nat java.lang.", "NumberFormatException.forInputString(NumberFormatException.java:48)\nat java.lang.", "Long.parseLong(Long.java:431)\nat java.lang.", "Long.parseLong(Long.java:468)\nat java.text.", "DigitList.getLong(DigitList.java:177)\nat java.text.", "DecimalFormat.parse(DecimalFormat.java:1297)\nat java.text.", "SimpleDateFormat.subParse(SimpleDateFormat.java:1589)\nat java.text.", "SimpleDateFormat.parse(SimpleDateFormat.java:1311)\nat java.text.", "DateFormat.parse(DateFormat.java:335)\nat org.plasma.sdo.helper.", "DataConverter.fromString(DataConverter.java:1768)\n\nA:\n\nthis was fixed in plasma 1.2.0 and is up on Maven Central. ", "See Plasma Release 1.2.0 for details. ", "I assume you are using cloudgraph.hbase or cloudgraph.rdb. ", "If so you can just upgrade to CloudGraph 0.6.0 beta which depends on plasma 1.2.0. ", "Note that some mapreduce classes under cloudgraph.hbase were promoted (moved up) in case you are using these. ", "So then your pom.xml looks something like:\n<dependency>\n <groupId>org.cloudgraph</groupId>\n <artifactId>cloudgraph-hbase</artifactId>\n <version>0.6.0</version>\n</dependency>\n\n--regards; \n\n" ]

{ "pile_set_name": "StackExchange" }

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[ "58?", "\n818.34\n1 * -338287\n-338287\nWork out -4.4045 * 2.", "\n-8.809\n0.0501*0.0928\n0.00464928\nProduct of 60088 and -0.26.", "\n-15622.88\nMultiply -11.05327 and 0.5.", "\n-5.526635\nWhat is -0.17 times -33.17?", "\n5.6389\nWork out 162 * 0.3638.", "\n58.9356\nProduct of -6.859 and -14.", "\n96.026\nWhat is the product of 9.13 and -0.211?", "\n-1.92643\nCalculate -3*25.8174.", "\n-77.4522\n-180.6 times 0.24\n-43.344\n0.1625 times -0.01\n-0.001625\nWhat is -36.97 times 38?", "\n-1404.86\nProduct of -4 and -80900.", "\n323600\nWork out 3 * -13306.", "\n-39918\n1070 times 20.5\n21935\nWork out 0.16 * -3872.", "\n-619.52\n-20 times -13036\n260720\n-30.3 times -0.1959\n5.93577\nWork out 1.18 * -7006.", "\n-8267.08\nProduct of -5530 and 3.6.", "\n-19908\n30499 * -0.2\n-6099.8\n-0.786 * -1039\n816.654\nCalculate 274*5.3.", "\n1452.2\nWork out 45.797 * -3.8.", "\n-174.0286\nCalculate 6*-0.06288.", "\n-0.37728\n-2.31 * -0.03856\n0.0890736\nProduct of -1096 and 6.66.", "\n-7299.36\nMultiply 0.1611 and -4.", "\n-0.6444\n-2479 times -27\n66933\n-0.087718 * 6\n-0.526308\nMultiply -1.9 and 0.210964.", "\n-0.4008316\nMultiply 0.4 and -9153.", "\n-3661.2\nCalculate 2.025*-0.01.", "\n-0.02025\n-5.2 * -1116\n5803.2\nMultiply 0.3 and -8152.", "\n-2445.6\nCalculate -0.4*1.11575.", "\n-0.4463\n10896*367\n3998832\nWhat is 11.31 times -29?", "\n-327.99\n1.6482 * -68\n-112.0776\n-16.5 * -6586\n108669\nWork out 7492 * 1.", "\n7492\nWork out 4883.7 * -0.9.", "\n-4395.33\nCalculate -40.2*-120.", "\n4824\n-0.257 times -149\n38.293\n19516 * 9\n175644\nWork out 1082 * -312.", "\n-337584\n59*-0.05234\n-3.08806\n1459 * -29\n-42311\nWork out 658 * 48.82.", "\n32123.56\nWhat is the product of -8741.8 and -0.3?", "\n2622.54\nProduct of 15.1 and 204.2.", "\n3083.42\n-175363*0.4\n-70145.2\n40 times -539\n-21560\nWork out 2028 * -0.24.", "\n-486.72\n-1 times 53740\n-53740\nMultiply 5 and -46368.", "\n-231840\nWhat is the product of -150.86 and 26?", "\n-3922.36\nCalculate 2292.1*-1.33.", "\n-3048.493\n22194 times -0.3\n-6658.2\n-15662.96 times -0.1\n1566.296\nMultiply -270948 and 2.", "\n-541896\nWork out -4.5 * -66012.", "\n297054\nWhat is the product of -0.1 and -1202.47?", "\n120.247\nWork out -44898 * -3.", "\n134694\nWhat is -75.23277 times -0.2?", "\n15.046554\nWhat is the product of 732.7 and 19?", "\n13921.3\nCalculate 1930*-42.", "\n-81060\nWhat is -0.23682 times -225?", "\n53.2845\n3*-47530\n-142590\n0.2 times -9.0158\n-1.80316\nWork out 0.2 * 919.82.", "\n183.964\n-5.9203*0.3\n-1.77609\nMultiply 245715 and 0.", "\n0\n-0.2*-16713.89\n3342.778\nWhat is -1873 times -0.115?", "\n215.395\nWork out -9137 * 0.14.", "\n-1279.18\nMultiply -8.3 and 68.1.", "\n-565.23\n-34*693\n-23562\nCalculate 0.5*-8680.", "\n-4340\nWork out 273 * 0.0338.", "\n9.2274\nWhat is the product of 17644 and 1.2?", "\n21172.8\nProduct of -25401 and 0.02.", "\n-508.02\nCalculate 0.04*8871.", "\n354.84\nWhat is the product of 2970 and -4.7?", "\n-13959\n0 * -1000670\n0\nMultiply -0.01 and 242359.", "\n-2423.59\nMultiply 0.32 and -91.", "\n-29.12\n-2640812*-1\n2640812\n0.05354*-22.4\n-1.199296\n-1527*-0.111\n169.497\n1.9394 times 0.3\n0.58182\n374.08*-0.3\n-112.224\nCalculate 72455*-5.", "\n-362275\nWhat is the product of 0.1 and 2677?", "\n267.7\n2 * 8699.66\n17399.32\nCalculate 1263*-0.6.", "\n-757.8\nMultiply 0.1 and -85671.", "\n-8567.1\n0.2 * 8523\n1704.6\nCalculate 144367.2*-0.3.", "\n-43310.16\n0.5149 times 1.05\n0.540645\nWork out -0.678 * -49.", "\n33.222\n-6.3794 * 0.4\n-2.55176\nCalculate -4*0.092.", "\n-0.368\nProduct of -4.6 and 12325.", "\n-56695\nMultiply 0.066 and -262.", "\n-17.292\nWork out 4 * 664113.", "\n2656452\nWork out 0.2424 * 15.", "\n3.636\nProduct of 59129 and 0.4.", "\n23651.6\nCalculate -44*0.04557.", "\n-2.00508\nWork out 7 * 336.01.", "\n2352.07\nMultiply 23 and -2941.", "\n-67643\n0.421 * 2842\n1196.482\n493531 times 0.3\n148059.3\nWhat is 6.17 times 10?", "\n61.7\n-10.8*449.2\n-4851.36\nWork out 0.03066 * -6.", "\n-0.18396\nWhat is 514 times 0.1124?", "\n57.7736\n120.2 times -0.053\n-6.3706\nWhat is -356 times -215?", "\n76540\nProduct of -0.126 and 22.3.", "\n-2.8098\n907690 * -0.1\n-90769\nWhat is 833 times -334?", "\n-278222\nMultiply 335219 and 4.", "\n1340876\n-56.082 * -4\n224.328\nWhat is -1699925 times 0.2?", "\n-339985\nMultiply -3 and -14484.9.", "\n43454.7\n-0.006 * 0.0408\n-0.0002448\n-8 * 688\n-5504\nWhat is the product of 3766 and -20.7?", "\n-77956.2\nProduct of -84618.1 and -4.", "\n338472.4\n-230*82\n-18860\nWhat is the product of -4964972 and -0.4?", "\n1985988.8\nWhat is the product of -0.07216 and -15?", "\n1.0824\nCalculate -10.6166*-0.1.", "\n1.06166\nWhat is 1.5 times 235.88?", "\n353.82\nWhat is the product of 71 and -172.9?", "\n-12275.9\nCalculate 4964*-0.5.", "\n-2482\n1257 * -4\n-5028\nMultiply 65.77 and 50.", "\n3288.5\nWork out -15045 * 0.4.", "\n-6018\n238*-363\n-86394\nMultiply -0.251 and 1.6.", "\n-0.4016\nProduct of -0.1 and -0.4655.", "\n0.04655\nWhat is the product of 68589 and 0.2?", "\n13717.8\nCalculate 0.09499*-0.4.", "\n-0.037996\nCalculate 0.8*-38760.", "\n-31008\nWhat is -3 times 10254?", "\n-30762\nWork out 978 * -24.", "\n-23472\nWhat is the product of -31 and 20.7?", "\n-641.7\nProduct of -3030 and 0.13.", "\n-393.9\nWhat is the product of -0.22305 and 0?", "\n0\nMultiply 0.3 and 925.34.", "\n277.602\nCalculate -0.4*-15424.", "\n6169.6\nWhat is -7964 times -10?", "\n79640\nCalculate 4.731*-25.", "\n-118.275\nMultiply 2778 and 648.", "\n1800144\nMultiply 0.2 and -0.641467.", "\n-0.1282934\nMultiply -6159504 and -4.", "\n24638016\nProduct of 0.115 and 4348.", "\n500.02\nWork out -0.19 * 5.34.", "\n-1.0146\nProduct of -1.3 and -6876.", "\n8938.8\n-193 times -27.9\n5384.7\nCalculate 1.2815*5.", "\n6.4075\nWhat is the product of -4 and 1533.6?", "\n-6134.4\nWhat is -0.0761 times 3?", "\n-0.2283\nWork out 892 * -0.5.", "\n-446\nProduct of 0.14 and -53.744.", "\n-7.52416\nWhat is the product of 41.30085 and -3?", "\n-123.90255\n-541 times 20.7\n-11198.7\n0.0262 times -100\n-2.62\nCalculate -32*26516.", "\n-848512\nWhat is 9170 times -0.7?", "\n-6419\n3 * 100.1173\n300.3519\n-30.7 * -6.6\n202.62\nWhat is 0.61412 times 0.05?", "\n0.030706\n-0.14 times 5659\n-792.26\nWork out -85.7 * -0.2.", "\n17.14\n-0.4*12348\n-4939.2\nMultiply -0.8 and -1081.", "\n864.8\nCalculate -4*1.6176.", "\n-6.4704\n-4.305 times -1.3\n5.5965\nWork out -2.9 * -7326.", "\n21245.4\n0.0165 times -333\n-5.4945\n2 * -1167684\n-2335368\nProduct of -0.7 and -0.05624.", "\n0.039368\nProduct of -0.02 and -48.8.", "\n0.976\n-0.4 times 116713\n-46685.2\nMultiply -8268 and 4.", "\n-33072\nWhat is -3.456245 times -0.3?", "\n1.0368735\nWhat is -5 times -65477?", "\n327385\nWhat is the product of 213 and 294?", "\n62622\nWhat is the product of -0.3 and 1.3685?", "\n-0.41055\n-8.057 times -0.3\n2.4171\nProduct of -3 and -2140.92.", "\n6422.76\nCalculate -167.6594*-0.3.", "\n50.29782\nWhat is -3.1 times -56110?", "\n173941\nWhat is the product of -1.43 and -8562?", "\n12243.66\nMultiply -0.88 and -850.", "\n748\n-4.5284 times 158\n-715.4872\nCalculate 0.09625*-0.2.", "\n-0.01925\n-241 times -4.549\n1096.309\nMultiply -8 and 110.72.", "\n-885.76\nWhat is 2737 times 1.3?", "\n3558.1\nCalculate -2418*127.", "\n-307086\nWhat is -179.51 times -0.1?", "\n17.951\nWhat is the product of -1.4 and -0.07299?", "\n0.102186\nWhat is the product of -187 and -18.3?", "\n3422.1\n13919460*0.5\n6959730\n6.9394 * -6\n-41.6364\nWhat is -1.00013 times -0.16?", "\n0.1600208\n-105541 times 0.04\n-4221.64\n-0.7196 * -0.18\n0.129528\n0.132 * 1.519\n0.200508\n0.0525 times 4399\n230.9475\n-11410 times -1\n11410\n-38030.5*5\n-190152.5\nWhat is the product of -139535 and 49?", "\n-6837215\n-84 times 85.3\n-7165.2\n26187 times -1\n-26187\nWork out -24639.3 * -0.2.", "\n4927.86\n26*0.0239\n0.6214\n4128*-0.0732\n-302.1696\nProduct of -28494 and 119.", "\n-3390786\nWhat is -2.6 times -13058?", "\n33950.8\n0.139171 * 9\n1.252539\n-1 times 316835\n-316835\n-10414 * -6\n62484\nProduct of 8070 and 0.3.", "\n2421\nProduct of -250.819 and -5.", "\n1254.095\nProduct of 0.11 and 2.161.", "\n0.23771\nCalculate -23.5*-357.", "\n8389.5\n1868 times 1.4\n2615.2\n-61961 times 0.1\n-6196.1\n35*-7\n-245\nWork out -0.0342 * -0.4.", "\n0.01368\nMultiply 3365 and 85.", "\n286025\n2440.08*1\n2440.08\nWork out 0.03 * -72.9.", "\n-2.187\nCalculate -289*26.", "\n-7514\nWork out 0.1636 * -8.4.", "\n-1.37424\nWhat is the product of -0.096 and 36735?", "\n-3526.56\n122521 times -32\n-3920672\nMultiply -1320 and 36.", "\n-47520\nWork out 4.4556 * 0.03.", "\n0.133668\n-1882341*4\n-7529364\nCalculate 34*43321.", "\n1472914\nWhat is -3.7 times -2.477?", "\n9.1649\nMultiply -2.31 and -5.776.", "\n13.34256\nProduct of -19111 and -5.", "\n95555\n-3.8 times -0.2478\n0.94164\nWork out -0.15558 * -0.08.", "\n0.0124464\nWhat is -36.33199 times -0.3?", "\n10.899597\nWhat is 0.2 times 116.2?", "\n23.24\n-2498 times -4.6\n11490.8\nCalculate 10*-0.738.", "\n-7.38\n0 * -38613\n0\nMultiply -0.4 and -297.25.", "\n118.9\nWhat is the product of -0.593482 and 0.4?", "\n-0.2373928\n-0.14759*-3\n0.44277\n3.65 times -166\n-605.9\n11637 times -1\n-11637\nWhat is 85 times 0.175?", "\n14.875\n9.68 * 513\n4965.84\nWhat is the product of -57 and 0.76?", "\n-43.32\n33479 times 5\n167395\n-0.052*-4.43\n0.23036\n1*17.5493\n17.5493\nWhat is the product of 0.118 and -182?", "\n-21.476\nWork out -1.0353 * -1.", "\n1.0353\n-2*104231\n-208462\nWhat is the product of 23635 and -0.3?" ]

{ "pile_set_name": "DM Mathematics" }

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[ "---\nabstract: |\n The photon sphere concept in Schwarzschild space-time is generalized to a definition of a photon surface in an arbitrary space-time. ", "A photon sphere is then defined as an $SO(3)\\times \n {\\mathbb{R}}$-invariant photon surface in a static spherically symmetric space-time. ", "It is proved, subject to an energy condition, that a black hole in any such space-time must be surrounded by a photon sphere. ", "Conversely, subject to an energy condition, any photon sphere must surround a black hole, a naked singularity or more than a certain amount of matter. ", "A second order evolution equation is obtained for the area of an $SO(3)$-invariant photon surface in a general non-static spherically symmetric space-time. ", "Many examples are provided.", "\n---\n\n[**THE GEOMETRY OF PHOTON SURFACES**]{}\\\n[CLARISSA-MARIE CLAUDEL[^1]]{}\\\n[*Mathematical Institute, University of Ume[å]{}, S-901 87 Ume[å]{}, Sweden*]{}\\\n[K. S. VIRBHADRA[^2] and G. F. R. ELLIS[^3]\\\n[*Department of Applied Mathematics, University of Cape Town,\\\nRondebosch 7701, South Africa.*]{}]{}", "\n\nIntroduction\n============\n\nThe exterior region of the maximally extended Schwarzschild space-time is described by the metric $${\\bf\n g} = -\\left(1-\\frac{2m}{r}\\right) dt^2 + \\left(1-\\frac{2m}{r}\\right)^{-1}\ndr^2\n + r^2 \\left(d\\theta^2 + \\sin^2\\theta d\\phi ^2 \\right), \\quad\n\\quad r > 2m \\ .", "\n \\label{sch}$$ For any null geodesic in this exterior region the null geodesic equations give $$\\frac{d^2r}{d\\lambda^2} = \\left(r-3m\\right)\n \\left\\{\n \\left(\\frac{d \\theta}{d \\lambda}\\right)^2\n + \\sin^2\\theta \\left(\\frac{d \\phi}{d \\lambda}\\right)^2\n \\right\\}$$ where $\\lambda$ is an affine parameter along the geodesic. ", "The right side here is evidently positive for $r > 3m$ and negative for $r : 2m <r < 3m$. It follows that any future endless null geodesic in the maximally extended Schwarzschild space-time starting at some point with $r > 3m$ and initially directed outwards, in the sense that $dr/d\\lambda$ is initially positive, will continue outwards and escape to infinity. ", "Any future endless null geodesic in the maximally extended Schwarzschild space-time starting at some point with $r: 2m <r <3m$ and initially directed inwards, in the sense that $dr/d\\lambda$ is initially negative, will continue inwards and fall into the black hole. ", "The hypersurface $\\{r = 3m\\}$, known as the Schwarzschild photon sphere, thus distinguishes the borderline between these two types of behaviour; any null geodesic starting at some point of the photon sphere and initially tangent to the photon sphere will remain in the photon sphere. (", "See Darwin [@Dar1; @Dar2] for a detailed analysis of the behaviour of null and timelike geodesics in Schwarzschild space-time.)", "\n\nThe Schwarzschild photon sphere also has physical significance for massive bodies. ", "For any timelike geodesic in the exterior region the geodesic equations give $$\\frac{d^2r}{ds^2} = -\\frac{m}{r^2} + \\left(r-3m\\right)\n \\left\\{\n \\left(\\frac{d \\theta}{ds}\\right)^2\n + \\sin^2\\theta \\left(\\frac{d \\phi}{ds}\\right)^2\n \\right\\}\n\\label{timegeodesic}$$ where $s$ is arc length along the geodesic. ", "At any point with $r>3m$ one may arrange for the two terms on the right of (\\[timegeodesic\\]) to cancel and so obtain a timelike geodesic at constant $r$. For $r:\n2m<r<3m$ the right hand side of (\\[timegeodesic\\]) is evidently negative. ", "Thus any future endless timelike geodesic in the maximally extended Schwarzschild space-time starting at some point between the event horizon at $r = 2m$ and the photon sphere at $r = 3m$ and initially directed inwards, in the sense that $dr/ds$ is initially negative, will continue inwards and fall into the black hole. ", "Any observer who traverses a Schwarzschild photon sphere must therefore engage some form of propulsion or else be drawn in to the black hole to meet an inevitable fate.", "\n\nA photon sphere has been defined by Virbhadra & Ellis [@VE99a] as a timelike hypersurface of the form $\\{ r\n= r_0 \\}$ where $r_0$ is the closest distance of approach for which the Einstein bending angle of a light ray is unboundedly large. ", "These authors subsequently [@VE99b] considered the Einstein deflection angle for a general static spherically symmetric metric and obtained an equation for a photon sphere. ", "The existence of a photon sphere in a space-time has important implications for gravitational lensing. ", "In any space-time containing a photon sphere, gravitational lensing will give rise to relativistic images [@VE99a].", "\n\nThe Schwarzschild photon sphere may be usefully be compared with the concept of a closed trapped surface. ", "Any null geodesic originating from any point on a closed trapped surface in Schwarzschild space-time is drawn into the singularity at $r=0$. By contrast, any null geodesic originating from any point on the photon sphere will be drawn into the singularity if and only if it is initially directed inwards.", "\n\nThe main objectives of the present paper are to give a geometric definition of a photon surface in a general space-time and of a photon sphere in a general static spherically symmetric space-time.", "\n\nAn evolution equation is obtained for the cross-sectional area of a photon surface in a dynamic spherically symmetric space-time. ", "It is shown, subject to suitable energy conditions, that in any static spherically symmetric space-time a black hole must be surrounded by a photon sphere, and a photon sphere must surround either a black hole, a naked singularity or more than a certain amount of matter. ", "Many examples are given of photon spheres in static spherically symmetric space-times. ", "Photon surface evolution is considered for the dynamic space-time example of Vaidya null dust collapse to a naked singularity.", "\n\nPhoton surfaces {#photonsurfacesection}\n===============\n\nThe hypersurface $S:=\\{ r=3m\\}$ in Schwarzschild space-time has two main properties, first that any null geodesic initially tangent $S$ will remain tangent to $S$, and second that $S$ does not evolve with time. ", "The following general definition of a photon surface is based on only the first of these properties. ", "A more restrictive class of photon surfaces may be defined when the space-time admits a group of symmetries (see Definition \\[photonspheredef\\]).", "\n\n\\[photonsurfacedef\\] [A photon surface of $(M,{\\bf g})$ is an immersed, nowhere-spacelike hypersurface $S$ of $(M, {\\bf g})$ such that, for every point $p \\in S$ and every null vector ${\\bf k} \\in T_pS$, there exists a null geodesic $\\gamma : (-\\epsilon, \\epsilon ) \\rightarrow M$ of $(M,{\\bf g})$ such that $\\dot{\\gamma}(0) = $[**k**]{}$, |\\gamma| \\subset S$.]{}\n\nAny null hypersurface is trivially a photon surface. ", "Photon surfaces are conformally invariant structures. ", "If $S$ is a photon surface of $(M,{\\bf g})$ then $S$ is a photon surface of $(M,\\Omega^2 {\\bf g})$ for any smooth function $\\Omega : M\n\\rightarrow (0,\\infty )$.", "\n\nNote that Definition \\[photonsurfacedef\\] is entirely local. ", "In particular, a photon surface $S$ need contain no endless null geodesics of $(M,{\\bf g})$. Moreover, a photon surface need only be immersed, rather than embedded in $M$, and so may have self-intersections. ", "If $(M,{\\bf g})$ is of dimension $n+1$ ($n \\geq 2$) then, through each point $p$ of a photon surface $S$ in $(M,{\\bf g})$, there is an $(n-2)$-parameter family of null geodesics of $(M,{\\bf g})$ that lie entirely in $S$.\n\nThe paper will be principally concerned with photon surfaces in space-times of $3+1$ dimensions. ", "The exceptions are Examples \\[Min3\\] and \\[deSitter\\] which give photon surfaces in space-times of dimension $2+1$ and $4+1$ respectively.", "\n\n\\[Min3\\]\n\nIn Minkowski 3-space ${\\mathbb{M}}^3$, consider the single-sheeted hyperboloid $S$ given by $$-t^2 + x^2 + y^2 = a^2 \\label{eq2}$$ for some constant $a > 0$. This surface is doubly ruled, the rulings being given by $$\\gamma^{\\pm}_{\\theta} \\left(t \\right) := a \\left(0,\\cos \\theta,\\sin\n\\theta \\right)\n +at \\left(1,\\mp \\sin \\theta, {\\pm}\\cos \\theta \\right)\n\\label{eq3}$$ ($-\\infty < t < \\infty, 0 \\leq \\theta < 2 \\pi$), where $\\theta$ identifies the intersection points with $ \\{t =0\\} $ and $t$ is the parameter along the ruling lines. ", "The tangents $\\dot{\\gamma}^{\\pm}_{\\theta}\\left(t \\right)$ to the ruling lines are null with respect to the ${\\mathbb{M}}^3$ metric. ", "Clearly they are geodesics in ${\\mathbb{M}}^3$. At each point of $S$ there can be just two null directions tangent to $S$. These must therefore be the directions of the two ruling lines through that point. ", "Hence $S$ is a photon surface in the sense of Definition \\[photonsurfacedef\\] (see Fig.", " \\[claire1\\]).", "\n\n![", "A photon surface in Minkowski $3$-space. ", "The two families of ruling lines are null geodesics with respect to both the Minkowski $3$-metric and the induced $2$-metric. ", "The lines may be regarded as the space-time paths of pulsed laser beams.[]{data-label=\"claire1\"}](fig1.eps){width=\"3.0in\"}\n\nNote that for any circle of the form $$C = \\left\\{ t_0, x_0+r \\cos \\theta, y_0+r \\sin \\theta \\right\\},\n\\quad \\quad r > 0, \\label{eq4}$$ and any future-directed timelike vector field ${\\bf X}$ along $C$ that respects the symmetry of $C$, in the sense of $${\\bf X} = \\left(X^t, X^r \\cos \\theta, X^r \\sin \\theta \\right),\n\\label{eq5}$$ for constant $X^t>0$, $X^r$ such that $(X^t)^2 >(X^r)^2$, there is a unique single-sheeted hyperboloid $S$ through $C$ such that ${\\bf X}$ is tangent to $S$ along $C$.", "\n\nIn the case $a=0$, equation (\\[eq2\\]) gives the null cone through the origin. ", "The complement of $p$ in this null cone is a null photon surface of ${\\mathbb{M}}^3$.\n\n\\[Min4\\] [One may generalize Example 1 to Minkowski 4-space ${\\mathbb{M}}^4$ as follows. ", "Let $S$ be a timelike hypersurface in ${\\mathbb{M}}^4$ of the form $$-t^2+x^2+y^2+z^2 = a^2 \\label{ellhyp4}$$ for some constant $a>0$. The two-parameter family of lines $$\\gamma^\\pm_{\\theta,\\phi}\\left(t \\right) =\n a \\left( 0,\\cos \\theta , \\sin \\theta \\sin \\phi , \\sin \\theta \\cos \\phi \\right)\n +at \\left( 1,\\mp \\sin \\theta , {\\pm}\\cos \\theta \\sin \\phi ,{\\pm}\\cos \\theta \\cos \\phi \\right)\n\\label{eq7}$$ foliate $S$ and are null geodesics with respect to the ${\\mathbb{M}}^4$ metric. ", "For each $p \\in S$, the tangents at $p$ to those $\\gamma^\\pm_{\\theta,\\phi}\\left(t \\right)$ that pass through $p$ can be shown to generate the null cone of $T_pS$. Hence $S$ is a photon surface in the sense of Definition \\[photonsurfacedef\\]. ", "In terms of the double null coordinates $$\\begin{aligned}\n u&:=t+r \\\\ v&:= t-r\\end{aligned}$$ for $r:= (x^2+y^2+z^2)^{1/2}$, equation (\\[ellhyp4\\]) assumes the simple form $$uv = -a^2 \\ .$$ In the future direction $S$ tends asymptotically to the null hypersurface $\\{ v=0\\}$, whilst in the past direction $S$ tends asymptotically to the null hypersurface $\\{ u=0\\}$. ]{}\n\n\\[deSitter\\] [De Sitter space-time may be regarded [@HE73] as a single-sheeted hyperboloid in Minkowski $5$-space ${\\mathbb{M}}^5$. By analogy with Examples 1 and 2, de Sitter space-time is thus realized as a photon surface in ${\\mathbb{M}}^5$. ]{}\n\n\\[RobWal\\] [Since all Robertson-Walker models are conformally flat and therefore locally conformally transformable to Minkowski space, the photon surfaces of any such model may thus be obtained, at least locally, by conformal transformations of Minkowski space. ]{}", "\n\n\\[maintheorem\\] Let $S$ be a timelike hypersurface of $\\left(M,{\\bf g}\\right)$. Let ${\\bf n}$ be a unit normal field to $S$ and let $h_{ab}$ be the induced metric on $S$. Let $\\chi_{ab}$ be the second fundamental form on $S$ and let $\\sigma_{ab}$ be the trace-free part of $\\chi_{ab}$. Then the following are equivalent:\n\ni) $S$ is a photon surface;\n\nii) $\\chi_{ab} k^a k^b =0$ $\\forall$ null ${\\bf k} \\in T_pS$ $\\forall p \\in S$;\n\niii) $\\sigma_{ab}=0$;\n\niv) every affine null geodesic of $(S,{\\bf h})$ is an affine null geodesic of $(M,{\\bf g})$.\n\n\\(i) $\\Rightarrow$ (ii). ", "Suppose $S$ is a photon surface. ", "Let $p \\in S$ and let ${\\bf k} \\in T_p S$ be null. ", "There exists an affine null geodesic $ \\gamma: \\left(-\\epsilon,\\epsilon\n\\right) \\rightarrow M $ of $\\left(M,{\\bf g}\\right)$ such that $\\dot{\\gamma}\\left(0\\right) = {\\bf{k}}, |\\gamma| \\subset S$. One has $$\\chi_{ab} \\dot{\\gamma }^a \\dot{\\gamma}^b = n_{a;b} \\dot{\\gamma}^a\n \\dot{\\gamma}^b = \\left(n_a \\dot{\\gamma}^a\\right)_{;b} \\dot{\\gamma}^b = 0\n \\label{eq8}$$ along $\\gamma$. At $p$ this gives $\\chi_{ab} k^a k^b = 0$.\n\n\\(ii) $\\Rightarrow$ (iii). ", "Let $p \\in S$. By (ii) one has $\\sigma_{ab}k^ak^b=\\chi_{ab}k^ak^b=0$ $\\forall$ null ${\\bf k}\\in\nT_pS$. Let $\\{ {\\bf e}_{(0)}, {\\bf e}_{(1)}, {\\bf e}_{(2)} \\}$ be an orthonormal basis for $T_pS$ with ${\\bf e}_{(0)}$ timelike and ${\\bf e}_{(1)}$, ${\\bf e}_{(2)}$ spacelike. ", "Any null ${\\bf k}\\in\nT_pS$, normalized such that $g({\\bf k},{\\bf e}_{(0)})=-1$, has components $k^a=(1,\\cos \\psi , \\sin \\psi )$ with respect to $\\{\n{\\bf e}_{(0)}, {\\bf e}_{(1)}, {\\bf e}_{(2)} \\}$ for some $\\psi\n\\in [ 0,2\\pi )$. ", "A calculation gives $$\\begin{gathered}\n\\sigma_{ab}k^ak^b = (\\sigma_{00}+\\smallfrac{1}{2}\\sigma_{11}\n+\\smallfrac{1}{2}\\sigma_{22})+ 2\\sigma_{01}\\cos \\psi\n+2\\sigma_{02}\\sin \\psi\n\\\\ + \\smallfrac{1}{2}(\\sigma_{11}-\\sigma_{22})\\cos 2\\psi +\n\\sigma_{12}\\sin 2\\psi \\ .\\end{gathered}$$ This must vanish for all $\\psi \\in [0,2\\pi )$. ", "One thus has $\\sigma_{01} =\\sigma_{02}=\\sigma_{12}=0$ and $-\\sigma_{00}=\\sigma_{11}=\\sigma_{22}$. Since $\\sigma_{ab}$ is trace-free one must also have $\\sigma_{00}=\\sigma_{11}+\\sigma_{22}$. There follows $\\sigma_{ab}=0$.\n\n\\(iii) $\\Rightarrow$ (iv). ", "For any curve in $S$ with null tangent ${\\bf k}$ one has $$k^a{\\protect \\rule{0.0em}{1.0ex}}_{||b}k^b = h^a{\\protect \\rule{0.0em}{1.0ex}}_c k^c{\\protect \\rule{0.0em}{1.0ex}}_{;b}k^b =\nk^a{\\protect \\rule{0.0em}{1.0ex}}_{;b}k^b +(\\sigma_{bc}k^bk^c)n^a \\label{lgrad}$$ where $||$ denotes covariant differentiation in $S$ with respect to ${\\bf h}$. The second term on the right of $(\\protect\\ref{lgrad})$ vanishes by hypothesis. ", "If ${\\bf k}$ is tangent to an affine null geodesic of $(S,{\\bf h})$ then the term on the left of $(\\protect\\ref{lgrad})$ also vanishes and so ${\\bf\nk}$ is tangent to an affine null geodesic of $(M,{\\bf g})$.\n\n\\(iv) $\\Rightarrow$ (i). ", "Let $p \\in S$ and let ${\\bf k} \\in T_p S$ be null. ", "Let $\\gamma : (-\\epsilon,\\epsilon ) \\rightarrow S$ be an affine null geodesic of $(S,{\\bf h})$ such that $\\dot{\\gamma}(0) =\n{\\bf k}$. Then, by (iv), $\\gamma$ is an affine null geodesic of $(M,{\\bf g})$ such that $\\dot{\\gamma}(0) = {\\bf k}$, $|\\gamma|\n\\subset S$.\n\nCondition (iii) of Theorem \\[maintheorem\\] is equivalent to a requirement that $\\chi_{ab}$ is pure trace in the sense of $$\\chi_{ab} = \\smallfrac{1}{3}\\Theta h_{ab} \\ ,\n\\label{2ffsimplifies}$$ where $\\Theta := h^{cd}\\chi_{cd}$ is the expansion of the unit normal to $S$. For Example \\[Min3\\] one has $\\Theta =\n2/a$; for Example \\[Min4\\] one has $\\Theta = 3/a$. (Note that, by a standard abuse of notation, $h_{ab}$ denotes both the induced metric on $S$ and the symmetric tensor field of rank $(0,2)$ along $S$ in $M$ which satisfies $h_{ab}n^b=0$ and pulls back to the induced metric on $S$.)\n\nIt is clear from condition (iii) of Theorem \\[maintheorem\\] that a space-time must be specialized in some respect in order to admit any timelike photon surfaces in the sense of Definition \\[photonsurfacedef\\]. ", "For this reason it is helpful to restrict attention to space-times which admit groups of symmetries.", "\n\n\\[photonspheredef\\] [Suppose $(M,{\\bf g})$ admits a group $G$ of isometries. ", "A photon surface $S$ of $(M,{\\bf g})$ that is invariant under $G$, in the sense that each $g \\in G$ maps $S$ onto itself, will be called a $G$-invariant photon surface.]{}", "\n\nClearly any $G$-invariant null hypersurface is a $G$-invariant photon surface. ", "In particular, if $G={\\mathbb{R}}$ or $G={\\mathbb{S}}$, then any Killing horizon [@Car66; @Boy69] is a $G$-invariant photon surface.", "\n\nDynamic Spherical symmetry: General theory {#dssgt}\n==========================================\n\nBy definition, a general spherically symmetric space-time admits an $SO(3)$ isometry group for which the group orbits are spacelike $2$-spheres. ", "The following result describes the evolution of the cross-sectional area of an $SO(3)$-invariant photon surface in a spherically symmetric space-time.", "\n\n\\[firstphotonspheretheorem\\] Let $(M,{\\bf g})$ be a spherically symmetric space-time. ", "Let $S$ be an $SO(3)$-invariant timelike hypersurface of $(M,{\\bf g})$ and let ${\\bf X}$ be the $SO(3)$-invariant unit future-directed timelike tangent vector field along $S$ orthogonal to the $SO(3)$-invariant $2$-spheres in $S$. Let $\\mathscr{T}$ be one such $SO(3)$-invariant $2$-sphere in $S$ and let $\\mathscr{T}_s$ be the $SO(3)$-invariant $2$-sphere in $S$ at arc-length $s$ from $\\mathscr{T}$ along the integral curves of ${\\bf X}$. Then $S$ is a photon surface of $(M,{\\bf g})$ iff the area ${\\,{\\protect \\rule{0.0em}{1.6ex}}^{(2)}}\\! ", "A_s$ of $\\mathscr{T}_s$ satisfies $$\\frac{d^2}{ds^2}{\\,{\\protect \\rule{0.0em}{1.6ex}}^{(2)}}\\! ", "A_s = \\frac{1}{4{\\,{\\protect \\rule{0.0em}{1.6ex}}^{(2)}}\\! ", "A_s}\\left(\n\\frac{d}{ds} {\\,{\\protect \\rule{0.0em}{1.6ex}}^{(2)}}\\! ", "A_s \\right)^2 +{\\,{\\protect \\rule{0.0em}{1.6ex}}^{(2)}}\\! ", "A_s\n\\left(\\smallfrac{1}{3}\\Theta^2 -G_{ab}n^an^b \\right) -4\\pi\n\\label{2areaevolution}$$ where $n^a$ is the unit normal to $S$, $\\Theta$ is the expansion of $n^a$ and $G_{ab}:= R_{ab}-\\frac{1}{2}Rg_{ab}$ is the Einstein tensor of $(M,{\\bf g})$.\n\nLet $h_{ab}$ be the induced Lorentzian $3$-metric on $S$ and, for each $s$, let ${\\,{\\protect \\rule{0.0em}{1.6ex}}^{(2)}}h_{ab}$ be the induced Riemannian $2$-metric on $\\mathscr{T}_s$. The expansion of ${\\bf\nX}$ in $(S, {\\bf h})$ is given by ${\\,{\\protect \\rule{0.0em}{1.6ex}}^{(2)}}\\Theta = {\\,{\\protect \\rule{0.0em}{1.6ex}}^{(2)}}h^{ab}X_{a;b}$ where the covariant derivative is that of $(M,{\\bf\ng})$. Since ${\\bf X}$ is both shear-free and vorticity-free in $(S,{\\bf h})$, the Raychaudhuri equation for ${\\bf X}$ in $(S,{\\bf\nh})$ assumes the form $$\\frac{d}{ds}{\\,{\\protect \\rule{0.0em}{1.6ex}}^{(2)}}\\Theta = -\\smallfrac{1}{2}({\\,{\\protect \\rule{0.0em}{1.6ex}}^{(2)}}\\Theta )^2\n- {\\,{\\protect \\rule{0.0em}{1.6ex}}^{(3)}}\\! ", "R_{ab}X^aX^b \\label{3dRay}$$ where ${\\,{\\protect \\rule{0.0em}{1.6ex}}^{(3)}}\\! ", "R_{ab}$ is the Ricci tensor of $(S,{\\bf h})$.\n\nFrom first principles one has $$\\begin{aligned}\n{\\,{\\protect \\rule{0.0em}{1.6ex}}^{(2)}}\\! ", "R &= {\\,{\\protect \\rule{0.0em}{1.6ex}}^{(3)}}\\! ", "R + 2{\\,{\\protect \\rule{0.0em}{1.6ex}}^{(3)}}\\! ", "R_{ab}X^aX^b - (\n{\\,{\\protect \\rule{0.0em}{1.6ex}}^{(2)}}\\chi^a{\\protect \\rule{0.0em}{1.0ex}}_a )^2\n+ {\\,{\\protect \\rule{0.0em}{1.6ex}}^{(2)}}\\chi^a{\\protect \\rule{0.0em}{1.0ex}}_b {\\,{\\protect \\rule{0.0em}{1.6ex}}^{(2)}}\\chi^b{\\protect \\rule{0.0em}{1.0ex}}_a \\label{2R}\\\\\n{\\,{\\protect \\rule{0.0em}{1.6ex}}^{(3)}}\\! ", "R &= R - 2R_{ab}n^an^b + \\left(\n\\chi^a{\\protect \\rule{0.0em}{1.0ex}}_a\\right)^2 -\\chi^a{\\protect \\rule{0.0em}{1.0ex}}_b\\chi^b{\\protect \\rule{0.0em}{1.0ex}}_a \\label{3R}\\end{aligned}$$ where ${\\,{\\protect \\rule{0.0em}{1.6ex}}^{(2)}}\\chi_{ab}$ is the second fundamental form of each $\\mathscr{T}_s$ in $(S,{\\bf h})$. Since $X^a$ is shear-free and vorticity free in $(S,{\\bf h})$ one has ${\\,{\\protect \\rule{0.0em}{1.6ex}}^{(2)}}\\chi_{ab}=\n\\frac{1}{2}{\\,{\\protect \\rule{0.0em}{1.6ex}}^{(2)}}\\Theta {\\,{\\protect \\rule{0.0em}{1.6ex}}^{(2)}}h_{ab}$. The second fundamental form of $S$ admits the canonical decomposition $\\chi_{ab}=\n\\frac{1}{3}\\Theta h_{ab} +\\sigma_{ab}$. Equations (\\[2R\\]) and (\\[3R\\]) therefore give $$\\begin{aligned}\n{\\,{\\protect \\rule{0.0em}{1.6ex}}^{(2)}}\\! ", "R &= {\\,{\\protect \\rule{0.0em}{1.6ex}}^{(3)}}\\! ", "R + 2{\\,{\\protect \\rule{0.0em}{1.6ex}}^{(3)}}\\! ", "R_{ab}X^aX^b -\n\\smallfrac{1}{2}\n{\\,{\\protect \\rule{0.0em}{1.6ex}}^{(2)}}\\Theta^2 \\\\\n{\\,{\\protect \\rule{0.0em}{1.6ex}}^{(3)}}\\! ", "R &= R -2R_{ab}n^an^b +\\smallfrac{2}{3}\\Theta^2\n-\\sigma^a{\\protect \\rule{0.0em}{1.0ex}}_b\\sigma^b{\\protect \\rule{0.0em}{1.0ex}}_a\\end{aligned}$$ which combine to yield $$2{\\,{\\protect \\rule{0.0em}{1.6ex}}^{(3)}}\\! ", "R_{ab}X^aX^b = {\\,{\\protect \\rule{0.0em}{1.6ex}}^{(2)}}\\! ", "R + 2G_{ab}n^an^b\n-\\smallfrac{2}{3}\\Theta^2 + \\smallfrac{1}{2}({\\,{\\protect \\rule{0.0em}{1.6ex}}^{(2)}}\\Theta )^2\n+\\sigma^a{\\protect \\rule{0.0em}{1.0ex}}_b\\sigma^b{\\protect \\rule{0.0em}{1.0ex}}_a \\ .$$ One may now substitute for the second term on the right of (\\[3dRay\\]) to obtain $$\\frac{d}{ds}{\\,{\\protect \\rule{0.0em}{1.6ex}}^{(2)}}\\Theta = -\\smallfrac{3}{4}({\\,{\\protect \\rule{0.0em}{1.6ex}}^{(2)}}\\Theta )^2\n+\\smallfrac{1}{3}\\Theta^2 - \\smallfrac{1}{2}{\\,{\\protect \\rule{0.0em}{1.6ex}}^{(2)}}\\! ", "R -\nG_{ab}n^an^b -\\smallfrac{1}{2}\\sigma^a{\\protect \\rule{0.0em}{1.0ex}}_b\\sigma^b{\\protect \\rule{0.0em}{1.0ex}}_a \\ .", "\n\\label{nearlythere}$$ From first principles one has ${\\,{\\protect \\rule{0.0em}{1.6ex}}^{(2)}}\\Theta = \\frac{d}{ds} \\ln\n{\\,{\\protect \\rule{0.0em}{1.6ex}}^{(2)}}\\! ", "A$, and the Gauss-Bonnet theorem gives ${\\,{\\protect \\rule{0.0em}{1.6ex}}^{(2)}}\\!", "\nR{\\,{\\protect \\rule{0.0em}{1.6ex}}^{(2)}}\\! ", "A = 8\\pi $. ", "Substituting for ${\\,{\\protect \\rule{0.0em}{1.6ex}}^{(2)}}\\Theta$ and ${\\,{\\protect \\rule{0.0em}{1.6ex}}^{(2)}}\\! ", "R$ in (\\[nearlythere\\]) one obtains $$\\frac{d^2}{ds^2}{\\,{\\protect \\rule{0.0em}{1.6ex}}^{(2)}}\\! ", "A_s = \\frac{1}{4{\\,{\\protect \\rule{0.0em}{1.6ex}}^{(2)}}\\! ", "A_s}\\left(\n\\frac{d}{ds} {\\,{\\protect \\rule{0.0em}{1.6ex}}^{(2)}}\\! ", "A_s \\right)^2 + {\\,{\\protect \\rule{0.0em}{1.6ex}}^{(2)}}\\! ", "A_s \\left(\n\\smallfrac{1}{3}\\Theta^2 -G_{ab}n^an^b -\n\\smallfrac{1}{2}\\sigma^a{\\protect \\rule{0.0em}{1.0ex}}_b\\sigma^b{\\protect \\rule{0.0em}{1.0ex}}_a \\right) -4\\pi \\ .$$ This agrees with (\\[2areaevolution\\]) iff $\\sigma^a{\\protect \\rule{0.0em}{1.0ex}}_b\\sigma^b{\\protect \\rule{0.0em}{1.0ex}}_a =0$.\n\nConstruct, for the tangent bundle $TS$ of $S$, an orthonormal basis field of the form $\\{ {\\bf X}, {\\bf e}_{(1)}, {\\bf e}_{(2)}\n\\}$, with ${\\bf e}_{(1)}$ and ${\\bf e}_{(2)}$ unit spacelike. ", "With respect to this basis one has $$\\sigma^a{\\protect \\rule{0.0em}{1.0ex}}_b\\sigma^b{\\protect \\rule{0.0em}{1.0ex}}_a = (\\sigma^0{\\protect \\rule{0.0em}{1.0ex}}_0)^2\n+(\\sigma^1{\\protect \\rule{0.0em}{1.0ex}}_1)^2 +(\\sigma^2{\\protect \\rule{0.0em}{1.0ex}}_2)^2\n+2(\\sigma^1{\\protect \\rule{0.0em}{1.0ex}}_2)^2 -2(\\sigma^1{\\protect \\rule{0.0em}{1.0ex}}_0)^2\n-2(\\sigma^2{\\protect \\rule{0.0em}{1.0ex}}_0)^2 \\ .$$ By spherical symmetry the vector field $\\sigma^a{\\protect \\rule{0.0em}{1.0ex}}_bX^b$ must be proportional to $X^a$. Hence one has $\\sigma^1{\\protect \\rule{0.0em}{1.0ex}}_0=\\sigma^2{\\protect \\rule{0.0em}{1.0ex}}_0=0$. The vanishing of $\\sigma^a{\\protect \\rule{0.0em}{1.0ex}}_b\\sigma^b{\\protect \\rule{0.0em}{1.0ex}}_a$ is thus equivalent to the vanishing of $\\sigma_{ab}$. One has $\\sigma_{ab}=0$ iff $S$ is a photon surface.", "\n\nA spherically symmetric metric is locally expressible in the form $$g_{ab} = \\left( \\begin{array}{cccc}\n g_{00} & g_{01} & 0 & 0 \\\\\n g_{10} & g_{11} & 0 & 0 \\\\\n 0 & 0 & g_{\\theta \\theta} & 0 \\\\\n 0 & 0 & 0 & g_{\\theta \\theta} \\sin^2 \\theta \\\\\n\\end{array} \\right)\n\\label{gss}$$ with respect to coordinates $\\left(x^0, x^1, \\theta, \\phi\n\\right)$ adapted to the spherical symmetry, where $g_{00}$, $g_{01} = g_{10}$, $g_{11}$ and $g_{\\theta \\theta}>0$ depend only on $x^0$ and $x^1$. It is often convenient to introduce a radial coordinate $r$, depending only on $x^0$ and $x^1$, such that $g_{\\theta \\theta}$ is a function of $r$ only. ", "One is free to specify $g_{\\theta\\theta}$ as a function of $r$ alone since to do so is, in effect, a definition of the coordinate $r$. This will be assumed to be done throughout this paper.", "\n\nThe following result is useful in the locating of $SO(3)$-invariant photon surfaces in dynamic spherically symmetric space-times.", "\n\n\\[mylemma\\] Let $(M,{\\bf g})$ be a spherically symmetric space-time. ", "Let $S$ be an $SO(3)$-invariant timelike hypersurface of $(M,{\\bf g})$ and let ${\\bf X}$ be the $SO(3)$-invariant unit future-directed timelike tangent vector field along $S$ that is orthogonal to the $SO(3)$-invariant $2$-spheres in $S$. Then $S$ is a photon surface of $(M,{\\bf g})$ iff $$X^a{\\protect \\rule{0.0em}{1.0ex}}_{;b}X^b =\n\\smallfrac{1}{2}(g^{\\theta\\theta}n^b\\partial_bg_{\\theta\\theta})n^a\n\\label{gradxx}$$ holds along $S$, where $n^a$ is the unit normal field to $S$ in $(M,{\\bf g})$.\n\nBy spherical symmetry, and since ${\\bf X}$ is unit timelike, the vector field $\\nabla_{\\bf X}{\\bf X}$ must be proportional to ${\\bf n}$. Hence it suffices to show that $S$ is a photon surface iff along $S$ one has $${\\bf n \\cdot}\\nabla_{\\bf X}{\\bf X} =\n\\smallfrac{1}{2}g^{\\theta\\theta}n^b\\partial_b g_{\\theta\\theta}$$ or equivalently $$\\chi_{ab}X^aX^b = -\\smallfrac{1}{2}g^{\\theta\\theta}n^a\\partial_a\ng_{\\theta\\theta} \\ . ", "\\label{L1}$$\n\nConstruct for $TS$ a local orthonormal basis field of the form $\\{ {\\bf X}, {\\bf e}_{(\\theta )},{\\bf e}_{(\\phi )}\\}$. With respect to this basis field the components of $\\chi^a{\\protect \\rule{0.0em}{1.0ex}}_b$ form a diagonal matrix with $$\\chi^{\\theta}{\\protect \\rule{0.0em}{1.0ex}}_{\\theta} =\n\\chi^{\\phi}{\\protect \\rule{0.0em}{1.0ex}}_{\\phi}=n^{\\theta}{\\protect \\rule{0.0em}{1.0ex}}_{;\\theta} =\n\\smallfrac{1}{2}g^{\\theta\\theta}n^a\\partial_a g_{\\theta\\theta} \\ .$$ Equation (\\[L1\\]) is thus equivalent to $\\chi^0{\\protect \\rule{0.0em}{1.0ex}}_0\n= \\chi^{\\theta}{\\protect \\rule{0.0em}{1.0ex}}_{\\theta}=\\chi^{\\phi}{\\protect \\rule{0.0em}{1.0ex}}_{\\phi}$ which is in turn equivalent to $\\sigma^0{\\protect \\rule{0.0em}{1.0ex}}_0=\\sigma^{\\theta}{\\protect \\rule{0.0em}{1.0ex}}_{\\theta}=\n\\sigma^{\\phi}{\\protect \\rule{0.0em}{1.0ex}}_{\\phi}$. In view of the trace-free property of $\\sigma^a {\\protect \\rule{0.0em}{1.0ex}}_b$, equation (\\[L1\\]) is thus equivalent to $\\sigma^a {\\protect \\rule{0.0em}{1.0ex}}_b=0$. From Theorem \\[maintheorem\\] one has that $\\sigma^a {\\protect \\rule{0.0em}{1.0ex}}_b =0$ holds along $S$ iff $S$ is a photon surface.", "\n\nLet us continue to work with respect to the coordinate system $\\{\nx^0,x^1,\\theta , \\phi \\}$ employed in (\\[gss\\]). ", "Let $x^a (s)$ be an integral curve of the vector field ${\\bf X}$ in Lemma \\[mylemma\\]. ", "One has $$\\frac{dx^a}{ds} = X^a$$ and equation $(\\protect\\ref{gradxx})$ becomes $$\\frac{d^2x^a}{ds^2}+\\Gamma^a_{bc} \\frac{dx^b}{ds} \\frac{dx^c}{ds}\n= \\smallfrac{1}{2} (g^{\\theta\\theta}n^b\\partial_b\ng_{\\theta\\theta})n^a \\ . ", "\\label{x2s}$$ Since ${\\bf X} = \\frac{dx^0}{ds} \\left(1, \\frac{dx^1}{dx^0}, 0, 0\n\\right)$ is unit timelike one has $$\\left(\\frac{ds}{dx^0}\\right)^2 = - g_{ab} \\frac{dx^a}{dx^0}\n\\frac{dx^b}{dx^0} \\ .$$ The $x^0$ and $x^1$ components of equation $(\\protect\\ref{x2s})$ thus combine to give $$\\frac{d^2x^1}{(dx^0)^2} = - \\\n\\smallfrac{1}{2}g^{\\theta\\theta}n^a\\partial_ag_{\\theta\\theta}\n\\left(n^1 - \\frac{dx^1}{dx^0} n^0 \\right) g_{bc}\n\\frac{dx^b}{dx^0} \\frac{dx^c}{dx^0} + \\left(\\frac{dx^1}{dx^0}\n\\Gamma^0_{ab} - \\Gamma^1_{ab} \\right) \\frac{dx^a}{dx^0}\n\\frac{dx^b}{dx^0} \\label{x12x0}$$ where the components of ${\\bf n}$ are given by $$n^0 = \\psi \\ g_{1a}\\ \\frac{dx^a}{dx^0}; \\quad n^1 = - \\psi \\\ng_{0a}\\ \\frac{dx^a}{dx^0}$$ for $$\\psi := \\left(- \\Delta \\right)^{- \\frac{1}{2}}\n \\left(-g_{ab} \\frac{dx^a}{dx^0}\\frac{dx^b}{dx^0}\\right)^{- \\frac{1}{2}}$$ where $$\\label{Deltadef}\n\\Delta:= g_{00}g_{11}-(g_{01})^2$$ is the determinant of the time-space part of $g_{ab}$ in (\\[gss\\]). ", "Equation (\\[x12x0\\]) is the coordinate equivalent of (\\[gradxx\\]) and provides for the easy determination of $SO(3)$-invariant photon surfaces (see Example \\[Vaidyaex\\]).", "\n\nStatic Spherical Symmetry: General Theory\n=========================================\n\nBy definition, a spherically symmetric space-time is static if it admits an $SO(3)\\times {\\mathbb{R}}$ group of isometries such that the ${\\mathbb{R}}$ orbits are generated by a Killing field ${\\bf K}$ which is both hypersurface orthogonal and orthogonal to the $SO(3)$ orbits. ", "The present section will be concerned with $SO(3)\\times {\\mathbb{R}}$-invariant photon surfaces in static spherically symmetric space-times. ", "Such surfaces may be termed photon spheres because, as will be seen, they are a natural generalization to general static spherically symmetric space-times of the Schwarzschild photon sphere concept. ", "The term “photon sphere” will be regarded as applicable only in static spherically symmetric space-times. ", "For clarity, the term “$SO(3)\\times {\\mathbb{R}}$-invariant photon surface” will usually be employed in preference to “photon sphere”.", "\n\nAlthough the space-times of Examples \\[Min3\\] and \\[Min4\\] are static and spherically symmetric, the photon surfaces in these space-times are not $SO(3)\\times {\\mathbb{R}}$-invariant and so are not photon spheres. ", "Of the Robertson-Walker space-times of Example \\[RobWal\\], only the Einstein cylinder is both spherically symmetric and static. ", "None of the photon surfaces of the Einstein cylinder are $SO(3)\\times {\\mathbb{R}}$-invariant. ", "Thus the Einstein cylinder has no photon spheres.", "\n\nOne may characterize an $SO(3)\\times {\\mathbb{R}}$-invariant photon surface, or photon sphere, in a static spherically symmetric space-time by means of the following special case of Theorem \\[firstphotonspheretheorem\\].", "\n\n\\[statssgeomtheorem\\] Let $(M,{\\bf g})$ be a static spherically symmetric space-time with Killing field ${\\bf K}$ and let $S$ be an $SO(3)\\times {\\mathbb{R}}$-invariant timelike hypersurface of $(M,{\\bf\ng})$. Then $S$ is an $SO(3)\\times {\\mathbb{R}}$-invariant photon surface of $(M,{\\bf g})$ if there exists an $SO(3)$-invariant $2$-sphere $\\mathscr{T} \\subset S$ satisfying $$A\\left( \\Theta^2 - 3G_{ab}n^an^b \\right) = 12\\pi\n\\label{mainequation}$$ where $A$ is the area of $\\mathscr{T}$, $n^a$ is the unit normal to $S$ and $\\Theta$ is the trace of the second fundamental form of $S$. Conversely, if $S$ is an $SO(3)\\times {\\mathbb{R}}$-invariant photon surface of $(M,{\\bf g})$ then (\\[mainequation\\]) holds for every $SO(3)$-invariant $2$-sphere $\\mathscr{T}\\subset\nS$.\n\nNote that the unit future-directed timelike tangent field ${\\bf X}$ along $S$ in Theorem \\[firstphotonspheretheorem\\] is proportional to the restriction to $S$ of the Killing field ${\\bf K}$.\n\nSuppose first that there exists an $SO(3)$-invariant $2$-sphere $\\mathscr{T}\\subset S$ such that (\\[mainequation\\]) holds. ", "The quantities $A$, $\\Theta$ and $G_{ab}n^an^b$ remain constant as $\\mathscr{T}$ is mapped along the flow lines of the Killing field ${\\bf K}$. So they also remain constant as they are mapped along the flow lines of ${\\bf X}$. Hence (\\[2areaevolution\\]) holds with the term on the left and the first term on the right both zero. ", "Thus, by Theorem \\[firstphotonspheretheorem\\], $S$ is a photon surface of $(M,{\\bf g})$. By hypothesis $S$ is $SO(3)\\times {\\mathbb{R}}$-invariant.", "\n\nFor the converse, suppose that $S$ is an $SO(3)\\times {\\mathbb{R}}$-invariant photon surface of $(M,{\\bf g})$. Then (\\[2areaevolution\\]) holds for every $SO(3)$-invariant $2$-sphere $\\mathscr{T}_s\\subset S$. Since ${\\bf K}$ induces groups of local isometries, the area $A_s$ of $\\mathscr{T}_s$ is independent of the parameter $s$. Hence the term on the left and the first term on the right of (\\[2areaevolution\\]) both vanish and one obtains (\\[mainequation\\]).", "\n\nIf one has $G_{ab}Y^aY^b\\geq 0$ $\\forall$ vectors ${\\bf Y}$ and $S$ is an $SO(3)\\times {\\mathbb{R}}$-invariant timelike photon surface of $(M,{\\bf g})$, then for any $SO(3)$-invariant $2$-sphere $\\mathscr{T}\\subset S$ one has $$A\\Theta^2 \\geq 12\\pi \\label{mainequationcor}$$ with equality holding iff $G_{ab}n^an^b=0$ along $S$.\n\nFor Schwarzschild space-time where (see Example \\[Schwarzschildex\\]) the only timelike photon sphere is at $r=3m$, one has $A=4\\pi (3m)^2$, $\\Theta = 1/(\\sqrt{3}m)$ and $G_{ab}=0$ which verifies (\\[mainequation\\]) and (\\[mainequationcor\\]) for this case.", "\n\nIf the Einstein equations hold with a zero cosmological constant then, in the corollary to Theorem \\[statssgeomtheorem\\], the hypothesis $G_{ab}Y^aY^b\n\\geq 0$ for all vectors ${\\bf Y}$ is equivalent to $T_{ab}Y^aY^b\\geq 0$ for all vectors ${\\bf Y}$. This is a physically reasonable energy condition. ", "In particular, for a perfect fluid with density $\\rho$ and pressure $p$, it is equivalent to a condition that $\\rho$ and $p$ are both non-negative. ", "More generally, the condition holds for an energy tensor with a single timelike eigenvector (type I in the classification of Hawking & Ellis [@HE73]) iff each energy tensor eigenvalue is non-negative.", "\n\nThe characterization of timelike photon surfaces provided by Theorem \\[statssgeomtheorem\\] involves derivatives of the metric components up to second order. ", "The following result (Theorem \\[genphotonspheretheorem\\]) provides an entirely different characterization of $SO(3)\\times{\\mathbb{R}}$-invariant photon surfaces in terms of derivatives of the metric components up to only first order.", "\n\nLet a general static spherically symmetric metric ${\\bf g}$ be expressed in the form (\\[gss\\]) with $g_{\\theta\\theta}$ a function of $r$ only. ", "The Killing equation $K_{(a;b)}=0$ and the orthogonality of ${\\bf K}$ to $\\partial_{\\theta}$ and $\\partial_{\\phi}$ gives $K^a\\partial_a g_{\\theta\\theta} =0$ and hence $\\nabla_{\\bf K}r=0$ where $r$ is to be regarded as a scalar field on $M$. Since $r$ is independent of $\\theta$ and $\\phi$ it follows that any $SO(3)\\times {\\mathbb{R}}$-invariant hypersurface $S$ of $(M,{\\bf g})$ must be of the form $\\{r=\\text{\\em const.}\\}$. If $S$ is also a timelike hypersurface then $r^{;a}$ is a spacelike vector field along $S$ and ${\\bf K}$ is a timelike vector field in a neighbourhood of $S$.\n\nIf the coordinates $x^0$ and $x^1$ implicit in (\\[gss\\]) are chosen such that ${\\bf K}=\\partial_{x^0}$ then the Killing equation gives that all the metric components $g_{ab}$ in (\\[gss\\]) are independent of $x^0$. Since $r$ is constant along the integral curves of ${\\bf K}$, the coordinate $x^1$ must be a function of $r$ only. ", "A natural choice is $x^1=r$. One may redefine $x^0$ according to $x^0\\rightarrow x^0-\\int(g_{01}/g_{00})dx^1$. This diagonalizes the time-space part of $g_{ab}$ and leaves the components of $g_{ab}$ independent of $x^0$. Furthermore the curves $\\{\nx^1,\\theta , \\phi =\\text{\\em const.}\\}$ are unchanged except that they are re-parametrized. ", "The vector field $\\partial_{x^0}$ then becomes a conformal Killing field.", "\n\nDefine the tensor field $$\\epsilon^{ab} := (-\\Delta )^{-1/2} \\left( \\begin{array}{cccc}\n0&1&0&0\\\\ -1&0&0&0 \\\\ 0&0&0&0 \\\\ 0&0&0&0 \\end{array} \\right)$$ on $M$, where the components are given with respect to the coordinate basis employed in (\\[gss\\]) and $\\Delta$ is the determinant of the time-space part of ${\\bf g}$ in (\\[gss\\]), as in (\\[Deltadef\\]).", "\n\n\\[genphotonspheretheorem\\] Let $(M,{\\bf g})$ be a static spherically symmetric space-time with ${\\bf g}$ of the form (\\[gss\\]), with $g_{\\theta\\theta}$ a function of the coordinate $r$ only. ", "Let $S$ be an $SO(3)\\times {\\mathbb{R}}$-invariant timelike hypersurface of $(M,{\\bf g})$ and suppose that $\\nabla\nr$ is nowhere-zero along $S$. Then $S$ is an $SO(3)\\times {\\mathbb{R}}$-invariant photon surface of $(M,{\\bf g})$ iff $$2g_{\\theta\\theta}\\epsilon^{ab}\\epsilon^{cd}r_{;ac}r_{;b}r_{;d}\n+r^{;a}r_{;a}r^{;c}\\partial_{c}g_{\\theta\\theta}=0\n\\label{genphotonsphere}$$ holds along $S$.\n\nSince $(M,{\\bf g})$ is both spherically symmetric and static, the surface $S$ is of the form $\\{ r=\\text{\\em\nconst.}\\}$. The unit spacelike normal to $S$ is therefore given by $$n^a = \\eta r^{;a}$$ for $$\\eta := (r^{;a}r_{;a})^{-1/2}\\ .$$ The second fundamental form of $S$ is given by $$\\chi_{ab}:= \\eta h_a{\\protect \\rule{0.0em}{1.6ex}}^ch_b{\\protect \\rule{0.0em}{1.6ex}}^d r_{;cd} \\ .$$ The vector fields $$\\begin{aligned}\n{\\bf X}^a &:= (-\\Delta g^{bc}r_{;b}r_{;c})^{-1/2}(r_{;1},-r_{;0},0,0)\\\\\n{\\bf e}_{(\\theta )} &:= (g_{\\theta\\theta})^{-1/2}\\partial_{\\theta}\\\\\n{\\bf e}_{(\\phi )} &:= (g_{\\theta\\theta}\\sin^2\\theta\n)^{-1/2}\\partial_{\\phi}\\end{aligned}$$ form an orthonormal frame field along $S$, with ${\\bf e}_{(\\theta\n)}$ and ${\\bf e}_{(\\phi )}$ unit spacelike and ${\\bf X}$ unit timelike. ", "One has $$\\chi_{ab}X^a{\\bf e}_{(\\theta )}^b = \\chi_{ab}X^a{\\bf e}_{(\\phi\n)}^b =\\chi_{ab}{\\bf e}_{(\\theta )}^a{\\bf e}_{(\\phi )}^b=0$$ $$\\chi_{ab}{\\bf e}_{(\\theta )}^a{\\bf e}_{(\\theta )}^b=\n\\chi_{ab}{\\bf e}_{(\\phi )}^a {\\bf e}_{(\\phi )}^b = \\frac{\\eta\nr^{;a}\\partial_{a}g_{\\theta\\theta}}{2g_{\\theta\\theta}}$$ $$\\chi_{ab}X^a X^b = \\eta^3\n\\epsilon^{ab}\\epsilon^{cd}r_{;ac}r_{;b}r_{;d} \\ .$$ Condition (iii) of Theorem \\[maintheorem\\] holds iff $\\chi_{ab}$ is proportional to $h_{ab}$ and hence iff $$-\\chi_{ab}X^a X^b =\n\\chi_{ab}{\\bf e}_{(\\theta )}^a{\\bf e}_{(\\theta )}^b =\n\\chi_{ab}{\\bf e}_{(\\phi )}^a{\\bf e}_{(\\phi )}^b \\ .$$ This is equivalent to $$-\\eta^2 \\epsilon^{ab}\\epsilon^{cd}r_{;ac}r_{;b}r_{;d}\n=\\frac{r^{;a}\\partial_a g_{\\theta\\theta}}{2g_{\\theta\\theta}}$$ which is in turn equivalent to (\\[genphotonsphere\\]).", "\n\nEquation (\\[genphotonsphere\\]) can have solutions such that $\\{ r=\\text{\\em const.}\\}$ is a spacelike hypersurface and therefore not a photon surface (see e.g. Example \\[rnex\\]). ", "It is therefore always necessary in the use of Theorem \\[genphotonspheretheorem\\] to check that the hypersurface $\\{ r=\\text{\\em const.}\\}$ is in fact timelike or null.", "\n\nNote that in a region of space-time where the Killing field ${\\bf\nK}$ is spacelike, for example behind the event horizon of Schwarzschild space-time, the hypersurfaces $\\{ r=\\text{\\em\nconst.}\\}$ are necessarily spacelike and so cannot be photon spheres.", "\n\n[**Case 1. (", "$x^1:= r$, components of $g_{ab}$ independent of $x^0$.)**]{} As discussed previously, for a static spherically symmetric metric it is possible to choose $x^1:=r$, with $g_{\\theta\\theta}$ depending only upon $r$ and with all the components of $g_{ab}$ independent of $x^0$. In this case (\\[genphotonsphere\\]) reduces to $$g_{00}\\partial_r g_{\\theta\\theta} = g_{\\theta\\theta}\\partial_r\ng_{00} \\ . ", "\\label{photonsphere}$$ This agrees with an equation obtained by Virbhadra & Ellis [@VE99b] on the basis of a different definition [@VE99a] of a photon sphere. ", "Note that even though the components $g_{rr}, g_{0r}=g_{r0}$ do not appear in (\\[photonsphere\\]), they are not assumed to vanish. ", "A particular sub-case of interest is that of time-space coordinates, with $t:=x^0$ timelike in the sense of $g^{tt}< 0$. Another sub-case of interest is that of single null (radiation) coordinates, with $u:=x^0$ null in the sense of $g^{uu}=0$.\n\n[**Case 2. (", "Double null coordinates $u, v$.)**]{} Let $x^0 := u$, $x^1 :=v$ be double null coordinates in the sense of $g^{uu}=g^{vv}=0$. The radial coordinate $r$ is to be regarded as a function of $u$ and $v$. Then (\\[genphotonsphere\\]) assumes the form $$g_{\\theta\\theta}\\{ r_{;uu} (r_{;v})^2-2r_{;uv}r_{;u}r_{;v}\n+r_{;vv}(r_{;u})^2\\}\n+2(r_{;u}r_{;v})^2\\partial_rg_{\\theta\\theta}=0 \\ .", "\n\\label{photonspheredoublenull}$$ The metric components $g_{uv}=g_{vu}$ enter here through the covariant derivatives of $r$.\n\nEquations (\\[genphotonsphere\\]), (\\[photonsphere\\]) and (\\[photonspheredoublenull\\]) may be referred to as photon sphere equations since they give the location of timelike photon spheres in static spherically symmetric space-times.", "\n\nIn order to facilitate further progress, a general static spherically symmetric metric will be written in such a form as to cast the Einstein tensor in a particularly simple and convenient form.", "\n\nOne has from previous remarks that a general static spherically symmetric metric is locally expressible in the form $${\\bf g} = g_{tt}dt^2 +g_{rr}dr^2 + r^2(d\\theta^2 +\\sin^2\\theta\nd\\phi^2 )$$ where $g_{tt}$ and $g_{rr}$ are functions of $r$ only. ", "Let $$\\begin{aligned}\nm(r) &:= \\smallfrac{1}{2}r \\left( 1 - \\frac{1}{g_{rr}}\\right) \\\\\n\\mu (r)&:= \\ln (-g_{tt}g_{rr}) \\ .\\end{aligned}$$ Then the metric assumes the form $${\\bf g} = -\\left( 1-\\frac{2m(r)}{r}\\right){\\rm e}^{\\mu (r)} dt^2\n+\\left(1-\\frac{2m(r)}{r}\\right)^{-1}dr^2 +r^2(d\\theta^2 +\n\\sin^2\\theta d\\phi^2 ) \\label{metricform}$$ and the Einstein tensor is given by $$G^a{\\protect \\rule{0.0em}{1.0ex}}_b = 8\\pi\\left( \\begin{array}{cccc} -\\rho (r) & 0 &0&0\\\\\n0&p_1(r)&0&0 \\\\ 0&0& p_2(r) &0\\\\ 0&0&0&p_2(r)\n\\end{array} \\right)$$ for $$\\begin{aligned}\n8\\pi \\rho (r) &:= \\frac{2m'(r)}{r^2} \\label{den}\\\\\n8\\pi p_1(r) &:= \\frac{1}{r^2}\\left\\{ (r-2m(r))\\mu\n'(r)-2m'(r)\\right\\}\n\\label{pr}\\\\\n8\\pi p_2(r)&:= \\frac{1}{4r^2}\\left\\{ (2(r+m(r)-3rm'(r))\\mu '(r)\n+r(r-2m(r))(\\mu '(r))^2 \\right. ", "\\nonumber \\\\\n& \\hspace*{12em}\\left. ", "-4rm''(r) +2r(r-2m(r))\\mu '' (r) \\right\\}\n\\ . ", "\\label{ptheta} \\end{aligned}$$ where a prime denotes differentiation with respect to $r$. For the right sides of (\\[den\\]), (\\[pr\\]) and (\\[ptheta\\]) to be defined at some radius $\\hat{r}>0$ one evidently needs $m(r)$ and $\\mu (r)$ to be twice differentiable at $r=\\hat{r}$. Equations (\\[den\\]) and (\\[pr\\]) combine to give $$\\mu '(r) =\n\\frac{8\\pi r(\\rho (r) +p_1(r))}{\\left( 1 - \\frac{2m(r)}{r}\n\\right)} \\label{lambdadash}$$ whereby one may rewrite (\\[ptheta\\]) in the more convenient form $$\\frac{2}{r}(p_2(r)-p_1(r))=\np_1'(r)+\\frac{ \\left( \\frac{m(r)}{r^2}+4\\pi r\np_1(r)\\right)\\left(\\rho (r)+p_1(r)\\right)} {\\left(\n1-\\frac{2m(r)}{r}\\right) } \\ .\\label{pressurediff}$$ In the perfect fluid case $p_1(r)=p_2(r)=:p(r)$ equation (\\[pressurediff\\]) reduces to the Tolman-Oppenheimer-Volkoff equation $$\\label{TOV}\np'(r)=-\\frac{ \\left( \\frac{m(r)}{r^2}+4\\pi r\np(r)\\right)\\left(\\rho (r)+p(r)\\right)} {\\left(\n1-\\frac{2m(r)}{r}\\right) } \\ .$$ By means of equations (\\[den\\]) and (\\[lambdadash\\]), the photon sphere equation (\\[photonsphere\\]) becomes $$1-\\frac{3m(r)}{r}-4\\pi r^2p_1(r)=0 \\ . ", "\\label{fluidphotonsphere}$$ For $r$ such that $2m(r)<r$, and hence such that the hypersurface $\\{ r=\\text{\\em const.}\\}$ is timelike, equation (\\[fluidphotonsphere\\]) gives the location of the $SO(3)\\times {\\mathbb{R}}$-invariant timelike photon surfaces for the metric (\\[metricform\\]).", "\n\nEquation (\\[fluidphotonsphere\\]) is the basis for the following result which shows that, subject to a suitable energy condition, any black hole in a static spherically symmetric space-time must be surrounded by an $SO(3)\\times {\\mathbb{R}}$-invariant photon surface. ", "For the purpose of this and subsequent results, a function $f: {\\mathbb R}\\supset I \\rightarrow {\\mathbb R}$ on an interval $I$ will be said to be piecewise $C^r$ if $I$ is the disjoint union of a locally finite collection of intervals $I_i$ such that $f|I_i$ is $C^r$. Each interval $I_i$ may be open, closed or half-open.", "\n\n\\[trappedsurfacetheorem\\] Suppose the metric ${\\bf g}$ has the form (\\[metricform\\]) for $r_0<r<\\infty$, for some $r_0>0$, with $m(r)$ and $\\mu (r)$ both $C^0$, piecewise $C^2$ functions of $r \\in (r_0, \\infty )$. ", "Suppose the following hold:\n\n1) $\\rho (r)$ and $p_1(r)$ are bounded functions of $r \\in (r_0,\\infty)$;\n\n2) $2m(r)<r$ $\\forall r \\in (r_0,\\infty)$;\n\n3) $\\rho (r) \\geq 0$, $p_1(r)\\geq 0$ $\\forall r \\in (r_0,\\infty)$;\n\n4) $\\lim_{r \\rightarrow \\infty}4\\pi r^2p_1(r)\n =\\lim_{r \\rightarrow \\infty}4\\pi r^2\\rho (r)=0$;\n\n5) for each value of $t$ the $2$-surfaces $\\mathscr{T}_{t,r}:=\n \\{ t=\\text{\\em const.}\\} \\cap \\{ r=\\text{\\em const.} ", "\\}$, $r_0<r<\\infty$, are such that $\\mathscr{T}_t := \\lim_{r \\searrow\n r_0} \\mathscr{T}_{t,r}$ exists as an embedded spacelike $2$-sphere in $(M,{\\bf g})$ and is marginally outer trapped.", "\n\nThen $(M,{\\bf g})$ admits an $SO(3)\\times {\\mathbb{R}}$-invariant timelike photon surface of the form $\\{ r=r_1\\}$ for some $r_1\\in (r_0,\\infty)$.\n\nFix $t$ and let ${\\bf k}$ be the outward future-directed null normal field along each $\\mathscr{T}_{t,r}$, $r_0<r<\\infty$, normalized such that ${\\bf g}({\\bf k},{\\bf n})=1$, where ${\\bf n}=\\left( 1 - \\frac{2m(r)}{r}\\right)^{1/2}\\partial_r$ is the outward radial unit tangent to $\\{ t= \\text{\\em const.}\\}$. Since ${\\bf k}$ is parallelly propagated along each of the geodesic integral curves of ${\\bf n}$, one has that $\\lim_{r\n\\searrow r_0}{\\bf k}$ is a well-defined, nowhere-zero null vector field along $\\mathscr{T}_t:= \\lim_{r \\searrow r_0}{\\mathcal\nT}_{t,r}$. For $r \\in (r_0,\\infty )$ the vector field ${\\bf k}$ has the form $k^a = (k^t,a(r)k^t,0,0)$ for $$a(r):=(-g_{tt}/g_{rr})^{1/2}=\\left( 1-\\frac{2m(r)}{r}\\right){\\rm\ne}^{\\mu (r)/2} \\ .$$ The expansion of ${\\bf k}$ is given by $$\\Theta_{\\text{\\em out}} = {\\,{\\protect \\rule{0.0em}{1.6ex}}^{(2)}}h^b {\\protect \\rule{0.0em}{1.0ex}}_a k^a {\\protect \\rule{0.0em}{1.0ex}}_{;b} =\n\\frac{2a(r)}{r}k^t \\ .$$ The condition that $\\mathscr{T}_t$ is marginally outer trapped therefore implies $$\\label{limit}\n0=\\lim_{r \\searrow r_0}a(r) = \\lim_{r \\searrow r_0}\\left( 1 -\n\\frac{2m(r)}{r}\\right) {\\rm e}^{\\mu (r)/2} \\ .$$ The non-negativity of $\\rho (r)$ and $p_1(r)$ gives, by means of (\\[den\\]) and (\\[lambdadash\\]), that $m(r)$ and $\\mu (r)$ are non-decreasing functions of $r \\in\n(r_0,\\infty)$. Thus (\\[limit\\]) holds iff at least one of $$\\lim_{r \\searrow r_0}\\left( 1 - \\frac{2m(r)}{r} \\right) = 0 \\ ;\n\\quad \\lim_{r \\searrow r_0}\\mu (r) = -\\infty \\label{limitpair}$$ holds.", "\n\nSuppose the first of (\\[limitpair\\]) fails. ", "Then the second must hold and one has $$\\lim_{r \\searrow r_0}\\left( 1 -\\frac{2m(r)}{r}\\right)^{-1} <\\infty \\ .", "\n\\label{finite}$$ From the boundedness of $\\rho (r)$ and $p_1(r)$ on $r \\in\n(0,\\infty )$ one has, by means of (\\[lambdadash\\]) and (\\[finite\\]), that $\\limsup_{r \\searrow r_0}\\mu '(r)$ is finite. ", "This is incompatible with the second of (\\[limitpair\\]). ", "Hence the first of (\\[limitpair\\]) must hold.", "\n\nLet $f: (r_0,\\infty )\\rightarrow {\\mathbb R}$ be the left side of (\\[fluidphotonsphere\\]). ", "By the non-negativity of $p_1(r)$ and the first of (\\[limitpair\\]) one has $\\lim_{r \\searrow r_0}f(r) \\leq -\\frac{1}{2}$. By condition (4), equation (\\[den\\]) and l’H[ô]{}pital’s rule one has $\\lim_{r \\rightarrow \\infty}m(r)/r = \\lim_{r \\rightarrow \\infty}\nr^2p_1(r)=0$ and hence $\\lim_{r \\rightarrow \\infty}f(r)=1$. Hence there exists some $r_1\\in (r_0,\\infty)$ such that $f(r_1)=0$. The hypersurface $\\{ r=r_1\\}$ is an $SO(3)\\times {\\mathbb{R}}$-invariant photon surface of $(M,{\\bf g})$.\n\nCondition (3) of Theorem \\[trappedsurfacetheorem\\] may be expressed more succinctly as $G_{ab}Y^aY^b\\geq 0$ $\\forall$ vectors ${\\bf Y}$. With regard to condition (5) of Theorem \\[trappedsurfacetheorem\\], to have required ${\\mathcal\nT}_t$ to be contained in the hypersurface $\\{ t=\\text{\\em\nconst.}\\}$ would have been too strong since, for Schwarzschild space-time, no spacelike hypersurface of the form $\\{ t=\\text{\\em\nconst.}\\}$ in the exterior region contains a marginally outer trapped $2$-surface.", "\n\nTheorem \\[trappedsurfacetheorem\\] may be interpreted to the effect that, subject to the energy conditions expressed in condition (3), any static spherically symmetric black hole must be surrounded by an $SO(3)\\times {\\mathbb{R}}$-invariant timelike photon surface. ", "The following result may then be regarded as a partial converse in that it shows, subject to a suitable energy condition, that if there exists an $SO(3)\\times{\\mathbb{R}}$-invariant timelike photon surface then there must be a naked singularity or a black hole, or more than a certain amount of matter.", "\n\n\\[nopsprop\\] Suppose the metric ${\\bf g}$ has the form (\\[metricform\\]) for $0 < r< \\infty$, with $m(r)$ and $\\mu (r)$ both $C^0$, piecewise $C^2$ functions of $r\\in\n(0,\\infty )$. ", "If the following all hold:\n\n1) $\\rho (r)$ is a non-increasing, bounded function of $r \\in (0,\\infty)$;\n\n2) $\\lim_{r \\rightarrow 0}m(r)=0$;\n\n3) $4m(r)<r$ $\\forall r \\in (0,\\infty)$;\n\n4) $p_1(r) \\leq \\rho (r)/3$ $\\forall r \\in (0,\\infty)$,\n\nthen $(M,{\\bf g})$ can contain no $SO(3)\\times {\\mathbb{R}}$-invariant timelike photon surfaces.", "\n\nBy conditions (1) and (2) with equation (\\[den\\]) one has $m(r)\\geq (4\\pi /3)r^3\\rho (r)$ $\\forall r > 0$. By condition (4) one therefore has $4\\pi\nr^2p_1(r)\\leq (4\\pi /3)r^2\\rho (r) \\leq m(r)/r$ $\\forall r>0$. The left side of (\\[fluidphotonsphere\\]) is thus bounded from below by $1-4m(r)/r$ $\\forall r>0$. This is positive by condition (3). ", "The left side of (\\[fluidphotonsphere\\]) is therefore non-vanishing for all $r>0$.\n\nNote that this result is valid even for negative $p_1(r)$ and $\\rho (r)$. Condition (2) of Proposition \\[nopsprop\\] prohibits any curvature singularity at $r=0$. Condition (3) may be interpreted as a requirement that there is no black hole and less than a certain amount of matter. ", "The result shows that one of these two conditions must fail if there is an $SO(3)\\times{\\mathbb{R}}$-invariant timelike photon surface and conditions (1) and (4) both hold.", "\n\nWhen the matter is a perfect fluid it is possible to improve condition (3) of Proposition \\[nopsprop\\] to condition (3) of the following result.", "\n\n\\[nopstheorem\\] Suppose the metric ${\\bf g}$ has the form (\\[metricform\\]) for $0 < r< \\infty$, with $m(r)$ and $\\mu (r)$ both $C^1$, piecewise $C^2$ functions of $r\\in\n(0,\\infty )$. ", "If the following all hold:\n\n1) the matter is a perfect fluid with pressure $p(r)$ and density $\\rho (r)$;\n\n2) $\\lim_{r\\rightarrow\\infty}4\\pi r^2p(r)\n =\\lim_{r\\rightarrow\\infty}4\\pi r^2\\rho (r) =0$;\n\n3) $(24/7)m(r)<r$ $\\forall r \\in (0,\\infty)$;\n\n4) $p(r) \\leq \\rho (r)/3$ $\\forall r \\in (0,\\infty)$,\n\nthen $(M,{\\bf g})$ can contain no $SO(3)\\times {\\mathbb{R}}$-invariant timelike photon surfaces.", "\n\nLet $f:(0,\\infty )\\rightarrow {\\mathbb{R}}$ be the left side of equation (\\[fluidphotonsphere\\]). ", "Since $m(r)$ and $\\mu (r)$ are $C^1$, piecewise $C^2$ functions of $r\\in\n(0,\\infty )$, one has by equation (\\[pr\\]) that $f(r)$ is a $C^0$, piecewise $C^1$ function of $r\\in (0,\\infty )$. ", "The function $f'(r)$ is then a piecewise $C^0$ function of $r\\in\n(0,\\infty )$ which, by means of of the Tolman-Oppenheimer-Volkoff equation (\\[TOV\\]), is given by $$\\label{feqn}\nrf'(r) = 3\\frac{m(r)}{r}-12\\pi r^2\\rho (r) -8\\pi r^2 p(r)\n+\\frac{\\left(\\frac{m(r)}{r}+4\\pi r^2p(r)\\right)}{\\left(\n1-2\\frac{m(r)}{r}\\right)}4\\pi r^2 (\\rho (r) +p(r)) \\ .$$ For $r=r_1\\in (0,\\infty )$ such that $$\\label{fiszero}\n0=f(r_1)=1-3\\frac{m(r_1)}{r_1}-4\\pi r_1^2p(r_1)$$ equation (\\[feqn\\]) reduces to $$\\label{feqn1}\nr_1 f'(r_1)= 1-8\\pi r_1^2 (\\rho (r_1) +p(r_1) ) \\ .$$ From condition (3) and equation (\\[fiszero\\]) one has $4\\pi r_1^2 p(r_1)>1/8$, whence by condition (4) one has $4\\pi\nr_1^2\\rho (r_1)>3/8$. Thus (\\[feqn1\\]) gives $f'(r_1)<0$.\n\nBy condition (2), equation (\\[den\\]) and l’H[ô]{}pital’s rule one has $\\lim_{r\\rightarrow\\infty}m(r)/r =\n\\lim_{r\\rightarrow\\infty} 4\\pi r^2p(r)=0$ and hence $\\lim_{r\\rightarrow\\infty}f(r)=1$. Since it has been established that $f'(r)$ is negative for all $r\\in (0,\\infty )$ such that $f(r)=0$, one must therefore have $f(r)>0$ for all $r\\in\n(0,\\infty )$. ", "Hence the space-time can contain no $SO(3)\\times {\\mathbb{R}}$-invariant timelike photon surfaces.", "\n\nNote that, as for Proposition \\[nopsprop\\], Theorem \\[nopstheorem\\] is valid even for negative pressure and density.", "\n\nOne would like to remove the insufficient matter parts of condition (3) of Proposition \\[nopsprop\\] and condition (3) of Theorem \\[nopstheorem\\], in other words to weaken these to a no-black-hole condition $2m(r)<r$ $\\forall\nr>0$. But no result to this effect is forthcoming. ", "On the other hand no counterexample is known.", "\n\nTo conclude this section it will be shown that the physical significance of the photon sphere in Schwarzschild space-time, as discussed in the Introduction, carries over to the general static spherically symmetric case. ", "Suppose the metric has the form (\\[metricform\\]) for $r_0 <r<\\infty$ and is asymptotically flat in the limit $r \\rightarrow \\infty$. Assume $p_1(r)\\geq 0$, $m(r)\\geq 0$ $\\forall r > r_0$. The matter need not be a perfect fluid. ", "Denote the left side of (\\[fluidphotonsphere\\]) by $f(r)$. The condition of asymptotic flatness gives $\\lim_{r\\rightarrow \\infty}f(r) =1$ so, if there are any $SO(3)\\times{\\mathbb{R}}$-invariant timelike photon surfaces, there will be an outermost such surface $S$. For simplicity assume $f'(r)\\neq 0$ at $S$. Let ${\\mathcal\nR}_{\\text{\\em ext}}$ be the connected component of $\\{ q \\in M:\nf(q)>0\\}$ that has $S$ as its inner boundary and extends to $r=\\infty$. Let $\\mathscr{R}_{\\text{\\em int}}$ be the connected component of $\\{ q \\in M: f(q)<0\\}$ that has $S$ as its outer boundary.", "\n\nConsider first the case of a future endless affine null geodesic $\\gamma (\\lambda )$. ", "The null geodesic equations for the metric (\\[metricform\\]) give $$\\label{gennullgeodesic}\n\\frac{d^2r}{d\\lambda^2} = rf(r) \\left\\{ \\left(\\frac{d \\theta}{d\n\\lambda}\\right)^2 + \\sin^2\\theta\\left(\\frac{d \\phi}{d\n\\lambda}\\right)^2\\right\\} -\\frac{\\mu '(r)}{2}\\left(\\frac{dr}{d\n\\lambda}\\right)^2 \\ .$$ At any point $p \\in |\\gamma |\\cap \\mathscr{R}_{\\text{\\em ext}}$ such that $dr/d\\lambda =0$ one has $d^2r/d\\lambda^2 >0$. At any point $p \\in |\\gamma |\\cap \\mathscr{R}_{\\text{\\em int}}$ such that $dr/d\\lambda =0$ one has $d^2r/d\\lambda^2 <0$. Thus if $\\gamma$ starts outside $S$ (i.e. in $\\mathscr{R}_{\\text{\\em\next}}$) and is initially directed outwards, in the sense that $dr/d\\lambda$ is initially positive, then $\\gamma$ will continue outwards. ", "If $\\gamma$ starts in $\\mathscr{R}_{\\text{\\em int}}$ and is initially directed inwards, in the sense that $dr/d\\lambda$ is initially negative, then $\\gamma$ will continue inwards until it falls either into a singularity or through an $SO(3)\\times {\\mathbb{R}}$-invariant photon surface other than $S$.\n\nConsider now a unit speed timelike geodesic $\\xi (s)$. The timelike geodesic equations give $$\\label{gentimelikegeodesic}\n\\frac{d^2r}{ds^2} = - \\frac{m(r)}{r^2} -4\\pi rp_1(r) + rf(r)\n\\left\\{ \\left(\\frac{d \\theta}{ds}\\right)^2 +\n\\sin^2\\theta\\left(\\frac{d \\phi}{ds}\\right)^2\\right\\} - \\frac{\\mu\n'(r)}{2}\\left( \\frac{dr}{ds} \\right)^2 \\ .$$ For any point $p \\in \\mathscr{R}_{\\text{\\em ext}}$ one can arrange for the first three terms on the right of (\\[gentimelikegeodesic\\]) to cancel and so obtain a unit speed timelike geodesic $ \\xi (s)$ through $p \\in {\\mathcal\nR}_{\\text{\\em ext}}$ at constant $r$. For $p \\in {\\mathcal\nR}_{\\text{\\em int}}$ the first three terms on the right of (\\[gentimelikegeodesic\\]) are evidently negative. ", "For $p \\in | \\xi |\\cap \\mathscr{R}_{\\text{\\em int}}$ such that $dr/ds\n= 0$ one has $d^2r/ds^2 <0$. Thus if $\\xi$ starts in ${\\mathcal\nR}_{\\text{\\em int}}$ and is initially directed inwards, in the sense that $dr/ds$ is initially negative, then $\\xi$ will continue inwards until it falls either into a singularity or through an $SO(3)\\times {\\mathbb{R}}$-invariant photon surface other than $S$.\n\nSpherical symmetry: Examples {#ssex}\n============================\n\nThe following are some examples of $SO(3)\\times {\\mathbb{R}}$-invariant and $SO(3)$-invariant photon surfaces in familiar space-times.", "\n\n\\[Schwarzschildex\\]\n\nThe metric of Schwarzschild space-time in single null (radiation) coordinates has the form $${\\bf g} =\n-\\left(1-\\frac{2m}{r}\\right) du^2\n + 2 du dr\n + r^2\n\\left(d\\theta^2 + \\sin^2\\theta d\\phi^2 \\right) . ", "\\label{Schmetric}$$ In this case equation $(\\protect\\ref{photonsphere})$ reduces to $r =\n3m$. The timelike hypersurface $\\{ r=3m\\}$ is thus an $SO(3)\\times {\\mathbb{R}}$-invariant photon surface, or photon sphere, as expected. ", "There are no other $SO(3)\\times {\\mathbb{R}}$-invariant timelike photon surfaces.", "\n\nFor a non-zero cosmological constant $\\Lambda$, the Schwarzschild metric (\\[Schmetric\\]) generalizes to the Schwarzschild-de Sitter metric\n\n$${\\bf g} = -\\left(1-\\frac{2m}{r}+\\frac{\\Lambda r^2}{3}\\right) du^2\n + 2 du dr\n + r^2 \\left(d\\theta^2 + \\sin^2\\theta d\\phi^2 \\right) \\ .", "\n\\label{schdesit}$$\n\nOne finds that equation (\\[photonsphere\\]) reduces to $r=3m$, independent of the value of $\\Lambda$. This is surprising since Schwarzschild and Schwarzschild-de Sitter space-times are not conformally related.", "\n\nThe Schwarzschild interior solution describes a spherically symmetric distribution of perfect fluid of radius $R$, bounded pressure $p$ and constant density $\\rho_0 >0$. The solution is to have a metric of the form (\\[metricform\\]) and is to be matched at $r=R$ to a Schwarzschild vacuum solution in such a way that the pressure is a continuous function of $r$. One thus has $p_1(r)=p_2(r)=:p(r)$ for all $r:0\\leq r<\\infty$, $\\rho\n(r)=\\rho_0$ for all $r:0\\leq r\\leq R$, $\\rho (r)= 0 $ for all $r:\nR <r<\\infty$ and $p(r)=0$ for all $r: R \\leq r<\\infty$. The pressure $p(r)$ for $r:0\\leq r\\leq R$ is to be obtained by an integration of the Tolman-Oppenheimer-Volkoff equation (\\[TOV\\]) subject to the boundary condition $p(R)=0$. This yields $$\\begin{aligned}\nm(r) &= \\frac{\\mbox{\\normalsize $4\\pi$}}{\\mbox{\\normalsize $3$}} \\rho_0 r^3 \\ ,\n& 0\\leq r \\leq R \\ , \\label{mconden} \\\\[2ex]\n{\\rm e}^{\\mu (r)} &=\n\\frac{\\mbox{\\normalsize $(3-u(r))^2$}}{\\mbox{\\normalsize $4u^2(r)$}} \\ ,\n& 0\\leq r \\leq R \\ , \\\\[2ex]\np(r) &= \\frac{\\mbox{\\normalsize $u(r)-1$}}{\\mbox{\\normalsize$ 3-u(r)$}} \\ \\rho_0 \\ ,\n& 0\\leq r \\leq R \\ , \\label{pconden}\\\\\n\\intertext{for}\nu(r) &:= \\left(\\frac{3-8\\pi\\rho_0 r^2}{3-8\\pi\\rho_0\nR^2}\\right)^{\\frac{1}{2}} \\ ,\n& 0\\leq r \\leq R \\ . ", "\\label{udef}\\end{aligned}$$ The spherically symmetric system described by the Schwarzschild interior solution can exist in a state of stable equilibrium iff $m(R)/R < 4/9$ (see in Stephani [@Ste82]). ", "This condition is equivalent to $8 \\pi \\rho_0 R^2 < 8/3$, which implies $p(r)\\geq0$ $\\forall r\\geq 0$, and implies that the absence of a black hole is a general feature of the Schwarzschild interior solution.", "\n\nThe left side of equation (\\[fluidphotonsphere\\]) now assumes the form $$\\label{intSchps}\n1-\\frac{3m(r)}{r}-4\\pi r^2 p(r) = \\left\\{ \\begin{array}{ll}\n1-\\frac{\\mbox{\\normalsize $8\\pi\\rho_0r^2$}}{\\mbox{\\normalsize\n$3-u(r)$}} &: 0< r \\leq R \\ ,\\\\[2ex] 1-\\frac{\\mbox{\\normalsize\n$3m(R)$}}{\\mbox{\\normalsize $r$}} & : r \\geq R \\ . ", "\\end{array}\n\\right.$$ For $m(R)/R <1/3$ one has that (\\[intSchps\\]) is positive for all $r>0$, so there are no timelike photon spheres. ", "For $m(R)/R=1/3$ there is a single timelike photon sphere which lies at the boundary $r=R$ of the matter. ", "For $1/3< m(R)/R<4/9$ there is one timelike photon sphere outside the matter at $r=3m(R)>R$ and one timelike photon sphere inside the matter at $$r= \\left( \\frac{1-3\\pi\\rho_0\nR^2}{\\pi\\rho_0(3-8\\pi\\rho_0R^2)}\\right)^{1/2}\n =\\frac{2R}{3}\n {\\left(\n \\frac{ 1-\\frac{9m\\left(R\\right)}{4R} }\n {\n \\left(1-\\frac{2m\\left(R\\right)}{R}\\right)\n\\frac{m\\left(R\\right)}{R}\n }\n \\right)}^{1/2} <R \\ .$$ For fixed $R$ the radius of the outer photon sphere is a strictly increasing function of $m(R)/R$ whilst the radius of the inner photon sphere is a strictly decreasing function of $m(R)/R$.\n\nThus a Schwarzschild interior solution matched to a Schwarzschild vacuum exterior solution contains no black hole, and contains one timelike photon sphere iff $1/3 = m(R)/R$ and two timelike photon spheres iff $m(R)/R$ lies in the range $1/3 < m(R)/R<4/9$. However for such values of $m(R)/R$ the space-time is unphysical in that the pressure at the center is $p(0)\\geq\n\\rho_0/\\sqrt{3}>\\rho_0/3$. Therefore under the reasonable energy condition $p(r) \\leq \\rho_0/3$ $\\forall r: 0 \\leq r < \\infty$ there are no photon spheres in this example.", "\n\nThe energy condition $0\\leq p(r)\\leq \\rho (r)/3$ $\\forall r \\in\n[0,\\infty )$ is in fact satisfied iff $m(R)/R$ lies in the range $0\\leq m(R)/R \\leq 5/18$. The corresponding space-times (in view of $5/18 <7/24$) satisfy all of conditions (1) to (4) of Theorem \\[nopstheorem\\], except the smoothness of $\\rho (r)$ at $r=R$. Thus considering a smoothed family of solutions approximating the solution above and having it as a strict limit, but each with smooth $\\rho (r)$ at $r=R$, we can apply Theorem \\[nopstheorem\\] to show no photon spheres exist in all the cases discussed in this section where this energy condition is satisfied. ", "On the other hand Proposition \\[nopsprop\\] is directly applicable without smoothing, but only applies to the subset of these cases with $0\\leq m(R)/R\n< 1/4$.\n\n\\[rnex\\]\n\nThe general static spherically symmetric solution to the Einstein-Maxwell equations is the Reissner-Nordstr[ö]{}m solution comprising a metric ${\\bf g}$ and an electromagnetic field $F_{ab}$ given by $$\\begin{aligned}\n{\\bf g} &= -\\left(1-\\frac{2m}{r}+\\frac{e^2}{r^2}\\right) du^2\n + 2du dr\n + r^2 \\left(d\\theta^2 + \\sin^2\\theta d\\phi^2 \\right) \\label{rn} \\\\\nF_{tr}&=-F_{rt} = \\frac{e}{r^2} \\ , \\quad \\text{\\em all other\ncomponents vanishing,}\\end{aligned}$$ where $m$ is the ADM mass and $e$ is the electric charge. ", "We assume $m>0$. There is an event horizon at $r=r_+:=m+\\sqrt{m^2-e^2}$ and a Cauchy horizon at $r=r_-:=m-\\sqrt{m^2-e^2}$. The event horizon exists for $0\\leq\n(e/m)^2\\leq 1$, and the Cauchy horizon exists for $0<(e/m)^2\\leq\n1$. For $(e/m)^2=1$ they both lie at $r=m$. There can be no timelike photon spheres between the event horizon and the Cauchy horizon because the Killing field ${\\bf K}$ is spacelike there. ", "Outside the event horizon the Killing field ${\\bf K}$ is timelike, so every hypersurface of the form $\\{ r=\\text{\\em\nconst.}\\}$ which lies outside the event horizon and satisfies the photon sphere equation (\\[photonsphere\\]) is necessarily a timelike photon sphere.", "\n\nEquation (\\[photonsphere\\]) assumes the form $$r^2 - 3 m r + 2 e^2 =0$$ which has solutions $r_{\\text{\\em ps}}^{\\pm}$ given by $$r_{\\text{\\em ps}}^{\\pm}/m = \\frac{3 {\\pm}\\sqrt{9-8(e/m)^2}}{2} \\ .", "\n\\label{rnphotonsphere}$$ The hypersurface $S^+ := \\{ r=r_{\\text{\\em ps}}^+\\}$ exists for $0\\leq (e/m)^2\\leq 9/8$ and lies outside the event horizon and is therefore a timelike photon sphere. ", "The hypersurface $S^- :=\\{\nr=r_{\\text{\\em ps}}^-\\}$ exists for $0< (e/m)^2\\leq 9/8$ but lies outside the event horizon only for $1< (e/m)^2 \\leq 9/8$, and so is a timelike photon sphere only then. ", "The hypersurfaces $S^+$ and $S^-$ coincide for $(e/m)^2=9/8$. The Cauchy horizon and event horizon are always null photon spheres.", "\n\nFor $0\\leq (e/m)^2 \\leq 1$ the curvature singularity at $r=0$ is locally naked but hidden behind an event horizon which lies strictly inside the only timelike photon sphere. ", "For $1<(e/m)^2$ the singularity at $r=0$ is globally naked and is surrounded by two timelike photon spheres in the case $1<(e/m)^2 < 9/8$, one timelike photon sphere in the case $(e/m)^2=9/8$ and by no photon spheres, either timelike or null, in the case $(e/m)^2> 9/8$ (see Fig.", " \\[rnfigure\\]).", "\n\n![", "The radii of the event horizon, Cauchy horizon and photon spheres for Reissner-Nordstr[ö]{}m space-time.[]{data-label=\"rnfigure\"}](fig2.eps){width=\"4.0in\"}\n\nThe most general static spherically symmetric solution to the Einstein massless scalar field equations for a scalar field $\\Phi$ satisfying $\\square \\Phi =0$ was obtained by Janis, Newman and Winicour [@JNW]. ", "The Ricci tensor has the form $R_{ab}=8\\pi \\Phi_{;a}\\Phi_{;b}$. The solution is known [@Vir97] to be expressible in the form $$\\begin{aligned}\n {\\bf g} &= -\\left(1-\\frac{b}{r}\\right)^{\\nu}\ndt^2\n +\\left(1-\\frac{b}{r}\\right)^{-\\nu} dr^2\n + \\left(1-\\frac{b}{r}\\right)^{1-\\nu} r^2 \\left(d\\theta^2\n +\\sin^2\\theta \\ d\\phi^2\\right) \\\\\n\\Phi &= \\frac{q}{b \\sqrt{4\\pi}} \\ln \\left(1-\\frac{b}{r}\\right)\n\\label{jnwle}\\end{aligned}$$ for $r: b<r<\\infty$ where the constants $b$, $\\nu$ are related to the ADM mass $m$ and scalar charge $q$ by $$\\nu = \\frac{2m}{b}, \\quad b = 2 \\sqrt{m^2+q^2}\\ .$$ We assume $b>0$. There is a curvature singularity at $r=b$. In order to obtain $m \\geq 0$ one must assume $0\\leq \\nu \\leq 1$. For $q=0$ the solution reduces to the Schwarzschild solution.", "\n\nSince all hypersurfaces of the form $\\{ r=\\text{\\em const.}\\}$ are timelike, one has from the photon sphere equation $(\\protect\\ref{photonsphere})$ that the only timelike photon sphere is at $$r= \\frac{b \\left(2\\nu +1\\right)}{2} \\ ,\n\\label{jnwps}$$ which exists only for $\\nu : \\frac{1}{2} < \\nu \\leq 1$, i.e. for $0\\leq q^2<3m^2$. For $\\frac{1}{2} < \\nu \\leq 1$ it is known [@Viretal98] that a photon coming from infinity is deflected through an unboundedly large angle, i.e. the photon passes increasingly many times around the singularity as the closest distance of approach tends to the right side of $(\\protect\\ref{jnwps})$.\n\nA static spherically symmetric space-time with a charged dilaton field was obtained by Horne & Horowitz [@HH92]. ", "It comprises a metric ${\\bf g}$, a dilaton field $\\Phi$ and an electromagnetic field $F_{ab}$ given by $$\\begin{aligned}\n{\\bf g} &= -\\left(1-\\frac{r_{+}}{r}\\right)\n\\left(1-\\frac{r_{-}}{r}\\right)^{\\omega} dt^2\n + \\left(1-\\frac{r_{+}}{r}\\right)^{-1}\n \\left(1-\\frac{r_{-}}{r}\\right)^{-\\omega} dr^2 \\nonumber \\\\\n &\\hspace*{18em} + \\left(1-\\frac{r_{-}}{r}\\right)^{1-\\omega} r^2 d\\Omega^2\n\\label{cdmetric}\\\\ {\\rm e}^{2\\Phi} &=\n\\left(1-\\frac{r_{-}}{r}\\right)^{(1-\\omega)/\\beta} \\\\\nF_{tr}&=-F_{rt} = \\frac{e}{r^2} \\ , \\quad \\text{\\em all other\ncomponents vanishing,} \\label{Fcd}\\end{aligned}$$ where $r_{+}$ and $r_{-}$ are related to the ADM mass $m$ and electric charge $e$ by $$\\begin{aligned}\nr_{+} + \\omega r_{-}&= 2m \\label{rprm1} \\\\ r_{+} r_{-} &= e^2\n(1+\\beta^2) \\label{rprm2}\\end{aligned}$$ and $\\beta$ is a free parameter which controls the coupling strength between the dilaton and Maxwell fields, with $\\omega$ defined in terms of $\\beta^2$ by $$\\omega := \\frac{1-{\\beta}^2}{1+{\\beta}^2} \\ . ", "\\label{omega}$$ We assume $m>0$.\n\nFor $\\beta=0$ the solution reduces to the Reissner-Nordstr[ö]{}m solution considered in Example \\[rnex\\]. ", "For $\\beta =0$ and $e=0$ the solution reduces to the Schwarzschild solution. ", "The solution also reduces to the Schwarzschild solution for $e=r_-=0$ and arbitrary $\\beta$. Here we shall consider the case $\\beta^2 =\n1$. In this case one has $(r_+,r_-)=(2m,e^2/m)$. There is an event horizon at $r = r_+=2m$ and a curvature singularity at $r= r_- =\ne^2/m$. For $0\\leq (e/m)^2<2$ the singularity at $r= r_-$ lies inside a black hole whilst for $(e/m)^2 > 2$ it is globally naked.", "\n\nFor $\\beta^2=1$ the photon sphere equation (\\[photonsphere\\]) reduces to $$r_{\\text{\\em ps}}^{\\pm}/m = \\frac{(6+(e/m)^2){\\pm}\\sqrt{36+(e/m)^4 -\n20(e/m)^2}}{4} \\ .$$ For $0\\leq (e/m)^2<2$ one has $r_{\\text{\\em ps}}^- \\leq r_- < r_+\n< r_{\\text{\\em ps}}^+$ so there is a single timelike photon sphere. ", "For $(e/m)^2=2$ one has $r_{\\text{\\em ps}}^- = r_- = r_+ =\nr_{\\text{\\em ps}}^+$ so there are no timelike photon spheres. ", "For $2<(e/m)^2<18$ both $r_{\\text{\\em ps}}^+$ and $r_{\\text{\\em\nps}}^-$ are complex so there are no timelike photon spheres. ", "For $(e/m)^2\\geq 18$ one has $r_{\\text{\\em ps}}^- \\leq r_{\\text{\\em\nps}}^+ < r_-$ so there are again no timelike photon spheres. ", "Thus in the black hole case $0\\leq (e/m)^2<2$ there is a single timelike photon sphere, whilst in the naked singularity case $(e/m)^2 > 2$ there are no timelike photon spheres. (", "See Fig.", " \\[ghsfig\\].)", "\n\n![", "The radii of the photon sphere, event horizon and curvature singularity are plotted against the electric charge for the charged dilaton solution.[]{data-label=\"ghsfig\"}](fig3.eps){width=\"4.0in\"}\n\n\\[Vaidyaex\\]\n\nThe Vaidya null dust collapse model is a non-static, spherically symmetric space-time with a metric which, in terms of single null (radiation) coordinates $(u,r,\\theta ,\\phi )$, assumes the form $${\\bf g} = -\\left(1-\\frac{2m(u)}{r}\\right)du^2 +2dudr +\nr^2(d\\theta^2 +\\sin^2 \\theta d\\phi^2 ) \\label{Vmetric}$$ where $m(u)$ is a freely specifiable function of $u$. Setting $x^0:=u$, $x^1:=r$ in (\\[x12x0\\]) one obtains $$\\begin{aligned}\n\\frac{d^2r}{du^2} &= \\frac{1}{r}\\left(\ng_{uu}+\\frac{dr}{du}\\right) \\left( g_{uu}+2\\frac{dr}{du}\\right)\n-\\smallfrac{3}{2}\\frac{dr}{du}\\partial_rg_{uu}\n-\\smallfrac{1}{2}\\left( g_{uu}\\partial_rg_{uu} +\\partial_ug_{uu}\\right)\\\\\n&=\\frac{1}{r}\\left\\{ \\left( 1-\\frac{3m(u)}{r}\\right) \\left( 1\n-\\frac{2m(u)}{r}-3\\frac{dr}{du}\\right) - \\frac{dm(u)}{du}\n+2\\left( \\frac{dr}{du}\\right)^2 \\right\\} \\ . ", "\\label{r2uV}\\end{aligned}$$ This is the evolution equation for a spherically symmetric photon surface of the Vaidya collapse metric (\\[Vmetric\\]).", "\n\nConsider the special case $$m(u) = \\left\\{ \\begin{array}{ll} 0&: -\\infty < u <0 \\\\[1ex]\n\\lambda u & :0\\leq u \\leq u_1 \\\\[1ex] m_1:= \\lambda u_1 &\n:u_1<u<\\infty\n\\end{array} \\right.$$ for given constants $\\lambda >0$, $u_1>0$. For $u<0$ the space-time is locally Minkowskian, for $u:0\\leq u \\leq u_1$ there is inward falling null dust, and for $u>u_1$ the space-time is locally isometric to Schwarzschild space-time with ADM mass $m_1>0$. It is well-known there is a curvature singularity at $r=0$ and that for $\\lambda : 0<\\lambda \\leq \\frac{1}{16}$ the part of this singularity at $u=0$ is locally naked.", "\n\n![", "The backwards evolution of the $r=3m_1$ Schwarzschild photon surface through collapsing Vaidya null dust. ", "The space-time coordinates of the evolved surface are plotted for $m(u)=u /16$ (above) and $m(u)=u/32$ (below) for various values of the null time $u_1>0$ of the junction between the null dust and Schwarzschild regions. ", "In each case the evolved photon surface fails to intersect the Minkowskian region $u<0$.[]{data-label=\"vaidyagraphs\"}](fig4a.eps \"fig:\"){width=\"4.0in\"}\\\n![", "The backwards evolution of the $r=3m_1$ Schwarzschild photon surface through collapsing Vaidya null dust. ", "The space-time coordinates of the evolved surface are plotted for $m(u)=u /16$ (above) and $m(u)=u/32$ (below) for various values of the null time $u_1>0$ of the junction between the null dust and Schwarzschild regions. ", "In each case the evolved photon surface fails to intersect the Minkowskian region $u<0$.[]{data-label=\"vaidyagraphs\"}](fig4b.eps \"fig:\"){width=\"4.0in\"}\n\n![", "The conformal diagram of the Vaidya null dust collapse model showing the photon surface $S$ arising from the backwards evolution of the Schwarzschild photon sphere. ", "Any partial Cauchy surface $\\mathscr{H}$ which extends to spatial infinity is cut into two components by $S$.[]{data-label=\"pendiag\"}](fig5.eps){width=\"4.0in\"}\n\nFix $\\lambda : 0<\\lambda \\leq \\frac{1}{16}$. For $u>u_1$ equation (\\[r2uV\\]) gives, as expected, that there is a photon surface at $r=3m_1$. We seek to evolve this photon surface backwards in time, though the in-falling null dust, to obtain a maximally extended photon surface $S$. The boundary conditions are $$\\left. ", "\\begin{array}{c} r=3m_1\\\\[1ex]\n\\frac{\\mbox{\\normalsize $dr$}}{\\mbox{\\normalsize $du$}}=0\n\\end{array} \\right\\} \\quad \\text{at $u = u_1$} \\ .$$ The results are shown in Fig.", " \\[vaidyagraphs\\] for $\\lambda =1/16$ and $\\lambda = 1/32$ for selected values of $u_1$. One sees that in all cases $S$ tends in the past direction to a null hypersurface of the form $\\{ u=\\text{\\em const.}\\}$. The conformal diagram must therefore be of the form sketched in Fig.", " \\[pendiag\\].", "\n\nIt is evident from Fig.", " \\[pendiag\\] that the naked central singularity is enclosed within the photon surface $S$ in the sense that any partial Cauchy surface $\\mathscr{H}$ extending to spatial infinity must intersect $S$ in a 2-sphere. ", "The physical significance of this may warrant further investigation.", "\n\nConcluding remarks\n==================\n\nThe definition of a photon surface given in Section \\[photonsurfacesection\\] is valid in an arbitrary space-time. ", "However the result that a photon surface must have a second fundamental form which is pure trace indicates that a space-time must be specialized in some respect if it is to contain any photon surfaces. ", "For spherically symmetric space-times there are always photon surfaces that respect the spherical symmetry. ", "For space-times that are not spherically symmetric, the definitions of a photon surface and $G$-invariant photon surface may seem too restrictive. ", "The problem is that, in general, one may not have orbiting null geodesics at a fixed radius. ", "In Kerr space-time for example, although there are orbiting null geodesics in the equatorial plane, those null geodesics which move in the direction of rotation do so at a different radius than those which move in the opposite direction. ", "But it seems implausible that a concept which is physically important in the case of exact spherical symmetry should become invalid when even a small amount of angular momentum is introduced. ", "A non-trivial generalization of the concepts of photon surface and $G$-invariant photon surface, at least to axially symmetric space-times, is thus required.", "\n\nAcknowledgements {#acknowledgements .unnumbered}\n================\n\nThis research was supported by the NFR of Sweden and NRF of South Africa.", "\n\n[VE99b]{} C. Darwin, Proc.", "  Roy.", "  Soc.", "  [**249**]{}, 180 (1958). ", "C. Darwin, Proc.", "  Roy.", "  Soc.", "  [**263**]{}, 39 (1961). ", "K. S. Virbhadra and G. F. R. Ellis, [*Schwarzschild Black Hole Lensing*]{}, astro-ph/9904193. ", "K. S. Virbhadra and G. F. R. Ellis, [*Gravitational Lensing by Naked Singularities*]{}, Phys.", " Rev. D. To be submitted. ", "S. W. Hawking and G. F. R. Ellis, [*The Large Scale Structure of Space-Time*]{} (Cambridge University Press, Cambridge, 1973). ", "B. Carter, Phys.", " Rev. [**141**]{}, 1242 (1966). ", "R. H. Boyer, Proc.", " Roy.", " Soc.", " A [**311**]{}, 245 (1969). ", "H. Stephani, [*General Relativity. ", "An Introduction to the Theory of the Gravitational Field*]{} (Cambridge University Press, Cambridge 1982), p.222. ", "A. I. Janis, E. T. Newman and J. Winicour, Phys.", " Rev. Lett., ", "878 (1968). ", "K. S. Virbhadra, Int.", " J. Mod.", "  Phys.", " A [**12**]{}, 4831 (1997). ", "K. S. Virbhadra, D. Narasimha, and S. M. Chitre, Astron.", " & Astrophys.", " [**337**]{}, 1 (1998). ", "J. H. Horne and G. T. Horowitz, Phys.", " Rev. D [**46**]{}, 1340 (1992).", "\n\n[^1]: e-mail: [clarissa@abel.math.umu.se]{}\n\n[^2]: e-mail: [shwetket@maths.uct.ac.za]{}\n\n[^3]: e-mail: [ellis@maths.uct.ac.za]{}\n" ]

{ "pile_set_name": "ArXiv" }

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[ "Middlebury College\n\nInnovative Users Group – a conference report\n\nThe annual Innovative Users Group conference was held in San Francisco April 23-26. ", "Three from Middlebury attended. ", "Here are some of the highlights from my perspective.", "\n\nNew CEO: In the last year or two, Innovative Interfaces, Inc. (the vendor of our “Integrated Library System”) was bought by a couple of private equity firms. ", "The new CEO, Kim Massana, who took the helm last August, opened the conference with a presentation that this reporter found surprisingly candid and mildly encouraging. ", "Among other things, he emphasized that Innovative is investing in staffing – they have hired 20 since last Fall and will add another 40 by the end of 2013 – and international outreach, opening offices and implementing library systems in China, many Middle Eastern and African countries, and Central and South America. ", "He spoke openly (and emphasized that “The New Innovative” strives to be more open), acknowledging problems with previous product roll-outs and saying they should have done better. ", "He also pointed out their new model of customer service – each library will be assigned a Library Relations Manager and communication of all kinds should go through the LRM.", "\n\nKeynote speaker:Garry Golden, a trained futurist (yes that’s his real name and real occupation – you can’t make this stuff up), spoke about some of the trends he sees that will impact libraries in the next 3-5 years. ", "One of his first points is that libraries have been communicating their primary value as “Access to Collections.” ", "In the near future, he suggests that may evolve to “Mastery of Learning.” ", "He described the learning environment over the past centuries as moving from the Era of Apprenticeship to, with the help of books and industrial work, the Era of Institutions (schools) and now, with the Web and the knowledge economy, it is becoming the Era of the Learner, as individuals develop self-directed curricula and “training.” ", "He described the Web as changing from purely informational to more social and it is now becoming “a platform for managing our lives and personal behavior change.” ", "Where the focus was formerly on access (“is it online or offline?”), ", "the focus is rapidly changing to outcomes (“is it software-guided?”) ", "He described adaptive learning platforms that actively respond to how the learner is learning, and suggested that “libraries need to get ahead of the adaptive” notion.", "\n\nConference sessions I attended focused on:\n\nCollection Development: One session focused on Decision Center, a new III product that will launch in June. ", "The general idea is that circulation data from item records and payment information from order records is uploaded nightly to a Postgres server that III hosts, enabling web-based querying using canned reports. ", "It will greatly simplify extracting data to help with data-driven decision making in budgeting, purchasing, and weeding. ", "The product manager is a former Collection Development librarian at a major public library system. ", "III hired her about six months ago. ", "Another presentation described an exhaustive weeding project. ", "Three other sessions were presentations about what data to extract from Millennium for various CollDev tasks, how best to get that data, and how to analyze it. ", "Let’s just say that Excel is a Millennium user’s best friend.", "\n\nCatalog/System management/administration: I attended multiple sessions focused on loading catalog records, particularly those for eBooks. ", "A particularly helpful presentation described intensive use of MarcEdit for pre-load cleanup. (", "They prefer to minimize the number of load profiles, because MarcEdit is so much easier, and it’s so nice to have streamlined load profiles.) ", "Another interesting session described one library’s approach to sharing responsibility for their ILS.", "\n\nBetween formal presentations and open forum discussions, I have a number of “new tools in my toolbox” that I will be putting to work and sharing with colleagues. ", "Additionally, while visiting Innovative’s Library Relations Manager booth, I learned that the New England Innovative Users Group will convene next month at the University of New Hampshire. ", "The last such meeting was apparently over seven years ago.", "\n\nI’ve been an advocate of MarcEdit for a while – I think it would simplify a lot of our tasks (e.g. adding specific fields/text to each bib record in a batch load, etc.) ", "and obviate the need to do that all via load tables." ]

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[ "Q:\n\nSharePoint: How to get a user's last logout or last session's end date/time\n\nhow could I determine the last login date/time of a user on a MOSS 2007 web application? ", "Till now I didn't find this information within the object model. ", "\nI've already thought about requesting the lastLogonTimeStamp form the AD/LDAP but this will be very imprecise. ", "\nAnother idea would be to write some code to store the login date/time in the user information list whenever a user logs in. ", "But till now I'm not really sure how to do this. ", "\nSo, does someone know a better solution?", "\nUPDATE\nAfter doing some tests and more thinking about my problem, I realized that in fact I don't need the timestamp of the last login but the timestamp of the last logout respectively of the end of the last session. ", "\nAs there is now way to get the timestamp of the last login via the object model I can imagine that there is also no way to get the end date and time of the last session. ", "\nSo how could I get this information?", "\n\nA:\n\nExtend the User Information List with LastSessionID, LastSessionTime\nAdd a little webcontrol to your master.", "\nThis webcontrol updates User Information List if the LastSessionID differs. ", "And adds the time.", "\nOfcourse on Site Collection RootWeb.", "\n\n" ]

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[ "On a muggy evening last summer, unit owners from the Five Condos tower in downtown Toronto gathered at the InterContinental Hotel for the meeting that would elect from among them five directors to oversee over their new building's $2.5-million budget.", "\n\nThree of the elected candidates, Darryl McGregor, Ray Blanchard and George Laczko, sat separately, not acknowledging that they knew one another. ", "They in fact represented the same unit, No. ", "1306.", "\n\n\"They never said, 'We're three hombres together running as a team to take the majority.' ", "They didn't act like they knew each other. ", "They didn't announce which apartment they owned,\" a defeated candidate, the retired brewing executive Richard Scully, recalled.", "\n\nStory continues below advertisement\n\nInvestigation: Inside the flipping frenzy at Toronto's X2 condo\n\nWithin weeks, the results were challenged and court claims filed.", "\n\nIt was part of a series of fierce battles punctuated by allegations of voting irregularities that have raised the spectre of a concerted attempt to seize control of Toronto condo boards and their multimillion dollar budgets.", "\n\nOne of the consequences of Toronto's condo boom has been the creation of hundreds of mini-governments run by elected directors. ", "These boards collect fees from unit owners and sign contracts for property management, security, cleaning and repairs.", "\n\nBudgets in some buildings in Toronto run as high as $3-million annually.", "\n\nCourt files, condo documents and interviews show that Mr. McGregor or Mr. Blanchard or people linked to them have been involved in elections in at least six different condo complexes in recent years.", "\n\nConflicts at condo boards aren't unusual, but the number of boards in which these individuals are involved and the trail of disputed elections have raised eyebrows.", "\n\nStory continues below advertisement\n\nMr. Blanchard says he is self-employed in the financial, restaurant and real estate industries, and is a cost-conscious investor who own several condos.", "\n\nMr. McGregor is the only listed officer at Perfect Clarity, a company that says on its website that it is one of Canada's largest energy procurement firms.", "\n\nReached by The Globe and Mail, Mr. McGregor said that condo election disputes are common and that \"I am flattered that I've became a source of adulation but I don't have anything to say.\"", "\n\nHe referred queries to his lawyer, Brian Horlick, who also acts for Mr. Blanchard. ", "Mr. Horlick did not respond to several phone calls and e-mails.", "\n\nMr. Blanchard and Mr. Laczko also did not respond to e-mailed questions and could not be reached by phone.", "\n\nReaction to their campaign has ranged from bafflement to outrage.", "\n\nStory continues below advertisement\n\n\"They're fighting hard to be on boards and that should raise a big question: Why? ", "I'm on one board and God, it's work. ", "Why would I want to be on a board in a building I'm not even living at?\" ", "Ray Chepesiuk, a unit owner at Icon I condos, said in an interview.", "\n\nFive Condos\n\nAt Five Condos, the acrimony started after Mr. McGregor acquired unit 1306 in June, 2016. ", "Property records only mention Mr. McGregor, but Mr. Blanchard said in a court affidavit that he, Mr. McGregor and Mr. Laczko co-own the unit.", "\n\nThe trio was elected to the board at the July 27 turnover meeting, the gathering at which control of a new building's corporation is handed to the unit owners. ", "However, a lawyer for the condo's developer later raised concerns because 34 proxy ballots didn't actually name specific candidates.", "\n\nAnother vote was ordered, but the three men got a court order postponing it to October. ", "Meanwhile, the interim board in which they held a majority voted in September to terminate the contract of the property management firm, FirstService Residential.", "\n\nFirstService said it was notified by e-mail at 9:40 p.m. on a Friday. ", "By 10 p.m., the office locks had been changed.", "\n\nStory continues below advertisement\n\nFirstService is now suing for $600,000 in damages, saying in its court claim that the directors \"acted deliberately and maliciously in pursuant of their own personal agendas.\"", "\n\nL Tower condos\n\nIt was not the first time that FirstService had crossed paths with Mr. Blanchard, Mr. McGregor and Mr. Laczko. ", "In 2015, the three were elected to the board at L Tower condos, a high-rise in the St. Lawrence district.", "\n\nThey then dismissed FirstService as the property manager, to be replaced by \"a lower-cost alternative,\" the Blanchard affidavit said.", "\n\nThe Element condos\n\nAt The Element condos, in the Entertainment District, Mr. Blanchard was named to the board on Sept. 14, 2016, despite the fact that he didn't own or reside there.", "\n\nStory continues below advertisement\n\nThe director who nominated him was Kaive Wong, a realtor who also served on the L Tower condo board with Mr. Blanchard and Mr. McGregor.", "\n\nMr. Wong said it was necessary to meet quorum and keep the board functioning.", "\n\n\"Ray Blanchard was appointed given his previous board experience and given that no other members of the ownership chose to run in the last election,\" Mr. Wong told The Globe in an e-mail. ", "He also denied being part of a group trying to win control of condo boards, saying he seeks board seats as a way to monitor his investments.", "\n\nMr. Blanchard then ran for election at the Dec. 14, 2016, annual general meeting. ", "Scrutineers' documents show he received 99 votes, all of them from proxies.", "\n\nIntrigued by the high number of proxies, some unit owners later asked to see them, but they were told that a flood had damaged them.", "\n\nIcon I condos\n\nStory continues below advertisement\n\nA week before Mr. Blanchard's election at The Element, Mr. McGregor was involved in another vote, at a nearby building, the Icon I condos. ", "On Dec. 2, 2016, he purchased a unit with his spouse, Liliane Vieira, financed with a mortgage at the high rate of 8 per cent.", "\n\nThe transaction took place five days before the building's annual assembly. ", "At the meeting, Mr. McGregor showed up with proxies supporting him and Ms. Vieira, according to a statement of claim filed this spring by the building's corporation. ", "Mr. Wong was also a candidate for the board, but was defeated.", "\n\nMs. Vieira withdrew from contention, but Mr. McGregor was elected.", "\n\nThe corporation now alleges the proxies had forged signatures. \"", "Without the invalid forged proxies, McGregor would not have been elected,\" the court claim said.", "\n\nMr. McGregor denies using tampered proxies and has filed his own court claim.", "\n\nCharlie Condos\n\nIn April, 2013, Mr. McGregor co-purchased a unit at the Charlie Condos, in the Entertainment District. ", "Mr. Blanchard and his spouse at the time, Celina, also bought a unit in the same building.", "\n\nMr. Blanchard and his wife ran for the board at the turnover meeting but weren't elected. ", "Mr. McGregor won a seat on the board.", "\n\nIn early 2016, an election for a board seat was won by a man named Tom Meta, who worked at Mr. Wong's brokerage. ", "But questions about the voting were raised by a condo resident who had signed a proxy and then decided to attend the meeting. ", "When he asked for his proxy back, he discovered there were two such ballots in his name. ", "Mr. Meta chose not to take his seat.", "\n\n\"Based on several of the owners concerns (myself included) that were raised at last night's AGM, specifically surrounding the integrity of the voting process, proxies etc., ", "and the perception of an unfair election, I feel that I have no choice in the matter,\" he said in his resignation e-mail.", "\n\nA building with a January, 2017, turnover\n\nAccording to a recent briefing document shared by two Ontario condo-law specialists that The Globe and Mail obtained, three members of a slate ran for the board of a building that held its turnover assembly in January, 2017.", "\n\nThe document said the meeting was cancelled because several proxies appeared forged and members of the slate acted in an aggressive manner. \"", "They were told that they were trespassing and that if they did not leave the premises the police would be called.\"", "\n\nThe names of the building and of the slate's members were redacted from the document, but it said they were criticized at another condo election for submitting 34 incomplete proxies and were involved in several litigations – an apparent reference to events at Five Condos.", "\n\nImperial Plaza condos\n\nThe turnover meeting for the newly renovated Imperial Plaza condos took place on March 29. ", "The property manager, FirstService, hired a company to conduct its proxy balloting through electronic voting.", "\n\nAccording to Audrey Loeb, a lawyer representing the condo's corporation, one of the candidates was a woman who identified herself as Lily Marques-Viera, a name that appears very similar to that of Mr. McGregor's spouse. ", "She was defeated.", "\n\nOn the website of a Brazilian law firm, a Liliane Vieira is identified as a lawyer who was once \"legal co-ordinator\" for Perfect Clarity. ", "The firm lists the Imperial Plaza as one of its addresses. ", "She did not reply to an e-mail requesting comments.", "\n\n\"Where are you going with this? … ", "Why is that an issue? ", "I mean, people run for condos all the time,\" Mr. McGregor said when asked about his spouse and the Imperial Plaza election.", "\n\nWhile he did not want to comment further, his involvement in condo elections is now part of two separate pieces of litigations that remain unresolved in Ontario Superior Court." ]

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[ "The fundamentals of playing on a slot machine, in a bricks and mortar casino, are If you play offline there is no guarantee if a machine will be free, this key. ", "Looking for free casino games to play offline? ", "Click This Link: mindcasino-best.xyz Enable Jungle Wild. ", "Slot Machine Free Games Online 2 Offline Casino Games Examples. ", "2 Offline Casino Games Examples win for x games gold slot machine free play queen of." ]

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[ "Large-scale in-vivo Caucasian facial soft tissue thickness database for craniofacial reconstruction.", "\nA large-scale study of facial soft tissue depths of Caucasian adults was conducted. ", "Over a 2-years period, 967 Caucasian subjects of both sexes, varying age and varying body mass index (BMI) were studied. ", "A user-friendly and mobile ultrasound-based system was used to measure, in about 20min per subject, the soft tissue thickness at 52 facial landmarks including most of the landmarks used in previous studies. ", "This system was previously validated on repeatability and accuracy [S. De Greef, P. Claes, W. Mollemans, M. Loubele, D. Vandermeulen, P. Suetens, G. Willems, Semi-automated ultrasound facial soft tissue depth registration: method and validation. ", "J. Forensic Sci. ", "50 (2005)]. ", "The data of 510 women and 457 men were analyzed in order to update facial soft tissue depth charts of the contemporary Caucasian adult. ", "Tables with the average thickness values for each landmark as well as the standard deviation and range, tabulated according to gender, age and BMI are reported. ", "In addition, for each landmark and for both sexes separately, a multiple linear regression of thickness versus age and BMI is calculated. ", "The lateral asymmetry of the face was analysed on an initial subset of 588 subjects showing negligible differences and thus warranting the unilateral measurements of the remaining subjects. ", "The new dataset was statistically compared to three datasets for the Caucasian adults: the traditional datasets of Rhine and Moore [J.S. Rhine, C.E. Moore, Tables of facial tissue thickness of American Caucasoids in forensic anthropology. ", "Maxwell Museum Technical series 1 (1984)] and Helmer [R. Helmer, Schädelidentifizierung durch elektronische bildmischung, Kriminalistik Verlag GmbH, Heidelberg, 1984] together with the most recent in vivo study by Manhein et al. [", "M.H. Manhein, G.A. Listi, R.E. Barsley, R. Musselman, N.E. Barrow, D.H. Ubelbaker, In vivo facial tissue depth measurements for children and adults. ", "J. Forensic Sci. ", "45 (2000) 48-60]. ", "The large-scale database presented in this paper offers a denser sampling of the facial soft tissue depths of a more representative subset of the actual Caucasian population over the different age and body posture subcategories. ", "This database can be used as an updated chart for manual and computer-based craniofacial approximation and allows more refined analyses of the possible factors affecting facial soft tissue depth." ]

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[ "During the big Star Trek: Discovery panel at Comic-Con this weekend, producer Alex Kurtzman revealed a major aspect of Season 3 that fans might not have expected. ", "Season 3 “will take place 1,000 years in the future” after the end of Season 2. ", "He went on to say that that is “the furthest that any Star Trek series has gone before.”", "\n\nThat’s a huge leap, and it’s a fascinating choice to make to continue this Star Trek journey! ", "He went on to tease that “there will be things you recognize and don’t recognize.” ", "In case you don’t remember, at the end of Season 2, Discovery headed into a time warp, and when they come out of it, Michael Burnham and her crew will be separated, and it won’t be in the same place.", "\n\nKurtzman went on to say, “they have big problems.” ", "Burnham actress Sonequa Martin-Green added, “We are not in Taralesium.” ", "Kurtzman went on to say that Burnham “goes through a lot of changes,” and she bears the responsibility of taking the Discovery crew through the wormhole. ", "Kurtzman also teased that the new Captain of Discovery will be revealed in Season 3.", "\n\nWhen talking about the creation process of the series the producer said, “I like to lead every conversation about how we create Star Trek with that we filter it through Gene Roddenberry’s vision off optimism… We get to honor canon, but we get to shake up everything.” ", "He then added, “We’re not erasing anything.”", "\n\nIt was also announced that David Ajala has joined the cast of Season 3 as a new character named Book. ", "Book has “a natural charisma and devil-may-care attitude that tends to get him into trouble as often as it gets him out.” ", "We can also expect new characters to be introduced.", "\n\nWe don’t know when Season 3 will debut on CBS All Access yet, but it’ll happen eventually! ", "What do you think of the changes coming to the series?" ]

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[ "(a) Technical Field of the Invention\nThe present invention relates to a moveable holder structure for the foot pedal of a drum, and in particular, to a holder structure having protruded lugs on an urging element formed with a long slot and having a moveable pressing block forming a circular protruded block corresponding to the protruded lugs. ", "The structure allows a rapid combination with the edge of a drum and also reduces the cost of manufacturing.", "\n(b) Description of the Prior Art\nFIGS. ", "1, 2A and 2B show a conventional foot pedal 10 of a drum, and the pedal beats onto the surface of the drum (not shown) by means of a chain. ", "The foot pedal 10 is mounted to the drum edge 40 of the big drum by means of a holding structure. ", "The base seat 11 of the foot pedal 10 is pivotally mounted with a moveable urging element 12 which can move forward and backward. ", "The urging element 12, corresponding to one end of the inner side of the foot pedal 10, is mounted with a locking blot 13, and the other end of the urging element 12 is provided with two corresponding protruded lugs 14 respectively having a pivotal hole 140. ", "There is a pressing block 15 pivotally mounted in between the two protruded lugs 14, and the top of the pressing block 15 is extended with a protruded block 16 having a pivotal hole 160. ", "A rivet 17 mounts in sequence into the protruded lugs 14 and the pivot holes 140, 160 of the pressing lugs 14 and the protruded block 16, and is then rivetted, such that the pressing block 15 is pivotally mounted to the urging element 12. ", "When the user rotates the locking bolt 13 to urge against the base seat 11, the pressing block 15 and the base seat 11 of the other end of the urging element 12 are correspondingly fastened to the drum edge 40.", "\nThis conventional holding structure has the following drawbacks:\n1) In combination of the pressing block 15, the pivotal hole 160 of the protruded block 16 has to be in alignment with the pivotal hole 140 of the protruded lug 14. ", "Next, the rivet 17 passes through the protruded lugs 14 and the pressing block 15 and the end of the rivot 17 is opened to allow the pressing block 15 to pivotally mounted onto the urging element 12. ", "The entire process of combination is complicated. ", "Besides, after rivetting, it is not easy to be dismantled. ", "PA1 2) It requires more materials, time and tools in order to combine the pressing block 15. ", "Thus, the cost of combination is high and the time taken is comparatively longer. ", "PA1 3) The pivotal holes 160, 140 of the protruded block 16 and the protruded lugs 14 are mounted by means of rivet. ", "The size of the pivotal holes 160, 140 and the external diameter of the rivet 17 are of similar size without tolerance. ", "If the pressing block 15 and the drum edge 40 are not in the located at the same level position, the pressing block 15 will press against the drum edge 40 at a single point. ", "Thus, the holding force is affected and the drum edge 40 may be damaged. ", "This will affect the sound output of the drum." ]

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[ "Q:\n\nSlash removed from URL when resolving page after changing site to ssl secure\n\nI recently made one of my websites ssl secure. ", " Since then I have noticed that if I paste a url of one of the pages on the website into a browser url bar, when the page tries to resolve, the url gets mangled and the page is not found. ", " What it always appears to do is remove the slash after the domain and the following directory, so\nwaynecbent.com/html/somefile.html\nbecomes:\nwaynecbent.comhtml/somefile.html\nAt first I thought this was something my browser was doing, but since then I have discovered this occurs on different browsers on different platforms.", "\nI contacted my domain provider (Namecheap) but they said it is a problem with the host.", "\nMy configuration for the site is as follows:\n<VirtualHost *:443>\n ServerName www.waynecbent.com\n DocumentRoot /home/<redacted>/public_html\n SSLEngine on\n SSLCertificateFile \"/home/<redacted>/ssl/<redacted>.crt\"\n SSLCertificateKeyFile \"/home/<redacted>/ssl/<redacted>.pem\"\n SSLCACertificateFile \"/home/<redacted>/ssl/<redacted>_bundle\"\n</VirtualHost>\n<VirtualHost *:443>\n ServerName waynecbent.com\n DocumentRoot /home/<redacted>/public_html\n SSLEngine on\n SSLCertificateFile \"/home/<redacted>/ssl/<redacted>.crt\"\n SSLCertificateKeyFile \"/home/<redacted>/ssl/<redacted>.pem\"\n SSLCACertificateFile \"/home/<redacted>/ssl/<redacted>_bundle\"\n</VirtualHost>\n\nDoes anyone know why this may be?", "\nThanks, Allasso\n\nA:\n\nYour domain registrar should have nothing to do with this issue. ", "They send requests to the domain waynecbent.com to your hoster, which then handles the request. ", "That action occurs correctly I believe based on your http headers.", "\nThis issue is almost certainly caused by a defective mod_rewrite rule, so you have to paste in all your htaccess or apache config rewrite rules to solve the issue.", "\nIf you have no rewrite rules, then your hoster has messed up something with the ssl handling, that would be my last guess however.", "\nA request to the url is 302 redirected to the bad url, which means there's a rewrite going on somewhere on your server, which is ubuntu with apache 2.2.22, so you can see the request hit your server, and was redirected to that non existent url.", "\n\n" ]

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[ "Q:\n\nUML Diagrams. ", "When are they used?", "\n\nSo ok I understand that UML diagrams help for the construction of a program, but when are they used? ", "Are they needed before you start coding? ", "do you need them so you know what you have to code? ", "Or do you use them after you have coded the program?", "\n\nA:\n\nI will take a somewhat different standpoint. ", "\nWith the exception of Sequence Diagrams that are often in the architecture/design phases we don't use UML in its strict sense. ", "I would say it is most useful in academia, when you describe something exact and theoretical. ", "\nIn every day work, any boxes and arrows on a piece of paper will due. ", "Actually a good rule to use is that if you can't explain your design on a single paper drawing it by hand, it is too complicated. ", "\n\nA:\n\nI tend to be somewhat cynical on the subject... and answer that UML diagrams should never be used.", "\nUML diagram tends to be used when you have to communicate whith people that does not really understand programming. ", "The nice graphical drawings makes them more at ease and comfortable but usually as clueless as before. ", "\nIn my experience UML is a big loss of time and tends to take the place of other tools both simpler and more efficient. ", "Pseudo-code is as easy to read as a class diagram (easier, for me) and much easier to type ; use case is less efficient than a good User Story like in scrum or XP ; etc. ", "All diagrams are a bother to maintain alongside code base and documentation. ", "and you can as easily make design errors drawing them than otherwise (and as a bonus when put in UML form, design errors will become much harder to detect and overcome, agreed you probably avoid the most obvious ones when thinking about your drawing).", "\nI believe I lost plenty of time drawing UML diagrams, but I'm still seeking for a case where they gave me any neat benefit.", "\n\nA:\n\nBefore, During and After.", "\nYou use them to describe requirements, intended architecture, software design, implementation and deployment.", "\nEven operational procedures for using the software can be described in UML diagram form.", "\n\n" ]

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[ "Menu\n\nMonthly Archives: April 2015\n\nGreetings everyone!", "\n\nJill and Carly: Botanical Me\n\nI started this Giving Back series because philanthropy is inherently part of my value system. ", "I find it fascinating to learn about how men and women of the Green Beauty community use their platform to help those in need. ", "Today, I want to share the mission of two humble and selfless women, who, in reality, are heroines of the modern day (they just don’t wear capes!). ", "I’m so proud and honored to feature the work of my friends and sisters, two beautiful souls: Jill Hansey and Carly Lodkey, sisters and founders of Botanical Me.", "\n\nTheir brand offers natural, plant-based beauty and body care that heal, inspire and most of all, give back! ", "Botanical Me is a beautiful range of beauty oils, pure essential oils, lip balms, and pulse-point roll-ons. ", "In addition, the brand offers gift items such as chocolate, tea, and honey imported from Africa. ", "Each skincare product leaves your skin protected and nourished, while your spirits are calmed and renewed. ", "Through Botanical Me, Jill and Carly literally save lives: they have a strong partnership with Malaria No More, an organization dedicated to eradicate malaria in the world. ", "The “ME” in Botanical Me actually has a double meaning. ", "First, ME stands for Malaria Eradication, which is connected to their charity work to stop malaria deaths. ", "Then, the “me” is also about a person’s journey to better health and awareness of toxins and chemicals in beauty products.", "\n\nBotanical Me’s range of products.", "\n\nHow it all began…\n\nJill and Carly had already been operating their retail store in San Diego for 8 years before Botanical Me was born. ", "One evening Jill was having a conversation about malaria with her husband, who is a native of Nigeria and a malaria survivor. ", "She had a “light bulb” moment that she and her sister could use their business as a platform to help people.", "\n\nIt is wonderful! ", "We’re honored to be a part of their charity and contribute to their life-saving work. ", "There are so many blessings: a broader world view, greater humility, increased empathy, a feeling of being part of something bigger, meeting other cool people from all walks of life who are also inspired to make a change. ", "Just thinking that something we have done has saved even one child’s life and given a family a healthier tomorrow is beyond words.", "\n\n– Jill & Carly, founders of Botanical Me\n\nWhat is malaria ?", "\n\nCredits: iStock\n\nMalaria is a blood disease caused by a mosquito bite (Plasmodium parasite) and can be transmitted from person to person. ", "It affects the lives of over 200 million people around the world every year.", "\n\nSymptoms: fever, headaches, vomiting, if treatment is not administered, illnesses such as anemia, hypoglycemia and death can occur.", "\n\nCredits: MalariaNoMore.org (logo)\n\nChild with severe malaria symptoms. ", "Credits: Standard-Tribune.com\n\nAccording to MalariaNoMore.org:\n\nMalaria is one of the top 3 killers in the world;\n\nEvery 60 seconds, a child dies of malaria, it means 453 000 children per year, so that’s 1 300 kids who have their lives cut short every day because of a mosquito bite!", "\n\nWhy it also concerns you…\n\nIf you think you’re safe, and therefore think to yourself it isn’t your problem because your country isn’t a malaria risk zone, think again! ", "This matter concerns ALL of us. ", "In 2013, there were an estimated 198 million cases of malaria worldwide, mostly women and children. ", "Although malaria was eliminated from the US in 1951, MNM makes a census of 1500 cases annually caused by returning travelers. ", "Because of what we’ve been shown in the media, we often associate Africa to poverty and death. ", "However, it is a beautiful continent, the second largest one in the world actually. ", "Africa offers such a wide range of natural resources, some of them, such as shea butter, are included in our coveted green beauty products. ", "It’s our duty and responsibility to protect that land and its people.", "\n\nJill in Africa\n\nThere is hope!", "\n\nSo, you know the bad news about malaria, it’s lethal. ", "Now, onto the good news, malaria is not only curable, but it is a preventable disease! ", "MalariaNoMore.org concurs that over the last decade, malaria mortality rates have fallen 58% among children under the age of 5. ", "That’s good, but the goal is to complete eradicate malaria. ", "Jill and Carly often travel to Africa to import natural ingredients and they donate 10% of their profits to Malaria No More. ", "The proceeds directly impact the daily lives of those they seek to help. ", "Here’s how…\n\nMosquito nets prevent from getting bitten at night. ", "Image: Wikipedia\n\nThe funds go towards:\n\nproviding diagnostic tests;\n\nbuying medicine and treatment; did you know that a full course of malaria treatment costs only 1$ and can cure a child in 1 to 3 days?", "\n\nbuying mosquito nets; don’t forget that malaria is caused by a mosquito bite, and the Plasmodium parasite bites at night between 9pm and 5am, so nets are an important prevention tool;\n\ncreating education programs.", "\n\nThe sister duo chose to partner with MNM because this organization has focused strategy and the widespread government, media and pharmaceutical relationships in Africa that are needed.", "\n\nWhy helping Botanical Me is very personal to me…\n\nI’m getting prepped for a femoral venous catheterization, before an apheresis treatment.", "\n\nI was born with a genetic blood disease commonly called Sickle Cell anemia (SCA). ", "Essentially, unlike normal round/oval red blood cells, mine are shaped like crescent moons, semicircular (hence the name “sickle”, a sickle is a tool made with a crescent-shaped blade). ", "Normal red cells travel easily through the blood vessels to take the oxygen to every part of the body. ", "However, my sickled cells get stuck in the blood vessels, which means the oxygen doesn’t get through. ", "This causes a lot of deep chronic pain and it damages my bones, my muscles and my organs. ", "Sickle cell anemia is a disease mostly diagnosed in patients of African descent.", "\n\nSo, what does that have to do with malaria?", "\n\nWhile my illness can be debilitating, it confers me somewhat of a protection against malaria. ", "How? ", "It is very complex. ", "Researchers are still trying to understand the mechanisms that create SCA patients’s resistance against malaria. ", "Let’s just say that my sickled red blood cells are not “healthy” or viable enough for the parasite to implant and lodge itself in my bloodstream.", "\n\nFinal thought…\n\nEvery time I think about Jill and Carly, I am reminded that this life is not about my ego, but that it’s about finding my purpose and answering my higher calling. ", "When they are not are not busy saving lives, the Botanical Me duo is learning more about the wonders of nature. ", "Women like them make the world go round! ", "I urge you to support their brand and their cause, your kindness will save lives. ", "When you purchase a product from the brand, you’re taking care of yourself (at a budget-friendly price, might I add), but more importantly, you are saving a child, a woman or a man’s life. ", "Please give back!", "\n\nUntil next time, take care!", "\n\nAlex xo\n\nTo support MalariaNoMore, click here. ", "Let’s defeat malaria! ", "World Malaria Day is April 25th 2015.", "\n\nNote: all information and statistics on malaria are sourced from MalariaNoMore and CDC." ]

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[ "Q:\n\nCalling constructor with different generic type than class is being created with\n\nI have this problem which I hope is a simple solution to. ", "I have the following class (extract) and I'd like to avoid having to make public myImage(myImage<int> image), public myImage(myImage<float> image), public myImage(myImage<double> image) and possible other variants as well (like bool).", "\nclass myImage<T> where T : struct\n{\n private int width;\n private int height;\n private T[] img;\n\n // constructor: allocate new image\n public myImage(int Width, int Height)\n {\n img = new T[Width*Height];\n width = Width;\n height = Height;\n }\n\n public myImage(myImage<byte> image)\n {\n // allocate space for new\n width = image.", "Width;\n height = image.", "Height;\n img = new T[width * height];\n\n if (typeof(T) == typeof(byte))\n {\n // in and out = same type? ", "use block copy\n Buffer.", "BlockCopy(image.", "Image, 0, img, 0, width * height * Marshal.", "SizeOf(typeof(T)));\n }\n else\n {\n // else copy image element by element\n for (int counter = 0; counter < width * height; counter++)\n img[counter] = (T)Convert.", "ChangeType(image[counter], typeof(T));\n }\n }\n\n public int Width\n { \n get { return width; } \n }\n\n public int Height\n {\n get { return height; }\n }\n\n public T[] Image\n {\n get { return img; }\n }\n\n public Object this[int index]\n {\n get { return img[index]; }\n set { img[index] = (T)Convert.", "ChangeType(value, typeof(T)); }\n }\n}\n\nI'd use it like this:\nmyImage<byte> img = new myImage<byte>(100,200); // create byte image\nmyImage<double> img2 = new myImage<double>(img); // create double-img2 from byte-img\nmyImage<int> img3 = new myImage<int>(img2); // or int-img3 from double-img2\n\nSo, do I have to create methods for byte, int, float, double or can 1 method do it all?", "\n\nA:\n\nYou cannot use a generic argument in the contructor, but you could define a static method like this:\nclass myImage<T> where T : struct {\n\n public static myImage<T> FromImage<X>(myImage<X> image) where X : struct {\n // create the object and return it...\n }\n}\n\nand then call it like\nmyImage<double> img2 = myImage<double>.FromImage<byte>(img);\n\n" ]

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[ "We noticed that you're using an unsupported browser. ", "The TripAdvisor website may not display properly.", "We support the following browsers:Windows: Internet Explorer, Mozilla Firefox, Google Chrome. ", "Mac: Safari.", "\n\nEnchanting waterfront cabin with everything you need for a peaceful and relaxing stay. ", "Landscaped gardens, private path to the Clark Fork River. ", "Sparkling clean and comfortable. ", "Romantic. ", "Pet friendly. ", "Children welcome. ", "Near Sandpoint, Idaho and just a half day&#39;s drive to Glacier National...\n\nImagine yourself at this scenic, waterfront setting with family and friends. ", "Blue ribbon fishing from 1 0f the two overlook decks, preparing lunch indoors while watching your family launch for a tubing adventure down the Clark Fork River - in your own back yard!", "\nEnjoy the riverside fire-pit at...\n\nThis private one bedroom apartment on the second floor of a spacious mountain lodge style house with spectacular views year round is located on the outskirts of Clark Fork, Idaho. ", "Clark Fork is a friendly little town nestled in the mountains of northern Idaho. ", "Close to Lake Ponderay, the Clark...\n\nThis Victorian-style home boasts a total of 5 bedrooms and 2.5 bathrooms. ", "It will sleep up to 13 people, and is in the perfect waterfront location in downtown Sandpoint! ", "Sand Creek is boatable, swimmable, and is part of the Sandpoint landscape. ", "The home was built as a duplex, with an upper and a...\n\nTwo condos wrapped up into one, Blue Beetle 7 &amp; 8 offers the perfect combination for hardcore skiiers looking for comfort and value. ", "This two story condo sleeps up to 9 people, offers a sauna, sunroom with fireplace, kitchen, washer and dryer, easy access to the slopes, and cozy comfort for all....\n\nSunlight streams through the many windows in this clean, comfortable, attractively decorated, , two bath home that is perfect for family vacations. ", "The large fenced backyard and deck complete with a huge willow tree is the perfect setting for a relaxing get away or family barbecue. ", "Or sit out on...\n\nWaterfront luxury at its finest... this new, privately furnished Seasons residence is just 2 blocks from downtown Sandpoint. ", "Features include a spacious 2 bedroom, 2 bath first-floor unit with a walk out lanai near the hot tub for ultimate convenience! ", "Master bedroom features a new Queen-size...\n\nBeautiful Waterfront vacation home located on Oden bay, Lake Pend Oreille. ", "This 3071 sqft home located on 3/4 of an acre land includes 3 bedrooms (2 masters) and 3.5 bathrooms. ", "This immaculately maintained home is very cozy and private with a professionally landscaped yard, rock walls, stone paver...\n\nTotal remodeled condo with One Of A Kind decor at the Seasons! ", "Great 4th floor location at the Seasons at Sandpoint! ", "Large flat screen TVs in living room and bedrooms, sonos music system throughout condo, custom fireplace in living room, and a total remodel to make this the best seasons condo...\n\nThe condo is just feet from the lake with great views, there is a year round heated pool spa workout room. ", "We have a large lobby it is run like a hotel.", "You can walk to the town center in just minutes. ", "WE have a marina there is a extra charge for boat use. ", "The condo is large and very comfortable...\n\nWaterfront vacation home on fabulous Murphy Bay on Lake Pend Oreille, Sandpoint Idaho. ", "Private dock with boat lift, grass area by waters edge, deck along the water, great swimming and great boating. ", "Quick boat ride to Dover Bay and to Downtown Sandpoint.", "\nThis vacation rental home features a...\n\nAbsolutely wonderful vacation home located overlooking Bottle Bay, Lake Pend Oreille with a private dock for our guest across a private road. ", "This home is across a private road from the lake with private access to picnic area and private dock. ", "The dock area is not contiguous with the home. ", "Great...\n\nAmazing Penthouse Residence for the perfect Ski or Summer Vacation!!! ", "This two story Lakeside Penthouse has an open, expansive floor plan and is perfect for any vacation. ", "After an active day skiing, boating, hiking or shopping, recline on the beautiful lanai while watching the sun reflect over the...\n\nLarge, family friendly one level, first floor two bedroom + den and 2 bathroom condo located within an easy walk of Downtown Sandpoint or a quick 15 mile drive to world class skiing at Schweitzer Mountain Ski Resort. ", "Silverwood is 30 minutes away.", "\nEnjoy all the amenities of home including WIFI, a...\n\nWe completely remodeled the condo in 2014 in an industrial, loft style. ", "It is only steps away from beautiful Lake Pend Oreille and one of two pools located in the condo complex. ", "Downtown Sandpoint and it&#39;s unique shopping and restaurants is a 5 minute walk. ", "The condo is perfectly situated for...\n\nThe Point at Sandpoint is where dreams become memories. ", "It&#39;s your own private, luxury retreat. ", "From the moment you enter the massive double wood doors, you&#39;ll feel a part of something magical. ", "Picture two private, wooded acres that open up to a custom home on over 360&#39; of flat, private Pend...\n\nThe fully furnished romantic and charming Guest house with gardens is approximately 1500 square feet and includes a full master bedroom with an attached full bath, and it&#39;s own sliding door out onto the deck overlooking the lake. ", "The parlor room doubles as a second bedroom with a fold out couch....\n\nNice 2 bedroom / 2 bath waterfront condo in Sandpoint. ", "Awesome views and easy walk to downtown Sandpoint. ", "Great pricing on this condo that sleeps up to 6 people! ", "Great value with family amenities, free WiFi, and great location.", "\nFeaturing a king bed in the upper master bedroom, queen bed in the...\n\nSchweitzer/Ullr Lodge is perfect for large family groups, ski teams, wedding parties, or as a multiple family shared unit. ", "Our unit is one of the largest available at Schweitzer/Sandpoint and features:\n4266 ft2 on 4 floors with lofts in four of the suites\n5 Suites with private bathrooms\nSleeps 18...\n\nIf you&#39;ve dreamed of the Quintessential North Idaho Cabin in the Woods , you&#39;re home! ", "This Wonderful A-Frame home is a PERFECT GETAWAY with 1 bedroom and a full bath on the upper floor of the house, dining room with French doors, kitchen with all appliances and condiments, fridge stocked with...\n\nLocated in the beautiful Idaho Club - Private Golf Community just out of Sandpoint. ", "Enjoy the golf course and all that the Sandpoint area has to offer. ", "Custom 5 bedroom home to sleep 10 with hot tub and easy access to North Idaho recreation and Schweitzer Mountain Ski Resort.", "\nIf elegance and...\n\nNewly remodeled home with Lake Pend Oreille waterfront right across the street from the home . ", "This waterfront access is not contiguous with the home. ", "Great location in the Sunnyside Peninsula, near Sandpoint, Schweitzer, hiking, and horseback riding. ", "Private dock with private waterfront just...\n\nWhether you&#39;re planning a family reunion or just hoping to explore Idaho with a group of friends, this spacious Sandpoint rental is the perfect choice. ", "With a private hot tub, outdoor firepit, and even a playset, this family-friendly four-bedroom home promises lots of fun for up to 13 guests!...", "\n\nIdaho Club Presidential Suites! ", "Sleeps up to 15. ", "On the fairway, private mountain setting yet close to Lake Pend Oreille and an easy short drive to Schweitzer Ski Resort. ", "Built for vacation rental luxury, this home offers 4 individual private suites. ", "2 Suites downstairs each have a King bed,...\n\nWith a private hot tub and views of Lake Pend Oreille, Aspen Sky is the perfect home away from home. ", "Recently remodeled, this three-bedroom lakeside lodge promises a memorable vacation for up to eight guests!", "\nWhether you&#39;re looking for a relaxing retreat or outdoor adventures, this rental has it...\n\nThis dog-friendly Sandpoint vacation condo is an amazing rental for all seasons, and offers a luxurious interior, a lakefront view, two seasonal shared swimming pools (open Memorial Day to Labor Day Weekend), and access to the lovely Lake Pend Oreille in Sandpoint, Idaho, and only a short drive...\n\nEnjoy a fabulous retreat in Idaho at this gorgeous lakefront home on Lake Pend Oreille. ", "Offering lake views, a private dock, a luxuriously soaking tub, and dog-friendly accommodations (available for a small nightly fee), up to 10 guests are sure to have a happy time!", "\nSitting on the shoreline on...\n\nWe welcome you to the Lodges at the Idaho Club, in Sandpoint Idaho. ", "This is a magnificent, custom home development just minutes away from a pristine beach on Lake Pend Oreille! ", "The Lodge Homes sit on a perfect, freshly manicured lots with surreal views in a peaceful, natural surrounding.", "\nBuilt on...\n\nThis cozy lakefront Sagle home has a gorgeous deck and a secluded location, making it an ideal vacation spot for anyone looking for rest and relaxation while surrounded with beautiful views.", "\nSituated on Lake Pend Oreille, this home is just three miles from Sagle and only nine miles away from...\n\nBeautiful waterfront private home with lots of privacy, large dock, great boat moorage, and wonderful location for summer and winter stays. ", "Easy boat to the big lake of Lake Pend Oreille and an easy drive to the chairlifts of Schweitzer Mountain Resort.", "\nWaterfront vacation home 5 minutes from...\n\nThis home in downtown Sandpoint is the perfect place for your next vacation, with a large yard, conveniences close by, and nearby beach and ski access.", "\nLocated less than a mile from downtown Sandpoint and near a bike path, you&#39;ll have abundant recreation opportunities as well as a waterfront at...\n\nAre you looking for a great adventure get-away with your friends and family? ", "Or to take that romantic getaway you&#39;ve been dreaming about but without a huge price tag? ", "This lovely dog-friendly house is nestled in the quiet heart of Sandpoint, but still walking distance to all Sandpoint has to offer....\n\nWaterfront Condo in Sandpoint with boat slip! ", "This beautiful, remodeled 2-bedroom, 1-bath condo is the ideal location for a summer getaway. ", "Just a few blocks from downtown Sandpoint and Lake Pend Oreille, this condo is truly the perfect location.", "\nKeep your boat at your private dock/boat slip,...\n\nTake a retreat to Idaho&#39;s Lake Pend Oreille at this beautiful lakefront lodge, with lake views, entertainment, and private beach access for as many as 12 guests!", "\nLocated on the northwest shore of the lake, you&#39;ll enjoy quiet surroundings and quick access to downtown Sandpoint, just an easy drive...\n\nThis delightful one-bedroom rental boasts an unbeatable location less than 100 feet from the shoreline, plus access to a shared pool, a private patio, and terrific views of the water, making it the perfect choice for your Sandpoint getaway.", "\nYou&#39;re just steps away from the shores of Lake Pend...\n\nCedar Cabin overlooking Lake Pend Oreille (on one acre of land), near Sandpoint, Idaho. ", "The cabin has a wrap-around deck with filtered views of the lake. ", "Two bedrooms in the basement with King size beds. ", "Upstairs loft has a Queen bed with plenty of space and mattresses for the kids. ", "Living room has...\n\nHave the mountain-meets-lakeside getaway of your dreams at this Sandpoint vacation rental. ", "Perfect for outdoor enthusiasts and groups of up to eight, this lakefront home features resort amenities and an awesome location on Lake Pend Oreille!", "\nLocated just two miles from downtown Sandpoint and just...\n\nThis spacious lakeview Sagle home has it all. ", "An expansive deck, two bedrooms and a loft, and a beautiful fireplace for cozy nights in mean that all seven to nine guests will have a relaxing and restful stay here.", "\nThis home is secluded yet still just moments away from Lake Pend Oreille and the...\n\nThis downtown Sandpoint gem is a light filled one bedroom 2 bath condo with sleeper sofa! ", "The open plan between the fully stocked kitchen and living room is great for entertaining, with ample floor space to also use a blow up mattress for max occupancy. ", "The comfortable living room includes a...\n\nRelax with a week at our bright new Sandpoint Vacation condo. ", "This 1240 square foot condo was purchased and furnished in the Spring of 2011. ", "We are very excited to use the condo ourselves, as well as to welcome our first guests this summer!", "\nThis two bedroom, two bathroom condo can comfortably...\n\nWonderful lakefront condo in the heart of Sandpoint. ", "1 bedroom with queen bed, 1 full bathroom, sleeper in living room, completely updated and clean! ", "Amazing views of the water, easy access for swimming and boating. ", "Great condo for a family and very economical. ", "Full kitchen, washer and dryer,...\n\nLOCATION * LOCATION * LOCATION!!! ", "This awesome 4 bedroom 4 1/2bath townhouse sleeps 11 people comfortably with private hot tub, ski in/ski out.. It&#39;s the only 4 bedroom townhouse on the mountain where you can ski up to your back door and still be right next to the Schweitzer Village. ", "Each...\n\nExclusive private home on Schweitzer Mountain Resort. ", "Featuring custom &#39;Honka&#39; log construction with beautiful detail work throughout. ", "3+ bedrooms and 3.5 baths make this a retreat perfect for two families looking for a unique ski vacation. ", "Each bedroom has its own full bathroom, complete with...\n\nDiscover this new luxury Seasons residence located on a pristine bay on Lake Pend Oreille. ", "Just two blocks from downtown Sandpoint, this spacious 2 bedroom / 2 bath corner unit has flat screen TVs in every room, all high-end leather furniture, a gas fireplace, and a kitchen that will make any...\n\nBeautiful and Spacious Home of the pristine waters of Pend O&#39;reille. ", "Perfect for entertaining. ", "This 9800 sq. ", "ft.custom home has a separate kids entertainment room attached to the kids bunk room with 2 bunk beds. ", "6 bedrooms with 6 full baths (5 king beds, 1 queen), a movie theater, and three large..." ]

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[ "# JSMS API JAVA CLIENT\n\n[Github](https://github.com/jpush/jsms-api-java-client)\n\n### Overview\n\nThis is a Java version development package of SMS Rest API. ", "It is officially provided by JPush and generally supports the latest API functions.", "\nCorresponding Rest API documentation: http://docs.jiguang.cn/server/rest_api_jsms/\n\n## Installation\n\n### Way of maven\n\nPlace the following dependencies in your project's maven pom.xml.", "\n\n> Slf4j can work with log frames such as logback, log4j, and commons-logging, and can be configured and used according to your needs.", "\n\n```xml\n<dependency>\n    <groupId>cn.jpush.api</groupId>\n <artifactId>jsms-client</artifactId>\n <version>1.2.8</version>\n</dependency>\n<dependency>\n\t<groupId>com.google.code.gson</groupId>\n\t<artifactId>gson</artifactId>\n\t<version>2.3</version>\n</dependency>\n<dependency>\n\t<groupId>org.slf4j</groupId>\n\t<artifactId>slf4j-api</artifactId>\n\t<version>1.7.7</version>\n</dependency>\n<dependency>\n <groupId>cn.jpush.api</groupId>\n <artifactId>jiguang-common</artifactId>\n <version>1.0.8</version>\n</dependency>\n<!-- ", "For log4j -->\n<dependency>\n\t<groupId>org.slf4j</groupId>\n\t<artifactId>slf4j-log4j12</artifactId>\n\t<version>1.7.7</version>\n</dependency>\n<dependency>\n\t<groupId>log4j</groupId>\n\t<artifactId>log4j</artifactId>\n\t<version>1.2.17</version>\n</dependency>\n```\n\n### Way of Jar Package\n\n* [slf4j](http://www.slf4j.org/) / log4j (Logger)\n* [gson](https://code.google.com/p/google-gson/) (Google JSON Utils)\n* [jiguang-common-client](https://github.com/jpush/jiguang-java-client-common)\n* [jsms-client](https://github.com/jpush/jsms-api-java-client/releases/download/jsms-client-1.2.5/jsms-client-1.2.5.zip)\n\nThe slf4j and gson jar packages can be found in the [project libs/ directory](https://github.com/jpush/jsms-api-java-client/tree/master/libs) and can be copied to your project.", "\n" ]

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[ "Neely Township, Butler County, Missouri\n\nNeely Township is one of ten townships in Butler County, Missouri, USA. ", " As of the 2000 census, its population was 1,259.", "\n\nNeely Township was organized in 1871, and named after Obadiah Neely, an early citizen.", "\n\nGeography\nNeely Township covers an area of and contains one incorporated settlement, Neelyville. ", " It contains seven cemeteries: Crab, Harris Ridge, Lutz, Neeleyville, Roberts, Sheely and Sims.", "\n\nThe streams of Big Cane Creek, Cane Creek, Cope Branch, Fox Branch and Gaines Slough run through this township.", "\n\nTransportation\nNeely Township contains one airport or landing strip: Wattle Landing Strip.", "\n\nReferences\n\n USGS Geographic Names Information System (GNIS)\n\nExternal links\n US-Counties.com\n City-Data.com\n\nCategory:Townships in Butler County, Missouri\nCategory:Townships in Missouri" ]

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[ "Q:\n\nRails route only if resource is present\n\nI want to have a rails route that triggers if the given id is present, but falls back to further route matching if not.", "\nSpecifically, I want to have promo codes at the root level of my site. ", " So, you can go to foo.com/save87 or foo.com/xmasspecial, and it'll treat it as a promo code, but if you go to a promo code that's not there (foo.com/badcode), that route will not match and rails will continue down the route list.", "\nIn an ideal world, I'd do something like this in my routes.rb file:\nget '/:promo_id' => 'promos#show, constraints => lambda { Promo.exists?(promo_id) }\n\nI know that the above code, without the constraints, would work as a catch-all for foo.com/*, and would sorta work if I put it as the last line in the routes file. ", " Unfortunately, that would result in foo.com/badcode a 'promocode not found' error, rather than a normal 'route not found' error.", "\nSo, is there a way to accomplish what I'm trying to accomplish? ", " This is in Rails 3, for reference.", "\n\nEdit: To clarify a bit-\n\nI want a wildcard url as described above so that our promocode urls are short and memorable (foo.com/save87 instead of foo.com/promo_codes/save87)\nI'd prefer to have the option of having other routes after this one. ", " I may, at some point, need another wildcard url at the root level- for example, if I want vanity urls for another resource in my system. ", " For example, if I sell a dozen varieties of widgets, I might want foo.com/widget_deluxe, foo.com/widget_extreme, etc in addition to my promo code urls. ", " I'd have to make sure that there's no collision between promo codes and widget varieties, but that's easily handled elsewhere.", "\n\nA:\n\nIn an ideal world, I'd do something like this in my routes.rb file:\n\nNo way. ", "In Rails World, this functionality should go inside controller. ", " \nIn controller you can do something like \ndef show\n if Promo.exists?(promo_id)\n #do something\n else\n raise ActionController::RoutingError.new('Not Found')\n end\nend\n\nUpdate\nWith routes, you can do something like this \nconstraints(lambda { |req| Promo.exists?(req.params[\"promo_id\"]) }) do\n get '/:promo_id' => 'promos#show\nend\n\nPlease keep in mind that this constraints will query the database for every request with a url matching the pattern /:promo_id (e.q. ", "/users, /faq). ", "To avoid unnecessary database queries that decrease your website performance, you should add this rule as far as possible to the end of your routes.rb.", "\n\n" ]

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[ "This invention relates to the preparation of nitrogen-containing, water-soluble polymers prepared from polyamines and a water-soluble piperazine/epihalohydrin prepolymer, and to their use as flocculants.", "\nThe condensation of epihalohydrins with piperazine is one which has been known for many years, and which has been carried out under a wide range of varying conditions. ", "For example, U.K. Pat. ", "Nos. ", "1,448,183 and 992,011 disclose methods in which epichlorohydrin is condensed with piperazine, in the presence of strong base, for example, KOH and NaOH, to produce various insoluble solids.", "\nSimilarly, U.S. Pat. ", "No. ", "2,963,483 describes a method for the preparation of N-glycidylpiperazine, and a product prepared by polymerization thereof. ", "The N-glycidylpiperazine is prepared by treatment of piperazine with epichlorohydrin, to produce an adduct of the formula ##STR1## and subsequent treatment of the adduct with a base, for example sodium hydroxide, potassium hydroxide, sodium or potassium alkoxide, calcium hydroxide, or an amine base, to eliminate HCl and thereby produce N-glycidylpiperazine. ", "The addition of epichlorohydrin, and dehydrohalogenation are carried out at a temperature of from 0.degree. ", "C. to 50.degree. ", "C., and the resulting N-glycidylpiperazine is a crystalline solid, which can be separated, and polymerized by heating to make a rubbery polymer. ", "However, the polymerization of N-glycidylpiperazine is very difficult to control, and in practice it is difficult or impossible to stop the polymerization at a point at which the polymer is not a solid, or at best a gel.", "\nGreat Britain Pat. ", "No. ", "1,416,454 purports to disclose a method for the preparation of a water-soluble polymer by condensation of epichlorohydrin and piperazine, at a mole ratio of approximately 1:1, and in the presence of strong base (NaOH). ", "However, the reaction there disclosed is notoriously difficult to control, and almost invariably results in the production of a solid or gelled product.", "\nEuropean Patent Application No. ", "0,033,104 and corresponding U.S. Pat. ", "No. ", "4,328,142 disclose the preparation of a water-soluble polymeric cross-linking agent for polyamines from epichlorohydrin and piperazine to produce a flocculant. ", "In this method, a complex two-stage reaction is required to produce the desired water-soluble prepolymer, the first stage of which is carried out in the presence of strong base (NaOH), and the result of the first stage is then acidified, before further epichlorohydrin is added at low pH, for the second stage. ", "Control of this reaction is difficult and therefore relatively expensive, because of the complex pH requirements. ", "Furthermore, the overall reaction for the production of the flocculant is a three-stage one, which is complicated to implement on an industrial scale.", "\nIn view of the aforementioned deficiencies of the prior art processes, an improved method for producing water-soluble polymer flocculants which eliminates one or more of such deficiencies would be highly desirable." ]

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[ "Q:\n\nIs Z discrete in its profinite completion?", "\n\nConsider the inclusion $\\phi: \\mathbb{Z} \\to \\hat{\\mathbb{Z}}$ where $\\hat{\\mathbb{Z}} : = \\varprojlim_n\\mathbb{Z}/n\\mathbb{Z}$. Is the subspace topology on $\\mathbb{Z}$ from this inclusion the discrete topology? ", "Is this true for all $G \\to \\hat{G}$?", "\n\nA:\n\nNo, the image of $Z$ is dense in its profinite completion which is a compact group. ", "https://en.wikipedia.org/wiki/Profinite_group#Profinite_completion\nYou can't have an infinite discrete subset in a compact space.", "\n\n" ]

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[ "Vent windows pivotally mounted for opening to an angular relation with the main side window plane are well known in the trade as \"Fisher no draft\" vents.", "\nPower windows having vent elements operating in the same vertical plane as the main window which are first to open and last to close under the operation of power window regulators are also known in the art, as a more recent alternative to the pivoted vent, to provide a relatively small opening for air circulation, venting of cigarette smoke and the like.", "\nSimilar manually operable vents vertically slidable in the plane of the main side window having a latch for engaging ratchet teeth to retain the vent window in a raised or adjusted open position have been contemplated which are subject to certain operating deficiencies, particularly in the raised closed position, due to the possibility of the vent window with its latch dropping slightly in reaching a seated position against the ratchet teeth effective to retain the vent window from lowering. ", "Thus, where the fully raised position of the vent window did not exactly match the seated latch position against the ratchet teeth gravity operating on vent window under normal road vibration could cause the vent window to creep downwardly in reaching full latch engagement resulting in air leakage and wind whistle at the top seal." ]

{ "pile_set_name": "USPTO Backgrounds" }

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[ "Protein phosphatase 2C (PP2C) is an archetype of the PPM Ser/Thr phosphatases, characterized by dependence on divalent magnesium or manganese cofactors, absence of known regulatory proteins, and resistance to all known Ser/Thr phosphatase inhibitors. ", "We have used virtual ligand screening with the AutoDock method and the National Cancer Institute Diversity Set to identify small-molecule inhibitors of PP2Calpha activity at a protein substrate. ", "These inhibitors are active in the micromolar range… CONTINUE READING" ]

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[ "Gulshan Town\n\nGulshan Town () is one of the towns in Karachi, Sindh, Pakistan. ", "The town is bordered by Gadap Town to the north, the Faisal and Malir Cantonments to the east, Jamshed Town to the southwest, and Gulberg and Liaquatabad to the west. ", "Gulshan town falls under the jurisdiction of District East Karachi.", "\n\nThe population of Gulshan Town was estimated to be about 650,000 at the 1998 census, of which 99% are Muslim. ", "There are several ethnic groups in Gulshan Town including Muhajirs, Sindhis, Punjabis, Kashmiris, Seraikis, Pakhtuns, Balochis, etc. ", "The population of Gulshan Town was estimated to be nearly one million before census 2017. ", "A small number of Konkani Muslims are also settled in the Kokan Cooperative Housing Society of Gulshan-e-Iqbal Town.", "\n\nHistory \nLate commissioner of Karachi Mr. (Syed Darbar Ali Shah) envisioned setting up a new town Gulshan e iqbal on April 16, 1966. ", "It was originally KDA scheme 24 which was renamed in the Name of Great poet Allama Muhammad Iqbal.", "\n\nTown saw lot of development after setting up of Civic Center and Expo Center Karachi. ", "\n\nThe federal government introduced local government reforms in the year 2000, which eliminated the previous third tier of government (administrative divisions) and raised the fourth tier (districts) to become the new third tier. ", "The effect in Karachi was the dissolution of the former Karachi Division and the merger of its five districts to form a new Karachi City-District with eighteen autonomous constituent towns including Gulshan Town.", "\nAfter the enactment of Sindh Local Government Act 2013, five districts of Karachi were revived and a new district named Korangi was established; furthermore, sub-division was formed to replace towns of the city. ", "Gulshan town was replaced with sub-division Gulshan and some parts of Gulshan town were made part of sub-division Jamshed & sub-division Gulzar-e-Hijri.", "\nPopulation of sub-division Gulshan were recorded at 644,362 in census 2017.", "\n\nNeighbourhoods \n\nGulshan Town is the location of the main University of Karachi campus, as well as the offices of the City District Government of Karachi and the Attorney General of Sindh province. ", "There are also few large parks which includes Aziz Bhatti Park, Askari Park, Aladin Park and the Safari Park.", "\n\nEducation\nGulshan-e-Iqbal may be called as a university town having more than a dozen of Higher Education institutions. ", "Few of the major institutions are as follows:\n University of Karachi\n NED-UET karachi\n IBA karachi\n SSUET\n Federal Urdu University\n Usman University\n Agha Khan University\n Liaquat National Medical University\n Indus University\n Karachi School of Arts\n Iqra University\n ICMAP\nand several others\n\nSee also \n Zeenatabad Society \n Sharfabad Society\n Bahadurabad\n City District Government\n Karachi\n Lahore\n\nReferences\n\nExternal links \n Karachi Website\n Sindh E-Centralized College Admission Program\n Karachi: Of encroachments and mega projects\n The issue of squatters on land needed for new projects\n Hospitals In Gulshan Town" ]

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[ "Propagation of vector fractional charge Laguerre-Gaussian light beams in the thermally nonlinear moving atmosphere.", "\nWe study numerically the mutual propagation of two fractional topological charge Laguerre-Gaussian (LG) light beams in the moving atmosphere with the thermal nonlinearity. ", "The fractional charge beam is constructed as a weighted superposition of a finite number of the standard LG modes with integer charges. ", "Numerical simulations demonstrate an enhanced stability of the cross-section intensity distribution of the fractional charge LG beams against the thermal blooming, as compared with the case of integer charge beams. ", "The dominant mechanism of such a stability results from the multimodal structure of the fractional charge beams." ]

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[ "Product Reviews\n\nFrom the Manufacturer|Powered by\n\nOverview\n\nThese Big Tab Write & Erase sturdy paper dividers let you write, erase and reuse your dividers for easy changes at any time. ", "Simply write directly on the tabs with a ballpoint pen or pencil, and erase as needed. ", "The Big Tab design offers 1.5 times more writing space than standard divider tabs, and the variety of colors allow for quick referencing. ", "The gold reinforced holes resist tearing in your binder for extra durability. ", "Ideal for your personal organization at home, work and school.", "\n\nWrite, Erase and Reuse!", "\n\nKeep your binders and planners organized and up to date with Avery Write & Erase Paper Dividers—perfect for when you need to make changes. ", "Just write directly on tabs with a ballpoint pen or pencil, and the unique material lets you erase and reuse your dividers again and again.", "\n\nKey Features\n\nBig Tabs\n\nAdd more information on your tabs with 50% more writing space than standard tabs.", "\n\nA Closer Look\n\n{\"hideMenu\":false,\"ipiOnly\":false,\"tourViews\":[{\"viewImage\":{\"sources\":[{\"src\":\"/_cp/products/23076/tab-8caf27d9-55b0-4d6a-b485-1a13b04fb82f/resource-9ea0c837-76ab-4afa-b3cf-7a2c262549dc.jpg.w1920.jpg\",\"width\":810,\"height\":1000},{\"src\":\"/_cp/products/23076/tab-8caf27d9-55b0-4d6a-b485-1a13b04fb82f/resource-9ea0c837-76ab-4afa-b3cf-7a2c262549dc.jpg.w960.jpg\",\"width\":810,\"height\":1000},{\"src\":\"/_cp/products/23076/tab-8caf27d9-55b0-4d6a-b485-1a13b04fb82f/resource-9ea0c837-76ab-4afa-b3cf-7a2c262549dc.jpg.w480.jpg\",\"width\":480,\"height\":592},{\"src\":\"/_cp/products/23076/tab-8caf27d9-55b0-4d6a-b485-1a13b04fb82f/resource-9ea0c837-76ab-4afa-b3cf-7a2c262549dc.jpg.w240.jpg\",\"width\":240,\"height\":296}],\"src\":{\"src\":\"/_cp/products/23076/tab-8caf27d9-55b0-4d6a-b485-1a13b04fb82f/resource-9ea0c837-76ab-4afa-b3cf-7a2c262549dc.jpg\",\"width\":810,\"height\":1000},\"runtimeSrc\":{\"src\":\"/_cp/products/23076/tab-8caf27d9-55b0-4d6a-b485-1a13b04fb82f/resource-9ea0c837-76ab-4afa-b3cf-7a2c262549dc.jpg.web.jpg\",\"width\":810,\"height\":1000},\"assetWrapper\":\"tour\",\"isAdaCompliant\":false},\"hotspots\":[{\"hotspotX\":0.11513157894736842,\"hotspotY\":0.6173333333333333,\"captionFromAttr\":\"Reinforced Edges\",\"description\":\"<p>Gold or clear reinforced holes resist tearing in your binder for extra durability.<\\/p>\",\"direction\":\"left\"},{\"hotspotX\":0.054276315789473686,\"hotspotY\":0.38266666666666665,\"captionFromAttr\":\"Three-hole punched\",\"description\":\"Ready to add to your binder\",\"direction\":\"left\"},{\"hotspotX\":0.6529605263157895,\"hotspotY\":0.2733333333333333,\"captionFromAttr\":\"Write & Erase\",\"description\":\"Write with a ballpoint pen or pencil, erase as needed and reuse again and again\",\"direction\":\"right\"},{\"hotspotX\":0.7467105263157895,\"hotspotY\":0.216,\"captionFromAttr\":\"Big Tabs\",\"description\":\"1.5 times more writing space than standard tabs\",\"direction\":\"right\"},{\"hotspotX\":0.9638157894736842,\"hotspotY\":0.444,\"captionFromAttr\":\"5 or 8 tabs\",\"description\":\"Choose the number of tabs you need\",\"direction\":\"right\"},{\"hotspotX\":0.5991189427312775,\"hotspotY\":0.7428571428571429,\"captionFromAttr\":\"Variety of colors\",\"description\":\"<p>Choose from multicolored paper, white paper with multicolored tabs or white paper with white tabs.<\\/p>\",\"direction\":\"left\"}]}],\"ipiCompatible\":false}" ]

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[ "Introduction {#s1}\n============\n\nRecent studies have shown that the choroid is closely associated with the physiology of the eye and the pathogenesis of various retinal diseases.[@R1]\n\nEnhanced depth imaging optical coherence tomography (EDI-OCT) and swept-source OCT have enabled clinicians to evaluate the choroidal structure in different kinds of retinal diseases. ", "However, because a layer-by-layer architecture is not distinct, the main structures measured in the OCT images have been the overall choroidal thickness, choroidal area and the shape of the chorioscleral border. ", "Only a limited number of studies have assessed the vascular structure of the choroid which unfortunately used custom-made software not in general use.[@R11] [@R12]\n\nA new method, called the binarisation method, that can differentiate and quantify the choroidal luminal area from the stromal area was recently published.[@R13] This method uses an open access software named ImageJ with a detailed protocol.[@R13] This method can be used by any researcher with easy accessibility. ", "We used the binarisation technique to differentiate the choroidal luminal area from the stromal area, and we reported that the choroidal thickness and the ratio of luminal area to total choroidal area (L/C ratio) decreased significantly with ageing and longer axial length in normal eyes.[@R14]\n\nRecent studies have shown that there is a significant diurnal variation in the choroidal thickness.[@R15] To the best of our knowledge, however, there has not been a study to determine whether changes of the luminal or stromal area of the choroid were mainly responsible for the circadian changes in the choroidal thickness. ", "This information should be useful in understanding the physiology in normal eyes and pathogenesis of chorioretinal diseases.", "\n\nThus, the purpose of this study was to determine whether there are diurnal variations in the luminal and stromal areas of the choroid using the binarisation technique.", "\n\nMaterials and methods {#s2}\n=====================\n\nThe procedures used conformed to the tenets of the Declaration of Helsinki, and an informed consent was obtained from all of the subjects. ", "This study was approved by the Institutional Review Board of Tokushima University Hospital and registered with the University Hospital Medical Network (UMIN)-clinical trials registry. ", "The registration title is 'UMIN000019060, Choroidal structure on EDI-OCT images' (17 September 2015).", "\n\nInclusion and exclusion criteria {#s2a}\n--------------------------------\n\nThis was a prospective, cross-sectional, observational study of 50 right eyes of 50 normal, non-smoking subjects with no ophthalmic or systemic symptoms. ", "The exclusion criteria included the age of \\<20 and \\>60 years, high myopia defined as a refractive error (spherical equivalent) of \\<−6.0 dioptres or an axial length of \\>26.5 mm, low EDI-OCT image quality defined as an image quality index of \\<30, abnormal EDI-OCT findings and previous ocular surgeries. ", "Slit-lamp biomicroscopy and indirect ophthalmoscopy were performed to determine whether ocular abnormalities such as corneal diseases, cataracts, vitreoretinal diseases and glaucoma were present. ", "Subjects with any systemic diseases such as hypertension and diabetes mellitus based on the results of their most recent physical examination were also excluded.", "\n\nSystemic and ophthalmic examinations {#s2b}\n------------------------------------\n\nThe systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate, intraocular pressure (IOP) and EDI-OCT were measured every 3 hours between 6:00 and 21:00 hours. ", "The central corneal thickness, the refractive error and the axial length were measured at 15:00 hours. ", "The SBP, DBP and heart rate were measured on the right arm with a commercial sphygmomanometer (BP-203 RVII, OMRON COLIN, Japan). ", "The mean arterial pressure (MAP) and the mean ocular perfusion pressure (MOPP) were calculated according to the following formulas and used for the analyses: MAP=DBP+1/3 (SBP−DBP) and MOPP=2/3 MAP−IOP. ", "All examinations were performed in the sitting position within 10 min for each subject at each time point.", "\n\nSpectral-domain optical coherence tomography {#s2c}\n--------------------------------------------\n\nSpectral-domain OCT was performed at six-time points with 3-hour intervals; 6:00, 9:00, 12:00, 15:00, 18:00 and 21:00 hours with Spectralis OCT instrument (Heidelberg Engineering, Heidelberg, Germany). ", "Cross-sectional horizontal images of 30° through the fovea were obtained by EDI-OCT for each eye. ", "Each image was recorded with the eye tracking system without pupil dilation, and 100 scans were averaged to improve the signal-to-noise ratio. ", "The Follow-up mode was used to obtain images of the same position of the fundus for each subject. ", "The first scan which was performed at 6:00 hours was set as the reference for each subject. ", "All subsequent scans were aligned to this. ", "All OCT scans were performed by an experienced orthoptist under standardised mesopic lighting conditions to minimise the possible light-evoked vasodilations and constrictions. ", "On the day of the examination, participants were instructed not to take food, drink and vigorous exercise before the initial examination at 6:00 hours, and then to eat according to their usual daily routine thereafter.", "\n\nThe examined area of the retina and choroid was 1500 μm wide and was centred on the fovea. ", "The parameters measured were the central choroidal thickness (CCT), luminal, stromal and total choroidal areas, the central foveal thickness (CFT) and retinal area. ", "The L/C ratio was calculated. ", "The CFT was defined as the distance between internal limiting membrane and the outer surface of the retinal pigment epithelium (RPE), and the CCT as the distance between the outer border of the RPE and the chorioscleral interface. ", "These distances were measured by two independent investigators (KSh and ME) using the calliper function of the measuring software embedded in the Heidelberg Spectralis OCT. ", "The averages of two measurements were used for statistical analyses.", "\n\nEvaluation of luminal, stromal and total choroidal areas by binarisation technique {#s2d}\n----------------------------------------------------------------------------------\n\nThe EDI-OCT images were evaluated by one of the authors (KSh) who was masked to the clinical findings. ", "The binarisation of the choroidal area in the EDI-OCT images was done by a modified Niblack method using the ImageJ software (ImageJ V.1.47, NIH, Bethesda, Maryland, USA) as described in detail ([figure 1](#BJOPHTHALMOL2016308594F1){ref-type=\"fig\"}).[@R13] The examined area was 1500 μm wide and located in the subfoveal choroid, and it extended vertically from the RPE to the chorioscleral border. ", "In the binarised images, the light pixels were defined as the stromal areas and the dark pixels were defined as the luminal areas. ", "After including the distance between each pixel, the luminal and stromal areas were automatically calculated. ", "Similarly, the retinal area of 1500 μm wide centred on the fovea was determined by measuring the area between internal limiting membrane and the outer border of the RPE.", "\n\n{#BJOPHTHALMOL2016308594F1}\n\nAll parameters were measured three times and the averages were used for the statistical analyses. ", "Although the method for the analysis of the choroid was demonstrated to have a high repeatability and reproducibility in normal eyes,[@R13] intra-rater correlation coefficients were calculated for the data obtained from the images recorded at 6:00 hours. ", "The correlations of the OCT parameters with the systemic parameters and IOP were also determined.", "\n\nStatistical analyses {#s2e}\n--------------------\n\nStatistical analyses were performed with the SPSS V.22 software (IBM, Armonk, New York, USA). ", "The significances of the diurnal variations in the retinal and choroidal parameters were determined using the repeated-measures analysis of variance with Greenhouse-Geisser corrections. ", "The Bonferroni test was used for post hoc analysis. ", "The correlations in the diurnal variation between choroidal OCT parameters and other parameters including the systemic parameters and IOP were determined by calculating the within-subject correlation coefficients using a general linear model.[@R18] The intra-rater correlation coefficients were calculated using one-way random effects model for measurements of agreement. ", "The inter-rater correlation coefficients were calculated using two-way mixed effects model for measurements of absolute agreement. ", "A two-sided p value of \\<0.05 was considered statistically significant.", "\n\nResults {#s3}\n=======\n\nBaseline demographic data {#s3a}\n-------------------------\n\nFifty subjects consisting of 28 men and 22 women were studied. ", "Eleven eyes of 11 subjects were excluded because of high myopia and one eye because of prior laser in situ keratomileusis. ", "No eye was excluded because of low image quality. ", "Thus, the data from 38 eyes of 38 subjects (20 men and 18 women) were used for the statistical analyses. ", "The age of the subjects ranged from 21 to 52 years (mean±SD, 30.5±9.11 years). ", "The axial length, the refractive errors and the central corneal thickness (mean±SD) were 24.5±1.07 mm, −2.8±2.07 dioptres and 537.3±31.18 μm, respectively.", "\n\nRepeatability of measurement of OCT parameters {#s3b}\n----------------------------------------------\n\nThe intra-rater agreement was high, with an intraclass correlation coefficient of 0.997(CI 0.994 to 0.998) for the total choroidal area, 0.996 (CI 0.993 to 0.998) for the luminal area, 0.964 (CI 0.939 to 0.980) for the stromal area and 0.974 (CI 0.956 to 0.986) for the L/C ratio. ", "The inter-rater agreement for the CCT and CFT were 0.997 (CI 0.994 to 0.998) and 0.994 (CI 0.989 to 0.997), respectively.", "\n\nDiurnal variations in optical coherence tomographic parameters {#s3c}\n--------------------------------------------------------------\n\nSignificant diurnal variations were observed in the mean CCT, the mean total choroidal area, the mean luminal area and the mean L/C ratio with the maximum values at 6:00 hours; 359.0±76.2 μm for the mean CCT, 535 243.1±113 295.7 μm^2^ for the mean total choroidal area, 352 586.1±113 295.7 μm^2^ for the mean luminal area and 65.2±4.13% of the mean L/C ratio ([figure 2](#BJOPHTHALMOL2016308594F2){ref-type=\"fig\"}). ", "The minimum values were found at 15:00 hours; 341.2±70.1 μm for the mean CCT (p\\<0.001), 508 696.8±104 240.4 μm^2^ for the mean total choroidal area (p=0.011), 330 806.8±85 029.5 μm^2^ for the mean luminal area (p\\<0.001) and 64.2±3.91% for the mean L/C ratio (p=0.014).", "\n\n{#BJOPHTHALMOL2016308594F2}\n\nThe mean stromal area was largest at 6:00 hours with a value of 182 657.0±25 959.9 μm^2^ and smallest at 21:00 hours with a value of 179 053.2±25 255.9 μm^2^. However, the difference was not statistically significant (p=0.216). ", "There was no significant variation in the CFT and the retinal area (p=0.497 and p=0.441, respectively).", "\n\nThe difference in the CCT between 6:00 and 15:00 hours was significantly correlated with the differences in the total choroidal area (r=0.972, p\\<0.001) and luminal area (r=0.767, p\\<0.001) in the partial regression coefficient in which the refractive error and age were set as the control variables ([figure 3](#BJOPHTHALMOL2016308594F3){ref-type=\"fig\"}). ", "However, there was no correlation between the fluctuation range in the CCT and that in the stromal area (r=0.287, p=0.095).", "\n\n{#BJOPHTHALMOL2016308594F3}\n\nDiurnal variations in the systemic parameters and intraocular pressure {#s3d}\n----------------------------------------------------------------------\n\nNone of the subjects had an IOP \\>20 mm Hg at any time.", "\n\nThere were no significant diurnal variations in the mean SBP, DBP, MAP and MOPP (p=0.434, p=0.088, p=0.268 and p=0.501, respectively; [figure 4](#BJOPHTHALMOL2016308594F4){ref-type=\"fig\"}). ", "There were significant diurnal variations in the mean heart rate (p=0.002) and IOP (p\\<0.001).", "\n\n{#BJOPHTHALMOL2016308594F4}\n\nCorrelations of OCT parameters with systemic parameters and intraocular pressure {#s3e}\n--------------------------------------------------------------------------------\n\nThere were several significant correlations in the diurnal variations between the OCT parameters and the DBP, MAP and IOP but they were not relevant (all \\|r\\|\\<0.2, [table 1](#BJOPHTHALMOL2016308594TB1){ref-type=\"table\"}).", "\n\n###### \n\nCorrelations of OCT parameters with systemic parameters and IOP\n\n Central choroidal thickness Total choroidal area Luminal area Stromal area L/C ratio\n ------ ----------------------------- ---------------------- -------------- -------------- -----------\n SBP r=0.111 r=0.075 r=0.110 r=0.082 r=0.019\n p=0.127 p=0.300 p=0.131 p=0.260 p=0.795\n DBP r=0.139 r=0.128 r=0.154 r=0.025 r=0.088\n p=0.055 p=0.077 p=0.033 p=0.733 p=0.226\n HR r=0.020 r=0.097 r=0.037 r=−0.004 r=0.024\n p=0.788 p=0.181 p=0.612 p=0.957 p=0.744\n IOP r=0.152 r=0.088 r=0.160 r=0.050 r=0.094\n p=0.036 p=0.224 p=0.027 p=0.488 p=0.197\n MAP r=0.139 r=0.116 r=0.148 r=0.055 r=0.064\n p=0.055 p=0.110 p=0.041 p=0.452 p=0.382\n MOPP r=0.087 r=0.083 r=0.093 r=0.037 r=0.032\n p=0.233 p=0.255 p=0.202 p=0.613 p=0.622\n\nDBP, diastolic blood pressure; HR, heart rate; IOP, intraocular pressure; L/C ratio, ratio of luminal area to total choroidal area; MAP, mean arterial pressure; MOPP, mean ocular perfusion pressure; OCT, optical coherence tomography; SBP, systolic blood pressure.", "\n\nDiscussion {#s4}\n==========\n\nOur results showed that there were significant diurnal variations in the CCT, total choroidal area and the luminal area. ", "These parameters were maximal at 6:00 hours, decreased during the day to the minimum values at 15:00 hours and then increased in the evening. ", "These variations are similar to the diurnal variations in the CCT reported in other studies.[@R16] [@R17] Our results demonstrated that the choroidal thickness at the fovea and the macular choroidal area had significant diurnal variations.", "\n\nImportantly, the fluctuations in the stromal area were not significant as well as CFT and retinal area which were used as negative controls. ", "On the other hand, the L/C ratio had significant diurnal variations. ", "The change in the CCT was significantly correlated with the change in the luminal area and the total choroidal area. ", "However, there was no correlation between the change in the CCT and that in the stromal area. ", "These results suggest that such fluctuations are mainly due to the diurnal variations in the luminal area. ", "At present, there are reports on the diurnal variations in the choroidal thickness and choroidal circulatory parameters,[@R15] [@R16] [@R19] [@R20] which make clinicians speculate that the diurnal variation in the choroidal thickness should be related to the diurnal circulatory fluctuations. ", "To the best of our knowledge; however, this is the first report which determined that the diurnal variations in the choroidal thickness and choroidal area should not be attributed to the variation in the stromal area but to the luminal area.", "\n\nThe vascular tone and diameters can be altered by various factors including the blood pressure and myogenic responses, metabolic influences, for example blood gases and pH, visual stimulation and vasoactive agents including angiotensin II and nitric oxide.[@R21] Usui *et al*[@R16] reported a significant negative correlation between the choroidal thickness and SBP during the diurnal variations in these two parameters. ", "Tan *et al*[@R15] reported a significant correlation between the change in the choroidal thickness and the change in the SBP. ", "On the other hand, Li *et al*[@R22] reported that they found no significant correlation between the SBP or DBP and the choroidal thickness. ", "Our results also showed no statistical relationship between the blood pressure and the choroidal parameters. ", "Although the reason for this discrepancy was not determined, the choroidal vessels are under neurogenic control, and the autoregulation of choroidal blood flow is restricted compared with that of the retina.[@R21] The degree of fluctuations in the systemic parameters including SBP, DBP, MAP and MOPP were small with no statistical significance. ", "This may explain the discrepancy between the earlier studies and ours. ", "Another possible explanation could be that diurnal variations in the choroid may be influenced by other factors than that examined in this study. ", "Further studies are needed to determine the relationship between choroidal circulatory and structural parameters.", "\n\nChanges in the IOP could also influence the choroidal parameters. ", "A recent report showed that the diurnal fluctuation of the IOP and choroidal thickness were out of phase,[@R17] but no correlation was detected in another report.[@R16] In this study, no statistical correlation was found between the choroidal parameters and the IOP. ", "The amplitude of the diurnal fluctuations in the mean IOP was approximately 1.0 mm Hg. ", "A significant correlation may not have been detected because of the small range of IOP fluctuations.", "\n\nEvaluating the choroidal structure including the L/C ratio should be useful for understanding the pathogenesis of chorioretinal diseases as we reported recently.[@R13] [@R23] [@R24] However, careful attention should be paid to the diurnal variations in the choroidal structure when evaluating the choroidal structure in various chorioretinal diseases.", "\n\nThere are some limitations in this study. ", "First, we did not examine the 24-hour diurnal variations. ", "The L/C ratio during midnight might provide some new information in the future. ", "Second, the scanned area of 1500 μm was not enough to assume the diurnal variation of the whole choroid. ", "A wider range of the examination area may be more conclusive.", "\n\nIn conclusion, there are significant diurnal variations in the total choroidal area, luminal area and the L/C ratio but not in the stromal area. ", "These findings indicate that the diurnal variations in the choroidal area are mainly due to the fluctuations in the luminal area.", "\n\nThe authors thank Professor Emeritus Duco Hamasaki of the Bascom Palmer Eye Institute of the University of Miami for providing critical discussions and suggestions for our study and revision of the manuscript.", "\n\n**Contributors:** All authors have given final approval of this version to be published. ", "Design of the study: TK, YM, ME, SS and TS. ", "Conduct of the study: TK, YM, KSh and ME. ", "Management of the data: YM, KSh, AI, AF, YO, KSe and KA. ", "Analysis of the data: TK, YM, KSh, ME, KSe, EU and SS. ", "Interpretation of the data: TK, YM, KSh, ME, AI, AF, YO, KSe, KA, SS and TS. ", "Preparation of the manuscript: TK, YM, EU, SS and TS. ", "Overall coordination: TS.", "\n\n**Funding:** This work was supported in part by grant-in-aid 16K11288 (to YM) from the Ministry of Education, Science, Sports and Culture, Japan.", "\n\n**Competing interests:** None declared.", "\n\n**Patient consent:** Obtained.", "\n\n**Ethics approval:** The Institutional Review Board of Tokushima University Hospital.", "\n\n**Provenance and peer review:** Not commissioned; externally peer reviewed.", "\n\n**Data sharing statement:** Data are available from the corresponding author upon request.", "\n" ]

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[ "1. ", "Field of the Invention\nThe present invention relates to touch panels and, particularly, to a carbon nanotube based touch panel and a display device using the same.", "\n2. ", "Discussion of Related Art\nFollowing the advancement in recent years of various electronic apparatuses, such as mobile phones, car navigation systems and the like, toward high performance and diversification, there has been continuous growth in the number of electronic apparatuses equipped with optically transparent touch panels at the front of their respective display devices (e.g., a display such as a liquid crystal panel). ", "A user of any such electronic apparatus operates it by pressing or touching the touch panel with a finger, a pen, a stylus, or a like tool while visually observing the display device through the touch panel. ", "A demand thus exists for touch panels that are superior in visibility and reliable in operation.", "\nUp to the present time, different types of touch panels, including resistance, capacitance, infrared, and surface sound wave types, have been developed. ", "The capacitance-type touch panel has advantages such as high accuracy and excellent transparency, and thus has been widely used.", "\nA conventional capacitance-type touch panel includes a glass substrate, a transparent conductive layer, and four electrodes. ", "The material of the transparent conductive layer is, selected from a group consisting of indium tin oxide (ITO) and antimony tin oxide (ATO). ", "The electrodes are made of metal and separately formed on a surface of the transparent conductive layer. ", "Further, a protective layer is formed on the surface of the transparent conductive layer that faces away from the substrate. ", "The material of the protective layer has insulative and transparent characteristics.", "\nIn operation, an upper surface of the touch panel is pressed/touched with a touch tool, such as a user's finger or an electrical pen/stylus. ", "Visual observation of a screen on the liquid crystal display device provided on a backside of the touch panel is provided. ", "In use, due to an electrical field of the user, a coupling capacitance forms between the user and the transparent conductive layer. ", "For high frequency electrical current, the coupled capacitance is a conductor, and thus the touch tool takes away a little current from the touch point. ", "Current flowing through the four electrodes cooperatively replaces the current lost at the touch point. ", "The quantity of current supplied by the four electrodes is directly proportional to the distances from the touch point to the electrodes. ", "A touch panel controller is used to calculate the proportion of the four supplied currents, thereby detecting coordinates of the touch point on the touch panel.", "\nThe optically transparent conductive layer (e.g., ITO layer) is generally formed by means of ion-beam sputtering, and this method is relatively complicated. ", "Furthermore, the ITO layer has generally poor mechanical durability, low chemical endurance, and uneven resistance over an entire area of the touch panel. ", "Additionally, the ITO layer has relatively low transparency. ", "All the above-mentioned problems of the ITO layer tend to yield a touch panel with somewhat low sensitivity, accuracy, and brightness.", "\nWhat is needed, therefore, is to provide a durable touch panel with high sensitivity, accuracy, and brightness, and a display device using the same." ]

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[ "Tag: Pascha (파스카)\n\nOne of the great things about being a fan of Korean cinema is that the industry is continually inventive. ", "Whether in mainstream or independent film, Korean filmmakers constantly generate shocks and thrills aplenty, featuring some truly memorable moments that resonate long after the final credits have rolled.", "\n\nAs the title of this feature implies, 2013 was no exception. ", "Shocking scenes frequently appeared throughout a variety of genres, and here are Hanguk Yeonghwa’s most memorable – disturbing, shocking, or just plain awesome – moments of the year.", "\n\nFinal warning – spoilers ahead!", "\n\nAzooma (공정사회) – Dental Revenge\n\nDisillusioned with patriarchal institutions, the ajumma prepares for her own brand of justice\n\nThere have been a number of films in recent years that have explored the serious crime – and soft punishment – of pedophilia in Korean society. ", "Few however can attest to providing such violent revenge as indie thriller Azooma. ", "Rejected by police as well as the child’s playboy father, the ‘ajumma’ (azooma) enlists the help of local gangsters to abduct the criminal and tie the pervert into a dentist chair. ", "Employing her skills as a dental nurse, the ajumma exacts her bloody and brutal – and incredibly cathartic – vengeance by drilling the teeth to the bone without anesthetic. ", "Even better however is that the surgery belongs to the child’s absent father, allowing mother and daughter to walk away and learn to heal.", "\n\nHan Gong-ju (한공주) – The Internet Video\n\nGong-ju’s trauma apears on the internet for all to see\n\nHeartbreaking and tragic, director Lee Su-jin’s break-out film centers on high school student Gong-ju who conceals an extremely traumatic event in her past. ", "While hints continually suggest that she was sexually assaulted, the truth is even worse – she was gang raped by dozens of her peers. ", "The depiction of the event is truly haunting. ", "However, as the film reaches its climax, Gong-ju’s unaware friends finally learn the truth about her suffering as a video of the assault appears on the internet. ", "Unable to move or speak, Gong-ju’s best friend can do nothing but watch in horror.", "\n\nOne of the most vibrant and enjoyable rom-coms in recent years, How to Use Guys with Secret Tips is brilliantly original largely due to one character – the mysterious Dr. Swalski. ", "In his audacious 1970s apparel, the doctor brilliantly gives advice on how to manipulate men to naive assistant director Choi Bo-na with superb comic timing, even appearing within her life when things don’t quite work out the way they should. ", "With wonderful tongue-in-cheek wit, Dr. Swalski is a fantastic creation from the mind of director Lee Won-seok.", "\n\nIntruders (조난자들) – The North Korean Spy\n\nSuspicions rise but the culprit comes out of left field\n\nDirector Noh Young-seok’s (노영석) film about a screenwriter seeking solitude in the mountains is a quirky story, with the slow build of suspense brilliantly executed as the murdered bodies begin piling up and suspicions rise. ", "When the survivors find a hidden basement full of victims tensions reach fever-pitch – until a short North Korean spy jumps out of a closet. ", "Simultaneously hilarious and shocking, the spy displays director Noh’s dark-comic sensibilities and adds a surprising element in an otherwise straightforward thriller.", "\n\nNew World (신세계) – Battle Royale\n\nJeong Cheong viciously battles his way through assassins\n\nThrough gangster epic New World, Chinese-Korean wiseguy Jeong Cheong – superbly portrayed by actor Hwang Jeong-min – is little more than a loser, a joker more interested in fake goods than in cementing his position within the crime syndicate. ", "That is, until a rival seeks to take him out of the running permanently. ", "Surrounded by assassins, Jeong Cheong displays stunning ferocity as he battles for his life pummeling his adversaries into submission, culminating in a brutal knife fight in an elevator. ", "And in the end, only one man is left standing.", "\n\nPascha (파스카) – The Abortion\n\nGa-eul must learn to endure the pain of loss\n\nBusan Film Festival winner Pascha depicts the relationship between 40-something screenwriter Ga-eul and her 17 year old lover. ", "The slow-moving indie drama presents their struggles to stay together, particularly after the news that Ga-eul is pregnant. ", "Forced to have abortion by her family, the deeply depressed screenwriter undergoes the procedure. ", "Yet as she leaves, something compels her to turn back and demand to see the remains. ", "The controversial scene has divided critics, but the haunting image resonates long after the credits.", "\n\nSnowpiercer (설국열차) – The Classroom\n\nThe entry into the psychedelic classroom is a surrealist nightmare\n\nDirector Bong Joon-ho’s epic sci-fi has several noteworthy moments, including the shattering of an iced-arm and discussing how babies taste, but the entry into the disturbingly bizarre school is so surreal it tops them all. ", "After battling through dark and grimy carriages in an extremely bloody and violent revolution, the next door opens to reveal a disneyfied classroom on acid full of psychotic fervour. ", "Alison Pill is phenomenal as the fanatical teacher, while the brainwashed students religiously chant the train driver’s name as if he is a deity. ", "With exceptional work by production designer Ondrej Nekvasil, the classroom is a disturbing reminder of the power of bias education on impressionable minds.", "\n\nThe Terror Live (더 테러 라이브) – The General\n\nThe general’s hat is all that remains as Yoon becomes frantic\n\nNewsroom drama The Terror Live was a big hit in Korea due to the open and frank exploration of corruption within the social elite, and the exploitation of workers. ", "As reporter Yoon Yeong-hwa (expertly performed by Ha Jeong-woo) converses with the terrorist who destroyed a bridge live on air, a military general comes to the studio and joins the debate. ", "The general rapidly makes the situation worse, goading the terrorist with lies and defamation building unbearable tension until a bomb in the general’s earpiece explodes splattering blood everywhere. ", "A shocking moment, yet also a victory for exploited workers.", "\n\nScreenwriter Ga-eul (Kim So-hee (김소희) lives a modest existence, working in dead-end jobs while she attempts to complete her screenplay. ", "The only comforts for the lonely 40 year old are the stray cats she tends to – and often adopts – from the neighbourhood, and her boyfriend Joseph (Sung Ho-jun (성호준). ", "Yet the relationship is quite scandalous as at 23 years her junior, Joseph has yet to complete high school let alone his required military service. ", "Keeping a low-profile the couple continue their relationship unabated, until unexpected complications arise that threaten to drive them apart forever.", "\n\nCrucial to the success of any romantic-drama is the core relationship. ", "Audiences are fully aware that circumstances will enter the film that will challenge the protagonists, with the enjoyment derived from being so invested in the relationship that they will it to succeed despite the odds. ", "In this sense, Pascha (파스카) falls far, far short of what is required as there is precious little romance or chemistry between Ga-eul and Joseph throughout the entire film. ", "Director Ahn Seon-kyoung (안선경) has decided to enter the relationship well into it’s maturity, which is certainly no bad thing, as she sets up events and situations that are both natural as well as allowing for the sincerity of long-term partners to emerge. ", "Yet even though the relationship is far from conventional such heartfelt emotions never appear, chiefly due to the awkwardness between the two lead actors which is incredibly distracting, particularly by Sung Ho-jun. ", "There is a distance and coldness between them that conveys a mother and son relationship rather than lovers. ", "Joseph’s Oedipal concerns are obviously an issue – hammered home with the song, “Sometimes I feel like a motherless child” – but scenes such as sharing a bath just appear clumsy and indifferent rather than passionate and intimate.", "\n\nGa-eul’s relationship with 17 year old Joseph is quite a scandal\n\nPascha‘smost interesting moments lie within scenes involving Ga-eul’s family. ", "When they discover her relationship with the 17 year old, the judgement and criticism Ga-eul receives conveys a deep-rooted misogyny that, even at the age of 40, she must humbly endure. ", "The abuse she suffers is indeed shocking and it is during such moments that actress Kim So-hee shines, displaying the frailty of the nervous and unconfident screenwriter with skill. ", "The pressure enforced upon Ga-eul also leads to film’s very strong – and very graphic – anti-abortion statement, that will likely appall the majority of audiences and outrage many others. ", "Commentators are likely to discuss how far directors could, or rather should, go when it comes to presenting such explicit and visceral portrayals of such a sensitive topic. ", "Yet it is also bizarrely ironic given that the film is so concerned with feminist issues only to undermine one area of debate in such an extreme manner.", "\n\nIt is also unfortunate that director Ahn only begins to show creative flair out of the ashes from such controversial scenes. ", "For the vast majority of the running time the film is an incredibly bland affair featuring a static camera and very little eye-catching cinematography. ", "The uninspiring camerawork and compositions in the early stages of the film do convey the depression, loneliness and solemnity Ga-eul endures, yet such technical issues are rather crude and also suggest directorial inexperience, further detracting from the supposed intimacy between her and Joseph. ", "This is indeed strange as director Ahn’s capabilities are impressive and wholly apparent during the film’s final scenes, a genuine shame as the relationship sorely requires such visual prowess much much earlier to be convincing and effective. ", "As such Pascha is a romantic-drama that is ironically not memorable for its central couple or the relationship, but for the debate on ‘how far is too far?’ ", "in representations of sensitive subject matter.", "\n\nGa-eul must learn to endure the pain of loss\n\nVerdict:\n\nIn the attempt to convey the scandalous relationship between a 40 year old screenwriter and her 17 year old boyfriend, Pascha falls far short of other romantic dramas. ", "The awkwardness and indifference displayed by the actors ultimately ruins any tension for when the relationship is predictably threatened. ", "Yet director Ahn Seon-kyoung does well when examining the issues of misogyny endured by the central protagonist. ", "Ironically however, Pascha, is not memorable for the scandalous relationship but for the explicit representation of abortion, which will likely upset critics and audiences alike.", "\n\nWith the 18th Busan International Film Festival (BIFF) due to commence on October the 3rd, it’s high time to profile the Korean entries that are due to be screened.", "\n\nThree of the big categories at BIFF – Gala Presentation, New Currents, and Open Cinema – showcase some of the incredible mainstream and independent films to emerge from the Korean film industry this year.", "\n\nGala Presentation focuses on a select group of important films from the Asian continent, and within this category are two Korean films – Bong Joon-ho’s Snowpiercer (설국열차) and Kim Jee-woon’sThe X (더 엑스).", "\n\nNew Currents, meanwhile, explores some of the more powerful independent features to emerge from the continent. ", "The manner in which the films within this category delve into social and cultural issues, often through experimentation of film form, make it one of the more fascinating areas. ", "Three Korean films – 10 Minutes (10분), Steel Cold Winter (소녀) andPascha (파스카) – appear, and receive their world premieres at BIFF 2013.", "\n\nRounding out the three, Open Cinema selects films to be presented on the Busan Cinema Center’s impressive outdoor screen. ", "Two big thrillers from Korea are within the category – Cold Eyes (감시자들) and The Terror Live (더 테러 라이브).", "\n\nPlease see below for more in-depth coverage of each film.", "\n\nGala Presentation\n\nThe class system on the train is kept in check by sinister matriach Mason\n\nSnowpiercer (설국열차) – Director Bong Joon-ho (봉준호)\n\nBong Joon-ho’s science-fiction epic was released in Korea earlier this year, earning over nine million admissions and over $50 million at the box office. ", "For many foreign visitors to BIFF 2013 this will be their first opportunity to see the film before it’s released in international markets, so it’s placement within the Gala Presentation category is quite deserved. ", "Snowpiercer is also notable as (currently) the most expensive Korean film ever made, as well as having Hollywood behemoth The Weinstein Company on board producing. ", "The film tells the story of the last survivors on Earth following a man-made ice age that covered the planet. ", "The last remnants of humanity struggle to survive on a train called ‘Snowpiercer’ which circumnavigates the globe every year. ", "Yet within the train an unfair class system has emerged, and a revolution begins between the ‘haves’ and ‘have nots.’ ", "For the review of Snowpiercer, please click here.", "\n\nThe X (더 엑스)\n\nThe X (더 엑스) – Director Kim Jee-woon (김지운)\n\nNew camera technology allows for a more immersive experience\n\nScreen X technology has been employed and experimented with in Kim Jee-woon’s latest film The X. Commissioned by cinema chain CGV, director Kim has used screen x – which allows for extra space on either side of the screen for a more immersive viewing experience – to produce this new 30 minute short action/thriller film. ", "The X also features an all-star cast with Kang Dong-won, Shin Min-ah, and E Som in the lead roles which is guaranteed to arouse interest amongst their respective fan bases.", "\n\nNew Currents\n\n10 Minutes (10분)\n\n10 Minutes (10분) – Director Lee Yong-seung (이용승)\n\n10 Minutes is concerned with examining the notoriously harsh environment of the Korean workplace. ", "The story follows a young intern as he enters employment at a government facility, and is promised a full-time position that will guarantee financial stability. ", "Yet when his boss promotes someone else into the position, the young man is forced to reevaluate his options. ", "10 Minutes is director Lee Yong-seung’s thesis film while at the Dankook Graduate School of Cinematic Content.", "\n\nSteel Cold Winter (소녀)\n\nSteel Cold Winter (소녀)– Director Choi Jin-seong (최진성)\n\nSteel Cold Winter is Choi Jin-seong’s first fiction film, after spending years helming successful documentaries. ", "The film depcits the story of high schooler Yoon-soo who moves to the mountains in Gangwon Province following his friend’s suicide. ", "Yet while he attempts to start a new life, he meets a mysterious girl called Hae-won and begins to fall in love. ", "However Hae-won has a secret and when her father suddenly disappears, Yoon-soo’s suspicions become aroused.", "\n\nGa-eul’s relationship with 17 year old Joseph is quite a scandal\n\nPascha (파스카) – Director Ahn Seon-kyoung (안선경)\n\nDirector Ahn’s Pascha tells the story of a lonely 40 year old screenwriter and her 17 year old boyfriend. ", "Their unconventional relationship, and penchant for adopting stray cats, is fine until some unexpected news forces the intervention of their families. ", "The pressure exerted on the couple results in plenty of judgement and heartache, as they must try to find a way to stay together. ", "Pascha could perhaps be an interesting and more feminist orientated companion piece with last year’s A Muse (은교), which explored similar themes with an older man and young girl.", "\n\nOpen Cinema\n\nRookie Yoon-jo must learn to observe and recall everything on a mission\n\nCold Eyes (감시자들) – Directors Jo Eui-seok (조의석), Kim Byeong-seo (김병서)\n\nA remake of Hong Kong thriller Eye in the Sky (2006), cat-and-mouse cop drama Cold Eyes performed very well upon its release over the summer. ", "The film is a slick and high-tech thrill-ride, featuring an impressively futuristic rendition of Seoul as a government surveillance team works day and night to catch professional criminals. ", "Cold Eyes depicts the story of talented rookie Yoon-joo (Han Hyo-joo) who joins a special division headed by Chief Hwang (Sol Kyeong-gu). ", "Their mission is to apprehend a group of professional thieves and their mastermind ‘Shadow’ (Jeong Woo-seong). ", "The A-list cast have all been superbly cast against the types of roles they usually portray, and the result is a highly engaging thriller.", "\n\nExploiting the opportunity to become a news anchor, Yeong-hwa begins to regret his decision\n\nThe Terror Live (더 테러 라이브) – Director Kim Byeong-woo (김병우)\n\nThe Terror Live was one of the surprise hits of the summer, notably going toe-to-toe with Snowpiercer and still gaining a large proportion of the audience. ", "The reasons are quite clear as the thriller is a well-crafted and suspense-filled, as well as striking a chord with Korean audiences due to governmental criticism within. ", "Superstar Ha Jeong-woo plays disgraced TV anchor Yeong-hwa, who has been demoted to radio due to a scandal. ", "When a terrorist calls the radio show threatening to blow up a bridge, his bluff is called, and shortly thereafter an explosion occurs. ", "Set entirely within a newsroom, The Terror Live is one of the more interesting thrillers in recent memory. ", "For the review of The Terror Live, please click here.", "\n\n2018 was quite a bizarre year for Korean cinema. ", "The year began much like any other. ", "The first few months of the year were typically dedicated to family-friendly fare. ", "News of Korean films that were invited to Cannes Film Festival arose. ", "And then...well, everything seemed to fall flat. ", "One by one, the big tentpole films... Read More\n\nMany years ago, a peasant uprising led by the legendary 3 Swords goes awry when Deok-gi (Lee Byung-hun) betrays the band of warriors by aligning with the corrupt king and murdering Poong-chun (Bae Soo-Bin). ", "Distraught,... Read More\n\nWhen the Korean and American governments announce that the military THAAD (Terminal High Altitude Area Defense) system is to be located in the rural county of Seongju, residents quickly become... Read More\n\nAcclaimed actress Jeon Do-yeon is to be honoured at the 21st Bucheon International Fantastic Film Festival (BiFan) this year, in celebration of her 20 year career that began with Contact back in 1997. ", "Entitled 'Contact, Jeon Do-yeon,' the special program is dedicated to the revered actress and will feature highlights from her incredible filmography, including Secret Sunshine... Read More\n\nWe are just one week away from the start of the 2nd Korea International Expat Film Festival (KIXFF). ", "Festival director Kevin Lambert took some time from his busy schedule to answer questions about the festival which... Read More\n\nWhile the films released throughout any particular year are indicative of a country's identity, for Korean cinema in 2017 the exploration of political and social issues were especially revealing of the cultural shift that has arisen in the wake of Park Geun-hye's presidency. ", "The political upheaval was echoed through several historical films/documentaries focused on past... Read More\n\nHaving a film selected to premiere at the Cannes Film Festival is an incredible achievement - having two is quite extraordinary. ", "Yet that is precisely what director Hong Sang-soo has done, as The Day After (그 후) and... Read More\n\nThe Villainess (악녀) has received an explosive trailer in the run-up to its debut at the Cannes Film Festival on May 21st. ", "Appearing in the 'Out of Competition - Midnight Projections' program, writer/director Jung Byung-gil's latest... Read More" ]

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[ "Pete Fournier Freelance Photography provided the couple with wedding photos on CD. ", "Family, friends, and the public can view the couple's wedding photo album on the last page of www.amoreweddingsswfl.com" ]

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[ "[Biometry of the anterior chamber of the eye in Nd:YAG laser iridectomy].", "\nIn a prospective clinical study covering 41 eyes (28 patients) with narrow-angle glaucoma the central and peripheral anterior chamber depths were determined biomicroscopically before and after Nd:YAG laser iridectomy. ", "In 29 eyes the central anterior chamber depth was also measured by ultrasonography. ", "In contrast to the increase in central anterior chamber depth, which was only slight, the increase in the peripheral anterior chamber depth was statistically significant (P less than 0.01)." ]

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[ "the food i eat, the books i read + the places i go\n\nMenu\n\nTag Archives: Le Pré Salé\n\nThough we both drank loads of beer on our trip (I mostly stuck with my beloved lambics), Keith was on a self-imposed mission to consume all of the Belgian Trappists. ", "Did he succeed? ", "Scroll down to find out." ]

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[ "Lettenkeuper Formation\n\nThe Lettenkeuper Formation, also called the Lower Keuper (, Lettenkeuper, Lettenkohle or Lettenkohlenkeuper), is a geologic formation in Germany. ", "It preserves fossils dating back to the Triassic period.", "\n\nSee also\n\n List of fossiliferous stratigraphic units in Germany\n\nReferences\n \n\nCategory:Triassic Germany" ]

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[ "With just a few days left to the commencement of CitiOS’ Initial Exchange Offer (IEO), Institutions are rushing to have a share of the CitiOS tokens before they are exhausted. ", "One of the institutions, a Singaporean institutional entity has taken up $30 million worth of R2R tokens (which translates to 100 million R2R tokens) with an undisclosed lock-up period.", "\n\nWith 100 million R2R tokens gone in one sale, it shall only require 9 more such investors to purchase the remaining 900 million R2R tokens. ", "As things stand, more Institutional investors are likely to invest in the project. ", "By the time the IEO will be opening for the public, there could be only a handful of R2R tokens left for grabs.", "\n\nA true sign that CitiOS IEO is a worthy investment\n\nWhen looking for an IEO to invest in, investors are very alive to the fact that the project could become successful or fail to become successful. ", "However, there are things that the investors look for to gauge whether the project has the prospect of conquering the world.", "\n\nOne of the indicators that a project is likely to succeed, is the presence of Venture Capital Investors. ", "These are normally professional Investors and in most cases institutional entities, who invest in projects once they are certain that the projects have a high likelihood of achieving their outlined goals.", "\n\nVenture Capitalists normally do a thorough background check and involve professionals in doing the research to ascertain that a project is a worthy investment. ", "Therefore investing in an IEO that has Venture Capital Investors is a huge advantage because as an investor you are assured that the project shall succeed.", "\n\nWith the institutional Investors, CitiOS development team is also assured that there are professionals out there who are confident that the project is viable." ]

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[ "Being the only writer to hold the coveted distinction of being a two-time Austin Film Festival Screenwriting Competition winner, Troy Anthony Miller attributes his affinity for screenwriting to the life-long lessons he picked up through traveling abroad, working in other careers and maintaining a determined and collaborative work ethic.", "\n\nWe speak with Troy about his feature scripts, The Hitch, a thriller focusing on a young Alfred Hitchcock, and the female centric sports comedy, The Olympian, and more from his career.", "\n\nRecently named by The New York Times as an \"Artist to Watch,\" Evette Vargas is an award-winning, cross-platform storyteller who is at the vanguard of the digital and virtual reality landscape.", "\n\nEvette recently spoke with us about becoming a multi-hyphenate artist and creator, her Web Development Studio, Digital-Reign, and about the enormous opportunity for filmmakers she sees in the emerging virtual reality markets.", "\n\n“It seems to me that there are so many ways to tell a story that it doesn’t necessarily need to be just through writing. ", "It can be through acting; I’m writing my own music right now; there’s a lot of different facets of storytelling which interest me so I try to explore as many as I can.”", "\n\nKnown for his work in 'Little Men' and 'True Places Never Are,' Actor-Writer-Director Theo Taplitz is wise beyond his years and shows no signs of slowing down. ", "We recently spoke with him about his process both behind and in front of the camera, and more.", "\n\nKelsey Scott is a screenwriter that has worked on shows such as Hollywood Girl as well as a creator of her own content. ", "We sat down with Scott to learn more about how she went from child actress to scribe under the influence of her grandmother.", "\n\nKelsey Scott is known for her acting roles in projects such as How to Get Away with Murder, 12 Years a Slave and HBO's Insecure, to name a few." ]

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[ "Q:\n\nFloat range validation using AngularJs\n\nI am following an example based on official docs to validate float. ", "My added requirement is that float value should lie between -90 to 90. ", "I added the min and max fields but still no luck.", "\nBelow is the code:\nHTML:\n<body ng-app=\"form-example1\">\n<form name=\"form\" class=\"css-form\" novalidate>\n\n<div>\n Length (float):\n <input type=\"text\" ng-model=\"length\" name=\"length\" min=\"-90\" max=\"90\" smart-float />\n {{length}}<br />\n <span ng-show=\"form.length.$error.float\">\n This is not a valid float number!</span>\n <span ng-show=\"form.length.$error.min || form.length.$error.max\">\n The value must be in range -90 to 90!</span>\n</div>\n\nJS:\nvar app = angular.module('form-example1', []);\nvar FLOAT_REGEXP = /^\\-?\\d+((\\.|\\,)\\d+)?$/;\napp.directive('smartFloat', function() {\nreturn {\n require: 'ngModel',\n link: function(scope, elm, attrs, ctrl) {\n ctrl.$parsers.unshift(function(viewValue) {\n if (FLOAT_REGEXP.test(viewValue)) {\n ctrl.$setValidity('float', true);\n return parseFloat(viewValue.replace(',', '.'));", "\n } else {\n ctrl.$setValidity('float', false);\n return undefined;\n }\n });\n }\n};\n});\n\nRight now validations for min and max fields are not working. ", "90 is allowed but anything higher than is not allowed (like 90.12345 is not allowed, 90 is allowed, 89.9999 is allowed, -90.1 is not allowed)\n\nA:\n\nBe sure to make your input of type number! ", "The min/max validation is only available for this type of input field. ", "Compare the docs for number to text.", "\n\n" ]

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[ "Acquisition and retention of Clostridium difficile by Musca domestica larvae and pupae during metamorphosis.", "\nTransfer of Clostridium difficile by Musca domestica has been demonstrated, revealing their potential for disseminating infection in the hospital environment. ", "To determine the ability of M. domestica larvae to acquire and retain C. difficile throughout their metamorphosis into adult flies. ", "Larvae were exposed to spores of C. difficile in a faecal emulsion, and examined externally and internally to determine carriage and internalization of spores through their development to adults. ", "Larvae harboured C. difficile externally, with means of 21.56+/-5.76 colony-forming units (cfu) at Day 0, 22.44+/-9.90 cfu at Day 2, decreasing to 0.56+/-0.34 cfu at Day 4, with no C. difficile isolated thereafter. ", "The same larvae harboured C. difficile internally, with means of 587.33+/-238.29 cfu at Day 0, decreasing to 297.44+/-155.21 cfu at Day 2, decreasing further to 73.67+/-46.74 cfu at Day 4, with no C. difficile isolated thereafter. ", "The zero recovery of C. difficile coincided with the development of M. domestica larvae into pupae. ", "From Day 6 onwards, all larvae had developed into the pupal stage and no C. difficile was recoverable from any pupae. ", "No C. difficile was recovered from adult flies (emerged on Day 12) or empty puparia. ", "Although C. difficile spores are readily acquired and internalized by larvae during feeding, they are not retained through development to adults. ", "Adult flies therefore acquire C. difficile contamination as adults. ", "The potential antimicrobial action of M. domestica larvae and their extracts against C. difficile spores warrants further investigation." ]

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[ "Anthony Sanborn looks to his attorney Amy Fairfield at the start of his post-conviction review on Oct. 10 at the Cumberland County Courthouse. ", "After serving 27 years in prison, Sanborn was released on bail in April pending a review of his case. ", "Staff photo by Gregory Rec\n\nTwo women testified Friday at Anthony Sanborn Jr.’s conviction review hearing that they were sexually assaulted by a friend of Sanborn’s but police did not pursue charges against the man because they needed him to testify against Sanborn at his 1992 murder trial.", "\n\nOne of the women testified that Portland police detectives investigating the 1989 slaying of Jessica L. Briggs had what appeared to be photographs showing Gerard Rossi assaulting her at the time. ", "Crystal Call, who was then known as Crystal Breen, said Friday that Detectives James Daniels and Daniel Young interviewed her but were more interested in talking about Sanborn.", "\n\nRelated Headlines\n\nRossi was a key witness at Sanborn’s murder trial, testifying that Sanborn confessed to the grisly killing, in increasing detail, on three occasions.", "\n\nCall said she was 14 or 15 when she was photographed in an Augusta motel room with Rossi partially nude and lying face-down between her legs, among other sexual poses. ", "She said that she told police at the time that she did not consent to the sexual contact or have any recollection of it.", "\n\nA second woman, Gloria Brosseau, who was 15 at the time and known as Gloria Staples, testified Friday that Rossi raped her in an Augusta hotel room some time after Briggs’ slaying.", "\n\nBrosseau also testified that she was there the night the Polaroid photographs of Call were taken, and that she took them at Rossi’s instruction. ", "Both women said separately that they were terrified of Rossi, who they said preyed on young girls who hung around Sanborn.", "\n\nBrosseau was the first to testify Friday, and said Rossi forced himself on her in an Augusta hotel room.", "\n\n“He said he was going to have his way with me,” Brosseau said. “", "He had a gun in the room and he did have his way with me.”", "\n\nHer testimony was in response to questions from Sanborn’s attorney, Amy Fairfield, who has alleged in court filings that Rossi testified against Sanborn at the behest of the police, and that officers made a silent deal with Rossi not to pursue the rape allegations against him in exchange for his testimony.", "\n\nThe state has denied those allegations, and Daniels, testifying previously, said he never made any deal and did not have the power to do so. ", "Brosseau said she reported the rapes to Portland police, but they would not press charges because they needed Rossi to testify against Sanborn.", "\n\nDuring a tense cross-examination, in which Brosseau appeared hostile to Assistant Attorney General Meg Elam, it was revealed that Daniels wrote a police report about the rape allegation.", "\n\n“Could you just answer the questions I ask you?” ", "said Elam, who tried to pick away at Brosseau’s credibility. ” ", "If Ms. Fairfield wants to ask you more questions she can.”", "\n\nDaniels previously said on the witness stand that he referred Brosseau to the Augusta police because the alleged crime did not occur within his jurisdiction.", "\n\nIt was unclear whether Brosseau ever made a complaint to Augusta police, or if police ever followed up on her allegations. ", "She said her mother, who survived polio, was partially paralyzed and could not drive.", "\n\nCall was second to testify and said two detectives came to her home sometime after Briggs was killed and wanted to bring her to the station. ", "Although Call’s mother asked if she should come, Call said the detectives said that was not necessary.", "\n\nOnce at the station, a detective produced four or five pornographic photos of Rossi and a young girl, “and the female was me,” Call said.", "\n\nShe had never seen the photos before, and was in shock, she said. ", "Call said she told police she did not consent to what the pictures showed.", "\n\n“It’s the most degrading feeling,” Call said. “", "I was so baffled and surprised because I didn’t expect to see anything of that sort and I did not expect that female to – I did not expect to see photos of what I saw.”", "\n\nShe told her mother that she felt a crime had been committed, but Call did not remember whether she said that to the police.", "\n\nBrosseau’s testimony contradicted a claim the state previously made in the post-conviction hearings, that Sanborn took the pictures. ", "Brosseau said Sanborn was present, but not involved in the alleged sexual assault.", "\n\nDaniels, who testified he was aware of the photos, said in previous testimony that the pictures did not clearly show penile-vaginal penetration, which was the legal standard to charge someone with rape in 1989. ", "Both Daniels and Young are now retired.", "\n\nThe state will have the opportunity to cross-examine Call on Monday.", "\n\nA third witness also testified Friday. ", "David Schwarz was 17 and had fled from the Maine Youth Center at the time Briggs was murdered.", "\n\nSchwarz said he was sleeping on a bench near the Maine State Pier, that he heard a couple of loud thuds followed by a splash and saw someone leave the area, but he didn’t get a clear look at the person.", "\n\nSchwarz testified that he was picked up for breaking into cars shortly after Briggs’ body was found, and that police at first accused him of killing Briggs.", "\n\n“Detective Young, he actually slapped me upside the head and said, ‘You killed her, you (expletive) punk,’ ” Schwarz testified. ", "The detectives played good-cop bad-cop for a few hours. ", "His guardian, the Department of Human Services, was never notified, he said.", "\n\nSchwarz said he was immediately asked about Sanborn. ", "During his testimony, Schwarz said he never saw Sanborn on the pier.", "\n\nSchwarz’s testimony was briefly interrupted because someone had reported to the court that he smelled of alcohol.", "\n\nHere at MaineToday Media we value our readers and are committed to growing our community by encouraging you to add to the discussion.", "\n\nTo ensure conscientious dialogue we have implemented a strict no-bullying policy. ", "To participate, you must follow our Terms of Use. ", "Click here to flag and report a comment that violates our terms of use." ]

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[ "Donald Trump has blamed his predecessor for anti-Trump rallies nationwide and suggested Barack Obama had something to do with embarrassing leaks from the White House.", "\n\nIn a wide-ranging interview with Fox News' Fox and Friends show ahead of his first speech to Congress, the President laid the blame on Mr Obama for mobilising those against him.", "\n\nHe also gave himself an A+ for effort in his first weeks as President, but marked himself down for his political messaging \"a C or C+\".", "\n\n\"I think President Obama is behind it because his people are certainly behind it and some of the leaks possibly come from that group which are very serious leaks because they're bad in terms of national security, but I also understand that's politics.\"", "\n\nThe White House has been trying to crackdown on leaks coming from the Trump administration, partly led by press secretary Sean Spicer.", "\n\nDetails of a secret meeting were leaked to media shortly after Mr Spicer brought his communications team in to warn them about leaking information.", "\n\nThey reportedly had their personal and government-issued phones checked in the presence of lawyers.", "\n\nAn unnamed source told Politico Mr Spicer was unhappy with the information which had been passed to media from a planning meeting.", "\n\nMr Trump said he was \"okay\" with the way Mr Spicer was trying to stem the leaks and how he handled the phone checks.", "\n\nHowever, he would have done it differently.", "\n\n\"I would have gone one-on-one with different people.\"", "\n\nAsked if he'd check their phones during that meeting, he said it would have been a possibility.", "\n\n\"There's a hell of a lot of worse than that, I'll be honest with you.\"", "\n\nHe said he wouldn't be surprised if his theory about Mr Obama was true.", "\n\n\"I understand how the world works - that's politics. ", "I'm changing things he's wanted to do.\"", "\n\nThat includes changing the Affordable Care Act, often called Obamacare.", "\n\nThe plan, in part, allowed those with pre-existing medical conditions such as Alzheimer's disease, HIV and epilepsy, to get insurance coverage.", "\n\nIt is estimated to have allowed around 22 million people to get insurance coverage.", "\n\n\"We have a really terrific, I believe, healthcare plan coming out, we have to understand Obamacare has been a disaster, it's way out of control, it doesn't work.\"", "\n\nMr Trump also addressed his decision not to attend the White House Correspondents' dinner a tradition for presidents past which gives them a chance to show off their humorous sides.", "\n\nHe said the rise of \"fake news\" was partly behind the decision.", "\n\n\"Over the years you make a mistake, I fully understand when they [criticise] you, but when they make stories up, when they create sources, because I believe that sometimes they don't have sources, that the sources don't exist, and sometimes they do exist, I'm not saying all sources, but I believe a lot of the sources are made up, a lot of the stories are made up, I believe a lot of the stories are pure fiction - they just pull it out of air.", "\n\n\"I just thought in light of the fact of fake news and all these things we're talking about now I thought it would be inappropriate.\"", "\n\nBut he didn't rule out possibly attending in the future.", "\n\n\"I have great respect for the press, for reporters and the whole profession, with all of that being said, I thought it would be better if I didn't do the dinner that doesn't mean I won't do it next year.\"", "\n\nAll eyes on Congress speech\n\nAfter a turbulent start to his presidency, Mr Trump is set to go before Congress to give a speech that will be closely watched for details of his plans for the economy and whether he can strike a more conciliatory tone.", "\n\nWorld financial markets will be scrutinising the Tuesday night (local time) address in the House of Representatives for specifics of how the Republican president aims to make good on promises to tackle tax reform, boost infrastructure spending and simplify business regulations.", "\n\nWhite House officials say the speech will include some gestures toward unifying a country polarised by a bitterly fought election and divided in the early days of his presidency.", "\n\nAn average of recent polls by Real Clear Politics put his approval rating at about 44 percent, low for a new president.", "\n\nMr Trump has signed a flurry of executive orders, pulled the United States out of a Pacific trade deal and nominated a conservative judge, Neil Gorsuch, to fill a vacant position on the Supreme Court. ", "But his first month has been characterised by missteps, internal dramas and acrimonious disputes with the news media, and he has yet to score any legislative accomplishments.", "\n\nThe President's party controls both the House and Senate, giving him a chance to reshape the economy with lawmakers. ", "He faces a host of questions going into his first speech before a joint session of Congress.", "\n\nSpecifics of his plan to overhaul former President Obama's signature healthcare law have not been released. ", "He has yet to describe how to pay for a sharp increase in planned spending on rebuilding US roads and bridges.", "\n\nHis proposals to cut taxes for millions of people and corporations have not been sketched out. ", "His strategy for renegotiating international trade deals remains unclear. ", "He took delivery on Monday of a Pentagon proposal for fighting Islamic State militants and must decide on it in the days ahead.", "\n\nTrump seeks a big increase in defence spending but that plan includes a demand that non-defence federal agencies cut funds to offset the cost, painful reductions likely to face opposition in Congress.", "\n\nTrump's lack of legislative success so far contrasts with most of his recent predecessors, though not all of them.", "\n\nTrump's travel ban, which he says was needed for national security reasons, caused wide disruption at airports, sparked protests and was blocked by a federal court. ", "He is expected to sign a replacement order on Wednesday (local time).", "\n\nDemocratic lawmakers plan to attend the speech. ", "But at least one, Representative Luis Gutierrez of Illinois, has said he will protest Trump by refusing to applaud or give him a standing ovation, as is a custom at presidential speeches.", "\n\nReuters / Newshub." ]

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[ "NEWS RELEASE TRANSMITTED BY CCNMatthews\nFOR: WESTJET\nTSX SYMBOL: WJA\nNOVEMBER 7, 2002 - 12:15 EST\nWestJet Announces Service to Halifax\nCALGARY, ALBERTA--WestJet today announced that it is adding\nservice to the new market of Halifax, Nova Scotia starting\nFebruary 28, 2003. ", "WestJet will offer four flights daily between\nHamilton and Halifax, with connecting service to other WestJet\ndestinations. ", "One-way fares between Halifax and Hamilton will\nstart as low as $124.", "\nThis new Halifax service is made possible by the addition of\nWestJet's fifteenth Next-Generation Boeing 737-700 series\naircraft to be delivered in the first quarter of 2003. ", "In March\n2003, WestJet will also add increased frequency between Hamilton\nand Ottawa, Hamilton and Calgary, and Hamilton and Moncton.", "\nBill Lamberton, WestJet's Vice-President of Marketing and Sales,\ncommented today: \"We are extremely pleased to announce the\naddition of our newest WestJet city - Halifax, Nova Scotia.", "\nCommencing our service to Halifax with two daily departures to\nHamilton will provide strong connectivity between Halifax and a\ngreat number of other WestJet destinations. ", "We are looking\nforward to entering our seventh Canadian province, and bringing\nto Nova Scotians our unique brand of low-fare, fun and friendly\nservice.\"", "\nWestJet serves the 22 Canadian cities of Victoria, Comox,\nVancouver, Abbotsford/Fraser Valley, Prince George, Kelowna,\nCalgary, Edmonton, Grande Prairie, Fort McMurray, Saskatoon,\nRegina, Winnipeg, Sudbury, Sault Ste. ", "Marie, Thunder Bay, London,\nOttawa, Hamilton, Toronto, Moncton, and Halifax (beginning\nFebruary 28, 2003). ", "WestJet is publicly traded on the Toronto\nStock Exchange under the symbol WJA.", "\n-30-" ]

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[ "Q:\n\nC# HtmlAgilityPack encoding problem when loads html\n\nI'm using HTMLAGILITYPACK to extract all of data from a HTML local page but still have problem with special characters ... look it: https://prnt.sc/p7xegw (I can't use ~,`,´,ç and others).", "\nThis is my code to call my HTML page:\nSystem.", "IO.StreamReader myFile = new System.", "IO.StreamReader(\"C:/Users/Dev-02/Desktop/Daniel/xml_project/schemaproject/portal.html\");\n\nstring arquivohtml = myFile.", "ReadToEnd();\nHtmlAgilityPack.", "HtmlDocument doc = new HtmlAgilityPack.", "HtmlDocument();\n\ndoc.", "LoadHtml(arquivohtml);\n\nIs there a way to set my encoding while I'm calling my HTML page?", "\n\nA:\n\nYou need to pass the encoding to the StreamReader constructor, which parses your file's bytes.", "\n\n" ]

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[ "me number?", "\nTrue\nLet f be ((-3)/(-15))/(2/50). ", "Suppose -2*s + 1819 = 2*s - f*i, 2243 = 5*s + 4*i. ", "Is s a composite number?", "\nTrue\nLet g = 5098 - -515. ", "Is g prime?", "\nFalse\nSuppose 5*g - 50860 = 5*b, -g + 1165 = -3*b - 9003. ", "Is g a prime number?", "\nFalse\nSuppose -4*u + 2*u - 6 = 0. ", "Let c be 7/1 - (-12)/u. ", "Let s = c - -3. ", "Is s a composite number?", "\nTrue\nLet y(m) = 2 + 3*m + 36*m**3 + 4*m**2 - 37*m**3 - 10. ", "Let p be y(4). ", "Suppose -q - p*q = -k - 58, -4*q + 47 = -k. ", "Is q composite?", "\nFalse\nLet q = 2344 - 1437. ", "Let f = 190 + q. Is f a composite number?", "\nFalse\nSuppose -3*a = -4*a + 4314. ", "Suppose 4*d = 2*x + a, -d = 6*x - 4*x - 1071. ", "Is d prime?", "\nFalse\nSuppose -q = -2*b - 6149, -2*b + 6133 = -3*q + 4*q. ", "Suppose 2*c + q = j, 3287 - 15571 = -2*j + 2*c. ", "Is j composite?", "\nFalse\nSuppose -2*a = 2*w - 8, -5*a - 2*w = -10*a + 27. ", "Suppose -19720 = -a*k + 5*v, -5*v = 2*k + 2*k - 15767. ", "Is k composite?", "\nFalse\nSuppose -5*h = u - 859, 4391 = 5*u - 0*u + h. Is u a composite number?", "\nTrue\nLet i = 264 + 2335. ", "Is i composite?", "\nTrue\nLet x = 134 - 133. ", "Is -5147*(-5 - -5 - x) composite?", "\nFalse\nLet x be -4 + 2 - 200*-6. ", "Let k = x - -273. ", "Is k a prime number?", "\nTrue\nLet l = 30 - 28. ", "Suppose r = f - 117, l = 5*r - 3. ", "Is f a prime number?", "\nFalse\nLet a(b) = 1806*b - 197. ", "Is a(10) composite?", "\nFalse\nSuppose 0 = -2*o - 7*o + 306. ", "Let p be (-4)/o - (-36)/17. ", "Is p - (-25)/10*122 prime?", "\nTrue\nLet l = 613 - -302. ", "Let k = 10 - 4. ", "Suppose -k*j + l = -j. ", "Is j a composite number?", "\nTrue\nIs 5464576/156 - (-3)/(-9)*1 prime?", "\nFalse\nLet z = 323 - 192. ", "Let o = 240 + z. Is o a prime number?", "\nFalse\nSuppose -5*u + 13 = 3*d, 5*u - 3 = 2*d - 20. ", "Suppose d*b = -2*k + b + 111, -k - 4*b + 60 = 0. ", "Let x = k + -14. ", "Is x composite?", "\nTrue\nLet t = -5 - -8. ", "Suppose -4*j - 1984 = -4*y, t*y + 3*j - 1989 = -519. ", "Is y composite?", "\nTrue\nSuppose 0 = 5*l - r - 8715, -5*r - 848 - 919 = -l. ", "Suppose -4*c + 5*q + l + 15 = 0, 5*c - 2*q - 2209 = 0. ", "Is c composite?", "\nFalse\nLet i(p) = 53*p**3 + 4*p**2 + p + 2. ", "Let y(q) = -q. ", "Let s(a) = -i(a) + 2*y(a). ", "Let n be s(-2). ", "Suppose 3*w - n + 73 = 0. ", "Is w prime?", "\nTrue\nSuppose 3*j = -0*j + 24. ", "Suppose -j = -5*v + 7, 5*p - 3*v - 906 = 0. ", "Is p composite?", "\nTrue\nLet t = -1576 - -604. ", "Let o = -653 - t. Is o composite?", "\nTrue\nLet o = -1702 + 2583. ", "Suppose -2673 = -3*z - 3*c, -z = -5*c + c - o. Is z a prime number?", "\nFalse\nSuppose -6*p + 10659 = 27*p. ", "Is p a prime number?", "\nFalse\nLet a(v) = v**2 + 3*v - 5. ", "Let w be a(2). ", "Suppose -2*k + 467 = k + c, w*k = -3*c + 773. ", "Is k prime?", "\nTrue\nLet v(p) = -p**3 + 33*p**2 - 19*p - 39. ", "Is v(28) prime?", "\nFalse\nLet h = -9 + 9. ", "Suppose 2*d + 5*a - 4*a - 633 = h, 5*d + a = 1590. ", "Is d a prime number?", "\nFalse\nLet t(h) = -70*h**2 - 8*h - 12. ", "Let o be t(-2). ", "Let b = -189 - o. Is b composite?", "\nTrue\nLet k(d) = 260*d**2 - 7*d + 26. ", "Is k(5) composite?", "\nFalse\nLet k(v) be the second derivative of -7*v**4/4 + 5*v**3/6 + 3*v**2/2 - 4*v. ", "Let z(h) be the first derivative of k(h). ", "Is z(-7) prime?", "\nFalse\nLet l(i) = 3*i + 9. ", "Let q be l(-3). ", "Suppose q*m = -2*m + 134. ", "Is m composite?", "\nFalse\nLet q(u) = u + 77. ", "Suppose -2*p = 7 - 9. ", "Let n = p + -1. ", "Is q(n) prime?", "\nFalse\nSuppose 3*t = 7*t + p - 35538, 5*p = -5*t + 44415. ", "Is t a composite number?", "\nTrue\nLet r(o) = -31*o**3 + 90*o**2 + 46*o + 60. ", "Let x(c) = 6*c**3 - 18*c**2 - 9*c - 12. ", "Let p(k) = 2*r(k) + 11*x(k). ", "Is p(9) a prime number?", "\nFalse\nSuppose 50031 = -39*w + 66*w. ", "Is w a composite number?", "\nTrue\nLet m(f) = 4152*f**2 - 27*f + 111. ", "Is m(6) a prime number?", "\nFalse\nIs (2 - -327)*26/26 a prime number?", "\nFalse\nLet p(f) = 33*f**3 + 10*f**2 - 22*f + 13. ", "Is p(6) composite?", "\nFalse\nSuppose -3*p = g - 0*g - 187, 5*g = -5*p + 975. ", "Suppose 0 = -h + 2*o + 225, 2*h + o - g - 241 = 0. ", "Is h a prime number?", "\nFalse\nSuppose 60*i = -17489 + 345869. ", "Is i composite?", "\nTrue\nSuppose n - 3*b - 235 = 2*b, n + 3*b - 227 = 0. ", "Suppose 2*z - 2*l + 5*l = -92, -5*z - n = -l. ", "Let s = z - -83. ", "Is s prime?", "\nTrue\nSuppose -1811312 - 109151 = -61*s. ", "Is s a composite number?", "\nTrue\nSuppose 219405 = 6*v - 113229. ", "Is v a prime number?", "\nTrue\nLet f be ((-12)/(-2))/(3 - 2). ", "Suppose -f*p + 1974 = -0*p. ", "Is p prime?", "\nFalse\nLet o(d) be the first derivative of -445*d**4/4 - d**3/3 - d**2 + 12. ", "Is o(-1) prime?", "\nFalse\nLet t(v) = -v**3 + v**2 - v + 623. ", "Let l = 49 + -49. ", "Is t(l) a composite number?", "\nTrue\nLet s(d) = 6189*d**3 + 4*d**2 - 3*d + 1. ", "Is s(1) prime?", "\nFalse\nSuppose -4*p = -p + 1485. ", "Let y = -4 + -728. ", "Let w = p - y. Is w a prime number?", "\nFalse\nLet q(h) = h**3 - 4*h**2 + 4*h - 3. ", "Let i be q(3). ", "Suppose -7*j + 6238 - 1065 = i. Is j a prime number?", "\nTrue\nLet z = -51 - -56. ", "Is (7 + z + -11)*(-1 + 1590) prime?", "\nFalse\nLet m be (2*1)/(27/162). ", "Is 682/6 + m/9 prime?", "\nFalse\nSuppose 8*r + 6 = 10*r. ", "Suppose 4*y - 3*i - 5605 = 0, 6*i = r*i - 9. ", "Is y prime?", "\nTrue\nLet n = 1 - -1. ", "Suppose -4*s + 0*s = -n*b, -s - 14 = 3*b. ", "Is 2*((-370)/b - -3) composite?", "\nFalse\nIs (1 - 163077/6)/(30/(-20)) a composite number?", "\nFalse\nLet y = -53 - -246. ", "Suppose y = -4*t + 37. ", "Is t*2/((-18)/21) prime?", "\nFalse\nLet o = -2 - 5. ", "Is -4 - (o - 4/4) a prime number?", "\nFalse\nSuppose -2*h - 3*d = -3734, -h - 4*d + 1867 = -0*h. ", "Suppose -h - 494 = -3*u. ", "Is u a composite number?", "\nFalse\nLet j(d) = -20*d**3 + 2*d**2 - 4*d - 1. ", "Let p be j(-3). ", "Let w = 812 - p. Let y = w - 132. ", "Is y a composite number?", "\nTrue\nSuppose -2738 = -4*l + 5*r, -4*r - 1368 = -2*l - 2*r. ", "Suppose -k - 1383 = 2*k. ", "Let y = k + l. Is y prime?", "\nFalse\nLet v = -738 + 7025. ", "Is v composite?", "\nFalse\nSuppose -2*t - 26 = -26. ", "Suppose 8*a - 11*a + 2001 = t. Is a a prime number?", "\nFalse\nSuppose 2*q + 3*q = 10. ", "Suppose 0 = 5*d + 2*g + 2845, q*d - 3*d - 551 = 4*g. ", "Let c = -273 - d. Is c prime?", "\nFalse\nLet l(h) = h**3 + 6*h**2 + 9*h - 2. ", "Let n be l(-5). ", "Let y = -7 + n. Let r = y + 38. ", "Is r composite?", "\nTrue\nSuppose 0*c = 2*c - 6. ", "Suppose 1 = -y - 4*g, 4*y - 19 = 4*g - c. Suppose -5*f - 185 = -y*n, -f = -4*f - 12. ", "Is n prime?", "\nFalse\nSuppose -11999 = -2*q + 5565. ", "Is q a prime number?", "\nFalse\nSuppose -5*o = x - 426490, -o - 5*x + 32520 + 52802 = 0. ", "Is o a composite number?", "\nFalse\nLet w be (-2 + 0)*-5*1. ", "Let l = w + -6. ", "Suppose 2*i - l*i - m = -577, -4*i - m = -1151. ", "Is i a prime number?", "\nFalse\nLet j(n) = -11 - 16*n + n + 2*n**3 - n**2 - n**3 - 3*n. ", "Is j(8) a prime number?", "\nTrue\nLet y(o) = -249*o + 3. ", "Let i be y(-2). ", "Let j = i - 286. ", "Is j a prime number?", "\nFalse\nSuppose -3*w + 21 = -3*g, 8 = 4*w + g - 10. ", "Let j(f) = 590*f + 16. ", "Is j(w) a composite number?", "\nTrue\nLet t = -12 + 7. ", "Let n(g) = -5 + 20*g**2 - 6 - 328*g + 162*g + 161*g. ", "Is n(t) composite?", "\nTrue\nIs 6381*((-260)/(-36) + -7) a prime number?", "\nFalse\nLet l(k) = k - 5. ", "Let d = 15 - 5. ", "Let z be l(d). ", "Suppose -969 - 686 = -z*j. ", "Is j a prime number?", "\nTrue\nLet i(x) = x**3 + 10*x**2 - 9*x + 16. ", "Let n be i(-11). ", "Let o = n + 10. ", "Suppose -u + o*u - 222 = 0. ", "Is u prime?", "\nFalse\nLet d(x) = -5*x**3 - 7*x**2 - 7*x + 6. ", "Is d(-5) a prime number?", "\nTrue\nSuppose 4*d + 3*u = 20822, d - 5201 = -3*u - 0*u. ", "Is d a composite number?", "\nTrue\nSuppose 291*n + 106181 = 3*o + 289*n, 3*o - 5*n = 106175. ", "Is o prime?", "\nFalse\nLet t = 3211 + -980. ", "Is t prime?", "\nFalse\nLet s be 6 + 2508 + 2*2. ", "Suppose 7*f = 5*f + s. Is f a composite number?", "\nFalse\nSuppose 356 - 7056 = -5*i. ", "Suppose 3*w = -w + i. Is w prime?", "\nFalse\nLet w = -8 - -10. ", "Suppose -c = -w*b + 8, -4*c - b = 3*b - 4. ", "Let p(n) = -44*n - 3. ", "Is p(c) a prime number?", "\nFalse\nLet z be 3*(-2 - -3) + 11445. ", "Let m = z - 5397. ", "Suppose -3*n - 1197 = 4*p - 4834, -m = -5*n + 4*p. ", "Is n composite?", "\nTrue\nSuppose 4 = 4*d - 2*d. ", "Suppose -1098 = -2*i + g + 4830, i = d*g + 2970. ", "Is i a prime number?", "\nFalse\nLet x = 499 + 104. ", "Let a = 4888 - x. Is a composite?", "\nTrue\nLet u = 1813 - 992. ", "Is u prime?", "\nTrue\nLet y(j) be the third derivative of 0 + 1/6*j**4 + 1/20*j**5 - 5/3*j**3 + 7*j**2 + 0*j. ", "Is y(5) a prime number?", "\nFalse\nSuppose -w = d - 13, 0*w - 3*d = -2*w + 26. ", "Suppose w*g - 15 = 8*g. ", "Suppose 5*s + y = 1050, 0*y + 628 = g*s + y. Is s a composite number?", "\nFalse\nLet z = 7 + -5. ", "Suppose 5*s - 196 = -2*p + 727, z*s + p = 369. ", "Is s prime?", "\nFalse\nIs (-40022)/(-6) - 4 - (-12)/18 prime?", "\nFalse\nLet q be (3*1/(-2))/((-3)/22340). ", "Suppose 5*g + 405 = q. Is g a prime number?", "\nTrue\nSuppose -5*a = -3*a - 3*l - 1840, 0 = -4*a - 3*l + 3698. ", "Suppose 569 = 4*y - a. Is y a composite number?", "\nFalse\nIs 8567915/170 - 2*(-3)/4 composite?", "\nTrue\nLet q(d) = 592*d**2 + 3*d - 18. ", "Is q(-5) prime?", "\nTrue\nLet n = -958 - -1356. ", "Let m = n - -723. ", "Suppose 414 = " ]

{ "pile_set_name": "DM Mathematics" }

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[ "Mariamman Temple, Irukkankudi\n\nMariamman Temple is located in Irukkankdi, Virudhunagar District. ", "Mariamman is the Moolavar in the temple.", "\n\nTemple History \nThis happened 300 years ago between Arjuna and Vaiparu rivers. ", " A priest – Poosari – woman filled her basket with the cow dung she gathered and was prepared to go home with the basket but could not lift it alone. ", " She asked others to help her. ", "They too could not lift the basket. ", "She herself was influenced by the power of Goddess and exclaimed that Amman was under the ground where the basket was placed and ordered them to take Her out and build a temple.", "\n\nThe villagers found the idol of Mother Amman, built the temple and are doing the pujas. ", " Since then, She is the deity for the villagers taking care of their welfare.", "\n\nThe sanctum sanctorum is under a beautiful vimana. ", " The Artha Mandap and Maha Mandap are close to the sanctum. ", " Sri Nandeeswara and flag post-Kodimaram are in a line. ", " Lord Vinayaka is under the Arasa Maram. ", " On the west are Vazha Vandha Amman and Rakachi Amman. ", " Pechi Amman and Muppidari Amman are in separate shrines on the northwest. ", " Kathavarayan and Vairavamurthi are in the east. ", " Karuppusami is in southeast corner. ", " Devotees worship all these deities and Mariamman in order.", "\n\nReferences \n\nCategory:Hindu temples in Virudhunagar district" ]

{ "pile_set_name": "Wikipedia (en)" }

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[ "Q:\n\nSaving month name and year from Ajax Calender into SQL Server 2005 DateTime Column\n\nI have a simple Asp.", "NET webform with a TextBox. ", "I have attached an AjaxControlToolkit CalendarExtender to this TextBox to provide for Calendar functionality. ", "I have set the CalenderExtender format property to \"MMMM\" such that the calender by default will display months rather than month days. ", "\nWHAT I WANT TO ACHIEVE:\nI have a table with a StartMonth column whose datatype is DateTime. ", "When the user selects say June or October from the calendar, I want to save that month in this DateTime column but unfortunately, strings \"June\" or \"October, .....\" can not be saved in a DateTime column. ", "\nHow should implement this better?, ", "I want to store the month name and year, I'm not interested in the day part.", "\n\nA:\n\ni take this as the answer to my question.", "\nhttp://www.aghausman.net/asp/how-to-show-and-select-monthyear-in-calendar-extender.html\n\n" ]

{ "pile_set_name": "StackExchange" }

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[ "Q:\n\nThe existence of a function with application in finding bounded gaps between primes\n\nLet $p_n$ denote the $n$'th prime number. ", "Can anything be said about the existence of a continuous differentiable function $f(x)$ and a positive constant $D > 0$ such that $$\\frac{f(p_{n+1})}{f(p_n)} < D\\cdot \\frac{f^{\\prime}(p_n)}{f(p_n) \\log(p_n)}$$ for all $p_n$ with $n > N$ where $N$ is an arbitrary fixed positive constant? ", "Further more the derivative must be monotone (increasing or decreasing). ", "One can use eventually the fact that $p_{n+1} - p_n < p_n^\\theta$ with $\\theta > 0.525$ for $n$ large enough. ", "The motivation for this is the following: \nSupposing that such a function exists and suppose $f'$ is increasing. ", "Also suppose that $p_{n+1} -p_n > D$. Then by mean value theorem $\\exists c_n \\in (p_n, p_{n+1})$ such that $$ f(p_{n+1}) = (p_{n+1} - p_n) f^{\\prime}(c_n) + f(p_n) \\geq D \\cdot f'(p_n) + f(p_n)$$ $\\forall n > N$ hence $$ f(p_{n+1}) \\geq D \\sum_{i=N}^n f'(p_i) + f(p_N)$$ Denote $S(p_n) = \\sum_{i=1}^n f'(p_i)$ and (if I am not wrong, again) $S(p_n) \\sim \\frac{f'(p_n)}{\\log(p_n)}$ Now this can be used to obtain a contradiction isn't it? ", " \n\nA:\n\nAs you observe, if $f$ and $f'$ are positive and increasing,\n$$\\frac{f(p_{n+1})}{f'(p_n)}>p_{n+1}-p_n.$$\nThe right hand side is not bounded (there exist large gaps between primes), hence the left hand side is not bounded either. ", "This contradicts your assumption, even when you omit $\\log(p_n)$.\n\n" ]

{ "pile_set_name": "StackExchange" }

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[ "Amplitude normalization applied to an artificial neural network-based automatic sleep spindle detection system.", "\nSleep spindles are significant rhythmic transients present in the sleep electroencephalogram (EEG) of non-rapid eye movement (NREM) sleep. ", "Automatic sleep spindle detection techniques are sought for the automation of sleep staging and the detailed study of sleep spindle patterns, of possible physiological significance. ", "A deficiency of many of the available automatic detection techniques is their reliance on the amplitude level of the recorded EEG voltage values. ", "In the present work, an automatic sleep spindle detection system that has been previously proposed, using a Multi-Layer Perceptron (MLP) Artificial Neural Network (ANN), was evaluated using a voltage amplitude normalization procedure, with the aim of making the performance of the ANN independent of the absolute voltage level of the individual subjects' recordings. ", "The application of the normalization procedure led to a reduction in the false positive rate (FPR) as well as in the sensitivity. ", "When the ANN was trained on a combination of data from healthy subjects, the reduction of FPR was from 42.6% to 19%, while the sensitivity of the ANN was kept at acceptable levels, i.e., 73.4% for the normalized procedure vs 84.6% for the non-normalized procedure." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "// Copyright 2017 Yahoo Holdings. ", "Licensed under the terms of the Apache 2.0 license. ", "See LICENSE in the project root.", "\n\n#pragma once\n\n#include \"intermediate.h\"\n#include \"querynodemixin.h\"\n#include \"term.h\"\n\nnamespace search::query {\n\nclass And : public QueryNodeMixin<And, Intermediate> {\npublic:\n virtual ~And() = 0;\n};\n\n//-----------------------------------------------------------------------------\n\nclass AndNot : public QueryNodeMixin<AndNot, Intermediate> {\npublic:\n virtual ~AndNot() = 0;\n};\n\n//-----------------------------------------------------------------------------\n\nclass Or : public QueryNodeMixin<Or, Intermediate> {\npublic:\n virtual ~Or() = 0;\n};\n\n//-----------------------------------------------------------------------------\n\nclass WeakAnd : public QueryNodeMixin<WeakAnd, Intermediate> {\n uint32_t _minHits;\n vespalib::string _view;\npublic:\n virtual ~WeakAnd() = 0;\n\n WeakAnd(uint32_t minHits, const vespalib::string & view) : _minHits(minHits), _view(view) {}\n\n uint32_t getMinHits() const { return _minHits; }\n const vespalib::string & getView() const { return _view; }\n};\n\n//-----------------------------------------------------------------------------\n\nclass Equiv : public QueryNodeMixin<Equiv, Intermediate> {\nprivate:\n int32_t _id;\n Weight _weight;\npublic:\n virtual ~Equiv() = 0;\n\n Equiv(int32_t id, Weight weight)\n : _id(id), _weight(weight)\n {}\n\n Weight getWeight() const { return _weight; }\n int32_t getId() const { return _id; }\n};\n\n//-----------------------------------------------------------------------------\n\nclass Rank : public QueryNodeMixin<Rank, Intermediate> {\npublic:\n virtual ~Rank() = 0;\n};\n\n//-----------------------------------------------------------------------------\n\nclass Near : public QueryNodeMixin<Near, Intermediate>\n{\n uint32_t _distance;\n\n public:\n Near(size_t distance) : _distance(distance) {}\n virtual ~Near() = 0;\n\n size_t getDistance() const { return _distance; }\n};\n\n//-----------------------------------------------------------------------------\n\nclass ONear : public QueryNodeMixin<ONear, Intermediate>\n{\n uint32_t _distance;\n\n public:\n ONear(size_t distance) : _distance(distance) {}\n virtual ~ONear() = 0;\n\n size_t getDistance() const { return _distance; }\n};\n\n//-----------------------------------------------------------------------------\n\nclass Phrase : public QueryNodeMixin<Phrase, Intermediate>, public Term {\npublic:\n Phrase(const vespalib::string &view, int32_t id, Weight weight)\n : Term(view, id, weight), _expensive(false) {}\n virtual ~Phrase() = 0;\n Phrase &set_expensive(bool value) {\n _expensive = value;\n return *this;\n }\n bool is_expensive() const { return _expensive; }\nprivate:\n bool _expensive;\n};\n\nclass SameElement : public QueryNodeMixin<SameElement, Intermediate> {\npublic:\n SameElement(const vespalib::string &view) : _view(view), _expensive(false) {}\n virtual ~SameElement() = 0;\n const vespalib::string & getView() const { return _view; }\n SameElement &set_expensive(bool value) {\n _expensive = value;\n return *this;\n }\n bool is_expensive() const { return _expensive; }\nprivate:\n vespalib::string _view;\n bool _expensive;\n};\n\nclass WeightedSetTerm : public QueryNodeMixin<WeightedSetTerm, Intermediate>, public Term {\npublic:\n WeightedSetTerm(const vespalib::string &view, int32_t id, Weight weight)\n : Term(view, id, weight) {}\n virtual ~WeightedSetTerm() = 0;\n};\n\nclass DotProduct : public QueryNodeMixin<DotProduct, Intermediate>, public Term {\npublic:\n DotProduct(const vespalib::string &view, int32_t id, Weight weight)\n : Term(view, id, weight) {}\n virtual ~DotProduct() = 0;\n};\n\nclass WandTerm : public QueryNodeMixin<WandTerm, Intermediate>, public Term {\nprivate:\n uint32_t _targetNumHits;\n int64_t _scoreThreshold;\n double _thresholdBoostFactor;\npublic:\n WandTerm(const vespalib::string &view, int32_t id, Weight weight,\n uint32_t targetNumHits, int64_t scoreThreshold, double thresholdBoostFactor)\n : Term(view, id, weight),\n _targetNumHits(targetNumHits),\n _scoreThreshold(scoreThreshold),\n _thresholdBoostFactor(thresholdBoostFactor) {}\n virtual ~WandTerm() = 0;\n uint32_t getTargetNumHits() const { return _targetNumHits; }\n int64_t getScoreThreshold() const { return _scoreThreshold; }\n double getThresholdBoostFactor() const { return _thresholdBoostFactor; }\n};\n\n}\n" ]

{ "pile_set_name": "Github" }

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[ "Max Coates\n\nMax Peter Coates (born 4 January 1994) is a British racing driver currently competing in the Clio Cup Championship, also currently competing in the 2019 Britcar Endurance Championship.", "\n\nRacing career\nAfter several years of karting, Coates made his car racing debut in 2010, racing in the Ginetta Junior Championship. ", " He spent two years in this series before graduating to the Ginetta GT Supercup for 2012, 2013 and 2014, but his racing programmes have often been stymied by a lack of budget, restricting him to part-seasons and guest appearances, such as a one-off outing in the Porsche Carrera Cup Great Britain in 2014.", "\n\nAfter four rounds of the 2015 British Touring Car Championship season, Coates was signed by the Support Our Paras team to drive its second entry for the remainder of the season, alongside Derek Palmer Jr.. He took the seat that was previously occupied by Richard Hawken and Martin Donnelly. ", "However, due a sponsorship problem, he lost his drive following just one round of the championship.", "\n\nAfter a successful season in 2018, Coates once again joined Guy Colclough in the DAT Racing TCR-spec SEAT to race in the 2019 Britcar Endurance Championship season.", "\n\nRacing record\n\nComplete Ginetta Junior Championship results\n(key) (Races in bold indicate pole position – 1 point awarded just in first race; races in italics indicate fastest lap – 1 point awarded all races;-\n\nComplete Ginetta GT4 Supercup results\n(key) (Races in bold indicate pole position – 1 point awarded just in first race; races in italics indicate fastest lap – 1 point awarded all races;-\n\nComplete British Touring Car Championship results\n(key) (Races in bold indicate pole position – 1 point awarded just in first race; races in italics indicate fastest lap – 1 point awarded all races; * signifies that driver led race for at least one lap – 1 point given all races)\n\nComplete Renault Clio Cup UK results\n(key) (Races in bold indicate pole position – 1 point awarded just in first race; races in italics indicate fastest lap – 1 point awarded all races;- Races with * indicate driver lead a lap in race – 1 point awarded all races (2018-2019);-\n\n{| class=\"wikitable\" style=\"text-align:center; font-size:85%\"\n! ", "Year\n! ", "Team\n! ", "1\n! ", "2\n! ", "3\n! ", "4\n! ", "5\n! ", "6\n! ", "7\n! ", "8\n! ", "9\n! ", "10\n! ", "11\n! ", "12\n! ", "13\n! ", "14\n! ", "15\n! ", "16\n! ", "17\n! ", "18\n! ", "DC\n! ", "Pts\n|-\n| 2016\n! ", "Ciceley Motorsport\n|style=\"background:#DFFFDF;\"| BHI16\n|style=\"background:#DFFFDF;\"| BHI28\n|style=\"background:#DFFFDF;\"| DON14\n|style=\"background:#DFFFDF;\"| DON25\n|style=\"background:#DFFFDF;\"| THR19\n|style=\"background:#DFFFDF;\"| THR210\n|style=\"background:#FFDF9F;\"| OUL13\n|style=\"background:#DFFFDF;\"| OUL25\n|style=\"background:#DFDFDF;\"| CRO12\n|style=\"background:#FFFFBF;\"| CRO21\n|style=\"background:#DFDFDF;\"| SNE12\n|style=\"background:#DFFFDF;\"| SNE25\n|style=\"background:#DFFFDF;\"| ROC18\n|style=\"background:#FFDF9F;\"| ROC23\n|style=\"background:#DFFFDF;\"| SIL15\n|style=\"background:#FFDF9F;\"| SIL25\n|style=\"background:#DFFFDF;\"| BHGP16\n|style=\"background:#DFDFDF;\"| BHGP22\n! ", "style=\"background:#FFDF9F;\"| 3rd\n! ", "style=\"background:#FFDF9F;\"| 361\n|-\n| 2017\n! ", "Ciceley Motorsport\n|style=\"background:#DFFFDF;\"| BHI16\n|style=\"background:#DFFFDF;\"| BHI26\n|style=\"background:#FFFFBF;\"| DON11\n|style=\"background:#FFDF9F;\"| DON23\n|style=\"background:#DFFFDF;\"| THR18\n|style=\"background:#EFCFFF;\"| THR2Ret<\n|style=\"background:#DFFFDF;\"| OUL16\n|style=\"background:#DFFFDF;\"| OUL25\n|style=\"background:#DFFFDF;\"| CRO16\n|style=\"background:#DFDFDF;\"| CRO22\n|style=\"background:#DFFFDF;\"| SNE17\n|style=\"background:#DFDFDF;\"| SNE22\n|style=\"background:#FFFFBF;\"| ROC11\n|style=\"background:#FFDF9F;\"| ROC23\n|style=\"background:#DFFFDF;\"| SIL19\n|style=\"background:#DFFFDF;\"| SIL24\n|style=\"background:#DFFFDF;\"| BHGP18\n|style=\"background:#DFFFDF;\"| BHGP29\n! ", "4th\n! ", "360\n|-\n| 2018\n! ", "Team Pyro\n|style=\"background:#DFFFDF;\"| BHI15*\n|style=\"background:#FFFFBF;\"| BHI21*\n|style=\"background:#DFFFDF;\"| DON16\n|style=\"background:#DFFFDF;\"| DON26\n|style=\"background:#DFDFDF;\"| THR12*\n|style=\"background:#FFDF9F;\"| THR23\n|style=\"background:#FFDF9F;\"| OUL13\n|style=\"background:#FFFFBF;\"| OUL21*\n|style=\"background:#DFDFDF;\"| CRO12\n|style=\"background:#FFFFBF;\"| CRO21*\n|style=\"background:#DFFFDF;\"| SNE111\n|style=\"background:#FFFFBF;\"| SNE21*\n|style=\"background:#EFCFFF;\"| ROC1Ret\n|style=\"background:#FFDF9F;\"| ROC23\n|style=\"background:#EFCFFF;\"| SIL1Ret\n|style=\"background:#DFFFDF;\"| SIL25\n|style=\"background:#DFFFDF;\"| BHGP15\n|style=\"background:#DFFFDF;\"| BHGP24\n! ", "style=\"background:#FFDF9F;\"| 3rd\n! ", "style=\"background:#FFDF9F;\"| 309\n|-\n| 2019\n! ", "Team HARD\n|style=\"background:#FFFFBF;\"| BHI11*\n|style=\"background:#FFFFBF;\"| BHI21*\n|style=\"background:#EFCFFF;\"| DON1Ret\n|style=\"background:#FFDF9F;\"| DON23\n|style=\"background:#FFFFBF;\"| CRO11*\n|style=\"background:#FFFFBF;\"| CRO21*\n|style=\"background:#FFDF9F;\"| OUL13\n|style=\"background:#FFFFBF;\"| OUL21*\n|style=\"background:#DFFFDF;\"| SNE16*\n|style=\"background:#FFFFBF;\"| SNE21\n|style=\"background:#DFDFDF;\"| THR12\n|style=\"background:#EFCFFF;\"| THR2Ret*\n|style=\"background:#FFFFBF;\"| KNO11*\n|style=\"background:#DFDFDF;\"| KNO22\n|style=\"background:#DFDFDF;\"| SIL12\n|style=\"background:#DFFFDF;\"| SIL211\n|style=\"background:#FFDF9F;\"| BRH13\n|style=\"background:#DFDFDF;\"| BRH22\n! ", "style=\"background:#DFDFDF;\"| 2nd\n! ", "style=\"background:#DFDFDF;\"| 357\n|-\n|}\n\nComplete Britcar results\n(key) (Races in bold indicate pole position in class – 1 point awarded just in first race; races in italics indicate fastest lap in class – 1 point awarded all races;-\n\nComplete TCR UK/Touring Car Trophy results\n(key) (Races in bold''' indicate pole position – 1 point awarded just in first race; races in italics'' indicate fastest lap – 1 point awarded all races; * signifies that driver led race for at least one lap – 1 point given all races)\n\nReferences\n\nExternal links\n Official website\n \n\nCategory:Living people\nCategory:British Touring Car Championship drivers\nCategory:English racing drivers\nCategory:British racing drivers\nCategory:Britcar drivers\nCategory:1994 births" ]

{ "pile_set_name": "Wikipedia (en)" }

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[ "Hannity: 'President Trump Has Been Vindicated' By Report of Spying on Manafort\n\nThreatening a 'War Crime': Mainstream Media Reacts to Trump's UN Speech\n\nJudge Andrew Napolitano says a report that former Trump campaign chairman Paul Manafort was wiretapped is \"absolutely consistent\" with President Donald Trump's claims from earlier this year.", "\n\nTrump was blasted for claiming in March that the Obama administration wiretapped Trump Tower.", "\n\nTerrible! ", "Just found out that Obama had my \"wires tapped\" in Trump Tower just before the victory. ", "Nothing found. ", "This is McCarthyism! — ", "Donald J. Trump (@realDonaldTrump) March 4, 2017\n\nAccording to a new report, Manafort was surveilled by the FBI before and after the election, although it’s unclear if Trump’s discussions were ever picked up.", "\n\nOn \"America's Newsroom\" today, Napolitano pointed out that before Manafort worked on the Trump campaign, he was a tenant at Trump Tower.", "\n\n\"It does appear as though the essence of President Trump's statement ... is true, even though he was ridiculed,\" Napolitano said.", "\n\nHe explained that it's not clear if Trump or Manafort was the primary target of the wiretaps, but it's possible that there was indeed surveillance of Trump Tower.", "\n\nBill Hemmer pointed out that Trump may have used the phrase \"Obama had my 'wires tapped' in Trump Tower\" because he was referring to \"wires\" that he had control over because he owned the building.", "\n\n\"That may very well be what he was talking about,\" Napolitano said. \"", "If that's the case, he was 100 percent correct, even though he was ridiculed for months.\"", "\n\nWatch more above.", "\n\nTucker Breaks Down New Trump Wiretap Report: 'Rogue' Intel Agencies or DC 'Collusion'\n\nHuckabee: Why Manafort Wiretap Should Be 'Frightening' for Every American" ]

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