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[ "EXPERIMENTAL", "and", "MOLECULAR", "MEDICINE,", "Vol.", "44,", "No.", "2,", "130-137,", "February", "2012", "Identification", "of", "novel", "peptides", "that", "stimulate", "human", "neutrophils", "Geon", "Ho", "Bae1*,", "Ha", "Young", "Lee1,2*,", "Young", "Su", "Jung1,2,", "Jae", "Woong", "Shim1,", "Sang", "Doo", "Kim1,2,", "Suk-Hwan", "Baek3,", "Jae", "Young", "Kwon1,", "Joon", "Seong", "Park4", "and", "Yoe-Sik", "Bae1,2,5", "1Department", "of", "Biological", "Sciences", "Sungkyunkwan", "University", "Suwon", "440-746,", "Korea", "2Mitochondria", "Hub", "Regulation", "Center", "College", "of", "Medicine,", "Dong-A", "University", "Busan", "602-714,", "Korea", "3Department", "of", "Biochemistry", "and", "Molecular", "Biology", "Yeungnam", "University", "Daegu", "705-030,", "Korea", "4Department", "of", "Hematology-Oncology", "Ajou", "University", "School", "of", "Medicine", "Suwon", "443-721,", "Korea", "5Corresponding", "author:", "Tel,", "82-31-290-5914;", "Fax,", "82-31-290-7015;", "E-mail,", "yoesik@skku.edu", "*These", "authors", "contributed", "equally", "to", "this", "work.", "http://dx.doi.org/10.3858/emm.2012.44.2.008", "Accepted", "14", "November", "2011", "Available", "Online", "16", "November", "2011", "Abbreviations:", "FPR,", "formyl", "peptide", "receptor;", "GMMWAI,", "Gly-", "Met-Met-Trp-Ala-Ile-CONH2;", "IP3,", "inositol-1,4,5-triphosphate;", "MMHWAM,", "Met-Met-His-Trp-Ala-Met-CONH2;", "MMHWFM,", "Met-Met-His-Trp-Phe-Met-CONH2;", "PLC,", "phospholipase", "C;", "PS-SPCL,", "positional", "scanning", "synthetic", "peptide", "combinatorial", "library;", "PTX,", "pertussis", "toxin", "Abstract", "Neutrophils", "play", "a", "key", "role", "in", "innate", "immunity,", "and", "the", "identification", "of", "new", "stimuli", "that", "stimulate", "neutrophil", "activity", "is", "a", "very", "important", "issue.", "In", "this", "study,", "we", "iden-", "tified", "three", "novel", "peptides", "by", "screening", "a", "synthetic", "hexapeptide", "combinatorial", "library.", "The", "identified", "pep-", "tides", "GMMWAI,", "MMHWAM,", "and", "MMHWFM", "caused", "an", "increase", "in", "intracellular", "Ca2+", "in", "a", "concentration-de-", "pendent", "manner", "via", "phospholipase", "C", "activity", "in", "human", "neutrophils.", "The", "three", "peptides", "acted", "specifically", "on", "neutrophils", "and", "monocytes", "and", "not", "on", "other", "non-leu-", "kocytic", "cells.", "As", "a", "physiological", "characteristic", "of", "the", "peptides,", "we", "observed", "that", "the", "three", "peptides", "induced", "chemotactic", "migration", "of", "neutrophils", "as", "well", "as", "stimu-", "lated", "superoxide", "anion", "production.", "Studying", "receptor", "specificity,", "we", "observed", "that", "two", "of", "the", "peptides", "(GMMWAI", "and", "MMHWFM)", "acted", "on", "formyl", "peptide", "re-", "ceptor", "(FPR)1", "while", "the", "other", "peptide", "(MMHWAM)", "act-", "ed", "on", "FPR2.", "Since", "the", "three", "novel", "peptides", "were", "specif-", "ic", "agonists", "for", "FPR1", "or", "FPR2,", "they", "might", "be", "useful", "tools", "to", "study", "FPR1-", "or", "FPR2-mediated", "immune", "response", "and", "signaling.", "Keywords:", "calcium;", "chemotaxis;", "neutrophils;", "pep-", "tide", "library;", "peptides;", "receptors,", "formyl", "peptide", "Introduction", "Neutrophils", "play", "an", "important", "role", "in", "the", "regulation", "of", "immune", "responses,", "especially", "in", "the", "innate", "immune", "response", "(Kumar", "and", "Sharma,", "2010).", "Neutrophils", "are", "recruited", "to", "infected", "areas", "or", "sites", "of", "injury", "according", "to", "a", "chemoattractant", "gradient", "(Borregaard,", "2010;", "Kumar", "and", "Sharma,", "2010).", "Recruited", "neutrophils", "can", "be", "activated", "by", "extra-", "cellular", "stimuli,", "resulting", "in", "the", "production", "of", "several", "reactive", "oxygen", "species", "(Dahlgren", "and", "Karlssson,", "1999;", "Walther", "et", "al.,", "2000;", "Tiffany", "et", "al.,", "2001).", "It", "is", "a", "critical", "aspect", "of", "resting", "neutrophils", "that", "they", "must", "be", "activated", "for", "host", "defense.", "The", "activation", "of", "neutrophils", "can", "be", "induced", "by", "various", "different", "stimuli,", "including", "pathogen-derived", "molecules", "and", "several", "chemoattractants", "(Walther", "et", "al.,", "2000;", "Tiffany", "et", "al.,", "2001;", "Sabroe", "et", "al.,", "2003;", "Kobayashi,", "2008).", "Among", "these,", "chemo-", "attractants,", "including", "several", "chemokines", "that", "regulate", "the", "activities", "of", "neutrophils,", "have", "received", "much", "attention", "over", "the", "last", "decade.", "These", "chemoattractants", "bind", "to", "specific", "cell", "surface", "receptors,", "which", "are", "coupled", "to", "pertussis", "toxin", "(PTX)-sensitive", "G-protein(s),", "resulting", "in", "intracel-", "lular", "Ca2+", "mobilization,", "cell", "migration,", "exocytosis,", "adhesion,", "and", "generation", "of", "bioactive", "lipids", "and/or", "reactive", "oxygen", "species", "(Walther", "et", "al.,", "2000;", "Tiffany", "et", "al.,", "2001;", "Kobayashi,", "2008).", "Keeping", "in", "mind", "the", "important", "roles", "of", "chemoattractants", "in", "Copyright", "ⓒ", "2012", "by", "the", "The", "Korean", "Society", "for", "Biochemistry", "and", "Molecular", "Biology", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "Non-Commercial", "License", "(http://creativecommons.org/licenses/", "by-nc/3.0)", "which", "permits", "unrestricted", "non-commercial", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Pope", "et", "al.", "Molecular", "Pain", "2010,", "6:67", "http://www.molecularpain.com/content/6/1/67", "S", "H", "O", "R", "T", "R", "E", "P", "O", "R", "T", "MOLECULAR", "PAIN", "Open", "Access", "Characterisation", "of", "the", "nociceptive", "phenotype", "of", "suppressible", "galanin", "overexpressing", "transgenic", "mice", "Robert", "JP", "Pope,", "Fiona", "E", "Holmes,", "Niall", "C", "Kerr,", "David", "Wynick*", "Abstract", "The", "neuropeptide", "galanin", "is", "widely", "expressed", "in", "both", "the", "central", "and", "peripheral", "nervous", "systems", "and", "is", "involved", "in", "many", "diverse", "biological", "functions.", "There", "is", "a", "substantial", "data", "set", "that", "demonstrates", "galanin", "is", "upregulated", "after", "injury", "in", "the", "DRG,", "spinal", "cord", "and", "in", "many", "brain", "regions", "where", "it", "plays", "a", "predominantly", "antinociceptive", "role", "in", "addition", "to", "being", "neuroprotective", "and", "pro-regenerative.", "To", "further", "characterise", "the", "role", "of", "galanin", "following", "nerve", "injury,", "a", "novel", "transgenic", "line", "was", "created", "using", "the", "binary", "transgenic", "tet-off", "system,", "to", "overexpress", "galanin", "in", "galaninergic", "tissue", "in", "a", "suppressible", "manner.", "The", "double", "transgenic", "mice", "express", "significantly", "more", "galanin", "in", "the", "DRG", "one", "week", "after", "sciatic", "nerve", "section", "(axotomy)", "compared", "to", "WT", "mice", "and", "this", "overexpression", "is", "suppressible", "upon", "administration", "of", "doxycycline.", "Phenotypic", "analysis", "revealed", "markedly", "attenuated", "allodynia", "when", "galanin", "is", "overexpressed", "and", "an", "increase", "in", "allodynia", "following", "galanin", "suppression.", "This", "novel", "transgenic", "line", "demonstrates", "that", "whether", "galanin", "expression", "is", "increased", "at", "the", "time", "of", "nerve", "injury", "or", "only", "after", "allodynia", "is", "established,", "the", "neuropeptide", "is", "able", "to", "reduce", "neuropathic", "pain", "behaviour.", "These", "new", "findings", "imply", "that", "administration", "of", "a", "galanin", "agonist", "to", "patients", "with", "established", "allodynia", "would", "be", "an", "effective", "treatment", "for", "neuropathic", "pain.", "Findings", "The", "29", "(30", "in", "human)", "amino", "acid", "neuropeptide", "galanin", "has", "a", "wide", "distribution", "in", "both", "the", "peripheral", "and", "cen-", "tral", "nervous", "systems.", "The", "galanin", "peptide", "shares", "homol-", "ogy", "with", "only", "two", "other", "known", "peptides,", "galanin-like", "peptide", "(GALP)", "[1]", "and", "the", "GALP", "splice", "variant", "alarin", "[2].", "Galanin", "is", "expressed", "at", "low", "levels", "in", "~5%", "of", "small", "diameter", "C-fibre", "neurons", "in", "the", "intact", "adult", "rodent", "dor-", "sal", "root", "ganglia", "(DRG)", "[3-5].", "Higher", "levels", "of", "the", "pep-", "tide", "are", "detected", "in", "the", "primary", "afferent", "terminals", "of", "the", "spinal", "cord", "(lamina", "II),", "the", "dorsal", "horn", "inter-neurons", "[6],", "and", "in", "a", "number", "of", "brain", "regions", "known", "to", "modu-", "late", "nociception,", "including", "the", "arcuate", "nucleus", "and", "peri-", "aqueductal", "grey", "[7,8].", "Galanin", "levels", "are", "strongly", "and", "persistently", "increased", "in", "the", "DRG", "and", "dorsal", "horn", "of", "the", "spinal", "cord", "as", "well", "as", "in", "many", "regions", "of", "the", "central", "nervous", "system", "following", "nerve", "injury.", "Axotomy", "of", "motor", "nerves", "elevates", "galanin", "mRNA", "levels", "by", "6-10", "fold", "in", "the", "dorsal", "motor", "nucleus", "of", "the", "vagus", "and", "nucleus", "*", "Correspondence:", "d.wynick@bris.ac.uk", "Department", "of", "Physiology", "and", "Pharmacology", "and", "Clinical", "Sciences", "at", "South", "Bristol,", "School", "of", "Medical", "Sciences,", "University", "Walk,", "University", "of", "Bristol,", "Clifton,", "Bristol,", "BS8", "1TD,", "UK", "ambiguus", "[9]", "and", "a", "similar", "increase", "is", "found", "in", "the", "facial", "nucleus", "following", "facial", "nerve", "axotomy", "[10].", "Galanin", "levels", "in", "the", "central", "nervous", "system", "are", "also", "upregulated", "in", "many", "disease", "states", "and", "in", "rodent", "models", "of", "these", "pathological", "conditions,", "including", "Alzheimer’s", "disease", "[11],", "stroke", "induced", "ischemia", "[11,12]", "and", "in", "multiple", "sclerosis", "[13].", "However,", "the", "most", "potent", "upregulation", "occurs", "in", "the", "DRG", "following", "peripheral", "nerve", "axotomy", "when", "galanin", "is", "rapidly", "up-regulated", "by", "up", "to", "120-fold", "and", "is", "expressed", "in", "40-50%", "of", "sensory", "neurons", "[14].", "A", "much", "smaller", "increase", "in", "galanin", "expression", "is", "observed", "in", "the", "dorsal", "horn", "after", "peripheral", "nerve", "injury", "[15]", "implying", "that", "much", "of", "the", "neuropeptide", "is", "anterogradely", "transported", "to", "the", "site", "of", "injury.", "Following", "the", "descrip-", "tion", "of", "galanin", "expression", "increasing", "after", "nerve", "injury,", "the", "role", "of", "galanin", "in", "nociception", "and", "neuropathic", "pain", "has", "been", "the", "subject", "of", "a", "substantial", "body", "of", "research.", "Studies", "of", "intact", "and", "nerve", "injured", "animals", "have", "described", "a", "bell-shaped", "response", "curve", "after", "intrathecal", "infusion", "of", "galanin", "and", "galanin", "agonists", "[16-18]", "with", "inhibition", "of", "nociceptive", "responses", "at", "high", "doses", "[19,20].", "To", "further", "define", "the", "role", "played", "by", "galanin", "in", "nocicep-", "tion,", "we", "have", "previously", "generated", "and", "characterised", "©", "2010", "Pope", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Post", "Clinical", "Sarcoma", "Research", "2012,", "2:20", "http://www.clinicalsarcomaresearch.com/content/2/1/20", "R", "E", "V", "I", "E", "W", "CLINICAL", "SARCOMA", "RESEARCH", "Open", "Access", "Mouse", "models", "of", "sarcomas:", "critical", "tools", "in", "our", "understanding", "of", "the", "pathobiology", "Sean", "M", "Post", "Abstract", "Sarcomas", "are", "neoplastic", "malignancies", "that", "typically", "arise", "in", "tissues", "of", "mesenchymal", "origin.", "The", "identification", "of", "novel", "molecular", "mechanisms", "leading", "to", "sarcoma", "formation", "and", "the", "establishment", "of", "new", "therapies", "has", "been", "hampered", "by", "several", "critical", "factors.", "First,", "this", "type", "of", "cancer", "is", "rarely", "observed", "in", "the", "clinic", "with", "fewer", "than", "15,000", "newly", "cases", "diagnosed", "each", "year", "in", "the", "United", "States.", "Another", "complicating", "factor", "is", "that", "sarcomas", "are", "extremely", "heterogeneous", "as", "they", "arise", "in", "a", "multitude", "of", "tissues", "from", "many", "different", "cell", "lineages", "(e.g.", "bone", "(osteosarcoma),", "fat", "(liposarcoma),", "and", "muscle", "(myosarcoma)).", "The", "scarcity", "of", "clinical", "samples", "coupled", "with", "its", "inherent", "heterogeneity", "creates", "a", "challenging", "experimental", "environment", "for", "clinicians", "and", "scientists.", "Faced", "with", "these", "challenges,", "there", "has", "been", "extremely", "limited", "advancement", "in", "treatment", "options", "available", "to", "patients", "as", "compared", "to", "other", "cancers.", "In", "order", "to", "glean", "insight", "into", "the", "pathobiology", "of", "sarcomas,", "scientists", "are", "now", "using", "in", "vivo", "mouse", "models", "whose", "genomes", "have", "been", "specifically", "tailored", "to", "carry", "gene", "deletions,", "gene", "amplifications,", "and", "point", "mutations", "commonly", "observed", "in", "human", "sarcomas.", "The", "use", "of", "these", "model", "organisms", "has", "been", "successful", "in", "increasing", "our", "knowledge", "and", "understanding", "of", "how", "alterations", "in", "relevant", "oncogenic,", "tumor", "suppressive,", "and", "signaling", "pathways", "directly", "impact", "sarcomagenesis.", "It", "is", "the", "goal", "of", "many", "in", "the", "biological", "community", "that", "the", "use", "of", "these", "mouse", "models", "will", "serve", "as", "powerful", "in", "vivo", "tools", "to", "further", "our", "understanding", "of", "sarcomagenesis", "and", "potentially", "identify", "new", "therapeutic", "strategies.", "Keywords:", "Sarcoma,", "Mouse", "models,", "p53,", "Retinoblastoma", "(Rb),", "Translocation", "Background", "Sarcomas", "are", "a", "rare", "form", "of", "cancer", "with", "less", "than", "15,000", "new", "cases", "diagnosed", "each", "year", "in", "the", "United", "States.", "Though", "rare,", "sarcomas", "are", "highly", "debilitating", "malignan-", "cies", "as", "they", "are", "often", "associated", "with", "significant", "morbidity", "and", "mortality.", "Sarcomas", "are", "biologically", "very", "heteroge-", "neous", "as", "evidenced", "by", "the", "fact", "that", "these", "cancers", "arise", "from", "a", "plethora", "of", "different", "tissues", "and", "cell", "types.", "They", "are", "classically", "defined", "by", "their", "tissue", "of", "origin", "and", "are", "add-", "itionally", "stratified", "by", "their", "histopathology", "or", "patient’s", "age", "at", "diagnosis", "[1,2].", "While", "these", "classifications", "have", "proven", "useful,", "modern", "biological", "and", "clinical", "techniques", "have", "the", "ability", "to", "further", "stratify", "sarcomas", "based", "on", "their", "genetic", "profile", "[1,3,4].", "Cytogenetic", "and", "karyotype", "analyses", "have", "revealed", "two", "divergent", "genetic", "profiles", "in", "sarcomas.", "The", "first", "and", "most", "simple", "genetic", "profile", "is", "the", "observation", "of", "translocation", "events", "in", "sarcomas", "with", "an", "otherwise", "Correspondence:", "spost@mdanderson.org", "Department", "of", "Leukemia,", "M.D.", "Anderson", "Cancer", "Center,", "1515", "Holcombe", "Blvd,", "Houston,", "TX", "77030,", "USA", "normal", "diploid", "karyotype.", "On", "the", "other", "hand,", "most", "sarco-", "mas", "display", "a", "more", "complex", "genetic", "phenotype,", "suggest-", "ing", "genomic", "instability", "plays", "an", "important", "role", "in", "many", "sarcomas.", "Historical", "perspective", "Much", "of", "our", "current", "knowledge", "regarding", "sarcoma", "biol-", "ogy", "has", "been", "ascertained", "through", "experimentation", "using", "high", "dose", "irradiation,", "viral", "infections,", "in", "vitro", "cell", "line", "studies,", "and", "xenografts", "models.", "One", "of", "the", "earliest", "animal", "studies", "investigated", "the", "impact", "of", "the", "Rous", "sarcoma", "virus", "on", "the", "development", "of", "soft", "tissue", "sarcomas", "[5].", "Our", "knowledge", "regarding", "radiation-induced", "sarcomagenesis", "largely", "stems", "from", "the", "observation", "of", "women", "occupation-", "ally", "exposed", "to", "radium", "and", "animal", "models", "subjected", "to", "high", "dose", "radiation", "developed", "sarcomas", "[6,7].", "While", "the", "plight", "of", "these", "patients", "and", "the", "subsequent", "animal", "experi-", "ments", "led", "to", "the", "identification", "of", "a", "cause", "and", "effect", "for", "some", "sarcomas,", "these", "observations", "were", "unable", "to", "identify", "the", "molecular", "events", "responsible", "for", "sarcomagenesis.", "©", "2012", "Post;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Int.", "J.", "Mol.", "Sci.", "2012,", "13,", "6800-6819;", "doi:10.3390/ijms13066800", "OPEN", "ACCESS", "International", "Journal", "of", "Molecular", "Sciences", "ISSN", "1422-0067", "www.mdpi.com/journal/ijms", "Opinion", "The", "Kiss-and-Run", "Model", "of", "Intra-Golgi", "Transport", "Alexander", "A.", "Mironov", "*", "and", "Galina", "V.", "Beznoussenko", "*", "IFOM", "Foundation,", "FIRC", "Institute", "of", "Molecular", "Oncology", "(IFOM-IEO", "Campus),", "Via", "Adamello", "16,", "20139,", "Milan,", "Italy", "*", "Authors", "to", "whom", "correspondence", "should", "be", "addressed;", "E-Mails:", "alexandre.mironov@ifom-ieo-campus.it", "(A.A.M.);", "galina.beznusenko@ifom-ieo-campus.it", "(G.V.B.);", "Tel.:", "+39-02-574-303-869", "(A.A.M.);", "Fax:", "+39-02-574-303-231", "(A.A.M.).", "Received:", "9", "April", "2012;", "in", "revised", "form:", "9", "May", "2012", "/", "Accepted:", "22", "May", "2012", "/", "Published:", "5", "June", "2012", "Abstract:", "The", "Golgi", "apparatus", "(GA)", "is", "the", "main", "station", "along", "the", "secretory", "pathway.", "Mechanisms", "of", "intra-Golgi", "transport", "remain", "unresolved.", "Three", "models", "compete", "with", "each", "other", "for", "the", "right", "to", "be", "defined", "as", "the", "paradigm.", "The", "vesicular", "model", "cannot", "explain", "the", "following:", "(1)", "lipid", "droplets", "and", "aggregates", "of", "procollagen", "that", "are", "larger", "than", "coatomer", "I", "(COPI)-dependent", "vesicles", "are", "transported", "across", "the", "GA;", "and", "(2)", "most", "anterograde", "cargoes", "are", "depleted", "in", "COPI", "vesicles.", "The", "compartment", "progression/maturation", "model", "has", "the", "following", "problems:", "(1)", "most", "Golgi-resident", "proteins", "are", "depleted", "in", "COPI", "vesicles;", "(2)", "there", "are", "no", "COPI", "vesicles", "for", "the", "recycling", "of", "the", "resident", "proteins", "in", "the", "trans-most-Golgi", "cisterna;", "and", "(3)", "different", "proteins", "have", "different", "rates", "of", "intra-Golgi", "transport.", "The", "diffusion", "model", "based", "on", "permanent", "inter-cisternal", "connections", "cannot", "explain", "the", "existence", "of", "lipid,", "ionic", "and", "protein", "gradients", "across", "the", "Golgi", "stacks.", "In", "contrast,", "the", "kiss-and-run", "model", "has", "the", "potential", "to", "explain", "most", "of", "the", "experimental", "observations.", "The", "kiss-and-run", "model", "can", "be", "symmetric", "when", "fusion", "and", "then", "fission", "occurs", "in", "the", "same", "place,", "and", "asymmetric", "when", "fusion", "takes", "place", "in", "one", "location,", "whereas", "fission", "takes", "place", "in", "another.", "The", "asymmetric", "kiss-and-run", "model", "resembles", "the", "carrier", "maturation", "mechanism,", "and", "it", "can", "be", "used", "to", "explain", "the", "transport", "of", "large", "cargo", "aggregates.", "Keywords:", "intra-Golgi", "transport;", "Golgi", "apparatus;", "vesicular", "model;", "cisterna", "maturation;", "kiss-and-run", "model" ]

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[ "Martin-Gallego", "et", "al.", "Nanoscale", "Research", "Letters", "2011,", "6:610", "http://www.nanoscalereslett.com/content/6/1/610", "N", "A", "N", "O", "E", "X", "P", "R", "E", "S", "S", "Open", "Access", "Thermal", "conductivity", "of", "carbon", "nanotubes", "and", "graphene", "in", "epoxy", "nanofluids", "and", "nanocomposites", "Mario", "Martin-Gallego1,", "Raquel", "Verdejo1,", "Mohamed", "Khayet2,", "Jose", "Maria", "Ortiz", "de", "Zarate2,", "Mohamed", "Essalhi2", "and", "Miguel", "Angel", "Lopez-Manchado1*", "Abstract", "We", "employed", "an", "easy", "and", "direct", "method", "to", "measure", "the", "thermal", "conductivity", "of", "epoxy", "in", "the", "liquid", "(nanofluid)", "and", "solid", "(nanocomposite)", "states", "using", "both", "rodlike", "and", "platelet-like", "carbon-based", "nanostructures.", "Comparing", "the", "experimental", "results", "with", "the", "theoretical", "model,", "an", "anomalous", "enhancement", "was", "obtained", "with", "multiwall", "carbon", "nanotubes,", "probably", "due", "to", "their", "layered", "structure", "and", "lowest", "surface", "resistance.", "Puzzling", "results", "for", "functionalized", "graphene", "sheet", "nanocomposites", "suggest", "that", "phonon", "coupling", "of", "the", "vibrational", "modes", "of", "the", "graphene", "and", "of", "the", "polymeric", "matrix", "plays", "a", "dominant", "role", "on", "the", "thermal", "conductivities", "of", "the", "liquid", "and", "solid", "states.", "PACS:", "74.25.fc;", "81.05.Qk;", "81.07.Pr.", "Keywords:", "carbon", "nanotubes,", "graphene,", "nanocomposites,", "nanofluids,", "thermal", "conductivity", "Introduction", "Due", "to", "the", "increasing", "importance", "of", "energy", "dissipation", "in", "the", "electronic", "industry,", "thermal", "conductivity", "of", "cured", "epoxy", "resins", "has", "been", "widely", "investigated", "over", "the", "years.", "One", "strategy", "to", "improve", "the", "thermal", "transport", "of", "epoxy", "resins", "has", "been", "the", "addition", "of", "highly", "conductive", "fillers,", "such", "as", "carbon-based", "or", "metallic", "fillers", "[1].", "However,", "the", "effect", "of", "such", "additions", "on", "either", "the", "uncured", "sys-", "tem", "or", "the", "cure", "reaction", "of", "resins", "has", "not", "yet", "been", "fully", "established.", "The", "thermal", "conductivity", "of", "the", "uncured", "liquid", "resin", "plays", "an", "important", "role", "to", "define", "the", "vari-", "ables", "involved", "in", "the", "transformation", "process,", "such", "as", "time,", "applied", "heat,", "or", "cooling", "time,", "which", "will", "then", "have", "a", "profound", "effect", "on", "the", "cross-link", "density", "and", "hence,", "on", "the", "final", "properties", "of", "the", "system.", "Thus,", "we", "aimed", "at", "studying", "the", "effect", "of", "two", "types", "of", "carbon-based", "nanofil-", "lers,", "in", "particular,", "nanotubes", "and", "graphene", "sheets,", "on", "the", "thermal", "conductivity", "of", "an", "uncured", "liquid", "epoxy", "resin.", "There", "have", "been", "considerable", "interest", "and", "effort", "in", "the", "transport", "properties", "of", "carbon", "nanotube", "[CNT]", "*", "Correspondence:", "lmanchado@ictp.csic.es", "1Instituto", "de", "Ciencia", "y", "Tecnologia", "de", "Polimeros,", "ICTP-CSIC,", "Juan", "de", "la", "Cierva", "3,", "Madrid,", "28006,", "Spain", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "filled", "polymer", "nanocomposites", "[2,3].", "Electrical", "conduc-", "tivity", "of", "epoxy", "nanocomposites", "increases", "by", "several", "orders", "of", "magnitude", "with", "CNT", "concentration", "[4];", "this", "effect", "can", "be", "explained", "by", "the", "established", "percolation", "theory", "[5]", "with", "the", "shift", "from", "an", "insulator", "into", "a", "con-", "ductive", "material", "when", "a", "critical", "concentration", "of", "the", "conductive", "filler", "is", "reached,", "commonly", "known", "as", "perco-", "lation", "threshold.", "However,", "the", "thermal", "conductivity", "has", "shown", "at", "best", "linear", "enhancements", "with", "nanotube", "con-", "tent", "with", "a", "lack", "of", "thermal", "percolation.", "The", "main", "reason", "for", "this", "fact", "is", "the", "relatively", "small", "thermal", "conductivity", "ratio", "(Kcnt/Kmatrix)", "by", "comparison", "with", "the", "correspond-", "ing", "ratio", "of", "electrical", "conductivities", "[6].", "Graphene", "is", "a", "two-dimensional", "carbon", "nanofiller", "with", "a", "one-atom-thick", "sheet", "of", "sp2", "bonded", "carbon", "atoms", "that", "are", "densely", "packed", "in", "a", "honeycomb", "crystal", "lattice", "[7,8].", "Single", "layer", "graphene", "is", "predicted", "to", "have", "a", "remarkable", "performance,", "such", "as", "high", "thermal", "conductivity", "of", "5,000", "W/mK,", "which", "corresponds", "to", "the", "upper", "bound", "of", "the", "highest", "values", "reported", "for", "single-walled", "carbon", "nano-", "tube", "bundles", "[9],", "high", "electrical", "conductivity", "of", "up", "to", "6,000", "S/cm", "[10],", "and", "superior", "mechanical", "properties", "with", "Young’s", "modulus", "of", "1", "TPa", "and", "ultimate", "strength", "of", "130", "GPa", "[11].", "In", "addition", "to", "these", "outstanding", "properties,", "the", "recent", "developments", "on", "graphene", "synthesis", "routes", "and", "©", "2011", "Martin-Gallego", "et", "al;", "licensee", "Springer.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "DAF-12", "Regulates", "a", "Connected", "Network", "of", "Genes", "to", "Ensure", "Robust", "Developmental", "Decisions", "Daniel", "Hochbaum1.,", "Yue", "Zhang2.,", "Carsten", "Stuckenholz3,", "Paul", "Labhart4,", "Vassili", "Alexiadis5,", "Rene´", "Martin6,7,", "Hans-Joachim", "Kno¨", "lker7,", "Alfred", "L.", "Fisher1*", "1", "Division", "of", "Geriatric", "Medicine,", "Department", "of", "Medicine,", "University", "of", "Pittsburgh,", "Pittsburgh,", "Pennsylvania,", "United", "States", "of", "America,", "2", "Department", "of", "Radiation", "Oncology,", "Beth", "Israel", "Deaconess", "Medical", "Center,", "Harvard", "Medical", "School,", "Boston,", "Massachusetts,", "United", "States", "of", "America,", "3", "Division", "of", "Hematology/Oncology,", "Department", "of", "Medicine,", "University", "of", "Pittsburgh,", "Pittsburgh,", "Pennsylvania,", "United", "States", "of", "America,", "4", "Active", "Motif,", "Carlsbad,", "California,", "United", "States", "of", "America,", "5", "Biocept,", "San", "Diego,", "California,", "United", "States", "of", "America,", "6", "ChiroBlock", "GmbH,", "Wolfen,", "Germany,", "7", "Department", "Chemie,", "Technische", "Universita¨t", "Dresden,", "Dresden,", "Germany", "Abstract", "The", "nuclear", "receptor", "DAF-12", "has", "roles", "in", "normal", "development,", "the", "decision", "to", "pursue", "dauer", "development", "in", "unfavorable", "conditions,", "and", "the", "modulation", "of", "adult", "aging.", "Despite", "the", "biologic", "importance", "of", "DAF-12,", "target", "genes", "for", "this", "receptor", "are", "largely", "unknown.", "To", "identify", "DAF-12", "targets,", "we", "performed", "chromatin", "immunoprecipitation", "followed", "by", "hybridization", "to", "whole-genome", "tiling", "arrays.", "We", "identified", "1,175", "genomic", "regions", "to", "be", "bound", "in", "vivo", "by", "DAF-12,", "and", "these", "regions", "are", "enriched", "in", "known", "DAF-12", "binding", "motifs", "and", "act", "as", "DAF-12", "response", "elements", "in", "transfected", "cells", "and", "in", "transgenic", "worms.", "The", "DAF-12", "target", "genes", "near", "these", "binding", "sites", "include", "an", "extensive", "network", "of", "interconnected", "heterochronic", "and", "microRNA", "genes.", "We", "also", "identify", "the", "genes", "encoding", "components", "of", "the", "miRISC,", "which", "is", "required", "for", "the", "control", "of", "target", "genes", "by", "microRNA,", "as", "a", "target", "of", "DAF-12", "regulation.", "During", "reproductive", "development,", "many", "of", "these", "target", "genes", "are", "misregulated", "in", "daf-12(0)", "mutants,", "but", "this", "only", "infrequently", "results", "in", "developmental", "phenotypes.", "In", "contrast,", "we", "and", "others", "have", "found", "that", "null", "daf-12", "mutations", "enhance", "the", "phenotypes", "of", "many", "miRISC", "and", "heterochronic", "target", "genes.", "We", "also", "find", "that", "environmental", "fluctuations", "significantly", "strengthen", "the", "weak", "heterochronic", "phenotypes", "of", "null", "daf-12", "alleles.", "During", "diapause,", "DAF-12", "represses", "the", "expression", "of", "many", "heterochronic", "and", "miRISC", "target", "genes,", "and", "prior", "work", "has", "demonstrated", "that", "dauer", "formation", "can", "suppress", "the", "heterochronic", "phenotypes", "of", "many", "of", "these", "target", "genes", "in", "post-", "dauer", "development.", "Together", "these", "data", "are", "consistent", "with", "daf-12", "acting", "to", "ensure", "developmental", "robustness", "by", "committing", "the", "animal", "to", "adult", "or", "dauer", "developmental", "programs", "despite", "variable", "internal", "or", "external", "conditions.", "Citation:", "Hochbaum", "D,", "Zhang", "Y,", "Stuckenholz", "C,", "Labhart", "P,", "Alexiadis", "V,", "et", "al.", "(2011)", "DAF-12", "Regulates", "a", "Connected", "Network", "of", "Genes", "to", "Ensure", "Robust", "Developmental", "Decisions.", "PLoS", "Genet", "7(7):", "e1002179.", "doi:10.1371/journal.pgen.1002179", "Editor:", "Stuart", "K.", "Kim,", "Stanford", "University", "Medical", "Center,", "United", "States", "of", "America", "Received", "November", "26,", "2010;", "Accepted", "May", "23,", "2011;", "Published", "July", "21,", "2011", "Copyright:", "2011", "Hochbaum", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "This", "work", "was", "supported", "by", "NIH", "grant", "AG028977", "to", "ALF", "(http://grants.nih.gov/grants/oer.htm),", "a", "pilot", "project", "from", "Pittsburgh", "Claude", "D", "Pepper", "Older", "Americans", "Independence", "Center", "P30", "AG024827", "(http://www.pepper.pitt.edu/),", "and", "a", "pilot", "grant", "from", "the", "University", "of", "Pittsburgh", "Institute", "Of", "Aging", "(http://www.", "aging.pitt.edu/).", "The", "funders", "had", "no", "role", "in", "study", "design,", "data", "collection", "and", "analysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "Competing", "Interests:", "The", "authors", "have", "declared", "that", "no", "competing", "interests", "exist.", "*", "E-mail:", "afisher@pitt.edu", ".", "These", "authors", "contributed", "equally", "to", "this", "work.", "Introduction", "From", "bacteria", "to", "humans,", "organisms", "sense", "environmental", "cues", "and", "reprogram", "life", "history", "by", "altering", "gene", "expression", "patterns.", "In", "the", "nematode", "C.", "elegans,", "the", "nuclear", "receptor", "DAF-12", "alters", "life", "history", "in", "response", "to", "the", "environment.", "During", "development,", "when", "conditions", "are", "unfavorable,", "due", "to", "starvation,", "crowding", "or", "high", "temperature,", "daf-12", "promotes", "diapause", "and", "formation", "of", "dauer", "larvae", "[1–3].", "In", "favorable", "conditions,", "the", "DAF-12", "receptor", "is", "activated", "by", "a", "group", "of", "steroidal", "carboxylic", "acids,", "termed", "dafachronic", "acids", "(DA)", "[4–6],", "produced", "from", "cholesterol", "via", "a", "multi-step", "pathway", "involving", "the", "daf-36", "Rieske-like", "oxygenase", "and", "the", "daf-9", "cytochrome", "P450", "enzyme", "[7–9].", "The", "activation", "of", "DAF-", "12", "by", "DA", "leads", "to", "bypass", "of", "dauer", "arrest", "and", "expression", "of", "later", "larval", "developmental", "and", "reproductive", "programs", "[10].", "On", "the", "other", "hand,", "in", "unfavorable", "conditions,", "DA", "is", "not", "produced,", "and", "DAF-12", "binds", "to", "the", "co-repressor", "DIN-1", "promoting", "dauer", "programs", "[11].", "DAF-12", "is", "also", "required", "for", "the", "normal", "lifespan", "of", "worms", "[12–14]", "and", "for", "the", "increased", "longevity", "of", "germline", "ablated", "animals", "[7,15,16].", "DAF-12", "also", "alters", "life", "history", "by", "regulation", "of", "the", "heterochronic", "circuit.", "The", "heterochronic", "pathway", "in", "C.", "elegans", "determines", "specific", "cell", "fate", "programs", "for", "each", "larval", "stage", "[17].", "Several", "daf-12", "alleles,", "especially", "those", "in", "phenotypic", "class", "1,", "have", "heterochronic", "phenotypes", "[10].", "These", "mutants", "repeat", "L2", "programs", "instead", "of", "progressing", "to", "L3", "programs,", "resulting", "in", "excessive", "hypodermal", "seam", "cell", "division", "in", "the", "L3", "stage", "and", "defects", "in", "distal", "tip", "cell", "migration", "in", "the", "L4", "stage", "[1,10].", "The", "heterochronic", "phenotypes", "depend", "on", "the", "activity", "of", "the", "co-repressor", "din-1,", "as", "daf-12(rh61);din-1", "mutants", "develop", "normally", "[11].", "In", "part,", "DAF-12", "regulates", "the", "heterochronic", "circuit", "by", "controlling", "expression", "of", "let-7", "family", "miRNAs", "[18,19],", "which", "are", "necessary", "to", "promote", "L3", "and", "adult", "programs", "through", "the", "down-regulation", "of", "the", "heterochronic", "genes", "hbl-1", "and", "lin-41", "respectively", "[20,21].", "DAF-12", "might", "also", "affect", "the", "heterochronic", "circuit", "via", "dauer", "formation,", "as", "many", "heterochronic", "phenotypes", "are", "suppressed", "in", "post", "dauer", "development", "[22–25].", "PLoS", "Genetics", "|", "www.plosgenetics.org", "1", "July", "2011", "|", "Volume", "7", "|", "Issue", "7", "|", "e1002179" ]

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[ "Kislov", "et", "al.", "Implementation", "Science", "2011,", "6:64", "http://www.implementationscience.com/content/6/1/64", "D", "E", "B", "A", "T", "E", "Implementation", "Science", "Open", "Access", "Collaborations", "for", "Leadership", "in", "Applied", "Health", "Research", "and", "Care:", "lessons", "from", "the", "theory", "of", "communities", "of", "practice", "Roman", "Kislov*,", "Gill", "Harvey", "and", "Kieran", "Walshe", "Abstract", "Background:", "The", "paper", "combines", "the", "analytical", "and", "instrumental", "perspectives", "on", "communities", "of", "practice", "(CoPs)", "to", "reflect", "on", "potential", "challenges", "that", "may", "arise", "in", "the", "process", "of", "interprofessional", "and", "inter-organisational", "joint", "working", "within", "the", "Collaborations", "for", "Leaderships", "in", "Applied", "Health", "Research", "and", "Care", "(CLAHRCs)–partnerships", "between", "the", "universities", "and", "National", "Health", "Service", "(NHS)", "Trusts", "aimed", "at", "conducting", "applied", "health", "research", "and", "translating", "its", "findings", "into", "day-to-day", "clinical", "practice.", "Discussion:", "The", "paper", "discusses", "seminal", "theoretical", "literature", "on", "CoPs", "as", "well", "as", "previous", "empirical", "research", "on", "the", "role", "of", "these", "communities", "in", "healthcare", "collaboration,", "which", "is", "organised", "around", "the", "following", "three", "themes:", "knowledge", "sharing", "within", "and", "across", "CoPs,", "CoP", "formation", "and", "manageability,", "and", "identity", "building", "in", "CoPs.", "It", "argues", "that", "the", "multiprofessional", "and", "multi-agency", "nature", "of", "the", "CLAHRCs", "operating", "in", "the", "traditionally", "demarcated", "organisational", "landscape", "of", "the", "NHS", "may", "present", "formidable", "obstacles", "to", "knowledge", "sharing", "between", "various", "professional", "groupings,", "formation", "of", "a", "shared", "‘collaborative’", "identity,", "and", "the", "development", "of", "new", "communities", "within", "the", "CLAHRCs.", "To", "cross", "multiple", "boundaries", "between", "various", "professional", "and", "organisational", "communities", "and", "hence", "enable", "the", "flow", "of", "knowledge,", "the", "CLAHRCs", "will", "have", "to", "create", "an", "effective", "system", "of", "‘bridges’", "involving", "knowledge", "brokers,", "boundary", "objects,", "and", "cross-disciplinary", "interactions", "as", "well", "as", "address", "a", "number", "of", "issues", "related", "to", "professional", "and", "organisational", "identification.", "Summary:", "The", "CoP", "approach", "can", "complement", "traditional", "‘stage-of-change’", "theories", "used", "in", "the", "field", "of", "implementation", "research", "and", "provide", "a", "basis", "for", "designing", "theory-informed", "interventions", "and", "evaluations.", "It", "can", "help", "to", "illuminate", "multiple", "boundaries", "that", "exist", "between", "professional", "and", "organisational", "groups", "within", "the", "CLAHRCs", "and", "suggest", "ways", "of", "crossing", "those", "boundaries", "to", "enable", "knowledge", "transfer", "and", "organisational", "learning.", "Achieving", "the", "aims", "of", "the", "CLAHRCs", "and", "producing", "a", "sustainable", "change", "in", "the", "ways", "applied", "health", "research", "is", "conducted", "and", "implemented", "may", "be", "influenced", "by", "how", "effectively", "these", "organisations", "can", "navigate", "through", "the", "multiple", "CoPs", "involved", "and", "promote", "the", "development", "of", "new", "multiprofessional", "and", "multi-organisational", "communities", "united", "by", "shared", "practice", "and", "a", "shared", "sense", "of", "belonging–an", "assumption", "that", "needs", "to", "be", "explored", "by", "further", "empirical", "research.", "Introduction", "Since", "being", "identified", "as", "a", "mechanism", "through", "which", "knowledge", "is", "held,", "transferred,", "and", "created,", "the", "commu-", "nities", "of", "practice", "(CoP)", "approach", "has", "become", "increas-", "ingly", "influential", "within", "management", "research", "and", "practice", "[1].", "Originally", "developed", "by", "Lave", "and", "Wenger", "[2]", "in", "a", "study", "of", "situated", "learning,", "the", "CoP", "theory", "is", "*", "Correspondence:", "roman.kislov@postgrad.mbs.ac.uk", "Manchester", "Business", "School,", "The", "University", "of", "Manchester,", "Booth", "Street", "West,", "Manchester,", "M15", "6PB,", "UK", "currently", "being", "used", "to", "analyse", "and", "facilitate", "knowledge", "sharing", "in", "a", "wide", "range", "of", "organisational", "environments,", "including,", "but", "not", "limited", "to,", "business", "sector,", "education,", "information", "technology", "(IT)", "and", "healthcare", "organisa-", "tions.", "In", "the", "healthcare", "sector,", "CoPs", "have", "been", "argued", "to", "play", "a", "role", "in", "the", "generation", "of", "social,", "human,", "organi-", "sational,", "professional,", "and", "patient", "capital,", "thus", "being", "potentially", "useful", "for", "enhancing", "care,", "providing", "learning", "opportunities,", "analysing", "practice,", "problem-solving,", "shar-", "ing", "knowledge,", "and", "generating", "ideas", "[3].", "©", "2011", "Kislov", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Hindawi", "Publishing", "Corporation", "Gastroenterology", "Research", "and", "Practice", "Volume", "2010,", "Article", "ID", "453563,", "13", "pages", "doi:10.1155/2010/453563", "Review", "Article", "Contribution", "of", "Gut", "Bacteria", "to", "Liver", "Pathobiology", "Gakuhei", "Son,1", "Michael", "Kremer,2", "and", "Ian", "N.", "Hines1,", "3", "1", "Division", "of", "Gastroenterology", "and", "Hepatology,", "Department", "of", "Medicine,", "University", "of", "North", "Carolina,", "Chapel", "Hill,", "NC", "27599,", "USA", "2", "Department", "of", "Surgery,", "University", "of", "Heidelberg,", "69120,", "Heidelberg,", "Germany", "3", "Department", "of", "Nutrition", "and", "Dietetics,", "College", "of", "Human", "Ecology,", "East", "Carolina", "University,", "110", "Rivers", "Building,", "Greenville,", "NC", "27858-4353,", "USA", "Correspondence", "should", "be", "addressed", "to", "Ian", "N.", "Hines,", "hinesi@euc.edu", "Received", "16", "April", "2010;", "Accepted", "17", "June", "2010", "Academic", "Editor:", "Ekihiro", "Seki", "Copyright", "©", "2010", "Gakuhei", "Son", "et", "al.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Emerging", "evidence", "suggests", "a", "strong", "interaction", "between", "the", "gut", "microbiota", "and", "health", "and", "disease.", "The", "interactions", "of", "the", "gut", "microbiota", "and", "the", "liver", "have", "only", "recently", "been", "investigated", "in", "detail.", "Receiving", "approximately", "70%", "of", "its", "blood", "supply", "from", "the", "intestinal", "venous", "outflow,", "the", "liver", "represents", "the", "first", "line", "of", "defense", "against", "gut-derived", "antigens", "and", "is", "equipped", "with", "a", "broad", "array", "of", "immune", "cells", "(i.e.,", "macrophages,", "lymphocytes,", "natural", "killer", "cells,", "and", "dendritic", "cells)", "to", "accomplish", "this", "function.", "In", "the", "setting", "of", "tissue", "injury,", "whereby", "the", "liver", "is", "otherwise", "damaged", "(e.g.,", "viral", "infection,", "toxin", "exposure,", "ischemic", "tissue", "damage,", "etc.),", "these", "same", "immune", "cell", "populations", "and", "their", "interactions", "with", "the", "infiltrating", "gut", "bacteria", "likely", "contribute", "to", "and", "promote", "these", "pathologies.", "The", "following", "paper", "will", "highlight", "recent", "studies", "investigating", "the", "relationship", "between", "the", "gut", "microbiota,", "liver", "biology,", "and", "pathobiology.", "Defining", "these", "connections", "will", "likely", "provide", "new", "targets", "for", "therapy", "or", "prevention", "of", "a", "wide", "variety", "of", "acute", "and", "chronic", "liver", "pathologies.", "1.", "Introduction", "Receiving", "approximately", "70%", "of", "its", "blood", "supply", "from", "the", "portal", "vein", "which", "is", "the", "direct", "venous", "outflow", "of", "the", "intestine,", "the", "liver", "is", "continually", "exposed", "to", "gut-derived", "factors", "including", "bacteria", "and", "bacterial", "components.", "To", "combat", "this", "influx,", "the", "liver", "contains", "a", "large", "number", "of", "resident", "immune", "cells", "including", "macrophages", "(i.e.,", "the", "Kupffer", "cell),", "lymphocytes,", "natural", "killer", "cells,", "dendritic", "cells,", "and", "B", "cells.", "Together,", "these", "immune", "cell", "populations", "in", "conjunction", "with", "other", "nonparenchymal", "cells", "including", "endothelial", "cells", "and", "stellate", "cells", "orchestrate", "a", "controlled", "and", "organized", "response", "to", "these", "potentially", "highly", "inflammatory", "factors.", "However,", "when", "normal", "liver", "physiology", "is", "disrupted", "and", "inflammatory", "cells", "are", "activated,", "gut-derived", "factors", "likely", "augment", "or", "exacerbate", "certain", "liver", "diseases", "leading", "to", "enhanced", "tissue", "damage", "and", "propagation", "of", "inflammation.", "Thus,", "understanding", "the", "mechanisms", "both", "of", "control", "and", "of", "activation", "by", "gut-derived", "factors", "as", "well", "as", "the", "functionality", "of", "the", "gut", "barrier", "are", "critical", "to", "the", "development", "of", "new", "therapeutic", "modalities", "to", "treat", "or", "prevent", "acute", "and", "chronic", "liver", "diseases", "such", "as", "viral", "hepatitis,", "alcoholic", "liver", "disease,", "and/or", "liver", "cancer.", "The", "current", "paper", "will", "provide", "an", "overview", "of", "gut", "bacterial", "populations,", "gut", "barrier", "function,", "and", "the", "potential", "interactions", "of", "gut", "bacteria", "with", "acute", "and", "chronic", "liver", "disease.", "2.", "The", "Gut", "Microbiome", "The", "human", "intestine", "provides", "residence", "to", "1", "×", "1013", "bac-", "teria,", "a", "number", "which", "dwarfs", "the", "total", "number", "of", "cells", "in", "the", "human", "body", "(1", "×", "1012)", "[1,", "2].", "Referred", "to", "as", "commensal", "bacteria,", "these", "microorganisms", "play", "a", "crucial", "role", "in", "human", "physiology", "and", "metabolism,", "providing", "key", "metabolic", "functions", "during", "absorption", "and", "waste", "breakdown", "[3].", "Moreover,", "they", "also", "contribute", "to", "gut", "epithelial", "cell", "responses", "including", "proliferation", "and", "differentiation", "and", "play", "a", "key", "role", "in", "barrier", "development", "and", "function", "[4].", "It", "is", "clear,", "however,", "that", "these", "same", "luminal", "contents", "may", "also", "contribute", "to", "intestinal", "pathology", "in", "the", "setting", "of", "colitis", "where", "immune", "cell", "dysfunction,", "barrier", "disruption,", "and/or" ]

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[ "BMC", "Genetics", "Software", "CapsID:", "a", "web-based", "tool", "for", "developing", "parsimonious", "sets", "of", "CAPS", "molecular", "markers", "for", "genotyping", "Jonathan", "Taylor1", "and", "Nicholas", "J", "Provart*2", "BioMed", "Central", "Open", "Access", "Address:", "1Department", "of", "Computer", "Science,", "University", "of", "Toronto,", "40", "St", "George", "Street,", "Toronto,", "ON", "M5S", "2E4,", "Canada", "and", "2Centre", "for", "the", "Analysis", "of", "Genome", "Evolution", "and", "Function,", "Department", "of", "Cell", "and", "Systems", "Biology,", "University", "of", "Toronto,", "25", "Willcocks", "Street,", "Toronto,", "ON", "M5S", "3B2,", "Canada", "Email:", "Jonathan", "Taylor", "-", "jonathan.taylor@utoronto.ca;", "Nicholas", "J", "Provart*", "-", "nicholas.provart@utoronto.ca", "*", "Corresponding", "author", "Published:", "10", "May", "2006", "BMC", "Genetics", "2006,", "7:27", "doi:10.1186/1471-2156-7-27", "This", "article", "is", "available", "from:", "http://www.biomedcentral.com/1471-2156/7/27", "Received:", "03", "March", "2006", "Accepted:", "10", "May", "2006", "©", "2006", "Taylor", "and", "Provart;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Background:", "Genotyping", "may", "be", "carried", "out", "by", "a", "number", "of", "different", "methods", "including", "direct", "sequencing", "and", "polymorphism", "analysis.", "For", "a", "number", "of", "reasons,", "PCR-based", "polymorphism", "analysis", "may", "be", "desirable,", "owing", "to", "the", "fact", "that", "only", "small", "amounts", "of", "genetic", "material", "are", "required,", "and", "that", "the", "costs", "are", "low.", "One", "popular", "and", "cheap", "method", "for", "detecting", "polymorphisms", "is", "by", "using", "cleaved", "amplified", "polymorphic", "sequence,", "or", "CAPS,", "molecular", "markers.", "These", "are", "also", "known", "as", "PCR-RFLP", "markers.", "Results:", "We", "have", "developed", "a", "program,", "called", "CapsID,", "that", "identifies", "snip-SNPs", "(single", "nucleotide", "polymorphisms", "that", "alter", "restriction", "endonuclease", "cut", "sites)", "within", "a", "set", "or", "sets", "of", "reference", "sequences,", "designs", "PCR", "primers", "around", "these,", "and", "then", "suggests", "the", "most", "parsimonious", "combination", "of", "markers", "for", "genotyping", "any", "individual", "who", "is", "not", "a", "member", "of", "the", "reference", "set.", "The", "output", "page", "includes", "biologist-friendly", "features,", "such", "as", "images", "of", "virtual", "gels", "to", "assist", "in", "genotyping", "efforts.", "CapsID", "is", "freely", "available", "at", "http://bbc.botany.utoronto.ca/capsid.", "Conclusion:", "CapsID", "is", "a", "tool", "that", "can", "rapidly", "provide", "minimal", "sets", "of", "CAPS", "markers", "for", "molecular", "identification", "purposes", "for", "any", "biologist", "working", "in", "genetics,", "community", "genetics,", "plant", "and", "animal", "breeding,", "forensics", "and", "other", "fields.", "Background", "DNA", "sequences", "from", "different", "varieties", "or", "accessions", "of", "a", "given", "species", "are", "becoming", "available", "through", "a", "number", "of", "sequencing", "projects.", "Single", "nucleotide", "polymorphisms", "(SNPs),", "together", "with", "insertion/deletions", "(InDels),", "are", "the", "most", "common", "type", "of", "polymorphism", "in", "the", "genomes", "studied", "so", "far.", "Large", "sets", "of", "predicted", "SNPs", "are", "publicly", "available", "for", "the", "human", "genome", "(SNP", "Consortium,", "http:/", "/snp.cshl.org),", "and", "for", "some", "genetic", "model", "organisms,", "including", "Caenorhabditis", "elegans", "[1],", "Drosophila", "mela-", "nogaster", "[2],", "and", "Arabidopsis", "thaliana", "[3].", "In", "addition,", "the", "generation", "of", "short", "stretches", "of", "DNA", "sequence", "informa-", "tion", "for", "non-model", "organisms,", "e.g.", "from", "ribosomal", "sequences,", "is", "becoming", "increasingly", "economical.", "Approx-", "imately", "30–40%", "of", "SNPs", "alter", "restriction", "endonuclease", "recognition", "sites", "and", "these", "are", "commonly", "referred", "to", "as", "snip-SNPs", "[1].", "Restriction", "enzyme", "digestion", "pattern", "poly-", "morphism", "may", "be", "used", "to", "create", "cleaved", "amplified", "poly-", "morphic", "sequence", "(CAPS)", "markers", "(also", "known", "as", "PCR-", "RFLP", "markers),", "which", "are", "codominant", "molecular", "markers", "that", "amplify", "a", "short", "genomic", "sequence", "around", "the", "poly-", "morphic", "endonuclease", "restriction", "site", "[4].", "They", "are", "easily", "Page", "1", "of", "5", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Sustained", "Fixation", "Induced", "Changes", "in", "Phoria", "and", "Convergence", "Peak", "Velocity", "Eun", "H.", "Kim1,", "Vincent", "R.", "Vicci2,", "Sang", "J.", "Han1,", "Tara", "L.", "Alvarez1*", "1", "Department", "of", "Biomedical", "Engineering,", "New", "Jersey", "Institute", "of", "Technology,", "Newark,", "New", "Jersey,", "United", "States", "of", "America,", "2", "Department", "of", "Vision,", "Private", "Practice,", "Westfield,", "New", "Jersey,", "United", "States", "of", "America,", "3", "Department", "of", "Vision", "Rehabilitation,", "Kessler", "Institute,", "West", "Orange,", "New", "Jersey,", "United", "States", "of", "America", "Abstract", "Purpose:", "This", "study", "sought", "to", "investigate", "the", "influence", "of", "phoria", "adaptation", "on", "convergence", "peak", "velocity", "from", "responses", "located", "at", "different", "initial", "vergence", "positions.", "Methods:", "Symmetrical", "4u", "convergence", "step", "responses", "and", "near", "dissociated", "phoria", "(measured", "at", "40", "cm", "from", "the", "subject’s", "midline)", "were", "recorded", "from", "six", "subjects", "with", "normal", "binocular", "vision", "using", "an", "infrared", "limbus", "tracking", "system", "with", "a", "haploscope.", "Two", "different", "sustained", "fixations", "(1u", "and", "16u", "convergent", "rotation", "along", "the", "subject’s", "midline)", "were", "used", "to", "study", "whether", "phoria", "had", "an", "influence", "on", "the", "peak", "velocity", "of", "convergence", "responses", "located", "at", "two", "initial", "vergence", "positions", "(1u", "or", "‘far’", "steps", "and", "12u", "or", "‘near’", "steps).", "Results:", "Phoria", "was", "significantly", "adapted", "after", "a", "sustained", "fixation", "task", "at", "near", "(16u)", "and", "far", "(1u)", "(p,0.002).", "A", "repeated", "measures", "ANOVA", "showed", "that", "convergence", "far", "steps", "were", "significantly", "faster", "than", "the", "near", "steps", "(p,0.03).", "When", "comparing", "convergence", "steps", "with", "the", "same", "initial", "vergence", "position,", "steps", "measured", "after", "near", "phoria", "adaptation", "were", "faster", "than", "responses", "after", "far", "adaptation", "(p,0.02).", "A", "regression", "analysis", "demonstrated", "that", "the", "change", "in", "phoria", "and", "the", "change", "in", "convergence", "peak", "velocity", "were", "significantly", "correlated", "for", "the", "far", "convergence", "steps", "(r", "=", "0.97,", "p", "=", "0.001).", "A", "weaker", "correlation", "was", "observed", "for", "the", "near", "convergence", "steps", "(r", "=", "0.59,", "p", "=", "0.20).", "Conclusion:", "As", "a", "result", "of", "sustained", "fixation,", "phoria", "was", "adapted", "and", "the", "peak", "velocity", "of", "the", "near", "and", "far", "convergence", "steps", "was", "modified.", "This", "study", "has", "clinical", "considerations", "since", "prisms,", "which", "evoke", "phoria", "adaptation,", "can", "be", "prescribed", "to", "help", "alleviate", "visual", "discomfort.", "Future", "investigations", "should", "include", "a", "systematic", "study", "of", "how", "prisms", "may", "influence", "convergence", "and", "divergence", "eye", "movements", "for", "those", "prescribed", "with", "prisms", "within", "their", "spectacles.", "Citation:", "Kim", "EH,", "Vicci", "VR,", "Han", "SJ,", "Alvarez", "TL", "(2011)", "Sustained", "Fixation", "Induced", "Changes", "in", "Phoria", "and", "Convergence", "Peak", "Velocity.", "PLoS", "ONE", "6(6):", "e20883.", "doi:10.1371/journal.pone.0020883", "Editor:", "Joel", "M.", "Miller,", "Smith-Kettlewell", "Eye", "Research", "Institute,", "United", "States", "of", "America", "Received", "February", "2,", "2011;", "Accepted", "May", "11,", "2011;", "Published", "June", "17,", "2011", "Copyright:", "2011", "Kim", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "This", "work", "was", "supported", "in", "part", "by", "a", "CAREER", "award", "from", "the", "National", "Science", "Foundation", "(BES-0447713).", "No", "additional", "external", "funding", "was", "received", "for", "this", "study.", "The", "funders", "had", "no", "role", "in", "study", "design,", "data", "collection", "and", "analysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "Competing", "Interests:", "The", "authors", "have", "declared", "that", "no", "competing", "interests", "exist.", "*", "E-mail:", "tara.l.alvarez@njit.edu", "Introduction", "Vergence,", "a", "binocular", "eye", "movement,", "is", "responsible", "for", "attaining", "visual", "information", "located", "at", "different", "distances.", "The", "two", "primary", "inputs", "to", "the", "vergence", "system", "are", "retinal", "blur", "and", "disparity[1].", "Retinal", "blur", "is", "the", "defocusing", "of", "images", "which", "stimulates", "the", "accommodative", "vergence", "system,", "whereas", "dispar-", "ity", "is", "the", "difference", "between", "where", "a", "new", "target", "is", "projected", "onto", "the", "retina", "and", "the", "fovea.", "Disparity", "stimulates", "the", "disparity-", "vergence", "system", "and", "allows", "a", "person", "to", "perceive", "and", "maintain", "a", "single", "binocular", "vision.", "The", "eyes", "may", "rotate", "inward", "(conver-", "gence)", "or", "outward", "(divergence)", "to", "project", "the", "line", "of", "sight", "onto", "the", "same", "point", "of", "interest.", "Through", "the", "use", "of", "different", "instruments,", "one", "can", "study", "accommodative-vergence", "or", "dispar-", "ity-vergence", "independently.", "A", "haploscope", "can", "systematically", "change", "where", "an", "object", "is", "projected", "onto", "the", "retina", "while", "maintaining", "a", "fixed", "focal", "length.", "Hence,", "when", "using", "a", "haploscope,", "any", "changes", "within", "eye", "movements", "can", "be", "assumed", "to", "be", "associated", "with", "the", "disparity-vergence", "system", "since", "the", "retinal", "blur", "stimulus", "is", "constant.", "When", "a", "binocular", "stimulus", "is", "eliminated,", "such", "as", "when", "one", "eye", "is", "occluded", "while", "the", "other", "eye", "is", "fixating", "on", "a", "target", "located", "along", "midline,", "the", "occluded", "eye", "will", "decay", "to", "its", "dissociated", "phoria", "level.", "Near-dissociated", "phoria", "is", "quantified", "when", "the", "viewing", "or", "non-", "occluded", "eye", "is", "fixated", "on", "a", "target", "located", "at", "40", "cm", "from", "the", "subject’s", "midline.", "Phoria", "can", "be", "classified", "as", "orthophoria,", "esophoria", "or", "exophoria,", "which", "are", "the", "absence,", "nasal", "or", "temporal", "rotation", "of", "the", "occluded", "eye,", "respectively.", "Phoria", "adaptation", "is", "a", "persistent", "modification", "in", "the", "eye", "alignment", "which", "can", "be", "due", "to", "a", "prolonged", "exposure", "to", "a", "binocular", "stimulus", "at", "different", "spatial", "depths.", "A", "rich", "history", "exists", "in", "the", "literature", "that", "describes", "model-", "representation", "of", "the", "neural", "control", "of", "disparity-vergence", "[2,3,4,5,6,7,8,9].", "These", "models", "can", "be", "classified", "into", "two", "types:", "1)", "negative", "feedback", "control", "or", "2)", "preprogrammed", "control", "operating", "synergistically", "with", "a", "negative", "feedback", "control.", "The", "models", "with", "only", "negative", "feedback", "control", "are", "continuously", "modified", "such", "that", "the", "error", "between", "the", "input", "and", "output", "is", "adjusted", "until", "it", "is", "negligible.", "Negative", "feedback", "control", "models", "can", "be", "further", "separated", "into", "a", "single", "negative", "feedback", "control,", "PLoS", "ONE", "|", "www.plosone.org", "1", "June", "2011", "|", "Volume", "6", "|", "Issue", "6", "|", "e20883" ]

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"of", "Biomedical", "Sciences,", "Nagasaki", "852-8501,", "Japan", "Correspondence", "should", "be", "addressed", "to", "Masayuki", "Obatake,", "mobatake@nagasaki-u.ac.jp", "Received", "25", "April", "2011;", "Accepted", "10", "August", "2011", "Academic", "Editor:", "E.", "N.", "Myers", "Copyright", "©", "2011", "Masayuki", "Obatake", "et", "al.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Tracheoinnominate", "artery", "fistula", "is", "known", "as", "a", "potentially", "fatal", "complication", "for", "patients", "who", "depend", "on", "tracheostomy", "or", "tracheoesophageal", "diversion.", "Since", "the", "bleeding", "from", "a", "TIF", "is", "often", "difficult", "to", "control,", "preventative", "procedures", "are", "recommended", "to", "avoid", "this", "complication.", "An", "11-year-old", "girl", "with", "hypoxic-ischemic", "encephalopathy", "and", "scoliosis", "developed", "tracheal", "stenosis", "caused", "by", "compression", "from", "the", "innominate", "artery.", "Respiratory", "control", "with", "intubation", "through", "the", "tracheal", "stenosis", "was", "needed,", "and", "the", "patient", "was", "at", "high", "risk", "for", "developing", "a", "TIF.", "She", "underwent", "ligation", "of", "the", "innominate", "artery", "at", "tracheostomy.", "Subsequent", "tracheostomy", "revealed", "a", "widened", "tracheal", "lumen", "and", "no", "further", "complications.", "Prophylactic", "ligation", "of", "the", "innominate", "artery", "and", "creation", "of", "tracheostomy", "might", "be", "considered", "as", "a", "valid", "option", "for", "patients", "at", "high", "risk", "of", "developing", "TIF.", "1.", "Introduction", "Neurologically", "impaired", "children", "often", "require", "tracheostomy", "or", "tracheoesophageal", "diversion", "for", "long-term", "mechanical", "ventilation.", "Under", "these", "circumstances,", "numerous", "compli-", "cations", "such", "as", "tracheal", "wall", "damage,", "tracheal", "granulation,", "and", "tracheoinnominate", "fistula", "(TIF)", "have", "been", "reported", "[1–3].", "TIF", "is", "a", "serious", "and", "often", "fatal", "complication.", "Since", "the", "survival", "rate", "is", "reported", "to", "be", "less", "than", "30%", "even", "with", "surgical", "intervention", "[4,", "5],", "preventive", "measures", "are", "recommended", "to", "avoid", "TIF.", "We", "report", "a", "case", "of", "ligation", "of", "the", "innominate", "artery", "before", "tracheostomy", "in", "a", "patient", "who", "had", "developed", "tracheal", "stenosis.", "2.", "Case", "Report", "An", "11-year-old", "girl", "with", "hypoxic-ischemic", "encephalopathy", "had", "gradually", "developed", "scoliosis,", "and", "she", "had", "experienced", "several", "episodes", "of", "mild", "wheezing", "associated", "with", "myotonia.", "Her", "SpO2", "levels", "had", "decreased", "to", "20–30%", "during", "episodes", "of", "severe", "myotonia.", "She", "was", "referred", "to", "a", "medical", "center", "after", "the", "abrupt", "onset", "of", "wheezing", "and", "respiratory", "distress.", "Chest", "X-ray", "revealed", "scoliosis", "(Figure", "1),", "and", "laryngoscopy", "showed", "neither", "supraglottic", "stenosis", "nor", "edema.", "Chest", "computed", "tomography", "(CT)", "revealed", "tracheal", "stenosis", "caused", "by", "com-", "pression", "by", "the", "innominate", "artery", "(Figure", "2).", "Bronchoscopy", "demonstrated", "narrowing", "of", "the", "trachea", "by", "external", "compres-", "sion", "of", "its", "anterior", "wall", "as", "well", "as", "tracheomalacia", "(Figure", "3)", "involving", "the", "middle", "trachea", "to", "the", "tracheal", "bifurcation.", "An", "uncuffed", "endotracheal", "tube", "was", "inserted", "distally", "to", "the", "stenosis,", "and", "this", "resulted", "in", "a", "prompt", "improvement", "in", "her", "respiratory", "condition.", "However,", "she", "was", "thought", "to", "require", "long-term", "tracheal", "intubation", "because", "of", "the", "tracheal", "stenosis", "and", "tracheomalacia.", "Furthermore,", "she", "was", "considered", "at", "increased", "risk", "of", "developing", "tracheal", "damage", "and", "subsequent", "formation", "of", "TIF", "from", "tracheal", "intubation." ]

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[ "Sensors", "2011,", "11,", "6685-6696;", "doi:10.3390/s110706685", "OPEN", "ACCESS", "sensors", "ISSN", "1424-8220", "www.mdpi.com/journal/sensors", "Article", "Label", "Free", "Inhibitor", "Screening", "of", "Hepatitis", "C", "Virus", "(HCV)", "NS5B", "Viral", "Protein", "Using", "RNA", "Oligonucleotide", "Changhyun", "Roh", "1,*,", "Sang", "Eun", "Kim", "2", "and", "Sung-Kee", "Jo", "1", "1", "Radiation", "Research", "Division", "for", "Biotechnology,", "Advanced", "Radiation", "Technology", "Institute", "(ARTI),", "Korea", "Atomic", "Energy", "Research", "Institute", "(KAERI),", "1266", "Shinjeong-dong,", "Jeongeup-si,", "Jeollabuk-do", "580-185,", "Korea;", "E-Mail:", "skjo@kaeri.re.kr", "2", "Department", "of", "Nuclear", "Medicine,", "Seoul", "National", "University", "College", "of", "Medicine,", "Seoul", "National", "University", "Bundang", "Hospital,", "Seongnam", "463-707,", "Korea;", "E-Mail:", "kse@snu.ac.kr", "*", "Author", "to", "whom", "correspondence", "should", "be", "addressed;", "E-Mail:", "chroh@kaeri.re.kr;", "Tel.:", "+82-63-570-3227;", "Fax:", "+82-63-570-3229.", "Received:", "11", "May", "2011;", "in", "revised", "form:", "22", "June", "2011", "/", "Accepted:", "27", "June", "2011", "/", "Published:", "27", "June", "2011", "Abstract:", "Globally,", "over", "170", "million", "people", "(ca.", "3%", "of", "the", "World’s", "population)", "are", "infected", "with", "the", "hepatitis", "C", "virus", "(HCV),", "which", "can", "cause", "serious", "liver", "diseases", "such", "as", "chronic", "hepatitis,", "evolving", "into", "subsequent", "health", "problems.", "Driven", "by", "the", "need", "to", "detect", "the", "presence", "of", "HCV,", "as", "an", "essential", "factor", "in", "diagnostic", "medicine,", "the", "monitoring", "of", "viral", "protein", "has", "been", "of", "great", "interest", "in", "developing", "simple", "and", "reliable", "HCV", "detection", "methods.", "Despite", "considerable", "advances", "in", "viral", "protein", "detection", "as", "an", "HCV", "disease", "marker,", "the", "current", "enzyme", "linked", "immunosorbent", "assay", "(ELISA)", "based", "detection", "methods", "using", "antibody", "treatment", "have", "several", "drawbacks.", "To", "overcome", "this", "bottleneck,", "an", "RNA", "aptamer", "become", "to", "be", "emerged", "as", "an", "antibody", "substitute", "in", "the", "application", "of", "biosensor", "for", "detection", "of", "viral", "protein.", "In", "this", "study,", "we", "demonstrated", "a", "streptavidin-biotin", "conjugation", "method,", "namely,", "the", "RNA", "aptamer", "sensor", "system", "that", "can", "quantify", "viral", "protein", "with", "detection", "level", "of", "700", "pg", "mL−1", "using", "a", "biotinylated", "RNA", "oligonucleotide", "on", "an", "Octet", "optical", "biosensor.", "Also,", "we", "showed", "this", "method", "can", "be", "used", "to", "screen", "inhibitors", "of", "viral", "protein", "rapidly", "and", "simply", "on", "a", "biotinylated", "RNA", "oligonucleotide", "biosensor.", "Among", "the", "inhibitors", "screened,", "(−)-Epigallocatechin", "gallate", "showed", "high", "binding", "inhibition", "effect", "on", "HCV", "NS5B", "viral", "protein.", "The", "proposed", "method", "can", "be", "considered", "a", "real-time", "monitoring", "method", "for", "inhibitor", "screening", "of", "HCV", "viral", "protein", "and", "is", "expected", "to", "be", "applicable", "to", "other", "types", "of", "diseases." ]

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[ "BMC", "Medical", "Education", "BioMed", "Central", "1BR2M0e0Cs1eM,aedriccahl", "Eadrutciactiloen", ":6", "Introducing", "evidence", "based", "medicine", "to", "the", "journal", "club,", "using", "a", "structured", "pre", "and", "post", "test:", "a", "cohort", "study", "J", "Steven", "Cramer*1", "and", "Martin", "C", "Mahoney2", "Address:", "1Department", "of", "Family", "Medicine,", "School", "of", "Medicine", "and", "Biomedical", "Sciences,", "State", "University", "of", "New", "York", "at", "Buffalo,", "Buffalo,", "New", "York,", "USA", "and", "2Department", "of", "Family", "Medicine,", "School", "of", "Medicine", "and", "Biomedical", "Sciences,", "State", "University", "of", "New", "York", "at", "Buffalo,", "Buffalo,", "New", "York,", "USA", "E-mail:", "J", "Steven", "Cramer*", "-", "CramerJS@email.msn.com;", "Martin", "C", "Mahoney", "-", "MMahone@acsu.buffalo.edu", "*Corresponding", "author", "Published:", "6", "November", "2001", "BMC", "Medical", "Education", "2001,", "1:6", "This", "article", "is", "available", "from:", "http://www.biomedcentral.com/1472-6920/1/6", "Received:", "28", "August", "2001", "Accepted:", "6", "November", "2001", "©", "2001", "Cramer", "and", "Mahoney;", "licensee", "BioMed", "Central", "Ltd.", "Verbatim", "copying", "and", "redistribution", "of", "this", "article", "are", "permitted", "in", "any", "medium", "for", "any", "non-commercial", "purpose,", "provided", "this", "notice", "is", "preserved", "along", "with", "the", "article's", "original", "URL.", "For", "commercial", "use,", "contact", "info@biomedcentral.com", "Abstract", "Background:", "Journal", "Club", "at", "a", "University-based", "residency", "program", "was", "restructured", "to", "introduce,", "reinforce", "and", "evaluate", "residents", "understanding", "of", "the", "concepts", "of", "Evidence", "Based", "Medicine.", "Methods:", "Over", "the", "course", "of", "a", "year", "structured", "pre", "and", "post-tests", "were", "developed", "for", "use", "during", "each", "Journal", "Club.", "Questions", "were", "derived", "from", "the", "articles", "being", "reviewed.", "Performance", "with", "the", "key", "concepts", "of", "Evidence", "Based", "Medicine", "was", "assessed.", "Study", "subjects", "were", "35", "PGY2", "and", "PGY3", "residents", "in", "a", "University", "based", "Family", "Practice", "Program.", "Results:", "Performance", "on", "the", "pre-test", "demonstrated", "a", "significant", "improvement", "from", "a", "median", "of", "54.5", "%", "to", "78.9", "%", "over", "the", "course", "of", "the", "year", "(F", "89.17,", "p", "<", ".001).", "The", "post-test", "results", "also", "exhibited", "a", "significant", "increase", "from", "63.6", "%", "to", "81.6%", "(F", "85.84,", "p", "<", ".001).", "Conclusions:", "Following", "organizational", "revision,", "the", "introduction", "of", "a", "pre-test/post-test", "instrument", "supported", "achievement", "of", "the", "learning", "objectives", "with", "a", "better", "understanding", "and", "utilization", "of", "the", "concepts", "of", "Evidence", "Based", "Medicine.", "Background", "The", "Residency", "Review", "Committee", "guidelines", "for", "Family", "Medicine", "require", "teaching", "the", "skills", "necessary", "for", "the", "critical", "appraisal", "of", "the", "medical", "literature.", "Most", "residen-", "cy", "training", "programs", "accomplish", "this", "in", "the", "setting", "of", "a", "monthly", "journal", "club.", "At", "our", "program,", "faculty", "involved", "with", "organizing", "these", "sessions", "noted", "an", "ongoing", "frustra-", "tion", "with", "the", "attendance,", "preparation,", "participation", "and", "focus", "of", "the", "residents.", "utility", "of", "the", "Journal", "Club.", "This", "opportunity", "to", "reorgan-", "ize", "also", "allowed", "reexamination", "of", "the", "goals", "and", "objec-", "tives", "for", "the", "Journal", "Club", "in", "line", "with", "those", "suggested", "by", "others", "[1].", "A", "formal", "curriculum", "review", "with", "new", "goals", "and", "objectives", "was", "put", "in", "place,", "acknowledged", "by", "renam-", "ing", "the", "sessions", "as", "\"Evidence", "Based", "Medicine", "/Journal", "Club\".", "Paramount", "was", "a", "focus", "on", "critical", "appraisal", "and", "clinical", "epidemiology", "from", "the", "Evidence-based", "perspec-", "tive.", "Within", "the", "framework", "of", "a", "needs", "assessment,", "residents", "were", "surveyed", "to", "identify", "issues", "directly", "related", "to", "the", "A", "syllabus", "of", "material", "on", "the", "approach", "to", "Evidence-", "based", "Medicine", "was", "chosen", "to", "provide", "the", "skills", "neces-" ]

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[ "Mostafa", "and", "AL-Ayadhi", "Journal", "of", "Neuroinflammation", "2011,", "8:71", "http://www.jneuroinflammation.com/content/8/1/71", "R", "E", "S", "E", "A", "R", "C", "H", "JOURNAL", "OF", "NEUROINFLAMMATION", "Open", "Access", "A", "lack", "of", "association", "between", "hyperserotonemia", "and", "the", "increased", "frequency", "of", "serum", "anti-myelin", "basic", "protein", "auto-antibodies", "in", "autistic", "children", "Gehan", "Ahmed", "Mostafa1,2*", "and", "Laila", "Yousef", "AL-Ayadhi1", "Abstract", "Background:", "One", "of", "the", "most", "consistent", "biological", "findings", "in", "autism", "is", "the", "elevated", "blood", "serotonin", "levels.", "Immune", "abnormalities,", "including", "autoimmunity", "with", "production", "of", "brain", "specific", "auto-antibodies,", "are", "also", "commonly", "observed", "in", "this", "disorder.", "Hyperserotonemia", "may", "be", "one", "of", "the", "contributing", "factors", "to", "autoimmunity", "in", "some", "patients", "with", "autism", "through", "the", "reduction", "of", "T-helper", "(Th)", "1-type", "cytokines.", "We", "are", "the", "first", "to", "investigate", "the", "possible", "role", "of", "hyperserotonemia", "in", "the", "induction", "of", "autoimmunity,", "as", "indicated", "by", "serum", "anti-myelin-basic", "protein", "(anti-MBP)", "auto-antibodies,", "in", "autism.", "Methods:", "Serum", "levels", "of", "serotonin", "and", "anti-MBP", "auto-antibodies", "were", "measured,", "by", "ELISA,", "in", "50", "autistic", "patients,", "aged", "between", "5", "and", "12", "years,", "and", "30", "healthy-matched", "children.", "Results:", "Autistic", "children", "had", "significantly", "higher", "serum", "levels", "of", "serotonin", "and", "anti-MBP", "auto-antibodies", "than", "healthy", "children", "(P", "<", "0.001", "and", "P", "<", "0.001,", "respectively).", "Increased", "serum", "levels", "of", "serotonin", "and", "anti-MBP", "auto-", "antibodies", "were", "found", "in", "92%", "and", "80%,", "respectively", "of", "autistic", "patients.", "Patients", "with", "severe", "autism", "had", "significantly", "higher", "serum", "serotonin", "levels", "than", "children", "with", "mild", "to", "moderate", "autism", "(P", "<", "0.001).", "Serum", "serotonin", "levels", "had", "no", "significant", "correlations", "with", "serum", "levels", "of", "anti-MBP", "auto-antibodies", "in", "autistic", "patients", "(P", "=", "0.39).", "Conclusions:", "Hyperserotonemia", "may", "not", "be", "one", "of", "the", "contributing", "factors", "to", "the", "increased", "frequency", "of", "serum", "anti-MBP", "auto-antibodies", "in", "some", "autistic", "children.", "These", "data", "should", "be", "treated", "with", "caution", "until", "further", "investigations", "are", "performed.", "However,", "inclusion", "of", "serum", "serotonin", "levels", "as", "a", "correlate", "may", "be", "useful", "in", "other", "future", "immune", "studies", "in", "autism", "to", "help", "unravel", "the", "long-standing", "mystery", "of", "hyperserotonemia", "and", "its", "possible", "role", "in", "the", "pathophysiology", "of", "this", "disorder.", "Keywords:", "Anti-myelin-basic", "protein", "antibodies,", "autism,", "autoimmunity,", "hyperserotonemia,", "serotonin", "1.", "Introduction", "Autoimmunity", "to", "CNS", "may", "have", "a", "pathogenic", "role", "in", "autism", "[1].", "This", "may", "be", "indicated", "by", "the", "presence", "of", "brain-specific", "auto-antibodies", "in", "some", "autistic", "children", "[2-8].", "There", "is", "also", "an", "increase", "in", "the", "frequency", "of", "auto-", "immune", "disorders", "among", "autistic", "families", "[9-15].", "Serotonin", "is", "formed", "by", "hydroxylation", "and", "decarboxy-", "lation", "of", "tryptophan.", "Serotonin", "is", "known", "to", "play", "a", "role", "*", "Correspondence:", "hafezg@softhome.net", "1Autism", "Research", "and", "Treatment", "Center,", "AL-Amodi", "Autism", "Research", "Chair,", "Department", "of", "Physiology,", "Faculty", "of", "Medicine,", "King", "Saud", "University,", "Riyadh,", "Saudi", "Arabia", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "in", "brain", "development", "prior", "to", "the", "time", "it", "assumes", "its", "role", "as", "a", "neurotransmitter.", "Disruption", "of", "serotonergic", "development", "can", "leave", "permanent", "alterations", "in", "brain", "function", "and", "behavior.", "This", "may", "be", "the", "case", "in", "autism", "[16,17].", "It", "was", "suggested", "that", "autism,", "without", "a", "discern-", "ible", "cause,", "may", "be", "a", "genetic", "disorder", "of", "serotonin", "meta-", "bolism.", "The", "interest", "in", "assessing", "serotonergic", "function", "in", "autism", "stems", "from", "its", "role", "in", "perception", "and", "filtering", "of", "sensory", "signals,", "social", "attachment", "and", "facilitation", "of", "formation", "of", "synapses", "which", "is", "crucial", "to", "acquire", "learn-", "ing", "and", "memory", "[18].", "Blood", "serotonin", "might", "serve", "as", "analogue", "marker", "for", "serotonergic", "function", "[19].", "©", "2011", "Mostafa", "and", "AL-Ayadhi;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "R", "E", "V", "I", "E", "W", "Differential", "diagnosis", "of", "leukocoria", "and", "strabismus,", "first", "presenting", "signs", "of", "retinoblastoma", "Aubin", "Balmer", "Francis", "Munier", "Jules", "Gonin", "University", "Eye", "Hospital,", "Lausanne,", "Switzerland", "Correspondence:Aubin", "Balmer", "Privat-Docent,", "Maître", "d’enseignement", "et", "de", "Recherche,", "Hôpital", "Ophtalmique", "Jules", "Gonin,", "15,Avenue", "de", "France,", "1004", "Lausanne,", "Switzerland", "Tel", "+41", "27", "323", "22", "12", "Fax", "+41", "27", "323", "22", "18", "Email", "aubin.balmer@bluewin.ch", "Abstract:", "Leukocoria", "in", "infants", "is", "always", "a", "danger", "signal", "as", "retinoblastoma,", "a", "malignant", "retinal", "tumor,", "is", "responsible", "for", "half", "of", "the", "cases", "in", "this", "age", "group.", "More", "common", "signs", "should", "also", "be", "considered", "suspicious", "until", "proved", "otherwise,", "such", "as", "strabismus,", "the", "second", "most", "frequent", "sign", "of", "retinoblastoma.", "Less", "frequent", "manifestations", "are", "inflammatory", "conditions", "resistant", "to", "treatment,", "hypopyon,", "orbital", "cellulitis,", "hyphema", "or", "heterochromia.", "Other", "causal", "pathologies,", "including", "persistent", "hyperplastic", "primary", "vitreous", "(PHPV),", "Coats’", "disease,", "ocular", "toxocariasis", "or", "retinopathy", "of", "prematurity,", "may", "also", "manifest", "the", "same", "warning", "signs", "and", "require", "special-", "ized", "differential", "diagnosis.", "Members", "of", "the", "immediate", "family", "circle", "are", "most", "likely", "to", "notice", "the", "first", "signs,", "the", "general", "practitioner,", "pediatrician", "or", "general", "ophthalmologist", "the", "first", "to", "be", "consulted.", "On", "their", "attitude", "will", "depend", "the", "final", "outcome", "of", "this", "vision", "and", "life-threatening", "disease.", "Early", "diagnosis", "is", "vital.", "Keywords:", "leukocoria,", "strabismus,", "retinoblastoma,", "Coats’", "disease,", "persistent", "hyperplastic", "primary", "vitreous", "(PHPV)", "Introduction", "Retinoblastoma", "represents", "the", "greatest", "challenge", "in", "the", "field", "of", "ophthalmology.", "Affecting", "very", "young", "infants,", "in", "most", "cases", "perfectly", "healthy", "in", "all", "other", "respects,", "this", "highly", "malignant", "cancer", "of", "the", "retina", "threatens", "those", "individuals", "with", "the", "longest", "potential", "lifespan.", "Survivors", "may", "be", "severely", "handicapped", "by", "lesions", "of", "the", "posterior", "pole", "affecting", "central", "visual", "function.", "These", "children", "can", "be", "cured,", "however,", "at", "low", "cost", "and", "with", "minimal", "suffering,", "provided", "that", "treatment", "is", "given", "in", "the", "early", "stages", "of", "disease.", "At", "later", "stages", "treatment", "is", "costly,", "burdensome,", "and", "with", "no", "certain", "outcome.", "Retinoblastoma", "is", "fortunately", "a", "rare", "disease,", "but", "other", "intraocular", "lesions", "may", "mimic", "the", "initial", "signs", "or", "clinical", "features", "and", "are", "sometimes", "called", "“pseudo-retinoblastomas”", "(Dollfus", "and", "Auvert", "1953).", "Retinoblastoma", "does,", "however,", "represent", "80%", "of", "primary", "ocular", "tumors", "in", "children", "under", "15", "years", "of", "age", "(Mahoney", "et", "al", "1990)", "17%", "of", "all", "neonatal", "cancers", "(Halperin", "2000)", "and", "1%", "of", "all", "deaths", "due", "to", "cancer", "(Miller", "1969).", "All", "ages", "considered,", "it", "is", "the", "third", "most", "frequent", "cancer", "of", "the", "eye", "and", "ocular", "adnexa", "(20%)", "and", "represents", "3%", "of", "all", "pediatric", "cancers", "(Scat", "et", "al", "1996).", "Thus", "the", "importance", "of", "keeping", "in", "mind", "the", "possibility", "of", "retinoblastoma", "when", "confronted", "with", "suspicious", "signs", "such", "as", "a", "white", "pupil", "or", "leukocoria", "(Figure1a),", "the", "most", "common", "first", "manifestation,", "strabismus", "or", "any", "other", "unexplained", "signs.", "In", "this", "article,", "other", "conditions", "to", "take", "into", "consideration", "in", "the", "differential", "diagnosis", "of", "leukocoria", "or", "other", "signs", "associated", "with", "retinoblastoma", "will", "be", "reviewed.", "Clinical", "Ophthalmology", "2007:1(4)", "431–439", "©", "2007", "Dove", "Medical", "Press", "Limited.", "All", "rights", "reserved", "431" ]

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[ "Psychopharmacology", "(2011)", "215:321–332", "DOI", "10.1007/s00213-010-2149-4", "ORIGINAL", "INVESTIGATION", "Residual", "effects", "of", "esmirtazapine", "on", "actual", "driving", "performance:", "overall", "findings", "and", "an", "exploratory", "analysis", "into", "the", "role", "of", "CYP2D6", "phenotype", "Johannes", "G.", "Ramaekers", "&", "Silke", "Conen", "&", "Pieter", "Jan", "de", "Kam", "&", "Sabine", "Braat", "&", "Pierre", "Peeters", "&", "Eef", "L.", "Theunissen", "&", "Neely", "Ivgy-may", "Received:", "25", "October", "2010", "/", "Accepted:", "8", "December", "2010", "/", "Published", "online:", "19", "January", "2011", "#", "The", "Author(s)", "2011.", "This", "article", "is", "published", "with", "open", "access", "at", "Springerlink.com", "Abstract", "Introduction", "Esmirtazapine", "is", "evaluated", "as", "a", "novel", "drug", "for", "treatment", "of", "insomnia.", "Purpose", "The", "present", "study", "was", "designed", "to", "assess", "residual", "effects", "of", "single", "and", "repeated", "doses", "of", "esmirtazapine", "1.5", "and", "4.5", "mg", "on", "actual", "driving", "in", "32", "healthy", "volunteers", "in", "a", "double-", "blind,", "placebo-controlled", "study.", "Treatment", "with", "single", "doses", "of", "zopiclone", "7.5", "mg", "was", "included", "as", "active", "control.", "Methods", "Treatments", "were", "administered", "in", "the", "evening.", "Driv-", "ing", "performance", "was", "assessed", "in", "the", "morning,", "11", "h", "after", "drug", "intake,", "in", "a", "standardized", "on-the-road", "highway", "driving", "test.", "The", "primary", "study", "parameter", "was", "standard", "deviation", "of", "lateral", "position", "(SDLP),", "a", "measure", "of", "“weaving”.", "All", "subjects", "were", "subjected", "to", "CYP2D6", "phenotyping", "in", "order", "to", "distinguish", "poor", "metabolizers", "from", "extensive", "metabolizers", "of", "esmirtazapine.", "Results", "Overall,", "esmirtazapine", "1.5", "mg", "did", "not", "produce", "any", "clinically", "relevant", "change", "in", "SDLP", "after", "single", "and", "repeated", "dosing.", "Driving", "impairment,", "i.e.,", "a", "rise", "in", "SDLP,", "did", "occur", "after", "a", "single-dose", "administration", "of", "esmirtazapine", "4.5", "mg", "but", "was", "resolved", "after", "repeated", "doses.", "Acute", "driving", "impairment", "was", "more", "pronounced", "after", "both", "doses", "of", "esmirtazapine", "in", "a", "This", "trial", "has", "been", "registered", "at", "ClinicalTrials.gov", "as", "NCT00798395", "http://", "www.clinicaltrials.gov/ct2/show/NCT00798395?term=21105&rank=1", "J.", "G.", "Ramaekers", "(*)", ":", "S.", "Conen", ":", "E.", "L.", "Theunissen", "Department", "of", "Neuropsychology", "and", "Psychopharmacology,", "Faculty", "of", "Psychology", "and", "Neuroscience,", "Maastricht", "University,", "Maastricht,", "The", "Netherlands", "e-mail:", "j.ramaekers@maastrichtuniversity.nl", "P.", "J.", "de", "Kam", ":", "S.", "Braat", ":", "P.", "Peeters", "MSD,", "Oss,", "The", "Netherlands", "N.", "Ivgy-may", "Merck", "&", "Co.,", "Summit,", "NJ,", "USA", "select", "group", "of", "poor", "metabolizers", "(N", "=", "7).", "A", "single-dose", "zopiclone", "7.5", "mg", "also", "increased", "SDLP", "as", "expected.", "Conclusion", "It", "is", "concluded", "that", "single", "and", "repeated", "doses", "of", "1.5", "mg", "esmirtazapine", "are", "generally", "not", "associated", "with", "residual", "impairment.", "Single-dose", "administration", "of", "4.5", "mg", "esmirtazapine", "was", "associated", "with", "residual", "impairment", "that", "generally", "resolved", "after", "repeated", "administration.", "Explorato-", "ry", "analysis", "in", "a", "small", "group", "of", "poor", "CYP", "2D6", "metabolizers", "suggested", "that", "these", "subjects", "are", "more", "sensitive", "to", "the", "impairing", "effects", "of", "esmirtazapine", "on", "car", "driving.", "Keywords", "Hypnotics", ".", "H1", "antagonism", ".", "Driving", ".", "Cognition", ".", "CYP2D6", "phenotype", "Introduction", "Esmirtazapine", "maleate", "(Org", "50081)", "is", "the", "maleate", "salt", "of", "the", "S(+)-enantiomer", "of", "the", "racemic", "drug", "mirtazapine.", "Racemic", "mirtazapine", "is", "marketed", "for", "the", "treatment", "of", "major", "depressive", "disorder.", "Mirtazapine", "is", "a", "close", "analog", "of", "its", "predecessor", "mianserin", "that", "also", "has", "been", "marketed", "for", "major", "depressive", "disorder.", "Esmirtazapine", "and", "mirtazapine", "bind", "to", "presynaptic", "α2", "receptors", "as", "well", "as", "to", "postsynaptic", "5HT2", "and", "H1", "receptors", "where", "they", "act", "as", "antagonists", "of", "the", "endogeneous", "ligands", "(de", "Boer", "and", "Ruigt", "1995b;", "Pinder", "and", "van", "Delft", "1983);", "however,", "compared", "with", "mirtazapine", "and", "R-mirtazapine,", "esmirtazapine", "has", "higher", "affinity", "to", "5-HT2", "receptors", "and", "low", "affinity", "to", "the", "5-HT3", "receptors", "and", "to", "the", "muscarinic", "receptors", "(de", "Boer", "et", "al.", "1988;", "Kooyman", "et", "al.", "1994).", "Esmirtazapine", "is", "under", "development", "for", "the", "treat-", "ment", "of", "primary", "insomnia", "and", "hot", "flushes.", "Antidepressants", "such", "as", "mirtazapine", "and", "mianserin", "are", "well", "known", "for", "their", "sedative", "properties", "(Biswas", "et", "al." ]

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[ "Roebke", "et", "al.", "Retrovirology", "2010,", "7:69", "http://www.retrovirology.com/content/7/1/69", "R", "E", "S", "E", "A", "R", "C", "H", "Open", "Access", "An", "N-terminally", "truncated", "envelope", "protein", "encoded", "by", "a", "human", "endogenous", "retrovirus", "W", "locus", "on", "chromosome", "Xq22.3", "Christina", "Roebke1†,", "Silke", "Wahl1†,", "Georg", "Laufer1,", "Christine", "Stadelmann2,", "Marlies", "Sauter1,", "Nikolaus", "Mueller-Lantzsch1,", "Jens", "Mayer3,", "Klemens", "Ruprecht1,4*", "Abstract", "Background:", "We", "previously", "showed", "that", "the", "envelope", "(env)", "sequence", "of", "a", "human", "endogenous", "retrovirus", "(HERV)-", "W", "locus", "on", "chromosome", "Xq22.3", "is", "transcribed", "in", "human", "peripheral", "blood", "mononuclear", "cells.", "The", "env", "open", "reading", "frame", "(ORF)", "of", "this", "locus", "is", "interrupted", "by", "a", "premature", "stop", "at", "codon", "39,", "but", "otherwise", "harbors", "a", "long", "ORF", "for", "an", "N-terminally", "truncated", "475", "amino", "acid", "Env", "protein,", "starting", "at", "an", "in-frame", "ATG", "at", "codon", "68.", "We", "set", "out", "to", "characterize", "the", "protein", "encoded", "by", "that", "ORF.", "Results:", "Transient", "expression", "of", "the", "475", "amino", "acid", "Xq22.3", "HERV-W", "env", "ORF", "produced", "an", "N-terminally", "truncated", "HERV-W", "Env", "protein,", "as", "detected", "by", "the", "monoclonal", "anti-HERV-W", "Env", "antibodies", "6A2B2", "and", "13H5A5.", "Remarkably,", "reversion", "of", "the", "stop", "at", "codon", "39", "in", "Xq22.3", "HERV-W", "env", "reconstituted", "a", "full-length", "HERV-W", "Xq22.3", "Env", "protein.", "Similar", "to", "the", "full-length", "HERV-W", "Env", "protein", "Syncytin-1,", "reconstituted", "full-length", "Xq22.3", "HERV-W", "Env", "is", "glycosylated,", "forms", "oligomers,", "and", "is", "expressed", "at", "the", "cell", "surface.", "In", "contrast,", "Xq22.3", "HERV-W", "Env", "is", "unglycosylated,", "does", "not", "form", "oligomers,", "and", "is", "located", "intracellularly,", "probably", "due", "to", "lack", "of", "a", "signal", "peptide.", "Finally,", "we", "reconfirm", "by", "immunohistochemistry", "that", "monoclonal", "antibody", "6A2B2", "detects", "an", "antigen", "expressed", "in", "placenta", "and", "multiple", "sclerosis", "brain", "lesions.", "Conclusions:", "A", "partially", "defective", "HERV-W", "env", "gene", "located", "on", "chromosome", "Xq22.3,", "which", "we", "propose", "to", "designate", "ERVWE2,", "has", "retained", "coding", "capacity", "and", "can", "produce", "ex", "vivo", "an", "N-terminally", "truncated", "Env", "protein,", "named", "N-Trenv.", "Detection", "of", "an", "antigen", "by", "6A2B2", "in", "placenta", "and", "multiple", "sclerosis", "lesions", "opens", "the", "possibility", "that", "N-Trenv", "could", "be", "expressed", "in", "vivo.", "More", "generally,", "our", "findings", "are", "compatible", "with", "the", "idea", "that", "defective", "HERV", "elements", "may", "be", "capable", "of", "producing", "incomplete", "HERV", "proteins", "that,", "speculatively,", "may", "exert", "functions", "in", "human", "physiology", "or", "pathology.", "Background", "Multiple", "sclerosis", "(MS)", "is", "a", "chronic", "inflammatory", "demyelinating", "disease", "of", "the", "central", "nervous", "system", "affecting", "primarily", "young", "adults.", "While", "its", "precise", "aetiol-", "ogy", "is", "unknown,", "MS", "is", "thought", "to", "be", "a", "multifactorial", "disorder", "resulting", "from", "the", "interaction", "of", "environmental", "and", "genetic", "factors", "[1].", "A", "multiple", "sclerosis-associated", "retrovirus", "(MSRV)", "has", "previously", "been", "suggested", "by", "cDNA", "clones", "that", "were", "generated", "from", "particle-", "*", "Correspondence:", "klemens.ruprecht@charite.de", "†", "Contributed", "equally", "1Institut", "für", "Virologie,", "Gebäude", "47,", "Universitätsklinikum", "des", "Saarlandes,", "66421", "Homburg,", "Germany", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "associated", "RNA", "from", "plasma", "or", "supernatants", "of", "cul-", "tured", "cells", "from", "patients", "with", "MS", "[2-4].", "Subsequent", "investigations", "revealed", "MSRV-related", "sequences", "in", "the", "human", "genome,", "the", "human", "endogenous", "retrovirus", "family", "type", "W", "(HERV-W)", "[5].", "HERVs", "are", "considered", "remnants", "of", "ancestral", "germ", "line", "infections", "by", "once", "active", "retroviruses", "and", "contribute", "approximately", "8%", "of", "the", "human", "genome", "(for", "review", "see", "[6,7]).", "Like", "their", "exogenous", "counterparts,", "HERVs", "typi-", "cally", "consist", "of", "an", "internal", "region", "containing", "gag,", "pro,", "pol,", "and", "env", "genes,", "flanked", "by", "two", "long", "terminal", "repeats", "(LTR).", "The", "number", "and", "phylogenetic", "relationships", "among", "HERV-W", "sequences", "in", "the", "human", "genome", "have", "been", "addressed", "before", "[8,9].", "HERV-W", "is", "a", "multicopy", "©", "2010", "Roebke", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Keikhaei", "and", "Soltani", "Shirazi", "Journal", "of", "Medical", "Case", "Reports", "2011,", "5:274", "http://www.jmedicalcasereports.com/content/5/1/274", "C", "A", "S", "E", "R", "E", "P", "O", "R", "T", "JOURNAL", "OF", "MEDICAL", "CASE", "REPORTS", "Open", "Access", "Spontaneous", "iliopsoas", "muscle", "hematoma", "in", "a", "patient", "with", "von", "Willebrand", "disease:", "a", "case", "report", "Bijan", "Keikhaei1*", "and", "Ahmad", "Soltani", "Shirazi2", "Abstract", "Introduction:", "Iliopsoas", "hemorrhage", "is", "a", "serious", "complication", "of", "bleeding", "disorders", "that", "occurs", "most", "commonly", "in", "patients", "with", "hemophilia", "and", "less", "commonly", "in", "patients", "with", "von", "Willebrand", "disease.", "It", "causes", "severe", "pain,", "muscle", "dysfunction", "and", "occasionally", "femoral", "nerve", "palsy.", "We", "describe", "the", "case", "of", "a", "patient", "with", "von", "Willebrand", "disease", "type", "3", "with", "a", "large", "iliopsoas", "hematoma", "who", "was", "treated", "with", "a", "von", "Willebrand", "factor", "concentrate", "(Humate-P).", "Case", "presentation:", "A", "20-year-old", "Iranian", "man", "was", "referred", "to", "our", "emergency", "ward", "because", "of", "the", "gradual", "onset", "of", "right", "flank", "pain.", "He", "was", "known", "to", "have", "been", "diagnosed", "with", "von", "Willebrand", "disease", "type", "3", "at", "age", "two", "years", "old.", "Magnetic", "resonance", "imaging", "showed", "a", "mass", "in", "the", "right", "iliopsoas", "muscle.", "The", "diagnosis", "of", "iliopsoas", "hemorrhage", "and", "partial", "femoral", "nerve", "palsy", "was", "established,", "and", "he", "responded", "to", "medical", "treatment.", "Conclusion:", "We", "report", "a", "case", "of", "von", "Willebrand", "disease", "type", "3", "with", "spontaneous", "iliopsoas", "hematoma", "associated", "with", "femoral", "nerve", "palsy", "that", "was", "well", "managed", "with", "Humate-P", "treatment.", "Introduction", "Von", "Willebrand", "disease", "(vWD)", "is", "a", "hereditary", "bleeding", "disorder", "caused", "by", "a", "quantitative", "or", "qualitative", "defect", "of", "von", "Willebrand", "factor.", "The", "prevalence", "of", "this", "disease", "is", "estimated", "to", "be", "1%", "to", "2%", "of", "the", "general", "population.", "Von", "Willebrand", "factor", "is", "a", "coagulation", "factor", "for", "initial", "stages", "of", "blood", "clotting", "and", "is", "also", "a", "carrier", "for", "factor", "VIII.", "Patients", "with", "vWD", "develop", "coagulation", "platelet", "plugs", "and", "red", "coagulation", "clots", "are", "unable", "to", "form.", "vWD", "consists", "of", "a", "broad", "variation", "of", "clinical", "manifesta-", "tions,", "with", "one", "extreme", "being", "a", "minimal", "bleeding", "ten-", "dency", "and", "the", "other", "being", "a", "severe", "presentation", "such", "as", "severe", "hemophilia", "A.", "Luckily,", "most", "of", "these", "patients", "present", "with", "mild", "to", "moderate", "clinical", "symptoms.", "The", "severe", "type", "of", "the", "vWD,", "type", "3,", "occurs", "in", "less", "than", "5%", "of", "patients.", "The", "inheritance", "pattern", "of", "this", "type", "is", "usually", "autosomal", "recessive.", "Patients", "with", "vWD", "usually", "show", "clinical", "features", "such", "as", "recurrent", "nosebleeds,", "easy", "bruising,", "bleeding", "post-tooth", "extraction,", "post-", "*", "Correspondence:", "keikhaeib@yahoo.com", "1Department", "of", "Thalassemia", "&", "Hemoglobinopathy", "Research", "Center,", "Ahvaz", "Jundishapur", "University", "of", "Medical", "Science,", "Shafa", "Hospital", "(Golestan", "Area),", "Ahvaz", "61357-33119,", "Iran", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "tonsillectomy", "or", "other", "surgical", "bleeding,", "and", "excessive", "menstrual", "bleeding.", "Musculoskeletal", "hemorrhage", "occurs", "commonly", "in", "vWD", "type", "3-like", "hemophilia", "A.", "Iliopsoas", "hemorrhage", "is", "a", "potentially", "serious", "complication", "because", "a", "delay", "in", "beginning", "treatment", "may", "result", "in", "permanent", "femoral", "nerve", "palsy", "[1].", "The", "present", "case", "report", "describes", "a", "man", "with", "vWD", "type", "3", "who", "had", "a", "spontaneous", "iliopsoas", "hematoma", "that", "responded", "well", "to", "Humate-P", "treatment", "(CSL", "Behring,", "King", "of", "Prussia,", "PA,", "USA)", "[2].", "Case", "presentation", "A", "20-year-old", "Iranian", "man", "came", "to", "our", "hospital", "because", "of", "the", "gradual", "onset", "of", "right", "flank", "pain.", "He", "was", "known", "to", "have", "had", "vWD", "type", "3", "since", "he", "was", "two", "years", "old.", "His", "laboratory", "findings", "were", "as", "follows:", "B-positive", "blood", "type,", "partial", "thromboplastin", "time", "56", "seconds,", "bleeding", "time", "more", "than", "12", "minutes,", "hemoglobin", "10", "g/dL,", "mean", "corpus-", "cular", "volume", "75", "fL,", "mean", "corpuscular", "hemoglobin", "24", "pg/", "red", "blood", "cell,", "factor", "VIIIc", "activity", "3%,", "vWF", "antigen", "level", "was", "undetectable,", "and", "vWF", "ristocetin", "cofactor", "activity", "was", "undetectable.", "He", "had", "experienced", "some", "occasional", "hemar-", "throsis,", "but", "he", "had", "been", "well", "for", "two", "months", "before", "he", "presented", "to", "our", "hospital.", "He", "had", "no", "history", "of", "trauma.", "©", "2011", "Keikhaei", "and", "Shirazi;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Human", "Reproduction", "Update,", "Vol.14,", "No.4", "pp.", "379–390,", "2008", "Advance", "Access", "publication", "June", "4,", "2008", "Cytogenetic", "determinants", "of", "male", "fertility", "doi:10.1093/humupd/dmn017", "R.H.", "Martin1", "1E-mail:", "rhmartin@ucalgary.ca", "Department", "of", "Medical", "Genetics,", "University", "of", "Calgary,", "Room", "287,", "Heritage", "Medical", "Research", "Building,", "3330", "Hospital", "Drive", "NW,", "Calgary,", "Alberta,", "Canada", "T2N", "4N1", "BACKGROUND:", "Cytogenetic", "abnormalities", "have", "been", "known", "to", "be", "important", "causes", "of", "male", "infertility", "for", "decades.", "METHODS:", "Research", "publications", "from", "1978", "to", "2008,", "from", "PubMed,", "have", "been", "reviewed.", "RESULTS:", "These", "studies", "have", "greatly", "improved", "our", "information", "on", "somatic", "chromosomal", "abnormalities", "such", "as", "translocations,", "inversions", "and", "sex", "chromosomal", "anomalies,", "and", "their", "consequences", "to", "the", "cytogenetic", "make-up", "of", "human", "sperm.", "Also,", "we", "have", "learned", "that", "infertile", "men", "with", "a", "normal", "somatic", "karyotype", "have", "an", "increased", "risk", "of", "chromosomally", "abnormal", "sperm", "and", "children.", "New", "techniques", "such", "as", "single", "sperm", "typing", "and", "synaptonemal", "complex", "analysis", "have", "provided", "valuable", "insight", "into", "the", "association", "between", "meiotic", "recombination", "and", "the", "production", "of", "aneuploid", "sperm.", "These", "meiotic", "studies", "have", "also", "unveiled", "errors", "of", "chromosome", "pairing", "and", "synapsis,", "which", "are", "more", "common", "in", "infertile", "men.", "CONCLUSIONS:", "These", "studies", "allow", "us", "to", "provide", "more", "precise", "information", "to", "infertile", "patients,", "and", "further", "our", "basic", "knowledge", "in", "the", "causes", "of", "male", "infertility.", "Keywords:", "male", "infertility;", "meiosis;", "sperm", "aneuploidy;", "sperm", "chromosome", "abnormalities", "Introduction", "Infertility", "is", "a", "significant", "problem,", "affecting", "up", "to", "15%", "of", "couples", "of", "reproductive", "age", "(de", "Kretser,", "1997).", "For", "many", "years,", "it", "was", "assumed", "that", "most", "reproductive", "problems", "could", "be", "attributed", "to", "the", "female", "partner", "but", "research", "in", "recent", "years", "has", "demonstrated", "that", "30", "–", "50%", "of", "infertility", "is", "caused", "by", "a", "male", "factor", "(Lipshultz", "and", "Howards,", "1997).", "Treatment", "of", "male-factor", "infertility", "by", "in", "vitro", "fertilization", "(IVF)", "was", "largely", "unsuccessful.", "However,", "the", "develop-", "ment", "of", "intracytoplasmic", "sperm", "injection", "(ICSI)", "(Palermo", "et", "al.,", "1992)", "revolutionized", "the", "treatment", "of", "male", "infertility,", "providing", "many", "men", "the", "chance", "to", "father", "their", "own", "children.", "ICSI", "also", "greatly", "stimulated", "research", "into", "the", "causes", "of", "male", "infertility,", "and", "our", "knowledge", "has", "increased", "tremendously", "in", "the", "past", "decade.", "The", "development", "of", "new", "techniques", "has", "provided", "a", "wealth", "of", "information", "on", "the", "cytogenetics", "of", "human", "sperm.", "The", "human", "sperm", "–", "hamster", "oocyte", "fusion", "system", "allowed", "the", "first", "analysis", "of", "human", "sperm", "chromosomes", "(Rudak", "et", "al.,", "1978;", "Martin", "et", "al.,", "1983;", "Brandriff", "et", "al.,", "1985;", "Mikamo", "et", "al.,", "1990;", "Templado", "et", "al.,", "1996).", "This", "technique", "provides", "precise", "karyotypes", "in", "which", "numerical", "and", "structural", "abnormalities", "can", "be", "assessed", "for", "each", "chromosome", "(Fig.", "1).", "Unfortunately,", "the", "technique", "is", "very", "difficult", "with", "only", "a", "handful", "of", "laboratories", "achieving", "success;", "also", "the", "data", "yield,", "though", "of", "great", "significance,", "is", "low.", "Fluorescence", "in", "situ", "hybridization", "(FISH)", "analysis", "with", "chromosome-specific", "DNA", "probes", "was", "developed", "in", "the", "1990s,", "providing", "a", "faster,", "cheaper,", "easier", "alternative", "for", "detecting", "aneu-", "ploidy", "in", "human", "sperm", "(Martin", "et", "al.,", "1993;", "Robbins", "et", "al.,", "1993;", "Wyrobek", "et", "al.,", "1994;", "Martin", "et", "al.,", "1996).", "Also,", "sperm", "hampered", "by", "abnormalities", "in", "motility", "or", "other", "aspects", "of", "fertiliza-", "tion", "can", "be", "assessed", "using", "FISH", "analysis", "(Downie", "et", "al.,", "1997;", "Egozcue", "et", "al.,", "1997;", "Robbins", "et", "al.,", "1997;", "Martin", "et", "al.,", "1999a;", "Hristova", "et", "al.,", "2002).", "This", "is", "a", "simple", "technique", "that", "has", "been", "embraced", "by", "many", "laboratories,", "but", "it", "must", "be", "remembered", "that", "it", "is", "indirect:", "fluorescent", "signals,", "rather", "than", "chromosomes,", "are", "counted", "(Fig.", "2).", "Single", "sperm", "polymerase", "chain", "reaction", "(PCR)", "or", "single", "sperm", "typing", "is", "a", "difficult,", "time-consuming", "technique", "but", "it", "can", "be", "used", "in", "a", "very", "powerful", "manner", "for", "specific", "studies", "on", "recombination", "in", "delimited", "areas", "of", "the", "genome", "(Shi", "et", "al.,", "2001,", "2002;", "Tiemann-", "Boege", "et", "al.,", "2006).", "The", "latest", "development", "to", "shed", "light", "on", "the", "causes", "of", "chromo-", "somal", "abnormalities", "and", "infertility", "is", "meiotic", "analysis", "of", "the", "synaptonemal", "complex", "(SC).", "Various", "important", "meiotic", "structures", "#", "The", "Author", "2008.", "Published", "by", "Oxford", "University", "Press", "on", "behalf", "of", "the", "European", "Society", "of", "Human", "Reproduction", "and", "Embryology.", "All", "rights", "reserved.", "For", "Permissions,", "please", "email:", "journals.permissions@oxfordjournals.org", "The", "online", "version", "of", "this", "article", "has", "been", "published", "under", "an", "open", "access", "model.", "Users", "are", "entitled", "to", "use,", "reproduce,", "disseminate,", "or", "display", "the", "open", "access", "version", "of", "this", "article", "for", "non-commercial", "purposes", "provided", "that:", "the", "original", "authorship", "is", "properly", "and", "fully", "attributed;", "the", "Journal", "and", "Oxford", "University", "Press", "are", "attributed", "as", "the", "original", "place", "of", "publication", "with", "the", "correct", "citation", "details", "given;", "if", "an", "article", "is", "subsequently", "reproduced", "or", "disseminated", "not", "in", "its", "entirety", "but", "only", "in", "part", "or", "as", "a", "derivative", "work", "this", "must", "be", "clearly", "indicated.", "For", "commercial", "re-use,", "please", "contact", "journals.permissions@oxfordjournals.org", "379" ]

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[ "Westrom", "et", "al.", "Trials", "2010,", "11:24", "http://www.trialsjournal.com/content/11/1/24", "S", "T", "U", "D", "Y", "P", "R", "O", "T", "O", "C", "O", "L", "TRIALS", "Open", "Access", "Individualized", "chiropractic", "and", "integrative", "care", "for", "low", "back", "pain:", "the", "design", "of", "a", "randomized", "clinical", "trial", "using", "a", "mixed-methods", "approach", "Kristine", "K", "Westrom*,", "Michele", "J", "Maiers,", "Roni", "L", "Evans,", "Gert", "Bronfort", "Abstract", "Background:", "Low", "back", "pain", "(LBP)", "is", "a", "prevalent", "and", "costly", "condition", "in", "the", "United", "States.", "Evidence", "suggests", "there", "is", "no", "one", "treatment", "which", "is", "best", "for", "all", "patients,", "but", "instead", "several", "viable", "treatment", "options.", "Additionally,", "multidisciplinary", "management", "of", "LBP", "may", "be", "more", "effective", "than", "monodisciplinary", "care.", "An", "integrative", "model", "that", "includes", "both", "complementary", "and", "alternative", "medicine", "(CAM)", "and", "conventional", "therapies,", "while", "also", "incorporating", "patient", "choice,", "has", "yet", "to", "be", "tested", "for", "chronic", "LBP.", "The", "primary", "aim", "of", "this", "study", "is", "to", "determine", "the", "relative", "clinical", "effectiveness", "of", "1)", "monodisciplinary", "chiropractic", "care", "and", "2)", "multidisciplinary", "integrative", "care", "in", "200", "adults", "with", "non-acute", "LBP,", "in", "both", "the", "short-term", "(after", "12", "weeks)", "and", "long-term", "(after", "52", "weeks).", "The", "primary", "outcome", "measure", "is", "patient-rated", "back", "pain.", "Secondary", "aims", "compare", "the", "treatment", "approaches", "in", "terms", "of", "frequency", "of", "symptoms,", "low", "back", "disability,", "fear", "avoidance,", "self-effi-", "cacy,", "general", "health", "status,", "improvement,", "satisfaction,", "work", "loss,", "medication", "use,", "lumbar", "dynamic", "motion,", "and", "torso", "muscle", "endurance.", "Patients’", "and", "providers’", "perceptions", "of", "treatment", "will", "be", "described", "using", "qualitative", "meth-", "ods,", "and", "cost-effectiveness", "and", "cost", "utility", "will", "be", "assessed.", "Methods", "and", "Design:", "This", "paper", "describes", "the", "design", "of", "a", "randomized", "clinical", "trial", "(RCT),", "with", "cost-effectiveness", "and", "qualitative", "studies", "conducted", "alongside", "the", "RCT.", "Two", "hundred", "participants", "ages", "18", "and", "older", "are", "being", "recruited", "and", "randomized", "to", "one", "of", "two", "12-week", "treatment", "interventions.", "Patient-rated", "outcome", "measures", "are", "collected", "via", "self-report", "questionnaires", "at", "baseline,", "and", "at", "4,", "12,", "26,", "and", "52", "weeks", "post-randomization.", "Objective", "outcome", "measures", "are", "assessed", "at", "baseline", "and", "12", "weeks", "by", "examiners", "blinded", "to", "treatment", "assignment.", "Health", "care", "cost", "data", "is", "collected", "by", "self-report", "questionnaires", "and", "treatment", "records", "during", "the", "intervention", "phase", "and", "by", "monthly", "phone", "interviews", "thereafter.", "Qualitative", "interviews,", "using", "a", "semi-structured", "format,", "are", "conducted", "with", "patients", "at", "the", "end", "of", "the", "12-week", "treatment", "period", "and", "also", "with", "providers", "at", "the", "end", "of", "the", "trial.", "Discussion:", "This", "mixed-methods", "randomized", "clinical", "trial", "assesses", "clinical", "effectiveness,", "cost-effectiveness,", "and", "patients’", "and", "providers’", "perceptions", "of", "care,", "in", "treating", "non-acute", "LBP", "through", "evidence-based", "individualized", "care", "delivered", "by", "monodisciplinary", "or", "multidisciplinary", "care", "teams.", "Trial", "registration:", "ClinicalTrials.gov", "NCT00567333", "Background", "It", "is", "well", "recognized", "that", "low", "back", "pain", "(LBP)", "is", "one", "of", "the", "most", "prevalent", "and", "costly", "problems", "facing", "the", "US", "health-care", "system", "[1-3].", "Approximately", "80%", "of", "indivi-", "duals", "will", "experience", "non-specific", "LBP", "in", "their", "lifetime[4]", "and", "75%", "will", "experience", "lingering", "problems", "one", "year", "*", "Correspondence:", "kwestrom@nwhealth.edu", "Northwestern", "Health", "Sciences", "University,", "Wolfe-Harris", "Center", "for", "Clinical", "Studies,", "2501", "West", "84th", "Street,", "Bloomington,", "MN", "55431,", "USA", "after", "onset[5].", "In", "the", "United", "Kingdom,", "the", "incidence", "of", "chronic", "low", "back", "disability", "rose", "exponentially", "for", "two", "decades", "through", "1994,[6]", "and", "for", "some", "patients", "the", "asso-", "ciated", "psychological", "distress", "and", "illness", "behaviors", "become", "as", "disabling", "as", "the", "LBP", "itself[7].", "In", "the", "United", "States,", "the", "costs", "attributable", "to", "LBP", "continue", "to", "soar", "and", "are", "estimated", "to", "exceed", "$100", "billion", "dollars", "annually[8].", "At", "present,", "more", "than", "500", "randomized", "controlled", "trials", "have", "been", "published", "evaluating", "conservative", "and", "alternative", "treatments", "for", "LBP.", "From", "the", "results", "of", "these", "©", "2010", "Westrom", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "ORIGINAL", "RESEARCH", "ARTICLE", "published:", "20", "February", "2012", "doi:", "10.3389/fpsyg.2012.00039", "Effects", "of", "speech", "rate", "and", "practice", "on", "the", "allocation", "of", "visual", "attention", "in", "multiple", "object", "naming", "Antje", "S.", "Meyer", "1*,", "Linda", "Wheeldon2,", "Femke", "van", "der", "Meulen2", "and", "Agnieszka", "Konopka3", "1", "Max", "Planck", "Institute", "for", "Psycholinguistics", "and", "Donders", "Institute", "for", "Brain,", "Cognition", "and", "Behavior,", "Radboud", "University,", "Nijmegen,", "Netherlands", "2", "School", "of", "Psychology,", "University", "of", "Birmingham,", "Birmingham,", "UK", "3", "Max", "Planck", "Institute", "for", "Psycholinguistics,", "Nijmegen,", "Netherlands", "Edited", "by:", "Andriy", "Myachykov,", "University", "of", "Glasgow,", "UK", "Reviewed", "by:", "Robert", "J.", "Hartsuiker,", "University", "of", "Ghent,", "Belgium", "Zenzi", "M.", "Griffin,", "University", "of", "Texas,", "USA", "*Correspondence:", "Antje", "S.", "Meyer", ",", "Max", "Planck", "Institute", "for", "Psycholinguistics", "and", "Donders", "Institute", "for", "Brain,", "Cognition", "and", "Behavior,", "Radboud", "University,", "Postbus", "310,", "6500", "AH", "Nijmegen,", "Netherlands.", "e-mail:", "antje.meyer@mpi.nl", "Earlier", "studies", "had", "shown", "that", "speakers", "naming", "several", "objects", "typically", "look", "at", "each", "object", "until", "they", "have", "retrieved", "the", "phonological", "form", "of", "its", "name", "and", "therefore", "look", "longer", "at", "objects", "with", "long", "names", "than", "at", "objects", "with", "shorter", "names.", "We", "examined", "whether", "this", "tight", "eye-to-speech", "coordination", "was", "maintained", "at", "different", "speech", "rates", "and", "after", "increas-", "ing", "amounts", "of", "practice.", "Participants", "named", "the", "same", "set", "of", "objects", "with", "monosyllabic", "or", "disyllabic", "names", "on", "up", "to", "20", "successive", "trials.", "In", "Experiment", "1,", "they", "spoke", "as", "fast", "as", "they", "could,", "whereas", "in", "Experiment", "2", "they", "had", "to", "maintain", "a", "fixed", "moderate", "or", "faster", "speech", "rate.", "In", "both", "experiments,", "the", "durations", "of", "the", "gazes", "to", "the", "objects", "decreased", "with", "increasing", "speech", "rate,", "indicating", "that", "at", "higher", "speech", "rates,", "the", "speakers", "spent", "less", "time", "planning", "the", "object", "names.", "The", "eye–speech", "lag", "(the", "time", "interval", "between", "the", "shift", "of", "gaze", "away", "from", "an", "object", "and", "the", "onset", "of", "its", "name)", "was", "independent", "of", "the", "speech", "rate", "but", "became", "shorter", "with", "increasing", "practice.", "Consistent", "word", "length", "effects", "on", "the", "durations", "of", "the", "gazes", "to", "the", "objects", "and", "the", "eye-speech", "lags", "were", "only", "found", "in", "Experiment", "2.", "The", "results", "indicate", "that", "shifts", "of", "eye", "gaze", "are", "often", "linked", "to", "the", "completion", "of", "phonological", "encoding,", "but", "that", "speakers", "can", "deviate", "from", "this", "default", "coordination", "of", "eye", "gaze", "and", "speech,", "for", "instance", "when", "the", "descriptive", "task", "is", "easy", "and", "they", "aim", "to", "speak", "fast.", "Keywords:", "utterance", "planning,", "speech", "rate,", "practice,", "eye", "movements,", "visual", "attention", "INTRODUCTION", "We", "can", "talk", "in", "different", "ways.", "We", "can,", "for", "instance,", "use", "a", "special", "reg-", "ister,", "child", "directed", "speech,", "to", "talk", "to", "a", "child,", "and", "we", "tend", "to", "deliver", "speeches,", "and", "formal", "lectures", "in", "a", "style", "that", "is", "different", "from", "casual", "dinner", "table", "conversations.", "The", "psychological", "processes", "underly-", "ing", "the", "implementation", "of", "different", "speech", "styles", "have", "rarely", "been", "studied.", "The", "present", "paper", "concerns", "one", "important", "feature", "distin-", "guishing", "different", "speech", "styles,", "i.e.,", "speech", "rate.", "It", "is", "evident", "that", "speakers", "can", "control", "their", "speech", "rate,", "yet", "little", "is", "known", "about", "how", "they", "do", "this.", "To", "begin", "to", "explore", "this", "issue", "we", "used", "a", "simple", "speech", "produc-", "tion", "task:", "speakers", "named", "sets", "of", "pictures", "in", "sequences", "of", "nouns", "(e.g.,", "“kite,", "doll,", "tap,", "sock,", "whale,", "globe”).", "Each", "set", "was", "shown", "on", "several", "successive", "trials.", "In", "the", "first", "experiment,", "the", "speakers", "were", "asked", "to", "name", "the", "pictures", "as", "fast", "as", "they", "could.", "In", "the", "second", "experiment,", "they", "had", "to", "maintain", "a", "fixed", "moderate", "or", "faster", "speech", "rate,", "which", "allowed", "us", "to", "separate", "the", "effects", "of", "speech", "rate", "and", "practice.", "Throughout", "the", "experiments,", "the", "speakers’", "eye", "move-", "ments", "were", "recorded", "along", "with", "their", "spoken", "utterances.", "In", "the", "next", "sections,", "we", "motivate", "this", "approach,", "discuss", "related", "studies,", "and", "explain", "the", "predictions", "for", "the", "experiments.", "SPEECH-TO-GAZE", "ALIGNMENT", "IN", "DESCRIPTIVE", "UTTERANCES", "In", "many", "language", "production", "studies", "participants", "have", "been", "asked", "to", "name", "or", "describe", "pictures", "of", "one", "or", "more", "objects.", "Though", "prob-", "ably", "not", "the", "most", "common", "way", "of", "using", "language,", "picture", "naming", "is", "popular", "in", "language", "production", "research", "because", "it", "offers", "good", "control", "of", "the", "content", "of", "the", "speakers’", "utterances", "and", "captures", "a", "central", "component", "of", "speech", "planning,", "namely", "the", "retrieval", "of", "words", "from", "the", "mental", "lexicon.", "In", "some", "picture", "naming", "studies,", "the", "speakers’", "eye", "movements", "were", "recorded", "along", "with", "their", "speech.", "This", "is", "useful", "because", "a", "person’s", "eye", "gaze", "reveals", "where", "their", "visual", "attention", "is", "focused,", "that", "is,", "which", "part", "of", "the", "environment", "they", "are", "processing", "with", "priority", "(e.g.,", "Deubel", "and", "Schneider,", "1996;", "Irwin,", "2004;", "Eimer", "et", "al.,", "2007).", "In", "picture", "naming,", "visual", "attention,", "and", "eye", "gaze", "are", "largely", "controlled", "endogenously", "(i.e.,", "governed", "by", "the", "speaker’s", "goals", "and", "intentions),", "rather", "than", "exogenously", "(i.e.,", "by", "environ-", "mental", "stimuli).", "That", "is,", "speakers", "actively", "direct", "their", "gaze", "to", "the", "objects", "they", "wish", "to", "focus", "on.", "Therefore,", "eye", "movements", "provide", "not", "only", "information", "about", "the", "speaker’s", "visual", "processing,", "but", "also,", "albeit", "more", "indirectly,", "about", "the", "executive", "control", "processes", "engaged", "in", "the", "task", "(for", "discussions", "of", "executive", "control", "processes", "see", "Baddeley,", "1986;", "Posner", "and", "Petersen,", "1990;", "Miyake", "et", "al.,", "2000).", "The", "eye", "movement", "studies", "of", "language", "production", "have", "yielded", "a", "number", "of", "key", "findings.", "First,", "when", "speakers", "name", "sets", "of", "objects", "they", "typically", "look", "at", "each", "of", "the", "objects", "in", "the", "order", "of", "mention,", "just", "before", "naming", "it", "(e.g.,", "Meyer", "et", "al.,", "1998;", "Griffin,", "2001).", "When", "speakers", "describe", "cartoons", "of", "events", "or", "actions,", "rather", "than", "nam-", "ing", "individual", "objects,", "there", "can", "be", "a", "brief", "apprehension", "phase", "during", "which", "speakers", "gain", "some", "understanding", "of", "the", "gist", "of", "the", "scene", "and", "during", "which", "their", "eye", "movements", "are", "not", "related", "in", "any", "obvious", "way", "to", "the", "structure", "of", "the", "upcoming", "utterances,", "but", "following", "this,", "there", "is", "again", "a", "tight", "coupling", "between", "eye", "gaze", "and", "www.frontiersin.org", "February", "2012", "|", "Volume", "3", "|", "Article", "39", "|", "1" ]

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[ "Invasion", "of", "Wolbachia", "into", "Anopheles", "and", "Other", "Insect", "Germlines", "in", "an", "Ex", "vivo", "Organ", "Culture", "System", "Grant", "L.", "Hughes1.,", "Andrew", "D.", "Pike2.,", "Ping", "Xue2,", "Jason", "L.", "Rasgon", "1", "*", "1", "The", "Department", "of", "Entomology,", "Center", "for", "Infectious", "Disease", "Dynamics", "and", "Huck", "Institutes", "of", "the", "Life", "Sciences,", "Pennsylvania", "State", "University,", "University", "Park,", "Pennsylvania,", "United", "States", "of", "America,", "2", "The", "W.", "Harry", "Feinstone", "Department", "of", "Molecular", "Microbiology", "and", "Immunology,", "Bloomberg", "School", "of", "Public", "Health,", "Johns", "Hopkins", "University,", "Baltimore,", "Maryland,", "United", "States", "of", "America", "Abstract", "The", "common", "bacterial", "endosymbiont", "Wolbachia", "manipulates", "its", "host’s", "reproduction", "to", "promote", "its", "own", "maternal", "transmission,", "and", "can", "interfere", "with", "pathogen", "development", "in", "many", "insects", "making", "it", "an", "attractive", "agent", "for", "the", "control", "of", "arthropod-borne", "disease.", "However,", "many", "important", "species,", "including", "Anopheles", "mosquitoes,", "are", "uninfected.", "Wolbachia", "can", "be", "artificially", "transferred", "between", "insects", "in", "the", "laboratory", "but", "this", "can", "be", "a", "laborious", "and", "sometimes", "fruitless", "process.", "We", "used", "a", "simple", "ex", "vivo", "culturing", "technique", "to", "assess", "the", "suitability", "of", "Wolbachia-host", "germline", "associations.", "Wolbachia", "infects", "the", "dissected", "germline", "tissue", "of", "multiple", "insect", "species", "when", "the", "host", "tissue", "and", "bacteria", "are", "cultured", "together.", "Ovary", "and", "testis", "infection", "occurs", "in", "a", "density-dependent", "manner.", "Wolbachia", "strains", "are", "more", "capable", "of", "invading", "the", "germline", "of", "their", "native", "or", "closely", "related", "rather", "than", "divergent", "hosts.", "The", "ability", "of", "Wolbachia", "to", "associate", "with", "the", "germline", "of", "novel", "hosts", "is", "crucial", "for", "the", "development", "of", "stably-transinfected", "insect", "lines.", "Rapid", "assessment", "of", "the", "suitability", "of", "a", "strain-host", "combination", "prior", "to", "transinfection", "may", "dictate", "use", "of", "a", "particular", "Wolbachia", "strain.", "Furthermore,", "the", "cultured", "germline", "tissues", "of", "two", "major", "Anopheline", "vectors", "of", "Plasmodium", "parasites", "are", "susceptible", "to", "Wolbachia", "infection.", "This", "finding", "further", "enhances", "the", "prospect", "of", "using", "Wolbachia", "for", "the", "biological", "control", "of", "malaria.", "Citation:", "Hughes", "GL,", "Pike", "AD,", "Xue", "P,", "Rasgon", "JL", "(2012)", "Invasion", "of", "Wolbachia", "into", "Anopheles", "and", "Other", "Insect", "Germlines", "in", "an", "Ex", "vivo", "Organ", "Culture", "System.", "PLoS", "ONE", "7(4):", "e36277.", "doi:10.1371/journal.pone.0036277", "Editor:", "Luciano", "A.", "Moreira,", "Centro", "de", "Pesquisas", "Rene´", "Rachou,", "Brazil", "Received", "November", "28,", "2011;", "Accepted", "April", "1,", "2012;", "Published", "April", "30,", "2012", "Copyright:", "2012", "Hughes", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "This", "research", "was", "supported", "by", "United", "States", "National", "Institutes", "of", "Health", "grant", "R21AI070178", "to", "JLR.", "GLH", "was", "supported", "by", "the", "Johns", "Hopkins", "School", "of", "Public", "Health", "(JHSPH)", "Jane", "Welsh", "Russell", "Scholarship", "and", "a", "Johns", "Hopkins", "Malaria", "Research", "Institute", "(JHMRI)", "postdoctoral", "fellowship.", "The", "funders", "had", "no", "role", "in", "study", "design,", "data", "collection", "and", "analysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "Competing", "Interests:", "The", "authors", "have", "declared", "that", "no", "competing", "interests", "exist.", "*", "E-mail:", "jlr54@psu.edu", ".", "These", "authors", "contributed", "equally", "to", "this", "work.", "Introduction", "Wolbachia", "are", "intracellular", "a-proteobacteria", "that", "infect", "approx-", "imately", "two-thirds", "of", "insect", "species", "along", "with", "numerous", "other", "arthropods", "[1,2].", "Generally", "classified", "as", "reproductive", "parasites,", "Wolbachia", "are", "able", "to", "manipulate", "their", "hosts", "reproduction", "in", "various", "ways", "[3].", "These", "reproductive", "manipulations", "exploit", "the", "maternal", "transmission", "route", "of", "the", "bacteria", "to", "the", "progeny", "of", "the", "host,", "facilitating", "the", "spread", "of", "Wolbachia", "into", "the", "host", "population.", "In", "addition", "to", "maternal", "transmission,", "the", "incongruence", "between", "the", "phylogenies", "of", "Wolbachia", "and", "their", "hosts", "suggests", "horizontal", "transmission", "has", "occurred", "repeatedly", "over", "evolutionary", "time,", "which", "has", "extended", "the", "host", "range", "of", "the", "bacteria", "[4,5,6].", "The", "ability", "of", "Wolbachia", "to", "invade", "new", "species", "has", "been", "reproduced", "in", "the", "laboratory,", "with", "artificial", "transfers", "into", "novel", "insect", "species.", "Despite", "transinfection", "of", "Wolbachia", "into", "many", "new", "insect", "species,", "it", "is", "uncertain", "why", "some", "species", "are", "capable", "of", "infection", "yet", "others", "are", "seemingly", "not.", "For", "either", "horizontal", "transmission", "or", "transinfection", "to", "occur,", "Wolbachia", "must", "establish", "in", "the", "female", "germline", "to", "allow", "the", "bacteria", "to", "be", "transmitted", "to", "the", "next", "generation.", "When", "artificially", "transferred", "into", "a", "new", "host,", "Wolbachia", "are", "usually", "microinjected", "into", "the", "preblastoderm", "embryo,", "a", "scenario", "that", "is", "unlikely", "to", "occur", "in", "nature.", "However,", "in", "experiments", "that", "more", "closely", "mimic", "potential", "natural", "routes", "of", "horizontal", "transfer,", "Wolbachia", "has", "been", "shifted", "between", "insects", "by", "adult", "injection,", "hemolymph", "transfer", "and", "co-rearing", "[7,8,9].", "When", "injected", "into", "uninfected", "Drosophila,", "Wolbachia", "migrate", "across", "numerous", "tissues", "to", "establish", "in", "the", "stem", "cell", "niche", "of", "the", "ovary", "[7].", "Hemolymph", "transfer", "between", "infected", "and", "uninfected", "pillbugs", "(Armadillidium", "vulgare,", "Porcellionides", "pruinosus", "and", "Chaetophiliscia", "elongate)", "resulted", "in", "stable", "intraspecific", "transfer", "of", "Wolbachia", "and", "manipulation", "of", "host", "reproductive", "[8].", "The", "capacity", "for", "Wolbachia", "to", "spread", "though", "host", "populations", "and", "interfere", "with", "pathogen", "development", "in", "insects", "makes", "them", "attractive", "agents", "for", "the", "control", "of", "vector-borne", "diseases.", "Currently,", "Wolbachia", "is", "being", "investigated", "to", "control", "malaria,", "a", "devastating", "disease", "transmitted", "by", "Anopheles", "mosquitoes.", "Wolbachia", "is", "capable", "of", "infecting", "Anopheles", "cells", "in", "vitro", "and", "Anopheles", "somatic", "tissues", "in", "vivo,", "and", "influences", "the", "expression", "of", "numerous", "host", "genes", "[10,11,12].", "After", "injection", "into", "adult", "Anopheles", "mosquitoes,", "Wolbachia", "influences", "Plasmodium", "levels,", "with", "wAlbB", "and", "wMelPop", "reducing", "P.", "falciparum", "intensity", "[10].", "Interestingly,", "somatic", "infection", "of", "An.", "gambiae", "with", "the", "wAlbB", "strains", "enhances", "oocyst", "density", "of", "P.", "berghei,", "the", "model", "murine", "malaria", "species", "[13].", "However,", "all", "Anopheles", "mosquitoes", "lack", "Wolbachia", "infection", "in", "the", "wild", "and", "despite", "numerous", "attempts", "seem", "impervious", "to", "stable", "transinfection", "in", "the", "lab", "[14,15].", "To", "increase", "the", "probability", "of", "infecting", "Anopheles", "mosquitoes,", "a", "variety", "of", "combinations", "of", "PLoS", "ONE", "|", "www.plosone.org", "1", "April", "2012", "|", "Volume", "7", "|", "Issue", "4", "|", "e36277" ]

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[ "Jaspan", "et", "al.", "BMC", "Pediatrics", "2011,", "11:104", "http://www.biomedcentral.com/1471-2431/11/104", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "Utility", "of", "clinical", "parameters", "to", "identify", "HIV", "infection", "in", "infants", "below", "ten", "weeks", "of", "age", "in", "South", "Africa:", "a", "prospective", "cohort", "study", "Heather", "B", "Jaspan1,2,3,9*,", "Landon", "Myer4,", "Shabir", "A", "Madhi5,", "Avy", "Violari6,", "Diana", "M", "Gibb7,", "Wendy", "S", "Stevens8,", "Els", "Dobbels1", "and", "Mark", "F", "Cotton1", "Abstract", "Background:", "As", "HIV-infected", "infants", "have", "high", "mortality,", "the", "World", "Health", "Organization", "now", "recommends", "initiating", "antiretroviral", "therapy", "as", "early", "as", "possible", "in", "the", "first", "year", "of", "life.", "However,", "in", "many", "settings,", "laboratory", "diagnosis", "of", "HIV", "in", "infants", "is", "not", "readily", "available.", "We", "aimed", "to", "develop", "a", "clinical", "algorithm", "for", "HIV", "presumptive", "diagnosis", "in", "infants", "<", "10", "weeks", "old", "using", "screening", "data", "from", "the", "Children", "with", "HIV", "Early", "Antiretroviral", "therapy", "(CHER)", "study", "in", "South", "Africa.", "HIV-infected", "and", "HIV-uninfected", "exposed", "infants", "<", "10", "weeks", "of", "age", "were", "identified", "through", "Vertical", "Transmission", "Prevention", "programs.", "Clinical", "and", "laboratory", "data", "were", "systematically", "recorded,", "groups", "were", "compared", "using", "Kruskal-Wallis,", "analysis", "of", "variance", "(ANOVA),", "and", "Fisher’s", "exact", "tests.", "Receiver", "Operating", "Characteristic", "(ROC)", "curves", "were", "compiled", "using", "combinations", "of", "clinical", "findings.", "Results:", "417", "HIV-infected", "and", "125", "HIV-exposed,", "uninfected", "infants,", "median", "age", "46", "days", "(IQR", "38-55),", "were", "included.", "The", "median", "CD4", "percentage", "in", "HIV-infected", "infants", "was", "34", "(IQR", "28-41)%.", "HIV-infected", "infants", "had", "lower", "weight-", "for-age,", "more", "lymphadenopathy,", "oral", "thrush,", "and", "hepatomegaly", "than", "exposed", "uninfected", "infants", "(Adjusted", "Odds", "Ratio", "0.51,", "8.8,", "5.6", "and", "23.5", "respectively;", "p", "<", "0.001", "for", "all).", "Sensitivity", "of", "individual", "signs", "was", "low", "(<", "20%)", "but", "specificity", "high", "(98-100%).", "If", "any", "one", "of", "oral", "thrush,", "hepatomegaly,", "splenomegaly,", "lymphadenopathy,", "diaper", "dermatitis,", "weight", "<", "50th", "centile", "are", "present,", "sensitivity", "for", "HIV", "infection", "amongst", "HIV-exposed", "infants", "was", "86%.", "These", "algorithms", "performed", "similarly", "when", "used", "to", "predict", "severe", "immune", "suppression.", "Conclusions:", "A", "combination", "of", "physical", "findings", "is", "helpful", "in", "identifying", "infants", "most", "likely", "to", "be", "HIV-infected.", "This", "may", "inform", "management", "algorithms", "and", "provide", "guidance", "for", "focused", "laboratory", "testing", "in", "some", "settings,", "and", "should", "be", "further", "validated", "in", "these", "settings", "and", "elsewhere.", "Background", "Identifying", "HIV", "infection", "in", "early", "infancy", "is", "an", "impor-", "tant", "challenge", "to", "effective", "paediatric", "HIV", "care", "and", "treat-", "ment.", "HIV-infected", "infants", "have", "a", "high", "mortality,", "particularly", "in", "heavily", "disease-burdened", "settings", "[1-6].", "The", "Children", "with", "HIV", "Early", "Antiretroviral", "Therapy", "(CHER)", "trial", "[4]", "recently", "showed", "that", "early", "antiretroviral", "therapy", "(ART),", "commenced", "at", "a", "median", "of", "7", "weeks", "of", "age", "was", "associated", "with", "a", "75%", "reduction", "in", "mortality", "*", "Correspondence:", "heather.jaspan@sbri.org", "1Children’s", "Infectious", "Diseases", "Clinical", "Research", "Unit,", "Department", "of", "Paediatrics", "and", "Child", "Health", "and", "Centre", "for", "Infectious", "Diseases,", "Faculty", "of", "Health", "Sciences,", "Stellenbosch", "University,", "Tygerberg,", "South", "Africa", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "versus", "the", "prevailing", "standard", "of", "care", "at", "the", "time", "(the", "WHO", "2006", "guidelines)", "[7].", "Importantly,", "most", "deaths", "occurred", "in", "the", "first", "few", "months", "of", "life", "and", "none", "of", "the", "infants", "had", "a", "CD4", "<", "25%", "or", "advanced", "HIV", "disease", "according", "to", "Centers", "for", "Diseases", "Control", "criteria", "[4].", "Diagnostic", "HIV-1", "DNA", "PCR", "is", "recommended", "at", "6", "weeks", "of", "age", "in", "HIV-exposed", "infants", "going", "through", "Ver-", "tical", "Transmission", "Prevention", "(VTP)", "programs", "[8].", "Although", "qualitative", "HIV-1", "PCR", "testing", "is", "becoming", "more", "available,", "turn-around", "time", "for", "results", "and", "subse-", "quent", "initiation", "of", "ART", "can", "take", "weeks.", "Clinical", "algo-", "rithms", "for", "HIV", "diagnosis", "in", "young", "infants", "could", "be", "useful", "for", "identifying", "those", "with", "probable", "HIV", "infection", "©", "2011", "Jaspan", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Kim", "et", "al.", "Journal", "of", "Hematology", "&", "Oncology", "2012,", "5:49", "http://www.jhoonline.org/content/5/1/49", "R", "E", "S", "E", "A", "R", "C", "H", "JOURNAL", "OF", "HEMATOLOGY", "&", "ONCOLOGY", "Open", "Access", "Prognostic", "factors", "in", "primary", "diffuse", "large", "B-cell", "lymphoma", "of", "adrenal", "gland", "treated", "with", "rituximab-CHOP", "chemotherapy", "from", "the", "Consortium", "for", "Improving", "Survival", "of", "Lymphoma", "(CISL)", "Yu", "Ri", "Kim1,", "Jin", "Seok", "Kim1,15*,", "Yoo", "Hong", "Min1,", "Dok", "HyunYoon2,", "Ho-Jin", "Shin3,", "Yeung-Chul", "Mun4,", "Yong", "Park5,", "Young", "Rok", "Do6,", "Seong", "Hyun", "Jeong7,", "Joon", "Seong", "Park7,", "Sung", "Yong", "Oh8,", "Suee", "Lee8,", "Eun", "Kyung", "Park9,", "Joung-Soon", "Jang9,", "Won-Sik", "Lee10,", "Hwe-Won", "Lee11,", "HyeonSeok", "Eom11,", "Jae-sook", "Ahn12,", "Jae-Heon", "Jeong13,", "Sun", "Kyung", "Baek13,", "Seok", "Jin", "Kim14,", "Won", "Seog", "Kim14", "and", "Cheolwon", "Suh2", "Abstract", "Background:", "The", "objective", "of", "this", "study", "was", "to", "identify", "prognostic", "factors", "for", "survival", "in", "patients", "with", "primary", "diffuse", "large", "B-cell", "lymphoma", "(DLBCL)", "of", "the", "adrenal", "gland.", "Methods:", "Thirty", "one", "patients", "diagnosed", "with", "primary", "adrenal", "DLBCL", "from", "14", "Korean", "institutions", "and", "treated", "with", "R-CHOP", "(rituximab,", "cyclophosphamide,", "doxorubicin,", "vincristine", "and", "prednisone)", "were", "analyzed.", "Results:", "Complete", "remission", "(CR)", "and", "overall", "response", "rate", "after", "R-CHOP", "chemotherapy", "were", "54.8%", "and", "87.0%.", "The", "2-year", "estimates", "of", "overall", "survival", "(OS)", "and", "progression-free", "survival", "(PFS)", "were", "68.3%", "and", "51.1%.", "In", "patients", "achieving", "CR,", "significant", "prolongations", "of", "OS", "(P", "=", "0.029)", "and", "PFS", "(P", "=", "0.005)", "were", "observed.", "Ann", "Arbor", "stage", "had", "no", "influence", "on", "OS.", "There", "was", "no", "significant", "difference", "in", "OS", "between", "patients", "with", "unilateral", "involvement", "of", "adrenal", "gland", "and", "those", "with", "bilateral", "involvement.", "When", "staging", "was", "modified", "to", "include", "bilateral", "adrenal", "involvement", "as", "one", "extranodal", "site,", "early", "stage", "(I", "or", "II)", "significantly", "correlated", "with", "longer", "OS", "(P", "=", "0.021)", "and", "PFS", "(P", "<0.001).", "Conclusions:", "Contrary", "to", "prior", "reports,", "our", "data", "suggests", "that", "outcomes", "of", "primary", "adrenal", "DLBCL", "are", "encouraging", "using", "a", "regimen", "of", "R-CHOP,", "and", "that", "achieving", "CR", "after", "R-CHOP", "is", "predictive", "of", "survival.", "Likewise,", "our", "modified", "staging", "system", "may", "have", "prognostic", "value.", "Keywords:", "Primary", "adrenal", "lymphoma,", "Diffuse", "large", "B-cell", "lymphoma,", "Prognostic", "factor,", "R-CHOP", "Background", "Primary", "extranodal", "non-Hodgkin’s", "lymphoma", "(NHL)", "is", "characterized", "by", "disease", "confined", "wholly", "or", "chiefly", "to", "an", "extranodal", "site", "[1].", "The", "adrenal", "gland", "is", "an", "extremely", "rare", "site", "of", "primary", "extranodal", "NHL,", "accounting", "for", "less", "than", "1%", "of", "all", "NHL", "and", "only", "3%", "of", "primary", "extranodal", "*", "Correspondence:", "hemakim@yuhs.ac", "1Department", "of", "Internal", "Medicine,", "Yonsei", "University", "College", "of", "Medicine,", "Seoul,", "Korea", "15Department", "of", "Internal", "Medicine,", "Division", "of", "Hematology,", "Yonsei", "University", "College", "of", "Medicine,", "50", "Yonsei-ro,", "Seodaemun-gu,", "Seoul", "120-752,", "Korea", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "lymphomas", "[2,3].", "While", "bilateral", "involvement", "of", "adrenal", "gland,", "predominantly", "male", "and", "elderly,", "and", "frequent", "as-", "sociation", "with", "adrenal", "insufficiency", "are", "commonly", "re-", "ported", "clinical", "features", "of", "primary", "adrenal", "NHL,", "diffuse", "large", "B-cell", "lymphoma", "(DLBCL)", "is", "the", "most", "common", "histologic", "subtype,", "with", "a", "non-germinal", "center", "B-cell", "(non-GCB)", "phenotype", "[4-7].", "To", "date,", "only", "about", "120", "publications", "(case", "reports", "or", "patient", "series)", "appear", "in", "the", "literature,", "each", "limited", "in", "scope.", "Conclusions", "have", "thus", "been", "drawn", "from", "clinical", "data", "and", "treatment", "outcomes", "©", "2012", "Kim", "et", "al.;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Ionic", "Components", "of", "Electric", "Current", "at", "Rat", "Corneal", "Wounds", "Ana", "Carolina", "Vieira1,2.,", "Brian", "Reid3*.,", "Lin", "Cao", "3", ",", "Mark", "J.", "Mannis1,", "Ivan", "R.", "Schwab", "1", ",", "Min", "Zhao1,3", "1", "Department", "of", "Ophthalmology,", "University", "of", "California", "Davis,", "Davis,", "California,", "United", "States", "of", "America,", "2", "Department", "of", "Ophthalmology,", "Federal", "University", "of", "Sao", "Paulo,", "Sao", "Paulo,", "Brazil,", "3", "Department", "of", "Dermatology,", "University", "of", "California", "Davis,", "Davis,", "California,", "United", "States", "of", "America", "Abstract", "Background:", "Endogenous", "electric", "fields", "and", "currents", "occur", "naturally", "at", "wounds", "and", "are", "a", "strong", "signal", "guiding", "cell", "migration", "into", "the", "wound", "to", "promote", "healing.", "Many", "cells", "involved", "in", "wound", "healing", "respond", "to", "small", "physiological", "electric", "fields", "in", "vitro.", "It", "has", "long", "been", "assumed", "that", "wound", "electric", "fields", "are", "produced", "by", "passive", "ion", "leakage", "from", "damaged", "tissue.", "Could", "these", "fields", "be", "actively", "maintained", "and", "regulated", "as", "an", "active", "wound", "response?", "What", "are", "the", "molecular,", "ionic", "and", "cellular", "mechanisms", "underlying", "the", "wound", "electric", "currents?", "Methodology/Principal", "Findings:", "Using", "rat", "cornea", "wounds", "as", "a", "model,", "we", "measured", "the", "dynamic", "timecourses", "of", "individual", "ion", "fluxes", "with", "ion-selective", "probes.", "We", "also", "examined", "chloride", "channel", "expression", "before", "and", "after", "wounding.", "After", "wounding,", "Ca2+", "efflux", "increased", "steadily", "whereas", "K+", "showed", "an", "initial", "large", "efflux", "which", "rapidly", "decreased.", "Surprisingly,", "Na+", "flux", "at", "wounds", "was", "inward.", "A", "most", "significant", "observation", "was", "a", "persistent", "large", "influx", "of", "Cl2,", "which", "had", "a", "time", "course", "similar", "to", "the", "net", "wound", "electric", "currents", "we", "have", "measured", "previously.", "Fixation", "of", "the", "tissues", "abolished", "ion", "fluxes.", "Pharmacological", "agents", "which", "stimulate", "ion", "transport", "significantly", "increased", "flux", "of", "Cl2,", "Na+", "and", "K+.", "Injury", "to", "the", "cornea", "caused", "significant", "changes", "in", "distribution", "and", "expression", "of", "Cl2", "channel", "CLC2.", "Conclusions/Significance:", "These", "data", "suggest", "that", "the", "outward", "electric", "currents", "occurring", "naturally", "at", "corneal", "wounds", "are", "carried", "mainly", "by", "a", "large", "influx", "of", "chloride", "ions,", "and", "in", "part", "by", "effluxes", "of", "calcium", "and", "potassium", "ions.", "Ca2+", "and", "Cl2", "fluxes", "appear", "to", "be", "mainly", "actively", "regulated,", "while", "K+", "flux", "appears", "to", "be", "largely", "due", "to", "leakage.", "The", "dynamic", "changes", "of", "electric", "currents", "and", "specific", "ion", "fluxes", "after", "wounding", "suggest", "that", "electrical", "signaling", "is", "an", "active", "response", "to", "injury", "and", "offers", "potential", "novel", "approaches", "to", "modulate", "wound", "healing,", "for", "example", "eye-drops", "targeting", "ion", "transport", "to", "aid", "in", "the", "challenging", "management", "of", "non-healing", "corneal", "ulcers.", "Citation:", "Vieira", "AC,", "Reid", "B,", "Cao", "L,", "Mannis", "MJ,", "Schwab", "IR,", "et", "al.", "(2011)", "Ionic", "Components", "of", "Electric", "Current", "at", "Rat", "Corneal", "Wounds.", "PLoS", "ONE", "6(2):", "e17411.", "doi:10.1371/journal.pone.0017411", "Editor:", "Che", "Connon,", "University", "of", "Reading,", "United", "Kingdom", "Received", "November", "9,", "2010;", "Accepted", "January", "31,", "2011;", "Published", "February", "25,", "2011", "Copyright:", "2011", "Vieira", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "This", "work", "was", "supported", "by", "the", "National", "Institutes", "of", "Health", "National", "Eye", "Institute", "grant", "1R01EY019101", "(to", "MZ", "and", "BR).", "The", "authors", "thank", "the", "Wellcome", "Trust", "for", "continuous", "support", "(068012).", "This", "work", "was", "also", "supported", "in", "part", "by", "Research", "to", "Prevent", "Blindness,", "Inc.,", "an", "NSFC", "grant", "(30628026),", "and", "UC", "Davis", "Dermatology", "Department", "developmental", "fund.", "MZ", "is", "also", "supported", "by", "grants", "from", "the", "California", "Institute", "of", "Regenerative", "Medicine", "RB1-01417,", "NSF", "MCB-", "0951199.", "The", "funders", "had", "no", "role", "in", "study", "design,", "data", "collection/analysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "Competing", "Interests:", "The", "authors", "have", "declared", "that", "no", "competing", "interests", "exist.", "*", "E-mail:", "brireid@ucdavis.edu", ".", "These", "authors", "contributed", "equally", "to", "this", "work.", "Introduction", "At", "human", "skin", "wounds,", "naturally", "occurring", "electric", "fields", "and", "currents", "were", "detected", "many", "years", "ago", "[1–4].", "Modern", "techniques", "have", "confirmed", "and", "significantly", "extended", "our", "understanding", "of", "these", "endogenous", "electric", "fields.", "Electric", "currents", "of", ",10–100", "mA/", "cm2", "and", "fields", "of", ",40–177", "mV/mm", "at", "wounds", "in", "humans", "and", "various", "animals", "have", "been", "measured", "in", "recent", "years", "with", "vibrating", "probes,", "micro-glass", "electrodes,", "micro-needle", "arrays,", "and", "bioelec-", "tric", "imagers", "[5–9].", "Endogenously", "induced", "electric", "fields", "at", "wounds", "have", "emerged", "as", "an", "important", "signal", "that", "plays", "a", "critical", "role", "in", "wound", "healing", "[10–13].", "Chemotaxis,", "haptotaxis", "(response", "to", "surface-bound", "molecules),", "contact", "guidance,", "free", "edges", "and", "other", "factors", "at", "wounds", "are", "directional", "cues", "for", "cell", "migration", "and", "wound", "healing.", "Recently,", "we", "demonstrated", "that", "electric", "signals", "in", "cell", "migration", "during", "wound", "healing", "are", "far", "more", "important", "than", "previously", "thought", "since", "they", "override", "other", "directional", "cues", "[6,10,14].", "Applied", "electric", "fields", "have", "been", 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"In", "the", "cornea,", "ions", "are", "constantly", "being", "transported", "across", "the", "corneal", "epithelium,", "which", "generates", "and", "maintains", "the", "TEPD", "with", "the", "outer", "side", "negative", "[25].", "Sodium", "ions", "are", "actively", "transported", "from", "the", "tears", "to", "the", "aqueous", "humor", "while", "chloride", "PLoS", "ONE", "|", "www.plosone.org", "1", "February", "2011", "|", "Volume", "6", "|", "Issue", "2", "|", "e17411" ]

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[ "Original", "Article", "Elmer", "Press", "J", "Clin", "Med", "Res", "•", "2010;2(3):117-120", "Latent", "Toxoplasmosis", "in", "Patients", "With", "Different", "Malignancy:", "A", "Hospital", "Based", "Study", "Amal", "Nimira,", "c,", "Amizah", "Othmanb,", "Soon", "Eeb,", "Zohdy", "Musab,", "Iffah", "Abd", "Majidb,", "Zalikha", "Kamarudinb,", "Chee", "Xianb,", "Noor", "Hayati", "Isab", "Abstract", "Background:", "Seroprevalence", "of", "toxoplasmosis", "in", "different", "popula-", "tions", "may", "vary", "according", "to", "different", "environments,", "social", "customs", "and", "habits.", "This", "study", "was", "designed", "to", "measure", "the", "seroprevalence", "of", "toxoplasmosis", "among", "patients", "with", "different", "malignancies", "and", "to", "ascertain", "the", "association", "between", "common", "risk", "factors", "and", "disease", "transmission.", "Methods:", "This", "Cross-sectional", "study", "was", "from", "January", "to", "April", "of", "2009.", "Four", "Oncology", "wards", "in", "Hospital", "Universiti", "Kebangsaan", "Ma-", "laysia", "(HUKM)", "were", "selected", "as", "the", "site", "for", "undertaking", "the", "present", "study.", "The", "survey", "involved", "129", "patients", "with", "different", "malignan-", "cies.", "Information", "was", "gathered", "by", "using", "study", "subject", "information", "sheet", "and", "a", "standardized", "structured", "questionnaire.", "Toxoplasma", "was", "screened", "by", "a", "standerd", "ELISA", "commercial", "kit", "in", "accordance", "with", "the", "manufacturer’s", "instructions", "and", "performed", "at", "the", "Department", "of", "Microbiology,", "HUKM", "Kuala", "Lumpur.", "A", "result", "of", ">", "51", "IU/ml", "of", "anti-Toxoplasma", "(IgG)", "antibody", "was", "regarded", "as", "positive,", "indicat-", "ing", "latent", "or", "pre-existing", "Toxoplasma", "infection.", "A", "result", "of", ">", "51", "IU/", "ml", "of", "anti-Toxoplasma", "(IgM)", "antibody", "was", "regarded", "as", "positive,", "indicating", "recently", "acquired", "Toxoplasma", "infection.", "Results:", "Total", "number", "of", "seropositive", "patients", "was", "54", "(67.6%),", "the", "mean", "age", "was", "51", "years", "(range15", "-", "88", "years).", "Toxoplasma", "IgG", "positivity", "was", "highest", "among", "Malaysian", "(32%).", "Male", "to", "female", "ra-", "tio", "was", "almost", "equal.", "There", "was", "a", "statistically", "significant", "difference", "in", "seropositivity", "between", "patients", "living", "in", "rural", "areas", "compared", "to", "those", "living", "in", "urban", "areas,", "positive", "history", "of", "consumption", "of", "undercooked", "meat", "and/or", "blood", "transfusion", "(p", "<", "0.05).", "Manuscript", "accepted", "for", "publication", "May", "26,", "2010", "aDepartment", "of", "Pathology,", "Cyberjaya", "University", "College", "of", "Medical", "Sciences,", "Malaysia", "bDepartment", "of", "Parasitology,", "Universiti", "Kebangsaan", "Malaysia,", "Malaysia", "cCorresponding", "author,", "Email:", "aralmadi@yahoo.com", "doi:10.4021/jocmr2010.06.375w", "Conclusions:", "These", "findings", "give", "some", "support", "to", "Toxoplasma", "screening", "program", "and", "health", "education,", "including", "promotion", "of", "a", "healthy", "lifestyle", "exclusively", "in", "seronegative", "patients", "in", "order", "to", "prevent", "seroconversion", "and", "the", "incidence", "of", "clinically", "evident", "op-", "portunistic", "infection.", "Keywords:", "Toxoplasma", "gondii;", "Risk", "factors;", "Immunocompro-", "mised;", "seroconversion;", "Seroprevalence", "Introduction", "Toxoplasma", "gondii", "(T.", "gondii)", "is", "a", "protozoan", "parasite", "that", "is", "endemic", "worldwide", "and", "is", "a", "major", "opportunistic", "pathogen", "in", "immunocompromised", "hosts.", "Infection", "is", "mainly", "acquired", "by", "ingestion", "of", "food,", "water", "or", "soil", "that", "is", "contaminated", "with", "oocysts", "shed", "by", "cats,", "or", "by", "eating", "undercooked", "or", "raw", "meat", "containing", "tissue", "cysts", "[1].", "Primary", "infection", "is", "usually", "subclinical,", "but", "in", "severely", "immunocompromised", "patients", "it", "may", "be", "life-threatening.", "Most", "primary", "infections", "subsequently", "phase", "into", "chronic", "in-", "fections", "in", "which", "the", "parasite", "persist", "in", "tissue", "cysts,", "mainly", "in", "the", "brain,", "retina,", "skeletal", "and", "cardiac", "muscles", "[2].", "These", "chronic", "infections", "probably", "persist", "indefinitely", "throughout", "the", "life", "and", "may", "remain", "undiagnosed", "until", "or", "unless", "it", "is", "re-", "activated", "as", "a", "result", "of", "severe", "immune", "suppression", "[3].", "For", "the", "diagnosis", "of", "T.", "gondii", "infection,", "detection", "of", "the", "organism", "itself", "is", "confirmative", "but", "very", "difficult.", "Thus,", "most", "clinical", "laboratories", "use", "serological", "tests", "to", "detect", "antibodies", "against", "T.", "gondii", "such", "as", "the", "latex", "agglutination", "(LA)", "test,", "ELISA", "and", "indirect", "fluorescent", "antibody", "test", "because", "of", "its", "high", "specificity", "and", "sensitivity", "[4].", "Seroprevalence", "in", "different", "populations", "may", "vary", "ac-", "cording", "to", "different", "environments,", "social", "customs", "and", "habits", "[5,", "6].", "Analysis", "of", "worldwide", "reports", "indicated", "that", "about", "38.5%", "humans,", "32.9%", "cats", "and", "24.2%", "goats", "were", "seroposi-", "tive", "for", "toxoplasmosis", "[7].", "This", "study", "was", "designed", "to", "measure", "the", "seroprevalence", "of", "toxoplasmosis", "among", "patients", "with", "different", "malignancies", "and", "to", "ascertain", "the", "association", "between", "common", "risk", "factors", "Articles", "©", "The", "authors", "|", "Journal", "compilation", "©", "J", "Clin", "Med", "Res", "and", "Elmer", "Press™", "|", "www.jocmr.org", "117" ]

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[ "Ophir", "et", "al.", "BMC", "Genomics", "2010,", "11:269", "http://www.biomedcentral.com/1471-2164/11/269", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "RHesiegarchh", "-atrthicleroughput", "marker", "discovery", "in", "melon", "using", "a", "self-designed", "oligo", "microarray", "Ron", "Ophir1,", "Ravit", "Eshed1,", "Rotem", "Harel-Beja2,", "Galil", "Tzuri2,", "Vitaly", "Portnoy2,", "Yoseph", "Burger2,", "Shai", "Uliel1,", "Nurit", "Katzir2", "and", "Amir", "Sherman*1", "Abstract", "Background:", "Genetic", "maps", "constitute", "the", "basis", "of", "breeding", "programs", "for", "many", "agricultural", "organisms.", "The", "creation", "of", "these", "maps", "is", "dependent", "on", "marker", "discovery.", "Melon,", "among", "other", "crops,", "is", "still", "lagging", "in", "genomic", "resources,", "limiting", "the", "ability", "to", "discover", "new", "markers", "in", "a", "high-throughput", "fashion.", "One", "of", "the", "methods", "used", "to", "search", "for", "molecular", "markers", "is", "DNA", "hybridization", "to", "microarrays.", "Microarray", "hybridization", "of", "DNA", "from", "different", "accessions", "can", "reveal", "differences", "between", "them--single-feature", "polymorphisms", "(SFPs).", "These", "SFPs", "can", "be", "used", "as", "markers", "for", "breeding", "purposes,", "or", "they", "can", "be", "converted", "to", "conventional", "markers", "by", "sequencing.", "This", "method", "has", "been", "utilized", "in", "a", "few", "different", "plants", "to", "discover", "genetic", "variation,", "using", "Affymetrix", "arrays", "that", "exist", "for", "only", "a", "few", "organisms.", "We", "applied", "this", "approach", "with", "some", "modifications", "for", "marker", "discovery", "in", "melon.", "Results:", "Using", "a", "custom-designed", "oligonucleotide", "microarray", "based", "on", "a", "partial", "EST", "collection", "of", "melon,", "we", "discovered", "6184", "putative", "SFPs", "between", "the", "parents", "of", "our", "mapping", "population.", "Validation", "by", "sequencing", "of", "245", "SFPs", "from", "the", "two", "parents", "showed", "a", "sensitivity", "of", "around", "79%.", "Most", "SFPs", "(81%)", "contained", "single-nucleotide", "polymorphisms.", "Testing", "the", "SFPs", "on", "another", "mapping", "population", "of", "melon", "confirmed", "that", "many", "of", "them", "are", "conserved.", "Conclusion:", "Thousands", "of", "new", "SFPs", "that", "can", "be", "used", "for", "genetic", "mapping", "and", "molecular-assisted", "breeding", "in", "melon", "were", "discovered", "using", "a", "custom-designed", "oligo", "microarray.", "A", "portion", "of", "these", "SFPs", "are", "conserved", "and", "can", "be", "used", "in", "different", "breeding", "populations.", "Although", "improvement", "of", "the", "discovery", "rate", "is", "still", "needed,", "this", "approach", "is", "applicable", "to", "many", "agricultural", "systems", "with", "limited", "genomic", "resources.", "Background", "Genetic", "maps", "based", "on", "molecular", "markers", "are", "a", "key", "step", "in", "marker-assisted", "selection", "(MAS)", "for", "plant", "breeding", "and", "for", "gene", "identification", "based", "on", "positional", "informa-", "tion", "[1].", "Discovery", "of", "novel", "genetic", "variation,", "enhanced", "selection", "techniques", "and", "the", "identification", "of", "genotypes", "with", "new", "or", "improved", "traits", "can", "lead", "to", "superior", "strains", "of", "interest.", "The", "density", "of", "the", "markers", "on", "a", "genetic", "map", "defines", "the", "map's", "resolution", "and", "the", "ability", "to", "introduce", "these", "traits", "using", "molecular", "means.", "New", "high-through-", "put", "technologies", "for", "the", "discovery", "of", "genetic", "markers", "and", "linkage", "analysis", "can", "enhance", "plant", "breeding", "efforts", "[2].", "In", "the", "last", "few", "years,", "genomic", "tools", "have", "begun", "to", "replace", "the", "traditional", "methods", "of", "molecular", "marker", "dis-", "*", "Correspondence:", "asherman@agri.gov.il", "1", "Genomic", "Unit,", "Plant", "Sciences", "Institute,", "Volcani", "Center,", "Agricultural", "Research", "Organization,", "PO", "Box", "6,", "Bet", "Dagan", "50250,", "Israel", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "covery.", "Use", "of", "computational", "tools", "to", "search", "sequence", "information", "for", "molecular", "markers", "[3,4],", "or", "genomic", "technologies", "such", "as", "whole-genome", "scanning", "(WGS),", "have", "enabled", "the", "discovery", "of", "thousands", "of", "markers", "in", "a", "single", "experiment", "[3].", "These", "markers", "can", "be", "mapped", "to", "create", "high-density", "genetic", "maps", "or", "used", "directly", "for", "MAS", "[3-5].", "However,", "use", "of", "these", "types", "of", "technologies", "for", "plant", "breeding", "is", "still", "restricted,", "as", "many", "agricultural", "systems", "have", "a", "limited", "amount", "of", "genomic", "resources.", "Furthermore,", "plant", "species", "contain", "wide", "genetic", "variation", "that", "cannot", "be", "explored", "by", "sequencing", "only", "one", "or", "two", "plants", "from", "each", "species.", "One", "of", "the", "technologies", "that", "has", "been", "used", "for", "identifi-", "cation", "of", "genetic", "variation", "is", "single-feature", "polymor-", "phism", "(SFP)", "[3-5].", "This", "approach", "is", "based", "on", "the", "concept", "that", "target", "DNA", "that", "perfectly", "matches", "its", "probes", "binds", "with", "greater", "affinity", "than", "one", "with", "a", "mismatch.", "Thus,", "nat-", "ural", "imperfections", "can", "be", "detected", "as", "a", "difference", "in", "sig-", "©", "2010", "Ophir", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "BioMed", "Central", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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"indicators:", "single-crystal", "X-ray", "study;", "T", "=", "293", "K;", "mean", "(C–C)", "=", "0.008", "A˚;", "R", "factor", "=", "0.037;", "wR", "factor", "=", "0.131;", "data-to-parameter", "ratio", "=", "12.4.", "The", "asymmetric", "unit", "of", "the", "title", "complex,", "[Cu(C11H16N3O)]-", "ClO4,", "consists", "of", "two", "CuII", "ions", "coordinated", "by", "Schiff", "base", "ligands", "and", "two", "perchlorate", "anions.", "The", "Schiff", "base", "molecules", "are", "linked", "to", "the", "CuII", "atoms", "via", "three", "N", "atoms", "and", "one", "O", "atom,", "resulting", "in", "a", "square-planar", "geometry.", "Intermolecular", "hydrogen", "bonds", "involving", "the", "NH", "groups", "as", "donors", "and", "O", "atoms", "of", "the", "perchlorate", "anions", "as", "acceptors", "are", "observed.", "Related", "literature", "For", "related", "structures,", "see:", "Ambrosi", "et", "al.", "(2003);", "Jiang", "et", "al.", "(2009).", "b", "=", "12.615", "(3)", "A˚", "c", 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"(4)", "162", "(4)", "148", "(3)", "168", "(4)", "131", "(4)", "139", "(4)", "Experimental", "Crystal", "data", "[Cu(C11H16N3O)]ClO4", "Mr", "=", "369.26", "m830", "Dieng", "et", "al.", "Triclinic,", "P1", "a", "=", "10.371", "(3)", "A˚", "Data", "collection:", "CAD-4", "EXPRESS", "(Enraf–Nonius,", "1994);", "cell", "refinement:", "CAD-4", "EXPRESS;", "data", "reduction:", "MolEN", "(Fair,", "1990);", "program(s)", "used", "to", "solve", "structure:", "SHELXS97", "(Sheldrick,", "2008);", "program(s)", "used", "to", "refine", "structure:", "SHELXL97", "(Sheldrick,", "2008);", "molecular", "graphics:", "ORTEP-3", "for", "Windows", "(Farrugia,", "1997);", "soft-", "ware", "used", "to", "prepare", "material", "for", "publication:", "SHELXL97.", "The", "authors", "thank", "the", "Agence", "Universitaire", "de", "la", "Franco-", "phonie", "for", "financial", "support", "(AUF-PSCI", "No.", "6314PS804).", "Supplementary", "data", "and", "figures", "for", "this", "paper", "are", "available", "from", "the", "IUCr", "electronic", "archives", "(Reference:", "AA2008).", "References", "Ambrosi,", "G.,", "Formica,", "M.,", "Fusi,", "V.,", "Giorgi,", "L.,", "Guerri,", "A.,", "Micheloni,", "M.,", "Pontellini,", "R.", "&", "Rossi,", "P.", "(2003).", "Polyhedron,", "22,", "1135–1146.", "doi:10.1107/S1600536811020095", "Acta", "Cryst.", "(2011).", "E67,", "m830–m831" ]

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[ "Research", "Low-Level", "Environmental", "Cadmium", "Exposure", "Is", "Associated", "with", "DNA", "Hypomethylation", "in", "Argentinean", "Women", "Mohammad", "Bakhtiar", "Hossain,1,2", "Marie", "Vahter,3", "Gabriela", "Concha,4", "and", "Karin", "Broberg", "1", "1Department", "of", "Laboratory", "Medicine,", "Division", "of", "Occupational", "and", "Environmental", "Medicine,", "Lund", "University,", "Lund,", "Sweden;", "2International", "Centre", "for", "Diarrhoeal", "Disease", "Research,", "Bangladesh,", "Dhaka,", "Bangladesh;", "3Institute", "of", "Environmental", "Medicine,", "Karolinska", "Institutet,", "Stockholm,", "Sweden;", "4Risk", "and", "Benefit", "Assessment", "Department,", "National", "Food", "Agency,", "Uppsala,", "Sweden", "Background", ":", "Cadmium,", "a", "common", "food", "pollutant,", "alters", "DNA", "methylation", "in", "vitro.", "Epigenetic", "effects", "might", "therefore", "partly", "explain", "cadmium’s", "toxicity,", "including", "its", "carcinogenicity;", "however,", "human", "data", "on", "epigenetic", "effects", "are", "lacking.", "o", "Bjectiv", ":", "We", "evaluated", "the", "effects", "of", "dietary", "cadmium", "exposure", "on", "DNA", "methylation,", "consider­", "ing", "other", "environmental", "exposures,", "genetic", "predisposition,", "and", "gene", "expression.", "Methods", ":", "Concentrations", "of", "cadmium,", "arsenic,", "selenium,", "and", "zinc", "in", "blood", "and", "urine", "of", "non­", "smoking", "women", "(n", "=", "202)", "from", "the", "northern", "Argentinean", "Andes", "were", "measured", "by", "inductively", "coupled", "mass", "spectrometry.", "Methylation", "in", "CpG", "islands", "of", "LINE-1", "(long", "interspersed", "nuclear", "element­1;", "a", "proxy", "for", "global", "DNA", "methylation)", "and", "promoter", "regions", "of", "p16", "[cyclin­dependent", "kinase", "inhibitor", "2A", "(CDKN2A)]", "and", "MLH1", "(mutL", "homolog", "1)", "in", "peripheral", "blood", "were", "measured", "by", "bisulfite", "polymerase", "chain", "reaction", "pyrosequencing.", "Genotyping", "(n", "=", "172)", "for", "the", "DNA", "(cytosine­", "5)­m­ethyltransferase", "1", "gene", "(", "DNMT1", "rs10854076", "and", "rs2228611)", "and", "DNA", "(cytosine5­)­m­ethyl­", "transferase", "3", "beta", "gene", "(DNMT3B", "rs2424913", "and", "rs2424932)", "was", "performed", "with", "Sequenom", "iPLEX", "GOLD", "SNP", "genotyping;", "and", "gene", "expression", "(n", "=", "90),", "with", "DirectHyb", "HumanHT­12", "(version", "3.0).", "r", "esult", ":", "Cadmium", "exposure", "was", "low:", "median", "concentrations", "in", "blood", "and", "urine", "were", "0.36", "and", "0.23", "µg/L,", "respectively.", "Urinary", "cadmium", "(natural", "log", "transformed)", "was", "inversely", "associated", "with", "LINE-1", "methylation", "(β", "=", "–0.50,", "p", "=", "0.0070;", "β", "=", "–0.44,", "p", "=", "0.026,", "adjusted", "for", "age", "and", "coca", "chew­", "ing)", "but", "not", "with", "p16", "or", "MLH1", "methylation.", "Both", "DNMT1", "rs10854076", "and", "DNMT1", "rs2228611", "polymorphisms", "modified", "associations", "between", "urinary", "cadmium", "and", "LINE-1", "(pv­alues", "for", "interaction", "in", "adjusted", "models", "were", "0.045", "and", "0.064,", "respectively).", "The", "rare", "genotypes", "demonstrated", "stronger", "hypomethylation", "with", "increasing", "urinary", "cadmium", "concentrations.", "Cadmium", "was", "inversely", "associated", "with", "DNMT3B", "(rS", "=", "–0.28,", "p", "=", "0.0086)", "but", "not", "with", "DNMT1", "expression", "(rS", "=", "–0.075,", "p", "=", "0.48).", "c", "onclusi", ":", "Environmental", "cadmium", "exposure", "was", "associated", "with", "DNA", "hypomethylation", "in", "peripheral", "blood,", "and", "DNMT1", "genotypes", "modified", "this", "association.", "The", "role", "of", "epigenetic", "modifica­", "tions", "in", "cadmiuma­ssociated", "diseases", "needs", "clarification.", "k", "ey", "w", "ords", ":", "cadmium,", "DNMT1,", "DNMT3B,", "epigenetic,", "genotype,", "LINE-1,", "MLH1,", "p16,", "pyro­", "sequencing.", "Environ", "Health", "Perspect", "120:879–884", "(2012).", "http://dx.doi.org/10.1289/ehp.1104600", "[Online", "1", "March", "2012]", "Cadmium", "is", "a", "widespread", "environmental", "pollutant", "associated", "with", "adverse", "health", "effects,", "including", "cancer,", "kidney", "damage,", "low", "bone-mineral", "density,", "bone", "fractures,", "and", "probably", "impaired", "early-life", "development", "(Engström", "A", "et", "al.", "2011;", "Järup", "and", "Åkesson", "2009;", "Kippler", "et", "al.", "2011).", "The", "general", "popu-", "lation", "is", "exposed", "to", "cadmium", "mainly", "through", "the", "diet,", "in", "particular,", "through", "cereals", "and", "vegetables,", "and", "through", "smoking.", "Potential", "mechanisms", "of", "cadmium", "toxicity", "described", "so", "far", "include", "interactions", "with", "sulfhydryl", "groups", "and", "endocrine", "disruption,", "as", "well", "as", "oxidative", "stress", "(Hartwig", "2010;", "Johnson", "et", "al.", "2003;", "Monroe", "and", "Halvorsen", "2006;", "Xu", "et", "al.", "2011;", "Yu", "et", "al.", "2010).", "DNA", "methylation", "is", "essential", "for", "embryo-", "genesis", "and", "for", "maintaining", "cell-lineage–", "specific", "gene", "expression", "throughout", "life.", "Dysregulation", "of", "epigenetic", "processes,", "such", "as", "DNA", "methylation,", "may", "lead", "to", "impaired", "child-", "hood", "development", "or", "chronic", "diseases", "later", "in", "life,", "including", "cancer", "(Faulk", "and", "Dolinoy", "2011;", "Feinberg", "2007;", "Robins", "et", "al.", "2011).", "In", "carcinogenesis,", "global", "DNA", "methylation", "is", "generally", "decreased,", "whereas", "specific", "regions", "of", "DNA", "that", "contain", "tumor", "suppressor", "genes", "often", "show", "hypermethylation", "(Chalitchagorn", "et", "al.", "2004;", "Deng", "et", "al.", "2006;", "Gaudet", "et", "al.", "2003;", "Robertson", "and", "Jones", "2000).", "In", "vitro", "studies", "have", "indicated", "that", "cadmium", "may", "interfere", "with", "epigenetic", "processes:", "Both", "gene-", "specific", "DNA", "hypermethylation", "with", "gene", "silencing", "of", "p16INK4a", "[CDKN2A", "(cyclin-", "dependent", "kinase", "inhibitor", "2A)],", "RASSF1", "[Ras", "association", "(RalGDS/AF-6)", "domain", "family", "member", "1],", "and", "MT1", "(metallothionein", "1)", "genes,", "and", "global", "DNA", "hypomethylation", "have", "been", "reported", "(Benbrahim-Tallaa", "et", "al.", "2007;", "Huang", "et", "al.", "2008;", "Jiang", "et", "al.", "2008;", "Martinez-Zamudio", "and", "Ha", "2011;", "Takiguchi", "et", "al.", "2003).", "However,", "there", "are", "no", "reports", "on", "the", "epigenetic", "effects", "of", "cadmium", "exposure", "in", "humans.", "The", "aim", "of", "this", "study", "was", "to", "evaluate", "whether", "environmental", "cadmium", "exposure,", "mainly", "through", "the", "normal", "diet,", "may", "affect", "DNA", "methylation,", "both", "of", "repetitive", "genetic", "Environmental", "Health", "Perspectives", "•", "volume", "120", "|", "number", "6", "|", "June", "2012", "elements", "(as", "a", "proxy", "for", "global", "methylation)", "and", "of", "specific", "genes.", "Materials", "and", "Methods", "Participants.", "We", "studied", "202", "women", "living", "in", "the", "Andean", "plateau", "(3,800", "m", "above", "sea", "level)", "in", "northern", "Argentina,", "an", "area", "that", "has", "minimal", "industrial", "or", "vehicle-derived", "pollu-", "tion.", "Most", "of", "the", "study", "participants", "(161)", "were", "from", "the", "village", "of", "San", "Antonio", "de", "los", "Cobres,", "which", "has", "about", "5,000", "inhabitants.", "The", "41", "remaining", "participants", "were", "from", "small", "surrounding", "villages.", "The", "study", "area", "is", "known", "to", "have", "elevated", "concentrations", "of", "arsenic", "(Vahter", "et", "al.", "1995),", "but", "not", "cadmium", "(Concha", "et", "al.", "2010),", "in", "the", "drinking", "water.", "The", "study", "individuals", "were", "recruited", "with", "the", "assistance", "of", "local", "medical", "personnel,", "except", "in", "the", "small", "mining", "village", "of", "Tolar", "Grande,", "where", "we", "went", "from", "house", "to", "house", "to", "explain", "the", "study", "and", "invited", "the", "adults", "to", "participate.", "We", "included", "only", "women", "because", "men", "were", "often", "away", "from", "home", "for", "longer", "periods", "for", "work", "and", "were", "therefore", "likely", "to", "be", "exposed", "to", "a", "different", "variety", "of", "environmental", "hazards.", "Furthermore,", "women", "may", "be", "more", "susceptible", "to", "cadmium", "exposure", "than", "are", "men", "because", "of", "their", "increased", "gastrointestinal", "cadmium", "absorption", "when", "iron", "stores", "are", "low", "(Berglund", "et", "al.", "1994),", "as", "is", "common", "in", "women", "of", "child-", "bearing", "age.", "Only", "four", "study", "participants", "smoked", "cigarettes,", "and", "one", "reported", "drinking", "alcohol,", "but", "almost", "half", "(46.5%)", "reported", "that", "they", "chewed", "coca", "leaves.", "As", "reported", "before,", "interviews", "with", "the", "study", "participants", "revealed", "that", "almost", "all", "women", "drank", "exclusively", "public", "water", "and", "that", "their", "diets", "consisted", "mainly", "of", "corn,", "beans,", "chicken,", "and", "pork", "(Broberg", "et", "al.", "2011).", "Only", "three", "women", "reported", "taking", "Address", "correspondence", "to", "K.", "Broberg,", "Department", "of", "Laboratory", "Medicine,", "Division", "of", "Occupational", "and", "Environmental", "Medicine,", "Lund", "University,", "Klinikgatan", "21,", "SE-22185", "Lund,", "Sweden.", "Telephone:", "46046173819.", "Fax:", "46046143207.", "E-mail:", "karin.", "broberg_palmgren@med.lu.se", "Supplemental", "Material", "is", "available", "online", "(http://", "dx.doi.org/10.1289/ehp.1104600).", "We", "thank", "the", "Department", "of", "Oncology,", "Lund", "University,", "for", "technical", "assistance.", "This", "research", "was", "supported", "by", "the", "Swedish", "Council", "for", "Working", "Life", "and", "Social", "Research,", "Karolinska", "Institutet,", "and", "Kungliga", "fysiografiska", "sällskapet,", "European", "Union", "(FP6;", "“PHIME”", "FOOD-CT-2006-", "016253).", "The", "authors", "declare", "they", "have", "no", "actual", "or", "potential", "competing", "financial", "interests.", "Received", "10", "October", "2011;", "accepted", "1", "March", "2012.", "879" ]

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[ "Hindawi", "Publishing", "Corporation", "Case", "Reports", "in", "Medicine", "Volume", "2012,", "Article", "ID", "529246,", "2", "pages", "doi:10.1155/2012/529246", "Case", "Report", "Unusual", "Cause", "of", "Intestinal", "Obstruction:", "Left", "Paraduodenal", "Hernia", "Sami", "Akbulut", "Department", "of", "Surgery,", "Diyarbakir", "Education", "and", "Research", "Hospital,", "21400", "Diyarbakir,", "Turkey", "Correspondence", "should", "be", "addressed", "to", "Sami", "Akbulut,", "akbulutsami@gmail.com", "Received", "13", "November", "2011;", "Accepted", "2", "January", "2012", "Academic", "Editor:", "Michail", "Varras", "Copyright", "©", "2012", "Sami", "Akbulut.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Internal", "intestinal", "hernia", "has", "been", "defined", "as", "bulging", "of", "the", "intestines", "through", "a", "normal", "or", "an", "abnormal", "peritoneal", "or", "mesenteric", "opening.", "Paraduodenal", "hernias", "comprise", "30%–53%", "of", "all", "internal", "intestinal", "herniations", "and", "account", "for", "0.2%–0.9%", "of", "all", "bowel", "obstructions.", "In", "this", "paper,", "we", "aimed", "to", "present", "a", "male", "patient", "of", "42", "years", "of", "age", "who", "developed", "intestinal", "obstruction", "due", "to", "left", "paraduodenal", "hernias.", "Left", "paraduodenal", "hernia", "should", "be", "taken", "into", "consideration", "in", "the", "differential", "diagnosis", "in", "patients", "of", "relatively", "younger", "ages", "with", "no", "prior", "abdominal", "surgery", "who", "frequently", "have", "bowel", "obstruction", "episodes.", "1.", "Introduction", "Internal", "intestinal", "hernia", "has", "been", "defined", "as", "bulging", "of", "the", "intestines", "through", "a", "normal", "or", "an", "abnormal", "peritoneal", "or", "mesenteric", "opening.", "This", "clinical", "entity", "can", "occur", "for", "con-", "genital", "or", "acquired", "reasons", "and", "accounts", "for", "around", "1%–", "5.8%", "of", "all", "intestinal", "obstructions", "[1–3].", "Although", "the", "intestinal", "herniations", "are", "divided", "into", "distinct", "subgroups", "based", "on", "the", "localizations,", "it", "is", "the", "paraduedonal", "hernias", "which", "are", "responsible", "in", "nearly", "half", "of", "the", "patients.", "Also", "known", "as", "Treitz’s", "hernia,", "the", "paraduedonal", "herniations", "even-", "tuate", "from", "abnormal", "rotation", "of", "intestine.", "Paraduedonal", "hernias", "comprise", "30%–53%", "of", "all", "intestinal", "herniations", "and", "account", "for", "0.2%–0.9%", "of", "all", "bowel", "obstructions", "[1–4].", "In", "this", "study,", "we", "aimed", "to", "present", "a", "male", "patient", "of", "42", "years", "of", "age", "who", "developed", "intestinal", "obstruction", "due", "to", "left", "para-", "duedonal", "hernias.", "2.", "Case", "Presentation", "A", "42-year-old", "male", "patient", "was", "admitted", "to", "our", "emergency", "department", "with", "the", "complaints", "of", "nausea,", "vomiting,", "and", "abdominal", "pain", "that", "had", "lasted", "for", "3", "days", "and", "had", "shown", "progressive", "worsening.", "The", "patient", "especially", "expressed", "that", "the", "pain", "had", "intensified", "around", "the", "umbilical", "region", "and", "that", "he", "had", "been", "unable", "to", "pass", "stool", "or", "gas.", "The", "patient’s", "history", "revealed", "no", "systemic", "disease", "or", "prior", "operation.", "As", "for", "the", "vital", "signs", "of", "the", "patient,", "the", "blood", "pressure,", "the", "pulse", "rate,", "and", "the", "body", "temperature", "were", "measured", "to", "be", "130/85", "mmHg,", "83", "beats/min", "and", "37.3◦C,", "respectively.", "Marked", "abdominal", "distension", "and", "rebound", "tenderness", "were", "detected", "in", "the", "physical", "examination", "performed,", "whereas", "no", "abdominal", "guarding", "was", "observed.", "In", "standing", "abdominal", "direct", "X-ray,", "widespread", "air-fluid", "levels", "were", "observed.", "While", "no", "pathological", "finding", "was", "detected", "other", "than", "mild", "uremia", "in", "the", "blood", "chemistry,", "leukocyte", "counts", "was", "reported", "to", "be", "16.450/mm3.", "We", "were", "not", "able", "to", "obtain", "ultrasonographic", "or", "contrast-enhanced", "abdominal", "CT", "evaluation", "because", "of", "the", "fact", "that", "the", "patient", "was", "admitted", "to", "our", "emergency", "depart-", "ment", "at", "11.00", "pm.", "Given", "the", "physical", "examination", "findings,", "plain", "X-ray", "imaging", "and", "the", "absence", "of", "any", "prior", "surgery", "in", "the", "case", "history,", "the", "patient", "was", "taken", "into", "surgery", "consid-", "ering", "that", "widespread", "peritonitis", "was", "likely", "to", "exist", "due", "to", "a", "possible", "congenital", "brid", "or", "a", "perforated", "appendicitis", "with", "delayed", "diagnosis.", "We", "observed,", "in", "the", "surgical", "exploration", "via", "midline", "incision,", "that", "all", "of", "the", "small", "intestinal", "segments", "except", "a", "distal", "ileal", "portion", "of", "50–60", "cm", "length", "was", "stuck", "in", "the", "sac", "of", "a", "left", "paraduedonal", "hernia.", "The", "inferior", "mesenteric", "vein", "constituted", "the", "anterior", "portion", "of", "the", "hernial", "sac", "from", "the", "orifice", "(Figure", "1).", "After", "reducing", "the", "intestinal", "segments", "in", "the", "hernial", "sac", "into", "the", "abdominal", "cavity,", "IMV", "was", "released", "alongside", "its", "length.", "Then", "followed", "sealing", "off" ]

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[ "structural", "communications", "Acta", "Crystallographica", "Section", "F", "Structural", "Biology", "and", "Crystallization", "Communications", "ISSN", "1744-3091", "Debanu", "Das,a,b", "Piotr", "Kozbial,a,c", "Gye", "Won", "Han,a,d", "Dennis", "Carlton,a,d", "Lukasz", "Jaroszewski,a,c,e", "Polat", "Abdubek,a,f", "Tamara", "Astakhova,a,e", "Herbert", "L.", "Axelrod,a,b", "Constantina", "Bakolitsa,a,c", "Connie", "Chen,a,f", "Hsiu-Ju", "Chiu,b", "Michelle", "Chiu,a,f", "Thomas", "Clayton,a,d", "Marc", "C.", "Deller,a,d", "Lian", "Duan,a,e", "Kyle", "Ellrott,a,e", "Marc-Andre´", "Elsliger,a,d", "Dustin", "Ernst,a,f", "Carol", "L.", "Farr,a,d", "Julie", "Feuerhelm,a,f", "Anna", "Grzechnik,a,d", "Joanna", "C.", "Grant,a,f", "Kevin", "K.", "Jin,a,b", "Hope", "A.", "Johnson,a,d", "Heath", "E.", "Klock,a,f", "Mark", "W.", "Knuth,a,f", "S.", "Sri", "Krishna,a,c,e", "Abhinav", "Kumar,a,b", "David", "Marciano,a,d", "Daniel", "McMullan,a,f", "Mitchell", "D.", "Miller,a,b", "Andrew", "T.", "Morse,a,e", "Edward", "Nigoghossian,a,f", "Amanda", "Nopakun,a,d", "Linda", "Okach,a,f", "Silvya", "Oommachen,a,b", "Jessica", "Paulsen,a,f", "Christina", "Puckett,a,f", "Ron", "Reyes,a,b", "Christopher", "L.", "Rife,a,b", "Natasha", "Sefcovic,a,c", "Henry", "J.", "Tien,a,d", "Christine", "B.", "Trame,a,b", "Henry", "van", "den", "Bedem,a,b", "Dana", "Weekes,a,c", "Tiffany", "Wooten,a,f", "Qingping", "Xu,a,b", "Keith", "O.", "Hodgson,a,g", "John", "Wooley,a,e", "Ashley", "M.", "Deacon,a,b", "Adam", "Godzik,a,c,e", "Scott", "A.", "Lesleya,d,f", "and", "Ian", "A.", "Wilsona,d*", "aJoint", "Center", "for", "Structural", "Genomics,", "http://www.jcsg.org,", "USA,", "bStanford", "Synchrotron", "Radiation", "Lightsource,", "SLAC", "National", "Accelerator", "Laboratory,", "Menlo", "Park,", "California,", "USA,", "cProgram", "on", "Bioinformatics", "and", "Systems", "Biology,", "Burnham", "Institute", "for", "Medical", "Research,", "La", "Jolla,", "California,", "USA,", "dDepartment", "of", "Molecular", "Biology,", "The", "Scripps", "Research", "Institute,", "La", "Jolla,", "California,", "USA,", "eCenter", "for", "Research", "in", "Biological", "Systems,", "University", "of", "California,", "San", "Diego,", "La", "Jolla,", "California,", "USA,", "fProtein", "Sciences", "Department,", "Genomics", "Institute", "of", "the", "Novartis", "Research", "Foundation,", "San", "Diego,", "California,", "USA,", "and", "gPhoton", "Science,", "SLAC", "National", "Accelerator", "Laboratory,", "Menlo", "Park,", "California,", "USA", "Correspondence", "e-mail:", "wilson@scripps.edu", "Received", "16", "April", "2009", "Accepted", "13", "May", "2009", "PDB", "Reference:", "KPN03535,", "3flz,", "r3f1zsf.", "The", "structure", "of", "KPN03535", "(gi|152972051),", "a", "novel", "putative", "lipoprotein", "from", "Klebsiella", "pneumoniae,", "reveals", "an", "OB-fold", "KPN03535", "(gi|152972051)", "is", "a", "putative", "lipoprotein", "of", "unknown", "function", "that", "is", "secreted", "by", "Klebsiella", "pneumoniae", "MGH", "78578.", "The", "crystal", "structure", "reveals", "that", "despite", "a", "lack", "of", "any", "detectable", "sequence", "similarity", "to", "known", "structures,", "it", "is", "a", "novel", "variant", "of", "the", "OB-fold", "and", "structurally", "similar", "to", "the", "bacterial", "Cpx-", "pathway", "protein", "NlpE,", "single-stranded", "DNA-binding", "(SSB)", "proteins", "and", "toxins.", "K.", "pneumoniae", "MGH", "78578", "forms", "part", "of", "the", "normal", "human", "skin,", "mouth", "and", "gut", "flora", "and", "is", "an", "opportunistic", "pathogen", "that", "is", "linked", "to", "about", "8%", "of", "all", "hospital-acquired", "infections", "in", "the", "USA.", "This", "structure", "provides", "the", "foundation", "for", "further", "investigations", "into", "this", "divergent", "member", "of", "the", "OB-fold", "family.", "1.", "Introduction", "KPN03535", "(gi|152972051)", "is", "an", "orphan", "protein", "that", "is", "exclusively", "found", "in", "Klebsiella", "pneumoniae", "MGH", "78578", "(an", "opportunistic", "human", "pathogen", "belonging", "to", "enterbacteriales", "of", "gammaproteo-", "bacteria;", "Galperin", "et", "al.,", "2007;", "Gill", "et", "al.,", "2006;", "Frank", "&", "Pace,", "2008;", "Ley", "et", "al.,", "2008)", "and", "K.", "pneumoniae", "342", "(three-residue", "substitution).", "It", "consists", "of", "132", "residues", "with", "a", "calculated", "pI", "of", "9.40", "and", "a", "predicted", "signal", "peptide.", "The", "N-terminus", "of", "KPN03535", "has", "a", "lipoprotein", "signature,", "indicated", "by", "the", "presence", "of", "an", "LSGC", "motif", "(von", "Heijne,", "1989),", "as", "well", "as", "predictions", "from", "LipoP", "1.0", "(Juncker", "et", "al.,", "2003).", "It", "is", "a", "singleton", "protein", "that", "has", "not", "been", "assigned", "to", "any", "Pfam", "family,", "but", "sequence-based", "fold-prediction", "methods", "(Ginalski", "et", "al.,", "2003)", "suggest", "similarity", "to", "members", "of", "the", "PF01336", "family", "(OB-fold", "nucleic", "acid-binding", "domain).", "We", "determined", "the", "crystal", "structure", "of", "KPN03535", "in", "order", "to", "explore", "this", "extremely", "divergent", "member", "of", "the", "commonly", "occurring", "OB-fold.", "Structural", "comparisons", "show", "similarities", "to", "the", "OB-fold-containing", "Cpx-pathway", "protein", "NlpE,", "single-stranded", "DNA-binding", "(SSB)", "proteins,", "bacterial", "OB-fold", "(BOF)", "and", "toxin", "proteins,", "which", "enable", "inferences", "about", "function", "that", "may", "now", "be", "tested", "biochemically.", "This", "structure", "should", "serve", "as", "a", "basis", "for", "understanding", "structure–function", "relationships", "in", "any", "newly", "discovered", "proteins", "with", "a", "similar", "sequence,", "such", "as", "those", "identified", "by", "whole", "microbial", "genome", "sequencing", "and", "metagenomic", "surveys", "of", "the", "human", "microbiome.", "2.", "Materials", "and", "methods", "2.1.", "KPN03535", "expression,", "purification", "and", "crystallization", "Clones", "were", "generated", "using", "the", "Polymerase", "Incomplete", "Primer", "Extension", "(PIPE;", "Klock", "et", "al.,", "2008)", "cloning", "method.", "The", "gene", "encoding", "KPN03535", "(gi|152972051;", "Swiss-Prot", "A6TEE6)", "was", "amplified", "by", "polymerase", "chain", "reaction", "(PCR)", "from", "K.", "pneumoniae", "MGH", "78578", "genomic", "DNA", "using", "PfuTurbo", "DNA", "polymerase", "(Stratagene)", "and", "I-PIPE", "(Insert)", "primers", "(forward", "primer,", "50-ctgtac-", "ttccagggcGCTTCTAAAGCCTTTTATTCCGCGGGAG-30;", "reverse", "primer,", "50-aattaagtcgcgttaTTTAACCACCTTGGGATTCTGTAGC-", "GTC-30;", "target", "sequence", "in", "upper", "case)", "that", "included", "sequences", "for", "the", "predicted", "50-", "and", "30-ends.", "The", "expression", "vector,", "pSpeedET,", "which", "encodes", "an", "amino-terminal", "tobacco", "etch", "virus", "(TEV)", "protease-", "cleavable", "expression", "and", "purification", "tag", "(MGSDKIHHHHHHEN-", "1254", "doi:10.1107/S1744309109018168", "Acta", "Cryst.", "(2010).", "F66,", "1254–1260" ]

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[ "Hindawi", "Publishing", "Corporation", "International", "Journal", "of", "Endocrinology", "Volume", "2012,", "Article", "ID", "420370,", "7", "pages", "doi:10.1155/2012/420370", "Research", "Article", "Free", "Triiodothyronine", "and", "Cholesterol", "Levels", "in", "Euthyroid", "Elderly", "T2DM", "Patients", "F.", "Strollo,1", "I.", "Carucci,1", "M.", "More`", ",1", "G.", "Marico,2", "G.", "Strollo,3", "M.", "A.", "Masini,4", "and", "S.", "Gentile2", "1", "Endocrine", "Unit,", "INRCA,", "Via", "Cassia", "1167,", "00189", "Rome,", "Italy", "2", "Department", "of", "Clinical", "and", "Experimental", "Medicine,", "Second", "University", "of", "Naples,", "Via", "Pansini", "5,", "80131", "Naples,", "Italy", "3", "Endocrinology", "and", "Diabetes", "Service,", "FBF", "St.", "Peter’s", "Hospital,", "Via", "Cassia", "600,", "001879", "Rome,", "Italy", "4", "DipTeRis,", "University", "of", "Genoa,", "Viale", "Benedetto", "XV", "3,", "16132", "Genoa,", "Italy", "Correspondence", "should", "be", "addressed", "to", "S.", "Gentile,", "sandro.gentile1@gmail.com", "Received", "30", "March", "2012;", "Revised", "5", "July", "2012;", "Accepted", "23", "July", "2012", "Academic", "Editor:", "Bronwen", "Martin", "Copyright", "©", "2012", "F.", "Strollo", "et", "al.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Thyroid", "function", "regulates", "lipid", "metabolism.", "Despite", "the", "fact", "that", "T2DM", "is", "more", "prevalent", "in", "the", "elderly,", "often", "associates", "with", "thyroid", "dysfunction", "and", "increases", "cardiovascular", "risk", "both", "per", "se", "and", "via", "high", "TC", "and", "LDL-C", "levels,", "the", "association", "of", "the", "latter", "with", "FT3", "and", "FT4", "levels", "has", "not", "yet", "been", "fully", "investigated", "in", "T2DM.", "While", "trying", "to", "fill", "this", "gap", "in", "296", "elderly", "outpatients", "with", "T2DM,", "we", "found", "that", "TC", "and", "LDL-C", "correlated", "negatively", "with", "FT4", "and", "positively", "with", "FT3.", "When", "divided", "according", "to", "treatment", "by", "oral", "hypoglycaemic", "agents", "(OHA)", "and", "insulin", "(IT),", "they", "reacted", "differently", "with", "respect", "to", "investigated", "associations:", "in", "the", "OHA’s", "TC", "and", "LDL-C", "correlated", "negatively", "with", "FT4", "and", "showed", "no", "association", "with", "FT3,", "whereas,", "in", "the", "IT’s", "TC", "and", "LDL-", "C", "correlated", "positively", "with", "FT3", "and", "negatively", "with", "FT4.", "When", "controlled", "for", "possible", "confounding", "factors,", "these", "associations", "did", "not", "change", "in", "the", "IT’s", "but", "were", "missing", "in", "the", "OHA’s.", "Recent", "literature", "reports", "upon", "complex", "hypothalamic", "and", "peripheral", "interactions", "between", "T2DM", "and", "thyroid,", "and", "suggests", "T3", "to", "enhance", "cholesterol", "synthesis", "and", "to", "have", "a", "role", "in", "insulin", "resistance", "states.", "Further", "investigations", "are", "needed", "to", "understand", "the", "intimate", "mechanisms", "of", "lipid", "metabolism", "in", "T2DM", "with", "respect", "to", "thyroid", "function.", "1.", "Introduction", "Thyroid", "function", "affects", "both", "lipid", "profiles", "and", "metabolic", "parameters", "[1].", "Thyroxine", "(T4)", "and", "triiodothyronine", "(T3),", "the", "two", "main", "thyroid", "hormones,", "are", "secreted", "after", "thyroglob-", "ulin", "macropinocytosis", "and", "hydrolysis", "under", "the", "stimulation", "of", "pituitary", "thyrotropin", "(TSH)", "and", "are", "present", "in", "the", "blood", "mainly", "in", "noncovalent", "interactions", "with", "thyroxine-binding", "globulin,", "prealbumin,", "and", "albumin.", "Only", "0.4%", "T3", "and", "0.04%", "T4", "dynamically", "escape", "binding", "and,", "since", "free", "to", "interact", "directly", "with", "peripheral", "organs", "and", "tissues,", "are", "called", "free", "T3", "(FT3)", "and", "free", "T4", "(FT4)", "and", "are", "the", "only", "fractions", "believed", "to", "be", "metabolically", "active", "[2].", "FT4", "levels", "are", "about", "100", "times", "higher", "than", "those", "of", "FT3,", "which", "is", "considered", "to", "be", "the", "most", "active", "form", "of", "thyroid", "hormone", "and", "into", "which", "FT4", "is", "converted", "within", "the", "peripheral", "tissue", "[3].", "Inside", "a", "variety", "of", "cells,", "both", "interact", "with", "different", "affinity", "with", "α1,", "α2,", "β1,", "and", "β2", "nuclear", "receptors", "in", "regulating", "the", "expression", "of", "target", "genes", "through", "the", "so-called", "thyroid", "response", "elements", "(TRE’s),", "thus", "exerting", "the", "typical", "physiological", "functions", "which", "characterize", "them.", "These", "are", "mostly", "represented", "by", "enhanced", "calorigenesis,", "increased", "stroke", "volume", "and", "heart", "rate,", "enhanced", "sensitivity", "to", "catecholamines,", "bone", "turnover,", "gluconeogenesis,", "glycogenolysis,", "and", "lipolysis.", "The", "latter", "is", "mainly", "due", "to", "enhanced", "lipoprotein-lipase", "activity", "and", "increased", "hepatic", "low-density", "lipoprotein", "(LDL)", "receptor", "concentrations", "[4].", "Besides", "genomic", "effects,", "widespread", "rapid", "onset", "nongenomic", "effects", "of", "FT3", "and", "FT4", "have", "been", "reported", "involving", "membrane-signalling", "pathways", "[5],", "the", "real", "extent", "of", "which", "has", "not", "been", "well", "defined", "yet", "[6]." ]

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[ "Inchingolo", "et", "al.", "Head", "&", "Face", "Medicine", "2010,", "6:13", "http://www.head-face-med.com/content/6/1/13", "H", "Y", "P", "O", "T", "H", "E", "S", "I", "S", "HEAD", "&", "FACE", "MEDICINE", "Open", "Access", "HAyphotyhepsisothetical", "correlation", "between", "hyaluronic", "acid", "gel", "and", "development", "of", "cutaneous", "metaplastic", "synovial", "cyst", "Francesco", "Inchingolo*1,", "Marco", "Tatullo2,", "Fabio", "M", "Abenavoli3,", "Massimo", "Marrelli4,", "Alessio", "D", "Inchingolo5,", "Andrea", "Servili6,", "Angelo", "M", "Inchingolo7", "and", "Gianna", "Dipalma8", "Abstract", "Thousands", "of", "patients", "receive", "hyaluronic", "acid", "filler", "injections,", "and", "the", "effects", "are", "generally", "considered", "acceptable.", "The", "acid", "rarely", "causes", "cutaneous", "reactions,", "which", "are", "only", "occasionally", "reported", "in", "the", "literature.", "The", "aim", "of", "the", "present", "work", "is", "to", "analyze", "a", "clinical", "case", "that", "has", "never", "been", "reported", "in", "the", "literature", "to", "our", "knowledge.", "This", "case", "is", "of", "a", "26-year-old", "woman", "who", "presented", "with", "a", "cyst", "in", "the", "infrazygomatic", "region", "that", "was", "injected", "with", "non-animal", "stabilized", "hyaluronic", "acid", "at", "another", "centre", "a", "few", "months", "ago.", "Consequently,", "we", "made", "an", "external", "incision", "to", "remove", "the", "neoplasm:", "histological", "examination", "of", "the", "capsule", "revealed", "it", "to", "be", "a", "cutaneous", "metaplastic", "synovial", "cyst.", "Introduction", "Thousands", "of", "patients", "receive", "hyaluronic", "acid", "filler", "injec-", "tions,", "the", "effects", "of", "which", "are", "generally", "considered", "acceptable.", "However,", "in", "all", "cases,", "the", "product", "is", "regarded", "as", "resorbable,", "and", "the", "risk", "of", "either", "local", "or", "systemic", "toxic", "reactions", "is", "reduced", "[1,2].", "Hyaluronic", "acid", "should", "be", "administered", "with", "caution,", "like", "any", "type", "of", "commonly", "employed", "dermal", "fillers,", "but", "the", "injection", "technique", "can", "be", "easily", "performed", "after", "a", "brief", "learning", "course.", "The", "acid", "rarely", "causes", "cutaneous", "reactions,", "which", "are", "reported", "only", "occasionally", "in", "the", "lit-", "erature.", "Case", "Report", "The", "aim", "of", "the", "present", "work", "is", "to", "analyze", "a", "clinical", "case", "that", "has", "never", "been", "reported", "in", "the", "literature", "to", "our", "knowledge.", "This", "case", "is", "of", "a", "26-year-old", "woman", "who", "pre-", "sented", "with", "a", "cyst", "in", "the", "infrazygomatic", "region", "(FIG.", "1)", "that", "was", "injected", "with", "non-animal", "stabilized", "hyaluronic", "acid", "(NASHA)", "at", "another", "centre", "a", "few", "months", "ago.", "The", "patient", "did", "not", "have", "a", "medical", "history", "of", "cystic", "forma-", "tions", "in", "that", "specific", "region", "before", "NASHA", "injection.", "However,", "the", "cyst", "tended", "to", "increase", "in", "volume", "without", "*", "Correspondence:", "f.inchingolo@doc.uniba.it", "1", "Department", "of", "Dental", "Sciences", "and", "Surgery,", "General", "Hospital,", "Bari,", "Italy", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "any", "painful", "sensation", "or", "appearance", "of", "other", "symptoms.", "We", "performed", "an", "MRI", "that", "revealed", "the", "presence", "of", "a", "cyst", "that", "strongly", "adhered", "to", "the", "bone", "surface.", "Conse-", "quently,", "we", "made", "an", "external", "incision", "to", "remove", "the", "neo-", "plasm.", "In", "the", "subcutis,", "we", "identified", "a", "cyst", "that", "we", "removed", "with", "some", "difficulty", "because", "it", "tenaciously", "adhered", "to", "the", "underlying", "bone", "surface.", "After", "opening", "the", "cyst,", "we", "observed", "a", "thick", "gelatinous", "fluid", "similar", "to", "hyaluronic", "acid", "(FIG.", "2),", "and", "histological", "examination", "of", "the", "capsule", "revealed", "the", "cyst", "to", "be", "a", "cuta-", "neous", "metaplastic", "synovial", "cyst", "(FIG.", "3).", "Cutaneous", "metaplastic", "synovial", "cyst", "is", "a", "rare", "cystic", "tumor", "that", "typically", "presents", "as", "a", "solitary", "tender", "subcuta-", "neous", "nodule.", "Histological", "examination", "revealed", "a", "cystic", "structure", "with", "villous-like", "projections", "and", "a", "lining", "that", "resembled", "hyperplastic", "synovium.", "Discussion", "Injection-site", "reactions", "result", "from", "acute", "inflammatory", "reactions", "in", "response", "to", "tissue", "damage", "after", "drug", "injec-", "tion.", "They", "are", "generally", "short-term", "and", "symptoms", "typi-", "cally", "include", "swelling,", "pain,", "tenderness,", "and", "bruising;", "these", "symptoms", "can", "be", "observed", "in", "most", "patients", "treated", "with", "injectable", "hyaluronic", "acid", "derivatives", "[3].", "Besides,", "the", "overall", "incidence", "of", "long-term", "adverse", "reactions", "sec-", "©", "2010", "Inchingolo", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Com-", "mons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduc-", "tion", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "CLINICS", "2011;66(S1):25-32", "10.1590/S1807-59322011001300004", "Future", "developments", "in", "brain-machine", "interface", "research", "Mikhail", "A.", "Lebedev,I", "Andrew", "J.", "Tate,I,II", "Timothy", "L.", "Hanson,I,II", "Zheng", "Li,I,II", "Joseph", "E.", "O’Doherty,I,II", "Jesse", "A.", "Winans,I", "Peter", "J.", "Ifft,I", "Katie", "Z.", "Zhuang,I", "Nathan", "A.", "Fitzsimmons,I", "David", "A.", "Schwarz,I", "Andrew", "M.", "Fuller,I", "Je", "Hi", "An,I", "Miguel", "A.", "L.", "NicolelisI,III", "I", "Neurobiology,Duke", "University,", "Durham,", "NC,", "USA.", "II", "Duke", "University", "Center", "for", "Neuroengineering,", "Duke", "University,", "Durham,", "NC,", "USA.", "III", "Edmond", "and", "Lily", "Safra", "International", "Institute", "of", "Neuroscience", "of", "Natal", "Neuroprosthetic", "devices", "based", "on", "brain-machine", "interface", "technology", "hold", "promise", "for", "the", "restoration", "of", "body", "mobility", "in", "patients", "suffering", "from", "devastating", "motor", "deficits", "caused", "by", "brain", "injury,", "neurologic", "diseases", "and", "limb", "loss.", "During", "the", "last", "decade,", "considerable", "progress", "has", "been", "achieved", "in", "this", "multidisciplinary", "research,", "mainly", "in", "the", "brain-machine", "interface", "that", "enacts", "upper-limb", "functionality.", "However,", "a", "considerable", "number", "of", "problems", "need", "to", "be", "resolved", "before", "fully", "functional", "limb", "neuroprostheses", "can", "be", "built.", "To", "move", "towards", "developing", "neuroprosthetic", "devices", "for", "humans,", "brain-machine", "interface", "research", "has", "to", "address", "a", "number", "of", "issues", "related", "to", "improving", "the", "quality", "of", "neuronal", "recordings,", "achieving", "stable,", "long-term", "performance,", "and", "extending", "the", "brain-machine", "interface", "approach", "to", "a", "broad", "range", "of", "motor", "and", "sensory", "functions.", "Here,", "we", "review", "the", "future", "steps", "that", "are", "part", "of", "the", "strategic", "plan", "of", "the", "Duke", "University", "Center", "for", "Neuroengineering,", "and", "its", "partners,", "the", "Brazilian", "National", "Institute", "of", "Brain-Machine", "Interfaces", "and", "the", "E´cole", "Polytechnique", "F", "e´de´", "rale", "de", "Lausanne", "(EPFL)", "Center", "for", "Neuroprosthetics,", "to", "bring", "this", "new", "technology", "to", "clinical", "fruition.", "KEYWORDS:", "Brain-machine", "interface;", "Neuroprosthetic;", "Primate;", "Bipedal", "locomotion;", "Intracortical", "microstimulation;", "Sensory", "substitution.", "Lebedev", "MA,", "Tate", "AJ,", "Hanson", "TL,", "Li", "Z,", "O’Doherty", "JE,", "Winans", "JA,", "Ifft", "PJ,", "Zhuang", "KZ,", "Fitzsimmons", "NA,", "Schwarz", "DA,", "Fuller", "AM,", "An", "JH,", "Nicolelis", "MAL.", "Future", "developments", "in", "brain-machine", "interface", "research.", "Clinics.", "2011;66(S1):25-32.", "Received", "for", "publication", "on", "January", "28,", "2011;", "Accepted", "for", "publicaiton", "on", "January", "30,", "2011", "E-mail:", "nicoleli@neuro.duke.edu", "Tel.:", "919", "684", "4580", "INTRODUCTION", "Millions", "of", "people", "worldwide", "suffer", "from", "sensorimotor", "deficits", "caused", "by", "neurologic", "injuries,", "diseases", "or", "limb", "loss.", "According", "to", "recent", "data", "reported", "in", "Medical", "News", "Today,", "five", "million", "people", "in", "the", "USA", "alone", "currently", "suffer", "from", "some", "type", "of", "severe", "body", "paralysis.1", "Currently,", "there", "is", "no", "cure", "for", "such", "devastating", "cases", "of", "paralysis,", "for", "example", "complete", "spinal", "cord", "injury", "(SCI).2", "Meanwhile,", "treatment", "is", "only", "partially", "effective", "in", "less", "severe", "cases.3", "Neural", "prosthetic", "devices", "based", "on", "brain-machine", "interfaces", "(BMIs)", "hold", "promise", "to", "restore", "both", "partial", "and", "full", "body", "mobility", "in", "paralyzed", "patients.4–10", "BMIs", "bypass", "the", "site", "of", "the", "neural", "lesion", "and", "connect", "the", "remaining", "healthy", "motor", "areas", "of", "the", "brain,", "particularly", "the", "motor", "cortex,", "directly", "to", "assistive", "and", "prosthetic", "devices", "that", "can", "take", "the", "shape", "of,", "for", "example,", "robotic", "limbs", "or", "a", "full", "body", "exoskeleton.", "The", "main", "idea", "behind", "BMIs", "is", "to", "employ", "the", "activity", "of", "healthy", "motor", "brain", "areas,", "which", "in", "many", "cases", "of", "paralysis", "remain", "capable", "of", "generating", "motor", "commands", "despite", "being", "disconnected", "from", "the", "body", "effectors,11", "to", "control", "artificial", "tools", "that", "restore", "the", "patient’s", "mobility.", "Copyright", "2011", "CLINICS", "–", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "Non-Commercial", "License", "(http://", "creativecommons.org/licenses/by-nc/3.0/)", "which", "permits", "unrestricted", "non-", "commercial", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "25", "During", "the", "last", "decade,", "the", "field", "of", "BMIs", "has", "experienced", "an", "explosive", "development.7,9", "Hence,", "it", "has", "generated", "high", "expectations", "among", "neuroscientists,", "physicians", "and", "patients", "alike,", "regarding", "its", "potential", "clinical", "applications.", "A", "number", "of", "BMI", "systems", "have", "been", "studied", "in", "rodents12", "and", "nonhuman", "primates.13–17", "BMI", "technology", "also", "entered", "human", "clinical", "research", "where", "both", "non-invasive", "EEG-", "based", "systems5,18,19", "and", "invasive", "BMIs", 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[ "Hindawi", "Publishing", "Corporation", "Clinical", "and", "Developmental", "Immunology", "Volume", "2011,", "Article", "ID", "439752,", "7", "pages", "doi:10.1155/2011/439752", "Review", "Article", "The", "Confluence", "of", "Stereotactic", "Ablative", "Radiotherapy", "and", "Tumor", "Immunology", "Steven", "Eric", "Finkelstein,1", "Robert", "Timmerman,2", "William", "H.", "McBride,3", "Do¨rthe", "Schaue,3", "Sarah", "E.", "Hoffe,4", "Constantine", "A.", "Mantz,1", "and", "George", "D.", "Wilson5", "1", "21st", "Century", "Oncology", "Translational", "Research", "Consortium,", "Scottsdale,", "AZ", "85251,", "USA", "2", "Department", "of", "Radiation", "Oncology", "and", "Neurologic", "Surgery,", "University", "of", "Texas", "Southwestern", "Medical", "Center,", "Dallas,", "TX", "75391,", "USA", "3", "Department", "of", "Radiation", "Oncology,", "David", "Geffen", "School", "of", "Medicine", "at", "UCLA,", "Los", "Angeles,", "CA", "90095,", "USA", "4", "Department", "of", "Radiation", "Oncology,", "Moffitt", "International,", "Tampa,", "FL", "33612,", "USA", "5", "Division", "of", "Radiation", "Biology,", "William", "Beaumont", "Hospital,", "Royal", "Oak,", "MI", "48073,", "USA", "Correspondence", "should", "be", "addressed", "to", "Steven", "Eric", "Finkelstein,", "sfinkels@rtsx.com", "Received", "25", "August", "2011;", "Accepted", "5", "September", "2011", "Academic", "Editor:", "Luca", "Gattinoni", "Copyright", "©", "2011", "Steven", "Eric", "Finkelstein", "et", "al.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Stereotactic", "radiation", "approaches", "are", "gaining", "more", "popularity", "for", "the", "treatment", "of", "intracranial", "as", "well", "as", "extracranial", "tumors", "in", "organs", "such", "as", "the", "liver", "and", "lung.", "Technology,", "rather", "than", "biology,", "is", "driving", "the", "rapid", "adoption", "of", "stereotactic", "body", "radiation", "therapy", "(SBRT),", "also", "known", "as", "stereotactic", "ablative", "radiotherapy", "(SABR),", "in", "the", "clinic", "due", "to", "advances", "in", "precise", "positioning", "and", "targeting.", "Dramatic", "improvements", "in", "tumor", "control", "have", "been", "demonstrated;", "however,", "our", "knowledge", "of", "normal", "tissue", "biology", "response", "mechanisms", "to", "large", "fraction", "sizes", "is", "lacking.", "Herein,", "we", "will", "discuss", "how", "SABR", "can", "induce", "cellular", "expression", "of", "MHC", "I,", "adhesion", "molecules,", "costimulatory", "molecules,", "heat", "shock", "proteins,", "inflammatory", "mediators,", "immunomodulatory", "cytokines,", "and", "death", "receptors", "to", "enhance", "antitumor", "immune", "responses.", "1.", "Introduction", "Stereotactic", "radiosurgery", "(SRS)", "was", "originally", "developed", "for", "the", "treatment", "of", "intracranial", "tumors", "and", "has", "demonstrated", "clinical", "effectiveness", "in", "treating", "a", "variety", "of", "benign", "and", "malignant", "conditions.", "Its", "extracranial", "counterpart,", "stereotac-", "tic", "body", "radiation", "therapy", "(SBRT),", "also", "known", "as", "stereotactic", "ablative", "radiotherapy", "(SABR),", "has", "more", "recently", "shown", "efficacy", "for", "the", "treatment", "of", "tumors", "in", "organs", "such", "as", "the", "liver", "and", "lung.", "The", "potential", "for", "using", "SABR", "is", "likely", "greater", "than", "for", "SRS", "given", "the", "larger", "volume", "of", "potential", "indications", "outside", "the", "central", "nervous", "system.", "Technology,", "rather", "than", "biology,", "is", "driving", "the", "rapid", "adoption", "of", "SABR", "in", "the", "clinic", "due", "to", "advances", "in", "precise", "positioning,", "motion", "control,", "dosimetry,", "and", "precise", "targeting", "with", "image", "guid-", "ance.", "Dramatic", "improvements", "in", "tumor", "control", "have", "been", "demonstrated", "in", "several", "studies", "due", "to", "the", "demonstration", "that", "very", "potent", "dose", "can", "be", "delivered", "by", "use", "of", "the", "mentioned", "technology.", "However,", "our", "knowledge", "of", "normal", "tissue", "biology", "response", "mechanisms", "to", "large", "fraction", "sizes", "is", "relatively", "lacking", "compared", "to", "conventional", "fractionation.", "2.", "Radiobiologic", "Considerations", "A", "fundamental", "issue", "in", "SABR", "is", "whether", "classical", "radiobi-", "ologic", "modeling", "with", "the", "linear-quadratic", "(LQ)", "model", "is", "a", "valid", "method", "to", "assess", "the", "biologically", "effective", "dose", "at", "the", "high", "doses", "typically", "encountered", "in", "radiosurgery.", "This", "point", "was", "debated", "in", "back-to-back", "papers", "in", "seminars", "in", "radiation", "oncology", "[1,", "2],", "where", "Brenner", "argued", "that", "LQ", "formalism", "was", "appropriate", "whilst", "Kirkpatrick", "and", "colleagues", "suggested", "it", "was", "inappropriate.", "Brenner’s", "argument", "is", "based", "on", "the", "robustness", "of", "the", "LQ", "model", "to", "predict", "fractionation", "and", "dose-rate", "effects", "in", "experimental", "models", "in", "vitro", "and", "in", "vivo", "at", "doses", "up", "to", "10", "Gy.", "This", "conclusion", "is", "based", "on", "the", "premise", "that", "cell", "killing", "is", "the", "dominant", "process", "mediating", "the", "radiotherapeutic", "response", "for", "both", "early", "and", "late", "effects", "including", "vascular", "effects.", "Brenner", "argued", "that,", "to", "date,", "there" ]

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[ "Reproductive", "Health", "Research", "Religiosity", "and", "teen", "birth", "rate", "in", "the", "United", "States", "Joseph", "M", "Strayhorn*1,2", "and", "Jillian", "C", "Strayhorn3", "BioMed", "Central", "Open", "Access", "Address:", "1Drexel", "University", "College", "of", "Medicine,", "Department", "of", "Psychiatry,", "2900", "W.", "Queen", "Lane,", "Philadelphia,", "PA", "19129,", "2University", "of", "Pittsburgh", "School", "of", "Medicine,", "Department", "of", "Psychiatry,", "3811", "O'Hara", "Street,", "Pittsburgh,", "PA", "15213", "and", "3263", "Seasons", "Drive,", "Wexford,", "Pennsylvania", "15090,", "USA", "Email:", "Joseph", "M", "Strayhorn*", "-", "joestrayhorn@gmail.com;", "Jillian", "C", "Strayhorn", "-", "jillianstrayhorn@gmail.com", "*", "Corresponding", "author", "Published:", "17", "September", "2009", "Reproductive", "Health", "2009,", "6:14", "doi:10.1186/1742-4755-6-14", "Received:", "28", "April", "2009", "Accepted:", "17", "September", "2009", "This", "article", "is", "available", "from:", "http://www.reproductive-health-journal.com/content/6/1/14", "©", "2009", "Strayhorn", "and", "Strayhorn;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Background:", "The", "children", "of", "teen", "mothers", "have", "been", "reported", "to", "have", "higher", "rates", "of", "several", "unfavorable", "mental", "health", "outcomes.", "Past", "research", "suggests", "several", "possible", "mechanisms", "for", "an", "association", "between", "religiosity", "and", "teen", "birth", "rate", "in", "communities.", "Methods:", "The", "present", "study", "compiled", "publicly", "accessible", "data", "on", "birth", "rates,", "conservative", "religious", "beliefs,", "income,", "and", "abortion", "rates", "in", "the", "U.S.,", "aggregated", "at", "the", "state", "level.", "Data", "on", "teen", "birth", "rates", "and", "abortion", "originated", "from", "the", "Center", "for", "Disease", "Control;", "on", "income,", "from", "the", "U.S.", "Bureau", "of", "the", "Census,", "and", "on", "religious", "beliefs,", "from", "the", "U.S.", "Religious", "Landscape", "Survey", "carried", "out", "by", "the", "Pew", "Forum", "on", "Religion", "and", "Public", "Life.", "We", "computed", "correlations", "and", "partial", "correlations.", "Results:", "Increased", "religiosity", "in", "residents", "of", "states", "in", "the", "U.S.", "strongly", "predicted", "a", "higher", "teen", "birth", "rate,", "with", "r", "=", "0.73", "(p", "<", "0.0005).", "Religiosity", "correlated", "negatively", "with", "median", "household", "income,", "with", "r", "=", "-0.66,", "and", "income", "correlated", "negatively", "with", "teen", "birth", "rate,", "with", "r", "=", "-0.63.", "But", "the", "correlation", "between", "religiosity", "and", "teen", "birth", "rate", "remained", "highly", "significant", "when", "income", "was", "controlled", "for", "via", "partial", "correlation:", "the", "partial", "correlation", "between", "religiosity", "and", "teen", "birth", "rate,", "controlling", "for", "income,", "was", "0.53", "(p", "<", "0.0005).", "Abortion", "rate", "correlated", "negatively", "with", "religiosity,", "with", "r", "=", "-0.45,", "p", "=", "0.002.", "However,", "the", "partial", "correlation", "between", "teen", "birth", "rate", "and", "religiosity", "remained", "high", "and", "significant", "when", "controlling", "for", "abortion", "rate", "(partial", "correlation", "=", "0.68,", "p", "<", "0.0005)", "and", "when", "controlling", "for", "both", "abortion", "rate", "and", "income", "(partial", "correlation", "=", "0.54,", "p", "=", "0.001).", "Conclusion:", "With", "data", "aggregated", "at", "the", "state", "level,", "conservative", "religious", "beliefs", "strongly", "predict", "U.S.", "teen", "birth", "rates,", "in", "a", "relationship", "that", "does", "not", "appear", "to", "be", "the", "result", "of", "confounding", "by", "income", "or", "abortion", "rates.", "One", "possible", "explanation", "for", "this", "relationship", "is", "that", "teens", "in", "more", "religious", "communities", "may", "be", "less", "likely", "to", "use", "contraception.", "Background", "The", "children", "of", "teen", "mothers", "in", "the", "U.S.,", "on", "the", "average,", "have", "worse", "outcomes", "in", "a", "number", "of", "ways.", "They", "score", "lower", "in", "school", "achievement", "tests,", "have", "a", "greater", "likeli-", "hood", "of", "repeating", "a", "grade,", "are", "rated", "more", "unfavorably", "by", "teachers", "while", "in", "high", "school,", "have", "worse", "physical", "health,", "are", "more", "likely", "to", "be", "indicated", "victims", "of", "abuse", "and", "neglect,", "have", "higher", "durations", "of", "foster", "care", "placement,", "Page", "1", "of", "7", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Comparison", "of", "CT-Guided", "Sclerotherapy", "with", "Using", "95%", "Ethanol", "and", "20%", "Hypertonic", "Saline", "for", "Managing", "Simple", "Renal", "Cyst", "Hulusi", "Egilmez,", "MD1", "Vedat", "Gok,", "MD1", "Ibrahim", "Oztoprak,", "MD1", "Mehmet", "Atalar,", "MD1", "Ali", "Cetin,", "MD2", "Mubeccel", "Arslan,", "MD1", "Yener", "Gultekin,", "MD3", "Orhan", "Solak,", "MD1", "Index", "terms", ":", "Kidney,", "cyst", "Kidney,", "interventional", "procedures", "Sclerotherapy", "Alcohol", "Kidney,", "CT", "Korean", "J", "Radiol", "2007;8:512-519", "Received", "July", "2,", "2006;", "accepted", "after", "revision", "December", "27,", "2006.", "Departments", "of", "1Radiology,", "2Obstetrics", "and", "Gynecology,", "and", "3Urology,", "Cumhuriyet", "University", "School", "of", "Medicine,", "58140", "Sivas,", "Turkey", "Address", "reprint", "requests", "to:", "Hulusi", "Egilmez,", "MD,", "Department", "of", "Radiology,", "Cumhuriyet", "University", "School", "of", "Medicine,", "58140", "Sivas,", "Turkey.", "Tel.", "+346", "2191300", "Fax.", "+346", "2191284", "e-mail:", "hegilmez@cumhuriyet.edu.tr", "512", "Objective:", "We", "wanted", "to", "compare", "the", "efficacies", "of", "95%", "ethanol", "and", "20%", "hypertonic", "saline", "(HS)", "sclerotherapies", "that", "were", "performed", "in", "a", "single", "session", "under", "CT", "guidance", "for", "the", "management", "of", "simple", "renal", "cysts.", "Materials", "and", "Methods:", "A", "prospective", "series", "of", "74", "consecutive", "patients", "(aver-", "age", "age:", "57.6", "8.1", "years)", "with", "simple", "renal", "cysts", "were", "enrolled", "in", "this", "study.", "They", "were", "randomized", "into", "two", "groups", "and", "95%", "ethanol", "or", "20%", "HS,", "respective-", "ly,", "corresponding", "to", "25%", "of", "the", "aspiration", "volume,", "was", "injected.", "Treatment", "suc-", "cess", "was", "determined", "six", "months", "later", "with", "follow-up", "clinical", "evaluation", "and", "per-", "forming", "ultrasonography.", "Results:", "The", "sclerotherapy", "was", "accepted", "as", "technically", "successful", "without", "major", "complications", "in", "all", "except", "two", "patients", "who", "were", "excluded", "because", "of", "a", "communication", "between", "the", "simple", "renal", "cyst", "and", "the", "pelvicalyceal", "collecting", "system.", "Thirty-six", "patients", "in", "the", "ethanol", "group", "received", "sclerotherapy", "with", "95%", "ethanol", "and", "36", "patients", "in", "the", "HS", "group", "underwent", "sclerotherapy", "with", "20%", "HS.", "The", "complete", "regression", "ratio", "of", "the", "ethanol", "group", "was", "significantly", "higher", "(94%", "versus", "72%,", "respectively)", "than", "that", "of", "the", "HS", "group.", "There", "was", "one", "patient", "with", "partial", "regression", "in", "each", "group.", "The", "failure", "ratio", "of", "the", "ethanol", "group", "was", "signifi-", "cantly", "lower", "(3%", "versus", "25%,", "respectively)", "than", "that", "of", "the", "HS", "group.", "Conclusion:", "Ethanol", "sclerotherapy", "under", "CT", "guidance", "is", "a", "successful", "and", "safe", "procedure", "and", "it", "can", "be", "used", "for", "the", "treatment", "of", "simple", "renal", "cysts.", "Sclerotherapy", "with", "95%", "ethanol", "is", "more", "effective", "than", "20%", "HS", "sclerotherapy.", "Sclerotherapy", "with", "HS", "may", "be", "an", "option", "for", "patients", "preferring", "to", "undergo", "a", "less", "painful", "treatment", "procedure.", "S", "for", "approximately", "65", "to", "70%", "of", "all", "of", "them", "(1).", "They", "often", "occur", "in", "imple", "renal", "cysts", "are", "the", "most", "common", "renal", "masses,", "and", "they", "account", "patients", "over", "the", "age", "of", "50", "as", "has", "been", "determined", "with", "performing", "postmortem", "examination", "or", "renal", "ultrasonography", "(US)", "(2,", "3).", "Simple", "renal", "cysts", "are", "often", "incidentally", "discovered", "on", "US,", "CT", "or", "urography", "examinations", "that", "are", "performed", "for", "urinary", "tract", "problems", "or", "other", "abdominal", "problems.", "The", "characteristic", "appearance", "of", "simple", "renal", "cysts", "on", "US,", "CT", "and", "magnetic", "resonance", "imaging", "allows", "the", "radiologist", "to", "make", "an", "accurate", "diagnosis.", "US", "is", "commonly", "used", "to", "exclude", "the", "possibility", "of", "benign", "or", "malignant", "pathology", "because", "the", "kidney", "is", "readily", "accessible", "for", "US", "examination", "(4).", "A", "small", "proportion", "of", "simple", "renal", "cysts", "may", "be", "associated", "with", "symptoms,", "of", "which", "pain", "is", "the", "commonest.", "Hematuria,", "hypertension,", "pelvicalyceal", "obstruction", "and", "cyst", "rupture", "are", "less", "common", "symptoms", "(2).", "When", "cysts", "are", "very", "large,", "they", "may", "produce", "the", "mechanical", "effects", "of", "a", "space-occupying", "lesion.", "Percutaneous", "or", "surgical", "interven-", "Korean", "J", "Radiol", "8(6),", "December", "2007" ]

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[ "BMC", "Health", "Services", "Research", "Research", "article", "Developing", "evidence-based", "clinical", "practice", "guidelines", "in", "hospitals", "in", "Australia,", "Indonesia,", "Malaysia,", "the", "Philippines", "and", "Thailand:", "values,", "requirements", "and", "barriers", "Tari", "J", "Turner", "BioMed", "Central", "Open", "Access", "Address:", "Monash", "Institute", "of", "Health", "Services", "Research,", "Monash", "University,", "Monash", "Medical", "Centre,", "Clayton,", "Victoria,", "Australia", "Email:", "Tari", "J", "Turner", "-", "tari.turner@med.monash.edu.au", "Published:", "15", "December", "2009", "BMC", "Health", "Services", "Research", "2009,", "9:235", "doi:10.1186/1472-6963-9-235", "This", "article", "is", "available", "from:", "http://www.biomedcentral.com/1472-6963/9/235", "Received:", "19", "May", "2009", "Accepted:", "15", "December", "2009", "©", "2009", "Turner;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Background:", "Evidence-based", "clinical", "practice", "guidelines", "support", "clinical", "decision-making", "by", "making", "recommendations", "to", "guide", "clinical", "practice.", "These", "recommendations", "are", "developed", "by", "integrating", "the", "expertise", "of", "a", "multidisciplinary", "group", "of", "clinicians", "with", "the", "perspectives", "of", "consumers", "and", "the", "best", "available", "research", "evidence.", "However", "studies", "have", "raised", "concerns", "about", "the", "quality", "of", "guideline", "development,", "and", "particularly", "the", "link", "between", "research", "and", "recommendations.", "The", "reasons", "why", "guideline", "developers", "are", "not", "following", "the", "established", "development", "methods", "are", "not", "clear.", "We", "aimed", "to", "explore", "the", "barriers", "to", "developing", "evidence-based", "guidelines", "in", "eleven", "hospitals", "in", "Australia,", "Indonesia,", "Malaysia,", "the", "Philippines", "and", "Thailand,", "so", "as", "to", "better", "understand", "how", "evidence-based", "guideline", "development", "could", "be", "facilitated", "in", "these", "settings.", "The", "research", "aimed", "to", "identify", "the", "value", "clinicians", "place", "on", "guidelines,", "what", "clinicians", "want", "in", "guidelines", "developed", "in", "hospital", "settings", "and", "what", "factors", "limit", "rigorous", "evidence-based", "guideline", "development", "in", "these", "settings.", "Methods:", "Semi-structured,", "face-to-face", "interviews", "were", "undertaken", "with", "senior", "and", "junior", "healthcare", "providers", "(nurses,", "midwives,", "doctors,", "allied", "health)", "from", "the", "maternal", "and", "neonatal", "services", "of", "the", "eleven", "participating", "hospitals.", "Interviews", "were", "audio-recorded,", "transcribed", "and", "a", "thematic", "analysis", "undertaken.", "Results:", "Ninety-three", "individual,", "25", "pair", "and", "eleven", "group", "interviews", "were", "conducted.", "Participants", "were", "clear", "that", "they", "want", "guidelines", "that", "are", "based", "on", "evidence", "and", "updated", "regularly.", "They", "were", "also", "clear", "that", "there", "are", "major", "barriers", "to", "this.", "Most", "of", "the", "barriers", "were", "shared", "across", "countries,", "and", "included", "lack", "of", "time,", "lack", "of", "skills", "in", "finding,", "appraising", "and", "interpreting", "evidence,", "lack", "of", "access", "to", "relevant", "evidence", "and", "difficulty", "arranging", "meetings", "and", "achieving", "consensus.", "Barriers", "that", "were", "primarily", "identified", "in", "Australian", "hospitals", "include", "cumbersome", "organisational", "processes", "and", "a", "feeling", "that", "guidelines", "are", "being", "developed", "for", "bureaucratic", "ends.", "Barriers", "that", "were", "primarily", "identified", "in", "South", "East", "Asian", "hospitals", "include", "difficulty", "accessing", "evidence", "due", "to", "limited", "resources", "available", "for", "computers,", "internet", "and", "journal", "subscriptions", "and", "limited", "skills", "in", "computing", "and", "English.", "Conclusions:", "The", "clinicians", "in", "these", "eleven", "very", "different", "hospitals", "want", "evidence-based", "guidelines.", "However", "they", "are", "frustrated", "by", "guideline", "development", "processes", "that", "are", "enormously", "time,", "skill", "and", "resource", "intensive.", "They", "feel", "strongly", "that", "\"there's", "got", "to", "be", "a", "better", "way\".", "The", "fact", "that", "the", "great", "majority", "of", "the", "identified", "barriers", "were", "shared", "across", "settings", "may", "provide", "an", "opportunity", "to", "develop", "a", "more", "pragmatic", "way", "of", "developing", "guidelines", "that", "can", "be", "applied", "in", "many", "contexts.", "Page", "1", "of", "7", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "4168–4177", "Nucleic", "Acids", "Research,", "2012,", "Vol.", "40,", "No.", "9", "doi:10.1093/nar/gkr1231", "Published", "online", "5", "January", "2012", "Visualization", "of", "a", "DNA-PK/PARP1", "complex", "Laura", "Spagnolo1,2,*,", "Jody", "Barbeau", "3", ",", "Nicola", "J.", "Curtin3,", "Edward", "P.", "Morris4", "and", "Laurence", "H.", "Pearl1,5", "1Cancer", "Research", "UK", "DNA", "Repair", "Enzymes", "Group,", "The", "Institute", "of", "Cancer", "Research,", "London", "SW3", "6JB,", "2Institute", "of", "Structural", "Molecular", "Biology,", "University", "of", "Edinburgh,", "EH9", "3JR,", "3Northern", "Institute", "for", "Cancer", "Research,", "Medical", "School,", "Newcastle", "University,", "Newcastle", "upon", "Tyne,", "4Structural", "Electron", "Microscopy", "Group,", "Section", "of", "Structural", "Biology,", "The", "Institute", "of", "Cancer", "Research,", "London", "SW3", "6JB", "and", "5School", "of", "Life", "Sciences,", "University", "of", "Sussex,", "Brighton,", "BN1", "9RH,", "UK", "Received", "June", "16,", "2011;", "Revised", "November", "23,", "2011;", "Accepted", "November", "24,", "2011", "ABSTRACT", "The", "DNA-dependent", "protein", "kinase", "(DNA-PK)", "and", "Poly(ADP-ribose)", "polymerase-1", "(PARP1)", "are", "critical", "enzymes", "that", "reduce", "genomic", "damage", "caused", "by", "DNA", "lesions.", "They", "are", "both", "activated", "by", "DNA", "strand", "breaks", "generated", "by", "physiological", "and", "envir-", "onmental", "factors,", "and", "they", "have", "been", "shown", "to", "interact.", "Here,", "we", "report", "in", "vivo", "evidence", "that", "DNA-PK", "and", "PARP1", "are", "equally", "necessary", "for", "rapid", "repair.", "We", "purified", "a", "DNA-PK/PARP1", "complex", "loaded", "on", "DNA", "and", "performed", "electron", "microscopy", "and", "single", "particle", "analysis", "on", "its", "tetra-", "meric", "and", "dimer-of-tetramers", "forms.", "By", "comparison", "with", "the", "DNA-PK", "holoenzyme", "and", "fitting", "crystal-", "lographic", "structures,", "we", "see", "that", "the", "PARP1", "density", "is", "in", "close", "contact", "with", "the", "Ku", "subunit.", "Crucially,", "PARP1", "binding", "elicits", "substantial", "con-", "formational", "changes", "in", "the", "DNA-PK", "synaptic", "dimer", "assembly.", "Taken", "together,", "our", "data", "support", "a", "func-", "tional,", "in-pathway", "role", "for", "DNA-PK", "and", "PARP1", "in", "double-strand", "break", "(DSB)", "repair.", "We", "also", "propose", "a", "NHEJ", "model", "where", "protein–protein", "interactions", "alter", "substantially", "the", "architecture", "of", "DNA-PK", "dimers", "at", "DSBs,", "to", "trigger", "subsequent", "interactions", "or", "enzymatic", "reactions.", "INTRODUCTION", "DNA", "double-strand", "breaks", "(DSBs)", "are", "the", "most", "cytotoxic", "form", "of", "DNA", "damage.", "If", "unrepaired", "or", "incorrectly", "repaired,", "they", "can", "lead", "to", "apoptosis", "or", "genome", "instability.", "Two", "major", "DSB", "repair", "pathways", "exist:", "homologous", "recombination", "(HR)", "and", "non-homologous", "end", "joining", "(NHEJ)", "(1).", "In", "the", "presence", "of", "sister", "chromatids", "acting", "as", "templates", "for", "repair,", "DSBs", "can", "be", "repaired", "by", "HR.", "In", "NHEJ,", "the", "DNA", "broken", "ends", "are", "resected", "and/or", "pro-", "cessed", "and", "the", "DNA", "backbones", "ligated", "to", "restore", "strand", "continuity", "without", "the", "need", "for", "a", "template.", "The", "DNA-dependent", "protein", "kinase", "(DNA-PK)", "heterotrimeric", "enzyme", "is", "the", "early", "player", "in", "mammalian", "NHEJ", "(2).", "DNA-PK", "is", "formed", "by", "a", "DSB", "recognition", "module,", "called", "Ku", "(preassembled", "as", "a", "heterodimer", "of", "the", "Ku70", "and", "Ku80", "proteins)", "(3)", "and", "a", "large", "catalytic", "subunit", "(DNA-PKcs,", "0.5", "MDa)", "(4,5).", "After", "recognizing", "and", "binding", "to", "a", "DSB,", "Ku", "recruits", "the", "catalytic", "subunit", "via", "the", "C-terminal", "domain", "of", "the", "Ku80", "subunit.", "DNA-PKcs", "is", "a", "serine/threonine", "kinase", "belonging", "to", "the", "phosphatidylinositol-3-OH", "kinase", "(PI3K)-related", "(PIKK)", "family.", "DNA-PK", "assembles", "on", "DNA", "as", "a", "bridging", "complex,", "where", "two", "heterotrimers", "maintain", "the", "two", "DNA", "broken", "ends", "in", "close", "proximity,", "providing", "a", "scaf-", "folding", "platform", "to", "recruit", "further", "NHEJ", "enzymes", "(6).", "These", "factors", "include", "Artemis", "and", "PNK,", "which", "are", "required", "to", "process", "the", "broken", "ends;", "X", "family", "polymer-", "ases,", "which", "promote", "microhomology", "and", "cohesion", "between", "the", "broken", "ends;", "DNA", "ligase", "IV-XRCC4,", "which", "closes", "the", "phospho-diester", "backbone", "on", "both", "strands,", "and", "the", "XLF/Cernunnos", "factor", "(7).", "Autophos-", "phorylation", "sites,", "crucial", "to", "NHEJ", "regulation,", "have", "been", "identified", "in", "DNA-PKcs", "at", "two", "main", "clusters,", "as", "well", "as", "within", "its", "catalytic", "domain", "(7).", "A", "recent", "electron", "micros-", "copy", "study", "visualized", "a", "substantial", "remodeling", "of", "DNA-PK", "on", "autophosphorylation", "(8).", "PARP", "enzymes", "use", "nicotinamide", "as", "a", "substrate", "to", "polymerize", "ADP-ribose", "moieties", "onto", "target", "proteins,", "a", "process", "called", "poly-ADP-ribosylation", "(or", "PARylation)", "(9).", "The", "best-studied", "PARP", "enzyme", "is", "PARP1,", "which", "has", "a", "key", "role", "in", "DNA", "repair", "and", "in", "particular", "single-", "strand", "break", "repair/base", "excision", "repair", "(10).", "PARP1", "detects", "and", "binds", "single", "strand", "DNA", "breaks", "and", "then", "poly-ADP-ribosylates", "itself", "(auto-PARylation)", "and", "other", "*To", "whom", "correspondence", "should", "be", "addressed.", "Tel.", "+44", "0", "131", "650", "7066;", "Fax", "+44", "0", "131", "650", "8650;", "Email:", "laura.spagnolo@ed.ac.uk", "The", "Author(s)", "2012.", "Published", "by", "Oxford", "University", "Press.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "Non-Commercial", "License", "(http://creativecommons.org/licenses/", "by-nc/3.0),", "which", "permits", "unrestricted", "non-commercial", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Hindawi", "Publishing", "Corporation", "Journal", "of", "Transplantation", "Volume", "2012,", "Article", "ID", "201754,", "7", "pages", "doi:10.1155/2012/201754", "Research", "Article", "Antibody-Mediated", "Rejection:", "Pathogenesis,", "Prevention,", "Treatment,", "and", "Outcomes", "Olivia", "R.", "Blume,1", "Sarah", "E.", "Yost,2", "and", "Bruce", "Kaplan3", "1", "Abdominal", "Transplantation,", "University", "of", "Arizona", "Medical", "Center,", "Tucson,", "AZ,", "USA", "2", "Abdominal", "Transplantation,", "Department", "of", "Pharmacy,", "University", "of", "Arizona", "Medical", "Center,", "Tucson,", "AZ,", "USA", "3", "University", "of", "Arizona", "College", "of", "Medicine,", "1501", "North", "Campbell", "Avenue,", "Tucson,", "AZ", "85724,", "USA", "Correspondence", "should", "be", "addressed", "to", "Olivia", "R.", "Blume,", "olivia.blume@uahealth.com", "Received", "19", "October", "2011;", "Revised", "4", "November", "2011;", "Accepted", "28", "December", "2011", "Academic", "Editor:", "Banu", "Sis", "Copyright", "©", "2012", "Olivia", "R.", "Blume", "et", "al.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Antibody-mediated", "rejection", "(AMR)", "is", "a", "major", "cause", "of", "late", "kidney", "transplant", "failure.", "It", "is", "important", "to", "have", "an", "understanding", "of", "human-leukocyte", "antigen", "(HLA)", "typing", "including", "well-designed", "studies", "to", "determine", "anti-MHC-class-I-related", "chain", "A", "(MICA)", "and", "antibody", "rejection", "pathogenesis.", "This", "can", "allow", "for", "more", "specific", "diagnosis", "and", "treatment", "which", "may", "improve", "long-term", "graft", "function.", "HLA-specific", "antibody", "detection", "prior", "to", "transplantation", "allows", "one", "to", "help", "determine", "the", "risk", "for", "AMR", "while", "detection", "of", "DSA", "along", "with", "a", "biopsy", "confirms", "it.", "It", "is", "now", "appreciated", "that", "biopsy", "for", "AMR", "does", "not", "have", "to", "include", "diffuse", "C4d,", "but", "does", "require", "a", "closer", "look", "at", "peritubular", "capillary", "microvasculature.", "Although", "plasmapheresis", "(PP)", "is", "effective", "in", "removing", "alloantibodies", "(DSAs)", "from", "the", "circulation,", "rebound", "synthesis", "of", "alloantibodies", "can", "occur.", "Splenectomy", "is", "used", "in", "desensitization", "protocols", "for", "ABO", "incompatible", "transplants", "as", "well", "as", "being", "found", "to", "treat", "AMR", "refractory", "to", "conventional", "treatment.", "Also", "used", "are", "agents", "targeted", "for", "plasma", "cells,", "B", "cells,", "and", "the", "complement", "cascade", "which", "are", "bortezomib", "rituximab", "and", "eculizumab,", "respectively.", "1.", "Understanding", "HLA", "There", "are", "20", "class", "I", "genes", "and", "in", "transplantation", "HLA-A,", "B,", "and", "C", "are", "the", "classic", "genes", "referenced", "to", "when", "typing", "the", "recipient", "[1].", "Class", "I", "major", "histocompatibility", "complex", "(MHC)", "molecule", "processing", "and", "loading", "of", "peptides", "occurs", "in", "all", "nucleated", "cells,", "where", "class", "II", "MHC", "molecule", "involves", "primarily", "B", "cells,", "macrophages,", "and", "dendritic", "cells", "by", "method", "of", "endocytosis", "and", "phagocytosis.", "Class", "II", "MHC", "molecule", "nomenclature", "is", "designated", "by", "class", "(D),", "family", "(M,", "O,", "P,", "Q,", "R),", "and", "chain", "(A", "or", "B).", "Late", "antibody-mediated", "rejection", "(AMR)", "is", "a", "major", "cause", "of", "late", "kidney", "transplant", "failure", "and", "several", "developments", "in", "understanding", "of", "patho-", "genesis", "allow", "for", "improvement", "of", "diagnosis,", "treatment,", "and", "prevention.", "This", "review", "will", "concentrate", "on", "reviewing", "the", "pathogenesis,", "diagnosis,", "and", "treatment", "of", "AMR.", "2.", "Pathogenesis", "of", "HLA", "Antibodies", "Not", "only", "can", "antibodies", "form", "against", "HLA", "molecules,", "but", "to", "endothelial-cell", "antigens", "and", "across", "ABO", "blood", "group", "[2].", "Sensitization", "prior", "to", "transplant", "can", "occur", "by", "pregnancy", "or", "blood", "transfusions.", "Previous", "transplantation", "can", "also", "sensitize", "patients", "against", "HLA", "molecules.", "Blood", "transfusions", "can", "induce", "humoral", "immunity", "by", "formation", "of", "HLA", "alloan-", "tibodies", "and", "are", "more", "likely", "to", "occur", "in", "individuals", "who", "have", "been", "previously", "pregnant.", "Our", "understanding", "of", "how", "blood", "transfusions", 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[ "Interleukin-13", "Induces", "Tissue", "Fibrosis", "by", "Selectively", "Stimulating", "and", "Activating", "Transforming", "Growth", "Factor", "1", "Chun", "Geun", "Lee,1", "Robert", "J.", "Homer,2,", "3", "Zhou", "Zhu,1", "Sophie", "Lanone,1", "Xiaoman", "Wang,1", "Victor", "Koteliansky,4", "J.", "Michael", "Shipley,5", "Philip", "Gotwals,4", "Paul", "Noble,1", "Qingsheng", "Chen,1", "Robert", "M.", "Senior,5", "and", "Jack", "A.", "Elias1", "1Yale", "University", "School", "of", "Medicine,", "Section", "of", "Pulmonary", "and", "Critical", "Care", "Medicine,", "Department", "of", "Internal", "Medicine", "and", "the", "2Department", "of", "Pathology,", "New", "Haven,", "CT", "06520", "3Pathology", "and", "Laboratory", "Medicine", "Service,VA-CT", "Health", "Care", "System,West", "Haven,", "CT", "06516", "4Biogen,", "Inc.,", "Cambridge,", "MA", "02142", "5Washington", "University", "School", "of", "Medicine,", "Section", "of", "Pulmonary", "and", "Critical", "Care", "Medicine,", "Barnes-Jewish", "Hospital,", "St.", "Louis,", "MO", "63110", "Abstract", "Interleukin", "(IL)-13", "is", "a", "key", "mediator", "of", "tissue", "fibrosis", "caused", "by", "T", "helper", "cell", "type", "2", "inflamma-", "tion.", "We", "hypothesized", "that", "the", "fibrogenic", "effects", "of", "IL-13", "are", "mediated", "by", "transforming", "growth", "factor", "(TGF)-", ".", "To", "test", "this", "hypothesis", "we", "compared", "the", "regulation", "of", "TGF-", "in", "lungs", "from", "wild-type", "mice", "and", "CC10-IL-13", "mice", "in", "which", "IL-13", "overexpression", "causes", "pul-", "monary", "fibrosis.", "IL-13", "selectively", "stimulated", "TGF-", "1", "production", "in", "transgenic", "animals", "and", "macrophages", "were", "the", "major", "site", "of", "TGF-", "1", "production", "and", "deposition", "in", "these", "tissues.", "IL-13", "also", "activated", "TGF-", "1", "in", "vivo.", "This", "activation", "was", "associated", "with", "decreased", "levels", "of", "mRNA", "encoding", "latent", "TGF-", "–binding", "protein-1", "and", "increased", "mRNA", "encoding", "urinary", "plasmino-", "gen", "activator,", "matrix", "metalloproteinase", "(MMP)-9,", "and", "CD44.", "TGF-", "1", "activation", "was", "abro-", "gated", "by", "the", "plasmin/serine", "protease", "antagonist", "aprotinin.", "It", "was", "also", "decreased", "in", "progeny", "of", "crosses", "of", "CC10-IL-13", "mice", "and", "MMP-9", "null", "mice", "but", "was", "not", "altered", "in", "crosses", "with", "CD44", "null", "animals.", "IL-13–induced", "fibrosis", "was", "also", "significantly", "ameliorated", "by", "treatment", "with", "the", "TGF-", "antagonist", "soluble", "TGF", "R-Fc", "(sTGF", "R-Fc).", "These", "studies", "demonstrate", "that", "IL-13", "is", "a", "potent", "stimulator", "and", "activator", "of", "TGF-", "1", "in", "vivo.", "They", "also", "demonstrate", "that", "this", "activation", "is", "mediated", "by", "a", "plasmin/serine", "protease-", "and", "MMP-9–dependent", "and", "CD44-independent", "mechanism(s)", "and", "that", "the", "fibrogenic", "effects", "of", "IL-13", "are", "mediated,", "in", "great", "extent,", "by", "this", "TGF-", "pathway.", "Key", "words:", "lung", "•", "plasmin", "•", "matrix", "metalloproteinase-9", "•", "CD44", "•", "asthma", "Introduction", "Tissue", "fibrosis", "is", "a", "well-documented", "consequence", "of", "Th2", "cytokine-dominated", "inflammatory", "responses.", "This", "is", "nicely", "illustrated", "in", "asthma", "where", "Th2-dominated", "inflammation", "is", "the", "cornerstone", "of", "the", "disorder", "(1,", "2)", "and", "airway", "remodel-", "ing", "with", "subepithelial", "fibrosis", "are", "believed", "to", "be", "adverse", "consequences", "of", "this", "inflammatory", "response", "(for", "a", "review,", "see", "reference", "3).", "Th2", "inflammation", "also", "plays", "a", "central", "role", "in", "the", "pathogenesis", "of", "a", "variety", "of", "other", "fibrotic", "disorders", "including", "progressive", "systemic", "sclerosis", "(4–6),", "idiopathic", "Address", "correspondence", "to", "Jack", "A.", "Elias,", "Yale", "University", "School", "of", "Med-", "icine,", "Section", "of", "Pulmonary", "and", "Critical", "Care", "Medicine,", "Dept.", "of", "Inter-", "nal", "Medicine,", "333", "Cedar", "St.", "-", "105", "LCI,", "New", "Haven,", "CT", "06520-8057.", "Phone:", "203-785-4163;", "Fax:", "203-785-3826;", "E-mail:", "jack.elias@yale.edu", "pulmonary", "fibrosis", "(IPF*;", "references", "5–8),", "radiation-", "induced", "pulmonary", "fibrosis", "(9),", "chronic", "lung", "allograft", "re-", "jection", "(10),", "bleomycin", "lung", "(11),", "and", "hepatic", "fibrosis", "(12–", "15).", "In", "vitro", "polarized", "Th2", "cells", "also", "induce", "tissue", "fibrosis", "when", "passively", "transferred", "and", "activated", "in", "vivo", "(16).", "In", "contrast,", "Th1", "cytokine-dominated", "responses", "eventuate", "in", "tissue", "fibrosis", "less", "frequently", "and", "IFN-", ",", "the", "prototypic", "Th1", "cytokine,", "has", "a", "variety", "of", "antifibrotic", "effector", "proper-", "*Abbreviations", "used", "in", "this", "paper:", "BAL,", "bronchoalveolar", "lavage;", "IPF,", "idio-", "pathic", "pulmonary", "fibrosis;", "ISH,", "in", "situ", "hybridization;", "LAP,", "latency-associ-", "ated", "peptide;", "LTBP,", "latent", "TGF-", "–binding", "protein;", "MMP,", "matrix", "me-", "talloproteinase;", "PAI,", "plasminogen", "activator", "inhibitor;", "RT,", "reverse", "transcription;", "s,", "soluble;", "uPA,", "urokinase", "type", "plasminogen", "activator;", "WT,", "wild-type.", "809", "J.", "Exp.", "Med.", "", "The", "Rockefeller", "University", "Press", "•", "0022-1007/2001/09/809/13", "$5.00", "Volume", "194,", "Number", "6,", "September", "17,", "2001", "809–821", "http://www.jem.org/cgi/content/full/194/6/809" ]

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[ "Published", "online", "25", "October", "2008", "Nucleic", "Acids", "Research,", "2009,", "Vol.", "37,", "Database", "issue", "D369–D373", "doi:10.1093/nar/gkn759", "RsiteDB:", "a", "database", "of", "protein", "binding", "pockets", "that", "interact", "with", "RNA", "nucleotide", "bases", "Alexandra", "Shulman-Peleg1,*,", "Ruth", "Nussinov2,3", "and", "Haim", "J.", "Wolfson1", "1School", "of", "Computer", "Science,", "Raymond", "and", "Beverly", "Sackler", "Faculty", "of", "Exact", "Sciences,", "Tel", "Aviv", "University,", "2Sackler", "Institute", "of", "Molecular", "Medicine,", "Sackler", "Faculty", "of", "Medicine,", "Tel", "Aviv", "University,", "Tel", "Aviv", "69978,", "Israel", "and", "3Basic", "Research", "Program,", "SAIC-Frederick,", "Inc.,", "Laboratory", "of", "Experimental", "and", "Computational", "Biology", "NCI-Frederick", "Bldg", "469,", "Rm", "151,", "Frederick,", "MD", "21702,", "USA", "Received", "August", "11,", "2008;", "Revised", "September", "30,", "2008;", "Accepted", "October", "6,", "2008", "ABSTRACT", "We", "present", "a", "new", "database", "and", "an", "on-line", "search", "engine,", "which", "store", "and", "query", "the", "protein", "binding", "pockets", "that", "interact", "with", "single-stranded", "RNA", "nucleotide", "bases.", "The", "database", "consists", "of", "a", "clas-", "sification", "of", "binding", "sites", "derived", "from", "protein–RNA", "complexes.", "Each", "binding", "site", "is", "assigned", "to", "a", "clus-", "ter", "of", "similar", "binding", "sites", "in", "other", "protein–RNA", "complexes.", "Cluster", "members", "share", "similar", "spatial", "arrangements", "of", "physico–chemical", "properties,", "thus", "can", "reveal", "novel", "similarity", "between", "proteins", "and", "RNAs", "with", "different", "sequences", "and", "folds.", "The", "clusters", "provide", "3D", "consensus", "binding", "patterns", "important", "for", "protein–nucleotide", "recognition.", "The", "database", "search", "engine", "allows", "two", "types", "of", "useful", "queries:", "first,", "given", "a", "PDB", "code", "of", "a", "protein–RNA", "complex,", "RsiteDB", "can", "detail", "and", "classify", "the", "proper-", "ties", "of", "the", "protein", "binding", "pockets", "accommodat-", "ing", "extruded", "RNA", "nucleotides", "not", "involved", "in", "local", "RNA", "base", "pairing.", "Second,", "given", "an", "unbound", "pro-", "tein", "structure,", "RsiteDB", "can", "perform", "an", "on-line", "structural", "search", "against", "the", "constructed", "database", "of", "3D", "consensus", "binding", "patterns.", "Regions", "similar", "to", "known", "patterns", "are", "predicted", "to", "serve", "as", "binding", "sites.", "Alignment", "of", "the", "query", "to", "these", "patterns", "with", "their", "corresponding", "RNA", "nucleotides", "allows", "making", "unique", "predictions", "of", "the", "protein–RNA", "interactions", "at", "the", "atomic", "level", "of", "detail.", "This", "database", "is", "acces-", "sable", "at", "http://bioinfo3d.cs.tau.ac.il/RsiteDB.", "INTRODUCTION", "Understanding", "and", "predicting", "protein–RNA", "interactions", "at", "the", "atomic", "level", "is", "crucial", "for", "our", "ability", "to", "interfere", "with", "such", "processes", "as", "gene", "expression", "and", "regulation.", "Several", "works", "have", "classified", "protein–RNA", "interactions", "based", "on", "the", "sequences", "and", "folds", "of", "the", "corresponding", "protein", "(1–3)", "or", "RNA", "molecules", "(4–6).", "However,", "these", "do", "not", "always", "capture", "the", "similarity", "in", "the", "local", "regions", "which", "are", "responsible", "for", "protein–RNA", "recognition.", "These", "regions", "are", "important", "since", "even", "proteins", "of", "the", "same", "family", "can", "form", "different", "interactions", "with", "RNA", "nucleotides", "(7,8).", "By", "analyzing", "the", "amino", "acid", "composi-", "tion", "in", "RNA", "binding", "sites,", "several", "successful", "methods", "for", "prediction", "of", "RNA", "binding", "regions", "were", "developed", "(9–12).", "However,", "there", "are", "only", "few", "methods", "(5)", "that", "distinguish", "between", "two", "main", "interaction", "types", "formed", "across", "protein–RNA", "interfaces:", "(i)", "interactions", "with", "the", "back-", "bone", "of", "double-stranded", "RNA", "molecules;", "(ii)", "interactions", "with", "single-stranded", "RNA", "bases", "that", "are", "buried", "in", "the", "protein", "binding", "pockets", "(14).", "Here,", "we", "focus", "on", "the", "classification", "and", "prediction", "of", "protein", "interactions", "formed", "with", "single-stranded", "nucleo-", "tide", "bases.", "Sequences", "of", "such", "nucleotides,", "which", "are", "not", "involved", "in", "local", "base", "pairs", "and", "are", "extruded", "from", "the", "surrounding", "double-stranded", "helix", "were", "also", "termed", "extruded", "helical", "single", "strands", "and", "described", "as", "Structural", "Classification", "of", "RNA", "(SCOR)", "motifs", "(6,15).", "As", "estimated", "by", "the", "recent", "study", "of", "Ellis", "and", "Jones", "(16),", "the", "flexibility", "in", "the", "protein", "binding", "sites", "is", "not", "significant", "and", "should", "allow", "structural", "prediction", "of", "protein–RNA", "interaction.", "In", "our", "recent", "work", "(17),", "we", "investigated", "the", "protein", "binding", "pockets", "that", "accommodate", "extruded", "nucleotides.", "We", "observed", "that", "most", "of", "the", "protein", "inter-", "acting", "nucleotides", "are", "part", "of", "a", "consecutive", "fragment", "of", "at", "least", "two", "nucleotides,", "whose", "rings", "have", "significant", "inter-", "actions", "with", "the", "protein.", "Many", "such", "pairs", "were", "observed", "to", "share", "the", "same", "protein", "binding", "cavity", "and", ">30%", "of", "these", "pairs", "are", "p-stacked.", "We", "showed", "that", "the", "classifica-", "tion", "of", "the", "nucleotide", "and", "dinucleotide", "binding", "sites", "reveals", "similarities", "in", "patterns", "important", "in", "protein–", "RNA", "recognition.", "We", "further", "showed", "that", "searching", "for", "*To", "whom", "correspondence", "should", "be", "addressed.", "Tel:", "+972-3-640", "8268", "or", "640", "5375;", "Fax:", "+972-3-640", "5728", "or", "640", "6476;", "Email:", "shulmana@post.tau.ac.il", "Correspondence", "may", "also", "be", "addressed", "to", "Haim", "J.", "Wolfson.", "Email:", "wolfson@post.tau.ac.il", "2008", "The", "Author(s)", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "Non-Commercial", "License", "(http://creativecommons.org/licenses/", "by-nc/2.0/uk/)", "which", "permits", "unrestricted", "non-commercial", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "www.kjurology.org", "DOI:10.4111/kju.2010.51.7.501", "Case", "Report", "Mesenteric", "Fibromatosis", "Causing", "Ureteral", "Stenosis", "Jae", "Young", "Choi,", "Kyung", "Mo", "Kang,", "Bum", "Soo", "Kim,", "Tae-Hwan", "Kim", "Department", "of", "Urology,", "School", "of", "Medicine,", "Kyungpook", "National", "University,", "Daegu,", "Korea", "Mesenteric", "fibromatosis", "is", "a", "rare", "benign", "disease", "characterized", "by", "proliferating", "fibrous", "tissue", "in", "the", "bowel", "mesentery.", "We", "report", "a", "case", "of", "aggressive", "mesenteric", "fibromatosis", "with", "ureteral", "stenosis", "arising", "in", "a", "46-year-old", "woman", "who", "suffered", "from", "intermittent", "right", "abdominal", "pain.", "Computed", "tomography", "revealed", "a", "right", "retroperitoneal", "mass", "with", "right", "ureteral", "stenosis", "at", "the", "level", "of", "the", "right", "common", "iliac", "vessel.", "The", "mass", "was", "excised", "with", "resection", "of", "the", "affected", "segment", "of", "the", "ileum,", "ascending", "colon,", "and", "ureter,", "and", "end-to-end", "ureter", "anastomosis", "was", "performed.", "Pathological", "examination", "con-", "firmed", "mesenteric", "fibromatosis.", "Key", "Words:", "Aggressive", "fibromatosis;", "Retroperitoneal", "neoplasms", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "Non-Commercial", "License", "(http://creativecommons.org/licenses/by-nc/3.0)", "which", "permits", "unrestricted", "non-commercial", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Article", "History:", "received", "18", "February,", "2010", "accepted", "18", "March,", "2010", "Corresponding", "Author:", "Tae-Hwan", "Kim", "Department", "of", "Urology,", "School", "of", "Medicine,", "Kyungpook", "National", "University,", "200,", "Dongduk-ro,", "Jung-gu,", "Daegu", "700-721,", "Korea", "TEL:", "+82-53-420-5841", "FAX:", "+82-53-421-9618", "E-mail:", "peak@urology.or.kr", "Mesenteric", "fibromatosis", "(MF)", "is", "a", "rare,", "benign,", "intra-ab-", "dominal", "tumor.", "MF", "is", "characterized", "by", "proliferating", "fi-", "brous", "tissue", "in", "the", "bowel", "mesentery.", "Although", "MF", "occa-", "sionally", "invades", "the", "bowel", "or", "adjacent", "tissues", "with", "ag-", "gressive", "myofibroblastic", "proliferation,", "MF", "lacks", "the", "ca-", "pacity", "of", "malignant", "tumorigenesis", "with", "distant", "metastasis", "[1].", "MF", "is", "frequently", "associated", "with", "Gardner’s", "syndrome,", "previous", "trauma,", "prolonged", "estrogen", "intake,", "and", "preg-", "nancy,", "but", "MF", "can", "occur", "as", "a", "primary", "condition", "in", "the", "ab-", "sence", "of", "predisposing", "factors", "[2].", "MF-induced", "ureteral", "stenosis", "is", "a", "very", "rare", "urological", "problem.", "We", "present", "a", "case", "of", "primary", "MF", "causing", "ureteral", "stenosis", "with", "a", "review", "of", "the", "relevant", "literature.", "CASE", "REPORT", "A", "46-year-old", "woman", "presented", "with", "intermittent", "right", "flank", "pain", "she", "had", "experienced", "for", "a", "year.", "The", "patient", "had", "previously", "been", "healthy", "and", "had", "no", "history", "of", "disease.", "Physical", "examination", "revealed", "no", "significant", "findings", "such", "as", "tenderness", "at", "the", "costovertebral", "angle", "area,", "a", "pal-", "pable", "mass,", "or", "peripheral", "lymphadenopathy.", "Urinalysis,", "a", "complete", "blood", "count,", "and", "routine", "blood", "biochemistry", "tests", "showed", "no", "abnormal", "findings.", "Plain", "abdominal", "radio-", "graphs", "were", "normal.", "There", "were", "no", "abnormal", "findings", "in", "urine", "cytology", "or", "cystoscopic", "examination.", "Computed", "to-", "mography", "(CT)", "showed", "a", "2.7x1.5", "cm", "diffuse,", "noncalcified,", "moderately", "infiltrating", "mass", "with", "ill-defined", "lobulated", "Korean", "Journal", "of", "Urology", "Ⓒ", "The", "Korean", "Urological", "Association,", "2010", "walls", "located", "at", "the", "right", "common", "iliac", "vessel", "level", "(Fig.", "1).", "The", "mass", "was", "located", "in", "the", "right", "ureter", "anteriorly,", "and", "mild", "focal", "enhancement,", "wall", "thickening,", "and", "luminal", "nar-", "rowing", "were", "found", "in", "the", "ureter", "(Fig.", "1).", "The", "mass", "looked", "as", "if", "it", "compressed", "the", "right", "ureter,", "resulting", "in", "moderate", "hydroureteronephrosis", "above", "the", "affected", "level", "(Fig.", "1).", "Retroperitoneal", "lymphadenopathy", "was", "not", "observed.", "　In", "a", "ureterorenoscopic", "examination,", "there", "was", "no", "in-", "trinsic", "obstructive", "lesion", "such", "as", "a", "ureteral", "tumor", "causing", "ipsilateral", "hydronephrosis.", "A", "laparoscopic", "exploration", "was", "undertaken", "to", "debulk", "the", "tumor", "due", "to", "the", "patient’s", "increasing", "symptoms.", "At", "the", "time", "of", "surgery,", "due", "to", "ex-", "tensive", "adhesion", "of", "the", "ileocecal", "valve", "area", "and", "mass,", "the", "laparoscopic", "exploration", "was", "converted", "to", "open", "surgery", "to", "safely", "perform", "the", "tumor", "resection.", "We", "could", "not", "rule", "out", "the", "possibility", "of", "a", "malignant", "tumor", "before", "final", "histo-", "pathological", "confirmation", "of", "the", "affected", "lesion.", "The", "pa-", "tient", "underwent", "extensive", "debulking", "of", "the", "mass", "including", "bowel", "segmentectomy", "with", "anastomosis", "and", "excision", "of", "the", "affected", "ureter.", "Then,", "end-to-end", "ureter", "anastomosis", "was", "performed,", "and", "a", "ureteral", "stent", "was", "deployed", "in", "the", "right", "urinary", "tract", "for", "decompression.", "A", "white", "wedge", "of", "tissue", "was", "obtained", "for", "pathological", "evaluation.", "　The", "specimen", "except", "of", "resected", "bowel", "segment", "was", "a", "5.5x3x3", "cm", "firm,", "poorly", "circumscribed", "mass.", "Upon", "section-", "ing,", "the", "cut", "surface", "of", "the", "mass", "revealed", "a", "white,", "whorled", "fibrous", "and", "trabecular", "appearance", "and", "ill-defined", "margins", "with", "the", "surrounding", "fat", "tissue", "(Fig.", "2).", "Microscopically,", "501", "Korean", "J", "Urol", "2010;51:501-504" ]

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[ "Hindawi", "Publishing", "Corporation", "Mediators", "of", "Inflammation", "Volume", "2008,", "Article", "ID", "129873,", "6", "pages", "doi:10.1155/2008/129873", "Review", "Article", "Proinflammatory", "Role", "of", "Vascular", "Endothelial", "Growth", "Factor", "in", "the", "Pathogenesis", "of", "Rheumatoid", "Arthritis:", "Prospects", "for", "Therapeutic", "Intervention", "Seung-Ah", "Yoo,", "Seung-Ki", "Kwok,", "and", "Wan-Uk", "Kim", "Division", "of", "Rheumatology,", "Department", "of", "Internal", "Medicine,", "School", "of", "Medicine,", "Catholic", "University", "of", "Korea,", "Seoul", "137040,", "South", "Korea", "Correspondence", "should", "be", "addressed", "to", "Wan-Uk", "Kim,", "wan725@catholic.ac.kr", "Received", "18", "July", "2008;", "Accepted", "1", "December", "2008", "Recommended", "by", "Yvette", "Mandi", "Recent", "experimental", "and", "clinical", "studies", "have", "placed", "new", "emphasis", "on", "the", "role", "of", "angiogenesis", "in", "chronic", "inflammatory", "disease.", "Vascular", "endothelial", "growth", "factor", "(VEGF)", "and", "its", "receptors", "are", "the", "best", "characterized", "system", "in", "the", "regulation", "of", "rheumatoid", "arthritis", "(RA)", "by", "angiogenesis.", "Furthermore,", "in", "addition", "to", "its", "angiogenic", "role,", "VEGF", "can", "act", "as", "a", "direct", "proinflammatory", "mediator", "during", "the", "pathogenesis", "of", "RA,", "and", "protect", "rheumatoid", "synoviocytes", "from", "apoptosis,", "which", "contributes", "to", "synovial", "hyperplasia.", "Therefore,", "the", "developments", "of", "synovial", "inflammation,", "hyperplasia,", "and", "angiogenesis", "in", "the", "joints", "of", "RA", "patients", "seem", "to", "be", "regulated", "by", "a", "common", "cue,", "namely,", "VEGF.", "Agents", "that", "target", "VEGF,", "such", "as", "anti-VEGF", "antibody", "and", "aptamer,", "have", "yielded", "promising", "clinical", "data", "in", "patients", "with", "cancer", "or", "macular", "degeneration,", "and", "in", "RA", "patients,", "pharmacologic", "modulations", "targeting", "VEGF", "or", "its", "receptor", "may", "offer", "new", "therapeutic", "approaches.", "In", "this", "review,", "the", "authors", "integrate", "current", "knowledge", "of", "VEGF", "signaling", "and", "information", "on", "VEGF", "antagonists", "gleaned", "experimentally", "and", "place", "emphasis", "on", "the", "use", "of", "synthetic", "anti-VEGF", "hexapeptide", "to", "prevent", "VEGF", "interacting", "with", "its", "receptor.", "Copyright", "©", "2008", "Seung-Ah", "Yoo", "et", "al.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "1.", "INTRODUCTION", "The", "pathology", "of", "rheumatoid", "arthritis", "(RA)", "is", "characterized", "by", "the", "proliferation", "of", "synovial", "cells", "and", "angiogenesis,", "pannus", "formation.", "Multiple", "cell", "types,", "including", "lympho-", "cytes,", "dendritic", "cells,", "macrophages,", "and", "synovial", "fibroblasts,", "contribute", "to", "the", "chronic", "inflammatory", "responses", "of", "RA,", "and", "comprise", "a", "major", "portion", "of", "the", "invasive", "pannus", "[1].", "In", "addition,", "angiogenesis,", "the", "process", "of", "new", "blood", "vessel", "formation,", "is", "highly", "active", "in", "RA,", "particularly", "during", "the", "earliest", "stages", "of", "the", "disease", "[2,", "3].", "Newly", "formed", "vessels", "can", "maintain", "the", "chronic", "inflammatory", "state", "by", "transporting", "inflammatory", "cells", "to", "sites", "of", "synovitis,", "and", "supply", "nutrients", "and", "oxygen", "to", "the", "pannus", "[2,", "3].", "Angiogenesis", "is", "strictly", "regulated", "by", "many", "inducers", "and", "inhibitors,", "and", "a", "number", "of", "proangiogenic", "factors", "have", "been", "suggested", "to", "be", "involved", "in", "neovascularization", "in", "RA", "joints.", "These", "include", "acidic", "and", "basic", "fibroblast", "growth", "factors,", "transforming", "growth", "factor", "(TGF)-β,", "angiopoietin,", "and", "placenta", "growth", "factor", "(PIGF)", "in", "addition", "to", "vascular", "endothelial", "growth", "factor", "(VEGF)", "[2–4].", "The", "final", "goal", "of", "RA", "treatment", "is", "complete", "disease", "remission,", "and", "not", "symptomatic", "relief.", "At", "one", "end", "of", "the", "spectrum", "of", "RA", "treatment", "outcomes", "lie", "a", "large", "group", "of", "patients", "who", "do", "not", "respond", "to", "single", "disease-modifying", "antirheumatic", "drugs", "(DMARDs)", "[5].", "Recent", "clinical", "trials", "have", "suggested", "that", "several", "biologic", "agents,", "such", "as", "TNF-α", "blockers,", "rituximab,", "abatacept,", "and", "anakinra,", "are", "effective", "at", "retarding", "joint", "destruction", "and", "at", "alleviating", "RA", "activity", "[5,", "6].", "However,", "these", "biologic", "agents", "may", "have", "serious", "side", "effects,", "such", "as", "predispositions", "to", "tuberculosis,", "lymphoma,", "progressive", "multifocal", "leukoencephalopathy,", "and", "high", "cost,", "which", "limit", "their", "use", "[7].", "It", "is", "also", "a", "concern", "that", "abrupt", "stoppages", "or", "reductions", "in", "these", "treatments", "may", "result", "in", "a", "relapse", "of", "disease", "activity.", "Moreover,", "the", "pathology", "of", "RA", "suggests", "that", "it", "is", "unlikely", "that", "a", "single", "biologic", "agent", "that", "targets", "a", "specific", "subset", "of", "immune", "cells", "is", "capable", "of", "effecting", "cure." ]

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[ "BMC", "Cancer", "Research", "article", "Effects", "of", "polymorphisms", "in", "ERCC1,", "ASE-1", "and", "RAI", "on", "the", "risk", "of", "colorectal", "carcinomas", "and", "adenomas:", "a", "case", "control", "study", "Camilla", "F", "Skjelbred†1,2,", "Mona", "Sæbø†2,", "Bjørn", "A", "Nexø3,", "Håkan", "Wallin4,", "Inger-", "Lise", "Hansteen1,", "Ulla", "Vogel4", "and", "Elin", "H", "Kure*2,5", "BioMed", "Central", "Open", "Access", "Address:", "1Department", "of", "Laboratory", "Medicine,", "Section", "of", "Medical", "Genetics,", "Telemark", "Hospital,", "N-3710", "Skien,", "Norway,", "2Telemark", "University", "College,", "Faculty", "of", "Arts", "and", "Sciences,", "Department", "of", "Environmental", "and", "Health", "Studies,", "Hallvard", "Eikas", "plass,", "N-3800", "Bø", "i", "Telemark,", "Norway,", "3Institute", "of", "Human", "Genetics,", "University", "of", "Aarhus,", "Aarhus,", "Denmark,", "4National", "Institute", "of", "Occupational", "Health,", "Copenhagen,", "Denmark", "and", "5Department", "of", "Pathology,", "Ullevaal", "University", "Hospital,", "Oslo,", "Norway", "Email:", "Camilla", "F", "Skjelbred", "-", "camilla-furu.skjelbred@sthf.no;", "Mona", "Sæbø", "-", "mona.sabo@hit.no;", "Bjørn", "A", "Nexø", "-", "nexo@humgen.au.dk;", "Håkan", "Wallin", "-", "hwa@ami.dk;", "Inger-Lise", "Hansteen", "-", "inger-lise.hansteen@sthf.no;", "Ulla", "Vogel", "-", "ubv@ami.dk;", "Elin", "H", "Kure*", "-", "elin.kure@hit.no", "*", "Corresponding", "author", "†Equal", "contributors", "Published:", "03", "July", "2006", "BMC", "Cancer", "2006,", "6:175", "doi:10.1186/1471-2407-6-175", "This", "article", "is", "available", "from:", "http://www.biomedcentral.com/1471-2407/6/175", "Received:", "24", "March", "2006", "Accepted:", "03", "July", "2006", "©", "2006", "Skjelbred", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Background:", "The", "risk", "of", "sporadic", "colorectal", "cancer", "is", "mainly", "associated", "with", "lifestyle", "factors", "and", "may", "be", "modulated", "by", "several", "genetic", "factors", "of", "low", "penetrance.", "Genetic", "variants", "represented", "by", "single", "nucleotide", "polymorphisms", "in", "genes", "encoding", "key", "players", "in", "the", "adenoma", "carcinoma", "sequence", "may", "contribute", "to", "variation", "in", "susceptibility", "to", "colorectal", "cancer.", "In", "this", "study,", "we", "aimed", "to", "evaluate", "whether", "the", "recently", "identified", "haplotype", "encompassing", "genes", "of", "DNA", "repair", "and", "apoptosis,", "is", "associated", "with", "increased", "risk", "of", "colorectal", "adenomas", "and", "carcinomas.", "Methods:", "We", "used", "a", "case-control", "study", "design", "(156", "carcinomas,", "981", "adenomas", "and", "399", "controls)", "to", "test", "the", "association", "between", "polymorphisms", "in", "the", "chromosomal", "region", "19q13.2-3,", "encompassing", "the", "genes", "ERCC1,", "ASE-1", "and", "RAI,", "and", "risk", "of", "colorectal", "adenomas", "and", "carcinomas", "in", "a", "Norwegian", "cohort.", "Odds", "ratio", "(OR)", "and", "95%", "confidence", "interval", "(CI)", "were", "estimated", "by", "binary", "logistic", "regression", "model", "adjusting", "for", "age", "and", "gender.", "Results:", "The", "ASE-1", "polymorphism", "was", "associated", "with", "an", "increased", "risk", "of", "adenomas,", "OR", "of", "1.39", "(95%", "CI", "1.06–1.81),", "which", "upon", "stratification", "was", "apparent", "among", "women", "only,", "OR", "of", "1.66", "(95%", "CI", "1.15–2.39).", "The", "RAI", "polymorphism", "showed", "a", "trend", "towards", "risk", "reduction", "for", "both", "adenomas", "(OR", "of", "0.70,", "95%", "CI", "0.49–1.01)", "and", "carcinomas", "(OR", "of", "0.49,", "95%", "CI", "0.21–1.13)", "among", "women,", "although", "not", "significant.", "Women", "who", "were", "homozygous", "carriers", "of", "the", "high", "risk", "haplotype", "had", "an", "increased", "risk", "of", "colorectal", "cancer,", "OR", "of", "2.19", "(95%", "CI", "0.95–5.04)", "compared", "to", "all", "non-carriers", "although", "the", "estimate", "was", "not", "statistically", "significant.", "Conclusion:", "We", "found", "no", "evidence", "that", "the", "studied", "polymorphisms", "were", "associated", "with", "risk", "of", "adenomas", "or", "colorectal", "cancer", "among", "men,", "but", "we", "found", "weak", "indications", "that", "the", "chromosomal", "region", "may", "influence", "risk", "of", "colorectal", "cancer", "and", "adenoma", "development", "in", "women.", "Page", "1", "of", "6", "(page", "number", "not", "for", "citation", "purposes)" ]

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"Wren", "ABSTRACT", "Motivation:", "Due", "to", "advances", "in", "molecular", "sequencing", "and", "the", "increasingly", "rapid", "collection", "of", "molecular", "data,", "the", "field", "of", "phyloinformatics", "is", "transforming", "into", "a", "computational", "science.", "Therefore,", "new", "tools", "are", "required", "that", "can", "be", "deployed", "in", "supercomputing", "environments", "and", "that", "scale", "to", "hundreds", "or", "thousands", "of", "cores.", "Results:", "We", "describe", "RAxML-Light,", "a", "tool", "for", "large-scale", "phylogenetic", "inference", "on", "supercomputers", "under", "maximum", "likelihood.", "It", "implements", "a", "light-weight", "checkpointing", "mechanism,", "deploys", "128-bit", "(SSE3)", "and", "256-bit", "(AVX)", "vector", "intrinsics,", "offers", "two", "orthogonal", "memory", "saving", "techniques", "and", "provides", "a", "fine-grain", "production-level", "message", "passing", "interface", "parallelization", "of", "the", "likelihood", "function.", "To", "demonstrate", "scalability", "and", "robustness", "of", "the", "code,", "we", "inferred", "a", "phylogeny", "on", "a", "simulated", "DNA", "alignment", "(1481", "taxa,", "20", "000", "000", "bp)", "using", "672", "cores.", "This", "dataset", "requires", "one", "terabyte", "of", "RAM", "to", "compute", "the", "likelihood", "score", "on", "a", "single", "tree.", "Code", "Availability:", "https://github.com/stamatak/RAxML-Light-1.0.5", "Data", "Availability:", "http://www.exelixis-lab.org/onLineMaterial.tar.bz2", "Contact:", "alexandros.stamatakis@h-its.org", "Supplementary", "Information:", "Supplementary", "data", "are", "available", "at", "Bioinformatics", "online.", "Received", "on", "March", "7,", "2012;", "revised", "on", "May", "15,", "2012;", "accepted", "on", "May", "18,", "2012", "1", "INTRODUCTION", "Phyloinformatics", "is", "facing", "a", "paradigm", "shift", "toward", "becoming", "a", "‘real’", "computational", "science.", "Molecular", "sequencing", "technologies", "are", "developing", "at", "a", "rapid", "pace,", "generating", "enormous", "amounts", "of", "new", "data.", "Due", "to", "the", "necessity", "to", "process", "(and", "store)", "huge", "amounts", "of", "data,", "we", "expect", "the", "field", "to", "undergo", "an", "analogous", "transition", "that", "physics", "or", "computational", "fluid", "dynamics", "underwent", "20–30", "years", "ago.", "Projects", "such", "as", "the", "1000", "insect", "transcriptome", "sequencing", "project", "(www.1kite.org)", "already", "face", "these", "challenges.", "Such", "evolutionary", "studies", "require", "software", "that", "scales", "beyond", "a", "single", "node,", "that", "can", "be", "checkpointed", "and", "restarted,", "and", "that", "can", "accommodate", "the", "memory", "requirements", "of", "whole-genome", "datasets", "under", "likelihood-based", "models.", "RAxML-Light", "is", "a", "production-level", "tool", "for", "phylogenetic", "inference", "on", "supercomputers", "that", "implements", "new", "approaches", "for", "handling", "load", "imbalance,", "checkpointing", "and", "reducing", "the", "RAM", "∗To", "whom", "correspondence", "should", "be", "addressed.", "requirements", "of", "likelihood", "computations.", "Implementation", "details", "are", "discussed", "in", "the", "online", "supplement.", "2", "FEATURES", "We", "briefly", "discuss", "the", "features", "that", "distinguish", "RAxML-Light", "from", "standard", "RAxML,", "other", "likelihood-based", "phylogeny", "programs,", "and", "the", "BEAGLE", "library", "(Ayres", "et", "al.,", "2011).", "One", "important", "feature", "(in", "contrast", "to", "BEAGLE,", "MrBayes", "(Ronquist", "and", "Huelsenbeck,", "2003)", "or", "GARLI", "(Zwickl,", "2006))", "is", "that", "RAxML-Light", "implements", "a", "fine-", "grain", "message", "passing", "interface", "(MPI)", "parallelization", "to", "compute", "the", "likelihood", "on", "a", "single", "huge", "dataset", "and", "a", "single", "tree", "across", "several", "nodes.", "We", "introduced", "the", "proof-of-concept", "implementation", "in", "(Ott", "et", "al.,", "2007).", "The", "work", "is", "split", "by", "distributing", "alignment", "sites", "or", "entire", "partitions", "(depending", "on", "the", "selected", "command", "line", "options)", "among", "processors.", "Another", "essential", "feature", "is", "the", "light-weight", "checkpointing", "and", "restart", "capability,", "that", "is", "required", "on", "typical", "HPC", "systems", "that", "have", "queues", "with", "24-", "or", "48-h", "run-time", "limits.", "Light", "weight", "means", "that", "only", "those", "data-structures", "are", "stored", "in", "a", "checkpoint", "which", "are", "really", "required", "to", "restart", "the", "code.", "The", "design", "goal", "is", "to", "minimize", "checkpoint", "writing/reading", "times", "and", "file", "sizes.", "To", "the", "best", "of", "our", "knowledge,", "RAxML-Light", "comprises", "the", "only", "fine-grain", "parallelization", "of", "the", "likelihood", "function", "that", "also", "incorporates", "load", "balance", "mechanisms", "as", "described", "in", "(Stamatakis", "and", "Ott,", "2009)", "and", "(Zhang", "and", "Stamatakis,", "2012).", "Load", "imbalance", "can", "deteriorate", "parallel", "efficiency", "in", "partitioned", "phylogenetic", "analyzes.", "RAxML-Light", "also", "contains", "a", "production-level", "implementation", "of", "two", "orthogonal", "memory", "saving", "techniques", "that", "can", "be", "used", "simultaneously", "(described", "in", "Izquierdo-Carrasco", "et", "al.,", "2011a,b).", "These", "techniques", "allow", "for", "deploying", "RAxML-Light", "on", "systems", "that", "do", "not", "have", "enough", "RAM", "to", "store", "all", "conditional", "probability", "vectors", "required", "for", "likelihood", "calculations.", "Finally,", "RAxML-Light", "also", "uses", "256-bit", "wide", "AVX", "vector", "intrinsics", "to", "accelerate", "likelihood", "computations", 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"provided", "the", "original", "work", "is", "properly", "cited.", "[12:10", "20/7/2012", "Bioinformatics-bts309.tex]", "Page:", "2064", "2064–2066" ]

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[ "Published", "online", "17", "October", "2008", "Nucleic", "Acids", "Research,", "2008,", "Vol.", "36,", "No.", "20", "6571–6584", "doi:10.1093/nar/gkn719", "The", "N-clasp", "of", "human", "DNA", "polymerase", "i", "promotes", "blockage", "or", "error-free", "bypass", "of", "adenine-", "or", "guanine-benzo[a]pyrenyl", "lesions", "Lei", "Jia1,", "Nicholas", "E.", "Geacintov2", "and", "Suse", "Broyde1,2,*", "1Department", "of", "Biology", "and", "2Department", "of", "Chemistry,", "New", "York", "University,", "100", "Washington", "Square", "East,", "New", "York,", "NY", "10003,", "USA", "Received", "August", "22,", "2008;", "Revised", "September", "29,", "2008;", "Accepted", "September", "30,", "2008", "ABSTRACT", "DNA", "bypass", "polymerases", "are", "utilized", "to", "transit", "bulky", "DNA", "lesions", "during", "replication,", "but", "the", "pro-", "cess", "frequently", "causes", "mutations.", "The", "structural", "origins", "of", "mutagenic", "versus", "high", "fidelity", "replication", "in", "lesion", "bypass", "is", "therefore", "of", "fundamental", "interest.", "As", "model", "systems,", "we", "investigated", "the", "molecular", "basis", "of", "the", "experimentally", "observed", "essentially", "faithful", "bypass", "of", "the", "guanine", "10S-(+)-trans-anti-", "benzo[a]pyrene-N2-dG", "adduct", "by", "the", "Y-family", "human", "DNA", "polymerase", "i,", "and", "the", "observed", "block-", "age", "of", "pol", "i", "produced", "by", "the", "adenine", "10S-(+)-trans-", "anti-benzo[a]pyrene-N2-dA", "adduct.", "These", "lesions", "are", "derived", "from", "the", "most", "tumorigenic", "metabolite", "of", "the", "ubiquitous", "cancer-causing", "pollutant,", "ben-", "zo[a]pyrene.", "We", "compare", "our", "results", "for", "the", "dG", "adduct", "with", "our", "earlier", "studies", "for", "the", "pol", "i", "archaeal", "homolog", "Dpo4,", "which", "processes", "the", "same", "lesion", "in", "an", "error-prone", "manner.", "Molecular", "modeling,", "mole-", "cular", "mechanics", "calculations", "and", "molecular", "dynamics", "simulations", "were", "utilized.", "Our", "results", "show", "that", "the", "pol", "i", "N-clasp", "is", "a", "key", "structural", "fea-", "ture", "that", "accounts", "for", "the", "dA", "adduct", "blockage", "and", "the", "near-error-free", "bypass", "of", "the", "dG", "lesion.", "Absence", "of", "the", "N-clasp", "in", "Dpo4", "explains", "the", "error-", "prone", "processing", "of", "the", "same", "lesion", "by", "this", "enzyme.", "Thus,", "our", "studies", "elucidate", "structure-function", "rela-", "tionships", "in", "the", "fidelity", "of", "lesion", "bypass.", "INTRODUCTION", "Bulky", "lesions", "normally", "block", "the", "progress", "of", "processive", "high", "fidelity", "DNA", "polymerases", "(1–5).", "Subsequently,", "the", "replicative", "polymerase", "may", "be", "replaced", "by", "one", "or", "more", "translesion", "bypass", "polymerases", "(6–10).", "The", "error-free", "bypass", "of", "DNA", "lesions", "during", "translesion", "synthesis", "(TLS)", "is", "a", "repair", "pathway,", "which", "plays", "an", "important", "role", "in", "coping", "with", "highly", "blocking", "lesions", "in", "all", "three", "domains", "of", "life", "(6,10).", "However,", "translesion", "synthesis", "is", "often", "carried", "out", "by", "low-fidelity", "bypass", "DNA", "polymerases", "(11–14).", "In", "error-prone", "TLS,", "the", "mismatched", "nucleotides", "incorporated", "opposite", "the", "lesion", "introduce", "mutations", "into", "the", "genome", "that", "can", "result", "in", "the", "development", "of", "cancer", "(15,16).", "In", "humans,", "there", "are", "four", "known", "Y-family", "bypass", "DNA", "polymerases,", "pol", "Z,", "pol", "i,", "pol", "k", "and", "Rev1", "(7,17).", "Pol", "k", "is", "the", "only", "Y-family", "polymerase", "found", "in", "humans", "which", "has", "homologs", "in", "both", "bacteria", "(DinB", "or", "Pol", "IV", "in", "Escherichia", "coli)", "and", "archaea", "(Dbh", "in", "Sulfolobus", "acidocaldarius", "and", "Dpo4", "in", "Sufolobus", "solfataricus)", "(18).", "The", "structural", "features", "of", "low-fidelity", "bypass", "poly-", "merases", "that", "allow", "for", "TLS", "of", "some", "lesions", "but", "not", "others,", "while", "high-fidelity", "polymerases", "are", "stalled", "by", "the", "same", "lesions,", "is", "a", "topic", "of", "significant", "interest", "(3,9,10).", "The", "structures", "of", "a", "number", "of", "Y-family", "polymerases", "have", "been", "investigated", "(10,19).", "A", "ternary", "complex", "crystal", "structure", "of", "pol", "k", "lacking", "its", "C-terminal", "domain", "has", "recently", "been", "determined", "(20).", "This", "structure", "contains", "the", "major", "domains", "of", "pol", "k", "including", "its", "signature", "N-terminal", "domain,", "namely,", "the", "‘N-clasp’,", "an", "unmodified", "DNA", "primer/template", "complex,", "and", "an", "incoming", "dTTP", "Watson–Crick", "paired", "with", "the", "templating", "base", "adenine", "(20).", "The", "N-clasp", "in", "pol", "k", "is", "at", "present", "unique,", "as", "it", "has", "not", "yet", "been", "observed", "in", "any", "other", "Y-family", "polymerase.", "With", "the", "N-clasp", "on", "the", "major", "groove", "side", "(Figure", "1)", "of", "the", "nascent", "duplex,", "pol", "k", "completely", "encircles", "a", "region", "of", "the", "DNA", "containing", "the", "template–primer", "junction", "at", "its", "active", "site.", "It", "is", "noteworthy", "that", "pol", "k", "lacking", "the", "N-clasp", "(pol", "k68–526)", "is", "severely", "impaired", "in", "its", "DNA", "synthesis", "activity", "(20).", "The", "ability", "of", "pol", "k", "to", "synthesize", "DNA", "both", "in", "the", "absence", "and", "presence", "of", "lesions", "has", "received", "considerable", "attention.", "In", "the", "case", "of", "unmodified", "DNA", "templates,", "pol", "k", "synthesizes", "DNA", "with", "low", "fidelity", "(21),", "and", "it", "has", "also", "been", "shown", "that", "it", "is", "promiscuous", "in", "extending", "primer", "strands", "past", "mispaired", "primer–template", "termini", "(22).", "The", "processing", "of", "DNA", "lesions", "by", "pol", "k,", "whether", "error-free", "or", "error-prone,", "has", "been", "shown", "to", "be", "highly", "lesion", "*To", "whom", "correspondence", "should", "be", "addressed.", "Tel:", "+1", "212", "998", "8231;", "Fax:", "+1", "212", "995", "4015;", "Email:", "broyde@nyu.edu", "2008", "The", "Author(s)", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "Non-Commercial", "License", "(http://creativecommons.org/licenses/", "by-nc/2.0/uk/)", "which", "permits", "unrestricted", "non-commercial", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "J", "Orthopaed", "Traumatol", "(2012)", "13:137–143", "DOI", "10.1007/s10195-012-0187-x", "O", "R", "I", "G", "I", "N", "A", "L", "A", "R", "T", "I", "C", "L", "E", "The", "migration", "pattern", "of", "the", "Charnley", "femoral", "stem:", "a", "five-year", "follow-up", "RSA", "study", "in", "a", "well-functioning", "patient", "group", "Kristin", "Haugan", "•", "Otto", "S.", "Husby", "•", "Jomar", "Klaksvik", "•", "Olav", "A.", "Foss", "Received:", "1", "July", "2011", "/", "Accepted:", "10", "March", "2012", "/", "Published", "online:", "11", "May", "2012", "The", "Author(s)", "2012.", "This", "article", "is", "published", "with", "open", "access", "at", "Springerlink.com", "Abstract", "Background", "Implant", "stability", "is", "considered", "vital", "to", "long-", "time", "implant", "survival", "in", "total", "hip", "arthroplasty", "(THA),", "since", "loose", "implants", "are", "reported", "to", "be", "a", "major", "cause", "of", "hip", "revision.", "There", "is", "an", "association", "between", "early", "implant", "micromotion", "and", "increased", "risk", "of", "revision.", "More", "implant-", "specific", "data", "are", "needed", "to", "establish", "acceptable", "levels", "of", "early", "implant", "movement.", "Materials", "and", "methods", "Thirty-five", "patients", "(36", "hips)", "undergoing", "Charnley", "THA", "were", "followed", "with", "repeated", "clinical,", "radiographic,", "and", "radiostereometric", "analysis", "(RSA)", "over", "5", "years.", "Twenty-three", "patients", "attended", "5", "years", "postoperatively.", "Results", "The", "patient", "group", "was", "well", "functioning", "based", "on", "the", "radiological", "and", "clinical", "evaluations.", "The", "stems", "con-", "stantly", "moved", "up", "to", "5", "years", "postoperatively,", "with", "subsi-", "dence,", "retroversion,", "and", "varus", "tilt,", "based", "on", "the", "RSA.", "Conclusion", "Continuous", "movement", "of", "the", "Charnley", "stem", "was", "observed", "up", "to", "5", "years", "postoperatively", "in", "a", "well-", "functioning", "patient", "group.", "The", "migration", "data", "presented", "herein", "could", "be", "useful", "when", "defining", "acceptable", "migration", "limits", "for", "certain", "types", "of", "cemented", "femoral", "stems.", "Keywords", "RSA", "Migration", "pattern", "Charnley", "THR", "Five-year", "follow-up", "K.", "Haugan", "(&)", "O.", "S.", "Husby", "J.", "Klaksvik", "O.", "A.", "Foss", "Orthopaedic", "Research", "Centre,", "Trondheim", "University", "Hospital,", "7006", "Trondheim,", "Norway", "e-mail:", "kristin.haugan@ntnu.no", "O.", "S.", "Husby", "Orthopaedic", "Department,", "Trondheim", "University", "Hospital,", "7006", "Trondheim,", "Norway", "Introduction", "Implant", "stability", "influences", "the", "revision", "rate", "observed", "in", "total", "hip", "arthroplasty", "(THA).", "According", "to", "the", "Swedish,", "Australian", "and", "Norwegian", "hip", "registers,", "aseptic", "loosening", "is", "the", "most", "common", "cause", "of", "revision", "[1–3].", "Revision", "surgery", "is", "expensive", "to", "both", "patients", "and", "the", "community.", "Major", "efforts", "have", "been", "made", "to", "reduce", "these", "numbers", "from", "the", "earliest", "days", "of", "THA.", "Radiostereometric", "analysis", "(RSA)", "has", "become", "a", "gold", "standard", "when", "measuring", "implant", "migrations", "with", "respect", "to", "the", "cement", "mantle", "as", "well", "as", "the", "surrounding", "bone", "[4].", "RSA", "can", "describe", "early", "implant", "migration,", "and", "is", "therefore", "well", "suited", "and", "recommended", "when", "introducing", "new", "implants", "into", "clinical", "use", "and", "minimizing", "the", "number", "of", "enrolled", "patients", "[5].", "The", "main", "rationale", "for", "monitoring", "early", "implant", "migration", "is", "based", "on", "results", "from", "clinical", "studies", "reporting", "an", "association", "between", "early", "subsidence", "and", "increased", "risk", "of", "early", "or", "mid-term", "hip", "implant", "revision.", "Early", "migration", "[6],", "continuous", "migration", "[7],", "and", "subsidence", "in", "combination", "with", "medial", "and", "posterior", "migration", "[6]", "are", "of", "concern.", "However,", "when", "defining", "acceptable", "limits", "for", "migration,", "factors", "such", "as", "measurement", "procedures,", "implant", "design,", "and", "fixation", "principles", "should", "be", "taken", "into", "account.", "The", "level", "of", "early", "implant", "stability", "is", "mainly", "determined", "by", "the", "fixation", "method", "used.", "In", "cement", "fixation", "of", "femoral", "stems,", "two", "different", "principles", "apply", "[8,", "9].", "In", "a", "composite", "construction,", "such", "as", "the", "Charnley", "stem,", "there", "should", "be", "perfect", "bonding", "between", "stem", "and", "cement.", "In", "contrast,", "there", "is", "the", "construction", "in", "which", "the", "stem", "is", "not", "intended", "to", "be", "bonded", "to", "the", "cement,", "but", "rather", "to", "act", "as", "a", "‘‘loaded", "taper’’", "that", "is", "constrained", "by", "its", "surrounding", "cement", "man-", "tle,", "such", "as", "the", "Exeter", "stem.", "123" ]

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"immune", "system", "and", "thus", "shaping", "both", "the", "tumor", "and", "its", "microenvironment.", "Cytokines", "represent", "part", "of", "the", "complex", "pattern", "of", "the", "immune", "response", "which", "can", "assist", "the", "development", "of", "cancer", "as", "well", "as", "to", "eliminate", "it.", "Simultaneously,", "a", "large", "number", "of", "cytokines", "may", "be", "involved", "in", "the", "complex", "interactions", "between", "host", "and", "tumor", "cells", "where", "this", "dynamic", "cross-talk,", "between", "tumors", "and", "the", "immune", "system,", "can", "either", "regulate", "tumor", "growth", "or", "tumor", "growth,", "invasion", "and", "metastasis", "take", "place.", "In", "this", "review,", "we", "are", "stressing", "on", "the", "interface", "between", "infiltrated", "immune", "cells", "and", "tumor", "cells", "with", "the", "emphasis", "on", "the", "bidirectional", "activities", "of", "specific", "cytokines:", "IFN-g,", "TGF-b", "and", "IL-17", "within", "the", "tumor", "microenvironment", "and", "their", "role", "in", "shaping", "it.", "In", "addition,", "the", "significance", "of", "modulating", "such", "cytokines", "in", "favor", "of", "anti-tumor", "response", "is", "discussed", "and", "merits", "the", "use", "of", "mixture", "of", "targeted", "modulators", "to", "overcome", "the", "network", "complexity", "of", "cytokines", "in", "the", "tumor", "microenvironment.", "Keywords:", "cytokines,", "transcription", "factors,", "crosstalk,", "tumor", "microenvironment", "1.", "Introduction", "The", "failure", "of", "the", "immune", "system", "to", "recognize", "and", "era-", "dicate", "cancer", "cells", "may", "partly", "be", "a", "result", "of", "insufficient", "immunological", "activation.", "It", "is", "now", "increasingly", "recog-", "nized", "that", "the", "microenvironment", "plays", "a", "critical", "role", "in", "the", "progression", "of", "tumors", "where", "immune-resistant", "tumor", "variants", "are", "selected", "initiating", "the", "process", "of", "can-", "cer", "immunoediting.", "Tumor-derived", "soluble", "factors", "can", "impel", "various", "mechanisms", "for", "escape", "from", "immune", "attack", "in", "the", "tumor", "microenvironment", "[1,2].", "The", "tumor", "microenvironment", "is", "a", "pivotal", "factor", "in", "the", "course", "of", "carcinogenesis", "and", "is", "largely", "dependent", "on", "its", "interac-", "tions", "with", "microenvironmental", "components", "in", "a", "bidirec-", "tional", "way", "and", "consequently", "tumor", "progression", "or", "regression", "[3,4].", "*", "Correspondence:", "kzm@uop.edu.jo", "Department", "of", "Pharmacology", "and", "Biomedical", "Sciences,", "Faculty", "of", "Pharmacy", "and", "Medical", "Sciences,", "Petra", "University,", "Amman,", "Jordan", "The", "tumor", "microenvironment", "was", "lately", "recognized", "as", "the", "product", "of", "a", "developing", "crosstalk", "between", "different", "cells", "types.", "In", "addition", "to", "tumor", "cells,", "the", "tumor", "microen-", "vironment", "is", "comprised", "of", "immune", "cells,", "fibroblasts,", "stro-", "mal", "cells", "and", "the", "extracellular", "matrix", "[3].", "Normal", "cellular", "microenvironment", "can", "inhibit", "tumor", "cell", "proliferation", "and", "cancer", "formation", "[4].", "Contrariwise,", "as", "tissue", "becomes", "can-", "cerous", "pathological", "interactions", "between", "cancer", "cells", "and", "host", "immune", "cells", "in", "the", "tumor", "microenvironment", "and", "lymphoid", "organs", "create", "an", "immunosuppressive", "network", "that", "protects", "the", "tumor", "from", "immune", "attack", "leading", "to", "tumor", "growth,", "progression", "as", "well", "as", "invasion", "and", "metas-", "tasis", "which", "is", "basically", "due", "to", "a", "deranged", "relationship", "between", "tumor", "and", "stromal", "cells", "[3-5].", "In", "this", "review,", "we", "are", "stressing", "on", "the", "interface", "between", "infiltrated", "immune", "cells", "and", "tumor", "cells", "with", "the", "emphasis", "on", "the", "bidirec-", "tional", "activities", "of", "cytokines", "mainly", "IFN-g,", "TGF-b", "and", "IL-17", "within", "the", "tumor", "microenvironment", "and", "their", "role", "©", "2011", "Alshaker", "and", "Matalka;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Chappell", "Arthritis", "Research", "&", "Therapy", "2010,", "12:128", "http://arthritis-research.com/content/12/3/128", "E", "D", "I", "T", "O", "R", "I", "A", "L", "Angiotensin-converting", "enzyme", "2", "autoantibodies:", "further", "evidence", "for", "a", "role", "of", "the", "renin–", "angiotensin", "system", "in", "inflammation", "Mark", "C", "Chappell*", "See", "related", "research", "by", "Takahashi", "et", "al.,", "http://arthritis-research.com/content/12/3/R85", "Abstract", "Traditionally", "viewed", "as", "important", "in", "the", "regulation", "of", "blood", "pressure,", "the", "renin–angiotensin", "system", "–", "and", "specifically", "the", "angiotensin-converting", "enzyme", "(ACE)–", "angiotensin", "(Ang)", "II–AT1", "receptor", "axis", "–", "may", "play", "a", "prominent", "role", "to", "promote", "inflammation", "and", "fibrosis.", "ACE2,", "a", "new", "component", "of", "the", "renin–angiotensin", "system,", "has", "emerged", "as", "a", "key", "enzyme", "that", "selectively", "degrades", "Ang", "II", "and", "generates", "Ang-(1–7),", "a", "bioactive", "peptide", "with", "anti-inflammatory", "and", "anti-fibrotic", "actions.", "Takahashi", "and", "colleagues", "demonstrate", "circulating", "titers", "of", "inhibitory", "autoantibodies", "against", "ACE2", "in", "patients", "with", "systemic", "sclerosis.", "The", "current", "study", "reveals", "a", "potentially", "novel", "mechanism", "to", "attenuate", "the", "catalytic", "activity", "of", "ACE2,", "thereby", "promoting", "the", "actions", "of", "Ang", "II.", "The", "discovery", "of", "the", "angiotensin-converting", "enzyme", "(ACE)", "homolog", "ACE2", "[EC", "3.4.15.1]", "has", "provoked", "intensive", "efforts", "to", "elucidate", "the", "role", "of", "this", "enzyme", "in", "various", "pathologies,", "including", "hypertension,", "diabetes,", "heart", "failure,", "viral", "infection,", "pulmonary", "injury", "and", "liver", "fibrosis.", "The", "biological", "relevance", "of", "ACE2", "reflects", "its", "critical", "location", "in", "the", "enzymatic", "cascade", "of", "the", "renin–", "angiotensin", "system", "to", "directly", "govern", "the", "local", "expression", "of", "angiotensin", "(Ang)", "II", "and", "Ang-(1–7),", "two", "bioactive", "hormones", "with", "significant", "and", "opposing", "actions.", "In", "the", "present", "issue", "of", "Arthritis", "Research", "&", "Therapy,", "Takahashi", "and", "colleagues", "assessed", "circulating", "levels", "of", "ACE2", "in", "patients", "with", "connective", "tissue", "pathologies", "including", "pulmonary", "hypertension", "and", "persistent", "digital", "*Correspondence:", "mchappel@wfubmc.edu", "Hypertension", "and", "Vascular", "Disease", "Center,", "Wake", "Forest", "School", "of", "Medicine,", "Medical", "Center", "Boulevard,", "Winston-Salem,", "NC", "27015,", "USA", "©", "2010", "BioMed", "Central", "Ltd", "©", "2010", "BioMed", "Central", "Ltd", "ischemia", "[1].", "In", "comparison", "with", "normal", "controls,", "patients", "with", "overt", "vasculopathy", "expressed", "significantly", "higher", "amounts", "of", "ACE2", "protein", "in", "the", "circulation.", "These", "patients,", "however,", "exhibited", "reduced", "ACE2", "activity", "in", "serum", "and", "circulating", "autoantibodies", "against", "the", "enzyme.", "There", "are", "few", "reports", "on", "the", "circulating", "levels", "of", "ACE2", "in", "humans", "or", "experimental", "models,", "possibly", "reflecting", "the", "difficulty", "of", "obtaining", "a", "consistent", "measurement", "of", "the", "enzymatic", "activity.", "The", "current", "study", "reveals", "a", "potentially", "novel", "mechanism", "to", "attenuate", "the", "catalytic", "activity", "of", "ACE2,", "thereby", "promoting", "the", "inflammatory", "actions", "of", "Ang", "II.", "ACE", "and", "ACE2", "are", "both", "chloride-activated", "metallo-", "peptidases", "that", "are", "predominantly", "associated", "with", "the", "cell", "membrane", "and", "are", "widely", "distributed", "in", "various", "tissues", "and", "vascular", "beds.", "In", "contrast", "to", "ACE,", "which", "cleaves", "two", "amino", "acid", "residues", "from", "the", "carboxyl", "terminus", "of", "Ang", "I", "to", "form", "Ang", "II,", "ACE2", "hydrolyzes", "a", "single", "amino", "acid", "from", "the", "carboxyl", "end", "of", "Ang", "II", "to", "form", "Ang-(1–7)", "[2].", "ACE", "is", "considered", "the", "primary", "enzymatic", "pathway", "that", "catalyzes", "the", "generation", "of", "Ang", "II", "in", "the", "circulation", "and", "tissues.", "ACE", "inhibitors,", "which", "have", "become", "standard", "therapies", "in", "the", "treatment", "of", "hyper-", "tension", "and", "other", "cardiovascular", "disease,", "have", "little", "or", "no", "inhibitory", "activity", "against", "ACE2,", "but", "they", "reduce", "the", "metabolism", "of", "Ang-(1–7)", "[2].", "Circulating", "levels", "of", "ACE", "activity", "are", "readily", "measurable", "in", "humans", "and", "other", "species", "using", "synthetic", "substrates", "or", "assessing", "the", "direct", "conversion", "of", "Ang", "I", "to", "Ang", "II.", "In", "comparison", "with", "serum", "ACE,", "Rice", "and", "colleagues", "reported", "that", "the", "circulating", "levels", "of", "ACE2", "were", "100-fold", "lower", "and", "that", "<10%", "(40", "out", "of", "494)", "of", "their", "patients", "expressed", "measurable", "ACE2", "activity", "[3].", "Nevertheless,", "families", "with", "detectable", "circulating", "ACE2", "exhibited", "a", "greater", "incidence", "of", "cardiovascular", "pathologies", "although", "the", "overall", "sample", "population", "was", "low.", "More", "recent", "studies", "by", "Epelman", "and", "colleagues", "find", "that", "circulating", "levels", "of", "ACE2", "are", "highly", "associated", "with", "increasing", "severity", "of", "progressive", "heart", "failure", "[4].", "However,", "patients" ]

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[ "RESEARCH", "First", "Isolation", "of", "West", "Nile", "virus", "from", "a", "Patient", "with", "Encephalitis", "in", "the", "United", "States", "Cinnia", "Huang,*", "Brett", "Slater,*", "Robert", "Rudd,*", "Nandakishore", "Parchuri,†", "Rene", "Hull,*", "Michelle", "Dupuis,*", "and", "Alexander", "Hindenburg†", "West", "Nile", "virus", "(WNV)", "was", "isolated", "from", "a", "patient", "who", "developed", "encephalitis", "while", "undergoing", "treatment", "with", "CHOP", "(cyclophosphamide,", "hydroxydoxorubicin,", "vincristine", "[Oncovin],", "predisone)", "and", "rituximab", "for", "a", "non-Hodgkin", "B-cell", "lymphoma.", "Both", "standard", "reverse", "transcription–polymerase", "chain", "reaction", "(RT-PCR)", "and", "Taqman", "RT-PCR", "established", "the", "diagnosis", "of", "WNV", "infection", "from", "cerebrospinal", "fluid", "(CSF).", "Several", "whole", "blood", "samples", "and", "one", "serum", "sample", "underwent", "further", "testing.", "CSF", "and", "serum", "samples", "were", "negative", "for", "WNV", "antibody;", "however,", "all", "samples", "were", "positive", "by", "both", "RT-PCR", "assays.", "Infectious", "virus", "was", "recovered", "from", "a", "blood", "sample,", "and", "its", "identity", "was", "confirmed", "by", "using", "a", "WNV-specific", "immunofluo-", "rescence", "assay.", "The", "complete", "WNV", "genomes", "determined", "from", "CSF", "and", "from", "the", "virus", "isolate", "adapted", "from", "cell", "culture", "were", "the", "same.", "The", "results", "represent", "the", "first", "complete", "WNV", "genome", "sequence", "obtained", "directly", "from", "human", "CSF", "and", "the", "first", "time", "that", "infectious", "WNV", "has", "been", "recovered", "from", "a", "patient", "with", "encephalitis", "in", "North", "America.", "W", "member", "of", "the", "Japanese", "encephalitis", "virus", "serocomplex", "est", "Nile", "virus", "(WNV),", "an", "arthropod-borne", "virus,", "is", "a", "of", "the", "genus", "Flavivirus,", "family", "Flaviviridae", "(1),", "discovered", "in", "Uganda", "in", "1937", "(2).", "Although", "WNV", "infections", "are", "usually", "mild", "or", "asymptomatic,", "in", "some", "instances,", "a", "severe", "and", "fatal", "encephalitis", "is", "produced,", "typically", "in", "the", "elderly", "(3).", "This", "virus", "was", "first", "recognized", "in", "the", "Western", "Hemisphere", "in", "an", "outbreak", "in", "New", "York", "in", "1999", "(4).", "As", "of", "October", "2,", "2002,", "a", "total", "of", "2.671", "cases", "of", "human", "illness", "in", "the", "United", "States", "have", "been", "reported", "to", "the", "Centers", "for", "Disease", "Control", "and", "Prevention", "(CDC).", "Although", "WNV", "has", "been", "recovered", "from", "mosquitoes,", "birds,", "and", "horses,", "no", "isolations", "from", "humans", "have", "been", "reported", "in", "the", "Western", "Hemisphere.", "Thus,", "all", "prior", "data", "regarding", "the", "virus", "responsible", "for", "human", "illness", "in", "North", "America", "have", "come", "from", "nucleic", "acid", "sequencing", "of", "the", "viral", "genome", "in", "either", "cerebrospinal", "fluid", "(CSF)", "or", "brain", "tissue.", "We", "describe", "the", "first", "isolation", "of", "WNV", "from", "a", "human", "case-patient", "associated", "with", "the", "U.S.", "outbreak.", "Because", "the", "virus", "was", "also", "directly", "detected", "by", "reverse", "transcription–polymerase", "chain", "reaction", "(RT-PCR)", "in", "specimens", "from", "the", "same", "patient,", "we", "were", "able", "to", "compare", "the", "entire", "genomic", "sequence", "of", "the", "directly", "detected", "virus", "with", "that", "of", "the", "cell-culture", "isolate.", "Case", "Report", "The", "patient", "was", "a", "70-year-old", "woman,", "who", "has", "been", "diag-", "nosed", "with", "intermediate-grade,", "CD", "20-positive,", "B-cell", "non-", "Hodgkin", "lymphoma,", "involving", "a", "left", "intraparotid", "lymph", "node.", "Staging", "workup", "demonstrated", "stage", "1-A", "disease.", "Treatment", "plans", "for", "the", "patient", "included", "three", "courses", "of", "CHOP", "(cyclo-", "*Wadsworth", "Center,", "New", "York", "State", "Department", "of", "Health,", "Albany,", "New", "York,", "USA;", "and", "†Winthrop", "University", "Hospital,", "Mineola,", "New", "York,", "USA", "phosphamide,", "hydroxydoxorubicin,", "vincristine", "[Oncovin],", "and", "predisone)", "chemotherapy", "plus", "rituximab", "(chimeric", "CD", "20", "monoclonal", "antibody),", "to", "be", "followed", "by", "involved", "field", "radia-", "tion.", "After", "the", "first", "cycle", "of", "chemotherapy", "in", "July", "2001,", "neu-", "tropenia", "developed", "and", "the", "patient", "was", "treated", "with", "granulocyte", "colony", "stimulating", "factor", "(GCSF)", "following", "both", "the", "second", "and", "third", "cycles", "of", "chemotherapy.", "The", "third", "cycle", "of", "chemotherapy", "was", "administered", "on", "September", "11,", "2001.", "Four", "days", "later,", "she", "was", "treated", "with", "oral", "levofloxacin", "for", "low-", "grade", "fever.", "On", "day", "7", "after", "chemotherapy,", "she", "was", "admitted", "to", "the", "hospital", "with", "fever,", "cough,", "chills,", "rhinorrhea,", "joint", "aches,", "decreased", "appetite,", "lethargy,", "and", "lightheadedness.", "She", "had", "no", "recollection", "of", "any", "ill", "contacts", "or", "insect", "bites.", "She", "was", "a", "resi-", "dent", "of", "southern", "Nassau", "County,", "New", "York,", "and", "did", "not", "have", "a", "history", "of", "travel.", "Physical", "examination", "was", "within", "normal", "lim-", "its.", "The", "patient", "was", "neutropenic;", "G-CSF", "was", "continued,", "and", "she", "was", "given", "cefipime", "and", "gentamicin.", "One", "day", "after", "admis-", "sion,", "she", "continued", "to", "have", "fever", "and", "experienced", "mild", "head-", "aches", "that", "responded", "to", "acetaminophen.", "Urine", "cultures", "showed", "penicillin-sensitive", "enterococci,", "and", "blood", "cultures", "were", "nega-", "tive.", "Two", "days", "after", "admission,", "the", "patient", "continued", "to", "have", "fever,", "headaches,", "and", "dizziness.", "A", "computed", "tomography", "(CT)", "scan", "of", "the", "brain", "revealed", "no", "acute", "cerebral", "processes.", "On", "the", "3rd", "day", "after", "admission,", "the", "patient", "was", "noted", "to", "be", "confused.", "Further", "deterioration", "of", "mental", "status", "was", "noted,", "with", "incom-", "prehensible", "speech,", "but", "she", "was", "able", "to", "follow", "commands.", "Arterial", "blood-gas", "analysis", "showed", "an", "acute", "respiratory", "acido-", "sis", "pattern,", "and", "the", "patient", "was", "subsequently", "intubated", "and", "transferred", "to", "the", "intensive", "care", "unit.", "The", "patient", "had", "a", "hypotensive", "episode", "secondary", "to", "atrial", "flutter,", "which", "required", "cardioversion", "for", "stabilization.", "Ceftriaxone", "and", "ampicillin", "were", "added", "to", "the", "antibiotic", "coverage,", "and", "antifungal", "treatment", "was", "also", "initiated", "with", "lipid", "complex", "amphotericin", "B.", "After", "Emerging", "Infectious", "Diseases", "•", "Vol.", "8,", "No.", "12,", "December", "2002", "1367" ]

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[ "Freeman", "et", "al.", "Fibrogenesis", "&", "Tissue", "Repair", "2010,", "3:17", "http://www.fibrogenesis.com/content/3/1/17", "R", "E", "S", "E", "A", "R", "C", "H", "Open", "Access", "Mast", "cells", "and", "hypoxia", "drive", "tissue", "metaplasia", "and", "heterotopic", "ossification", "in", "idiopathic", "arthrofibrosis", "after", "total", "knee", "arthroplasty", "Theresa", "A", "Freeman1,", "Javad", "Parvizi2,", "Craig", "J", "Dela", "Valle3,", "Marla", "J", "Steinbeck4*", "Abstract", "Background:", "Idiopathic", "arthrofibrosis", "occurs", "in", "3-4%", "of", "patients", "who", "undergo", "total", "knee", "arthroplasty", "(TKA).", "However,", "little", "is", "known", "about", "the", "cellular", "or", "molecular", "changes", "involved", "in", "the", "onset", "or", "progression", "of", "this", "condition.", "To", "classify", "the", "histomorphologic", "changes", "and", "evaluate", "potential", "contributing", "factors,", "periarticular", "tissues", "from", "the", "knees", "of", "patients", "with", "arthrofibrosis", "were", "analyzed", "for", "fibroblast", "and", "mast", "cell", "proliferation,", "heterotopic", "ossification,", "cellular", "apoptosis,", "hypoxia", "and", "oxidative", "stress.", "Results:", "The", "arthrofibrotic", "tissue", "was", "composed", "of", "dense", "fibroblastic", "regions,", "with", "limited", "vascularity", "along", "the", "outer", "edges.", "Within", "the", "fibrotic", "regions,", "elevated", "numbers", "of", "chymase/fibroblast", "growth", "factor", "(FGF)-expressing", "mast", "cells", "were", "observed.", "In", "addition,", "this", "region", "contained", "fibrocartilage", "and", "associated", "heterotopic", "ossification,", "which", "quantitatively", "correlated", "with", "decreased", "range", "of", "motion", "(stiffness).", "Fibrotic,", "fibrocartilage", "and", "ossified", "regions", "contained", "few", "terminal", "dUTP", "nick", "end", "labeling", "(TUNEL)-positive", "or", "apoptotic", "cells,", "despite", "positive", "immunostaining", "for", "lactate", "dehydrogenase", "(LDH)5,", "a", "marker", "of", "hypoxia,", "and", "nitrotyrosine,", "a", "marker", "for", "protein", "nitrosylation.", "LDH5", "and", "nitrotyrosine", "were", "found", "in", "the", "same", "tissue", "areas,", "indicating", "that", "hypoxic", "areas", "within", "the", "tissue", "were", "associated", "with", "increased", "production", "of", "reactive", "oxygen", "and", "nitrogen", "species.", "Conclusions:", "Taken", "together,", "we", "suggest", "that", "hypoxia-associated", "oxidative", "stress", "initiates", "mast", "cell", "proliferation", "and", "FGF", "secretion,", "spurring", "fibroblast", "proliferation", "and", "tissue", "fibrosis.", "Fibroblasts", "within", "this", "hypoxic", "environment", "undergo", "metaplastic", "transformation", "to", "fibrocartilage,", "followed", "by", "heterotopic", "ossification,", "resulting", "in", "increased", "joint", "stiffness.", "Thus,", "hypoxia", "and", "associated", "oxidative", "stress", "are", "potential", "therapeutic", "targets", "for", "fibrosis", "and", "metaplastic", "progression", "of", "idiopathic", "arthrofibrosis", "after", "TKA.", "Background", "Limited", "range", "of", "motion", "is", "a", "disabling", "complication", "of", "total", "knee", "arthroplasty", "(TKA)", "[1-8].", "Idiopathic", "arthrofi-", "brosis,", "clinically", "defined", "as", "abnormal", "tissue", "scarring", "within", "the", "joint,", "represents", "the", "most", "severe", "form", "of", "stiff-", "ness.", "Even", "with", "surgical", "intervention", "or", "revision", "arthro-", "plasty,", "the", "formation", "of", "dense", "fibrous", "tissue", "and", "tissue", "contractions", "can", "recur,", "leading", "to", "increased", "severity", "of", "the", "fibrotic", "condition", "and", "eventual", "disability,", "with", "all", "the", "negative", "psychological", "and", "societal", "implications", "this", "carries", "[8].", "Unfortunately,", "there", "is", "no", "clear", "method", "by", "*", "Correspondence:", "mjs348@drexel.edu", "4School", "of", "Biomedical", "Engineering", "and", "College", "of", "Drexel", "Medicine,", "Drexel", "University,", "3120", "Market", "Street,", "323", "Bossone,", "Philadelphia,", "PA", "19104,", "USA", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "which", "patients", "who", "are", "at", "risk", "of", "developing", "arthrofibro-", "sis", "can", "be", "identified.", "It", "is", "known", "that", "arthrofibrosis", "develops", "in", "response", "to", "surgical", "intervention", "in", "approximately", "3-4%", "of", "patients", "undergoing", "TKA,", "and", "the", "resulting", "pain", "and", "loss", "of", "range", "of", "motion", "leads", "to", "patient", "disability.", "Thus,", "to", "have", "the", "possibility", "of", "developing", "a", "diagnostic", "test", "to", "pre-", "screen", "patients", "undergoing", "TKA", "and/or", "of", "implement-", "ing", "postoperative", "treatments", "that", "may", "improve", "the", "functional", "outcome,", "it", "is", "important", "to", "understand", "the", "pathoetiology", "behind", "the", "condition.", "In", "this", "study,", "we", "aimed", "to", "identify", "the", "specific", "factor(s)", "responsible", "for", "initiating", "tissue", "fibrosis,", "metaplasia", "and", "other", "histologi-", "cal", "changes", "that", "occur", "in", "arthrofibrosis.", "In", "agreement", "with", "other", "investigators,", "we", "have", "pre-", "viously", "reported", "the", "presence", "of", "aggressive", "fibroblast", "©", "2010", "Freeman", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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"5–10%", "of", "the", "splenic", "B", "cells", "in", "an", "adult", "mouse", "(4).", "Another", "B", "cell", "subset,", "consisting", "of", "the", "so-called", "B-1", "cells,", "has", "self-renewing", "capacity", "and", "predominates", "in", "the", "peritoneal", "and", "pleural", "cavities", "(5).", "Recent", "data", "on", "the", "function", "of", "MZ", "B", "cells", "(6–8)", "and", "B-1", "cells", "(9,", "10)", "suggest", "that", "these", "cells", "provide", "a", "first", "line", "of", "defense", "against", "anti-", "Address", "correspondence", "to", "Klaus", "Rajewsky,", "Department", "of", "Immu-", "nology,", "Institute", "for", "Genetics,", "University", "of", "Cologne,", "Weyertal", "121,", "D-50931", "Cologne,", "Germany.", "Phone:", "49-221-4702467;", "Fax:", "49-221-", "4705185;", "E-mail:", "klaus.rajewsky@mac.genetik.uni-koeln.de", "*Abbreviations", "used", "in", "this", "paper:", "BM,", "bone", "marrow;", "BrdU,", "bromo", "deoxyuridine;", "ELISPOT,", "enzyme-linked", "immunospot;", "ES,", "embryonic", "stem;", "FO,", "follicular;", "HSA,", "heat", "shock", "antigen;", "MZ,", "marginal", "zone;", "RAG,", "recombination-activating", "gene.", "gens", "in", "the", "blood,", "and", "in", "the", "peritoneal", "and", "pleural", "cavities,", "respectively.", "FO", "B", "cells", "are", "involved", "in", "T", "cell–dependent", "antibody", "responses,", "in", "which", "memory", "and", "plasma", "cells", "are", "generated", "(7).", "About", "1–2", "107", "immature", "B", "cells", "are", "generated", "daily", "in", "the", "adult", "murine", "BM", "(11).", "Of", "these,", "only", "3%", "enter", "the", "pool", "of", "mature", "B", "cells", "of", "the", "various", "subsets", "(12).", "Periph-", "eral", "B", "cell", "pools", "represent", "dynamic,", "yet", "stable", "compart-", "ments", "where", "the", "input", "contributed", "by", "BM", "immigrants", "and", "antigen", "driven", "cell", "proliferation", "is", "balanced", "by", "apoptosis", "and", "terminal", "differentiation", "(13).", "For", "an", "understanding", "of", "this", "homeostatic", "control", "it", "is", "of", "critical", "importance", "to", "determine", "the", "life", "spans", "of", "B", "cells", "of", "various", "subsets", "under", "physiological", "conditions.", "It", "is", "there-", "fore", "not", "surprising", "that", "B", "cell", "life", "spans", "have", "been", "the", "sub-", "ject", "of", "many", "investigations", "in", "the", "past.", "However,", "while", "it", "is", "generally", "agreed", "that", "newly", "generated", "immature", "B", "cells", "in", "adult", "mice", "have", "life", "spans", "of", "3-4", "d", "(12,", "14),", "the", "life", "spans", "of", "mature", "B", "cells", "are", "still", "controversial.", "Experiments", "based", "on", "(a)", "adoptive", "transfer", "of", "LPS-reactive", "B", "cells", "into", "LPS-", "nonreactive", "recipient", "mice", "(15);", "(b)", "the", "ablation", "of", "cycling", "B", "cell", "precursors", "with", "cytotoxic", "drugs", "which", "selectively", "kill", "cycling", "cells", "(16,", "17);", "and", "(c)", "induction", "of", "BM", "aplasia", "using", "a", "radioactive", "strontium", "isotope,", "89S", "(18)", "support", "the", "hy-", "pothesis", "that", "most", "mature", "B", "cells", "have", "a", "life", "span", "of", "just", "a", "few", "days", "(13).", "In", "contrast,", "experiments", "in", "which", "B", "cell", "de-", "velopment", "was", "blocked", "by", "anti–IL-7", "(19),", "or", "anti–IL-7", "re-", "ceptor", "antibodies", "(20)", "or", "cells", "were", "labeled", "by", "[3H]thymi-", "1151", "J.", "Exp.", "Med.", "", "The", "Rockefeller", "University", "Press", "•", "0022-1007/2001/10/1151/13", "$5.00", "Volume", "194,", "Number", "8,", "October", "15,", "2001", "1151–1163", "http://www.jem.org/cgi/content/full/194/8/1151" ]

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[ "Sun", "et", "al.", "Nanoscale", "Research", "Letters", "2011,", "6:556", "http://www.nanoscalereslett.com/content/6/1/556", "N", "A", "N", "O", "E", "X", "P", "R", "E", "S", "S", "Open", "Access", "Improved", "characteristics", "of", "near-band-edge", "and", "deep-level", "emissions", "from", "ZnO", "nanorod", "arrays", "by", "atomic-layer-deposited", "Al", "O", "and", "ZnO", "shell", "layers", "2", "3", "Wen-Cheng", "Sun1,2,", "Yu-Cheng", "Yeh1,2,", "Chung-Ting", "Ko1,", "Hau", "He", "Jr2*", "and", "Miin-Jang", "Chen1*", "Abstract", "We", "report", "on", "the", "characteristics", "of", "near-band-edge", "(NBE)", "emission", "and", "deep-level", "band", "from", "ZnO/Al2O3", "and", "ZnO/", "ZnO", "core-shell", "nanorod", "arrays", "(NRAs).", "Vertically", "aligned", "ZnO", "NRAs", "were", "synthesized", "by", "an", "aqueous", "chemical", "method,", "and", "the", "Al2O3", "and", "ZnO", "shell", "layers", "were", "prepared", "by", "the", "highly", "conformal", "atomic", "layer", "deposition", "technique.", "Photoluminescence", "measurements", "revealed", "that", "the", "deep-level", "band", "was", "suppressed", "and", "the", "NBE", "emission", "was", "significantly", "enhanced", "after", "the", "deposition", "of", "Al2O3", "and", "ZnO", "shells,", "which", "are", "attributed", "to", "the", "decrease", "in", "oxygen", "interstitials", "at", "the", "surface", "and", "the", "reduction", "in", "surface", "band", "bending", "of", "ZnO", "core,", "respectively.", "The", "shift", "of", "deep-level", "emissions", "from", "the", "ZnO/ZnO", "core-shell", "NRAs", "was", "observed", "for", "the", "first", "time.", "Owing", "to", "the", "presence", "of", "the", "ZnO", "shell", "layer,", "the", "yellow", "band", "associated", "with", "the", "oxygen", "interstitials", "inside", "the", "ZnO", "core", "would", "be", "prevailed", "over", "by", "the", "green", "luminescence,", "which", "originates", "from", "the", "recombination", "of", "the", "electrons", "in", "the", "conduction", "band", "with", "the", "holes", "trapped", "by", "the", "oxygen", "vacancies", "in", "the", "ZnO", "shell.", "PACS", "68.65.Ac;", "71.35.-y;", "78.45.+h;", "78.55.-m;", "78.55.Et;", "78.67.Hc;", "81.16.Be;", "85.60.Jb.", "Introduction", "Because", "of", "large", "surface-to-volume", "ratio", "and", "spatial", "con-", "finement", "of", "carriers,", "researches", "on", "one-dimensional", "(1D)", "nanostructures", "have", "attracted", "great", "interest", "[1-3],", "and", "remarkable", "progress", "has", "been", "achieved", "in", "various", "electro-", "nic,", "photonic,", "and", "sensing", "devices", "[3-7].", "Novel", "synthetic", "approaches", "to", "the", "fabrication", "of", "high-quality", "semiconduc-", "tor", "nanotubes", "have", "been", "reviewed", "by", "Yan", "et", "al.", "[8].", "Zinc", "oxide", "(ZnO)", "has", "been", "regarded", "as", "one", "of", "the", "most", "promis-", "ing", "materials", "for", "1D", "nanostructures", "due", "to", "its", "distin-", "guished", "characteristics", "such", "as", "direct", "and", "wide", "band", "gap", "(approximately", "3.37", "eV),", "large", "excitonic", "binding", "energy", "(up", "to", "60", "meV),", "and", "high", "piezoelectricity", "[9-11].", "The", "synthesis", "of", "well-aligned", "ZnO", "nanorod", "arrays", "(NRAs)", "is", "crucially", "important", "for", "the", "practical", "applications", "such", "as", "field", "emitters", "[12],", "nanogenerators", "[13],", "solar", "cells", "[14],", "and", "nanolasers", "[15].", "One", "of", "the", "popular", "techniques", "for", "fabricating", "ZnO", "NRAs", "is", "to", "use", "Au", "as", "catalyst", "on", "a", "lattice-", "*", "Correspondence:", "jhhe@cc.ee.ntu.edu.tw;", "mjchen@ntu.edu.tw", "1Department", "of", "Materials", "Science", "and", "Engineering,", "National", "Taiwan", "University,", "Taipei", "10617,", "Taiwan", "2Graduate", "Institute", "of", "Photonics", "and", "Optoelectronics,", "National", "Taiwan", "University,", "Taipei", "10617,", "Taiwan", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "matched", "substrate", "[16].", "Since", "the", "optical", "properties", "of", "ZnO", "NRAs", "are", "strongly", "dependent", "on", "surface", "conditions", "[17-20]", "and", "natural", "defect", "states", "[21-24],", "a", "large", "variety", "of", "surface", "modifications", "on", "ZnO", "NRAs", "have", "been", "carried", "out", "by", "depositing", "a", "shell", "layer.", "For", "instance,", "the", "enhance-", "ment", "of", "photoluminescence", "(PL)", "has", "been", "observed", "in", "ZnO/Er2O3", "and", "ZnO/MgZnO", "core-shell", "NRAs", "[25,26].", "The", "enhanced", "surface-excitonic", "emission", "together", "with", "the", "suppression", "in", "deep-level", "emission", "has", "also", "been", "reported", "in", "ZnO/amorphous-Al2O3", "core-shell", "nanowires", "[27].", "Apart", "from", "the", "enhancement", "of", "light", "emission,", "strong", "photoconductivity", "[28],", "photocatalytic", "activity", "[29],", "and", "quantum", "confinement", "[30]", "have", "been", "observed", "in", "var-", "ious", "1D", "ZnO", "nanostructures.", "In", "this", "paper,", "vertically", "aligned", "ZnO", "NRAs", "were", "synthe-", "sized", "using", "an", "aqueous", "chemical", "method,", "which", "is", "benefi-", "cial", "for", "low", "reaction", "temperature,", "low", "cost,", "catalyst-free", "synthesis,", "and", "large-scale", "production.", "The", "growth", "of", "ZnO", "NRAs", "was", "assisted", "by", "a", "ZnO", "seed", "layer", "prepared", "by", "atomic", "layer", "deposition", "(ALD).", "The", "self-limiting", "and", "layer-by-layer", "growth", "of", "ALD", "contribute", "to", "many", "advan-", "tages", "such", "as", "easy", "and", "accurate", "thickness", "control,", "confor-", "mal", "step", "coverage,", "high", "uniformity", "over", "a", "large", "area,", "low", "defect", "density,", "good", "reproducibility,", "and", "low", "deposition", "©", "2011", "Sun", "et", "al;", "licensee", "Springer.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "BMC", "Public", "Health", "Research", "article", "The", "health", "of", "people", "classified", "as", "lesbian,", "gay", "and", "bisexual", "attending", "family", "practitioners", "in", "London:", "a", "controlled", "study", "Michael", "King1", "and", "Irwin", "Nazareth*2", "BioMed", "Central", "Open", "Access", "Address:", "1Professor", "of", "Primary", "Care", "Psychiatry,", "Department", "of", "Mental", "Health", "Sciences,", "Royal", "Free", "and", "University", "College", "Medical", "School,", "University", "College", "London,", "Royal", "Free", "Campus,", "Rowland", "Hill", "Street,", "London", "NW3", "2PF,", "UK", "and", "2Professor", "of", "Primary", "Care", "&", "Population", "Sciences", "&", "Director", "MRC", "General", "Practice", "Research", "Framework,", "Department", "of", "Primary", "Care", "and", "Population", "Sciences,", "Royal", "Free", "and", "University", "College", "Medical", "School,", "University", "College", "London", "(UCL),", "Rowland", "Hill", "Street,", "London", "NW3", "2PF,", "UK", "Email:", "Michael", "King", "-", "m.king@medsch.ucl.ac.uk;", "Irwin", "Nazareth*", "-", "i.nazareth@pcps.ucl.ac.uk", "*", "Corresponding", "author", "Published:", "08", "May", "2006", "BMC", "Public", "Health", "2006,", "6:127", "doi:10.1186/1471-2458-6-127", "This", "article", "is", "available", "from:", "http://www.biomedcentral.com/1471-2458/6/127", "Received:", "24", "October", "2005", "Accepted:", "08", "May", "2006", "©", "2006", "King", "and", "Nazareth;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Background:", "The", "morbidity", "of", "gay,", "lesbian", "or", "bisexual", "people", "attending", "family", "practice", "has", "not", "been", "previously", "assessed.", "We", "compared", "health", "measures", "of", "family", "practice", "attendees", "classified", "as", "lesbian,", "gay", "and", "bisexual.", "Methods:", "We", "conducted", "a", "cross-sectional,", "controlled", "study", "conducted", "in", "13", "London", "family", "practices", "and", "compared", "the", "responses", "of", "26", "lesbian", "and", "85", "bisexual", "classified", "women,", "with", "that", "of", "934", "heterosexual", "classified", "women", "and", "38", "gay", "and", "23", "bisexual", "classified", "men", "with", "that", "of", "373", "heterosexual", "classified", "men.", "Our", "outcomes", "of", "interest", "were:", "General", "health", "questionnaire;", "CAGE", "questionnaire;", "short", "form12;", "smoking", "status;", "sexual", "experiences", "during", "childhood;", "number", "of", "sexual", "partners", "and", "sexual", "function", "and", "satisfaction.", "Results:", "In", "comparison", "to", "people", "classified", "as", "heterosexuals:", "men", "classified", "as", "gay", "reported", "higher", "levels", "of", "psychological", "symptoms", "(OR", "2.48,", "CI", "1.05–5.90);", "women", "classified", "as", "bisexual", "were", "more", "likely", "to", "misuse", "alcohol", "(OR", "2.73,", "1.70–4.40);", "women", "classified", "as", "bisexual", "(OR", "2.53,", "1.60–4.00)", "and", "lesbian", "(OR", "3.13,", "1.41–6.97)", "and", "men", "classified", "as", "bisexual", "(OR", "2.48,", "1,04,", "5.86)", "were", "more", "likely", "to", "be", "smokers", "and", "women", "classified", "as", "bisexual", "(OR", "3.27,", "1.97–5.43)", "and", "men", "classified", "as", "gay", "(OR", "4.86,", "2.28–10.34)", "were", "much", "more", "likely", "to", "report", "childhood", "sexual", "experiences", "in", "childhood.", "Psychological", "distress", "was", "associated", "with", "reporting", "sexual", "experiences", "in", "childhood", "in", "men", "classified", "as", "gay", "and", "bisexual", "and", "women", "classified", "as", "heterosexual.", "Men", "classified", "as", "bisexual", "(OR", "5.00,", "1.73–14.51)", "and", "women", "classified", "as", "bisexual", "(OR", "2.88,", "1.24-", "6.56)", "were", "more", "likely", "than", "heterosexuals", "to", "report", "more", "than", "one", "sexual", "partner", "in", "the", "preceding", "four", "weeks.", "Lesbian,", "gay", "and", "bisexual", "classified", "people", "encountered", "no", "more", "sexual", "function", "problems", "than", "heterosexuals", "but", "men", "classified", "as", "bisexual", "(OR", "2.74,", "1.12–6.70)", "were", "more", "dissatisfied", "with", "their", "sex", "lives.", "Conclusion:", "Bisexual", "and", "lesbian", "classified", "people", "attending", "London", "general", "practices", "were", "more", "likely", "to", "be", "smokers", "and", "gay", "classified", "men", "were", "at", "increased", "risk", "of", "psychological", "distress", "in", "comparison", "to", "heterosexual", "classified", "people.", "Increased", "awareness", "of", "the", "sexuality", "of", "people", "seen", "in", "primary", "care", "can", "provide", "opportunities", "for", "health", "promotion.", "Page", "1", "of", "12", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "ORIGINAL", "ARTICLE", "The", "Effects", "of", "a", "10-Week", "Water", "Aerobic", "Exercise", "on", "the", "Resting", "Blood", "Pressure", "in", "Patients", "with", "Essential", "Hypertension", "Ali", "Vasheghani", "Farahani", "1,2,", "MD;", "Mohammad-Ali", "Mansournia*1,", "MD,", "MPH;", "Hossein", "Asheri1,", "MD;", "Akbar", "Fotouhi3,", "MD,", "PhD;", "Masud", "Yunesian3,", "MD,", "PhD;", "Mohsen", "Jamali1,", "MD;", "Vahid", "Ziaee1,", "MD", "Authors’", "Affiliation:", "1.", "Sports", "Medicine", "Research", "Center,", "Tehran", "University", "of", "Medical", "Sciences,", "Tehran,", "IR", "Iran", "2.", "Department", "of", "Cardiology,", "Tehran", "University", "of", "Medical", "Sciences,", "Tehran,", "IR", "Iran", "3.", "School", "of", "Public", "Health,", "Tehran", "University", "of", "Medical", "Sciences,", "Tehran,", "IR", "Iran", "*", "Corresponding", "Author;", "Address:", "Sports", "Medicine", "Research", "Center,", "No", "7,", "Al-e-Ahmad", "Highway,", "P.O.", "Box", "14395-578,", "Tehran,", "IR", "Iran", "E-mail:", "mansournia_ma@yahoo.com", "Received:", "May", "29,", "2010", "Accepted:", "Jul", "23,", "2010", "Key", "Words:", "Water", "aerobic", "exercise;", "Swimming;", "Essential", "hypertension;", "Blood", "pressure", "Abstract", "Purpose:", "To", "investigate", "the", "effects", "of", "a", "10-week", "water", "aerobic", "exercise", "on", "the", "resting", "blood", "pressure", "in", "patients", "with", "stage", "1", "or", "2", "hypertension", "referring", "to", "Tehran", "University", "Clinics.", "Methods:", "Forty", "men", "with", "stage", "1", "or", "2", "essential", "hypertension", "were", "assigned", "to", "two", "groups", "of", "intervention", "[n=12;", "aged", "48.33", "±", "10.74", "years", "(mean", "±", "SD)]", "and", "control", "[n=28;", "aged", "46.96", "±", "11.58", "years", "(mean", "±", "SD)].", "Subjects", "in", "the", "intervention", "group", "participated", "in", "a", "supervised", "10-week", "water", "aerobic", "training", "program", "of", "55", "min", "sessions,", "3", "days", "per", "week", "on", "alternate", "days,", "while", "those", "in", "the", "control", "group", "were", "not", "involved", "in", "any", "regular", "training", "program", "during", "this", "period.", "Blood", "pressure", "of", "the", "participants", "was", "recorded", "and", "compared", "at", "the", "beginning", "and", "at", "the", "end", "of", "the", "study", "(48", "hours", "after", "the", "last", "training", "session).", "Results:", "Exercise", "lowered", "systolic", "blood", "pressure", "and", "mean", "arterial", "pressure", "by", "11.71", "(95%", "confidence", "interval:", "5.07", "to", "18.35)", "and", "5.90", "(95%", "confidence", "interval:", "1.17", "to", "10.63)", "mm", "Hg", "respectively.", "The", "lowering", "effect", "of", "exercise", "on", "diastolic", "blood", "pressure", "was", "neither", "statistically", "significant", "nor", "clinically", "important", "(0.55", "mm", "Hg;", "P.", "value", "=", "0.8).", "There", "was", "no", "significant", "effect", "of", "age,", "baseline", "body", "mass", "index", "and", "stage", "of", "hypertension", "on", "the", "exercise-induced", "changes", "in", "blood", "pressure.", "Conclusion:", "A", "10-week", "course", "of", "water", "aerobic", "exercise", "markedly", "reduced", "the", "systolic", "and", "mean", "arterial", "blood", "pressure", "of", "patients", "with", "essential", "hypertension", "and", "is", "especially", "recommended", "for", "the", "obese", "and", "the", "elderly", "who", "have", "orthopedic", "problems", "or", "bronchospasm.", "Asian", "Journal", "of", "Sports", "Medicine,", "Vol", "1", "(No", "3),", "Sep", "2010,", "Pages:", "159-167", "159", "INTRODUCTION", "Hpressure", "of", ">=", "140", "and/or", "diastolic", "blood", "ypertension,", "defined", "as", "resting", "systolic", "blood", "pressure", "of", ">=", "90", "mmHg,", "remains", "the", "most", "common", "risk", "factor", "for", "cardiovascular", "morbidity", "and", "mortality.", "Currently,", "more", "than", "a", "quarter", "of", "the", "world", "adult", "population", "suffer", "from", "hypertension", "and", "it", "is", "expected", "that", "this", "number", "will", "increase", "to", "1.56", "billion", "(29%)", "by", "2025[1,2].", "The", "primary", "goal", "of", "the", "treatment", "of", "©", "2010", "by", "Sports", "Medicine", "Research", "Center,", "Tehran", "University", "of", "Medical", "Sciences,", "All", "rights", "reserved." ]

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[ "BMC", "Medical", "Imaging", "Technical", "advance", "Extended", "Field", "Laser", "Confocal", "Microscopy", "(EFLCM):", "Combining", "automated", "Gigapixel", "image", "capture", "with", "in", "silico", "virtual", "microscopy", "Emilie", "Flaberg1,2,", "Per", "Sabelström3,", "Christer", "Strandh3", "and", "Laszlo", "Szekely*1,2", "BioMed", "Central", "Open", "Access", "Address:", "1Department", "of", "Microbiology,", "Tumor", "and", "Cell", "Biology", "(MTC)", "and", "Center", "for", "Integrative", "Recognition", "in", "the", "Immune", "System", "(IRIS),", "Karolinska", "Institute,", "Box", "280", "S-17177", "Stockholm,", "2Sweden", "Karolinska", "Institute", "Visualization", "Core", "Facility", "(KIVIF)", "and", "3Aragon", "System", "Poppelvägen", "11", "SE-832", "54", "Froson", "Sweden", "Email:", "Emilie", "Flaberg", "-", "Emilie.Flaberg@ki.se;", "Per", "Sabelström", "-", "pesa@aragonsystem.com;", "Christer", "Strandh", "-", "christer.strandh@aragonsystem.com;", "Laszlo", "Szekely*", "-", "lassze@ki.se", "*", "Corresponding", "author", "Published:", "16", "July", "2008", "BMC", "Medical", "Imaging", "2008,", "8:13", "doi:10.1186/1471-2342-8-13", "This", "article", "is", "available", "from:", "http://www.biomedcentral.com/1471-2342/8/13", "Received:", "19", "November", "2007", "Accepted:", "16", "July", "2008", "©", "2008", "Flaberg", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Background:", "Confocal", "laser", "scanning", "microscopy", "has", "revolutionized", "cell", "biology.", "However,", "the", "technique", "has", "major", "limitations", "in", "speed", "and", "sensitivity", "due", "to", "the", "fact", "that", "a", "single", "laser", "beam", "scans", "the", "sample,", "allowing", "only", "a", "few", "microseconds", "signal", "collection", "for", "each", "pixel.", "This", "limitation", "has", "been", "overcome", "by", "the", "introduction", "of", "parallel", "beam", "illumination", "techniques", "in", "combination", "with", "cold", "CCD", "camera", "based", "image", "capture.", "Methods:", "Using", "the", "combination", "of", "microlens", "enhanced", "Nipkow", "spinning", "disc", "confocal", "illumination", "together", "with", "fully", "automated", "image", "capture", "and", "large", "scale", "in", "silico", "image", "processing", "we", "have", "developed", "a", "system", "allowing", "the", "acquisition,", "presentation", "and", "analysis", "of", "maximum", "resolution", "confocal", "panorama", "images", "of", "several", "Gigapixel", "size.", "We", "call", "the", "method", "Extended", "Field", "Laser", "Confocal", "Microscopy", "(EFLCM).", "Results:", "We", "show", "using", "the", "EFLCM", "technique", "that", "it", "is", "possible", "to", "create", "a", "continuous", "confocal", "multi-colour", "mosaic", "from", "thousands", "of", "individually", "captured", "images.", "EFLCM", "can", "digitize", "and", "analyze", "histological", "slides,", "sections", "of", "entire", "rodent", "organ", "and", "full", "size", "embryos.", "It", "can", "also", "record", "hundreds", "of", "thousands", "cultured", "cells", "at", "multiple", "wavelength", "in", "single", "event", "or", "time-lapse", "fashion", "on", "fixed", "slides,", "in", "live", "cell", "imaging", "chambers", "or", "microtiter", "plates.", "Conclusion:", "The", "observer", "independent", "image", "capture", "of", "EFLCM", "allows", "quantitative", "measurements", "of", "fluorescence", "intensities", "and", "morphological", "parameters", "on", "a", "large", "number", "of", "cells.", "EFLCM", "therefore", "bridges", "the", "gap", "between", "the", "mainly", "illustrative", "fluorescence", "microscopy", "and", "purely", "quantitative", "flow", "cytometry.", "EFLCM", "can", "also", "be", "used", "as", "high", "content", "analysis", "(HCA)", "instrument", "for", "automated", "screening", "processes.", "Background", "The", "introduction", "of", "laser", "scanning", "confocal", "fluorescence", "microscopy", "represented", "a", "major", "breakthrough", "in", "biology.", "The", "elimination", "of", "the", "disturbing", "out", "of", "focus", "light", "allowed", "the", "visualization", "of", "delicate", "sub-cellular", "struc-", "tures", "that", "were", "hidden", "in", "the", "blur", "of", "thick", "samples", "[1-4].", "Although", "the", "technique", "reveals", "structures", "with", "unprece-", "dented", "sharpness,", "it", "also", "suffers", "from", "limitations.", "The", "images", "generate", "by", "scanning", "a", "sample", "with", "a", "single", "laser", "beam,", "where", "the", "in-focus", "signal", "passes", "a", "pinhole", "and", "is", "Page", "1", "of", "13", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Histochem", "Cell", "Biol", "(2008)", "129:5–11", "DOI", "10.1007/s00418-007-0355-x", "R", "E", "V", "I", "E", "W", "Physiological", "importance", "of", "RNA", "and", "protein", "mobility", "in", "the", "cell", "nucleus", "Tom", "Misteli", "Accepted:", "27", "October", "2007", "/", "Published", "online:", "10", "November", "2007", "©", "Springer-Verlag", "2007", "Abstract", "TraYcking", "of", "proteins", "and", "RNAs", "is", "essential", "for", "cellular", "function", "and", "homeostasis.", "While", "it", "has", "long", "been", "appreciated", "that", "proteins", "and", "RNAs", "move", "within", "cells,", "only", "recently", "has", "it", "become", "possible", "to", "visualize", "traYcking", "events", "in", "vivo.", "Analysis", "of", "protein", "and", "RNA", "motion", "within", "the", "cell", "nucleus", "have", "been", "particularly", "intriguing", "as", "they", "have", "revealed", "an", "unanticipated", "degree", "of", "dynamics", "within", "the", "organelle.", "These", "methods", "have", "revealed", "that", "the", "intra-", "nuclear", "traYcking", "occurs", "largely", "by", "energy-independent", "mechanisms", "and", "is", "driven", "by", "diVusion.", "RNA", "molecules", "and", "non-DNA", "binding", "proteins", "undergo", "constrained", "diVusion,", "largely", "limited", "by", "the", "spatial", "constraint", "imposed", "by", "chro-", "matin,", "and", "chromatin", "binding", "proteins", "move", "by", "a", "stop-and-", "go", "mechanism", "where", "their", "free", "diVusion", "is", "interrupted", "by", "random", "association", "with", "the", "chromatin", "Wber.", "The", "ability", "and", "mode", "of", "motion", "of", "proteins", "and", "RNAs", "has", "implications", "for", "how", "they", "Wnd", "nuclear", "targets", "on", "chromatin", "and", "in", "nuclear", "subcompartments", "and", "how", "macromolecular", "com-", "plexes", "are", "assembled", "in", "vivo.", "Most", "importantly,", "the", "dynamic", "nature", "of", "proteins", "and", "RNAs", "is", "emerging", "as", "a", "means", "to", "control", "physiological", "cellular", "responses", "and", "path-", "ways.", "Keywords", "Nuclear", "architecture", "·", "Dynamics", "·", "DiVusion", "·", "RNA", "T.", "Misteli", "(&)", "National", "Cancer", "Institute,", "National", "Institutes", "of", "Health,", "41", "Library", "Drive,", "Bethesda,", "MD", "20892,", "USA", "e-mail:", "mistelit@mail.nih.gov", "Introduction", "It", "is", "an", "irony", "of", "science", "that", "the", "discovery", "of", "fundamental", "principles", "is", "often", "delayed.", "A", "case", "in", "point", "is", "the", "cell", "bio-", "logical", "investigation", "of", "the", "cell", "nucleus.", "The", "nucleus", "is", "arguably", "the", "functionally", "most", "prominent", "cellular", "orga-", "nelle", "as", "it", "houses", "the", "vast", "majority", "of", "the", "genetic", "informa-", "tion", "and", "is", "the", "exclusive", "site", "of", "essential", "processes", "including", "transcription,", "RNA", "processing,", "replication", "and", "DNA", "repair.", "Yet,", "our", "understanding", "of", "how", "the", "nucleus", "is", "organized", "and", "how", "nuclear", "architecture", "contributes", "to", "cel-", "lular", "function", "is", "only", "now", "emerging", "and", "still", "lags", "behind", "that", "of", "most", "other", "cellular", "compartments.", "Fortunately,", "pioneering", "studies", "over", "the", "past", "decade", "have", "uncovered", "several", "of", "the", "fundamental", "principles", "which", "determine", "nuclear", "architecture", "and", "function", "(Lanctot", "et", "al.", "2007;", "Misteli", "2001;", "Spector", "2003).", "These", "studies", "have", "revealed", "the", "presence", "of", "distinct", "structural", "elements,", "particularly", "lamin", "proteins", "and", "possibly", "short", "actin", "Wlaments,", "within", "the", "nucleus", "and", "they", "have", "led", "to", "the", "identiWcation", "of", "a", "large", "number", "of", "distinct", "nuclear", "subcompartments", "in", "which", "speciWc", "nuclear", "functions,", "such", "as", "the", "synthesis", "and", "processing", "of", "ribosomal", "RNA", "in", "the", "nucleolus,", "occur", "(Burke", "and", "Stewart", "2006;", "Gruenbaum", "et", "al.", "2005;", "Hand-", "werger", "and", "Gall", "2006;", "Hernandez-Verdun", "2006;", "Lamond", "and", "Sleeman", "2003)", "(Fig.", "1a).", "In", "addition,", "it", "has", "become", "clear", "that", "the", "genome", "is", "non-randomly", "organized", "within", "the", "spatial", "conWnes", "of", "the", "nucleus", "with", "speciWc", "chromo-", "somes", "and", "genes", "preferentially", "localizing", "to", "speciWc", "sites", "(Lanctot", "et", "al.", "2007;", "Meaburn", "and", "Misteli", "2007)", "(Fig.", "1b,", "c).", "These", "observations", "paint", "a", "picture", "of", "a", "highly", "complex", "and", "heterogeneous", "cell", "nucleus.", "They", "also", "indicate", "that", "some", "properties", "of", "the", "nucleus", "are", "counterintuitive.", "For", "example,", "despite", "the", "requirement", "to", "accommodate", "»2", "m", "of", "DNA", "within", "the", "cell", "nucleus", "of", "a", "diameter", "of", "typically", "123" ]

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[ "Hindawi", "Publishing", "Corporation", "Journal", "of", "Tropical", "Medicine", "Volume", "2012,", "Article", "ID", "132583,", "8", "pages", "doi:10.1155/2012/132583", "Clinical", "Study", "A", "Single", "Dose", "of", "Oral", "BCG", "Moreau", "Fails", "to", "Boost", "Systemic", "IFN-γ", "Responses", "to", "Tuberculin", "in", "Children", "in", "the", "Rural", "Tropics:", "Evidence", "for", "a", "Barrier", "to", "Mucosal", "Immunization", "Maritza", "Vaca,1", "Ana-Lucia", "Moncayo,1", "Catherine", "A.", "Cosgrove,2", "Martha", "E.", "Chico,1,", "3", "Luiz", "R.", "Castello-Branco,4,", "5", "David", "J.", "Lewis,2", "and", "Philip", "J.", "Cooper1,", "3,", "6,", "7", "1", "Centro", "de", "Investigacio´nes", "FEPIS,", "Esmeraldas", "Quinind´e,", "Ecuador", "2", "Vaccine", "Centre,", "St", "George’s", "University", "of", "London,", "Cranmer", "Terrace,", "London", "SW17", "ORE,", "UK", "3", "Laboratorio", "de", "Biologia", "Molecular,", "Hospital", "de", "Los", "Valles,", "Via", "Interoceanica", "Km", "12.5,", "Cumbaya´,", "Quito,", "Ecuador", "4", "Fundacao", "Ataulpho", "de", "Paiva,", "Avenida", "Pedro", "II,", "226", "Sao", "Cristovao,", "20941-000", "Rio", "de", "Janeiro,", "RJ,", "Brazil", "5", "Department", "of", "Immunology,", "Fundacao", "Instituto", "Oswaldo", "Cruz,", "4365", "Avenida", "Brasil,", "21040-360", "Rio", "de", "Janeiro,", "RJ,", "Brazil", "6", "Molecular", "and", "Biochemical", "Parasitology,", "Liverpool", "School", "of", "Tropical", "Medicine,", "Pembroke", "Place,", "Liverpool", "L3", "5QA,", "UK", "7", "Colegio", "de", "Ciencias", "de", "la", "Salud,", "Universidad", "San", "Francisco", "de", "Quito,", "Via", "Interoceanica", "S/N", "y", "Avenida", "Pampite,", "Quito,", "Ecuador", "Correspondence", "should", "be", "addressed", "to", "Philip", "J.", "Cooper,", "p.j.cooper@liv.ac.uk", "Received", "16", "May", "2011;", "Revised", "9", "September", "2011;", "Accepted", "28", "September", "2011", "Academic", "Editor:", "Ann-Mari", "Svennerholm", "Copyright", "©", "2012", "Maritza", "Vaca", "et", "al.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Immune", "responses", "to", "oral", "vaccines", "are", "impaired", "in", "populations", "living", "in", "conditions", "of", "poverty", "in", "developing", "countries,", "and", "there", "is", "evidence", "that", "concurrent", "geohelminth", "infections", "may", "contribute", "to", "this", "effect.", "We", "vaccinated", "48", "children", "living", "in", "rural", "communities", "in", "Ecuador", "with", "a", "single", "oral", "dose", "of", "100", "mg", "of", "BCG", "Moreau", "RDJ", "and", "measured", "the", "frequencies", "of", "tuberculin-", "stimulated", "peripheral", "blood", "mononuclear", "cells", "expressing", "IFN-γ", "before", "and", "after", "vaccination.", "Vaccinated", "children", "had", "active", "ascariasis", "(n", "=", "20)", "or", "had", "been", "infected", "but", "received", "short-", "(n", "=", "13)", "or", "long-term", "(n", "=", "15)", "repeated", "treatments", "with", "albendazole", "prior", "to", "vaccination", "to", "treat", "ascariasis.", "All", "children", "had", "a", "BCG", "scar", "from", "neonatal", "vaccination.", "There", "was", "no", "evidence", "of", "a", "boosting", "of", "postvaccination", "IFN-γ", "responses", "in", "any", "of", "the", "3", "study", "groups.", "Our", "data", "provide", "support", "for", "the", "presence", "of", "a", "barrier", "to", "oral", "vaccination", "among", "children", "from", "the", "rural", "tropics", "that", "appeared", "to", "be", "independent", "of", "concurrent", "ascariasis.", "1.", "Introduction", "The", "use", "of", "oral", "vaccines", "in", "children", "and", "adults", "from", "poor", "populations,", "particularly", "in", "the", "tropics,", "has", "been", "associated", "with", "reduced", "efficacy", "and", "impaired", "immune", "responses.", "Impaired", "immune", "responses", "have", "been", "reported", "for", "both", "live-attenuated", "and", "killed", "vaccines", "including", "Sabin", "oral", "polio", "vaccine", "[1],", "rotavirus", "[2,", "3],", "cholera", "[4],", "Shigella", "[2,", "5],", "and", "a", "killed", "Vibrio", "cholerae", "O1", "plus", "B", "subunit", "vaccine", "[6].", "Such", "effects", "are", "observed", "at", "doses", "that", "are", "highly", "immunogenic", "in", "subjects", "from", "North", "America", "or", "Europe", "and,", "in", "some", "circumstances,", "may", "be", "overcome", "by", "an", "increase", "in", "the", "size", "of", "vaccine", "dose", "or", "the", "number", "of", "doses", "administered", "[4,", "7–9].", "Barriers", "to", "effective", "vaccination", "with", "oral", "vaccines", "in", "poor", "populations", "living", "in", "the", "tropics", "include", "nutritional", "deficiencies", "(e.g.,", "vitamin", "A", "and", "zinc),", "chronic", "diarrhoea,", "pre-existing", "mucosal", "immunity", "(e.g.,", "intestinal", "secretory", "IgA),", "the", "presence", "of", "maternal", "antibodies", "in", "breast", "milk,", "environmental", "enteropathy", "[3,", "4],", "and", "coinfections", "with", "enteric", "bacterial", "infections,", "and", "protozoal", "(e.g.,", "Giardia", "intestinalis)", "and", "geohelminth", "parasites", "[10].", "The", "geo-", "helminth", "parasites,", "Ascaris", "lumbricoides,", "Trichuris", "trichiura,", "and", "hookworm", "have", "a", "worldwide", "distribution", "and", "are", "strongly", "associated", "with", "poverty.", "Geohelminths", "infect", "an", "estimated", "2", "billion", "humans", "[11]", "and", "prevalence,", "in", "the", "case", "of", "A.", "lumbricoides,", "is", "highest", "among", "preschool", "and", "school", "age", "children.", "Infections", "are", "chronic,", "tend", "to", "be", "acquired", "during", "the", "second", "year", "of", "life,", "and", "may", "persist", "into", "adulthood", "through", "residence", "in", "an", "environment", "that", "is", "heavily", "contaminated", "with", "human", "faeces.", "Geohelminth" ]

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[ "Journal", "of", "Child", "Psychology", "and", "Psychiatry", "53:10", "(2012),", "pp", "1082–1083", "doi:10.1111/j.1469-7610.2012.02610.x", "Commentary:", "Unravelling", "the", "effects", "of", "additional", "sex", "chromosomes", "on", "cognition", "and", "communication", "–", "reflections", "on", "Lee", "et", "al.", "(2012)", "Dorothy", "V.M.", "Bishop", "Department", "of", "Experimental", "Psychology,", "University", "of", "Oxford,", "Oxford,", "UK", "Most", "people", "have", "23", "pairs", "of", "chromosomes;", "one", "set", "from", "the", "mother", "and", "one", "from", "the", "father.", "However,", "nondisjunction", "errors", "during", "meiosis", "can", "lead", "to", "a", "case", "of", "trisomy,", "where", "there", "are", "three", "rather", "than", "two", "chromosomes.", "Although", "such", "events", "are", "not", "uncommon,", "they", "are", "usually", "lethal,", "and", "account", "for", "a", "high", "proportion", "of", "spontaneous", "abortions.", "The", "most", "common", "trisomy", "compatible", "with", "survival", "to", "birth", "involves", "chromosome", "21,", "one", "of", "the", "smallest", "chromosomes.", "This", "is", "associated", "with", "serious", "developmental", "abnormalities", "affecting", "a", "range", "of", "organs", "(Down", "syndrome).", "In", "comparison,", "the", "effects", "of", "a", "sex", "chromosome", "trisomy", "are", "relatively", "mild.", "Most", "children", "with", "XXX,", "XXY", "or", "XYY", "constitutions", "attend", "regular", "school", "and,", "apart", "from", "a", "tendency", "to", "be", "somewhat", "taller", "than", "average,", "appear", "physically", "normal.", "The", "reason", "for", "this", "can", "be", "found", "in", "the", "peculiar", "nature", "of", "the", "sex", "chromosomes.", "The", "Y", "chromosome", "is", "very", "small", "and", "is", "thought", "to", "contain", "fewer", "than", "100", "genes,", "com-", "pared", "with", "over", "1000", "on", "the", "X", "chromosome.", "All", "else", "being", "equal,", "females", "should", "have", "considerably", "more", "gene", "product", "than", "males.", "However,", "in", "normal", "XX", "females,", "most", "of", "one", "X-chromosome", "is", "inactivated.", "A", "process", "of", "methylation", "causes", "the", "DNA", "to", "be", "packed", "in", "a", "tight", "ball,", "preventing", "gene", "expression.", "This", "process", "of", "‘dosage", "compensation’", "has", "the", "effect", "of", "reducing", "the", "difference", "between", "males", "and", "females", "in", "amount", "of", "gene", "product.", "X-inactivation", "is", "not", "complete;", "there", "are", "regions", "on", "the", "tips", "of", "the", "sex", "chromosomes", "that", "remain", "active", "and", "behave", "just", "like", "autosomes;", "these", "are", "referred", "to", "as", "the", "pseudoautosomal", "region.", "In", "addition,", "there", "are", "areas", "of", "the", "X-chromosome", "outside", "the", "pseudoaut-", "osomal", "region", "that", "escape", "inactivation,", "where", "both", "copies", "of", "a", "gene", "are", "expressed.", "There", "appears", "to", "be", "quite", "substantial", "individual", "variation", "in", "the", "number", "and", "location", "of", "genes", "that", "escape", "inactivation.", "If", "we", "put", "these", "pieces", "of", "information", "together,", "we", "start", "to", "see", "why", "the", "impact", "of", "an", "additional", "sex", "chromosome", "is", "relatively", "mild.", "For", "boys", "with", "XYY", "constitution,", "the", "additional", "Y", "chromosome", "contains", "relatively", "few", "genes.", "For", "girls", "or", "boys", "with", "an", "extra", "X,", "only", "one", "X", "chromosome", "is", "completely", "activated,", "and", "so", "a", "minority", "of", "X-linked", "genes", "are", "expressed", "in", "extra", "dose.", "The", "author", "has", "declared", "that", "she", "has", "no", "competing", "or", "poten-", "tial", "conflicts", "of", "interest.", "Nevertheless,", "there", "are", "cognitive", "impacts", "of", "an", "extra", "sex", "chromosome,", "as", "discussed", "in", "the", "article", "by", "Lee", "et", "al.", "(2012),", "with", "intriguing", "differences", "between", "those", "with", "an", "extra", "X", "or", "Y.", "There", "is", "surprisingly", "little", "research", "on", "sex", "chromosome", "trisomies:", "The", "expla-", "nation", "is", "largely", "due", "to", "the", "mild", "impact", "of", "the", "tri-", "somy,", "which", "means", "that", "many", "people", "who", "have", "a", "sex", "chromosome", "trisomy", "would", "not", "be", "aware", "of", "their", "status.", "Most", "of", "the", "information", "we", "have", "about", "prev-", "alence", "and", "consequences", "of", "sex", "chromosome", "triso-", "mies", "comes", "from", "a", "set", "of", "studies", "carried", "out", "in", "the", "1960–1970s", "in", "which", "newborn", "babies", "underwent", "chromosome", "screening.", "Such", "studies", "are", "unlikely", "to", "be", "repeated", "now", "for", "two", "reasons.", "First,", "they", "are", "highly", "labour-intensive:", "given", "that,", "for", "instance,", "XXX", "chromosome", "constitution", "is", "found", "in", "around", "1", "in", "1,000", "girls,", "this", "means", "we", "would", "have", "to", "screen", "10,000", "cases", "to", "get", "a", "sample", "of", "just", "10", "affected", "cases.", "Research", "is", "also", "limited", "by", "ethical", "concerns.", "The", "studies", "done", "in", "the", "1960s", "proved", "problematic", "as", "the", "researchers", "started", "to", "realise", "that", "telling", "parents", "that", "their", "newborn", "child", "had", "a", "sex", "chromosome", "tri-", "somy", "was", "bound", "to", "cause", "anxiety", "and", "distress,", "especially", "since", "information", "about", "its", "likely", "impact", "was", "so", "uncertain.", "Findings", "from", "the", "newborn", "screening", "studies", "were", "summarized", "in", "a", "systematic", "review", "by", "Leggett,", "Jacobs,", "Nation,", "Scerif,", "and", "Bishop", "(2010),", "who", "noted", "a", "reduction", "in", "IQ", "in", "XXX,", "XXY", "and", "XYY", "groups,", "with", "both", "groups", "of", "males", "showing", "evidence", "of", "disproportionate", "verbal", "impairments.", "Such", "deficits", "are", "assumed", "to", "be", "caused", "by", "the", "excess", "proteins", "that", "arise", "from", "supernumerary", "X-", "or", "Y-", "linked", "genes", "that", "escape", "inactivation.", "The", "report", "by", "Lee", "et", "al.", "makes", "a", "unique", "contribu-", "tion", "by", "extending", "the", "study", "of", "the", "impact", "of", "super-", "numerary", "sex", "chromosomes", "to", "include", "rare", "cases", "of", "children", "with", "four", "or", "five", "sex", "chromosomes.", "They", "demonstrate", "a", "clear", "‘dosage’", "effect,", "whereby", "the", "more", "chromosomes,", "the", "greater", "the", "negative", "impact", "on", "IQ", "and", "development.", "Each", "additional", "X-", "or", "Y-", "chromosome", "was", "associated", "with", "a", "decrease", "in", "IQ", "of", "around", "1", "SD.", "Intriguingly,", "they", "also", "found", "that", "additional", "X", "chromosomes", "had", "a", "greater", "effect", "on", "structural", "language", "skills,", "whereas", "additional", "Y", "chromosomes", "had", "disproportionate", "effect", "on", "prag-", "matic", "problems", "and", "autistic", "features.", "It", "should", "be", "noted,", "however,", "that", "those", "with", "extra", "X", "chromo-", "somes", "included", "both", "girls", "and", "boys,", "whereas", "the", "extra-Y", "chromosome", "group", "were", "all", "male.", "Bishop", "2012", "The", "Authors.", "Journal", "of", "Child", "Psychology", "and", "Psychiatry", "2012", "Association", "for", "Child", "and", "Adolescent", "Mental", "Health.", "Published", "by", "Blackwell", "Publishing,", "9600", "Garsington", "Road,", "Oxford", "OX4", "2DQ,", "UK", "and", "350", "Main", "St,", "Malden,", "MA", "02148,", "USA" ]

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[ "Osteoporos", "Int", "(2012)", "23:2219–2226", "DOI", "10.1007/s00198-011-1854-0", "ORIGINAL", "ARTICLE", "Growth", "hormone", "effects", "on", "cortical", "bone", "dimensions", "in", "young", "adults", "with", "childhood-onset", "growth", "hormone", "deficiency", "L.", "Hyldstrup", "&", "G.", "S.", "Conway", "&", "K.", "Racz", "&", "A.", "Keller", "&", "P.", "Chanson", "&", "M.", "Zacharin", "&", "A.", "L.", "Lysgaard", "&", "A.", "H.", "Andreasen", "&", "A.-M.", "Kappelgaard", "Received:", "11", "August", "2011", "/", "Accepted:", "26", "October", "2011", "/", "Published", "online:", "29", "November", "2011", "#", "The", "Author(s)", "2011.", "This", "article", "is", "published", "with", "open", "access", "at", "Springerlink.com", "Abstract", "Summary", "Growth", "hormone", "(GH)", "treatment", "in", "young", "adults", "with", "childhood-onset", "GH", "deficiency", "has", "beneficial", "effects", "on", "bone", "mass.", "The", "present", "study", "shows", "that", "cortical", "bone", "dimensions", "also", "benefit", "from", "GH", "treatment,", "with", "endosteal", "L.", "Hyldstrup", "(*)", ":", "A.", "L.", "Lysgaard", "Department", "of", "Endocrinology", "(541),", "Hvidovre", "University", "Hospital,", "DK-2650", "Hvidovre,", "Denmark", "e-mail:", "hyld@dadlnet.dk", "G.", "S.", "Conway", "Department", "of", "Endocrinology", "and", "Diabetes,", "University", "College", "London", "Hospitals,", "London,", "UK", "K.", "Racz", "2nd", "Department", "of", "Medicine,", "Semmelweis", "University,", "Budapest,", "Hungary", "A.", "Keller", "Children’s", "Hospital,", "University", "of", "Leipzig,", "Leipzig,", "Germany", "P.", "Chanson", "Service", "d’Endocrinologie", "et", "des", "Maladies", "de", "la", "Reproduction,", "and", "Centre", "de", "Référence", "des", "Maladies", "Endocriniennes", "Rares", "de", "la", "Croissance,", "Assistance-Publique", "Hôpitaux", "de", "Paris,", "Hôpital", "de", "Bicêtre,", "University", "Paris-Sud,", "Le", "Kremlin-Bicêtre,", "France", "M.", "Zacharin", "Department", "of", "Endocrinology", "and", "Diabetes,", "Royal", "Children’s", "Hospital,", "Parkville,", "VIC,", "Australia", "A.", "H.", "Andreasen", ":", "A.-M.", "Kappelgaard", "GHT", "Medical", "Affairs,", "Global", "Marketing,", "Novo", "Nordisk,", "Bagsvaerd,", "Denmark", "expansion", "and", "increased", "cortical", "thickness", "leading", "to", "improved", "bone", "strength.", "Introduction", "In", "young", "adults", "with", "childhood-onset", "growth", "hormone", "deficiency", "(CO", "GHD),", "GH", "treatment", "after", "final", "height", "is", "reached", "has", "been", "shown", "to", "have", "beneficial", "effects", "on", "spine", "and", "hip", "bone", "mineral", "density.", "The", "objective", "of", "the", "study", "was", "to", "evaluate", "the", "influence", "of", "GH", "on", "cortical", "bone", "dimensions.", "Methods", "Patients", "(n", "=", "160;", "mean", "age,", "21.2", "years;", "63%", "males)", "with", "CO", "GHD", "were", "randomised", "2:1", "to", "GH", "or", "no", "treatment", "for", "24", "months.", "Cortical", "bone", "dimensions", "were", "evaluated", "by", "digital", "x-ray", "radiogrammetry", "of", "the", "metacar-", "pal", "bones", "every", "6", "months.", "Results", "After", "24", "months,", "cortical", "thickness", "was", "increased", "compared", "with", "the", "controls", "(6.43%,", "CI", "3.34", "to", "9.61%;", "p=", "0.0001)", "and", "metacarpal", "index", "(MCI)", "(6.14%,", "CI", "3.95", "to", "8.38%;", "p<0.0001),", "while", "the", "endosteal", "diameter", "decreased", "(−4.64%,", "CI", "−7.15", "to", "−2.05;", "p<0.001).", "Total", "bone", "width", "did", "not", "change", "significantly", "(0.68%,", "CI", "−1.17", "to", "2.57%;", "not", "significant", "(NS)).", "A", "gender", "effect", "was", "seen", "on", "bone", "width", "(p", "<", "0.0001),", "endosteal", "diameter", "(p", "<", "0.01)", "and", "cortical", "thickness", "(p<0.01),", "but", "not", "with", "MCI", "(NS).", "Conclusions", "Cortical", "bone", "reacts", "promptly", "to", "reinstitution", "of", "GH", "beyond", "the", "attainment", "of", "final", "height", "by", "increasing", "the", "cortical", "thickness", "through", "endosteal", "bone", "growth.", "This", "leads", "to", "a", "higher", "peak", "bone", "mass", "and", "may", "reduce", "the", "risk", "of", "cortical", "bone", "fragility", "later", "in", "life.", "Keywords", "Bone", "strength", ".", "Cortical", "bone", ".", "Growth", "hormone", "deficiency", ".", "Growth", "hormone", "treatment", ".", "Metacarpal", "index", "Introduction", "Young", "adults", "with", "childhood-onset", "growth", "hormone", "defi-", "ciency", "(CO", "GHD)", "have", "lower", "bone", "mineral", "density", "than" ]

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[ "BMC", "Public", "Health", "Research", "article", "Improvements", "in", "readiness", "to", "change", "and", "drinking", "in", "primary", "care", "patients", "with", "unhealthy", "alcohol", "use:", "a", "prospective", "study", "Nicolas", "Bertholet*1,2,", "Nicholas", "J", "Horton3", "and", "Richard", "Saitz1,4,5", "BioMed", "Central", "Open", "Access", "Address:", "1Clinical", "Addiction", "Research", "and", "Education", "(CARE)", "Unit,", "Section", "of", "General", "Internal", "Medicine,", "Boston", "Medical", "Center,", "Boston", "University", "School", "of", "Medicine,", "Boston,", "Massachusetts,", "USA,", "2Clinical", "Epidemiology", "Center,", "Institute", "of", "Social", "and", "Preventive", "Medicine,", "Centre", "Hospitalier", "Universitaire", "Vaudois,", "University", "of", "Lausanne,", "Lausanne,", "Switzerland,", "3Department", "of", "Mathematics", "and", "Statistics,", "Smith", "College,", "Northampton,", "Massachusetts,", "USA,", "4Youth", "Alcohol", "Prevention", "Center,", "Boston", "University", "School", "of", "Public", "Health,", "Boston,", "Massachusetts,", "USA", "and", "5Department", "of", "Epidemiology,", "Boston", "University", "School", "of", "Public", "Health,", "Boston,", "Massachusetts,", "USA", "Email:", "Nicolas", "Bertholet*", "-", "nberthol@bu.edu;", "Nicholas", "J", "Horton", "-", "nhorton@email.smith.edu;", "Richard", "Saitz", "-", "rsaitz@bu.edu", "*", "Corresponding", "author", "Published:", "9", "April", "2009", "BMC", "Public", "Health", "2009,", "9:101", "doi:10.1186/1471-2458-9-101", "This", "article", "is", "available", "from:", "http://www.biomedcentral.com/1471-2458/9/101", "Received:", "17", "September", "2008", "Accepted:", "9", "April", "2009", "©", "2009", "Bertholet", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Background:", "The", "course", "of", "alcohol", "consumption", "and", "cognitive", "dimensions", "of", "behavior", "change", "(readiness", "to", "change,", "importance", "of", "changing", "and", "confidence", "in", "ability", "to", "change)", "in", "primary", "care", "patients", "are", "not", "well", "described.", "The", "objective", "of", "the", "study", "was", "to", "determine", "changes", "in", "readiness,", "importance", "and", "confidence", "after", "a", "primary", "care", "visit,", "and", "6-month", "improvements", "in", "both", "drinking", "and", "cognitive", "dimensions", "of", "behavior", "change,", "in", "patients", "with", "unhealthy", "alcohol", "use.", "Methods:", "Prospective", "cohort", "study", "of", "patients", "with", "unhealthy", "alcohol", "use", "visiting", "primary", "care", "physicians,", "with", "repeated", "assessments", "of", "readiness,", "importance,", "and", "confidence", "(visual", "analogue", "scale", "(VAS),", "score", "range", "1–10", "points).", "Improvements", "6", "months", "later", "were", "defined", "as", "no", "unhealthy", "alcohol", "use", "or", "any", "increase", "in", "readiness,", "importance,", "or", "confidence.", "Regression", "models", "accounted", "for", "clustering", "by", "physician", "and", "adjusted", "for", "demographics,", "alcohol", "consumption", "and", "related", "problems,", "and", "discussion", "with", "the", "physician", "about", "alcohol.", "Results:", "From", "before", "to", "immediately", "after", "the", "primary", "care", "physician", "visit,", "patients", "(n", "=", "173)", "had", "increases", "in", "readiness", "(mean", "+1.0", "point),", "importance", "(+0.2),", "and", "confidence", "(+0.5)", "(all", "p", "<", "0.002).", "In", "adjusted", "models,", "discussion", "with", "the", "physician", "about", "alcohol", "was", "associated", "with", "increased", "readiness", "(+0.8,", "p", "=", "0.04).", "At", "6", "months,", "many", "participants", "had", "improvements", "in", "drinking", "or", "readiness", "(62%),", "drinking", "or", "importance", "(58%),", "or", "drinking", "or", "confidence", "(56%).", "Conclusion:", "Readiness,", "importance", "and", "confidence", "improve", "in", "many", "patients", "with", "unhealthy", "alcohol", "use", "immediately", "after", "a", "primary", "care", "visit.", "Six", "months", "after", "a", "visit,", "most", "patients", "have", "improvements", "in", "either", "drinking", "or", "these", "cognitive", "dimensions", "of", "behavior", "change.", "Background", "Unhealthy", "alcohol", "use", "(the", "spectrum", "from", "at-risk", "drink-", "ing", "amounts", "through", "alcohol", "dependence)", "and", "its", "conse-", "quences", "represent", "a", "major", "burden", "of", "disease", "in", "the", "general", "population", "[1,2].", "Among", "those", "with", "unhealthy", "alcohol", "use,", "brief", "intervention", "(BI)", "and", "motivational", "interviewing", "have", "demonstrated", "evidence", "of", "efficacy", "[3-5].", "In", "primary", "care,", "BI", "is", "recommended", "by", "national", "practice", "guidelines", "(US", "Preventive", "Services", "Task", "Force,", "2004),", "and,", "as", "part", "of", "BI,", "clinicians", "are", "encouraged", "to", "assess", "motivation", "and", "Page", "1", "of", "9", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Voss", "and", "Entschladen", "Cell", "Communication", "and", "Signaling", "2010,", "8:21", "http://www.biosignaling.com/content/8/1/21", "R", "E", "V", "I", "E", "W", "Open", "Access", "Tumor", "interactions", "with", "soluble", "factors", "and", "the", "nervous", "system", "Melanie", "J", "Voss,", "Frank", "Entschladen*", "Abstract", "In", "the", "genomic", "era", "of", "cancer", "research,", "the", "development", "of", "metastases", "has", "been", "attributed", "to", "mutations", "in", "the", "tumor", "that", "enable", "the", "cells", "to", "migrate.", "However,", "gene", "analyses", "revealed", "that", "primary", "tumors", "and", "metastases", "were", "in", "some", "cases", "genetically", "identical", "and", "the", "question", "was", "raised", "whether", "metastasis", "formation", "might", "be", "an", "inher-", "ent", "feature", "of", "certain", "tumor", "cells.", "In", "contradiction", "to", "this", "view,", "the", "last", "decade", "of", "cancer", "research", "has", "brought", "to", "light,", "that", "tumor", "cell", "migration,", "similar", "to", "leukocyte", "and", "fibroblast", "migration,", "is", "a", "highly", "regulated", "process.", "The", "ner-", "vous", "system", "plays", "an", "important", "role", "in", "this", "regulation,", "at", "least", "in", "two", "respects:", "firstly,", "neurotransmitters", "are", "known", "to", "regulate", "the", "migratory", "activity", "of", "tumor", "cells,", "and", "secondly,", "nerve", "fibers", "are", "used", "as", "routes", "for", "perineural", "inva-", "sion.", "We", "also", "summarize", "here", "the", "current", "knowledge", "on", "the", "innervation", "of", "tumors.", "Such", "a", "process", "might", "establish", "a", "neuro-neoplastic", "synapse,", "with", "the", "close", "interaction", "of", "tumor", "cells", "and", "nerve", "cells", "supporting", "metastasis", "formation.", "Introduction", "In", "January", "1971,", "the", "US", "president", "Richard", "Nixon", "intro-", "duced", "in", "his", "State", "of", "the", "Union", "Address", "the", "‘War", "on", "Cancer’", "with", "the", "aim", "to", "find", "ways", "to", "cure", "cancer", "within", "the", "next", "25", "years.", "Although", "significant", "efforts", "and", "advances", "have", "been", "made", "since", "then,", "we", "are", "still", "in", "a", "war", "with", "cancer", "and", "far", "away", "from", "a", "definite", "victory.", "With", "reference", "to", "president", "Nixon’s", "State", "of", "the", "Union", "Address,", "Michael", "Sporn", "published", "an", "article", "in", "The", "Lancet", "in", "1996,", "in", "which", "he", "reviewed", "the", "progress", "that", "was", "made", "since", "1971,", "and", "he", "pointed", "out", "the", "future", "goals", "of", "cancer", "research", "[1].", "One", "key", "statement", "of", "this", "article", "was:", "“It", "is", "local", "invasion", "and", "distant", "metastasis", "that", "kill", "rather", "than", "excessive", "cell", "proliferation", "per", "se.”", "In", "fact", "today", "over", "90", "percent", "of", "those", "patients", "that", "die", "from", "their", "cancer", "disease", "do", "not", "die", "due", "to", "the", "primary", "tumor", "but", "due", "to", "the", "development", "of", "metastases.", "Thus,", "there", "is", "a", "pressing", "need", "of", "research", "on", "how", "metastases", "occur,", "and", "on", "ways", "to", "prevent", "or", "treat", "this", "ultimate", "step", "in", "cancer", "progression.", "The", "end", "of", "the", "previous", "century", "was", "called", "the", "geno-", "mic", "era", "with", "respect", "not", "only", "to", "cancer", "research.", "Deci-", "phering", "the", "human", "genome", "was", "probably", "the", "most", "ambitious", "project,", "which", "actually", "succeeded", "in", "the", "year", "*", "Correspondence:", "entschladen@uni-wh.de", "Institute", "of", "Immunology,", "ZBAF,", "Witten/Herdecke", "University,", "Stockumer", "Str.", "10,", "58448", "Witten,", "Germany", "2000", "[2].", "At", "this", "time,", "genetic", "models", "for", "the", "develop-", "ment", "of", "cancer", "have", "been", "established", "which", "have", "deliv-", "ered", "a", "molecular", "fundament", "for", "the", "understanding", "of", "processes", "in", "cancer", "cells.", "One", "of", "the", "earliest", "and", "most", "famous", "is", "the", "model", "by", "Fearon", "and", "Vogelstein", "(1990)", "which", "gives", "a", "precise", "line", "of", "genetic", "events", "that", "occur", "during", "the", "transformation", "of", "normal", "colon", "epithelium", "to", "a", "carcinoma", "[3].", "However,", "this", "model", "of", "colorectal", "tumorigenesis", "does", "not", "specify", "mutations", "that", "may", "con-", "stitute", "the", "step", "from", "carcinoma", "to", "metastasis.", "Since", "then", "a", "still", "ongoing", "debate", "was", "raised", "to", "what", "extent", "metastasis", "formation", "might", "be", "genetically", "determined.", "Bernards", "and", "Weinberg", "provided", "a", "concept", "that", "the", "ten-", "dency", "to", "metastasize", "is", "acquired", "early", "in", "tumorigenesis", "[4].", "This", "assumption", "is", "based", "on", "observations", "that", "pri-", "mary", "tumors", "are", "genetically", "similar", "or", "maybe", "even", "equal", "to", "their", "metastases.", "However,", "some", "genes", "have", "been", "identified", "that", "are", "associated", "with", "metastasis", "formation.", "For", "example,", "the", "analysis", "of", "the", "Smad4", "gene", "in", "colorec-", "tal", "carcinomas", "showed", "mutations", "in", "7", "percent", "of", "the", "samples", "of", "primary", "invasive", "carcinoma", "without", "distant", "metastasis,", "but", "mutations", "in", "35", "percent", "of", "the", "samples", "of", "primary", "invasive", "carcinoma", "with", "distant", "metastasis", "[5].", "In", "2008,", "MACC1,", "a", "yet", "largely", "uncharacterized", "pro-", "tein", "with", "putative", "adaptor", "function,", "was", "also", "shown", "to", "be", "a", "prominent", "driver", "of", "colorectal", "metastasis", "[6].", "More", "recently", "an", "amplification", "of", "the", "MTDH", "gene", "encoding", "©", "2010", "Voss", "and", "Entschladen;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Vera", "et", "al.", "BMC", "Research", "Notes", "2011,", "4:415", "http://www.biomedcentral.com/1756-0500/4/415", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "Prolonged", "exposure", "for", "the", "treatment", "of", "Spanish-", "speaking", "Puerto", "Ricans", "with", "posttraumatic", "stress", "disorder:", "a", "feasibility", "study", "Mildred", "Vera1*,", "María", "L", "Reyes-Rabanillo2,", "Deborah", "Juarbe3,", "Coralee", "Pérez-Pedrogo3,", "Alicia", "Olmo2,", "Rafael", "Kichic4", "and", "William", "F", "Chaplin5", "Abstract", "Background:", "Most", "of", "the", "empirical", "studies", "that", "support", "the", "efficacy", "of", "prolonged", "exposure", "(PE)", "for", "treating", "posttraumatic", "stress", "disorder", "(PTSD)", "have", "been", "conducted", "on", "white", "mainstream", "English-speaking", "populations.", "Although", "high", "PTSD", "rates", "have", "been", "reported", "for", "Puerto", "Ricans,", "the", "appropriateness", "of", "PE", "for", "this", "population", "remains", "unclear.", "The", "purpose", "of", "this", "study", "was", "to", "examine", "the", "feasibility", "of", "providing", "PE", "to", "Spanish", "speaking", "Puerto", "Ricans", "with", "PTSD.", "Particular", "attention", "was", "also", "focused", "on", "identifying", "challenges", "faced", "by", "clinicians", "with", "limited", "experience", "in", "PE.", "This", "information", "is", "relevant", "to", "help", "inform", "practice", "implications", "for", "training", "Spanish-", "speaking", "clinicians", "in", "PE.", "Results:", "Fourteen", "patients", "with", "PTSD", "were", "randomly", "assigned", "to", "receive", "PE", "(n", "=", "7)", "or", "usual", "care", "(UC)", "(n", "=", "7).", "PE", "therapy", "consisted", "of", "15", "weekly", "sessions", "focused", "on", "gradually", "confronting", "and", "emotionally", "processing", "distressing", "trauma-related", "memories", "and", "reminders.", "Five", "patients", "completed", "PE", "treatment;", "all", "patients", "attended", "the", "15", "sessions", "available", "to", "them.", "In", "UC,", "patients", "received", "mental", "health", "services", "available", "within", "the", "health", "care", "setting", "where", "they", "were", "recruited.", "They", "also", "had", "the", "option", "of", "self-referring", "to", "a", "mental", "health", "provider", "outside", "the", "study", "setting.", "The", "Clinician-Administered", "PTSD", "Scale", "(CAPS)", "was", "administered", "at", "baseline,", "mid-treatment,", "and", "post-", "treatment", "to", "assess", "PTSD", "symptom", "severity.", "Treatment", "completers", "in", "the", "PE", "group", "demonstrated", "significantly", "greater", "reductions", "in", "PTSD", "symptoms", "than", "the", "UC", "group.", "Forty", "percent", "of", "the", "PE", "patients", "showed", "clinically", "meaningful", "reductions", "in", "PTSD", "symptoms", "from", "pre-", "to", "post-treatment.", "Conclusions:", "PE", "appears", "to", "be", "viable", "for", "treating", "Puerto", "Rican", "Spanish-speaking", "patients", "with", "PTSD.", "This", "therapy", "had", "good", "patient", "acceptability", "and", "led", "to", "improvements", "in", "PTSD", "symptoms.", "Attention", "to", "the", "clinicians’", "training", "process", "contributed", "strongly", "to", "helping", "them", "overcome", "the", "challenges", "posed", "by", "the", "intervention", "and", "increased", "their", "acceptance", "of", "PE.", "Background", "Exposure", "therapy", "and", "posttraumatic", "stress", "disorder", "Prolonged", "exposure", "(PE),", "a", "form", "of", "cognitive", "behavioral", "therapy,", "has", "received", "strong", "support", "for", "of", "the", "treatment", "of", "posttraumatic", "stress", "disorder", "(PTSD)", "[1-3].", "A", "com-", "mittee", "convened", "by", "the", "Institute", "of", "Medicine", "(IOM)", "to", "assess", "evidence", "about", "the", "efficacy", "of", "treatments", "for", "PTSD", "concluded", "that", "while", "the", "evidence", "was", "inadequate", "*", "Correspondence:", "mildred.vera@upr.edu", "1Center", "for", "Evaluation", "and", "Sociomedical", "Research", "and", "Department", "of", "Health", "Services", "Administration,", "School", "of", "Public", "Health,", "Medical", "Science", "Campus,", "University", "of", "Puerto", "Rico,", "San", "Juan,", "Puerto", "Rico", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "for", "most", "psychological", "and", "pharmacological", "treatment", "modalities,", "the", "efficacy", "of", "exposure", "therapies", "for", "treating", "PTSD", "was", "strongly", "supported", "[4].", "The", "superior", "efficacy", "of", "PE", "for", "treating", "PTSD", "has", "been", "demonstrated", "across", "a", "wide", "range", "of", "traumatized", "populations,", "including", "victims", "of", "rape,", "violent", "assault,", "child", "abuse,", "combat-related", "trauma,", "motor", "vehicle", "accidents,", "and", "disasters", "[1,5-7].", "Although", "strong", "empirical", "evidence", "sustains", "the", "effi-", "cacy", "of", "PE", "for", "PTSD,", "the", "adoption", "of", "exposure", "therapy", "in", "clinical", "practice", "has", "been", "slow", "[8-11].", "Lack", "of", "adequate", "training", "has", "been", "identified", "as", "a", "contributing", "factor", "to", "the", "low", "use", "of", "exposure", "therapy", "by", "clinicians", "in", "treating", "PTSD", "[12].", "Other", "common", "obstacles", "have", "been", "discussed", "©", "2011", "Vera", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "e", "n", "i", "c", "i", "d", "e", "M", "l", "a", "t", "n", "e", "m", "i", "r", "e", "p", "x", "E", "f", "o", "l", "a", "n", "r", "u", "o", "J", "e", "h", "T", "CORRESPONDENCE", "A.Villa:", "villa.anna@hsr.it", "B", "R", "I", "E", "F", "D", "E", "F", "I", "N", "I", "T", "I", "V", "E", "R", "E", "P", "O", "RT", "The", "Wiskott-Aldr", "ich", "syndrome", "protein", "is", "required", "for", "iNKT", "cell", "maturation", "and", "function", "Michela", "Locci,1,2", "Elena", "Draghici,3", "Francesco", "Marangoni,3", "Marita", "Bosticardo,1", "Marco", "Catucci,3", "Alessandro", "Aiuti,2,3", "Caterina", "Cancrini,2", "Laszlo", "Marodi,4", "Teresa", "Espanol,5", "Robbert", "G.M.", "Bredius,6", "Adrian", "J.", "Thrasher,7", "Ansgar", "Schulz,8", "Jiri", "Litzman,9", "Maria", "Grazia", "Roncarolo,1,3", "Giulia", "Casorati,10", "Paolo", "Dellabona,10", "and", "Anna", "Villa3,11", "1Vita-Salute", "San", "Raffaele", "University,", "20132", "Milan,", "Italy", "2Tor", "Vergata", "University,", "00133", "Rome,", "Italy", "3San", "Raffaele", "Telethon", "Institute", "for", "Gene", "Therapy,", "20132", "Milan,", "Italy", "4Department", "of", "Infectious", "and", "Pediatric", "Immunology,", "University", "of", "Debrecen", "Medical", "and", "Health", "Science", "Center,", "H4012", "Debrecen,", "Hungary", "5Paediatric", "Immunology", "and", "Infectious", "Disease", "Unit,", "Vall", "d’Hebron", "Hospital,", "08035", "Barcelona,", "Spain", "6Department", "of", "Pediatrics,", "Leiden", "University", "Medical", "Center,", "2300", "RC", "Leiden,", "Netherlands", "7Institute", "of", "Child", "Health,", "University", "College", "London", "and", "Great", "Ormond", "Street", "Hospital", "for", "Children,", "WCIN", "1EH", "London,", "England,", "UK", "8Department", "of", "Pediatrics", "and", "Adolescent", "Medicine,", "University", "Hospital", "Ulm,", "89075", "Ulm,", "Germany", "9Department", "of", "Clinical", "Immunology", "and", "Allergology,", "Faculty", "of", "Medicine,", "Masaryk", "University,", "St.", "Anne’s", "University", "Hospital,", "656", "91", "Brno,", "Czech", "Republic", "10Experimental", "Immunology", "Unit,", "Cancer", "Immunotherapy", "and", "Gene", "Therapy", "Program,", "Dipartimento", "di", "Biotecnologie,", "San", "Raffaele", "Scientific", "Institute,", "20132", "Milan,", "Italy", "11Istituto", "Tecnologie", "Biomediche,", "Consiglio", "Nazionale", "delle", "Ricerche,", "20090", "Segrate-Milan,", "Italy", "The", "Wiskott-Aldrich", "syndrome", "(WAS)", "protein", "(WASp)", "is", "a", "regulator", "of", "actin", "cytoskeleton", "in", "hematopoietic", "cells.", "Mutations", "of", "the", "WASp", "gene", "cause", "WAS.", "Although", "WASp", "is", "in-", "volved", "in", "various", "immune", "cell", "functions,", "its", "role", "in", "invariant", "natural", "killer", "T", "(iNKT)", "cells", "has", "never", "been", "investigated.", "Defects", "of", "iNKT", "cells", "could", "indeed", "contribute", "to", "several", "WAS", "features,", "such", "as", "recurrent", "infections", "and", "high", "tumor", "incidence.", "We", "found", "a", "profound", "reduction", "of", "circulating", "iNKT", "cells", "in", "WAS", "patients,", "directly", "correlating", "with", "the", "severity", "of", "clinical", "phenotype.", "To", "better", "characterize", "iNKT", "cell", "defect", "in", "the", "absence", "of", "WASp,", "we", "analyzed", "was/", "mice.", "iNKT", "cell", "numbers", "were", "significantly", "reduced", "in", "the", "thymus", "and", "periphery", "of", "was/", "mice", "as", "compared", "with", "wild-type", "controls.", "Moreover", "analysis", "of", "was/", "iNKT", "cell", "maturation", "revealed", "a", "complete", "arrest", "at", "the", "CD44+", "NK1.1", "intermediate", "stage.", "Notably,", "generation", "of", "BM", "chimeras", "demonstrated", "a", "was/", "iNKT", "cell-autonomous", "devel-", "opmental", "defect.", "was/", "iNKT", "cells", "were", "also", "functionally", "impaired,", "as", "suggested", "by", "the", "reduced", "secretion", "of", "interleukin", "4", "and", "interferon", "", "upon", "in", "vivo", "activation.", "Altogether,", "these", "results", "demonstrate", "the", "relevance", "of", "WASp", "in", "integrating", "signals", "critical", "for", "develop-", "ment", "and", "functional", "differentiation", "of", "iNKT", "cells", "and", "suggest", "that", "defects", "in", "these", "cells", "may", "play", "a", "role", "in", "WAS", "pathology.", "Invariant", "natural", "killer", "T", "(iNKT)", "cells", "consti-", "tute", "a", "peculiar", "T", "lymphocyte", "subset,", "which", "is", "characterized", "by", "the", "coexpression", "of", "NK", "mark-", "ers", "and", "an", "invariant", "TCR-", "chain", "(V14J18", "in", "mouse", "or", "V24J18", "in", "human),", "which", "pairs", "with", "a", "restricted", "number", "of", "TCR-", "chains", "(V8,", "V7,", "and", "V2", "in", "mice", "and", "V11", "in", "human).", "iNKT", "cells", "recognize", "glycolipid", "antigens,", "such", "as", "-galactosylceramide", "(-GalCer),", "presented", "in", "the", "context", "of", "CD1d", "molecules", "(1).", "iNKT", "cells", "develop", "in", "the", "thymus", "from", "CD4+", "CD8+", "double-positive", "(DP)", "cells", "that", "have", "randomly", "rearranged", "the", "semiinvariant", "TCR", "and", "are", "©", "2009", "Locci", "et", "al.", "This", "article", "is", "distributed", "under", "the", "terms", "of", "an", "Attribu-", "tion–Noncommercial–Share", "Alike–No", "Mirror", "Sites", "license", "for", "the", "first", "six", "months", "after", "the", "publication", "date", "(see", "http://www.jem.org/misc/terms.shtml).", "After", "six", "months", "it", "is", "available", "under", "a", "Creative", "Commons", "License", "(Attribution–Noncom-", "mercial–Share", "Alike", "3.0", "Unported", "license,", "as", "described", "at", "http://creativecommons", ".org/licenses/by-nc-sa/3.0/).", "The", "Rockefeller", "University", "Press", "$30.00", "J.", "Exp.", "Med.", "Vol.", "206", "No.", "4", "735-742", "www.jem.org/cgi/doi/10.1084/jem.20081773", "735" ]

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[ "Research", "|", "Children’s", "Health", "Exposure", "to", "Asbestos-Containing", "Vermiculite", "Ore", "and", "Respiratory", "Symptoms", "among", "Individuals", "Who", "Were", "Children", "While", "the", "Mine", "Was", "Active", "in", "Libby,", "Montana", "Lisa", "C.", "Vinikoor,1", "Theodore", "C.", "Larson,2", "Thomas", "F.", "Bateson,3", "and", "Linda", "Birnbaum4", "1U.S.", "Environmental", "Protection", "Agency,", "Research", "Triangle", "Park,", "North", "Carolina,", "USA;", "2Agency", "for", "Toxic", "Substances", "and", "Disease", "Registry,", "Atlanta,", "Georgia,", "USA;", "3U.S.", "Environmental", "Protection", "Agency,", "Washington,", "DC,", "USA;", "4National", "Institute", "of", "Environmental", "Health", "Sciences,", "National", "Institutes", "of", "Health,", "Department", "of", "Health", "and", "Human", "Services,", "Research", "Triangle", "Park,", "North", "Carolina,", "USA", "Background", ":", "Libby,", "Montana,", "was", "home", "to", "the", "largest", "vermiculite", "ore", "mine", "in", "the", "United", "States.", "The", "processing,", "use,", "and", "transport", "of", "the", "ore,", "which", "was", "contaminated", "with", "amphibole", "asbestos,", "led", "to", "generalized", "contamination", "of", "the", "community.", "The", "mine", "closed", "in", "1990.", "o", "Bjectivs", ":", "We", "examined", "the", "prevalence", "of", "respiratory", "symptoms", "in", "2000–2001", "and", "their", "associa-", "tion", "with", "history", "of", "vermiculite", "exposure", "among", "people", "who", "were", "≤", "18", "years", "of", "age", "when", "the", "mine", "closed.", "Methods", ":", "Information", "on", "respiratory", "symptoms", "and", "exposure", "history", "was", "collected", "by", "question-", "naire", "in", "2000–2001,", "at", "which", "time", "participants", "were", "10–29", "years", "old.", "Logistic", "regression", "was", "used", "to", "model", "the", "associations", "between", "exposures", "and", "outcomes", "adjusted", "for", "age,", "sex,", "and", "tobacco", "smoke", "exposure.", "r", "esult", ":", "Of", "the", "1,003", "individuals", "included", "in", "the", "study,", "10.8%", "reported", "usually", "having", "a", "cough,", "14.5%", "reported", "experiencing", "shortness", "of", "breath", "when", "walking", "up", "a", "slight", "hill", "or", "hurrying", "on", "level", "ground,", "and", "5.9%", "reported", "having", "coughed", "up", "bloody", "phlegm", "in", "the", "past", "year.", "These", "respiratory", "symptoms", "were", "positively", "associated", "with", "frequently", "handling", "vermiculite", "insulation", "compared", "with", "never", "handling", "vermiculite", "insulation.", "We", "found", "no", "association", "between", "vermiculite", "insulation", "in", "the", "house", "and", "respiratory", "symptoms.", "Respiratory", "symptoms", "were", "associated", "with", "other", "vermiculite", "expo-", "sures", "as", "well,", "and", "the", "number", "and", "frequency", "of", "these", "activities", "showed", "a", "positive", "trend", "with", "usually", "having", "a", "cough.", "We", "found", "no", "association", "between", "any", "of", "the", "activities", "and", "abnormal", "spirometry.", "c", "onclusi", ":", "These", "data", "suggest", "that", "residents", "of", "Libby,", "Montana,", "who", "were", "children", "when", "the", "mine", "closed", "experienced", "some", "respiratory", "symptoms", "associated", "with", "asbestos-contaminated", "ver-", "miculite", "exposure.", "k", "ey", "words", ":", "asbestos,", "children,", "Libby,", "Montana,", "respiratory", "symptoms,", "spirometry,", "vermiculite", "ore.", "Environ", "Health", "Perspect", "118:1033–1038", "(2010).", "doi:10.1289/ehp.0901680", "[Online", "23", "March", "2010]", "Libby", "is", "a", "small", "community", "located", "in", "the", "Kootenai", "River", "Valley", "of", "northwestern", "Montana", "approximately", "6", "miles", "southwest", "of", "Zonolite", "Mountain,", "a", "mountain", "containing", "high", "concentrations", "of", "vermiculite", "ore.", "The", "ore", "was", "mined", "beginning", "in", "the", "1920s", "by", "the", "Zonolite", "Company", "and", "then", "later", "by", "W.R.", "Grace,", "which", "bought", "the", "mine", "in", "1963.", "It", "is", "estimated", "that", "between", "1924", "and", "1990,", "when", "the", "mine", "was", "closed,", "a", "total", "of", "5.8", "million", "tons", "of", "vermiculite", "ore", "was", "mined", "and", "dis-", "tributed", "(Kuntz", "et", "al.", "2009),", "making", "Zonolite", "Mountain", "the", "largest", "vermiculite", "ore", "mine", "in", "the", "United", "States.", "In", "addition", "to", "the", "mine,", "processing,", "exfoliation,", "and", "shipping", "prepara-", "tions", "were", "performed", "in", "Libby.", "The", "ore", "was", "then", "used", "in", "many", "products", "ranging", "from", "insulation", "to", "soil", "additives", "and", "fertilizers.", "The", "vermiculite", "ore", "contained", "amphibole", "asbestos.", "Libby", "amphibole", "asbestos", "was", "deter-", "mined", "to", "be", "composed", "of", "tremolite,", "winchite,", "and", "richterite", "(Meeker", "et", "al.", "2003).", "The", "International", "Agency", "for", "Research", "on", "Cancer", "recently", "concluded", "that", "“all", "forms", "of", "asbestos", "are", "‘carcinogenic", "to", "humans’”", "and", "that", "“min-", "eral", "substances", "(e.g.,", "talc", "or", "vermiculite)", "that", "contain", "asbestos", "should", "also", "be", "regarded", "as", "‘carcinogenic", "to", "humans’”", "(Straif", "et", "al.", "2009).", "As", "with", "other", "forms", "of", "asbestos,", "exposure", "to", "Libby", "amphibole", "asbestos", "has", "been", "shown", "to", "negatively", "affect", "human", "health.", "Occupational", "studies", "have", "shown", "increased", "morbidity", "and", "mortality", "(specifically", "from", "respiratory", "can-", "cers", "and", "other", "respiratory", "diseases,", "including", "asbestosis)", "associated", "with", "exposure", "to", "the", "asbestos-contaminated", "vermiculite", "from", "Libby", "(Amandus", "and", "Wheeler", "1987;", "Amandus", "et", "al.", "1987;", "McDonald", "et", "al.", "1986,", "2004;", "Sullivan", "2007).", "Studies", "have", "also", "shown", "increased", "morbidity", "and", "mortality", "among", "individuals", "living", "in", "Libby,", "Montana,", "who", "did", "not", "work", "at", "the", "mine", "[Agency", "for", "Toxic", "Substances", "and", "Disease", "Registry", "(ATSDR)", "2000,", "2002;", "Muravov", "et", "al.", "2005;", "Noonan", "et", "al.", "2006;", "Peipins", "et", "al.", "2003;", "Whitehouse", "et", "al.", "2008].", "Health", "effects", "continue", "to", "be", "seen", "in", "for-", "mer", "workers", "and", "community", "members.", "In", "2000–2001", "the", "ATSDR", "began", "a", "screening", "program", "for", "individuals", "living", "and/or", "work-", "ing", "in", "Libby.", "Using", "these", "data", "researchers", "have", "found", "positive", "associations", "between", "asbestos-contaminated", "vermiculite", "exposure", "and", "pleural", "abnormalities", "seen", "by", "radiograph", "(Peipins", "et", "al.", "2003)", "and", "self-reported", "history", "of", "systemic", "autoimmune", "diseases", "(Noonan", "et", "al.", "2006).", "Despite", "the", "mine’s", "closure,", "there", "Environmental", "Health", "Perspectives", "•", "volume", "118", "|", "number", "7", "|", "July", "2010", "is", "concern", "about", "the", "long-term", "effects", "of", "the", "mining", "operation", "for", "both", "those", "exposed", "in", "childhood", "and", "those", "exposed", "to", "lingering", "environmental", "contamination.", "This", "age", "group", "is", "of", "particular", "importance", "because", "lung", "development", "continues", "through", "adolescence", "until", "about", "18", "years", "of", "age", "in", "girls", "and", "the", "early", "20s", "in", "boys.", "Previous", "research", "has", "shown", "reduced", "lung", "development", "in", "children", "10–18", "years", "of", "age", "who", "were", "exposed", "to", "ambient", "air", "pollution", "(Bateson", "and", "Schwartz", "2008;", "Gauderman", "et", "al.", "2004).", "Using", "the", "avail-", "able", "ATSDR", "survey", "data,", "we", "examined", "the", "prevalence", "of", "respiratory", "symptoms", "and", "their", "association", "with", "vermiculite", "exposure", "among", "individuals", "who", "were", "no", "older", "than", "18", "years", "of", "age", "while", "the", "mine", "was", "in", "operation", "and", "who", "were", "continually", "exposed", "through", "linger-", "ing", "environmental", "contamination.", "This", "has", "not", "been", "addressed", "by", "previous", "research.", "Materials", "and", "Methods", "In", "2000", "and", "2001,", "ATSDR", "conducted", "a", "study", "of", "individuals", "who", "resided,", "worked,", "attended", "school,", "or", "participated", "in", "other", "activities", "in", "the", "Libby", "area", "for", "at", "least", "6", "months", "before", "31", "December", "1990.", "In-person", "interviews", "and", "medical", "tests", "were", "performed", "in", "2000", "(July–November)", "and", "2001", "(July–September).", "Trained", "interviewers", "administered", "a", "computer-assisted", "question-", "naire", "to", "obtain", "information", "on", "demographics,", "residential", "history,", "household", "contact", "with", "a", "W.R.", "Grace", "employee,", "occupational", "his-", "tory,", "recreational", "activity", "history,", "history", "of", "other", "potential", "vermiculite", "exposures,", "indi-", "vidual", "and", "household", "members’", "smoking", "status/history,", "medical", "history,", "and", "current", "symptoms/illnesses.", "Parents", "completed", "proxy", "interviews", "for", "children", "<", "18", "years", "of", "age.", "In", "Address", "correspondence", "to", "L.C.", "Vinikoor,", "U.S.", "Environmental", "Protection", "Agency,", "MD", "B243-01,", "109", "T.W.", "Alexander", "Dr.,", "Research", "Triangle", "Park,", "NC", "27711", "USA.", "Telephone:", "(919)", "541-2931.", "Fax:", "(919)", "541-4284.", "E-mail:", "vinikoor.lisa@epa.gov", "The", "views", "expressed", "in", "this", "article", "are", "those", "of", "the", "authors", "and", "do", "not", "necessarily", "reflect", "the", "views", "or", "policies", "of", "the", "U.S.", "Environmental", "Protection", "Agency,", "Agency", "for", "Toxic", "Substances", "and", "Disease", "Registry,", "or", "National", "Institute", "of", "Environmental", "Health", "Sciences.", "The", "authors", "declare", "they", "have", "no", "actual", "or", "potential", "competing", "financial", "interests.", "Received", "10", "November", "2009;", "accepted", "12", "March", "2010.", "1033" ]

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[ "Color", "Stability", "of", "Silicone", "or", "Acrylic", "Denture", "Liners:", "An", "in", "Vitro", "Investigation", "Gulfem", "Erguna,", "DDS,", "PhD", "Isil", "Cekic", "Nagasb,", "DDS", "AbstrAct", "Objectives:", "The", "aim", "of", "this", "study", "was", "to", "compare", "the", "color", "stability", "of", "three", "acrylic", "based", "hard", "liners", "(Ufi", "gel", "hard,", "Dura-Liner", "II,", "Tokuso", "Rebase)", "and", "two", "silicone", "based", "soft", "liners", "(Ufi", "gel", "perma-", "nent,", "Molloplast", "B)", "by", "using", "the", "colorimeter.", "Methods:", "Sixty", "disc-shaped", "samples,", "with", "uniform", "size", "of", "10", "mm", "diameter", "and", "2", "mm", "in", "thick-", "ness", "were", "fabricated", "for", "each", "material.", "Thirty", "samples", "were", "made", "as", "control", "group", "in", "distilled", "water", "and", "the", "remaining", "thirty", "samples", "were", "weathered", "in", "accelerated", "aging", "chamber.", "Color", "mea-", "surements", "were", "made", "before", "and", "after", "distilled", "water", "and", "aging.", "Data", "were", "statistically", "analyzed", "using", "nonparametric", "Kruskal-Wallis", "and", "Mann-Whitney", "U", "tests.", "Results:", "Data", "showed", "that", "there", "are", "significant", "differences", "among", "materials", "in", "both", "after", "dis-", "tilled", "water", "and", "aging", "treatments", "(P<.001).", "These", "results", "indicated", "that", "the", "most", "discolored", "liner", "material", "was", "Dura", "Liner", "II", "after", "aging", "(∆E*=16.30)", "and", "the", "least", "discolored", "material", "was", "Ufi", "gel", "permanent", "after", "distilled", "water", "(∆E*=0.41).", "Conclusions:", "Based", "on", "the", "results", "of", "this", "study,", "silicone", "based", "liner", "materials", "are", "considered", "to", "be", "more", "color", "stable", "than", "acrylic", "based", "liner", "materials.", "(Eur", "J", "Dent", "2007;1:144-151)", "Key", "words:", "Silicone;", "Acrylic", "liners;", "Color", "stability.", "IntroducIno", "Denture", "lining", "materials", "are", "widely", "used", "for", "the", "base", "of", "a", "denture", "to", "reduce", "pain", "or", "to", "improve", "the", "fit", "between", "the", "denture", "and", "mucous", "membrane.1", "They", "act", "as", "a", "cushion", "and", "provide", "an", "even", "distri-", "bution", "of", "functional", "load", "onto", "the", "stress-bearing", "mucosa.2", "Application", "of", "a", "soft", "lining", "material", "to", "the", "dentures", "can", "also", "increase", "the", "patient’s", "mas-", "ticatory", "performance,", "biting", "force", "and", "improve", "the", "chewing", "rhythm.3", "Denture", "lining", "materials", "can", "be", "classified", "a", "Associate", "Professor,", "Department", "of", "Prosthodontics,", "Faculty", "of", "Dentistry,", "Gazi", "University,", "Ankara,", "Türkiye", "b", "Research", "Assistant,", "Department", "of", "Prosthodontics,", "Faculty", "of", "Dentistry,", "Gazi", "University,", "Ankara,", "Türkiye", "Corresponding", "Author:", "Dr.", "Gulfem", "Ergun", "Address:", "Süslü", "sok.", "14/9Tandoğan/Ankara", "06580", "Türkiye", "Tel.:", "+90", "312", "213", "97", "01", "Fax:", "+90", "312", "223", "92", "26", "E-mail", ":", "gulfem@gazi.edu.tr,", "ergungulfem@yahoo.com.", "as", "provisional", "or", "permanent,", "silicone", "rubber", "or", "acrylic", "resin,", "and", "can", "be", "either", "chemically", "or", "heat", "polymerized.4", "A", "provisional", "liner", "is", "the", "one", "used", "intraorally", "for", "up", "to", "30", "days", "and", "a", "long-term", "liner", "is", "categorized", "as", "the", "one", "that", "maintains", "its", "soft-", "ness", "and", "elasticity", "for", "more", "than", "30", "days.5", "Fur-", "thermore,", "in", "a", "study,", "a", "long", "term", "liner", "was", "clas-", "sified", "to", "be", "the", "one", "used", "for", "1", "year", "or", "longer.6", "Silicone", "based", "lining", "materials", "are", "basically", "di-", "methylsiloxane", "polymers", "and", "do", "not", "contain", "plas-", "ticizer", "to", "produce", "softening", "effect.7", "These", "lining", "materials", "are", "hydrophobic;", "this", "reduces", "water", "sorption,", "but", "simultaneously", "inhibits", "good", "affin-", "ity", "to", "the", "supporting", "tissues.8", "Acrylic", "based", "lining", "materials", "are", "composed", "of", "the", "powder", "consisting", "of", "a", "higher", "methacrylate", "polymer", "(usually", "poly", "ethyl", "methacrylate)", "and", "a", "liquid", "of", "a", "higher", "meth-", "acrylate", "monomer", "(e.g.", "ethyl,", "n-butyl),", "in", "addition", "a", "plasticizer,", "commonly", "a", "phythalate.9,10", "When", "im-", "144", "European", "Journal", "of", "Dentistry" ]

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"similarities,", "and", "plug-ins", "*To", "whom", "correspondence", "should", "be", "addressed.", "available", "with", "software", "such", "as", "Cytoscape", "(Smoot", "et", "al.,", "2011)", "allow", "creation", "of", "small", "PSNs", "(Wittkop", "et", "al.,", "2010),", "no", "software", "solution", "exists", "to", "create", "and", "manage", "large", "PSNs.", "And", "while", "PSNs", "are", "inherently", "amenable", "to", "association", "with", "orthogonal", "information", "sources,", "the", "many", "information", "types", "available", "com-", "plicate", "development", "of", "a", "single", "software", "solution", "for", "managing", "such", "diverse", "features.", "Pythoscape", "addresses", "these", "issues", "and", "pro-", "vides", "a", "software", "framework", "to", "create", "PSNs", "and", "develop", "new", "analyses", "for", "inference", "of", "functional", "properties", "in", "proteins.", "2", "DESCRIPTION", "AND", "SIGNIFICANCE", "Pythoscape", "is", "an", "extensible", "computational", "framework", "imple-", "mented", "in", "Python", "to", "generate", "and", "analyze", "PSNs.", "For", "the", "user", "interested", "in", "generating", "large", "networks,", "the", "Pythoscape", "package", "has", "a", "core", "set", "of", "plug-ins", "(Supplementary", "Table", "S1)", "and", "tutorials,", "so", "that", "no", "development", "is", "needed", "to", "create", "simple", "networks", "painted", "with", "useful", "metadata.", "For", "software", "developers,", "Pythos-", "cape", "provides", "a", "framework", "for", "rapid", "modification", "along", "with", "well-documented", "application", "programming", "interfaces", "for", "devel-", "opment", "of", "additional", "plug-ins", "using", "new", "sources", "of", "metadata.", "Unlike", "sparser", "networks", "such", "as", "interaction", "networks,", "PSNs", "are", "frequently", "close", "to", "complete,", "often", "requiring", "storage", "and", "management", "of", "large", "quantities", "of", "data,", "and", "fast", "calculation", "(Supplementary", "Table", "S2).", "Pythoscape", "allows", "for", "flexible", "storage", "of", "data", "through", "the", "use", "of", "storage", "interfaces.", "Appropriate", "stor-", "age", "solutions", "can", "be", "chosen", "based", "on", "network", "size", "or", "developed", "as", "needed", "allowing", "for", "easy", "updating", "for", "faster", "and", "more", "reliable", "database", "software", "solutions.", "Pythoscape", "can", "create,", "store", "and", "manage", "large", "networks,", "then,", "using", "representative", "nodes", "and", "edges", "to", "compress", "the", "information,", "output", "smaller", "summary", "net-", "works", "for", "visualization", "(Fig.", "1A", "and", "B).", "Users", "can", "choose", "how", "distances", "between", "representative", "nodes", "are", "calculated", "and,", "im-", "portantly,", "the", "full", "set", "of", "sequences", "in", "each", "node", "is", "retained", "for", "later", "use.", "Additionally,", "Pythoscape", "has", "plug-ins", "for", "creating", "structure", "similarity", "networks", "and", "for", "generating", "correlations", "for", "edge", "distances", "between", "networks", "generated", "from", "a", "set", "of", "sequences", "and", "a", "corresponding", "set", "of", "available", "structures", "(Supplementary", "Table", "S1", "and", "Supplementary", "Figs.", "S2", "and", "S3).", "3", "EXAMPLE", "USAGE", "Glutathione", "transferases", "(GSTs)", "are", "enzymes", "that", "typically", "cata-", "lyze", "the", "addition", "of", "glutathione", "to", "substrate", "compounds.", "They", "play", "roles", "in", "many", "biological", "processes,", "including", "metabolism", "of", "endogenous", "compounds", "and", "xenobiotics", "such", "as", "drugs.", "Of", "the", "The", "Author", "2012.", "Published", "by", "Oxford", "University", "Press.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/3.0/),", "which", "permits", "unrestricted,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "BMC", "Medical", "Research", "Methodology", "BioMed", "Central", "BR2M0e0Cs1eM,aedriccahl", "RaesretaircchleMethodology", "1", "Quality", "control", "and", "data-handling", "in", "multicentre", "studies:", "the", "case", "of", "the", "Multicentre", "Project", "for", "Tuberculosis", "Research", "Teresa", "Caloto1,", "Consuelo", "Huerta1,", "Teresa", "Moreno1,", "Dolores", "Guerra1,", "José", "Alcaide2,", "Concha", "Castells3,", "José", "I", "Cardenal4,", "Angela", "Domínguez2,", "Pilar", "Gayoso5,", "Gonzalo", "Gutiérrez6,", "Maria", "J", "López7,", "Francisco", "Muñoz8,", "Carmen", "Navarro9,", "Miguel", "Picó10,", "Francisco", "Pozo1,", "José", "R", "Quirós11,", "Francisco", "Robles12,", "José", "M", "Sánchez13,", "Hermelinda", "Vanaclocha14,", "Tomás", "Vega15", "and", "Mercedes", "Diez*1", "for", "the", "MPTR", "Study", "Group", "Address:", "1Unidad", "de", "Investigación", "en", "Tuberculosis,", "Instituto", "de", "Salud", "Carlos", "III,", "Sinesio", "Delgado,", "6,", "28029", "Madrid,", "Spain;,", "2Departamento", "de", "Sanidad", "y", "Seguridad", "Social,", "Dirección", "General", "de", "Salud", "Pública,", "Travessera", "de", "les", "Corts", "131-159,", "08028", "Barcelona", "Spain;,", "3Departamento", "de", "Sanidad,", "Delegación", "Territorial,", "María", "Díaz", "de", "Haro", "60,", "48010", "Bilbao", "Spain;,", "4Consejería", "de", "Bienestar", "Social,", "Servicio", "Territorial,", "Plaza", "de", "Alféreces", "Provisionales", "s/n,", "10071", "Caceres,", "Spain;,", "5Complejo", "Hospitalario", "Cristal-Piñor,", "Ramón", "Puga", "54,", "32005", "Orense,", "Spain;,", "6Dirección", "General", "de", "Salud", "Pública,", "Avenida", "de", "Francia", "4,", "45071", "Toledo,", "Spain;,", "7Consejería", "de", "Salud", "Consumo", "y", "Bienestar", "Social,", "Dirección", "General", "de", "Salud", "y", "Consumo,", "Villamediana", "17,", "26071", "Logroño,", "Spain;,", "8Hospital", "Universitario", "de", "Valme,", "Carretera", "de", "Cádiz", "s/n,", "41014", "Sevilla,", "Spain;,", "9Consejería", "de", "Sanidad", "y", "Política", "Social,", "Dirección", "General", "de", "Salud,", "Ronda", "de", "Levante", "11,", "30008", "Murcia,", "Spain;,", "10Dirección", "General", "de", "Salud", "Pública,", "Avenida", "de", "la", "Innovación", "s/n,", "Edificio", "Arena", "1,", "41020", "Sevilla,", "Spain;,", "11Dirección", "Regional", "de", "Salud", "Pública,", "General", "Elorza", "32,", "33001", "Oviedo,", "Spain;,", "12Dirección", "Provincial", "de", "Sanidad", "de", "Melilla,", "Plaza", "1", "de", "Mayo", "s/n,", "29803", "Melilla,", "Spain;,", "13Dirección", "Provincial", "de", "Sanidad", "de", "Ceuta,", "Carretera", "San", "Amaro", "12,", "51001", "Ceuta,", "Spain;,", "14Dirección", "General", "de", "Salud", "Pública,", "Doctor", "Rodríguez", "Fornos", "4,", "46010", "Valencia,", "Spain;", "and", "15Dirección", "General", "de", "Salud", "Pública", "y", "Asistencia,", "Avenida", "de", "Burgos", "5,", "47071", "Valladolid,", "Spain", "E-mail:", "Teresa", "Caloto", "-", "Teresa_caloto@merck.com;", "Consuelo", "Huerta", "-", "chuerta@ceife.es;", "Teresa", "Moreno", "-", "mmoreno@isciii.es;", "Dolores", "Guerra", "-", "lola@enterprise.eui.upm.es;", "José", "Alcaide", "-", "jalcaide@dsss.scs.es;", "Concha", "Castells", "-", "depidebi-san@eg-gv.es;", "José", "I", "Cardenal", "-", "jicardenal@bme.es;", "Angela", "Domínguez", "-", "angelad@dsss.scs.es;", "Pilar", "Gayoso", "-", "pgayoso@cristalp.es;", "Gonzalo", "Gutiérrez", "-", "ve@jccm.es;", "Maria", "J", "López", "-", "mjose.lopez@larioja.org;", "Francisco", "Muñoz", "-", "med000552@nacom.es;", "Carmen", "Navarro", "-", "Carmen.Navarro@carm.es;", "Miguel", "Picó", "-", "sito@arrakis.es;", "Francisco", "Pozo", "-", "fpozo@h120.es;", "José", "R", "Quirós", "-", "ramonqg@princast.es;", "Francisco", "Robles", "-", "froblesf@camelilla.es;", "José", "M", "Sánchez", "-", "sanfer@teleline.es;", "Hermelinda", "Vanaclocha", "-", "vanaclocha_her@gva.es;", "Tomás", "Vega", "-", "sybs.epi@dvnet.es;", "Mercedes", "Diez*", "-", "mdiez@isciii.es", "*Corresponding", "author", "Published:", "21", "December", "2001", "BMC", "Medical", "Research", "Methodology", "2001,", "1:14", "This", "article", "is", "available", "from:", "http://www.biomedcentral.com/1471-2288/1/14", "Received:", "9", "October", "2001", "Accepted:", "21", "December", "2001", "©", "2001", "Caloto", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "Verbatim", "copying", "and", "redistribution", "of", "this", "article", "are", "permitted", "in", "any", "medium", "for", "any", "purpose,", "provided", "this", "notice", "is", "preserved", "along", "with", "the", "article's", "original", "URL.", "Abstract", "Background:", "The", "Multicentre", "Project", "for", "Tuberculosis", "Research", "(MPTR)", "was", "a", "clinical-", "epidemiological", "study", "on", "tuberculosis", "carried", "out", "in", "Spain", "from", "1996", "to", "1998.", "In", "total,", "96", "centres", "scattered", "all", "over", "the", "country", "participated", "in", "the", "project,", "19935", "\"possible", "cases\"", "of", "tuberculosis", "were", "examined", "and", "10053", "finally", "included.", "Data-handling", "and", "quality", "control", "procedures", "implemented", "in", "the", "MPTR", "are", "described.", "Methods:", "The", "study", "was", "divided", "in", "three", "phases:", "1)", "preliminary", "phase,", "2)", "field", "work", "3)", "final", "phase.", "Quality", "control", "procedures", "during", "the", "three", "phases", "are", "described.", "Results:", "Preliminary", "phase:", "a)", "organisation", "of", "the", "research", "team;", "b)", "design", "of", "epidemiological", "tools;", "training", "of", "researchers.", "Field", "work:", "a)", "data", "collection;", "b)", "data", "computerisation;", "c)", "data", "transmission;", "d)", "data", "cleaning;", "e)", "quality", "control", "audits;", "f)", "confidentiality.", "Final", "phase:", "a)", "final", "data", "cleaning;", "b)", "final", "analysis.", "Conclusion:", "The", "undertaking", "of", "a", "multicentre", "project", "implies", "the", "need", "to", "work", "with", "a", "heterogeneous", "research", "team", "and", "yet", "at", "the", "same", "time", "attain", "a", "common", "goal", "by", "following", "a", "homogeneous", "methodology.", "This", "demands", "an", "additional", "effort", "on", "quality", "control.", "Page", "1", "of", "6", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Journal", "of", "Translational", "Medicine", "Research", "Survivin", "gene", "levels", "in", "the", "peripheral", "blood", "of", "patients", "with", "gastric", "cancer", "independently", "predict", "survival", "Loris", "Bertazza1,2,", "Simone", "Mocellin*1,", "Alberto", "Marchet1,", "Pierluigi", "Pilati1,", "Joseph", "Gabrieli1,", "Romano", "Scalerta1", "and", "Donato", "Nitti1", "BioMed", "Central", "Open", "Access", "Address:", "1Department", "of", "Oncological", "&", "Surgical", "Sciences,", "Section", "of", "Clinica", "Chirurgica", "2,", "University", "of", "Padova,", "via", "Giustiniani", "2,", "35128,", "Padua,", "Italy", "and", "2Istituto", "Oncologico", "Veneto", "IRCCS,", "via", "Gattamelata", "64,", "35128,", "Padua,", "Italy", "Email:", "Loris", "Bertazza", "-", "loris.bertazza@unipd.it;", "Simone", "Mocellin*", "-", "simone.mocellin@unipd.it;", "Alberto", "Marchet", "-", "marchet@unipd.it;", "Pierluigi", "Pilati", "-", "pl.pilati@unipd.it;", "Joseph", "Gabrieli", "-", "josephgabrieli@yahoo.it;", "Romano", "Scalerta", "-", "romano.scalerta@unipd.it;", "Donato", "Nitti", "-", "donato.nitti@unipd.it", "*", "Corresponding", "author", "Published:", "22", "December", "2009", "Journal", "of", "Translational", "Medicine", "2009,", "7:111", "doi:10.1186/1479-5876-7-111", "This", "article", "is", "available", "from:", "http://www.translational-medicine.com/content/7/1/111", "Received:", "24", "August", "2009", "Accepted:", "22", "December", "2009", "©", "2009", "Bertazza", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Background:", "The", "detection", "of", "circulating", "tumor", "cells", "(CTC)", "is", "considered", "a", "promising", "tool", "for", "improving", "risk", "stratification", "in", "patients", "with", "solid", "tumors.", "We", "investigated", "on", "whether", "the", "expression", "of", "CTC", "related", "genes", "adds", "any", "prognostic", "power", "to", "the", "TNM", "staging", "system", "in", "patients", "with", "gastric", "carcinoma.", "Methods:", "Seventy", "patients", "with", "TNM", "stage", "I", "to", "IV", "gastric", "carcinoma", "were", "retrospectively", "enrolled.", "Peripheral", "blood", "samples", "were", "tested", "by", "means", "of", "quantitative", "real", "time", "PCR", "(qrtPCR)", "for", "the", "expression", "of", "four", "CTC", "related", "genes:", "carcinoembryonic", "antigen", "(CEA),", "cytokeratin-19", "(CK19),", "vascular", "endothelial", "growth", "factor", "(VEGF)", "and", "Survivin", "(BIRC5).", "Results:", "Gene", "expression", "of", "Survivin,", "CK19,", "CEA", "and", "VEGF", "was", "higher", "than", "in", "normal", "controls", "in", "98.6%,", "97.1%,", "42.9%", "and", "38.6%", "of", "cases,", "respectively,", "suggesting", "a", "potential", "diagnostic", "value", "of", "both", "Survivin", "and", "CK19.", "At", "multivariable", "survival", "analysis,", "TNM", "staging", "and", "Survivin", "mRNA", "levels", "were", "retained", "as", "independent", "prognostic", "factors,", "demonstrating", "that", "Survivin", "expression", "in", "the", "peripheral", "blood", "adds", "prognostic", "information", "to", "the", "TNM", "system.", "In", "contrast", "with", "previously", "published", "data,", "the", "transcript", "abundance", "of", "CEA,", "CK19", "and", "VEGF", "was", "not", "associated", "with", "patients'", "clinical", "outcome.", "Conclusions:", "Gene", "expression", "levels", "of", "Survivin", "add", "significant", "prognostic", "value", "to", "the", "current", "TNM", "staging", "system.", "The", "validation", "of", "these", "findings", "in", "larger", "prospective", "and", "multicentric", "series", "might", "lead", "to", "the", "implementation", "of", "this", "biomarker", "in", "the", "routine", "clinical", "setting", "in", "order", "to", "optimize", "risk", "stratification", "and", "ultimately", "personalize", "the", "therapeutic", "management", "of", "these", "patients.", "Background", "Gastric", "cancer", "represents", "the", "fourth", "most", "common", "cancer", "and", "second", "leading", "cause", "of", "cancer-related", "death", "world-", "wide.", "The", "estimated", "current", "incidence", "of", "gastric", "cancer", "is", "approximately", "16.2/100", "000", "persons/year", "(world", "stand-", "ardized", "rate,", "WSR),", "with", "highest", "incidences", "in", "Eastern", "Page", "1", "of", "8", "(page", "number", "not", "for", "citation", "purposes)" ]

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"are", "centrally", "installed", "and", "maintained", "by", "the", "RZG.", "Currently,", "supported", "tasks", "comprise", "sequence", "similarity", "searches", "in", "public", "or", "user-", "supplied", "databases,", "computation", "and", "validation", "of", "multiple", "sequence", "alignments,", "phylogenetic", "analysis", "and", "protein–structure", "prediction.", "Individual", "tools", "can", "be", "seamlessly", "chained", "into", "pipelines", "allowing", "the", "user", "to", "conveniently", "process", "complex", "workflows", "without", "the", "necessity", "to", "take", "care", "of", "any", "format", "con-", "versions", "or", "tedious", "parsing", "of", "intermediate", "results.", "The", "toolkit", "is", "part", "of", "the", "Max-Planck", "Integrated", "Gene", "Analysis", "System", "(MIGenAS)", "of", "the", "Max", "Planck", "Society", "available", "at", "www.migenas.org", "(click", "‘Start", "Toolkit’).", "INTRODUCTION", "A", "large", "pool", "of", "individual", "websites", "offering", "convenient", "access", "to", "basic", "bioinformatics", "software", "and", "data", "have", "certainly", "greatly", "helped", "to", "establish", "many", "computational", "methods", "as", "standard", "tools", "in", "life", "sciences.", "Meanwhile,", "almost", "any", "newly", "published", "bioinformatics", "software", "package", "which", "is", "distrib-", "uted", "for", "installation", "on", "PCs", "is", "supplemented", "by", "a", "web", "server", "(hosted", "by", "the", "software", "developers", "and/or", "provided", "for", "down-", "load", "and", "local", "installation)", "in", "order", "to", "enhance", "usability,", "attract", "and", "guide", "users,", "and", "to", "promote", "visibility", "of", "the", "software", "in", "the", "scientific", "community.", "NCBI’s", "BLAST", "services", "are", "the", "proto-", "typical", "example.", "Advanced", "analysis,", "however,", "most", "often", "requires", "the", "con-", "certed", "interoperation", "of", "different", "tools", "and", "heterogeneous", "data.", "Processing", "the", "corresponding", "workflows", "by", "consecutively", "visiting", "websites", "dispersed", "over", "the", "Internet", "is", "apparently", "very", "cumbersome,", "if", "not", "impracticable.", "Apart", "from", "a", "small", "subset", "of", "well-defined", "applications", "which", "are", "well", "supported", "by", "exist-", "ing", "special", "purpose", "software", "[e.g.", "the", "ARB", "package", "for", "sequence-based", "phylogenetic", "analysis", "(1)]", "surprisingly", "few", "integrated", "software", "environments", "for", "managing", "such", "workflows", "of", "basic", "analysis", "steps", "in", "a", "versatile", "and", "user-friendly", "way", "are", "publicly", "available.", "Existing", "client–server", "applications", "may", "be", "subdivided", "into", "classic", "web", "portals", "(2,3)", "and—emerging", "more", "recently—solutions", "based", "on", "so-called", "rich", "clients", "for", "harvest-", "ing", "services", "and", "data", "which", "are", "dispersed", "across", "the", "Internet", "[cf.", "Ref.", "(4)", "for", "an", "example", "and", "recent", "overview;", "see", "also", "www.", "kepler-project.org].", "Owing", "to", "its", "service-oriented", "software", "architecture", "our", "sys-", "tem", "can", "serve", "both", "purposes:", "while", "in", "this", "article", "we", "shall", "mainly", "focus", "on", "functionalities", "offered", "by", "a", "powerful", "web", "interface,", "the", "MIGenAS", "infrastructure", "also", "provides", "SOAP-", "based", "web", "services", "that", "can", "be", "be", "utilized", "by", "third-party", "(remote)", "client", "applications.", "FEATURES", "AND", "FUNCTIONALITIES", "The", "MIGenAS", "bioinformatics", "toolkit", "is", "a", "new", "web", "application", "for", "processing", "basic", "bioinformatics", "tasks", "as", "well", "as", "orchestrat-", "ing", "them", "into", "complex", "workflows", "within", "a", "single,", "coherent", "web", "interface.", "Target", "users", "are", "only", "assumed", "to", "be", "familiar", "with", "the", "basic", "functionality", "offered", "by", "the", "popular", "sequence", "analysis", "tools.", "Neither", "additional", "computational", "prerequisites", "(A", "mod-", "ern", "version", "of", "one", "of", "the", "popular", "web", "browsers,", "Mozilla/Firefox,", "Opera", "or", "Internet", "Explorer", "is", "required", "with", "JavaScript", "enabled.)", "nor", "in-depth", "bioinformatics", "experience", "is", "considered", "to", "be", "necessary", "for", "working", "with", "the", "toolkit.", "The", "system", "has", "been", "developed", "with", "support", "of", "the", "MIGenAS", "consortium", "of", "the", "Max-Planck-Society.", "Founding", "members", "are", "the", "Max-Planck-", "Institute", "(MPI)", "of", "Biochemistry", "(Department", "of", "Oesterhelt),", "MPI", "for", "Computer", "Science", "(Department", "of", "Lengauer),", "MPI", "for", "Developmental", "Biology", "(Department", "of", "Lupas,", "and", "Group", "S.C.", "Schuster:", "presently", "at", "Pennsylvania", "State", "Univer-", "sity,", "USA),", "MPI", "for", "Marine", "Microbiology", "(Department", "of", "Amann)", "and", "the", "RZG.", "Services", "are", "provided", "and", "hosted", "by", "*To", "whom", "correspondence", "should", "be", "addressed.", "Tel:", "+49", "0", "89", "3299", "2176;", "Fax:", "+49", "0", "80", "3299", "1301;", "Email:", "markus.rampp@rzg.mpg.de", "The", "Author", "2006.", "Published", "by", "Oxford", "University", "Press.", "All", "rights", "reserved.", "The", "online", "version", "of", "this", "article", "has", "been", "published", "under", "an", "open", "access", "model.", "Users", "are", "entitled", "to", "use,", "reproduce,", "disseminate,", "or", "display", "the", "open", "access", "version", "of", "this", "article", "for", "non-commercial", "purposes", "provided", "that:", "the", "original", "authorship", "is", "properly", "and", "fully", "attributed;", "the", "Journal", "and", "Oxford", "University", "Press", "are", "attributed", "as", "the", "original", "place", "of", "publication", "with", "the", "correct", "citation", "details", "given;", "if", "an", "article", "is", "subsequently", "reproduced", "or", "disseminated", "not", "in", "its", "entirety", "but", "only", "in", "part", "or", "as", "a", "derivative", "work", "this", "must", "be", "clearly", "indicated.", "For", "commercial", "re-use,", "please", "contact", "journals.permissions@oxfordjournals.org" ]

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[ "Tomkinson", "et", "al.", "BMC", "Clinical", "Pharmacology", "2011,", "11:3", "http://www.biomedcentral.com/1472-6904/11/3", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "Pharmacokinetics", "and", "tolerability", "of", "zibotentan", "(ZD4054)", "in", "subjects", "with", "hepatic", "or", "renal", "impairment:", "two", "open-label", "comparative", "studies", "Helen", "Tomkinson*,", "John", "Kemp,", "Stuart", "Oliver,", "Helen", "Swaisland,", "Maria", "Taboada,", "Thomas", "Morris", "Abstract", "Background:", "Zibotentan", "(ZD4054)", "is", "a", "specific", "endothelin", "A", "(ETA)", "receptor", "antagonist", "being", "investigated", "for", "the", "treatment", "of", "prostate", "cancer.", "As", "zibotentan", "is", "eliminated", "by", "renal", "and", "metabolic", "routes,", "clearance", "may", "be", "reduced", "in", "patients", "with", "hepatic", "or", "renal", "impairment,", "leading", "to", "greater", "drug", "exposure.", "Methods:", "Open-label", "studies", "investigated", "the", "PK", "and", "tolerability", "of", "zibotentan", "in", "subjects", "with", "hepatic", "or", "renal", "impairment,", "compared", "with", "those", "with", "normal", "organ", "function.", "In", "the", "hepatic", "and", "renal", "studies,", "respectively,", "subjects", "were", "divided", "into", "categories", "using", "Child-Pugh", "classification", "or", "24-hour", "urine", "creatinine", "clearance", "(mild,", "moderate,", "or", "severe", "impairment", "and", "normal", "function).", "Each", "subject", "received", "a", "single", "oral", "dose", "of", "zibotentan", "10", "mg", "and", "PK", "sampling", "was", "undertaken.", "Within", "the", "hepatic", "study,", "AUC", "and", "Cmax", "were", "expressed", "as", "the", "ratio", "of", "geometric", "means", "and", "90%", "CI", "for", "each", "impairment", "group", "compared", "with", "the", "normal", "function", "group.", "The", "possibility", "that", "hepatic", "impairment", "had", "a", "clinically", "relevant", "effect", "on", "exposure", "was", "considered", "if", "the", "upper", "90%", "CI", "for", "the", "ratio", "exceeded", "2.", "In", "the", "renal", "study,", "AUC,", "Cmax", "and", "t1/2", "were", "analyzed", "using", "linear", "regression", "fitting", "effects", "for", "creatinine", "clearance", "and", "age.", "Results:", "In", "the", "hepatic", "and", "renal", "studies", "respectively,", "32", "subjects", "(eight", "per", "group)", "and", "48", "subjects", "received", "treatment", "(n", "=", "18", "normal,", "n", "=", "12", "mild,", "n", "=", "9", "moderate,", "n", "=", "9", "severe).", "Zibotentan", "Cmax", "was", "not", "significantly", "affected", "by", "hepatic", "or", "renal", "impairment.", "Compared", "with", "the", "normal", "function", "group,", "zibotentan", "AUC", "was", "40%", "(1.40;", "90%", "CI", "0.91-2.17),", "45%", "(1.45;", "90%", "CI", "0.94-2.24)", "and", "190%", "(2.90;", "90%", "CI", "1.88-4.49)", "higher", "in", "subjects", "with", "mild,", "moderate", "and", "severe", "hepatic", "impairment,", "respectively,", "and", "66%", "(1.66;", "90%", "CI", "1.38-1.99),", "89%", "(1.89;", "90%", "CI", "1.50-", "2.39)", "and", "117%", "(2.17;", "90%", "CI", "1.64-2.86)", "higher", "in", "subjects", "with", "mild,", "moderate", "and", "severe", "renal", "impairment,", "respectively.", "In", "both", "studies", "mean", "t1/2", "increased", "and", "zibotentan", "clearance", "decreased", "with", "the", "degree", "of", "impairment.", "Headache", "was", "the", "most", "common", "AE", "in", "all", "groups.", "Conclusions:", "Zibotentan", "absorption", "was", "unchanged,", "however,", "exposure", "was", "higher", "in", "subjects", "with", "hepatic", "or", "renal", "impairment", "due", "to", "slower", "clearance.", "This", "increased", "exposure", "did", "not", "result", "in", "differences", "in", "the", "range", "or", "severity", "of", "AEs", "observed.", "Trial", "Registration:", "ClinicalTrials.gov:", "NCT00672581", "and", "AstraZeneca", "study", "number", "D4320C00016", "(renal", "trial;", "conducted", "in", "Germany).", "Background", "Prostate", "cancer", "is", "a", "leading", "cause", "of", "death", "in", "men", "in", "the", "Western", "world,", "accounting", "for", "an", "estimated", "28%", "of", "new", "cancer", "cases", "in", "men", "in", "the", "US", "in", "2010", "[1].", "Patients", "with", "advanced", "prostate", "cancer", "are", "initially", "treated", "with", "andro-", "gen", "deprivation", "therapy;", "however,", "disease", "progression", "will", "*", "Correspondence:", "helen.tomkinson@astrazeneca.com", "AstraZeneca,", "Alderley", "Park,", "Macclesfield,", "UK", "eventually", "occur", "in", "many", "men", "despite", "castrate", "serum", "androgen", "levels.", "This", "stage", "of", "disease", "is", "defined", "as", "castra-", "tion-resistant", "prostate", "cancer", "(CRPC)", "for", "which", "treatment", "is", "currently", "limited", "to", "further", "hormonal", "manipulation", "or", "cytotoxic", "chemotherapy", "[2].", "The", "endothelin", "(ET)", "axis", "has", "been", "implicated", "in", "several", "mechanisms", "that", "promote", "cancer", "progression.", "Endothe-", "lin-1", "(ET-1)", "acting", "through", "the", "endothelin", "A", "(ETA)", "©", "2011", "Tomkinson", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Frontiers", "in", "Zoology", "Research", "Bacterial", "feeding", "induces", "changes", "in", "immune-related", "gene", "expression", "and", "has", "trans-generational", "impacts", "in", "the", "cabbage", "looper", "(Trichoplusia", "ni)", "Dalial", "Freitak*,", "David", "G", "Heckel", "and", "Heiko", "Vogel", "BioMed", "Central", "Open", "Access", "Address:", "Max", "Planck", "Institute", "for", "Chemical", "Ecology,", "Department", "of", "Entomology,", "Hans", "Knöll", "Strasse", "8,", "07745", "Jena,", "Germany", "Email:", "Dalial", "Freitak*", "-", "dfreitak@ice.mpg.de;", "David", "G", "Heckel", "-", "heckel@ice.mpg.de;", "Heiko", "Vogel", "-", "hvogel@ice.mpg.de", "*", "Corresponding", "author", "Published:", "7", "May", "2009", "Frontiers", "in", "Zoology", "2009,", "6:7", "doi:10.1186/1742-9994-6-7", "This", "article", "is", "available", "from:", "http://www.frontiersinzoology.com/content/6/1/7", "Received:", "17", "December", "2008", "Accepted:", "7", "May", "2009", "©", "2009", "Freitak", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Background:", "Poly-", "and", "oligophagous", "insects", "are", "able", "to", "feed", "on", "various", "host", "plants", "with", "a", "wide", "range", "of", "defense", "strategies.", "However,", "diverse", "food", "plants", "are", "also", "inhabited", "by", "microbiota", "differing", "in", "quality", "and", "quantity,", "posing", "a", "potential", "challenge", "for", "immune", "system", "mediated", "homeostasis", "in", "the", "herbivore.", "Recent", "studies", "highlight", "the", "complex", "interactions", "between", "environmentally", "encountered", "microorganisms", "and", "herbivorous", "insects,", "pointing", "to", "a", "potential", "adaptational", "alteration", "of", "the", "insects'", "physiology.", "We", "performed", "a", "differential", "gene", "expression", "analysis", "in", "whole", "larvae", "and", "eggs", "laid", "by", "parents", "grown", "on", "different", "diets", "to", "identify", "potential", "novel", "genes", "related", "to", "elevated", "microbial", "content", "in", "the", "caterpillars'", "food.", "Results:", "We", "used", "GeneFishing,", "a", "novel", "differential", "display", "method,", "to", "study", "the", "effects", "of", "dietary", "bacteria", "on", "the", "general", "gene", "expression", "in", "different", "life", "stages", "and", "tissues", "of", "the", "cabbage", "looper", "(Trichoplusia", "ni).", "We", "were", "able", "to", "visualize", "several", "hundred", "transcripts", "on", "agarose", "gels,", "one", "fifth", "of", "which", "were", "differentially", "expressed", "between", "treatments.", "The", "largest", "number", "of", "differentially", "expressed", "genes", "was", "found", "in", "defense-related", "processes", "(13)", "and", "in", "recognition", "and", "metabolism", "(16).", "21", "genes", "were", "picked", "out", "and", "further", "tested", "for", "differential", "gene", "expression", "by", "an", "independent", "method", "(qRT-PCR)", "in", "various", "tissues", "of", "larvae", "grown", "on", "bacterial", "and", "bacteria-free", "diet,", "and", "also", "in", "adults.", "We", "detected", "a", "number", "of", "genes", "indicative", "of", "an", "altered", "physiological", "status", "of", "the", "insect,", "depending", "on", "the", "diet,", "developmental", "stage", "and", "tissue.", "Conclusion:", "Changes", "in", "immune", "status", "are", "accompanied", "by", "specific", "changes", "in", "the", "transcript", "levels", "of", "genes", "connected", "to", "metabolism", "and", "homeostasis", "of", "the", "organism.", "Our", "findings", "show", "that", "larval", "feeding", "on", "bacteria-rich", "diet", "leads", "to", "substantial", "gene", "expression", "changes,", "potentially", "resulting", "in", "a", "reorganization", "of", "the", "insects'", "metabolism", "to", "maintain", "organismal", "homeostasis,", "not", "only", "in", "the", "larval", "but", "also", "in", "the", "adult", "stage.", "Furthermore,", "differences", "in", "gene", "expression", "levels", "can", "also", "be", "seen", "in", "the", "next", "generation,", "strongly", "influenced", "by", "parental", "diet.", "Background", "Most", "Lepidopteran", "larvae", "are", "herbivorous", "and", "many", "among", "them", "are", "important", "pests", "in", "agriculture,", "causing", "severe", "damage", "to", "various", "crop", "plants", "growing", "in", "monoc-", "ultures.", "The", "level", "of", "specialization", "even", "within", "a", "Lepidop-", "teran", "family", "can", "vary", "dramatically.", "Larval", "feeding", "can", "be", "Page", "1", "of", "11", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "organic", "compounds", "Acta", "Crystallographica", "Section", "E", "Structure", "Reports", "Online", "ISSN", "1600-5368", "(20S)-22-Acetoxymethyl-6b-methoxy-", "3a,5-dihydro-30H-cyclopropa[3a,5]-5a-", "pregnane", "Kamal", "Aziz", "Ketuly,", "A.", "Hamid", "A.", "Hadi", "and", "Seik", "Weng", "Ng*", "Department", "of", "Chemistry,", "University", "of", "Malaya,", "50603", "Kuala", "Lumpur,", "Malaysia", "Correspondence", "e-mail:", "seikweng@um.edu.my", "Received", "27", "May", "2009;", "accepted", "31", "May", "2009", "Key", "indicators:", "single-crystal", "X-ray", "study;", "T", "=", "100", "K;", "mean", "(C–C)", "=", "0.002", "A˚;", "R", "factor", "=", "0.033;", "wR", "factor", "=", "0.092;", "data-to-parameter", "ratio", "=", "10.4.", "In", "the", "title", "steroid", "derivative,", "C25H40O3,", "the", "fused", "cyclo-", "propane", "unit", "that", "corresponds", "to", "a", "part", "of", "the", "A", "ring", "has", "a", "-", "configuration", "and", "the", "associated", "cyclopentane", "ring", "an", "envelope-shaped", "conformation.", "Related", "literature", "For", "the", "synthesis", "and", "crystal", "structure", "of", "the", "iodo-substituted", "compound,", "see:", "Ketuly", "et", "al.", "(2009).", "The", "absolute", "configura-", "tion", "of", "the", "acetoxymethyl", "title", "compound", "is", "that", "of", "the", "iodo-", "substituted", "compound.", "Experimental", "Crystal", "data", "C25H40O3", "Mr", "=", "388.57", "Monoclinic,", "P21", "a", "=", "9.8222", "(1)", "A˚", "b", "=", "7.6128", "(1)", "A˚", "c", "=", "15.2309", "(2)", "A˚", "=", "107.604", "(1)", "Data", "collection", "Bruker", "SMART", "APEX", "diffractometer", "Absorption", "correction:", "none", "10411", "measured", "reflections", "Refinement", "R[F", "2", ">", "2", "(F", "2)]", "=", "0.033", "wR(F", "2)", "=", "0.092", "S", "=", "1.05", "2674", "reflections", "258", "parameters", "V", "=", "1085.55", "(2)", "A˚", "3", "Z", "=", "2", "Mo", "K", "radiation", "=", "0.08", "mm", "1", "T", "=", "100", "K", "0.30", "0.10", "0.02", "mm", "2674", "independent", "reflections", "2550", "reflections", "with", "I", ">", "2", "(I)", "Rint", "=", "0.023", "1", "restraint", "H-atom", "parameters", "constrained", "max", "=", "0.30", "e", "A˚", "3", "min", "=", "0.18", "e", "A˚", "3", "Data", "collection:", "APEX2", "(Bruker,", "2008);", "cell", "refinement:", "SAINT", "(Bruker,", "2008);", "data", "reduction:", "SAINT;", "program(s)", "used", "to", "solve", "structure:", "SHELXS97", "(Sheldrick,", "2008);", "program(s)", "used", "to", "refine", "structure:", "SHELXL97", "(Sheldrick,", "2008);", "molecular", "graphics:", "X-", "SEED", "(Barbour,", "2001);", "software", "used", "to", "prepare", "material", "for", "publication:", "publCIF", "(Westrip,", "2009).", "We", "thank", "the", "University", "of", "Malaya", "for", "supporting", "this", "study.", "Supplementary", "data", "and", "figures", "for", "this", "paper", "are", "available", "from", "the", "IUCr", "electronic", "archives", "(Reference:", "XU2534).", "References", "Barbour,", "L.", "J.", "(2001).", "J.", "Supramol.", "Chem.", "1,", "189–211.", "Bruker", "(2008).", "APEX2", "and", "SAINT.", "Bruker", "AXS", "Inc.,", "Madison,", "Wisconsin,", "USA.", "Ketuly,", "K.", "A.", "A.,", "Hadi,", "A.", "H.", "&", "Ng,", "S.", "W.", "(2009).", "Acta", "Cryst.", "E65,", "o1125.", "Sheldrick,", "G.", "M.", "(2008).", "Acta", "Cryst.", "A64,", "112–122.", "Westrip,", "S.", "P.", "(2009).", "publCIF.", "In", "preparation.", "o1486", "Ketuly", "et", "al.", "doi:10.1107/S1600536809020674", "Acta", "Cryst.", "(2009).", "E65,", "o1486" ]

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[ "inorganic", "compounds", "Acta", "Crystallographica", "Section", "E", "Structure", "Reports", "Online", "ISSN", "1600-5368", "Robertsite,", "Ca2MnIII3O2(PO4)3", "3H2O", "Marcelo", "B.", "Andrade,a*", "Shaunna", "M.", "Morrison,a", "Adrien", "J.", "Di", "Domizio,a", "Mark", "N.", "Feinglosb", "and", "Robert", "T.", "Downsa", "aDepartment", "of", "Geosciences,", "University", "of", "Arizona,", "1040", "E.", "4th", "Street,", "Tucson,", "Arizona", "85721-0077,", "USA,", "and", "bDuke", "University", "Medical", "Center,", "Box", "3921,", "Durham,", "North", "Carolina", "27710,", "USA", "Correspondence", "e-mail:", "mabadean@terra.com.br", "Received", "13", "August", "2012;", "accepted", "30", "August", "2012", "Key", "indicators:", "single-crystal", "X-ray", "study;", "T", "=", "293", "K;", "mean", "(P–O)", "=", "0.006", "A˚;", "R", "factor", "=", "0.045;", "wR", "factor", "=", "0.107;", "data-to-parameter", "ratio", "=", "18.7.", "Robertsite,", "ideally", "Ca2Mn3O2(PO4)3", "3H2O", "[calcium", "manga-", "nese(III)", "tris(orthophosphate)", "trihydrate],", "can", "be", "associated", "with", "the", "arseniosiderite", "structural", "group", "characterized", "by", "the", "general", "formula", "Ca2A3O2(TO4)3", "nH2O,", "with", "A", "=", "Fe,", "Mn;", "T", "=", "As,", "P;", "and", "n", "=", "2", "or", "3.", "In", "this", "study,", "single-crystal", "X-ray", "diffraction", "data", "were", "used", "to", "determine", "the", "robertsite", "structure", "from", "a", "twinned", "crystal", "from", "the", "type", "locality,", "the", "Tip", "Top", "mine,", "Custer", "County,", "South", "Dakota,", "USA,", "and", "to", "refine", "anisotropic", "displacement", "parameters", "for", "all", "atoms.", "The", "general", "structural", "feature", "of", "robertsite", "resembles", "that", "of", "the", "other", "two", "members", "of", "the", "arseniosiderite", "group,", "the", "structures", "of", "which", "have", "previously", "been", "reported.", "It", "is", "characterized", "by", "sheets", "of", "[MnO6]", "octahedra", "in", "the", "form", "of", "nine-membered", "pseudo-trigonal", "rings.", "Located", "at", "the", "center", "of", "each", "nine-", "membered", "ring", "is", "a", "PO4", "tetrahedron,", "and", "the", "other", "eight", "PO4", "tetrahedra", "sandwich", "the", "Mn–oxide", "sheets.", "The", "six", "different", "Ca2+", "ions", "are", "seven-coordinated", "in", "form", "of", "distorted", "penta-", "gonal", "bipyramids,", "[CaO5(H2O)2],", "if", "Ca—O", "distances", "less", "than", "2.85", "A˚", "are", "considered.", "Along", "with", "hydrogen", "bonding", "invol-", "ving", "the", "water", "molecules,", "they", "hold", "the", "manganese–phosphate", "sheets", "together.", "All", "nine", "[MnO6]", "octahedra", "are", "distorted", "by", "the", "Jahn–Teller", "effect.", "Related", "literature", "For", "information", "on", "the", "arseniosiderite", "group", "minerals,", "see:", "Moore", "&", "Ito", "(1974);", "Moore", "&", "Araki", "(1977);", "van", "Kauwen-", "bergh", "et", "al.", "(1988);", "Voloshin", "et", "al.", "(1982).", "For", "details", "of", "sailaufite,", "see:", "Wildner", "et", "al.", "(2003).", "For", "studies", "on", "para-", "robertsite,", "see:", "Roberts", "et", "al.", "(1989);", "Kampf", "(2000).", "For", "research", "involving", "Mn3+", "pairing", "in", "phosphate", "minerals,", "see:", "Fransolet", "(2000).", "For", "information", "on", "crystalline", "manganese", "phosphate-based", "adsorbers,", "see:", "Kulprathipanja", "et", "al.", "(2001).", "Experimental", "Crystal", "data", "Ca2Mn3O2(PO4)3", "3H2O", "Mr", "=", "615.94", "Monoclinic,", "Aa", "a", "=", "17.3400", "(9)", "A˚", "b", "=", "19.4464", "(10)", "A˚", "c", "=", "11.2787", "(6)", "A˚", "=", "96.634", "(3)", "Data", "collection", "Bruker", "APEXII", "CCD", "area-detector", "diffractometer", "Absorption", "correction:", "multi-scan", "(SADABS;", "Bruker,", "2004)", "Tmin", "=", "0.755,", "Tmax", "=", "0.784", "Refinement", "R[F", "2", ">", "2", "(F", "2)]", "=", "0.045", "wR(F", "2)", "=", "0.107", "S", "=", "1.02", "12635", "reflections", "677", "parameters", "2", "restraints", "Table", "1", "Hydrogen-bond", "geometry", "(A˚", ").", "V", "=", "3777.7", "(3)", "A˚", "3", "Z", "=", "12", "Mo", "K", "radiation", "=", "4.26", "mm", "1", "T", "=", "293", "K", "0.07", "0.06", "0.06", "mm", "28397", "measured", "reflections", "12635", "independent", "reflections", "9678", "reflections", "with", "I", ">", "2", "(I)", "Rint", "=", "0.037", "max", "=", "1.74", "e", "A˚", "3", "min", "=", "1.09", "e", "A˚", "3", "Absolute", "structure:", "Flack", "(1983),", "5755", "Friedel", "pairs", "Flack", "parameter:", "0.676", "(18)", "D", "A", "D", "A", "D", "A", "D", "A", "O25iii", "Ow5", "2.792", "(7)", "Ow1", "O17", "2.964", "(7)", "O13iv", "Ow6", "2.977", "(6)", "Ow1", "O33", "2.889", "(8)", "Ow9ii", "Ow6", "2.651", "(7)", "Ow2", "O33", "2.815", "(7)", "O9v", "Ow7", "2.768", "(7)", "Ow2", "Ow8", "2.655", "(8)", "Ow3vi", "Ow7", "2.645", "(7)", "Ow3", "O1i", "2.957", "(4)", "Ow8", "O13", "2.710", "(8)", "Ow3", "O17", "2.821", "(6)", "Ow8", "Ow1", "2.635", "(7)", "Ow4", "O29", "2.764", "(7)", "O12v", "Ow9", "2.989", "(7)", "Ow4", "Ow9", "2.631", "(8)", "O21vii", "Ow9", "2.743", "(8)", "Ow5", "Ow7ii", "2.682", "(8)", "Symmetry", "codes:", "(i)", "x", "þ", "2;", "1", "y", "þ", "21;", "z", "þ", "21;", "(ii)", "x;", "y;", "z", "þ", "1;", "(iii)", "x", "þ", "21;", "y", "þ", "1;", "z;", "(iv)", "x;", "y", "12;", "z", "þ", "21;", "(v)", "x", "þ", "12;", "y", "þ", "21;", "z", "12;", "(vi)", "x;", "y", "þ", "21;", "z", "12;", "(vii)", "x;", "y;", "z", "1.", "Data", "collection:", "APEX2", "(Bruker,", "2004);", "cell", "refinement:", "SAINT", "(Bruker,", "2004);", "data", "reduction:", "SAINT;", "program(s)", "used", "to", "solve", "structure:", "SHELXS97", "(Sheldrick,", "2008);", "program(s)", "used", "to", "refine", "structure:", "SHELXL97", "(Sheldrick,", "2008);", "molecular", "graphics:", "Xtal-", "Draw", "(Downs", "&", "Hall-Wallace,", "2003);", "software", "used", "to", "prepare", "material", "for", "publication:", "publCIF", "(Westrip,", "2010).", "We", "are", "very", "grateful", "to", "A.", "R.", "Kampf", "and", "T.", "A.", "Loomis", "for", "providing", "the", "rare", "pararobertsite", "samples", "to", "the", "RRUFF", "project.", "Support", "of", "this", "study", "was", "given", "by", "the", "Arizona", "Science", "Foundation,", "CNPq", "202469/2011-5", "from", "the", "Brazilian", "government,", "and", "NASA", "NNX11AN75A,", "Mars", "Science", "Laboratory", "Investigations.", "Any", "opinions,", "findings,", "and", "conclusions", "or", "recommendations", "expressed", "in", "this", "material", "are", "those", "of", "the", "author(s)", "and", "do", "not", "reflect", "the", "views", "of", "the", "National", "Aeronautics", "and", "Space", "Administration.", "Supplementary", "data", "and", "figures", "for", "this", "paper", "are", "available", "from", "the", "IUCr", "electronic", "archives", "(Reference:", "WM2672).", "References", "Bruker", "(2004).", "APEX2,", "SAINT", "and", "SADABS.", "Bruker", "AXS", "Inc.,", "Madison,", "Wisconsin,", "USA.", "i74", "Andrade", "et", "al.", "doi:10.1107/S160053681203735X", "Acta", "Cryst.", "(2012).", "E68,", "i74–i75" ]

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[ "O", "R", "I", "G", "I", "N", "A", "L", "R", "E", "S", "E", "A", "R", "C", "H", "Lack", "of", "association", "between", "angiotensin-", "conver", "ting", "enzyme", "and", "dementia", "of", "the", "Alzheimer’s", "type", "in", "an", "elderly", "Arab", "population", "in", "Wadi", "Ara,", "Israel", "Abdalla", "Bowirrat1,2,3", "Jing", "Cui4", "Kristin", "Waraska5", "Robert", "P", "Friedland10", "Marlene", "Oscar-Berman2,3,6", "Lindsay", "A", "Farrer1,6,7,8,9", "Amos", "Korczyn11", "Clinton", "T", "Baldwin1,5,7", "1Genetic", "Program,", "2Department", "of", "Anatomy", "and", "Neurobiology,", "3Division", "of", "Psychiatry,", "4Hypertension", "Section,", "5Center", "for", "Human", "Genetics,", "6Department", "of", "Neurology,", "7Department", "of", "Genetics", "and", "Genomics,", "Boston", "University", "School", "of", "Medicine,", "Boston,", "MA,", "USA;", "8Department", "of", "Epidemiology,", "9Department", "of", "Biostatistics,", "Boston", "University", "School", "of", "Public", "Health,", "Boston,", "MA,", "USA;", "10Department", "of", "Neurology,", "Case", "Western", "Reserve", "University,", "Cleveland,", "OH,", "USA;", "11Department", "of", "Neurology,", "Tel", "Aviv", "University,", "Tel", "Aviv,", "Israel", "Correspondence:", "Abdalla", "Bowirrat", "Department", "of", "Anatomy", "and", "Neurobiology,", "Laboratory", "of", "Neuropsychology,", "Boston", "University", "School", "of", "Medicine,", "715", "Albany", "Street,", "L-815", "Boston,", "MA", "02118,", "USA", "Tel", "+1", "617", "638", "4807", "Fax", "+1", "617", "638", "4806", "Email", "bowirrat@bu.edu", "Abstract:", "The", "angiotensin-converting", "enzyme", "(ACE),", "a", "protease", "involved", "in", "blood", "pressure", "regulation,", "has", "been", "implicated", "as", "an", "important", "candidate", "gene", "for", "Alzheimer’s", "disease", "(AD).", "This", "study", "investigated", "whether", "the", "ACE", "gene", "insertion–deletion", "(ID)", "polymorphism", "is", "associated", "with", "risk", "of", "developing", "dementia", "of", "Alzheimer’s", "type", "(DAT)", "in", "an", "Arab–Israeli", "community,", "a", "unique", "genetic", "isolate", "where", "there", "is", "a", "high", "prevalence", "of", "DAT.", "In", "contrast", "to", "several", "other", "studies,", "we", "found", "no", "evidence", "of", "an", "association", "between", "this", "polymorphism", "and", "either", "DAT", "or", "age-related", "cognitive", "decline", "(ARCD).", "Keywords:", "angiotensin-converting", "enzyme,", "dementia", "of", "the", "Alzheimer’s", "type,", "age-related", "cognitive", "decline,", "insertion–deletion", "polymorphism,", "Arab", "population", "Introduction", "Alzheimer’s", "disease", "(AD)", "is", "a", "catastrophic", "affliction", "of", "the", "middle", "and", "later", "years", "of", "life.", "Clinically,", "it", "is", "marked", "by", "an", "irreversible", "decline", "in", "mental", "abilities,", "including", "progressive", "loss", "of", "memory,", "confusion,", "and", "dementia,", "and", "culminates", "in", "childlike", "helplessness.", "In", "the", "United", "States,", "the", "incidence", "of", "AD", "is", "exponentially", "increasing", "and", "is", "projected", "to", "affect", "8.64", "million", "people", "by", "the", "year", "2047", "(Grossberg", "2003).", "Median", "survival", "times", "range", "from", "8.3", "years", "for", "persons", "diagnosed", "at", "age", "65,", "to", "3.4", "years", "for", "persons", "diagnosed", "at", "age", "90", "(Brookmeyer", "et", "al", "2002).", "Angiotensin-converting", "enzyme", "(ACE)", "catalyzes", "the", "conversion", "of", "angiotensin", "I", "into", "a", "physiologically", "active", "peptide,", "angiotensin", "II.", "This", "reaction", "is", "an", "important", "process", "in", "blood", "pressure", "regulation.", "In", "addition", "to", "this", "well", "known", "physiologic", "role,", "ACE", "is", "able", "to", "cleave", "other", "proteins,", "including", "bradykinin", "and", "substance", "P,", "and", "has", "been", "shown", "to", "inhibit", "and", "cleave", "amyloid", "β-peptide", "(Aβ)", "aggregation", "and", "amyloid", "plaque", "formation", "in", "vitro", "(Hu", "et", "al", "2001).", "ACE", "may", "contribute", "to", "the", "pathogenesis", "of", "AD.", "To", "test", "the", "hypothesis", "of", "association", "between", "ACE", "and", "DAT,", "we", "evaluated", "an", "insertion–deletion", "(ID)", "polymorphism", "in", "the", "ACE", "gene", "as", "a", "potential", "risk", "factor", "for", "dementia", "of", "the", "Alzheimer’s", "type", "(DAT)", "in", "an", "Arab", "community", "in", "Wadi", "Ara,", "Israel.", "The", "population", "comprised", "853", "persons", "over", "the", "age", "of", "65", "(Bowirrat", "et", "al", "2001;", "Bowirrat,", "Friedland,", "Farrer,", "et", "al", "2002).", "Family", "studies", "revealed", "that", "more", "than", "one-", "third", "of", "DAT", "cases", "are", "members", "of", "one", "extended", "family.", "We", "hypothesized", "that", "DAT", "in", "Wadi", "Ara", "may", "be", "due", "to", "a", "founder", "effect", "enhanced", "by", "consanguinity;", "thus,", "a", "specific", "disease", "susceptibility", "allele", "may", "be", "overrepresented", "in", "cognitively", "impaired", "subjects", "compared", "with", "cognitively", "healthy", "residents.", "Our", "results", "suggest", "that", "the", "Neuropsychiatric", "Disease", "and", "Treatment", "2005:1(1)", "73", "–76", "©", "2005", "Dove", "Medical", "Press", "Limited.", "All", "rights", "reserved", "73" ]

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[ "Akech", "et", "al.", "BMC", "Pediatrics", "2010,", "10:71", "http://www.biomedcentral.com/1471-2431/10/71", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "Phase", "II", "trial", "of", "isotonic", "fluid", "resuscitation", "in", "Kenyan", "children", "with", "severe", "malnutrition", "and", "hypovolaemia", "Samuel", "O", "Akech1,", "Japhet", "Karisa1,", "Phellister", "Nakamya1,", "Mwanamvua", "Boga1,", "Kathryn", "Maitland1,2,3*", "Abstract", "Background:", "Children", "with", "severe", "malnutrition", "who", "develop", "shock", "have", "a", "high", "mortality.", "Contrary", "to", "contemporaneous", "paediatric", "practice,", "current", "guidelines", "recommend", "use", "of", "low", "dose", "hypotonic", "fluid", "resuscitation", "(half-strength", "Darrows/5%", "dextrose", "(HSD/5D).", "We", "evaluated", "the", "safety", "and", "efficacy", "of", "this", "guideline", "compared", "to", "resuscitation", "with", "a", "standard", "isotonic", "solution.", "Methods:", "A", "Phase", "II", "randomised", "controlled,", "safety", "and", "efficacy", "trial", "in", "Kenyan", "children", "aged", "over", "6", "months", "with", "severe", "malnutrition", "and", "shock", "including", "children", "with", "severe", "dehydration/shock", "and", "presumptive", "septic", "shock", "(non-diarrhoeal", "shock).", "Eligible", "children", "were", "randomised", "to", "HSD/5D", "or", "Ringer’s", "Lactate", "(RL).", "A", "maximum", "of", "two", "boluses", "of", "15", "ml/kg", "of", "HSD/5D", "were", "given", "over", "two", "hours", "(as", "recommended", "by", "guidelines)", "while", "those", "randomised", "to", "RL", "received", "10", "ml/kg", "aliquots", "half", "hourly", "(maximum", "40", "ml/kg).", "Primary", "endpoint", "was", "resolution", "of", "shock", "at", "8", "and", "24", "hours.", "Secondary", "outcomes", "included", "resolution", "of", "acidosis,", "adverse", "events", "and", "mortality.", "Results:", "61", "children", "were", "enrolled:", "41", "had", "shock", "and", "severe", "dehydrating", "diarrhoea,", "20", "had", "presumptive", "septic", "shock;", "69%", "had", "decompensated", "shock.", "By", "8", "hours", "response", "to", "volume", "resuscitation", "was", "poor", "with", "shock", "persisting", "in", "most", "children:-HSD/5D", "15/22", "(68%)", "and", "RL14/25", "(52%),", "p", "=", "0.39.", "Oliguria", "was", "more", "prevalent", "at", "8", "hours", "in", "the", "HSD/5D", "group,", "9/22", "(41%),", "compared", "to", "RL-3/25", "(12%),", "p", "=", "0.02.", "Mortality", "was", "high,", "HSD/5D-15/26", "(58%)", "and", "RL", "13/29(45%);", "p", "=", "0.42.", "Most", "deaths", "occurred", "within", "48", "hours", "of", "admission.", "Neither", "pulmonary", "oedema", "nor", "cardiogenic", "failure", "was", "detected.", "Conclusions:", "Outcome", "was", "universally", "poor", "characterised", "by", "persistence", "of", "shock,", "oliguria", "and", "high", "case", "fatality.", "Isotonic", "fluid", "was", "associated", "with", "modest", "improvement", "in", "shock", "and", "survival", "when", "compared", "to", "HSD/5D", "but", "inconclusive", "due", "to", "the", "limitations", "of", "design", "and", "effectiveness", "of", "either", "resuscitation", "strategy.", "Although", "isotonic", "fluid", "resuscitation", "did", "not", "result", "in", "cardiogenic", "heart", "failure,", "as", "previously", "feared,", "we", "conclude", "that", "the", "modest", "volumes", "used", "and", "rate", "of", "infusion", "were", "insufficient", "to", "promptly", "correct", "shock.", "The", "adverse", "performance", "of", "the", "recommended", "fluid", "resuscitation", "guideline", "for", "severe", "malnutrition", "should", "prompt", "clinical", "investigation", "of", "isotonic", "fluids", "for", "resuscitation", "of", "compensated", "shock,", "defining", "rate", "and", "volumes", "required", "to", "inform", "future", "guidelines.", "Trial", "Registration:", "The", "trial", "is", "registered", "as", "ISCRTN:", "61146418.", "Background", "Severe", "malnutrition", "is", "a", "common", "cause", "of", "admission", "to", "hospital", "in", "young", "children", "in", "Africa", "and", "outcome", "remains", "poor.", "The", "World", "Health", "Organization", "(WHO)", "10-step", "treatment", "has", "improved", "case", "fatality,", "in", "some", "*", "Correspondence:", "kmaitland@kilifi.kemri-wellcome.org", "1KEMRI-Wellcome", "Trust", "Research", "Programme,", "Centre", "for", "Geographic", "Medicine", "Research-Coast,", "Kilifi,", "Kenya", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "settings,", "to", "under", "5%", "[1-3],", "however,", "in", "African", "hospitals", "implementation", "of", "the", "same", "guideline", "has", "achieved", "poorer", "results", "with", "numerous", "reports", "of", "unacceptably", "high", "case", "fatality", "rates", "[4,5].", "At", "our", "hospital", "on", "the", "Ken-", "yan", "coast,", "we", "have", "recently", "reported", "that", "mortality", "rates", "in", "children", "with", "severe", "malnutrition,", "treated", "in", "accor-", "dance", "with", "WHO", "guidelines,", "were", "20%.", "Thirty", "percent", "of", "the", "fatalities", "occurred", "within", "48", "hours", "of", "admission", "©", "2010", "Akech", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "SAGE-Hindawi", "Access", "to", "Research", "Stroke", "Research", "and", "Treatment", "Volume", "2011,", "Article", "ID", "304921,", "7", "pages", "doi:10.4061/2011/304921", "Review", "Article", "The", "Migraine-Ischemic", "Stroke", "Relation", "in", "Young", "Adults", "Alessandro", "Pezzini,1", "Elisabetta", "Del", "Zotto,2", "Alessia", "Giossi,1", "Irene", "Volonghi,1", "Paolo", "Costa,1", "Giorgio", "Dalla", "Volta,3", "and", "Alessandro", "Padovani1", "1", "Dipartimento", "di", "Scienze", "Mediche", "e", "Chirurgiche,", "Clinica", "Neurologica,", "Universita`", "degli", "Studi", "di", "Brescia,", "Piazzale", "Spedali", "Civili,", "1,", "25100", "Brescia,", "Italy", "2", "Dipartimento", "di", "Scienze", "Biomediche", "e", "Biotecnologie,", "Universita`", "degli", "Studi", "di", "Brescia,", "25100", "Brescia,", "Italy", "3", "Unita`", "di", "Neurologia,", "Istituto", "Clinico", "Citta`", "di", "Brescia,", "25123", "Brescia,", "Italy", "Correspondence", "should", "be", "addressed", "to", "Alessandro", "Pezzini,", "ale", "pezzini@hotmail.com", "Received", "19", "September", "2010;", "Accepted", "22", "November", "2010", "Academic", "Editor:", "Halvor", "Naess", "Copyright", "©", "2011", "Alessandro", "Pezzini", "et", "al.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "In", "spite", "of", "the", "strong", "epidemiologic", "evidence", "linking", "migraine", "and", "ischemic", "stroke", "in", "young", "adults,", "the", "mechanisms", "explaining", "this", "association", "remain", "poorly", "understood.", "The", "observation", "that", "stroke", "occurs", "more", "frequently", "during", "the", "interictal", "phase", "of", "migraine", "prompts", "to", "speculation", "that", "an", "indirect", "relation", "between", "the", "two", "diseases", "might", "exist.", "In", "this", "regard,", "four", "major", "issues", "might", "be", "considered", "which", "may", "be", "summarized", "as", "follows:", "(1)", "the", "migraine-ischemic", "stroke", "relation", "is", "influenced", "by", "specific", "risk", "factors", "such", "as", "patent", "foramen", "ovale", "or", "endothelial", "dysfunction", "and", "more", "frequent", "in", "particular", "conditions", "like", "spontaneous", "cervical", "artery", "dissection;", "(2)", "migraine", "is", "associated", "with", "an", "increased", "prevalence", "of", "cardiovascular", "risk", "factors;", "(3)", "the", "link", "is", "caused", "by", "migraine-specific", "drugs;", "(4)", "migraine", "and", "ischemic", "vascular", "events", "are", "linked", "via", "a", "genetic", "component.", "In", "the", "present", "paper,", "we", "will", "review", "epidemiological", "studies,", "discuss", "potential", "mechanisms", "of", "migraine-induced", "stroke", "and", "comorbid", "ischemic", "stroke,", "and", "pose", "new", "research", "questions.", "1.", "Introduction", "Migraine", "affects", "about", "15%", "of", "people", "in", "developed", "countries", "[1]", "and", "is", "three", "times", "more", "common", "in", "women", "than", "in", "men.", "Patients", "have", "a", "median", "of", "one", "attack", "per", "month,", "and", "25%", "have", "at", "least", "two", "attacks", "per", "month", "[2].", "Patients", "with", "more", "than", "one", "attack", "per", "month", "are", "at", "increased", "risk", "of", "brain", "lesions", "[3].", "In", "the", "last", "decades,", "several", "studies", "have", "emphasized", "the", "high", "prevalence", "of", "migraine", "among", "young", "individuals", "with", "stroke", "as", "well", "as", "a", "dysfunction", "of", "cerebral", "arteries", "during", "migraine", "attacks", "and", "the", "finding", "of", "silent", "infarct-like", "brain", "lesions", "in", "migraineurs,", "thus", "leading", "to", "the", "hypothesis", "that", "a", "comorbidity", "between", "migraine", "and", "cerebral", "ischemia", "exists", "[4].", "2.", "Evidence", "of", "Association", "The", "first", "epidemiological", "suggestion", "that", "migraine", "may", "be", "an", "independent", "risk", "factor", "for", "stroke", "came", "from", "the", "Col-", "laborative", "Group", "for", "the", "Study", "of", "Stroke", "in", "Young", "Women,", "published", "in", "1975,", "which", "showed", "an", "increased", "relative", "risk", "of", "stroke", "with", "migraine", "compared", "with", "neighbor", "controls", "[5].", "Since", "then,", "the", "association", "of", "migraine", "with", "the", "risk", "of", "stroke", "has", "been", "investigated", "in", "several", "observational", "studies,", "most", "of", "which", "have", "been", "summarized", "in", "a", "recent", "meta-analysis", "[6].", "According", "to", "this", "meta-analysis,", "the", "pooled", "relative", "risk", "of", "ischemic", "stroke", "among", "patients", "with", "any", "type", "of", "migraine", "is", "1.73", "(95%", "CI,", "1.31", "to", "2.29).", "The", "relative", "risk", "for", "women", "is", "increased", "(RR", "2.08,", "95%", "CI", "1.13", "to", "3.84)", "but", "not", "for", "men", "(RR", "1.37,", "95%", "CI", "0.89", "to", "2.11).", "Stratifying", "analysis", "by", "age,", "people", "with", "migraine", "aged", "less", "than", "45", "have", "an", "higher", "risk", "than", "the", "overall", "group", "(RR", "2.65,", "95%", "CI", "1.41", "to", "4.97),", "which", "was", "further", "increased", "among", "young", "women", "(RR", "3.95,", "95%", "CI", "2.21", "to", "6.04).", "The", "risk", "is", "apparently", "more", "than", "tripled", "by", "smoking", "(RR", "9.09,", "95%", "CI", "4.22", "to", "19.34)", "and", "more", "pronounced", "by", "oral", "contraceptives", "(OCs)", "use", "(RR", "7.02,", "95%", "CI", "1.51", "to", "32.68).", "In", "line", "with", "this", "analysis,", "data", "from", "the", "Stroke", "Prevention", "in", "Young", "Women", "study", "(SPYW)", "showed", "a", "higher", "risk", "of", "stroke", "in", "women", "with", "probable", "migraine", "with", "visual", "aura", "who", "were", "cigarette", "smokers", "and", "oral", "contraceptive", "users" ]

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[ "Galtier", "BMC", "Biology", "2011,", "9:61", "http://www.biomedcentral.com/1741-7007/9/61", "C", "O", "M", "M", "E", "N", "TA", "R", "Y", "Open", "Access", "The", "intriguing", "evolutionary", "dynamics", "of", "plant", "mitochondrial", "DNA", "Nicolas", "Galtier", "See", "research", "article:", "http://www.biomedcentral.com/1741-7007/9/64", "Abstract", "The", "mitochondrial", "genome", "of", "plants", "is", "-", "in", "every", "respect", "and", "for", "yet", "unclear", "reasons", "-", "very", "different", "from", "the", "well-studied", "one", "of", "animals.", "Thanks", "to", "next-generation", "sequencing", "technologies,", "Davila", "et", "al.", "precisely", "characterized", "the", "role", "played", "by", "recombination", "and", "DNA", "repair", "in", "controlling", "mitochondrial", "variations", "in", "Arabidopsis", "thaliana,", "thus", "opening", "new", "perspectives", "on", "the", "long-term", "evolution", "of", "this", "intriguing", "genome.", "The", "mitochondrial", "genome", "of", "plants", "is", "a", "challenge", "to", "molecular", "evolutionary", "biologists.", "Its", "content", "is", "highly", "dynamic:", "plant", "mitochondrial", "DNA", "(mtDNA)", "is", "large", "and", "variable", "in", "size", "(200", "to", "2,500", "kb),", "contains", "many", "introns", "and", "repeated", "elements", "(typically", "90%", "of", "the", "total", "sequence),", "and", "experiences", "frequent", "gene", "gain/loss/", "transfer/duplication,", "and", "genome", "rearrangements", "[1].", "Its", "nucleotide", "substitution", "rate,", "paradoxically,", "is", "remarkably", "low", "-", "even", "lower", "than", "for", "nuclear", "DNA.", "These", "features", "are", "in", "sharp", "contrast", "with", "the", "highly", "studied", "mtDNA", "of", "animals,", "which", "is", "small-sized,", "structurally", "conserved,", "devoid", "of", "selfish", "elements,", "and", "has", "a", "very", "fast", "nucleotide", "substitution", "rate", "[2].", "Why", "these", "two", "genomes", "behave", "so", "differently", "is", "one", "of", "the", "most", "head-scratching", "questions", "of", "current", "comparative", "genomics.", "The", "study", "by", "Davila", "et", "al.", "[3]", "contributes", "a", "potentially", "decisive", "argument", "by", "connecting", "the", "plant", "mtDNA", "mutation", "rate", "to", "yet", "another", "intriguing", "feature", "of", "this", "organellar", "genome - recombination.", "been", "detected", "in", "various", "species,", "and", "are", "involved", "in", "a", "number", "of", "phenotypic", "traits,", "including", "thermotolerance", "and", "male", "sterility.", "The", "nuclear-encoded", "MSH1", "gene,", "which", "is", "the", "product", "of", "fusion", "between", "a", "homologue", "of", "the", "bacterial", "DNA-repair", "gene", "MutS", "and", "an", "endonuclease", "gene,", "is", "involved", "in", "the", "control", "of", "plant", "mtDNA", "recom-", "bination.", "Using", "next-generation", "sequencing", "technologies,", "Davila", "et", "al.", "[3]", "have", "examined", "the", "recombination", "pattern", "in", "wild-type", "versus", "MSH1-mutant", "ecotypes", "of", "the", "Brassicaceae", "Arabidopsis", "thaliana", "model.", "They", "report", "that", "MSH1", "mutants", "experience", "mitochondrial", "recombi-", "nation", "at", "a", "much", "higher", "rate", "than", "the", "wild", "type,", "as", "reflected", "by", "the", "frequent", "detection", "of", "rearranged", "mito-", "chondrial", "molecules", "generated", "by", "illegitimate", "(ectopic)", "recombination", "between", "repeated", "elements.", "Interestingly,", "recombination", "in", "MSH1", "mutants", "is", "shown", "to", "be", "asso-", "ciated", "with", "asymmetrical", "genetic", "exchanges:", "in", "a", "window", "of", "a", "few", "hundred", "bases", "surrounding", "the", "recombination", "breakpoint,", "one", "of", "the", "two", "recombining", "DNA", "sequences", "is", "copied", "and", "pasted", "onto", "the", "other", "one.", "This", "process,", "known", "as", "gene", "conversion,", "is", "mediated", "by", "efficient", "DNA", "mismatch", "repair", "activity,", "and", "contributes", "to", "sequence", "homogenization", "of", "recombinogenic", "motifs.", "An", "analysis", "of", "mitochondrial", "variations", "across", "72", "natural", "ecotypes", "of", "A.", "thaliana", "reveals", "similar", "patterns,", "suggesting", "that", "the", "processes", "described", "by", "Davila", "et", "al.", "actually", "impact", "on", "the", "evolution", "of", "plant", "mtDNA.", "This", "study,", "therefore,", "provides", "us", "with", "a", "proximal", "explanation", "for", "the", "low", "substitution", "rate", "of", "plant", "mtDNA,", "namely", "the", "existence", "of", "efficient", "recombination-", "associated", "DNA", "repair", "activity.", "Ectopic", "recombination", "is", "potentially", "harmful", "in", "generating", "chromosomal", "rearrange-", "ments", "that", "disrupt", "coding", "frames", "or", "impede", "gene", "expres-", "DNA", "repair:", "keeping", "a", "watch", "on", "repeated", "elements", "sion", "regulation.", "Mechanisms", "of", "recombination", "surveil-", "Unlike", "in", "animal", "mitochondria,", "recombination", "is", "wide-", "lance", "and", "repair", "of", "recombination-induced", "DNA", "damage,", "spread", "in", "plant", "mtDNA.", "Recombinant", "molecules", "have", "including", "mismatch", "repair,", "appear", "necessary", "for", "plant", "mtDNA.", "Animal", "mtDNA,", "in", "contrast,", "is", "essentially", "devoid", "of", "repeated", "elements,", "so", "illegitimate", "recombina-", "tion", "is", "much", "less", "an", "issue", "in", "these", "genomes.", "Selective", "pressure", "for", "efficient", "DNA", "repair", "might", "thus", "be", "relaxed,", "©", "2011", "Galtier;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Correspondence:", "galtier@univ-montp2.fr", "Université", "Montpellier", "2,", "CNRS", "UMR", "5554", "-", "Institut", "des", "Sciences", "de", "l’Evolution,", "Place", "E", "Bataillon", "-", "CC64,", "34095", "Montpellier,", "France" ]

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"structure,", "the", "reliabilities", "of", "the", "scores,", "and", "their", "association", "with", "implementation", "outcome", "variables.", "The", "aim", "was", "also", "to", "compare", "implementation", "profiles", "of", "the", "two", "evidence-based", "programs", "based", "on", "multi", "informant", "assessments.", "Methods:", "The", "218", "participants", "in", "the", "study", "were", "therapists,", "supervisors,", "and", "agency", "leaders", "working", "with", "Parent", "Management", "Training,", "the", "Oregon", "model", "(PMTO),", "and", "Multisystemic", "Therapy", "(MST)", "in", "Norway.", "Interviewers", "filled", "in", "an", "electronic", "version", "of", "the", "Implementation", "Components", "Questionnaire", "during", "a", "telephone", "interview.", "Results:", "The", "factor", "analysis", "of", "the", "eight", "one-dimensional", "subscales", "resulted", "in", "an", "individual", "clinical-level", "factor", "and", "an", "organizational", "system-level", "factor.", "Age,", "experience,", "and", "number", "of", "colleagues", "in", "the", "workplace", "were", "negatively", "correlated", "with", "positive", "ratings", "of", "the", "implementation", "process,", "but", "the", "number", "of", "colleagues", "working", "with", "the", "same", "program", "predicted", "positive", "ratings.", "MST", "and", "PMTO", "had", "different", "implementation", "profiles", "and", "therapists,", "supervisors,", "and", "managers", "evaluated", "some", "of", "the", "implementation", "drivers", "significantly", "differently.", "Conclusions:", "The", "psychometric", "quality", "of", "the", "questionnaire", "was", "supported", "by", "measures", "of", "internal", "consistency,", "factor", "analyses", "of", "the", "implementation", "components,", "and", "the", "comparisons", "of", "implementation", "profiles", "between", "programs", "and", "respondent", "groups.", "A", "moderate,", "but", "consistent", "association", "in", "the", "expected", "direction", "was", "found", "with", "the", "implementation", "outcome", "variables.", "Keywords:", "Implementation", "measurement,", "Implementation", "components,", "Empirically", "supported", "treatment", "programs,", "Parent", "management", "training,", "Multisystemic", "therapy", "Background", "Implementation", "is", "the", "movement", "of", "evidence-based", "pro-", "grams", "(EBPs)", "from", "science", "to", "practice,", "or", "the", "active", "and", "planned", "effort", "to", "mainstream", "a", "new", "intervention", "within", "a", "practice", "organization", "[1].", "Implementation", "also", "describes", "a", "transition", "period", "in", "which", "practitioners", "become", "increasingly", "skillful,", "consistent,", "and", "committed", "in", "their", "use", "of", "a", "new", "intervention", "[2].", "Even", "if", "new", "intervention", "programs", "are", "accepted", "and", "adopted,", "they", "are", "not", "necessarily", "put", "into", "practice.", "This", "is", "referred", "to", "as", "the", "‘knowing-doing", "gap,’", "in", "which", "practitioners", "fail", "to", "do", "what", "might", "improve", "*", "Correspondence:", "terje.ogden@atferdssenteret.no", "Norwegian", "Center", "for", "Child", "Behavioral", "Development,", "University", "of", "Oslo,", "P.O.", "Box", "7053,", "Majorstuen,", "0306", "Oslo,", "Norway", "performance", "and", "‘substitute", "talk", "for", "action’", "[3].", "Further-", "more,", "when", "interventions", "are", "properly", "implemented", "they", "are", "threatened", "by", "program", "drift", "or", "dilution", "over", "time.", "The", "rather", "slow", "and", "limited", "success", "of", "transferring", "EBPs", "to", "or-", "dinary", "service,", "and", "the", "limited", "impact", "and", "sustainability", "of", "programs", "once", "adoption", "has", "occurred,", "have", "been", "the", "focus", "of", "several", "researchers", "working", "with", "implementation", "[4-7].", "The", "failure", "of", "EBPs", "to", "produce", "expected", "outcomes", "may", "be", "attributable", "to", "the", "effectiveness", "of", "intervention", "or", "the", "qual-", "ity", "of", "the", "implementation", "[2];", "therefore,", "both", "the", "program", "effectiveness", "and", "its", "implementation", "into", "regular", "practice", "should", "be", "evaluated.", "In", "a", "national", "implementation", "project", "initiated", "in", "1999,", "two", "treatment", "programs", "targeting", "conduct", "problems", "in", "©", "2012", "Ogden", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "292", "Acta", "Orthopaedica", "2010;", "81", "(3):", "292–295", "The", "posterior", "approach", "reduces", "the", "risk", "of", "thin", "cement", "mantles", "with", "a", "straight", "femoral", "stem", "design", "Gavin", "J", "Macpherson,", "Christian", "Hank,", "Michael", "Schneider,", "Morag", "Trayner,", "Robert", "Elton,", "Colin", "R", "Howie,", "and", "Steffen", "J", "Breusch", "Department", "of", "Orthopaedic", "Surgery,", "University", "of", "Edinburgh,", "The", "Royal", "Infirmary", "of", "Edinburgh,", "UK", "Correspondence:", "steffen.breusch@ukonline.co.uk", "Submitted", "09-03-13.", "Accepted", "09-12-13", "Background", "and", "purpose", "The", "properties", "of", "the", "cement", "mantle", "around", "a", "prosthesis", "are", "important.", "We", "investigated", "whether", "the", "surgical", "approach", "to", "the", "hip", "influences", "the", "quality", "and", "thickness", "of", "the", "cement", "mantle", "when", "using", "a", "straight", "femoral", "stem", "design.", "Methods", "In", "a", "consecutive", "multi-surgeon", "series,", "we", "reviewed", "the", "radiographs", "of", "270", "patients", "after", "cemented", "Exeter", "total", "hip", "arthroplasty.", "135", "stems", "were", "introduced", "using", "an", "antero-lateral", "(transgluteal)", "approach", "and", "135", "stems", "were", "introduced", "using", "a", "posterior", "approach.", "Anterior-posterior", "and", "lateral", "radiographs", "were", "reviewed", "and", "cement", "mantle", "thickness", "was", "measured", "in", "Gruen", "zones", "1–14.", "We", "graded", "cement", "mantle", "quality", "according", "to", "the", "Barrack", "classification.", "Results", "Barrack", "grading", "did", "not", "reveal", "any", "difference", "in", "cement", "mantle", "quality", "between", "the", "two", "groups.", "AP", "and", "lateral", "radiographs", "showed", "no", "difference", "in", "stem", "alignment", "between", "the", "groups.", "The", "risk", "of", "a", "thin", "cement", "mantle", "(<", "2", "mm)", "was", "lower", "with", "a", "posterior", "approach", "(OR", "=", "1.8,", "95%", "CI:", "1–3;", "p", "=", "0.03).", "The", "greatest", "risk", "of", "a", "cement", "mantle", "thickness", "of", "<", "2", "mm", "occurred", "in", "Gruen", "zones", "8–9", "regardless", "of", "the", "surgical", "approach", "used.", "Interpretation", "With", "a", "straight", "femoral", "stem", "design,", "the", "pos-", "terior", "approach", "to", "the", "hip", "joint", "appears", "to", "give", "a", "lower", "risk", "of", "a", "thin", "cement", "mantle.", "Irrespective", "of", "the", "approach,", "there", "was", "a", "risk", "of", "thin", "cement", "mantles", "in", "Gruen", "zones", "8", "and", "9,", "which", "highlights", "the", "importance", "of", "lateral", "radiographs", "in", "the", "postoperative", "radio-", "graphic", "assessment", "of", "total", "hip", "replacements.", "", "There", "is", "no", "data", "available", "that", "defines", "the", "optimal", "cement", "mantle", "thickness", "in", "total", "hip", "arthroplasty.", "There", "is,", "however,", "evidence", "that", "a", "cement", "mantle", "of", "2–3", "mm", "is", "associated", "with", "a", "better", "long-term", "radiographic", "outcome", "(Ebramzadeh", "et", "al.", "1994,", "Joshi", "et", "al.", "1998).", "Thin", "cement", "mantles", "are", "more", "prone", "to", "crack", "(Kwak", "et", "al.", "1979,", "Kawate", "et", "al.", "1998),", "thus", "open-", "ing", "the", "bone-cement", "interface", "to", "wear", "particles", "and", "fluid", "pres-", "sure", "(Bartlett", "et", "al.", "2008).", "This", "has", "been", "documented", "to", "cause", "localized", "osteolysis", "(Huddleston", "1988,", "Anthony", "et", "al.", "1990,", "Schmalzried", "et", "al.", "1997)", "and", "failure", "(Olsson", "and", "Jernberger", "1981,", "Jasty", "et", "al", "1991,", "Cristofolini", "et", "al.", "2007).", "Several", "fac-", "tors", "influence", "the", "quality", "of", "the", "cement", "mantle:", "the", "cement-", "ing", "technique", "(Mulroy", "et", "al.", "1990,", "Britton", "et", "al.", "1996,", "Mal-", "chau", "and", "Herberts", "1998),", "femoral", "anatomy", "(Crawford", "et", "al.", "1999,", "Breusch", "et", "al.", "2001),", "stem", "design", "and", "instrumentation", "(Garellick", "et", "al.", "1999,", "Östgaard", "et", "al.", "2001),", "centralizer", "usage", "(Berger", "et", "al.", "1997),", "and", "stem", "size", "(Krismer", "et", "al.", "1991,", "Mas-", "soud", "et", "al.", "1997,", "Scheerlinck", "et", "al.", "2008).", "Due", "to", "the", "anatomical", "shape", "of", "the", "proximal", "femur,", "there", "is", "a", "risk", "of", "producing", "thin", "cement", "mantles", "anterior-proximally", "(Garellick", "et", "al.", "1999,", "Breusch", "et", "al.", "2001,", "Valdivia", "et", "al.", "2001).", "An", "antero-lateral", "surgical", "approach", "has", "been", "shown", "to", "adversely", "affect", "the", "orientation", "of", "the", "tip", "of", "the", "femoral", "com-", "ponent", "(Vaughan", "et", "al.", "2007),", "but", "little", "else", "is", "known", "about", "the", "effect", "of", "the", "surgical", "approach", "to", "the", "hip", "with", "regard", "to", "stem", "alignment", "and", "cement", "mantle", "thickness", "or", "quality.", "We", "investigated", "the", "influence", "of", "surgical", "approach", "on", "cement", "mantle", "thickness", "and", "cement", "mantle", "quality", "using", "the", "straight", "Exeter", "femoral", "stem", "by", "comparison", "of", "posterior", "and", "antero-lateral", "approach", "in", "a", "multi-surgeon", "series.", "Patients", "and", "methods", "This", "was", "a", "prospective,", "consecutive,", "multi-surgeon", "series", "of", "270", "cemented", "primary", "total", "hip", "replacements", "performed", "in", "2005", "at", "our", "university", "teaching", "hospital", "(Table", "1).", "Patients", "with", "a", "previous", "femoral", "osteotomy", "were", "not", "included.", "The", "Exeter", "stem", "(Stryker", "Orthopaedics,", "Mahwah,", "NJ)", "was", "used", "in", "all", "cases.", "All", "procedures", "were", "carried", "out", "with", "the", "patient", "in", "a", "lateral", "decubitus", "position.", "135", "patients", "were", "operated", "on", "using", "an", "antero-lateral", "approach", "to", "the", "hip", "joint", "and", "135", "patients", "using", "a", "posterior", "approach.", "Preoperative", "templating", "on", "AP", "radiographs", "was", "under-", "taken", "to", "determine", "the", "optimum", "femoral", "implant", "allowing", "for", "a", "cement", "mantle", "of", "at", "least", "2", "mm.", "All", "operations", "were", "per-", "Open", "Access", "-", "This", "article", "is", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "Noncommercial", "License", "which", "permits", "any", "noncommercial", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "source", "is", "credited.", "DOI", "10.3109/17453674.2010.487239" ]

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[ "W638–W643", "Nucleic", "Acids", "Research,", "2005,", "Vol.", "33,", "Web", "Server", "issue", "doi:10.1093/nar/gki490", "RACE:", "Remote", "Analysis", "Computation", "for", "gene", "Expression", "data", "Michael", "Psarros,", "Steffen", "Heber1,", "Manuela", "Sick,", "Gnanasekaran", "Thoppae,", "Keith", "Harshman", "and", "Beate", "Sick*", "DNA", "Array", "Facility,", "Center", "for", "Integrative", "Genomics,", "University", "of", "Lausanne,", "Lausanne,", "Switzerland", "and", "1Bioinformatics", "Research", "Center,", "North", "Carolina", "State", "University,", "Raleigh,", "NC,", "USA", "Received", "February", "14,", "2005;", "Revised", "April", "12,", "2005;", "Accepted", "April", "25,", "2005", "ABSTRACT", "The", "Remote", "Analysis", "Computation", "for", "gene", "Expression", "data", "(RACE)", "suite", "is", "a", "collection", "of", "bioin-", "formatics", "web", "tools", "designed", "for", "the", "analysis", "of", "DNA", "microarray", "data.", "RACE", "performs", "probe-level", "data", "pre-", "processing,", "extensive", "quality", "checks,", "data", "visualiza-", "tion", "and", "data", "normalization", "for", "Affymetrix", "GeneChips.", "In", "addition,", "it", "offers", "differential", "expression", "analysis", "on", "normalized", "expression", "levels", "from", "any", "array", "platform.", "RACE", "estimates", "the", "false", "discovery", "rates", "of", "lists", "of", "potentially", "regulated", "genes", "and", "provides", "a", "Gene", "Ontology-term", "analysis", "tool", "for", "GeneChip", "data", "to", "support", "the", "biological", "interpretation", "and", "annotation", "of", "results.", "The", "analysis", "is", "fully", "automated", "but", "can", "be", "customized", "by", "flexible", "parameter", "settings.", "To", "offer", "a", "convenient", "starting", "point", "for", "subsequent", "analyses,", "and", "to", "provide", "maximum", "transparency,", "the", "R", "scripts", "used", "to", "generate", "the", "results", "can", "be", "downloaded", "along", "with", "the", "output", "files.", "RACE", "is", "freely", "available", "for", "use", "at", "http://race.unil.ch.", "INTRODUCTION", "DNA", "microarrays", "are", "standard", "tools", "in", "biology", "and", "medicine.", "An", "increasingly", "long", "list", "of", "applications", "includes", "the", "identi-", "fication", "of", "gene", "expression", "changes", "associated", "with", "changes", "in", "cell", "state", "(1,2),", "classifying", "clinical", "samples", "based", "on", "the", "under-", "lying", "pathological", "characteristics", "(3,4),", "drug", "development", "(5)", "and", "the", "functional", "annotation", "of", "genes", "(6).", "A", "typical", "micro-", "array", "experiment", "might", "measure", "expression", "levels", "of", "tens", "of", "thousands", "of", "genes,", "and", "systematic", "variations", "introduced", "into", "the", "datasets", "(e.g.", "variations", "in", "labeling", "efficiencies", "or", "scanner", "settings)", "can", "often", "obscure", "the", "biological", "variation", "that", "is", "of", "real", "interest.", "Furthermore,", "once", "differentially", "expressed", "genes", "have", "been", "identified,", "inferring", "function", "based", "simply", "on", "their", "expression", "pattern", "can", "be", "both", "arduous", "and", "ineffective.", "Hence,", "bioinformatics", "tools", "that", "facilitate", "rigorous", "data", "analysis", "and", "interpretation", "are", "of", "the", "highest", "importance.", "Presented", "here", "is", "Remote", "Analysis", "Computation", "for", "gene", "Expression", "data", "(RACE),", "a", "web", "server", "which", "provides", "some", "solutions", "to", "these", "problems.", "Microarray", "data", "analysis", "typically", "begins", "with", "data", "quality", "checks", "and", "data", "normalization", "(7).", "Once", "normalized", "expres-", "sion", "levels", "are", "determined,", "expression", "ratios", "can", "be", "calculated", "and", "differentially", "expressed", "genes", "identified.", "At", "this", "stage", "of", "data", "analysis,", "the", "magnitude", "and", "significance", "of", "gene", "expres-", "sion", "changes", "as", "well", "as", "the", "false", "discovery", "rate", "are", "important", "measures.", "Once", "a", "list", "of", "differentially", "expressed", "genes", "is", "iden-", "tified,", "the", "task", "often", "turns", "to", "describing", "and", "interpreting", "the", "biological", "significance", "of", "the", "results.", "An", "often", "useful", "approach", "is", "to", "compile", "a", "list", "of", "the", "Gene", "Ontology", "(GO)", "terms", "associ-", "ated", "with", "the", "differentially", "expressed", "genes", "(8).", "This", "provides", "an", "overview", "of", "the", "biological,", "physiological", "and", "cellular", "pro-", "cesses", "potentially", "involved", "in", "the", "biological", "phenomena", "and", "suggests", "directions", "for", "further", "studies.", "A", "number", "of", "very", "useful", "web", "tools", "for", "microarray", "data", "analysis", "exist", "(e.g.", "9–13).", "RACE", "contributes", "to", "the", "field", "by", "providing", "access", "to", "a", "wide", "range", "of", "quality", "checks,", "probe-level", "methods", "and", "state-of-the-art", "normalization", "techniques", "for", "Affymetrix", "raw", "data.", "To", "the", "best", "of", "our", "knowledge,", "these", "are", "not", "provided", "by", "any", "other", "publicly", "available", "server.", "Addi-", "tionally,", "RACE", "provides", "tools", "to", "identify", "lists", "of", "different-", "ially", "expressed", "genes", "and", "to", "determine", "and", "investigate", "the", "associated", "GO-term", "composition", "of", "those", "genes.", "To", "facilitate", "subsequent", "analyses", "and", "guarantee", "maximal", "transparency", "and", "reproducibility,", "the", "R", "script", "used", "to", "generate", "the", "results", "is", "provided.", "SYSTEM", "AND", "MODULE", "DESIGN", "RACE", "is", "divided", "into", "two", "components:", "the", "user", "interface", "and", "the", "analysis", "part.", "RACE", "uses", "basic", "authentication", "provided", "by", "Apache.", "HTTP", "communication", "is", "exclusively", "via", "port", "80,", "making", "the", "system", "easily", "accessible", "through", "a", "firewall.", "*To", "whom", "correspondence", "should", "be", "addressed.", "Tel:", "+1", "41", "21", "692", "3909;", "Fax:", "+1", "41", "21", "692", "3905;", "Email:", "Beate.Sick@unil.ch", "The", "Author", "2005.", "Published", "by", "Oxford", "University", "Press.", "All", "rights", "reserved.", "The", "online", "version", "of", "this", "article", "has", "been", "published", "under", "an", "open", "access", "model.", "Users", "are", "entitled", "to", "use,", "reproduce,", "disseminate,", "or", "display", "the", "open", "access", "version", "of", "this", "article", "for", "non-commercial", "purposes", "provided", "that:", "the", "original", "authorship", "is", "properly", "and", "fully", "attributed;", "the", "Journal", "and", "Oxford", "University", "Press", "are", "attributed", "as", "the", "original", "place", "of", "publication", "with", "the", "correct", "citation", "details", "given;", "if", "an", "article", "is", "subsequently", "reproduced", "or", "disseminated", "not", "in", "its", "entirety", "but", "only", "in", "part", "or", "as", "a", "derivative", "work", "this", "must", "be", "clearly", "indicated.", "For", "commercial", "re-use,", "please", "contact", "journals.permissions@oupjournals.org" ]

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[ "Pediatr", "Nephrol", "(2008)", "23:1257–1267", "DOI", "10.1007/s00467-008-0801-6", "ORIGINAL", "ARTICLE", "Glomerular", "angiotensinogen", "protein", "is", "enhanced", "in", "pediatric", "IgA", "nephropathy", "Masanori", "Takamatsu", "&", "Maki", "Urushihara", "&", "Shuji", "Kondo", "&", "Maki", "Shimizu", "&", "Tetsuo", "Morioka", "&", "Takashi", "Oite", "&", "Hiroyuki", "Kobori", "&", "Shoji", "Kagami", "Received:", "14", "November", "2007", "/", "Revised:", "30", "January", "2008", "/", "Accepted:", "18", "February", "2008", "/", "Published", "online:", "18", "April", "2008", "#", "The", "Author(s)", "2008", "Abstract", "Enhanced", "intrarenal", "renin-angiotensin", "system", "(RAS)", "is", "implicated", "in", "the", "development", "and", "progression", "of", "renal", "injury.", "To", "investigate", "whether", "angiotensinogen", "(AGT)", "expression", "is", "involved", "in", "glomerular", "RAS", "activity", "and", "glomerular", "injury,", "we", "examined", "glomerular", "AGT", "expression", "and", "its", "correlation", "with", "expression", "of", "other", "RAS", "components,", "and", "levels", "of", "glomerular", "injury", "in", "samples", "from", "patients", "with", "immunoglobulin", "A", "nephropathy", "(IgAN)", "(23)", "and", "minor", "glomerular", "abnormalities", "(MGA)", "(8).", "Immunohistochemistry", "showed", "that", "AGT", "protein", "was", "highly", "expressed", "by", "glomerular", "endothelial", "cells", "(GEC)", "and", "mesangial", "cells", "in", "nephritic", "glomeruli", "of", "IgAN", "compared", "with", "glomeruli", "of", "MGA.", "Levels", "of", "glomerular", "AGT", "protein", "were", "well", "correlated", "with", "levels", "of", "glomerular", "angiotensin", "II", "(ang", "II),", "transforming", "growth", "factor-β", "(TGF-β),", "α-smooth-muscle", "actin,", "glomerular", "cell", "M.", "Takamatsu", ":", "M.", "Urushihara", ":", "S.", "Kondo", ":", "M.", "Shimizu", ":", "S.", "Kagami", "(*)", "Department", "of", "Pediatrics,", "The", "Institute", "of", "Health", "Bioscience,", "The", "University", "of", "Tokushima", "Graduate", "School,", "Kuramoto-cho-3-chome,", "Tokushima", "770-8503,", "Japan", "e-mail:", "kagami@clin.med.tokushima-u.ac.jp", "T.", "Morioka", ":", "T.", "Oite", "Department", "of", "Cellular", "Physiology,", "Institute", "of", "Nephrology,", "Niigata", "University", "Graduate", "School", "of", "Medical", "and", "Dental", "Sciences,", "Niigata,", "Japan", "H.", "Kobori", "Department", "of", "Medicine,", "Tulane", "University", "Health", "Sciences", "Center,", "New", "Orleans,", "LA,", "USA", "H.", "Kobori", "Department", "of", "Physiology,", "Tulane", "University", "Health", "Sciences", "Center,", "New", "Orleans,", "LA,", "USA", "number,", "and", "glomerulosclerosis", "score", "but", "not", "with", "those", "of", "glomerular", "angiotensin-converting", "enzyme", "and", "ang", "II", "type", "1", "receptor.", "Real-time", "polymerase", "chain", "reaction", "(RT-PCR)", "and", "Western", "blot", "analyses", "using", "cultured", "human", "GEC", "indicated", "that", "ang", "II", "upregulated", "AGT", "messenger", "ribonucleic", "acid", "(mRNA)", "and", "protein", "expression", "in", "a", "dose-", "and", "time-", "dependent", "manner.", "These", "data", "suggest", "that", "activated", "glomerular", "AGT", "expression", "is", "likely", "involved", "in", "elevated", "local", "ang", "II", "production", "and,", "thereby,", "may", "contribute", "to", "increased", "TGF-β", "production", "and", "development", "of", "glomerular", "injury", "in", "IgAN.", "Augmentation", "of", "GEC-AGT", "production", "with", "ang", "II", "stimulation", "might", "drive", "further", "glomerular", "injury", "in", "a", "positive-feedback", "loop.", "Keywords", "Renin-angiotensin", "system", ".", "Transforming", "growth", "factor-β", ".", "Glomerular", "endothelial", "cells", ".", "α-smooth", "muscle", "actin", ".", "Mesangial", "cells", "Introduction", "Clinical", "and", "experimental", "studies", "have", "provided", "considerable", "evidence", "for", "the", "role", "of", "the", "renin-angiotensin", "system", "(RAS)", "in", "the", "development", "of", "hypertension", "and", "progression", "of", "renal", "diseases", "[1,", "2].", "It", "is", "now", "established", "that", "all", "components", "of", "the", "RAS", "are", "widely", "distributed", "in", "several", "tissues,", "including", "the", "kidney", "[3,", "4].", "The", "local", "RAS", "in", "the", "kidney", "has", "several", "pathophysiologic", "functions", "for", "not", "only", "regulating", "blood", "pressure", "but", "also", "renal", "cell", "growth", "and", "production", "of", "glomerulosclerosis,", "which", "is", "involved", "in", "the", "development", "of", "renal", "fibrosis", "[5–8].", "Indeed,", "previous", "studies", "have", "shown", "beneficial", "effects", "of", "angiotensin-converting", "enzyme", "inhibitor", "(ACEi)", "and/or", "angiotensin", "II", "(ang", "II)", "type", "1", "receptor", "(AT1R)", "blocker", "(ARB)", "on", "various", "renal", "diseases", "in", "rats", "and", "humans," ]

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[ "DOI", "10.4110/in.2009.9.3.90", "PISSN", "1598-2629", "ORIGINAL", "ARTICLE", "The", "Stimulation", "of", "CD147", "Induces", "MMP-9", "Expression", "through", "ERK", "and", "NF-κB", "in", "Macrophages:", "Implication", "for", "Atherosclerosis", "Ju-Young", "Kim1,", "Won-Jung", "Kim1,", "Ho", "Kim1,", "Kyoungho", "Suk2", "and", "Won-Ha", "Lee1*", "1The", "School", "of", "Life", "Sciences", "and", "Biotechnology,", "2Department", "of", "Pharmacology,", "School", "of", "Medicine,", "Kyungpook", "National", "University,", "Daegu", "702-701,", "Korea", "Background:", "CD147,", "as", "a", "cellular", "receptor", "for", "cyclophilin", "A", "(CypA),", "is", "a", "multifunctional", "protein", "involved", "in", "tumor", "in-", "vasion,", "inflammation,", "tissue", "remodeling,", "neural", "function,", "and", "reproduction.", "Recent", "observations", "showing", "the", "expression", "of", "CD147", "in", "leukocytes", "indicate", "that", "this", "molecule", "may", "have", "roles", "in", "inflammation.", "Methods:", "In", "order", "to", "investigate", "the", "role", "of", "CD147", "and", "its", "ligand", "in", "the", "pathogenesis", "of", "athero-", "sclerosis,", "human", "atherosclerotic", "plaques", "were", "analyzed", "for", "the", "expression", "pattern", "of", "CD147", "and", "CypA.", "The", "cellular", "re-", "sponses", "and", "signaling", "molecules", "activated", "by", "the", "stimulation", "of", "CD147", "were", "then", "investigated", "in", "the", "human", "macrophage", "cell", "line,", "THP-1,", "which", "expresses", "high", "basal", "level", "of", "CD147", "on", "the", "cell", "surface.", "Results:", "Staining", "of", "both", "CD147", "and", "CypA", "was", "detected", "in", "endothelial", "cell", "layers", "facing", "the", "lu-", "men", "and", "macrophage-rich", "areas.", "Stimulation", "of", "CD147", "with", "its", "specific", "monoclonal", "antibody", "induced", "the", "expression", "of", "matrix", "metalloproteinase", "(MMP)-9", "in", "THP-1", "cells", "and", "it", "was", "suppressed", "by", "inhibitors", "of", "both", "ERK", "and", "NF-κB.", "Accordingly,", "the", "stimulation", "of", "CD147", "was", "observed", "to", "in-", "duce", "phosphorylation", "of", "ERK,", "phosphorylation-associated", "degradation", "of", "IκB,", "and", "nuclear", "translocation", "of", "NF-κB", "p65", "and", "p50", "subunits.", "Conclusion:", "These", "results", "suggest", "that", "CD147", "mediates", "the", "inflammatory", "activation", "of", "macro-", "phages", "that", "leads", "to", "the", "induction", "of", "MMP-9", "expression,", "which", "could", "play", "a", "role", "in", "the", "pathogenesis", "of", "inflammatory", "diseases", "such", "as", "atherosclerosis.", "[Immune", "Network", "2009;9(3):90-97]", "INTRODUCTION", "CD147", "(EMMPRIN/basigin/HAb18G/neurothelin/M6/TCSF),", "which", "has", "two", "immunoglobulin-like", "extracellular", "domains,", "is", "a", "mul-", "tifunctional", "transmembrane", "glycoprotein", "with", "short", "(39", "amino", "acids", "long)", "intracellular", "domain", "(1).", "CD147", "plays", "a", "critical", "role", "in", "many", "pathological", "and", "physiological", "processes", "involv-", "ing", "a", "variety", "of", "cell", "types", "such", "as", "various", "cancer", "cells,", "leuko-", "cytes,", "fibroblasts,", "and", "endothelial", "cells", "(2-7).", "As", "a", "tu-", "mor-derived", "MMP", "inducer,", "CD147", "stimulates", "fibroblast", "and", "endothelial", "cells", "to", "facilitate", "tumor", "invasion,", "metastasis,", "and", "angiogenesis", "(7).", "In", "addition,", "CD147", "enhances", "angiogenesis", "through", "stimulation", "of", "the", "production", "of", "vascular", "endothelial", "growth", "factor", "(VEGF)", "(8).", "The", "expression", "of", "CD147", "has", "been", "shown", "to", "be", "induced", "in", "activated", "leukocytes", "such", "as", "gran-", "ulocytes,", "lymphocytes,", "and", "macrophages", "(4).", "Stimulation", "of", "CD147", "in", "leukocytes", "is", "believed", "to", "be", "involved", "in", "in-", "flammatory", "processes", "associated", "with", "lung", "injury,", "rheumatoid", "arthritis", "(RA),", "chronic", "liver", "disease,", "heart", "failure,", "and", "athero-", "sclerosis", "(9-13).", "The", "ligands", "for", "CD147", "were", "identified", "to", "be", "the", "two", "cyclo-", "sporin", "A", "binding", "proteins:", "cyclophilin", "A", "and", "B", "(CypA", "and", "CypB)", "(14,15).", "A", "secreted", "form", "of", "CypA,", "which", "are", "expressed", "by", "smooth", "muscle", "cells", "(SMCs)", "and", "macrophages", "during", "in-", "flammatory", "conditions", "(16-18),", "has", "been", "shown", "to", "have", "cyto-", "kine-like", "functions", "(17,19).", "The", "expression", "of", "CypA", "and", "CD147", "was", "detected", "in", "synovial", "macrophages", "of", "RA", "patients", "and", "stimulation", "of", "CD147", "induced", "NF-κB-mediated", "ex-", "pression", "of", "MMP-9", "and", "proinflammatory", "cytokines", "and", "en-", "Received", "on", "March", "24,", "2009.", "Revised", "on", "April", "1,", "2009.", "Accepted", "on", "April", "15,", "2009.", "*Corresponding", "Author.", "Tel:", "82-53-950-5388;", "Fax:", "82-53-943-6925;", "E-mail:", "whl@knu.ac.kr", "Keywords:", "macrophage,", "atherosclerosis,", "inflammation,", "CD147,", "cyclophilin", "A", "90", "IMMUNE", "NETWORK", "http://www.ksimm.or.kr", "Volume", "9", "Number", "3", "June", "2009" ]

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[ "Kuang", "et", "al.", "BMC", "Public", "Health", "2012,", "12:418", "http://www.biomedcentral.com/1471-2458/12/418", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "Epidemic", "features", "affecting", "the", "performance", "of", "outbreak", "detection", "algorithms", "Jie", "Kuang1,", "Wei", "Zhong", "Yang2,", "Ding", "Lun", "Zhou1,", "Zhong", "Jie", "Li2", "and", "Ya", "Jia", "Lan1*", "Abstract", "Background:", "Outbreak", "detection", "algorithms", "play", "an", "important", "role", "in", "effective", "automated", "surveillance.", "Although", "many", "algorithms", "have", "been", "designed", "to", "improve", "the", "performance", "of", "outbreak", "detection,", "few", "published", "studies", "have", "examined", "how", "epidemic", "features", "of", "infectious", "disease", "impact", "on", "the", "detection", "performance", "of", "algorithms.", "This", "study", "compared", "the", "performance", "of", "three", "outbreak", "detection", "algorithms", "stratified", "by", "epidemic", "features", "of", "infectious", "disease", "and", "examined", "the", "relationship", "between", "epidemic", "features", "and", "performance", "of", "outbreak", "detection", "algorithms.", "Methods:", "Exponentially", "weighted", "moving", "average", "(EWMA),", "cumulative", "sum", "(CUSUM)", "and", "moving", "percentile", "method", "(MPM)", "algorithms", "were", "applied.", "We", "inserted", "simulated", "outbreaks", "into", "notifiable", "infectious", "disease", "data", "in", "China", "Infectious", "Disease", "Automated-alert", "and", "Response", "System", "(CIDARS),", "and", "compared", "the", "performance", "of", "the", "three", "algorithms", "with", "optimized", "parameters", "at", "a", "fixed", "false", "alarm", "rate", "of", "5%", "classified", "by", "epidemic", "features", "of", "infectious", "disease.", "Multiple", "linear", "regression", "was", "adopted", "to", "analyse", "the", "relationship", "of", "the", "algorithms’", "sensitivity", "and", "timeliness", "with", "the", "epidemic", "features", "of", "infectious", "diseases.", "Results:", "The", "MPM", "had", "better", "detection", "performance", "than", "EWMA", "and", "CUSUM", "through", "all", "simulated", "outbreaks,", "with", "or", "without", "stratification", "by", "epidemic", "features", "(incubation", "period,", "baseline", "counts", "and", "outbreak", "magnitude).", "The", "epidemic", "features", "were", "associated", "with", "both", "sensitivity", "and", "timeliness.", "Compared", "with", "long", "incubation,", "short", "incubation", "had", "lower", "probability", "(β*", "=", "−0.13,", "P", "<", "0.001)", "but", "needed", "shorter", "time", "to", "detect", "outbreaks", "(β*", "=", "−0.57,", "P", "<", "0.001).", "Lower", "baseline", "counts", "were", "associated", "with", "higher", "probability", "(β*", "=", "−0.20,", "P", "<", "0.001)", "and", "longer", "time", "(β*", "=", "0.14,", "P", "<", "0.001).", "The", "larger", "outbreak", "magnitude", "was", "correlated", "with", "higher", "probability", "(β*", "=", "0.55,", "P", "<", "0.001)", "and", "shorter", "time", "(β*", "=", "−0.23,", "P", "<", "0.001).", "Conclusions:", "The", "results", "of", "this", "study", "suggest", "that", "the", "MPM", "is", "a", "prior", "algorithm", "for", "outbreak", "detection", "and", "differences", "of", "epidemic", "features", "in", "detection", "performance", "should", "be", "considered", "in", "automatic", "surveillance", "practice.", "Keywords:", "Epidemic", "feature,", "Outbreak", "detection", "algorithms,", "Performance,", "Automated", "infectious", "disease", "surveillance", "Background", "Infectious", "diseases", "remain", "the", "major", "causes", "of", "morbidity", "and", "mortality", "in", "China", "despite", "substantial", "progress", "in", "their", "control", "[1].", "The", "outbreaks", "of", "infectious", "diseases", "pose", "serious", "threats", "on", "public", "health.", "Early", "detection", "of", "aberration", "and", "rapid", "control", "actions,", "which", "the", "Chinese", "Ministry", "of", "Health", "has", "taken", "as", "important", "strategies", "for", "*", "Correspondence:", "lanyajia@sina.com", "1Department", "of", "Occupational", "Health,", "West", "China", "School", "of", "Public", "Health,", "Sichuan", "University,", "17", "South", "Section", "3", "Renmin", "Road,", "Chengdu,", "Sichuan", "610041,", "China", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "emergency", "infectious", "disease", "prevention", "and", "control", "[2],", "are", "prerequisites", "for", "preventing", "the", "spread", "of", "outbreaks", "and", "reducing", "the", "morbidity", "and", "death", "caused", "by", "diseases.", "Therefore,", "China", "Infectious", "Disease", "Automated-alert", "and", "Response", "System", "(CIDARS)", "was", "successfully", "implemen-", "ted", "and", "began", "to", "operate", "nationwide", "in", "2008", "[3].", "At", "the", "end", "of", "2010,", "analysis", "results", "of", "the", "operation", "of", "CIDARS", "in", "nationwide", "showed", "that", "a", "large", "number", "of", "outbreaks", "of", "infectious", "diseases", "could", "be", "timely", "detected,", "but", "it", "was", "also", "found", "that", "there", "were", "many", "of", "false-posi-", "tive", "signals;", "large", "differences", "existed", "between", "outbreak", "signal", "counts", "and", "final", "identified", "outbreaks", "in", "different", "©", "2012", "Kuang", "et", "al.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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"suicidal", "threats", "which", "consequently", "led", "to", "his", "psychiatric", "emergency", "room", "admission.", "Neuropsychiatric", "Disease", "and", "Treatment", "2010:6", "67–69", "©", "2010", "Nejtek", "et", "al,", "publisher", "and", "licensee", "Dove", "Medical", "Press", "Ltd.This", "is", "an", "Open", "Access", "article", "which", "permits", "unrestricted", "noncommercial", "use,", "provided", "the", "original", "work", "is", "properly", "cited.", "67" ]

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[ "Health", "and", "Quality", "of", "Life", "Outcomes", "BioMed", "Central", "Research", "Open", "Access", "Reliability", "of", "a", "1-week", "recall", "period", "for", "the", "Medical", "Outcomes", "Study", "Sleep", "Scale", "(MOS-SS)", "in", "patients", "with", "fibromyalgia", "Alesia", "Sadosky*1,", "Ellen", "Dukes1", "and", "Chris", "Evans2", "Address:", "1Pfizer", "Global", "Outcomes", "Research,", "235", "East", "42nd", "Street,", "New", "York,", "NY", "10017,", "USA", "and", "2Mapi", "Values,", "15", "Court", "Square,", "Suite", "620,", "Boston,", "MA", "02108,", "USA", "Email:", "Alesia", "Sadosky*", "-", "alesia.sadosky@pfizer.com;", "Ellen", "Dukes", "-", "ellen.dukes@pfizer.com;", "Chris", "Evans", "-", "chris.evans@mapivalues.com", "*", "Corresponding", "author", "Published:", "10", "February", "2009", "Health", "and", "Quality", "of", "Life", "Outcomes", "2009,", "7:12", "doi:10.1186/1477-7525-7-12", "This", "article", "is", "available", "from:", "http://www.hqlo.com/content/7/1/12", "Received:", "29", "August", "2008", "Accepted:", "10", "February", "2009", "©", "2009", "Sadosky", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Objective:", "To", "evaluate", "the", "reliability", "of", "a", "one-week", "versus", "a", "four-week", "recall", "period", "of", "the", "Medical", "Outcomes", "Study", "Sleep", "Scale", "(MOS-SS)", "in", "patients", "with", "fibromyalgia", "(FM).", "Methods:", "The", "MOS-SS", "was", "administered", "by", "mail", "to", "patients", "with", "a", "confirmed", "diagnosis", "of", "FM", "and", "a", "current", "pain", "rating", "of", ">", "2", "(0–10", "point", "numerical", "rating", "scale)", "recruited", "through", "newspapers,", "support", "groups,", "and", "the", "Internet.", "Reliability", "of", "MOS-SS", "subscale", "domains", "was", "evaluated", "using", "test-", "retest", "methodology", "separated", "by", "a", "1–3", "day", "interval", "for", "the", "4-week", "recall", "period", "and", "a", "7-day", "interval", "for", "the", "1-week", "recall", "period.", "Patient", "Impression", "of", "Change", "was", "evaluated", "for", "sleep,", "and", "for", "patients", "with", "no", "change,", "the", "intraclass", "correlation", "coefficient", "(ICC)", "and", "the", "Pearson", "correlation", "coefficient", "was", "calculated", "for", "MOS-SS", "subscales.", "Results:", "Of", "129", "patients", "enrolled,", "91.3%", "were", "female,", "mean", "age", "was", "49.4", "±", "11.0", "years;", "self-rated", "FM", "severity", "was", "moderate-to-severe", "in", "88.1%", "of", "patients.", "MOS-SS", "subscale", "scores", "were", "similar", "for", "both", "recall", "periods", "with", "little", "variation", "between", "test-retest.", "The", "9-item", "Sleep", "Problems", "Index", "scores", "ranged", "from", "57.2", "±", "14.5", "to", "61.9", "±", "15.8", "across", "all", "assessments", "and", "demonstrated", "high", "reliability", "which", "was", "similar", "for", "the", "1-week", "(ICC", "0.81)", "and", "4-week", "(ICC", "0.89)", "recall", "periods.", "For", "the", "other", "MOS-SS", "subscales,", "the", "1-week", "recall", "period", "also", "showed", "good", "reliability,", "which", "was", "consistent", "for", "the", "ICC", "and", "Pearson", "correlation", "coefficients.", "Conclusion:", "A", "1-week", "recall", "period", "is", "adequately", "reliable", "for", "use", "of", "the", "MOS-SS", "in", "studies", "evaluating", "sleep", "disturbance", "in", "patients", "with", "FM.", "Although", "the", "etiology", "of", "fibromyalgia", "(FM)", "is", "uncertain,", "it", "is", "generally", "diagnosed", "according", "to", "the", "American", "Col-", "lege", "of", "Rheumatology", "(ACR)", "criteria,", "which", "include", "chronic,", "widespread", "pain", "for", "at", "least", "3", "months,", "and", "the", "presence", "of", "11", "out", "of", "18", "tender", "points", "[1].", "It", "has", "been", "esti-", "mated", "that", "approximately", "5", "million", "individuals", "in", "the", "U.S.", "have", "FM,", "with", "a", "higher", "prevalence", "among", "women", "(3.4%)", "than", "men", "(0.5%)", "[2].", "In", "other", "countries,", "the", "prev-", "alence", "of", "FM", "has", "been", "estimated", "to", "range", "between", "0.5%", "to", "5%,", "also", "with", "a", "higher", "prevalence", "among", "women", "[3].", "FM", "is", "associated", "with", "a", "substantial", "socioeconomic", "burden", "resulting", "from", "excess", "health", "resource", "utilization,", "reduc-", "tions", "in", "productivity", "and", "quality", "of", "life,", "and", "a", "health", "sta-", "tus", "that", "is", "poorer", "than", "other", "chronic", "pain", "conditions", "such", "as", "rheumatoid", "arthritis", "and", "osteoarthritis", "[4-7].", "This", "bur-", "Page", "1", "of", "6", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Sensors", "2010,", "10,", "5063-5073;", "doi:10.3390/s100505063", "OPEN", "ACCESS", "sensors", "ISSN", "1424-8220", "www.mdpi.com/journal/sensors", "Article", "Novel", "Microwave-Assisted", "Synthesis", "of", "Poly(D,L-lactide):", "The", "Influence", "of", "Monomer/Initiator", "Molar", "Ratio", "on", "the", "Product", "Properties", "Ljubisa", "Nikolic", "1,*,", "Ivan", "Ristic", "2,", "Borivoj", "Adnadjevic", "3,", "Vesna", "Nikolic", "1,", "Jelena", "Jovanovic", "3", "and", "Mihajlo", "Stankovic", "1", "1", "2", "3", "Faculty", "of", "Technology,", "University", "of", "Nis,", "Bulevar", "oslobodjenja", "124,", "16000", "Leskovac,", "Serbia;", "E-Mails:", "nvesna@yahoo.com", "(V.N.);", "mstankovic_99@yahoo.com", "(M.S.)", "Faculty", "of", "Technology,", "University", "of", "Novi", "Sad,", "Cara", "Lazara", "1,", "21000", "Novi", "Sad,", "Serbia;", "E-Mail:", "ivancekaris@yahoo.com", "Faculty", "for", "Physical", "Chemistry,", "University", "of", "Belgrade,", "Studentski", "trg", "12-16,", "11000", "Belgrade,", "Serbia;", "E-Mails:", "adnadjevic@nadlanu.com", "(B.A.);", "jelenaj@ffh.bg.ac.yu", "(J.J.)", "*", "Author", "to", "whom", "correspondence", "should", "be", "addressed;", "E-Mail:", "nljubisa@yahoo.com.", "Received:", "29", "March", "2010;", "in", "revised", "form:", "26", "April", "2010", "/", "Accepted:", "28", "April", "2010", "/", "Published:", "20", "May", "2010", "Abstract:", "Poly(D,L-lactide)", "synthesis", "using", "tin(II)", "2-ethylhexanoate", "initiated", "ring-opening", "polymerization", "(ROP)", "takes", "over", "30", "hours", "in", "bulk", "at", "120", "°C.", "The", "use", "of", "microwave", "makes", "the", "same", "bulk", "polymerization", "process", "with", "the", "same", "initiator", "much", "faster", "and", "energy", "saving,", "with", "a", "reaction", "time", "of", "about", "30", "minutes", "at", "100", "°C.", "Here,", "the", "poly(lactide)", "synthesis", "was", "done", "in", "a", "microwave", "reactor,", "using", "frequency", "of", "2.45", "GHz", "and", "maximal", "power", "of", "150", "W.", "The", "reaction", "temperature", "was", "controlled", "via", "infra-red", "system", "for", "in-bulk-", "measuring,", "and", "was", "maintained", "at", "100", "°C.", "Different", "molar", "ratios", "of", "monomer", "and", "initiator,", "[M]/[I],", "of", "1,000,", "5,000", "and", "10,000", "were", "used.", "The", "achieved", "average", "molar", "masses", "for", "the", "obtained", "polymers", "(determined", "by", "gel", "permeation", "chromatography)", "were", "in", "the", "interval", "from", "26,700", "to", "112,500", "g/mol.", "The", "polydispersion", "index", "was", "from", "2.436", "to", "3.425.", "For", "applicative", "purposes,", "the", "obtained", "material", "was", "purified", "during", "the", "procedure", "of", "microsphere", "preparation.", "Microspheres", "were", "obtained", "by", "spraying", "a", "fine", "fog", "of", "polymer", "(D,L-lactide)", "solution", "in", "tetrahydrofuran", "into", "the", "water", "solution", "of", "poly(vinyl", "alcohol)", "with", "intensive", "stirring." ]

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[ "6454–6465", "Nucleic", "Acids", "Research,", "2009,", "Vol.", "37,", "No.", "19", "doi:10.1093/nar/gkp650", "Published", "online", "26", "August", "2009", "Yeast", "genome", "analysis", "identifies", "chromosomal", "translocation,", "gene", "conversion", "events", "and", "several", "sites", "of", "Ty", "element", "insertion", "Yoshiyuki", "Shibata,", "Ankit", "Malhotra,", "Stefan", "Bekiranov", "and", "Anindya", "Dutta*", "Department", "of", "Biochemistry", "and", "Molecular", "Genetics,", "University", "of", "Virginia,", "Charlottesville,", "VA", "22908,", "USA", "Received", "April", "3,", "2009;", "Revised", "July", "20,", "2009;", "Accepted", "July", "20,", "2009", "ABSTRACT", "Paired", "end", "mapping", "of", "chromosomal", "fragments", "has", "been", "used", "in", "human", "cells", "to", "identify", "numerous", "structural", "variations", "in", "chromosomes", "of", "individuals", "and", "of", "cancer", "cell", "lines;", "however,", "the", "molecular,", "biological", "and", "bioinformatics", "methods", "for", "this", "technology", "are", "still", "in", "development.", "Here,", "we", "present", "a", "parallel", "bioinformatics", "approach", "to", "analyze", "chromosomal", "paired-end", "tag", "(ChromPET)", "sequence", "data", "and", "demonstrate", "its", "application", "in", "identifying", "gene", "rearrangements", "in", "the", "model", "organism", "Saccharomyces", "cerevisiae.", "We", "detected", "several", "expected", "events,", "including", "a", "chromo-", "somal", "rearrangement", "of", "the", "nonessential", "arm", "of", "chromosome", "V", "induced", "by", "selective", "pressure,", "rearrangements", "introduced", "during", "strain", "construc-", "tion", "and", "gene", "conversion", "at", "the", "MAT", "locus.", "In", "addition,", "we", "discovered", "several", "unannotated", "Ty", "element", "insertions", "that", "are", "present", "in", "the", "reference", "yeast", "strain,", "but", "not", "in", "the", "reference", "genome", "sequence,", "suggesting", "a", "few", "revisions", "are", "necessary", "in", "the", "latter.", "These", "data", "demonstrate", "that", "application", "of", "the", "chromPET", "technique", "to", "a", "genetically", "tractable", "organism", "like", "yeast", "provides", "an", "easy", "screen", "for", "studying", "the", "mechanisms", "of", "chromosomal", "rearrangements", "during", "the", "propaga-", "tion", "of", "a", "species.", "INTRODUCTION", "The", "precise", "identification", "of", "sites", "of", "chromosomal", "trans-", "locations,", "deletions", "and", "insertions", "holds", "the", "promise", "of", "cataloging", "recurrent", "gene", "rearrangements", "in", "diseases.", "This", "has", "been", "the", "primary", "impetus", "for", "the", "development", "of", "paired", "end", "mapping", "techniques", "in", "humans", "(1,2).", "The", "basic", "principle", "is", "to", "identify", "the", "short", "sequences", "at", "the", "ends", "of", "linear", "genomic", "DNA", "fragments", "of", "a", "specified", "size.", "In", "contrast", "to", "a", "complete", "sequencing", "strategy,", "mapping", "the", "‘paired-end-tag’", "(PET)", "sequences", "back", "to", "the", "genome", "allows", "one", "to", "identify", "structural", "variations", "such", "as", "insertions,", "inversions", "and", "translocations", "with", "far", "fewer", "sequence", "reads.", "Unlike", "array", "Comparative", "Genomic", "Hybridization", "(a-CGH),", "PET", "analysis", "provides", "quantita-", "tive", "digital", "information", "with", "no", "detectable", "signal", "satura-", "tion", "and", "ability", "to", "sample", "rare", "events", "by", "sequencing", "more", "DNA.", "In", "addition,", "a", "significant", "advantage", "to", "sequencing", "is", "the", "identification", "of", "the", "specific", "genomic", "location", "of", "these", "chromosomal", "rearrangements,", "and", "the", "emphasis", "till", "now", "has", "been", "on", "identifying", "such", "structural", "variations", "in", "unique", "chromosomal", "sequences.", "In", "clinical", "samples,", "such", "disease-specific", "junctional", "fragments", "can", "be", "useful", "molecular", "markers", "for", "the", "diagnosis", "of", "various", "diseases.", "Many", "oncogenes", "can", "be", "activated", "by", "recurrent", "chromo-", "somal", "aberration", "and", "are", "frequently", "observed", "in", "hematological", "and", "solid", "tumors.", "For", "example,", "the", "t(9;22)(q34;q11)", "translocation", "results", "in", "the", "fusion", "of", "the", "BCR", "and", "ABL1", "genes", "in", "chronic", "myelogenous", "leukemia,", "and", "the", "t(8;14)(q24;q32)", "translocation", "fuses", "MYC", "with", "the", "immunoglobulin", "heavy", "chain", "gene", "in", "Burkitt", "lymphoma", "(3,4).", "Recently,", "paired-end", "mapping", "studies", "have", "revealed", "extensive", "structural", "variation", "in", "the", "human", "genome", "(5,6)", "and", "identified", "somatically", "acquired", "rearrangements", "in", "cancer", "(7–9).", "This", "raises", "the", "question", "of", "the", "presence", "and", "extent", "of", "similar", "structural", "variation", "in", "other", "model", "organisms.", "In", "this", "study,", "we", "establish", "the", "experimental", "and", "computational", "methodology", "for", "paired-end", "mapping", "and", "use", "it", "to", "study", "structural", "variation", "in", "Saccharomyces", "cerevisiae.", "Saccharomyces", "cerevisiae", "is", "a", "useful", "eukaryotic", "model", "organism", "for", "establishing", "PET", "applications", "for", "several", "reasons.", "Specifically,", "it", "is", "easy", "to", "produce", "uniform", "population", "of", "cells,", "since", "S.", "cerevisiae", "grow", "stably", "as", "either", "a", "haploid", "or", "diploid", "and", "are", "genetically", "tractable.", "The", "S.", "cerevisiae", "genome", "is", "12", "Mbp,", "which", "is", "2", "orders", "of", "magnitude", "smaller", "than", "the", "human", "genome.", "In", "addition,", "S.", "cerevisiae", "is", "used", "as", "a", "model", "organism", "for", "system", "biology", "and", "has", "a", "well-annotated", "*To", "whom", "correspondence", "should", "be", "addressed.", "Tel:", "+1", "(434)", "924", "1227;", "Fax:", "+1", "(434)", "924", "5069;", "Email:", "ad8q@virginia.edu", "The", "authors", "wish", "it", "to", "be", "known", "that,", "in", "their", "opinion,", "the", "first", "two", "authors", "should", "be", "regarded", "as", "joint", "First", "Authors", "The", "Author(s)", "2009.", "Published", "by", "Oxford", "University", "Press.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "Non-Commercial", "License", "(http://creativecommons.org/licenses/", "by-nc/2.5/uk/)", "which", "permits", "unrestricted", "non-commercial", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "HH", "Kwon", "and", "KH", "Kim", "Ann", "Dermatol", "Vol.", "24,", "No.", "1,", "2012", "CASE", "REPORT", "http://dx.doi.org/10.5021/ad.2012.24.1.66", "Intravenous", "Immunoglobulin", "Treatment", "in", "a", "Child", "with", "Resistant", "Atopic", "Dermatitis", "Hyuck", "Hoon", "Kwon,", "M.D.,", "Kyu", "Han", "Kim,", "M.D.,", "Ph.D.", "Department", "of", "Dermatology,", "Seoul", "National", "University", "College", "of", "Medicine,", "Seoul,", "Korea", "In", "a", "subgroup", "of", "patients", "suffering", "from", "atopic", "dermatitis", "(AD),", "treatment", "is", "quite", "difficult", "even", "after", "taking", "oral", "immunosuppressants.", "High-dose", "intravenous", "immunoglo-", "bulin", "(IVIG)", "treatment", "has", "been", "reported", "to", "be", "beneficial", "for", "them", "in", "a", "few", "uncontrolled", "trials.", "Herein", "we", "report", "a", "case", "of", "intractable", "AD", "in", "a", "5-year-old", "girl", "who", "had", "significant", "clinical", "improvement", "after", "receiving", "3", "cycles", "of", "IVIG", "treatment", "(2", "g/kg)", "without", "notable", "side", "effects.", "Since", "the", "first", "infusion", "of", "IVIG,", "the", "patient’s", "skin", "lesions", "improved", "steadily", "and", "the", "improvement", "persisted", "until", "the", "8-month", "follow-up.", "The", "eczema", "area", "and", "severity", "index", "score", "decreased", "remarkably,", "while", "immunologic", "parameters", "did", "not", "cor-", "relate", "with", "clinical", "improvement.", "This", "case", "suggests", "that", "IVIG", "therapy", "can", "be", "quite", "effective", "and", "safe", "for", "children", "with", "resistant", "AD.", "(Ann", "Dermatol", "24(1)", "66∼69,", "2012)", "-Keywords-", "Atopic", "dermatitis,", "Intravenous", "immunoglobulins", "INTRODUCTION", "Atopic", "dermatitis", "(AD)", "is", "one", "of", "the", "most", "common", "derma-", "tologic", "diseases,", "affecting", "approximately", "20%", "of", "children", "living", "in", "industrialized", "countries.", "Moreover,", "approxima-", "tely", "70%", "of", "cases", "of", "AD", "affect", "children", "less", "than", "5", "years", "of", "Received", "July", "21,", "2010,", "Revised", "August", "10,", "2010,", "Accepted", "for", "publication", "August", "10,", "2010", "Corresponding", "author:", "Kyu", "Han", "Kim,", "M.D.,", "Ph.D.,", "Department", "of", "Dermatology,", "Seoul", "National", "University", "College", "of", "Medicine,", "28", "Yeongeon-dong,", "Jongno-gu,", "Seoul", "110-744,", "Korea.", "Tel:", "82-2-2072-", "3463,", "Fax:", "82-2-747-5130,", "E-mail:", "kyuhkim@snu.ac.kr", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "Non-Commercial", "License", "(http://", "creativecommons.org/licenses/by-nc/3.0)", "which", "permits", "unrestricted", "non-commercial", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "66", "Ann", "Dermatol", "age1,2.", "Most", "cases", "of", "AD", "are", "effectively", "treated", "with", "topical", "steroids,", "topical", "calcineurin", "inhibitors", "and", "inter-", "mittent", "use", "of", "immunosuppressive", "agents,", "including", "oral", "corticosteroids", "and", "cyclosporine.", "However,", "for", "recalci-", "trant", "AD,", "continuous", "use", "of", "systemic", "immunosuppressive", "agents", "is", "used", "but", "is", "limited", "by", "the", "adverse", "effects,", "es-", "pecially", "for", "children.", "For", "this", "subgroup", "of", "patients,", "a", "num-", "ber", "of", "clinical", "trials", "based", "on", "immunomodulatory", "drugs", "have", "been", "conducted", "with", "limited", "success3-5,", "and", "high-", "dose", "intravenous", "immunoglobulin", "(IVIG)", "therapy", "has", "been", "reported", "to", "be", "effective", "in", "some", "recent", "trials6-12;", "in", "particular,", "children", "have", "shown", "much", "higher", "responses", "than", "adults6-8,", "and", "no", "serious", "side", "effects", "accompanied", "the", "therapy.", "In", "the", "current", "report,", "we", "present", "the", "case", "of", "a", "5-year-old", "female", "with", "treatment-refractory", "AD", "who", "was", "remarkably", "improved", "with", "IVIG", "therapy", "without", "notable", "side", "effects.", "Her", "state", "of", "remission", "continued", "for", "8", "months", "without", "disease", "recurrence.", "CASE", "REPORT", "A", "5-year-old", "female", "with", "a", "3-year", "history", "of", "treatment-", "refractory", "AD", "was", "referred", "to", "our", "Pediatric", "Dermatology", "Clinic.", "She", "had", "failed", "to", "respond", "to", "2", "years", "of", "topical", "steroids", "and", "calcineurin", "inhibitors.", "Oral", "steroid", "treatments", "as", "an", "inpatient", "and", "outpatient", "during", "the", "last", "year", "were", "not", "much", "help.", "Recurrent", "staphylococcal", "infections", "and", "severe", "pruritus", "resulted", "in", "numerous", "hospital", "admissions.", "She", "was", "clinically", "depressed", "and", "needed", "a", "psychiatric", "consultation.", "She", "didn’t", "show", "any", "symptoms", "of", "allergic", "rhinitis", "and", "asthma.", "There", "was", "also", "no", "family", "history", "of", "AD,", "allergic", "rhinitis", "and", "asthma.", "Quantitative", "measure-", "ment", "of", "the", "extent", "and", "severity", "of", "the", "AD", "was", "made", "using", "an", "eczema", "area", "and", "severity", "index", "(EASI)", "scoring", "system,", "the", "initial", "value", "of", "which", "was", "30", "(Fig.", "1A).", "Laboratory", "results", "showed", "a", "total", "IgE", "of", "11,000", "kU/L", "and", "multiple", "allergen", "stimultaneous", "tests", "(RIDA", "Allergy", "Screening" ]

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[ "Biochemistry", "2010,", "49,", "2615–2626", "2615", "DOI:", "10.1021/bi901516d", "2", "Structure", "of", "the", "1,N", "-Etheno-20-deoxyguanosine", "Lesion", "in", "the", "30-G(εdG)T-50", "Sequence", "Opposite", "a", "One-Base", "Deletion†", "Ganesh", "Shanmugam,‡", "Ivan", "D.", "Kozekov,‡", "F.", "Peter", "Guengerich,§", "Carmelo", "J.", "Rizzo,‡,§", "and", "Michael", "P.", "Stone*,‡,§", "‡Department", "of", "Chemistry", "and", "§Department", "of", "Biochemistry,", "Vanderbilt", "Institute", "of", "Chemical", "Biology,", "Center", "in", "Molecular", "Toxicology,", "and", "Vanderbilt-Ingram", "Cancer", "Center,", "Vanderbilt", "University,", "Nashville,", "Tennessee", "37235", "Received", "August", "28,", "2009;", "Revised", "Manuscript", "Received", "November", "19,", "2009", "ABSTRACT:", "The", "structure", "of", "the", "1,N2-ethenodeoxyguanosine", "lesion", "(1,N2-εdG)", "has", "been", "characterized", "in", "50-d(CGCATXGAATCC)-30", "3", "50-d(GGATTCATGCG)-30", "(X", "=", "1,N2-εdG),", "in", "which", "there", "is", "no", "dC", "opposite", "the", "lesion.", "This", "duplex", "(named", "the", "1-BD", "duplex)", "models", "the", "product", "of", "translesion", "bypass", "of", "1,N2-εdG", "by", "Sulfolobus", "solfataricus", "P2", "DNA", "polymerase", "IV", "(Dpo4)", "[Zang,", "H.,", "Goodenough,", "A.", "K.,", "Choi,", "J.", "Y.,", "Irimia,", "A.,", "Loukachevitch,", "L.", "V.,", "Kozekov,", "I.", "D.,", "Angel,", "K.", "C.,", "Rizzo,", "C.", "J.,", "Egli,", "M.,", "and", "Guengerich,", "F.", "P.", "(2005)", "J.", "Biol.", "Chem.", "280,", "29750-29764],", "leading", "to", "a", "one-base", "deletion.", "The", "Tm", "of", "this", "duplex", "is", "6", "C", "higher", "than", "that", "of", "the", "duplex", "in", "which", "dC", "is", "present", "opposite", "the", "1,N2-εdG", "lesion", "and", "8", "C", "higher", "than", "that", "of", "the", "unmodified", "1-BD", "duplex.", "Analysis", "of", "NOEs", "between", "the", "1,N2-εdG", "imidazole", "and", "deoxyribose", "H10", "protons", "and", "between", "the", "1,N2-εdG", "etheno", "H6", "and", "H7", "protons", "and", "DNA", "protons", "establishes", "that", "1,N2-εdG", "adopts", "the", "anti", "conformation", "about", "the", "glycosyl", "bond", "and", "that", "the", "etheno", "moiety", "is", "accommodated", "within", "the", "helix.", "The", "resonances", "of", "the", "1,N2-εdG", "H6", "and", "H7", "etheno", "protons", "shift", "upfield", "relative", "to", "the", "monomer", "1,N2-εdG,", "attributed", "to", "ring", "current", "shielding,", "consistent", "with", "their", "intrahelical", "location.", "NMR", "data", "reveal", "that", "Watson-Crick", "base", "pairing", "is", "maintained", "at", "both", "the", "50", "and", "30", "neighbor", "base", "pairs.", "The", "structure", "of", "the", "1-BD", "duplex", "has", "been", "refined", "using", "molecular", "dynamics", "calculations", "restrained", "by", "NMR-derived", "distance", "and", "dihedral", "angle", "restraints.", "The", "increased", "stability", "of", "the", "1,N2-εdG", "lesion", "in", "the", "absence", "of", "the", "complementary", "dC", "correlates", "with", "the", "one-base", "deletion", "extension", "product", "observed", "during", "the", "bypass", "of", "the", "1,N2-εdG", "lesion", "by", "the", "Dpo4", "polymerase,", "suggesting", "that", "stabilization", "of", "this", "bulged", "intermediate", "may", "be", "significant", "with", "regard", "to", "the", "biological", "processing", "of", "the", "lesion.", "Ethenobases", "(1)", "are", "five-membered", "annelation", "products", "arising", "from", "the", "reactions", "of", "electrophiles", "derived", "from", "vinyl", "halides", "and", "other", "vinyl", "monomers,", "including", "chloroacetaldehyde,", "with", "dC,", "dA,", "and", "dG", "nucleotides", "in", "DNA", "(2-9).", "They", "also", "arise", "from", "endogenous", "exposure", "to", "lipid", "peroxidation", "products", "(10),", "parti-", "cularly", "4,5-epoxy-2(E)-decanal", "(11,", "12)", "and", "4-hydroperoxynone-", "nal", "(13);", "related", "etheno", "adducts", "from", "4-oxo-2(E)-nonenal", "(14,", "15),", "4-oxohexenal", "(16),", "and", "9,12-dioxo-10(E)-dodecanoic", "acid", "(17)", "have", "also", "been", "characterized", "(15,", "17).", "The", "1,N2-ethenodeoxy-", "guanosine", "(1,N2-εdG)1", "adduct", "(18)", "(Scheme", "1)", "is", "one", "of", "two", "εdG", "lesions,", "the", "other", "being", "the", "N2,3-εdG", "adduct.", "One", "of", "our", "laboratories", "has", "elucidated", "the", "mechanism", "for", "formation", "of", "†This", "work", "was", "supported", "by", "National", "Institutes", "of", "Health", "(NIH)", "Grants", "P01", "ES005355", "(C.J.R.,", "I.D.K.,", "and", "M.P.S.)", "and", "R01", "ES010375", "(F.P.G.).", "Funding", "for", "the", "NMR", "spectrometers", "was", "supplied", "by", "Vanderbilt", "University,", "the", "Vanderbilt", "Center", "in", "Molecular", "Toxicology", "(P30", "ES000267),", "and", "by", "NIH", "Grant", "RR005805.", "The", "Vanderbilt", "Ingram", "Cancer", "Center", "is", "supported", "by", "NIH", "Grant", "P30", "CA068485.", "*To", "whom", "correspondence", "should", "be", "addressed.", "Phone:", "(615)", "322-2589.", "Fax:", "(615)", "322-7591.", "E-mail:", "michael.p.stone@vanderbilt.edu.", "1Abbreviations:", "1,N2-εdG,", "3-(20-deoxy-β-D-erythro-pentofuranosyl)-", "3,4-dihydro-9H-imidazo[1,2-a]purin-9-one", "or", "1,N2-etheno-20-deoxy-", "guanosine;", "M1dG,", "3-(20-deoxy-β-D-erythro-pentofuranosyl)pyrimido-", "[1,2-R]purin-10(3H)-one;", "PdG,", "1,N2-propano-20-deoxyguanosine;", "1-BD,", "one-base", "deletion;", "NOE,", "nuclear", "Overhauser", "enhancement;", "NOESY,", "two-", "dimensional", "NOE", "spectroscopy;", "COSY,", "correlation", "spectroscopy;", "DQF-", "COSY,", "double-quantum-filtered", "correlation", "spectroscopy;", "TPPI,", "time-", "proportional", "phase", "increment.", "A", "right", "superscript", "refers", "to", "the", "numerical", "position", "in", "the", "sequence", "starting", "from", "the", "50", "terminus", "of", "chain", "A", "and", "proceeding", "to", "the", "30", "terminus", "of", "chain", "A", "and", "then", "from", "the", "50", "terminus", "of", "chain", "B", "to", "the", "30", "terminus", "of", "chain", "B.", "1,N2-εdG", "(19,", "20).", "It", "has", "been", "detected", "in", "DNA", "treated", "with", "vinyl", "chloride", "metabolites", "(21)", "and", "β-carotene", "oxidation", "pro-", "ducts", "(22),", "isolated", "using", "immunohistochemistry", "techniques", "(23),", "and", "identified", "by", "mass", "spectrometry", "in", "liver", "DNA", "of", "rodents", "(24-27).", "The", "1,Ν2-εdG", "lesion", "blocks", "the", "Watson-Crick", "hydrogen", "bonding", "face", "of", "dG", "and", "is", "mutagenic", "in", "Escherichia", "coli", "(28)", "and", "in", "mammalian", "(29)", "cells.", "The", "insertion", "of", "1,N2-εdG", "into", "a", "30-G(1,N2-εdG)TACT-50", "template", "and", "its", "replication", "by", "the", "Sulfolobus", "solfataricus", "P2", "DNA", "polymerase", "IV", "(Dpo4)", "were", "reported", "by", "Zang", "et", "al.", "(30),", "who", "showed", "that", "dATP", "was", "preferentially", "incorporated.", "Crystallographic", "analyses", "(30)", "of", "either", "binary", "or", "ternary", "complexes", "with", "the", "Dpo4", "polymerase", "led", "to", "the", "conclusion", "that", "this", "occurs", "via", "formation", "of", "a", "“type", "II”", "bypass", "structure", "at", "the", "active", "site", "of", "the", "polymerase,", "in", "which", "the", "incoming", "dATP", "pairs", "with", "the", "50", "neighboring", "T", "of", "the", "template", "strand,", "as", "opposed", "to", "the", "damaged", "1,N2-εdG", "nucleotide", "(31).", "Further", "extension", "presumably", "led", "to", "the", "observed", "-1", "frameshift", "event", "and", "the", "50-CATGA-30", "product", "(30).", "To", "improve", "our", "understanding", "of", "the", "structural", "basis", "of", "-1", "frameshift", "events,", "we", "inserted", "1,N2-εdG", "into", "the", "12-mer", "3", "11-mer", "duplex", "[50-d(CGCATXGAATCC)-30", "3", "50-d(GGATTC_ATGCG)-30", "(X", "=", "1,N2-εdG)]", "containing", "a", "30-G(1,N2-εdG)TAC-50", "template", "sequence", "(underlined)", ".", "This", "will", "be", "termed", "the", "1-BD", "duplex", "(Scheme", "1).", "It", "models", "the", "situation", "following", "“type", "II”", "insertion", "of", "dATP", "in", "which", "the", "Dpo4", "polymerase", "skips", "the", "damaged", "base", "in", "the", "30-G(1,N2-εdG)TACT-50", "template", "and", "instead", "utilizes", "the", "50", "neighbor", "thymine", "(underlined)", "to", "incorporate", "dATP", "(31),", "r", "2010", "American", "Chemical", "Society", "Published", "on", "Web", "03/04/2010", "pubs.acs.org/Biochemistry" ]

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[ "metal-organic", "compounds", "Acta", "Crystallographica", "Section", "E", "Structure", "Reports", "Online", "ISSN", "1600-5368", "l-Bromido-bis{l-2,20-[4,7-diazadecane-", "1,10-diylbis(nitrilomethanylylidene)]-", "diphenolato}tricopper(II)", "bromide", "dimethylformamide", "disolvate", "Gervas", "Assey,", "Ray", "J.", "Butcher*", "and", "Yilma", "Gultneh", "Department", "of", "Chemistry,", "Howard", "University,", "525", "College", "Street", "NW,", "Washington,", "DC", "20059,", "USA", "Correspondence", "e-mail:", "rbutcher99@yahoo.com", "Experimental", "Crystal", "data", "Received", "21", "July", "2011;", "accepted", "1", "August", "2011", "Key", "indicators:", "single-crystal", "X-ray", "study;", "T", "=", "200", "K;", "mean", "(C–C)", "=", "0.006", "A˚;", "disorder", "in", "solvent", "or", "counterion;", "R", "factor", "=", "0.030;", "wR", "factor", "=", "0.062;", "data-to-", "parameter", "ratio", "=", "17.6.", "The", "complex", "molecule", "of", "the", "title", "compound,", "[Cu3Br(C22H28-", "N4O2)2]Br", "2C3H7NO,", "contains", "three", "copper", "atoms,", "two", "of", "which", "are", "five-coordinate", "within", "a", "square-pyramidal", "environ-", "ment", "and", "linked", "by", "a", "bridging", "Br", "atom", "occupying", "the", "apical", "position", "in", "each", "square", "pyramid.", "The", "remaining", "Cu", "atom", "is", "four-coordinate", "but", "with", "considerable", "tetrahedral", "disortion", "[the", "dihedral", "angle", "between", "the", "two", "chelate", "planes", "is", "69.21", "(7)", "].", "There", "are", "two", "molecules", "of", "dimethylformamide", "(DMF)", "present", "as", "solvent", "molecules,", "one", "of", "which", "is", "disordered", "over", "two", "equivalent", "conformations", "with", "occupan-", "cies", "of", "0.603", "(5)", "and", "0.397", "(5).", "The", "amine", "H", "atoms", "are", "involved", "in", "both", "inter-", "and", "intramolecular", "hydrogen-bonding", "interactions", "with", "the", "Br", "and", "O", "atoms", "of", "the", "cation,", "as", "well", "as", "with", "the", "O", "atom", "of", "the", "ordered", "DMF", "molecule.", "Related", "literature", "For", "information", "concerning", "the", "parameter,", "see:", "Addison", "et", "al.", "(1984).", "For", "background", "to", "the", "use", "of", "multi-nuclear", "copper", "complexes", "in", "metallo-enzymes", "for", "catalyzing", "the", "four-electron", "reduction", "of", "oxygen", "to", "water,", "see:", "Yoon", "et", "al.", "(2005);", "Solomon", "et", "al.", "(1996);", "Mukherjee", "et", "al.", "(2003);", "Mirica", "&", "Stack", "(2005);", "Augustine", "et", "al.", "(2010);", "Chaudhuri", "et", "al.", "(1992).", "For", "general", "background", "to", "multinuclear", "copper", "types,", "see:", "Miessler", "&", "Tarr", "(2005);", "Mukherjee", "et", "al.", "(2003);", "Chen", "et", "al.", "(2010);", "Lawton", "et", "al.", "(2009);", "Hakulinen", "et", "al.", "(2008).", "For", "information", "concerning", "the", "Type", "II", "and", "Type", "III", "site:", "Pompidor", "et", "al.", "(2008);", "Li", "et", "al.", "(2009).", "For", "model", "studies", "of", "the", "multi-copper", "site:", "Cole", "et", "al.", "(1996);", "Kataoka", "et", "al.", "(2009);", "Paine", "et", "al.", "(2004).", "[Cu3Br(C22H28N4O2)2]Br", "2C3H7NO", "Mr", "=", "1257.60", "Hexagonal,", "P61", "a", "=", "18.7450", "(2)", "A˚", "c", "=", "28.2531", "(5)", "A˚", "V", "=", "8597.4", "(2)", "A˚", "3", "Data", "collection", "Oxford", "Diffraction", "Gemini", "R", "diffractometer", "Absorption", "correction:", "multi-scan", "(CrysAlis", "RED;", "Oxford", "Diffraction,", "2009)", "Tmin", "=", "0.782,", "Tmax", "=", "1.000", "Refinement", "R[F", "2", ">", "2", "(F", "2)]", "=", "0.030", "wR(F", "2)", "=", "0.062", "S", "=", "0.91", "11660", "reflections", "662", "parameters", "85", "restraints", "Z", "=", "6", "Mo", "K", "radiation", "=", "2.55", "mm", "1", "T", "=", "200", "K", "0.51", "0.42", "0.38", "mm", "95983", "measured", "reflections", "11660", "independent", 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[ "Malaria", "Journal", "Research", "Efficacy", "and", "tolerability", "of", "four", "antimalarial", "combinations", "in", "the", "treatment", "of", "uncomplicated", "Plasmodium", "falciparum", "malaria", "in", "Senegal", "Babacar", "Faye*,", "Jean-Louis", "Ndiaye,", "Daouda", "Ndiaye,", "Yemou", "Dieng,", "Oumar", "Faye", "and", "Oumar", "Gaye", "Address:", "Laboratoire", "de", "Parasitologie-Mycologie,", "Faculté", "de", "Médecine,", "Pharmacie", "et", "Odontologie.", "Université", "Cheikh", "Anta", "Diop,", "Dakar,", "Senegal", "Email:", "Babacar", "Faye*", "-", "bfaye67@yahoo.fr;", "Jean-Louis", "Ndiaye", "-", "jlndiaye@yahoo.com;", "Daouda", "Ndiaye", "-", "dndiaye@hsph.harvard.edu;", "Yemou", "Dieng", "-", "Yemoud@yahoo.fr;", "Oumar", "Faye", "-", "katafaye@yahoo.fr;", "Oumar", "Gaye", "-", "ogaye@refer.sn", "*", "Corresponding", "author", "Published:", "14", "June", "2007", "Malaria", "Journal", "2007,", "6:80", "doi:10.1186/1475-2875-6-80", "This", "article", "is", "available", "from:", "http://www.malariajournal.com/content/6/1/80", "Received:", "3", "February", "2007", "Accepted:", "14", "June", "2007", "©", "2007", "Faye", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "BioMed", "Central", "Open", "Access", "Abstract", "Background:", "In", "view", "of", "the", "high", "level", "of", "chloroquine", "resistance", "in", "many", "countries,", "WHO", "has", "recommended", "the", "use", "of", "combination", "therapy", "with", "artemisinin", "derivatives", "in", "the", "treatment", "of", "uncomplicated", "malaria", "due", "to", "Plasmodium", "falciparum.", "Four", "antimalarial", "drug", "combinations,", "artesunate", "plus", "amodiaquine", "(Arsucam®),", "artesunate", "plus", "mefloquine", "(Artequin®),", "artemether", "plus", "lumefantrine", "(Coartem®;", "four", "doses", "and", "six", "doses),", "and", "amodiaquine", "plus", "sulphadoxine-", "pyrimethamine,", "were", "studied", "in", "five", "health", "districts", "in", "Senegal.", "Methods:", "This", "is", "a", "descriptive,", "analytical,", "open,", "randomized", "study", "to", "evaluate", "the", "efficacy", "and", "tolerability", "of", "these", "four", "antimalarial", "combinations", "in", "the", "treatment", "of", "uncomplicated", "falciparum", "malaria", "using", "the", "2002", "WHO", "protocol.", "Results:", "All", "drug", "combinations", "demonstrated", "good", "efficacy.", "On", "day", "28,", "all", "combinations", "resulted", "in", "an", "excellent", "clinical", "and", "parasitological", "response", "rate", "of", "100%", "after", "correction", "for", "PCR", "results,", "except", "for", "the", "four-dose", "artemether-lumefantrine", "regimen", "(96.4%).", "Follow-up", "of", "approximately", "10%", "of", "each", "treatment", "group", "on", "day", "42", "demonstrated", "an", "efficacy", "of", "100%.", "The", "combinations", "were", "well", "tolerated", "clinically", "and", "biologically.", "No", "unexpected", "side-effect", "was", "observed", "and", "all", "side-effects", "disappeared", "at", "the", "end", "of", "treatment.", "No", "serious", "side-effect", "requiring", "premature", "termination", "of", "treatment", "was", "observed.", "Conclusion:", "The", "four", "combinations", "are", "effective", "and", "well-tolerated.", "Background", "Approximately", "35%", "of", "in-patient", "and", "out-patient", "clinic", "attendance", "in", "Senegal", "are", "due", "to", "malaria", "[1].", "Studies", "car-", "ried", "out", "by", "staff", "of", "the", "Parasitology", "Laboratory,", "Faculté", "de", "Médecine,", "Université", "Cheikh", "Anta", "Diop,", "Dakar,", "have", "demonstrated", "high", "levels", "of", "resistance", "to", "chloroquine,", "which", "was", "used", "as", "the", "first-line", "treatment", "of", "uncompli-", "cated", "malaria", "and", "as", "chemoprophylaxis", "in", "pregnant", "women", "[2,3].", "Clinical", "failure", "rates", "higher", "than", "25%", "have", "been", "observed", "at", "more", "than", "half", "of", "the", "sites", "surveyed.", "Page", "1", "of", "9", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Kim", "et", "al.", "BMC", "Infectious", "Diseases", "2010,", "10:315", "http://www.biomedcentral.com/1471-2334/10/315", "C", "A", "S", "E", "R", "E", "P", "O", "R", "T", "Open", "Access", "Enterobacter", "nimipressuralis", "as", "a", "cause", "of", "pseudobacteremia", "Dong-Min", "Kim1,4†,", "Sook", "Jin", "Jang2,4†,", "Ganesh", "Prasad", "Neupane1,", "Mi-Sun", "Jang1,5,", "Se-Hoon", "Kwon1,", "Seok", "Won", "Kim3*,", "Won", "Yong", "Kim6", "Abstract", "Background:", "The", "clinical", "significance", "of", "the", "Enterobacter", "nimipressuralis", "as", "human", "pathogens", "remains", "unclear.", "Case", "presentations:", "The", "microbiologic", "culture", "monitoring", "system", "of", "sterile", "body", "fluids", "revealed", "on", "an", "episode", "of", "Enterobacter", "cloacae", "and", "Enterobacter", "amnigenus", "in", "blood", "culture", "results", "on", "the", "same", "day;", "the", "antibiotic", "sensitivity", "and", "MIC", "were", "nearly", "the", "same", "for", "both", "species.", "First", "patient", "was", "a", "healthy", "woman", "with", "postmenopausal", "syndrome,", "while", "second", "patient", "with", "herpes", "zoster.", "Both", "patients", "had", "febrile", "sensations", "without", "signs", "of", "bacteremia.", "E.", "amnigenus", "was", "also", "cultured", "from", "the", "unused", "package", "of", "salined", "cotton", "in", "the", "container", "through", "epidemiologic", "investigation.", "The", "cultured", "Enterobacter", "species", "were", "all", "identified", "as", "E.", "nimipressuralis", "through", "hsp60", "gene", "sequencing", "and", "infrequent-restriction-site", "PCR", "(IRS-PCR).", "Conclusion:", "When", "an", "unusual", "microorganisms", "such", "as", "E.", "nimipressuralis", "is", "isolated", "from", "blood", "of", "a", "patient", "with", "no", "clinical", "signs", "of", "sepsis,", "a", "pseudobacteremia", "should", "be", "suspected.", "When", "the", "antibiogram", "and", "MIC", "test", "results", "of", "bacterial", "cultures", "from", "two", "or", "more", "patients", "are", "nearly", "the", "same,", "although", "the", "species", "involved", "may", "appear", "different,", "it", "may", "be", "necessary", "to", "prove", "that", "they", "are", "the", "same", "species", "through", "molecular", "methods.", "The", "microbiologic", "cultures", "monitoring", "system", "will", "probably", "help", "to", "detect", "pseudobacteremia", "and", "other", "pseudo", "infections", "through", "reliable", "and", "fast", "identification.", "Background", "Chosun", "University", "Hospital,", "Gwang-ju,", "Korea,", "is", "a", "650-", "bed,", "tertiary", "care", "teaching", "hospital.", "Every", "day", "in", "our", "hospital,", "an", "infectious", "disease", "specialist", "monitors", "all", "the", "results", "of", "the", "hospital’s", "microbiologic", "cultures", "from", "ster-", "ile", "body", "fluids", "such", "as", "blood,", "cerebrospinal", "fluid", "(CSF),", "pleural", "fluid,", "ascites,", "joint", "fluid", "and", "localized", "fluid", "col-", "lection", "using", "a", "computerized", "monitoring", "system.", "This", "monitoring", "system", "revealed", "an", "episode", "of", "Enterobacter", "nimipressuralis", "pseudobacteremia", "caused", "by", "con-", "taminated", "saline", "cotton", "during", "the", "preparation", "of", "blood", "culture", "samples.", "Here", "we", "describe", "two", "cases", "of", "Entero-", "bacter", "species", "pseudobacteremia.", "*", "Correspondence:", "chosunns@hanmail.net", "†", "Contributed", "equally", "3Department", "of", "Neurosurgery,", "Chosun", "University,", "School", "of", "Medicine", "Gwangju", "City,", "Republic", "of", "Korea", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "Case", "presentation", "Case", "1", "A", "54-year-old", "female", "patient", "presented", "with", "myalgia", "and", "febrile", "sensation", "to", "outpatient", "Division", "of", "Gastroenterol-", "ogy", "and", "Hepatology", "in", "Chosun", "University", "Hospital.", "She", "had", "a", "history", "of", "liver", "cirrhosis", "due", "to", "hepatitis", "B", "virus,", "and", "had", "gone", "surgery", "because", "of", "a", "pituitary", "adenoma", "1", "year", "ago.", "The", "patient", "did", "not", "have", "any", "limitations", "of", "daily", "living", "without", "major", "health", "issues", "after", "the", "surgery.", "Her", "physical", "examination", "revealed", "newly", "formed", "painful", "grouped", "vesicles", "on", "the", "trunk.", "Blood", "culture", "resulted", "in", "the", "growth", "of", "Enterobacter", "amnigenus.", "The", "vital", "signs", "and", "laboratory", "data", "did", "not", "correlate", "with", "the", "finding", "of", "the", "bacteremia.", "Antiviral", "agent", "for", "the", "herpes", "zoster", "was", "used", "with", "improvement", "in", "pain", "and", "crust", "formation", "of", "the", "vesicles.", "The", "patient", "was", "treated", "with", "ciprofloxacin", "according", "to", "the", "culture", "results.", "The", "follow", "up", "blood", "culture", "revealed", "no", "sign", "of", "any", "growth", "of", "bacteria.", "The", "patient", "was", "discharged", "on", "the", "10th", "hospital", "day", "without", "any", "complications.", "©", "2010", "Kim", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Int.", "J.", "Mol.", "Sci.", "2010,", "11,", "354-369;", "doi:10.3390/ijms11010354", "OPEN", "ACCESS", "International", "Journal", "of", "Molecular", "Sciences", "ISSN", "1422-0067", "www.mdpi.com/journal/ijms", "Review", "Surface", "Modification", "of", "Biomedical", "and", "Dental", "Implants", "and", "the", "Processes", "of", "Inflammation,", "Wound", "Healing", "and", "Bone", "Formation", "Clark", "M.", "Stanford", "Dows", "Institute", "for", "Dental", "Research,", "College", "of", "Dentistry,", "University", "of", "Iowa,", "IA", "52242,", "USA;", "E-Mail:", "Clark-Stanford@uiowa.edu;", "Tel.:", "+1-319-335-7381;", "Fax:", "+1-319-335-8895", "Received:", "24", "December", "2009;", "in", "revised", "form:", "18", "January", "2010", "/", "Accepted:", "20", "January", "2010", "/", "Published:", "25", "January", "2010", "Abstract:", "Bone", "adaptation", "or", "integration", "of", "an", "implant", "is", "characterized", "by", "a", "series", "of", "biological", "reactions", "that", "start", "with", "bone", "turnover", "at", "the", "interface", "(a", "process", "of", "localized", "necrosis),", "followed", "by", "rapid", "repair.", "The", "wound", "healing", "response", "is", "guided", "by", "a", "complex", "activation", "of", "macrophages", "leading", "to", "tissue", "turnover", "and", "new", "osteoblast", "differentiation", "on", "the", "implant", "surface.", "The", "complex", "role", "of", "implant", "surface", "topography", "and", "impact", "on", "healing", "response", "plays", "a", "role", "in", "biological", "criteria", "that", "can", "guide", "the", "design", "and", "development", "of", "future", "tissue-implant", "surface", "interfaces.", "Keywords:", "implant;", "surfaces;", "wound", "healing;", "macrophage", "1.", "Introduction", "Endosseous", "dental", "implants", "have", "created", "a", "revolution", "in", "the", "routine", "approach", "to", "dental", "care", "for", "patients", "missing", "one", "or", "more", "teeth.", "The", "clinical", "success", "for", "this", "procedure", "occurs", "through", "a", "series", "of", "clinical", "and", "biological", "steps", "starting", "with", "initial", "primary", "stability", "provided", "by", "the", "amount,", "quality", "and", "distribution", "of", "bone", "within", "the", "proposed", "implant", "site", "[1].", "Following", "placement", "of", "the", "dental", "implant", "a", "series", "of", "bone", "modeling", "and", "remodeling", "steps", "take", "place.", "Bone", "adaptation", "or", "integration", "of", "an", "implant", "is", "characterized", "by", "a", "series", "of", "biological", "reactions", "that", "start", "with", "bone", "turnover", "at", "the", "interface", "(a", "process", "of", "localized", "necrosis),", "followed", "by", "rapid", "repair", "[2].", "The", "common", "clinical", "end", "point", "of", "this", "process", "is", "measured", "by", "a", "lack", "of", "signs", "and", "symptoms", "of", "aggressive", "chronic", "inflammation,", "a", "lack", "of", "mobility", "and", "a", "radiographic", "assessment", "of", "bone", "adapted", "to", "the", "interface", "[3,4].", "While", "high", "success", "rates", "hold", "for", "certain", "anatomic", "regions,", "the", "bony", "response", "within", "the", "thin", "cortical", "plates", "and", "diminished" ]

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[ "Arrest", "of", "Nuclear", "Division", "in", "Plasmodium", "through", "Blockage", "of", "Erythrocyte", "Surface", "Exposed", "Ribosomal", "Protein", "P2", "Sudipta", "Das1,", "Himanish", "Basu1,", "Reshma", "Korde1,", "Rita", "Tewari2,", "Shobhona", "Sharma", "1", "*", "1", "Department", "of", "Biological", "Sciences,", "Tata", "Institute", "of", "Fundamental", "Research,", "Mumbai,", "India,", "2", "Centre", "for", "Genetics", "and", "Genomics,", "Queen’s", "Medical", "Centre,", "The", "University", "of", "Nottingham,", "Nottingham,", "United", "Kingdom", "Abstract", "Malaria", "parasites", "reside", "inside", "erythrocytes", "and", "the", "disease", "manifestations", "are", "linked", "to", "the", "growth", "inside", "infected", "erythrocytes", "(IE).", "The", "growth", "of", "the", "parasite", "is", "mostly", "confined", "to", "the", "trophozoite", "stage", "during", "which", "nuclear", "division", "occurs", "followed", "by", "the", "formation", "of", "cell", "bodies", "(schizogony).", "The", "mechanism", "and", "regulation", "of", "schizogony", "are", "poorly", "understood.", "Here", "we", "show", "a", "novel", "role", "for", "a", "Plasmodium", "falciparum", "60S", "stalk", "ribosomal", "acidic", "protein", "P2", "(PfP2)", "(PFC0400w),", "which", "gets", "exported", "to", "the", "IE", "surface", "for", "6–8", "hrs", "during", "early", "schizogony,", "starting", "around", "26–28", "hrs", "post-", "merozoite", "invasion.", "The", "surface", "exposure", "is", "demonstrated", "using", "multiple", "PfP2-specific", "monoclonal", "antibodies,", "and", "is", "confirmed", "through", "transfection", "using", "PfP2-GFP.", "The", "IE", "surface-exposed", "PfP2-protein", "occurs", "mainly", "as", "SDS-resistant", "P2-", "homo-tetramers.", "Treatment", "with", "anti-PfP2", "monoclonals", "causes", "arrest", "of", "IEs", "at", "the", "first", "nuclear", "division.", "Upon", "removal", "of", "the", "antibodies,", "about", "80–85%", "of", "synchronized", "parasites", "can", "be", "released", "even", "after", "24", "hrs", "of", "antibody", "treatment.", "It", "has", "been", "reported", "that", "a", "tubovesicular", "network", "(TVN)", "is", "set", "up", "in", "early", "trophozoites", "which", "is", "used", "for", "nutrient", "import.", "Anti-P2", "monoclonal", "antibodies", "cause", "a", "complete", "fragmentation", "of", "TVN", "by", "36", "hrs,", "and", "impairs", "lipid", "import", "in", "IEs.", "These", "may", "be", "downstream", "causes", "for", "the", "cell-cycle", "arrest.", "Upon", "antibody", "removal,", "the", "TVN", "is", "reconstituted,", "and", "the", "cell", "division", "progresses.", "Each", "of", "the", "above", "properties", "is", "observed", "in", "the", "rodent", "malaria", "parasite", "species", "P.", "yoelii", "and", "P.", "berghei.", "The", "translocation", "of", "the", "P2", "protein", "to", "the", "IE", "surface", "is", "therefore", "likely", "to", "be", "of", "fundamental", "importance", "in", "Plasmodium", "cell", "division.", "Citation:", "Das", "S,", "Basu", "H,", "Korde", "R,", "Tewari", "R,", "Sharma", "S", "(2012)", "Arrest", "of", "Nuclear", "Division", "in", "Plasmodium", "through", "Blockage", "of", "Erythrocyte", "Surface", "Exposed", "Ribosomal", "Protein", "P2.", "PLoS", "Pathog", "8(8):", "e1002858.", "doi:10.1371/journal.ppat.1002858", "Editor:", "Joe", "Smith,", "Seattle", "Biomedical", "Research", "Institute,", "United", "States", "of", "America", "Received", "February", "14,", "2012;", "Accepted", "June", "27,", "2012;", "Published", "August", "9,", "2012", "Copyright:", "2012", "Das", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "This", "work", "was", "supported", "by", "an", "intramural", "grant", "from", "Tata", "Institute", "of", "Fundamental", "Research,", "India", "and", "grant", "of", "MRC", "Investigator", "Award,", "United", "Kingdom.", "The", "funders", "had", "no", "role", "in", "study", "design,", "data", "collection", "and", "analysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "Competing", "Interests:", "I", "have", "read", "the", "journal’s", "policy", "and", "have", "the", "following", "conflicts:", "This", "work", "was", "filed", "for", "Indian", "Patent", "on", "17/06/11", "and", "the", "patent", "number", "is", "1773/MUM/2011.", "This", "does", "not", "alter", "our", "adherence", "to", "all", "PLoS", "Pathogens", "policies", "on", "sharing", "data", "and", "materials.", "*", "E-mail:", "sharma@tifr.res.in", "Introduction", "Malaria,", "caused", "by", "the", "species", "Plasmodium,", "is", "a", "prevalent", "tropical", "infectious", "disease,", "which", "continues", "to", "take", "a", "large", "toll", "on", "lives", "(WHO", "guidelines,", "2008).", "The", "malarial", "pathology", "is", "largely", "caused", "by", "the", "cyclic", "growth", "of", "the", "parasite", "within", "the", "infected", "erythrocytes", "(IE).", "Very", "little", "is", "known", "about", "molecular", "mechanisms", "of", "replication", "of", "Plasmodium", "in", "the", "erythrocytes.", "Cell", "division", "in", "Plasmodium", "occurs", "largely", "through", "a", "schizogonic", "process,", "in", "which", "the", "nuclei", "divide", "asynchronously", "at", "first", "into", "about", "16–24", "nuclei,", "followed", "by", "the", "formation", "of", "cell", "bodies", "[1–5].", "Unlike", "classical", "eukaryotic", "cell", "division,", "the", "nuclear", "cell", "membrane", "appears", "to", "remain", "intact", "during", "such", "divisions.", "Similar", "nuclear", "division", "without", "cytokinesis", "occurs", "in", "Drosophila", "embryonic", "syncytial", "divisions", "[6,7].", "It", "is", 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"into", "G0", "phase", "or", "into", "a", "post-mitotic,", "possibly", "more", "differentiated", "state.", "The", "eukaryotic", "cells", "also", "undergo", "internal", "checkpoint", "controls", "[13–16].", "During", "a", "check-", "point,", "the", "cell", "ascertains", "that", "its", "metabolic", "household", "is", "in", "order,", "that", "its", "genome", "is", "intact,", "and", "that", "previous", "steps", "in", "its", "cell", "cycle", "have", "been", "executed", "properly", "before", "it", "moves", "ahead.", "Molecular", "players", "in", "both", "these", "steps", "have", "been", "worked", "out", "to", "great", "details", "in", "animal", "cells", "[17–20].", "Virtually", "nothing", "is", "known", "about", "the", "start", "of", "the", "nuclear", "division", "in", "Plasmodium,", "or", "check-point", "controls", "in", "schizogony.", "PLoS", "Pathogens", "|", "www.plospathogens.org", "1", "August", "2012", "|", "Volume", "8", "|", "Issue", "8", "|", "e1002858" ]

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[ "e", "n", "i", "c", "i", "d", "e", "M", "l", "a", "t", "n", "e", "m", "i", "r", "e", "p", "x", "E", "f", "o", "l", "a", "n", "r", "u", "o", "J", "e", "h", "T", "CORRESPONDENCE", "Harald", "von", "Boehmer:", "harald_von_boehmer@", "dfci.harvard.edu", "Abbreviations", "used:", "array", "CGH,", "array-based", "comparative", "ge-", "nomic", "hybridization;", "BMT,", "BM", "transfer;", "DAPK,", "death-", "associated", "protein", "kinase;", "DNMAML1,", "dominant-nega-", "tive", "mastermind-like", "1;", "ICN,", "intracellular", "Notch;", "SKY,", "spec-", "tral", "karyotype;", "T-ALL,", "T", "cell", "acute", "lymphoblastic", "leukemia.", "The", "Rockefeller", "University", "Press", "$30.00", "J.", "Exp.", "Med.", "Vol.", "205", "No.", "12", "2851-2861", "www.jem.org/cgi/doi/10.1084/jem.20081561", "A", "RT", "I", "C", "L", "E", "Oncogenesis", "of", "T-ALL", "and", "nonmalignant", "consequences", "of", "overexpressing", "intracellular", "NOTCH1", "Xiaoyu", "Li,1", "Fotini", "Gounari,1,2", "Alexei", "Protopopov,1", "Khashayarsha", "Khazaie,1,3", "and", "Harald", "von", "Boehmer1", "1Dana-Farber", "Cancer", "Institute,", "Harvard", "Medical", "School,", "Boston,", "MA", "02115", "2Department", "of", "Medicine,", "University", "of", "Chicago,", "Chicago,", "IL", "60637", "3Department", "of", "Microbiology-Immunology,", "Northwestern", "University,", "Chicago,", "IL", "60611", "Mutations", "resulting", "in", "overexpression", "of", "intracellular", "Notch1", "(ICN1)", "are", "frequently", "ob-", "served", "in", "human", "T", "cell", "acute", "lymphoblastic", "leukemia", "(T-ALL).", "We", "have", "determined", "the", "consequences", "of", "ICN1", "overexpression", "from", "retroviral", "vectors", "introduced", "into", "bone", "marrow", "cells.", "Early", "consequences", "are", "the", "generation", "of", "polyclonal", "nontumorigenic", "CD4+8+", "T", "cell", "receptor", "(TCR)-", "+", "cells", "that", "do", "not", "qualify", "as", "tumor", "precursors", "despite", "the", "observation", "that", "they", "overexpress", "Notch", "1", "and", "c-Myc", "and", "degrade", "the", "tumor", "suppressor", "E2A", "by", "post-", "translational", "modification.", "The", "first", "tumorigenic", "cells", "are", "detected", "among", "more", "immature", "CD4", "8+TCR-", "cells", "that", "give", "rise", "to", "monoclonal", "tumors", "with", "a", "single,", "unique", "TCR-", "chain", "and", "diverse", "TCR-", "chains,", "pinpointing", "malignant", "transformation", "to", "a", "stage", "after", "pre-", "TCR", "signaling", "and", "before", "completion", "of", "TCR-", "rearrangement.", "In", "T-ALL,", "E2A", "deficiency", "is", "accompanied", "by", "further", "transcriptional", "up-regulation", "of", "c-Myc", "and", "concomitant", "dysregu-", "lation", "of", "the", "c-Myc-p53", "axis", "at", "the", "transcriptional", "level.", "Even", "though", "the", "tumors", "consist", "of", "phenotypically", "heterogeneous", "cells,", "no", "evidence", "for", "tumor", "stem", "cells", "was", "found.", "As", "judged", "by", "array-based", "comparative", "genomic", "hybridization", "(array", "CGH)", "and", "spectral", "karyo-", "type", "(SKY)", "analysis,", "none", "of", "the", "tumors", "arise", "because", "of", "genomic", "instability.", "Notch", "receptors", "play", "an", "important", "role", "in", "cell", "growth", "and", "differentiation.", "When", "binding", "to", "their", "ligands,", "these", "transmembrane", "receptors", "un-", "dergo", "a", "series", "of", "proteolytic", "cleavages", "that", "result", "in", "the", "generation", "of", "intracellular", "Notch", "(ICN),", "which", "regulates", "transcription", "in", "a", "transcriptional", "complex", "with", "several", "other", "proteins", "after", "nu-", "clear", "translocation", "(1).", "Mutations", "that", "result", "in", "overexpression", "of", "ICN1", "can", "be", "found", "in", "more", "than", "half", "of", "human", "T", "cell", "acute", "lymphoblastic", "lymphoma", "(T-ALL)", "samples", "(2–4).", "These", "find-", "ings", "have", "sparked", "renewed", "interest", "in", "ICN1-", "initiated", "lymphomagenesis.", "Recent", "results", "have", "indicated", "that", "c-Myc", "is", "a", "target", "of", "ICN1", "and", "contributes", "in", "a", "major", "way", "to", "the", "growth", "of", "Notch-dependent", "T-ALL", "cell", "lines", "(5,", "6).", "However,", "overexpression", "of", "c-Myc", "by", "itself", "is", "insufficient", "to", "cause", "T-ALL,", "and", "additional", "events", "are", "required", "to", "initiate", "clonal", "growth", "of", "tumor", "cells", "(7,", "8).", "Girard", "et", "al.", "observed", "that", "frequent", "proviral", "insertions", "into", "the", "Notch1", "locus", "en-", "hanced", "T-ALL", "in", "c-Myc", "transgenic", "mice,", "sug-", "The", "online", "version", "of", "this", "article", "contains", "supplemental", "material.", "gesting", "a", "collaboration", "of", "c-Myc", "and", "Notch1", "in", "oncogenesis", "that", "may", "result", "from", "the", "obser-", "vation", "that", "ICN1", "and", "c-Myc", "target", "overlap-", "ping", "genes", "(5),", "or", "that", "ICN1", "targets", "distinct", "genes", "that", "facilitate", "c-Myc–dependent", "onco-", "genesis.", "One", "of", "the", "genes", "that", "is", "affected", "by", "Notch1", "is", "the", "tumor", "suppressor", "E2A,", "which", "has", "an", "important", "role", "in", "the", "differentiation", "of", "T", "and", "B", "lymphocytes", "(9).", "Crucial", "events", "that", "eventually", "lead", "to", "ma-", "lignant", "transformation", "are", "difficult", "to", "study", "ret-", "rospectively", "in", "cell", "lines", "with", "unknown", "etiology", "that", "may", "have", "accumulated", "additional", "muta-", "tions", "permitting", "growth", "in", "vitro.", "Therefore,", "we", "have", "systematically", "studied", "the", "consequences", "of", "overexpression", "of", "intracellular", "Notch", "1", "intro-", "duced", "into", "BM", "cells", "by", "retroviral", "vectors", "(10).", "The", "results", "identify", "a", "series", "of", "cellular", "and", "mo-", "lecular", "changes", "that", "accompany", "the", "generation", "©", "2008", "Li", "et", "al.", "This", "article", "is", "distributed", "under", "the", "terms", "of", "an", "Attribution–Non-", "commercial–Share", "Alike–No", "Mirror", "Sites", "license", "for", "the", "first", "six", "months", "after", "the", "publication", "date", "(see", "http://www.jem.org/misc/terms.shtml).", "After", "six", "months", "it", "is", "available", "under", "a", "Creative", "Commons", "License", "(Attribution–Noncommercial–Share", "Alike", "3.0", "Unported", "license,", "as", "described", "at", "http://creativecommons.org/licenses/", "by-nc-sa/3.0/).", "2851" ]

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[ "RESEARCH", "Multijurisdictional", "Approach", "to", "Biosur", "veillance,", "Kansas", "City", "Mark", "A.", "Hoffman,*", "Tiffany", "H.", "Wilkinson,†", "Aaron", "Bush,*", "Wayne", "Myers,*", "Ron", "G.", "Griffin,†", "Gerald", "L.", "Hoff,†", "and", "Rex", "Archer†", "An", "electronic", "reporting", "system", "for", "a", "network", "of", "22", "lab-", "oratories", "was", "implemented", "in", "Kansas", "City,", "Missouri,", "with", "an", "independent", "organization", "acting", "as", "a", "data", "clearing-", "house", "between", "the", "reporting", "laboratories", "and", "public", "health", "departments.", "The", "system", "ran", "in", "tandem", "with", "conventional", "reporting", "methods.", "Laboratory", "test", "orders", "and", "results", "were", "aggregated", "and", "mapped", "to", "a", "common", "nomenclature.", "Reports", "were", "delivered", "through", "a", "secure", "Internet", "connec-", "tion", "to", "the", "Kansas", "City", "Health", "Department", "(KCHD);", "during", "the", "first", "200", "days", "of", "operation,", "359", "qualified", "results", "were", "delivered", "electronically", "to", "KCHD.", "Data", "were", "received", "more", "quickly", "than", "they", "were", "with", "conventional", "reporting", "meth-", "ods:", "notification", "of", "chlamydia", "cases", "arrived", "2", "days", "earlier,", "invasive", "group", "A", "streptococcal", "disease", "cases", "arrived", "2.3", "days", "sooner,", "and", "salmonellosis", "cases", "arrived", "2.7", "days", "sooner.", "Data", "were", "more", "complete", "for", "all", "demographic", "fields,", "including", "address,", "age,", "sex,", "race,", "and", "date", "of", "birth.", "Two", "hundred", "fourteen", "cases", "reported", "electronically", "were", "not", "received", "by", "conventional", "means.", "Bmation", "sources", "of", "potential", "value", "in", "detecting", "an", "iosurveillance", "is", "the", "automated", "monitoring", "of", "infor-", "emerging", "epidemic,", "whether", "naturally", "occurring", "or", "the", "result", "of", "bioterrorism.", "Information", "sources", "that", "can", "be", "monitored", "for", "early", "warning", "include", "purchases", "of", "nonpre-", "scription", "medication", "(1)", "and", "symptoms", "reported", "during", "ambulatory", "care", "(2).", "Although", "these", "sources", "offer", "opportu-", "nities", "for", "early", "detection,", "they", "may", "also", "lead", "to", "high", "rates", "of", "false-positive", "reactions.", "A", "more", "definitive", "tool", "for", "bio-", "surveillance", "is", "the", "electronic", "reporting", "of", "diagnostic", "results", "confirming", "the", "presence", "of", "a", "pathogen.", "Heightened", "concerns", "about", "bioterrorism", "have", "led", "pub-", "lic", "health", "organizations", "to", "reevaluate", "methods", "used", "to", "report", "diseases.", "Currently,", "most", "healthcare", "providers", "noti-", "fy", "public", "health", "organizations", "of", "reportable", "diseases", "by", "telephone,", "fax,", "or", "mail", "(3).", "These", "techniques", "generally", "delay", "the", "communication", "of", "confirmatory", "test", "results", "and", "notification", "of", "the", "appropriate", "public", "health", "organization", "*Cerner", "Corporation,", "Kansas", "City,", "Missouri,", "USA;", "and", "†Kansas", "City", "Health", "Department,", "Kansas", "City,", "Missouri,", "USA", "(4).", "Underreporting", "is", "a", "major", "concern", "with", "traditional", "dis-", "ease", "surveillance", "strategies", "(5);", "even", "cases", "of", "severe", "dis-", "eases", "sometimes", "go", "unreported", "(6).", "In", "addition,", "substantial", "variability", "exists", "in", "the", "completeness", "of", "the", "information", "sent", "to", "public", "health;", "initial", "reports", "often", "include", "only", "the", "test", "result", "and", "the", "patient", "name.", "They", "lack", "demographic", "details", "that", "are", "useful", "to", "public", "health", "officials,", "requiring", "them", "to", "perform", "followup", "calls", "to", "get", "the", "additional", "infor-", "mation", "(7).", "These", "delays", "and", "inconsistencies", "may", "impair", "the", "ability", "of", "public", "health", "officials", "to", "detect", "or", "respond", "to", "a", "bioterrorist", "event.", "One", "solution", "to", "these", "deficiencies", "is", "to", "use", "an", "electronic", "system", "to", "report", "disease", "to", "public", "health", "authorities.", "Three", "approaches", "to", "electronic", "disease", "reporting", "are", "feasible.", "The", "first", "approach", "(Figure", "1A)", "requires", "each", "healthcare", "provider", "to", "standardize", "clinical", "results", "(i.e.,", "by", "using", "the", "Systematized", "Nomenclature", "of", "Medicine", "[SNOMED])", "before", "sending", "results", "electronically", "to", "the", "appropriate", "authority.", "Researchers", "in", "Pittsburgh,", "working", "in", "an", "integrated", "delivery", "network", "that", "used", "a", "single", "data", "dictionary", "to", "minimize", "the", "difficulty", "of", "reconciling", "dis-", "parate", "coding", "systems,", "found", "this", "approach", "effective", "for", "electronic", "disease", "reporting", "(8).", "However,", "developing", "this", "type", "of", "system", "can", "be", "challenging", "because", "of", "the", "difficul-", "ty", "in", "updating", "multiple", "data", "dictionaries", "(translation", "tables", "that", "associate", "terms", "from", "multiple", "organizations).", "The", "sec-", "ond", "approach", "(Figure", "1B)", "requires", "the", "use", "of", "result", "stan-", "dardization", "software", "(which", "collects", "data", "from", "multiple", "sites", "and", "attempts", "to", "automatically", "associate", "terms", "to", "stan-", "dard", "terms)", "at", "public", "health", "facilities.", "This", "approach", "places", "the", "responsibility", "for", "technology", "and", "personnel", "with", "the", "public", "health", "organizations.", "The", "third", "approach", "to", "elec-", "tronic", "reporting", "(Figure", "1C)", "involves", "an", "intermediary", "organization", "that", "aggregates", "the", "data", "and", "distributes", "stan-", "dardized", "reports", "to", "public", "health", "organizations.", "Single", "jurisdiction", "systems", "using", "this", "approach", "have", "been", "devel-", "oped", "in", "Hawaii", "and", "Indianapolis", "(9,10).", "We", "developed", "a", "multiple-jurisdiction", "data", "clearinghouse", "system", "(11)", "and", "assessed", "the", "benefits", "of", "the", "system", "in", "terms", "of", "timeliness,", "data", "completeness,", "and", "geographic", "depth", "of", "coverage.", "Emerging", "Infectious", "Diseases", "•", "Vol.", "9,", "No.", "10,", "October", "2003", "1281" ]

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