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[ "4686–4703", "Nucleic", "Acids", "Research,", "2007,", "Vol.", "35,", "No.", "14", "doi:10.1093/nar/gkm441", "Published", "online", "29", "June", "2007", "Reconstructing", "the", "evolution", "of", "the", "mitochondrial", "ribosomal", "proteome", "Paulien", "Smits1,", "Jan", "A.", "M.", "Smeitink", "1", ",", "Lambert", "P.", "van", "den", "Heuvel1,", "Martijn", "A.", "Huynen2", "and", "Thijs", "J.", "G.", "Ettema2,*", "1Nijmegen", "Center", "for", "Mitochondrial", "Disorders,", "Nijmegen", "Center", "for", "Molecular", "Life", "Sciences,", "Radboud", "University", "Nijmegen", "Medical", "Center,", "Geert–Grooteplein-Zuid", "10", "and", "2Center", "for", "Molecular", "and", "Biomolecular", "Informatics,", "Nijmegen", "Center", "for", "Molecular", "Life", "Sciences,", "Radboud", "University", "Nijmegen", "Medical", "Center,", "Geert-Grooteplein", "28,", "6525", "GA", "Nijmegen,", "The", "Netherlands", "Received", "March", "20,", "2007;", "Revised", "May", "16,", "2007;", "Accepted", "May", "17,", "2007", "ABSTRACT", "For", "production", "of", "proteins", "that", "are", "encoded", "by", "the", "mitochondrial", "genome,", "mitochondria", "rely", "on", "their", "own", "mitochondrial", "translation", "system,", "with", "the", "mitoribosome", "as", "its", "central", "component.", "Using", "extensive", "homology", "searches,", "we", "have", "reconstructed", "the", "evolutionary", "history", "of", "the", "mitoribosomal", "proteome", "that", "is", "encoded", "by", "a", "diverse", "subset", "of", "eukaryotic", "genomes,", "revealing", "an", "ancestral", "ribosome", "of", "alpha-proteobacterial", "descent", "that", "more", "than", "doubled", "its", "protein", "content", "in", "most", "eukaryotic", "lineages.", "We", "observe", "large", "variations", "in", "the", "protein", "content", "of", "mitoribosomes", "between", "different", "eukaryotes,", "with", "mammalian", "mitoribosomes", "sharing", "only", "74", "and", "43%", "of", "its", "proteins", "with", "yeast", "and", "Leishmania", "mitoribosomes,", "respectively.", "We", "detected", "many", "previously", "unidentified", "mitochondrial", "ribosomal", "proteins", "(MRPs)", "and", "found", "that", "several", "have", "increased", "in", "size", "compared", "to", "their", "bacterial", "ancestral", "counterparts", "by", "addition", "of", "functional", "domains.", "Several", "new", "MRPs", "have", "originated", "via", "duplication", "of", "existing", "MRPs", "as", "well", "as", "by", "recruitment", "from", "outside", "of", "the", "mitoribosomal", "proteome.", "Using", "sensitive", "profile–profile", "homology", "searches,", "we", "found", "hitherto", "undetected", "homology", "between", "bacterial", "and", "eukaryotic", "ribosomal", "proteins,", "as", "well", "as", "between", "fungal", "and", "mammalian", "ribosomal", "proteins,", "detecting", "two", "novel", "human", "MRPs.", "These", "newly", "detected", "MRPs", "constitute,", "along", "with", "evolu-", "tionary", "conserved", "MRPs,", "excellent", "new", "screening", "targets", "for", "human", "patients", "with", "unresolved", "mitochondrial", "oxidative", "phosphorylation", "disorders.", "INTRODUCTION", "Mitochondria", "are", "primary", "ATP-producing", "organelles", "which", "originated", "from", "an", "ancestral", "alpha-proteobacterial", "endosymbiont", "(1,2).", "The", "oxidative", "phosphorylation", "(OXPHOS)", "pathway,", "consisting", "of", "the", "mitochondrial", "respiratory", "chain", "and", "the", "ATP", "synthase", "complex,", "is", "the", "final", "biochemical", "pathway", "in", "energy", "conversion", "(3).", "However,", "mitochondria", "have", "been", "found", "to", "perform", "pivotal", "roles", "in", "many", "other", "metabolic,", "regulatory", "and", "developmental", "processes.", "During", "the", "evolution", "of", "the", "mitochondria,", "most", "genes", "of", "the", "ancestral", "endosymbiont", "have", "been", "transferred", "from", "the", "mitochondrial", "to", "the", "nuclear", "genome.", "The", "genes", "that", "reside", "on", "the", "mitochondrial", "DNA", "(mtDNA),", "e.g.", "13", "OXPHOS-related", "genes", "in", "human,", "are", "translated", "into", "their", "respective", "protein", "products", "by", "the", "mitochondrial", "translation", "machin-", "ery,", "which", "resembles", "the", "prokaryotic", "translation", "system", "(4),", "comprising", "a", "mitochondrial", "ribosome", "(mito-", "ribosome)", "and", "several", "translation", "factors.", "In", "mammals,", "all", "proteins", "that", "constitute", "the", "mitochondrial", "translation", "machinery", "are", "encoded", "by", "the", "nuclear", "genome.", "Also", "the", "mitochondrial", "genomes", "of", "fungi", "generally", "encode", "only", "very", "few", "mitochondrial", "ribosomal", "proteins", "(MRPs).", "In", "contrast,", "the", "mitochondrial", "genome", "of", "many", "protozoa", "and", "plants", "encode", "numerous", "MRPs.", "Most", "notably,", "the", "‘primitive’", "mitochondrial", "genome", "of", "the", "freshwater", "protist", "Reclinomonas", "americana", "was", "found", "to", "contain", "as", "many", "as", "27", "MRP-encoding", "genes", "(5).", "Mitoribosomes", "have", "undergone", "major", "remodeling", "during", "their", "evolution.", "For", "instance,", "it", "has", "been", "found", "that,", "despite", "the", "fact", "that", "their", "rRNA", "content", "is", "only", "half", "the", "content", "of", "bacterial", "ribosomes", "(6),", "mitoribosomes", "generally", "exceed", "the", "bacterial", "ribosomes", "both", "in", "molecular", "mass", "as", "well", "as", "in", "physical", "dimensions", "(6–8).", "Mass", "spectrometry", "studies", "of", "the", "bovine", "and", "yeast", "*To", "whom", "correspondence", "should", "be", "addressed.", "Email:", "thijs.ettema@ebc.uu.se", "Present", "address:", "Thijs", "J.", "G.", "Ettema,", "Department", "of", "Molecular", "Evolution,", "Evolutionary", "Biology", "Centre,", "Uppsala", "University,", "Norbyva¨", "gen", "18C,", "752", "36", "Uppsala,", "Sweden.", "2007", "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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[ "ABSTRACT", "Complications", "produced", "by", "the", "sectioning", "of", "a", "nonvisu-", "alized", "duct", "of", "Luschka", "are", "uncommon", "during", "laparo-", "scopic", "cholecystectomy.", "From", "1999", "through", "2003,", "we", "performed", "1351", "laparoscopic", "cholecystectomies", "in", "our", "department", "and", "observed", "2", "cases", "(0.15%)", "of", "bile", "leakage", "due", "to", "duct", "of", "Luschka", "injury.", "Injury", "during", "laparoscopic", "cholecystectomy", "is", "usually", "produced", "by", "an", "excessively", "deep", "plane", "of", "dissection", "and", "by", "the", "anatomical", "localiza-", "tion", "of", "this", "accessory", "duct.", "Clinical", "symptoms", "are", "scarce", "after", "duct", "of", "Luschka", "injury.", "Numerous", "diagnostic", "meth-", "ods", "have", "been", "used", "to", "detect", "these", "injuries.", "Nevertheless,", "careful", "clinical", "examination", "is", "still", "of", "the", "utmost", "impor-", "tance.", "Noninvasive", "treatments", "are", "usually", "effective.", "In", "patients", "who", "present", "with", "acute", "abdomen,", "as", "in", "our", "cases,", "or", "who", "are", "not", "cured", "by", "noninvasive", "treatments,", "exploratory", "lap-", "arotomy", "is", "the", "best", "approach.", "The", "surgical", "treatment", "con-", "sists", "of", "a", "lavage", "of", "the", "abdominal", "cavity,", "closure", "of", "the", "duct", "of", "Luschka,", "and", "intraoperative", "cholangiography", "to", "confirm", "that", "the", "biliary", "tree", "is", "intact.", "Key", "Words:", "Luchska,", "Laparoscopy,", "Cholecystectomy,", "Re-", "view.", "Liver", "Transplantation", "and", "Hepatobiliary", "Unit,", "Department", "of", "Surgery,", "Hospital", "Universitario", "Virgen", "de", "las", "Nieves,", "Granada,", "Spain", "(all", "authors).", "Address", "reprint", "requests", "to:", "J.", "M.", "Ramia,", "PhD,", "C/Buensuceso", "6,", "4D,", "18002", "Granada,", "Spain.", "Telephone:", "0034958536859,", "E-mail:", "jose_ramia@hotmail.com", "©", "2005", "by", "JSLS,", "Journal", "of", "the", "Society", "of", "Laparoendoscopic", "Surgeons.", "Published", "by", "the", "Society", "of", "Laparoendoscopic", "Surgeons,", "Inc.", "216", "JSLS", "(2005)9:216", "–217", "CASE", "REPORT", "Postlaparoscopic", "Cholecystectomy", "Bile", "Leak", "Secondary", "to", "an", "Accessory", "Duct", "of", "Luschka", "J.", "M.", "Ramia,", "PhD,", "K.", "Muffak,", "MD,", "A.", "Mansilla,", "PhD,", "J.", "Villar,", "PhD,", "D.", "Garrote,", "PhD,", "J.", "A.", "Ferron,", "PhD", "INTRODUCTION", "The", "gold", "standard", "treatment", "for", "cholelithiasis", "is", "cur-", "rently", "laparoscopic", "cholecystectomy", "(LC).", "During", "the", "learning", "curve", "phase,", "LC", "bile", "duct", "injuries", "appear", "to", "be", "more", "numerous", "and", "severe", "than", "those", "caused", "by", "open", "cholecystectomy.1", "Currently,", "the", "biliary", "complication", "rate", "of", "these", "2", "procedures", "is", "similar.2,3", "Complication", "produced", "by", "the", "sectioning", "of", "a", "nonvisualized", "duct", "of", "Luschka", "are", "uncommon", "during", "LC,", "although", "the", "true", "incidence", "is", "unknown,", "especially", "because", "published", "studies", "focus", "on", "so-called", "major", "biliary", "lesions.1,3,4", "From", "1999", "through", "2003,", "we", "performed", "1351", "LCs", "in", "our", "department", "and", "observed", "2", "cases", "(0.15%)", "of", "bile", "leak-", "age", "due", "to", "duct", "of", "Luschka", "injury.", "We", "present", "these", "2", "cases", "and", "discuss", "the", "appropriate", "diagnostic", "and", "ther-", "apeutic", "approach.", "CASE", "1", "A", "51-year-old", "man", "was", "referred", "to", "our", "department", "for", "repeated", "colic", "abdominal", "pain", "in", "the", "right", "hypochon-", "drium.", "He", "had", "a", "history", "of", "hepatic", "and", "renal", "polycystosis", "that", "produced", "severe", "chronic", "renal", "insufficiency.", "He", "un-", "derwent", "a", "surgical", "laparoscopy", "that", "revealed", "multiple", "cysts", "of", "various", "sizes", "on", "both", "lobes", "of", "the", "liver.", "Laparo-", "scopic", "defenestration", "of", "the", "dominant", "hepatic", "cysts", "and", "laparoscopic", "cholecystectomy", "were", "performed.", "In", "the", "postoperative", "period,", "the", "patient", "was", "afebrile", "and", "expe-", "rienced", "diffuse", "moderate", "pain", "of", "the", "whole", "abdomen,", "with", "no", "other", "symptoms.", "Two", "abdominal", "ultrasound", "scans", "showed", "a", "small", "amount", "of", "liquid", "in", "the", "abdominal", "cavity;", "the", "blood", "analysis", "results", "were", "normal.", "The", "liquid", "was", "assumed", "to", "derive", "from", "the", "fenestrated", "cysts.", "On", "the", "sixth", "postoperative", "day,", "the", "patient", "reported", "the", "abrupt", "onset", "of", "intense", "abdominal", "pain,", "and", "a", "new", "ultrasound", "scan", "showed", "an", "increase", "in", "the", "abdominal", "liquid.", "An", "exploratory", "laparotomy", "revealed", "biliary", "peritonitis", "due", "to", "bile", "leakage", "from", "the", "duct", "of", "Luschka", "in", "the", "liver", "bed.", "An", "intraoperative", "cholangiography", "confirmed", "that", "the", "biliary", "tree", "was", "intact.", "The", "duct", "of", "Luchska", "was", "then", "closed,", "with", "thorough", "lavage", "of", "the", "abdominal", "cavity.", "The", "second", "postoperative", "period", "was", "free", "of", "complications,", "and", "the", "patient", "was", "discharged", "from", "the", "hospital", "5", "days", "after", "the", "second", "surgery." ]

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[ "Shenoy", "et", "al.", "Nutrition", "Journal", "2010,", "9:38", "http://www.nutritionj.com/content/9/1/38", "R", "E", "S", "E", "A", "R", "C", "H", "Open", "Access", "The", "use", "of", "a", "commercial", "vegetable", "juice", "as", "a", "practical", "means", "to", "increase", "vegetable", "intake:", "a", "randomized", "controlled", "trial", "Sonia", "F", "Shenoy1,", "Alexandra", "G", "Kazaks2,", "Roberta", "R", "Holt1,", "Hsin", "Ju", "Chen1,", "Barbara", "L", "Winters3,", "Chor", "San", "Khoo4,", "Walker", "SC", "Poston5,", "C", "Keith", "Haddock5,", "Rebecca", "S", "Reeves6,", "John", "P", "Foreyt6,", "M", "Eric", "Gershwin7,", "Carl", "L", "Keen1,8*", "Abstract", "Background:", "Recommendations", "for", "daily", "dietary", "vegetable", "intake", "were", "increased", "in", "the", "2005", "USDA", "Dietary", "Guidelines", "as", "consumption", "of", "a", "diet", "rich", "in", "vegetables", "has", "been", "associated", "with", "lower", "risk", "of", "certain", "chronic", "health", "disorders", "including", "cardiovascular", "disease.", "However,", "vegetable", "consumption", "in", "the", "United", "States", "has", "declined", "over", "the", "past", "decade;", "consequently,", "the", "gap", "between", "dietary", "recommendations", "and", "vegetable", "intake", "is", "widening.", "The", "primary", "aim", "of", "this", "study", "is", "to", "determine", "if", "drinking", "vegetable", "juice", "is", "a", "practical", "way", "to", "help", "meet", "daily", "dietary", "recommendations", "for", "vegetable", "intake", "consistent", "with", "the", "2005", "Dietary", "Guidelines", "and", "the", "Dietary", "Approaches", "to", "Stop", "Hypertension", "(DASH)", "diet.", "The", "secondary", "aim", "is", "to", "assess", "the", "effect", "of", "a", "vegetable", "juice", "on", "measures", "of", "cardiovascular", "health.", "Methods:", "We", "conducted", "a", "12-week,", "randomized,", "controlled,", "parallel-arm", "study", "consisting", "of", "3", "groups", "of", "free-", "living,", "healthy", "volunteers", "who", "participated", "in", "study", "visits", "at", "the", "Ragle", "Human", "Nutrition", "Research", "Center", "at", "the", "University", "of", "California,", "Davis.", "All", "subjects", "received", "education", "on", "the", "DASH", "diet", "and", "0,", "8", "or", "16", "fluid", "ounces", "of", "vegetable", "juice", "daily.", "Assessments", "were", "completed", "of", "daily", "vegetable", "servings", "before", "and", "after", "incorporation", "of", "vegetable", "juice", "and", "cardiovascular", "health", "parameters", "including", "blood", "pressure.", "Results:", "Without", "the", "juice,", "vegetable", "intake", "in", "all", "groups", "was", "lower", "than", "the", "2005", "Dietary", "Guidelines", "and", "DASH", "diet", "recommendations.", "The", "consumption", "of", "the", "vegetable", "juice", "helped", "participants", "reach", "recommended", "intake.", "In", "general,", "parameters", "associated", "with", "cardiovascular", "health", "did", "not", "change", "over", "time.", "However,", "in", "the", "vegetable", "juice", "intervention", "groups,", "subjects", "who", "were", "pre-hypertensive", "at", "the", "start", "of", "the", "study", "showed", "a", "significant", "decrease", "in", "blood", "pressure", "during", "the", "12-week", "intervention", "period.", "Conclusion:", "Including", "1-2", "cups", "of", "vegetable", "juice", "daily", "was", "an", "effective", "and", "acceptable", "way", "for", "healthy", "adults", "to", "close", "the", "dietary", "vegetable", "gap.", "Increase", "in", "daily", "vegetable", "intake", "was", "associated", "with", "a", "reduction", "in", "blood", "pressure", "in", "subjects", "who", "were", "pre-hypertensive", "at", "the", "start", "of", "the", "trial.", "Trial", "Registration:", "Clinicaltrials.gov", "NCT01161706", "Background", "For", "almost", "two", "decades,", "the", "United", "States", "Department", "of", "Agriculture", "(USDA)", "has", "recommended", "that", "Ameri-", "cans", "consume", "a", "minimum", "of", "5", "servings", "of", "vegetables", "and", "fruits", "a", "day", "[1].", "These", "recommendations", "are", "based", "on", "numerous", "studies", "showing", "that", "meeting", "the", "*", "Correspondence:", "clkeen@ucdavis.edu", "1Department", "of", "Nutrition,", "University", "of", "California", "Davis,", "One", "Shields", "Ave,", "Davis,", "California", "95616,", "USA", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "recommended", "daily", "intake", "of", "fruit", "and", "vegetables", "is", "associated", "with", "a", "reduced", "risk", "for", "a", "number", "of", "chronic", "diseases,", "with", "the", "evidence", "for", "cardiovascular", "disease", "and", "stroke", "being", "particularly", "strong", "[2-5].", "In", "2005", "the", "Department", "of", "Health", "and", "Human", "Services", "updated", "the", "Dietary", "Guidelines", "which", "recommended", "an", "increase", "in", "fruit", "and", "vegetable", "intake", "and", "changed", "the", "recommen-", "dations", "from", "servings", "to", "cups", "[6].", "The", "new", "goal", "was", "2-", "6.5", "cups", "(equivalent", "to", "4", "-", "13", "servings)", "according", "to", "an", "individual’s", "sex,", "physical", "activity", "and", "age", "[6].", "For", "this", "©", "2010", "Shenoy", "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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[ "Eur", "J", "Epidemiol", "(2010)", "25:569–580", "DOI", "10.1007/s10654-010-9473-1", "P", "S", "Y", "C", "H", "I", "A", "T", "R", "I", "C", "E", "P", "I", "D", "E", "M", "I", "O", "L", "O", "G", "Y", "Cognitive", "ability,", "parental", "socioeconomic", "position", "and", "internalising", "and", "externalising", "problems", "in", "adolescence:", "Findings", "from", "two", "European", "cohort", "studies", "Martijn", "Huisman", "•", "Ricardo", "Araya", "•", "Debbie", "A.", "Lawlor", "•", "Johan", "Ormel", "•", "Frank", "C.", "Verhulst", "•", "Albertine", "J.", "Oldehinkel", "Received:", "28", "January", "2010", "/", "Accepted:", "27", "May", "2010", "/", "Published", "online:", "10", "June", "2010", "The", "Author(s)", "2010.", "This", "article", "is", "published", "with", "open", "access", "at", "Springerlink.com", "Abstract", "We", "investigated", "whether", "cognitive", "ability", "(CA)", "may", "be", "a", "moderator", "of", "the", "relationship", "of", "parental", "socio-", "economic", "position", "(SEP)", "with", "internalising", "and", "external-", "ising", "problems", "in", "adolescents.", "We", "used", "data", "from", "two", "longitudinal", "cohort", "studies;", "the", "Avon", "Longitudinal", "Study", "of", "Parents", "and", "Children", "(ALSPAC)", "and", "the", "Tracking", "Adolescents’", "Individual", "Lives", "Survey", "(TRAILS).", "Indica-", "tors", "of", "SEP", "were", "mother’s", "education", "and", "household", "income.", "CA", "was", "estimated", "with", "IQ", "scores,", "derived", "from", "the", "Wechsler", "Intelligence", "Scale", "for", "Children.", "Internalising", "and", "externalising", "problems", "were", "measured", "with", "the", "Strengths", "and", "Difficulties", "Questionnaire", "in", "ALSPAC", "and", "with", "the", "Child", "Behavior", "Checklist", "in", "TRAILS.", "Logistic", "regression", "analyses", "were", "used", "to", "estimate", "the", "relative", "index", "of", "inequality", "(RII)", "for", "each", "outcome;", "the", "RII", "provides", "the", "odds", "ratio", "comparing", "the", "most", "to", "least", "deprived", "for", "each", "measure", "of", "SEP.", "In", "fully", "adjusted", "models", "an", "association", "of", "mother’s", "education", "with", "externalising", "problems", "was", "M.", "Huisman", "(&)", "J.", "Ormel", "A.", "J.", "Oldehinkel", "Interdisciplinary", "Center", "for", "Psychiatric", "Epidemiology,", "University", "Medical", "Center", "Groningen,", "Groningen,", "The", "Netherlands", "e-mail:", "ma.huisman@vumc.nl", "R.", "Araya", "Academic", "Unit", "of", "Psychiatry,", "Community", "Based", "Medicine", "Department,", "University", "of", "Bristol,", "Bristol,", "UK", "D.", "A.", "Lawlor", "MRC", "Centre", "for", "Causal", "Analyses", "in", "Translational", "Epidemiology,", "Department", "of", "Social", "Medicine,", "University", "of", "Bristol,", "Bristol,", "UK", "F.", "C.", "Verhulst", "Department", "of", "Child", "and", "Adolescent", "Psychiatry,", "Erasmus", "MC-", "Sophia,", "University", "Medical", "Center,", "Rotterdam,", "The", "Netherlands", "observed", "[ALSPAC", "RII", "1.42", "(95%CI:", "1.01–1.99);", "TRAILS", "RII", "2.21", "(95%CI:", "1.37–3.54)],", "and", "of", "household", "income", "with", "internalising", "and", "externalising", "problems", "[pooled", "ALSPAC", "&", "TRAILS", "internalising", "RII", "1.30", "(95%CI:", "0.99–", "1.71);", "pooled", "ALSPAC", "&", "TRAILS", "externalising", "RII", "1.38", "(95%CI:", "1.03–1.84)].", "No", "consistent", "associations", "were", "observed", "between", "mother’s", "education", "and", "internalising", "problems.", "Results", "of", "stratified", "analyses", "and", "interaction-", "terms", "showed", "no", "evidence", "that", "CA", "moderated", "the", "associ-", "ation", "of", "SEP", "with", "internalising", "or", "externalising", "problems.", "Keywords", "Adolescence", "Mental", "health", "ALSPAC", "Socioeconomic", "factors", "TRAILS", "Cognitive", "ability", "Abbreviations", "CA", "Cognitive", 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"behaviour", "[1,", "6,", "7].", "123" ]

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[ "Hindawi", "Publishing", "Corporation", "Sarcoma", "Volume", "2011,", "Article", "ID", "160369,", "5", "pages", "doi:10.1155/2011/160369", "Case", "Report", "Scalp", "Angiosarcoma", "Remission", "with", "Bevacizumab", "and", "Radiotherapy", "without", "Surgery:", "A", "Case", "Report", "and", "Review", "of", "the", "Literature", "Jocelyn", "T.", "De", "Yao,1,", "2", "Danyu", "Sun,1,", "2", "Angela", "T.", "Powell,2,", "3", "and", "Esther", "H.", "Rehmus1,", "2", "1", "Department", "of", "Medicine,", "Akron", "General", "Medical", "Center,", "400", "Wabash", "Avenue,", "Akron,", "OH", "44307,", "USA", "2", "Department", "of", "Medicine,", "Northeastern", "Ohio", "Universities,", "College", "of", "Medicine", "and", "Pharmacy,", "Rootstown,", "OH", "44272,", "USA", "3", "Department", "of", "Pathology,", "Akron", "General", "Medical", "Center,", "400", "Wabash", "Avenue,", "Akron,", "OH", "44307,", "USA", "Correspondence", "should", "be", "addressed", "to", "Jocelyn", "T.", "De", "Yao,", "jdeyao@agmc.org", "Received", "18", "October", "2010;", "Accepted", "27", "February", "2011", "Academic", "Editor:", "Marcus", "Schlemmer", "Copyright", "©", "2011", "Jocelyn", "T.", "De", "Yao", "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.", "Angiosarcoma", "(AS)", "is", "a", "rare", "and", "aggressive", "vascular", "neoplasm", "with", "very", "poor", "prognosis.", "Patients", "with", "extensive", "cutaneous", "AS", "who", "are", "not", "surgical", "candidates", "have", "very", "limited", "options", "since", "there", "is", "no", "standard", "treatment.", "Treatment", "options", "include", "radiation,", "chemotherapy,", "and", "angiogenesis", "inhibitor", "with", "varying", "success", "rates.", "Here,", "we", "report", "a", "case", "an", "88", "year", "old", "patient", "with", "extensive", "scalp", "angiosarcoma", "having", "biopsy", "proven", "remission", "with", "bevacizumab", "and", "radiotherapy", "without", "undergoing", "surgery.", "1.", "Introduction", "Angiosarcoma", "(AS)", "is", "a", "rare", "and", "aggressive", "vascular", "neo-", "plasm", "comprising", "less", "than", "2%", "of", "all", "soft", "tissue", "sarcomas", "[1–", "3].", "Angiosarcomas", "comprise", "approximately", "15%", "of", "all", "head", "and", "neck", "sarcomas", "[4–6]", "and", "less", "than", "1%", "of", "all", "malignancies", "in", "the", "region", "[6,", "7].", "Head", "and", "neck", "ASs", "are", "frequently", "seen", "in", "the", "scalp", "[1–3,", "6–15]", "and", "are", "common", "in", "the", "elderly", "population", "with", "the", "mean", "age", "greater", "than", "60", "years.", "AS", "also", "has", "a", "slight", "predilection", "for", "Caucasian", "patients", "and", "the", "male", "gender", "[1,", "2,", "7–10,", "12–14].", "Prognosis", "is", "poor", "since", "AS", "is", "very", "aggressive", "with", "disease-free", "survival", "of", "less", "than", "50%", "at", "five", "years", "[1,", "4,", "5,", "8–14]", "due", "to", "its", "high", "propensity", "for", "local", "recurrence", "[4,", "5,", "8,", "11].", "However,", "some", "studies", "report", "survival", "of", "10–20%", "after", "five", "years", "[1,", "5,", "8–11],", "which", "may", "indicate", "lesions", "that", "are", "located", "in", "the", "scalp", "and", "face", "have", "a", "lower", "survival", "rate", "and", "higher", "rate", "of", "recurrence", "[10].", "The", "most", "important", "prognostic", "factors", "include", "tumor", "size", "and", "ability", "to", "achieve", "negative", "margins", "with", "tumor", "grade", "also", "being", "considered", "to", "be", "a", "prognostic", "factor", "for", "recurrence", "[5,", "12]", "and", "overall", "survival", "[11].", "Patients", "with", "facial", "or", "scalp", "AS", "of", "less", "than", "5", "cm", "in", "size", "tend", "to", "do", "better", "than", "those", "with", "tumor", "size", "greater", "than", "5", "cm", "[6,", "10].", "Patients", "with", "cutaneous", "AS", "who", "are", "not", "surgical", "candidates", "due", "to", "multiple", "comorbid", "conditions", "have", "limited", "treatment", "options.", "Due", "to", "its", "rapid", "progression,", "achieving", "local", "control", "and", "prevention", "of", "metastasis", "in", "AS", "has", "been", "a", "challenge.", "Few", "reports", "have", "described", "successful", "treatment", "of", "AS", "using", "adjuvant", "chemotherapy", "with", "radiotherapy", "[16].", "Different", "treatment", "modalities", "used", "in", "cutaneous", "angiosarcoma", "are", "depicted", "in", "Table", "1.", "Here,", "we", "report", "a", "successful", "response", "of", "AS", "to", "bevacizumab", "with", "concurrent", "radiation", "therapy", "in", "a", "patient", "not", "eligible", "for", "surgical", "intervention.", "2.", "Case", "Report", "An", "88-year-old", "Caucasian", "male", "with", "a", "37-pack-year", "history", "of", "smoking", "noticed", "purplish", "lumps", "on", "his", "scalp", "with", "scaling", "and", "erythema", "for", "two", "months", "prior", "to", "presentation.", "He", "had", "a", "complicated", "past", "medical", "history", "of", "Stage", "II", "prostate", "cancer", "treated", "with", "radiation", "treatments,", "abdominal", "aortic", "aneurysm", "repair,", "macular", "degeneration", "treated", "with", "pho-", "todynamic", "therapy,", "torn", "retina,", "inguinal", "hernia", "repair,", "and", "four-vessel", "coronary", "artery", "bypass", "graft.", "The", "patient", "noted", "the", "violaceous", "papules", "increasing", "in", "size", "and", "nodularity", "and", "extending", "down", "to", "the", "level", "of", "the", "eyebrows", "bilaterally.", "He" ]

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[ "Zhang", "et", "al.", "Lipids", "in", "Health", "and", "Disease", "2010,", "9:24", "http://www.lipidworld.com/content/9/1/24", "R", "E", "S", "E", "A", "R", "C", "H", "Open", "Access", "Fatty", "acid", "extracts", "from", "Lucilia", "sericata", "larvae", "promote", "murine", "cutaneous", "wound", "healing", "by", "angiogenic", "activity", "Zhen", "Zhang1,", "Shouyu", "Wang1,", "Yunpeng", "Diao2,", "Jianing", "Zhang3,", "Decheng", "Lv1*", "Abstract", "Background:", "fatty", "acids", "are", "considered", "to", "be", "effective", "components", "to", "promote", "wound", "healing", "and", "Lucilia", "sericata", "larvae", "are", "applied", "clinically", "to", "treat", "intractable", "wounds.", "We", "aimed", "to", "investigat", "the", "effect", "of", "fatty", "acid", "extracts", "from", "dried", "Lucilia", "sericata", "larvae", "on", "murine", "cutaneuous", "wound", "healing", "as", "well", "as", "angiogenesis.", "Results:", "On", "day", "7", "and", "10", "after", "murine", "acute", "excision", "wounds", "creation,", "the", "percent", "wound", "contraction", "of", "fatty", "acid", "extracts", "group", "was", "higher", "than", "that", "of", "vaseline", "group.", "On", "day", "3,", "7", "and", "10", "after", "wounds", "creation,", "the", "wound", "healing", "quality", "of", "fatty", "acid", "extracts", "group", "was", "better", "than", "that", "of", "vaseline", "group", "on", "terms", "of", "granulation", "formation", "and", "collagen", "organization.", "On", "day", "3", "after", "wounds", "creation,", "the", "micro", "vessel", "density", "and", "vascular", "endothelial", "growth", "factor", "expression", "of", "fatty", "acid", "extracts", "group", "were", "higher", "than", "that", "of", "vaseline", "group.", "Component", "analysis", "of", "the", "fatty", "acid", "extracts", "by", "gas", "chromatography-mass", "spectrometry", "showed", "there", "were", "10", "kinds", "of", "fatty", "acids", "in", "total", "and", "the", "ratio", "of", "saturated", "fatty", "acid,", "monounsaturated", "fatty", "acid", "and", "polyunsaturated", "fatty", "acid", "(PUFA)", "was:", "20.57%:60.32%:19.11%.", "Conclusions:", "Fatty", "acid", "extracts", "from", "dried", "Lucilia", "sericata", "larvae,", "four", "fifths", "of", "which", "are", "unsaturated", "fatty", "acids,", "can", "promote", "murine", "cutaneous", "wound", "healing", "probably", "resulting", "from", "the", "powerful", "angiogenic", "activity", "of", "the", "extracts.", "Background", "Fatty", "acids,", "as", "a", "family", "of", "bioactive", "moleculars,", "partici-", "pate", "in", "many", "metabolic", "processes.", "The", "deficiency", "of", "fatty", "acids", "may", "result", "in", "diseases,", "vice", "versa", "supplement-", "ing", "fatty", "acids", "can", "treat", "diseases.", "Since", "a", "kind", "of", "disease", "is", "a", "result", "of", "multiple", "etiological", "factors,", "it", "is", "difficult", "to", "get", "a", "satisfactory", "therapeutic", "outcome", "using", "a", "single", "compound", "as", "drug.", "Therefore", "more", "and", "more", "doctors", "focus", "on", "ethnopharmacolgical", "theory,", "which", "records", "folk", "plants", "or", "animals", "containing", "many", "effective", "compo-", "nents.", "The", "therapeutic", "utilization", "of", "Lucilia", "sericata", "lar-", "vae", "commonly", "called", "maggot", "therapy", "for", "wound", "healing", "can", "date", "back", "to", "the", "beginning", "of", "civilization", "[1].", "According", "to", "traditional", "Chinese", "medicine", "principle", "and", "the", "book", "Compendium", "of", "Materia", "Medica", "records,", "Luci-", "lia", "sericata", "larvae", "which", "has", "been", "given", "the", "name", "of", "“WuGuChong”", "is", "salty", "in", "taste,", "cold", "in", "nature", "and", "non-", "*", "Correspondence:", "lvdecheng88@sina.com", "1Department", "of", "Orthopedic", "Surgery,", "First", "Affiliated", "Hospital,", "Dalian", "Medical", "University,", "Dalian,", "Liaoning", "Province,", "China", "toxic.", "It", "is", "mainly", "produced", "in", "Guangdong", "Province", "in", "China", "and", "local", "people", "use", "“WuGuChong”", "to", "treat", "superficial", "purulent", "diseases", "such", "as", "furuncle", "or", "carbun-", "cle.", "Recently,", "maggot", "therapy", "has", "been", "widely", "used", "to", "treat", "various", "refractory", "wounds", "including", "diabetes", "foot", "and", "venous", "ulcers", "[2-5].", "The", "therapeutic", "action", "com-", "prises", "biological", "debridement", "and", "enhancement", "of", "wound", "healing.", "The", "mechanisms", "of", "debriding", "effect", "of", "maggots", "were", "due", "to", "their", "mechanical", "wriggling", "and", "excretions/secretions", "degrading", "extracellular", "matrix", "[6,7].", "However,", "there", "are", "no", "in", "vivo", "reports", "regarding", "wound", "healing", "mechanisms", "of", "maggot", "therapy.", "In", "addi-", "tion,", "complications", "such", "as", "larvae", "loss,", "persistent", "pain", "or", "severe", "systemic", "infection", "[8]", "induced", "by", "live", "maggot", "limits", "the", "clinical", "use", "of", "maggot", "therapy,", "so", "the", "theory", "and", "practice", "of", "new", "delivery", "method", "is", "urgent.", "Cutaneous", "wound", "healing", "is", "a", "complex", "process,", "con-", "sisting", "of", "an", "orderly", "progression", "of", "inflammation,", "angio-", "genesis,", "collagen", "deposition,", "re-epithlization", "and", "tissue", "remolding", "[9].", "The", "purpose", "of", "repairing", "events", "is", "to", "©", "2010", "Zhang", "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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[ "Integrated", "Analyses", "of", "microRNAs", "Demonstrate", "Their", "Widespread", "Influence", "on", "Gene", "Expression", "in", "High-Grade", "Serous", "Ovarian", "Carcinoma", "Chad", "J.", "Creighton1,2*.,", "Anadulce", "Hernandez-Herrera11.,", "Anders", "Jacobsen4.,", "Douglas", "A.", "Levine3,", "Parminder", "Mankoo", "4", ",", "Nikolaus", "Schultz4,", "Ying", "Du", "5", ",", "Yiqun", "Zhang1,", "Erik", "Larsson", "4", ",", "Robert", "Sheridan", "4", ",", "Weimin", "Xiao11,", "Paul", "T.", "Spellman", "7", ",", "Gad", "Getz8,", "David", "A.", "Wheeler9,", "Charles", "M.", "Perou", "5", ",", "Richard", "A.", "Gibbs9,", "Chris", "Sander4,", "D.", "Neil", "Hayes5,6,", "Preethi", "H.", "Gunaratne10,11*,", "The", "Cancer", "Genome", "Atlas", "Research", "Network", "1", "Dan", "L.", "Duncan", "Cancer", "Center,", "Baylor", "College", "of", "Medicine,", "Houston,", "Texas,", "United", "States", "of", "America", ",", "2", "Department", "of", "Medicine,", "Baylor", "College", "of", "Medicine,", "Houston,", "Texas,", "United", "States", "of", "America,", "3", "Gynecology", "Service,", "Department", "of", "Surgery,", "Memorial", "Sloan-Kettering", "Cancer", "Center,", "New", "York,", "New", "York,", "United", "States", "of", "America,", "4", "Computational", "Biology", "Center,", "Memorial", "Sloan-Kettering", "Cancer", "Center,", "New", "York,", "New", "York,", "United", "States", "of", "America,", "5", "Lineberger", "Comprehensive", "Cancer", "Center,", "University", "of", "North", "Carolina,", "Chapel", "Hill,", "North", "Carolina,", "United", "States", "of", "America,", "6", "Department", "of", "Internal", "Medicine,", "Division", "of", "Medical", "Oncology,", "University", "of", "North", "Carolina,", "Chapel", "Hill,", "North", "Carolina,", "United", "States", "of", "America,", "7", "Life", "Sciences", "Division,", "Lawrence", "Berkeley", "National", "Laboratory,", "Berkeley,", "California,", "United", "States", "of", "America,", "8", "Broad", "Institute", "of", "MIT", "and", "Harvard,", "Cambridge,", "Massachusetts,", "United", "States", "of", "America,", "9", "Department", "of", "Molecular", "and", "Human", "Genetics,", "Baylor", "College", "of", "Medicine,", "Houston,", "Texas,", "United", "States", "of", "America,", "10", "Department", "of", "Pathology,", "Baylor", "College", "of", "Medicine,", "Houston,", "Texas,", "United", "States", "of", "America,", "11", "Department", "of", "Biology", "&", "Biochemistry,", "University", "of", "Houston,", "Houston,", "Texas,", "United", "States", "of", "America", "Abstract", "Background:", "The", "Cancer", "Genome", "Atlas", "(TCGA)", "Network", "recently", "comprehensively", "catalogued", "the", "molecular", "aberrations", "in", "487", "high-grade", "serous", "ovarian", "cancers,", "with", "much", "remaining", "to", "be", "elucidated", "regarding", "the", "microRNAs", "(miRNAs).", "Here,", "using", "TCGA", "ovarian", "data,", "we", "surveyed", "the", "miRNAs,", "in", "the", "context", "of", "their", "predicted", "gene", "targets.", "Methods", "and", "Results:", "Integration", "of", "miRNA", "and", "gene", "patterns", "yielded", "evidence", "that", "proximal", "pairs", "of", "miRNAs", "are", "processed", "from", "polycistronic", "primary", "transcripts,", "and", "that", "intronic", "miRNAs", "and", "their", "host", "gene", "mRNAs", "derive", "from", "common", "transcripts.", "Patterns", "of", "miRNA", "expression", "revealed", "multiple", "tumor", "subtypes", "and", "a", "set", "of", "34", "miRNAs", "predictive", "of", "overall", "patient", "survival.", "In", "a", "global", "analysis,", "miRNA:mRNA", "pairs", "anti-correlated", "in", "expression", "across", "tumors", "showed", "a", "higher", "frequency", "of", "in", "silico", "predicted", "target", "sites", "in", "the", "mRNA", "39-untranslated", "region", "(with", "less", "frequency", "observed", "for", "coding", "sequence", "and", "59-untranslated", "regions).", "The", "miR-29", "family", "and", "predicted", "target", "genes", "were", "among", "the", "most", "strongly", "anti-", "correlated", "miRNA:mRNA", "pairs;", "over-expression", "of", "miR-29a", "in", "vitro", "repressed", "several", "anti-correlated", "genes", "(including", "DNMT3A", "and", "DNMT3B)", "and", "substantially", "decreased", "ovarian", "cancer", "cell", "viability.", "Conclusions:", "This", "study", "establishes", "miRNAs", "as", "having", "a", "widespread", "impact", "on", "gene", "expression", "programs", "in", "ovarian", "cancer,", "further", "strengthening", "our", "understanding", "of", "miRNA", "biology", "as", "it", "applies", "to", "human", "cancer.", "As", "with", "gene", "transcripts,", "miRNAs", "exhibit", "high", "diversity", "reflecting", "the", "genomic", "heterogeneity", "within", "a", "clinically", "homogeneous", "disease", "population.", "Putative", "miRNA:mRNA", "interactions,", "as", "identified", "using", "integrative", "analysis,", "can", "be", "validated.", "TCGA", "data", "are", "a", "valuable", "resource", "for", "the", "identification", "of", "novel", "tumor", "suppressive", "miRNAs", "in", "ovarian", "as", "well", "as", "other", "cancers.", "Citation:", "Creighton", "CJ,", "Hernandez-Herrera", "A,", "Jacobsen", "A,", "Levine", "DA,", "Mankoo", "P,", "et", "al.", "(2012)", "Integrated", "Analyses", "of", "microRNAs", "Demonstrate", "Their", "Widespread", "Influence", "on", "Gene", "Expression", "in", "High-Grade", "Serous", "Ovarian", "Carcinoma.", "PLoS", "ONE", "7(3):", "e34546.", "doi:10.1371/journal.pone.0034546", "Editor:", "Aed´ın", "C.", "Culhane,", "Harvard", "School", "of", "Public", "Health,", "United", "States", "of", "America", "Received", "January", "10,", "2012;", "Accepted", "March", "1,", "2012;", "Published", "March", "29,", "2012", "Copyright:", "2012", "Creighton", "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", "the", "Ovarian", "Cancer", "Research", "Fund", "(CJC,", "PHG),", "National", "Institutes", "of", "Health", "(NIH)", "grant", "P30CA125123", "(CJC,", "YZ),", "TCGA", "GCC", "at", "Baylor:", "National", "Cancer", "Institue", "(NCI)", "grant", "U24CA143843", "(CJC,", "DAW,", "RAG),", "TCGA", "GCC", "at", "University", "of", "North", "Carolina:", "NCI-U24CA143848", "(YD,", "CMP,", "DNH),", "TCGA", "GDAC", "at", "Memorial", "Sloan-Kettering", "Cancer", "Center:", "NCI-U24CA143840", "(AJ,", "PM,", "NS,", "EL,", "RS,", "CS),", "CPRIT-RP110355", "(PHG),", "a", "Cullen", "Foundation", "Grant", "(PHG),", "the", "Mexican", "National", "Council", "for", "Science", "and", "Technology", "(CONACyT)", "(AH),", "and", "the", "Danish", "Research", "Council", "(AJ).", "The", "funders", "had", "no", "role", "in", "study", "design,", "data", "collection", "and", "analysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "Competing", "Interests:", "CJC", "serves", "as", "an", "Academic", "Editor", "for", "PLoS", "ONE.", "This", "does", "not", "alter", "the", "authors’", "adherence", "to", "all", "the", "PLoS", "ONE", "policies", "on", "sharing", "data", "and", "materials.", "*", "E-mail:", "creighto@bcm.edu", "(CJC);", "phgunaratne@uh.edu", "(PHG)", ".", "These", "authors", "contributed", "equally", "to", "this", "work.", "Introduction", "MicroRNAs", "(miRNAs", "or", "miRs)", "are", ",22", "nt", "noncoding", "RNAs", "which", "target", "complementary", "gene", "transcripts", "for", "translational", "repression", "or", "mRNA", "cleavage", "[1].", "Having", "been", "implicated", "in", "the", "initiation", "and", "progression", "of", "human", "cancers,", "miRNAs", "regulate", "processes", "such", "as", "cell", "growth,", "differentiation,", "and", "apoptosis", "[2].", "A", "productive", "miRNA:mRNA", "interaction", "can", "occur", "with", "as", "little", "as", "six", "consecutive", "nucleotides,", "through", "pairing", "between", "the", "59-seed", "of", "the", "miRNA", "(located", "in", "nucleotides", "2–7)", "and", "sequences", "which", "are", "PLoS", "ONE", "|", "www.plosone.org", "1", "March", "2012", "|", "Volume", "7", "|", "Issue", "3", "|", "e34546" ]

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[ "Barvkar", "et", "al.", "BMC", "Genomics", "2012,", "13:175", "http://www.biomedcentral.com/1471-2164/13/175", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "Phylogenomic", "analysis", "of", "UDP", "glycosyltransferase", "1", "multigene", "family", "in", "Linum", "usitatissimum", "identified", "genes", "with", "varied", "expression", "patterns", "Vitthal", "T", "Barvkar,", "Varsha", "C", "Pardeshi,", "Sandip", "M", "Kale,", "Narendra", "Y", "Kadoo", "and", "Vidya", "S", "Gupta*", "Abstract", "Background:", "The", "glycosylation", "process,", "catalyzed", "by", "ubiquitous", "glycosyltransferase", "(GT)", "family", "enzymes,", "is", "a", "prevalent", "modification", "of", "plant", "secondary", "metabolites", "that", "regulates", "various", "functions", "such", "as", "hormone", "homeostasis,", "detoxification", "of", "xenobiotics", "and", "biosynthesis", "and", "storage", "of", "secondary", "metabolites.", "Flax", "(Linum", "usitatissimum", "L.)", "is", "a", "commercially", "grown", "oilseed", "crop,", "important", "because", "of", "its", "essential", "fatty", "acids", "and", "health", "promoting", "lignans.", "Identification", "and", "characterization", "of", "UDP", "glycosyltransferase", "(UGT)", "genes", "from", "flax", "could", "provide", "valuable", "basic", "information", "about", "this", "important", "gene", "family", "and", "help", "to", "explain", "the", "seed", "specific", "glycosylated", "metabolite", "accumulation", "and", "other", "processes", "in", "plants.", "Plant", "genome", "sequencing", "projects", "are", "useful", "to", "discover", "complexity", "within", "this", "gene", "family", "and", "also", "pave", "way", "for", "the", "development", "of", "functional", "genomics", "approaches.", "Results:", "Taking", "advantage", "of", "the", "newly", "assembled", "draft", "genome", "sequence", "of", "flax,", "we", "identified", "137", "UDP", "glycosyltransferase", "(UGT)", "genes", "from", "flax", "using", "a", "conserved", "signature", "motif.", "Phylogenetic", "analysis", "of", "these", "protein", "sequences", "clustered", "them", "into", "14", "major", "groups", "(A-N).", "Expression", "patterns", "of", "these", "genes", "were", "investigated", "using", "publicly", "available", "expressed", "sequence", "tag", "(EST),", "microarray", "data", "and", "reverse", "transcription", "quantitative", "real", "time", "PCR", "(RT-qPCR).", "Seventy-three", "per", "cent", "of", "these", "genes", "(100", "out", "of", "137)", "showed", "expression", "evidence", "in", "15", "tissues", "examined", "and", "indicated", "varied", "expression", "profiles.", "The", "RT-qPCR", "results", "of", "10", "selected", "genes", "were", "also", "coherent", "with", "the", "digital", "expression", "analysis.", "Interestingly,", "five", "duplicated", "UGT", "genes", "were", "identified,", "which", "showed", "differential", "expression", "in", "various", "tissues.", "Of", "the", "seven", "intron", "loss/gain", "positions", "detected,", "two", "intron", "positions", "were", "conserved", "among", "most", "of", "the", "UGTs,", "although", "a", "clear", "relationship", "about", "the", "evolution", "of", "these", "genes", "could", "not", "be", "established.", "Comparison", "of", "the", "flax", "UGTs", "with", "orthologs", "from", "four", "other", "sequenced", "dicot", "genomes", "indicated", "that", "seven", "UGTs", "were", "flax", "diverged.", "Conclusions:", "Flax", "has", "a", "large", "number", "of", "UGT", "genes", "including", "few", "flax", "diverged", "ones.", "Phylogenetic", "analysis", "and", "expression", "profiles", "of", "these", "genes", "identified", "tissue", "and", "condition", "specific", "repertoire", "of", "UGT", "genes", "from", "this", "crop.", "This", "study", "would", "facilitate", "precise", "selection", "of", "candidate", "genes", "and", "their", "further", "characterization", "of", "substrate", "specificities", "and", "in", "planta", "functions.", "Background", "Flax", "or", "linseed", "(Linum", "usitatissimum", "L.)", "is", "one", "of", "the", "earliest", "domesticated", "crops.", "It", "is", "a", "self-pollinating", "diploid", "species", "cultivated", "as", "a", "source", "of", "fibre,", "oil", "and", "medicinal", "compounds.", "Historically", "it", "has", "been", "used", "as", "a", "model", "for", "developmental", "studies", "and", "has", "a", "different", "evolutionary", "history", "than", "other", "model", "plants", "like", "Arabidopsis", "[1].", "Among", "plant", "foods,", "flaxseed", "has", "the", "highest", "contents", "of", "the", "essential", "omega-3", "fatty", "acid,", "alpha-linolenic", "acid", "*", "Correspondence:", "vs.gupta@ncl.res.in", "Plant", "Molecular", "Biology", "Group,", "Biochemical", "Sciences", "Division,", "National", "Chemical", "Laboratory,", "Pune,", "411008,", "India", "(ALA)", "[2]", "and", "bioactive", "phenolic", "compounds", "such", "as", "lignans,", "predominantly", "secoisolariciresinol", "diglucoside", "(SDG)", "[3],", "phenolic", "acids", "and", "flavonoids", "[4].", "ALA", "dampens", "inflammatory", "reactions,", "thereby", "reducing", "a", "risk", "of", "heart", "attack", "or", "stroke;", "while", "lignans", "are", "strong", "antioxidants", "inhibiting", "breast", "and", "prostate", "cancers.", "Given", "the", "economic", "and", "health", "benefits", "of", "these", "bioactive", "compounds,", "it", "would", "be", "useful", "to", "comprehensively", "analyze", "the", "genes", "involved", "in", "their", "biosynthesis.", "In", "plants,", "glycosylation", "represents", "the", "last", "step", "in", "the", "biosynthesis", "of", "numerous", "natural", "compounds", "like", "terpenes,", "phenylpropanoids,", "cyanogenic", "glucosides", "and", "glucosinolates.", "It", "is", "an", "important", "©", "2012", "Barvkar", "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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[ "http://dx.doi.org/10.4110/in.2011.11.6.368", "pISSN", "1598-2629", "eISSN", "2092-6685", "ORIGINAL", "ARTICLE", "Blockade", "of", "Vascular", "Endothelial", "Growth", "Factor", "(VEGF)", "Aggravates", "the", "Severity", "of", "Acute", "Graft-versus-host", "Disease", "(GVHD)", "after", "Experimental", "Allogeneic", "Hematopoietic", "Stem", "Cell", "Transplantation", "(allo-HSCT)", "Ai-Ran", "Kim1,", "Ji-Young", "Lim2,", "Dae", "Chul", "Jeong1,", "Gyeongsin", "Park3,", "Byung", "Churl", "Lee1", "and", "Chang-Ki", "Min2*", "Departments", "of", "1Pediatrics,", "2Internal", "Medicine,", "and", "3Hospital", "Pathology,", "The", "Catholic", "University", "of", "Korea,", "Seoul", "137-701,", "Korea", "Background:", "Recent", "clinical", "observation", "reported", "that", "there", "was", "a", "significant", "correlation", "between", "change", "in", "circulating", "vascular", "endothelial", "growth", "factor", "(VEGF)", "levels", "and", "the", "oc-", "currence", "of", "severe", "acute", "graft-versus-host", "disease", "(GVHD)", "following", "allogeneic", "hematopoietic", "stem", "cell", "transplantation", "(allo-HSCT),", "but", "the", "action", "mechanisms", "of", "VEGF", "in", "GVHD", "have", "not", "been", "demonstrated.", "Methods:", "This", "study", "inves-", "tigated", "whether", "or", "not", "blockade", "of", "VEGF", "has", "an", "effect", "on", "acute", "GVHD", "in", "a", "lethally", "irradiated", "murine", "allo-HSCT", "model", "of", "B6", "(H-2b)", "→B6D2F1", "(H-2b/d).", "Syngeneic", "or", "allogeneic", "re-", "cipient", "mice", "were", "injected", "subcutaneously", "with", "anti-VEGF", "peptides,", "dRK6", "(50μg/dose)", "or", "control", "diluent", "every", "other", "day", "for", "2", "weeks", "(total", "7", "doses).", "Results:", "Administration", "of", "the", "dRK6", "peptide", "after", "allo-HSCT", "significantly", "reduced", "sur-", "vival", "with", "greaterclinical", "GVHD", "scores", "and", "body", "weight", "loss.", "Allogeneic", "recipients", "injected", "with", "the", "dRK6", "peptide", "ex-", "hibited", "significantly", "increased", "circulating", "levels", "of", "VEGF", "and", "expansion", "of", "donor", "CD3＋", "T", "cells", "on", "day", "＋7", "compared", "to", "control", "treated", "animals.", "The", "donor", "CD4＋", "and", "CD8＋", "T-cell", "subsets", "have", "differential", "expansion", "caused", "by", "the", "dRK6", "injection.", "The", "circulating", "VEGF", "levels", "were", "reduced", "on", "day", "＋14", "regardless", "of", "blockade", "of", "VEGF.", "Conclusion:", "Together", "these", "findings", "demonstrate", "that", "the", "allo-reactive", "responses", "after", "allo-HSCT", "are", "exaggerated", "by", "the", "blockade", "of", "VEGF.", "VEGF", "seems", "to", "be", "consumed", "during", "the", "progression", "of", "acute", "GVHD", "in", "this", "murine", "allo-HSCT", "model.", "[Immune", "Network", "2011;11(6):368-375]", "INTRODUCTION", "Allogeneic", "hematopoietic", "stem", "cell", "transplantation", "(allo-", "HSCT)", "is", "the", "treatment", "of", "choice", "for", "manyhematological", "ma-", "lignancies", "as", "well", "as", "for", "severe", "immunodeficiency.", "However,", "the", "main", "causes", "of", "patient", "mortality", "and", "morbidity", "after", "al-", "lo-HSCT", "are", "relapse,", "graft-versus-host", "disease", "(GVHD),", "and", "infections", "(1,2).", "Various", "complications", "occurring", "after", "al-", "lo-HSCT", "are", "believed", "to", "be", "manifestations", "of", "systemic", "in-", "flammatory", "response", "syndrome", "(SIRS)", "(3).", "SIRS", "is", "caused", "by", "hypercytokinemia", "with", "the", "excess", "production", "of", "proinflam-", "matory", "cytokines", "(4).", "It", "is", "generally", "recognized", "that", "cross-", "linking", "of", "the", "cytokine", "network", "plays", "an", "important", "role", "in", "the", "inflammatory", "processes.", "Dysregulation", "of", "cytokine", "pro-", "duction", "may", "initiate", "and", "perpetuate", "tissue", "damage", "in", "those", "who", "undergo", "allo-HSCT.", "Organ", "impairment", "in", "SIRS", "is", "believed", "to", "occur", "as", "a", "sequel", "to", "vascular", "endothelial", "damage", "(5).", "Vascular", "endothelial", "growth", "factor", "(VEGF)", "is", "a", "dimeric", "glycoprotein", "that", "increases", "the", "vascular", "permeability", "and", "induces", "the", "proliferation", "and", "migration", "of", "endothelial", "cells", "to", "form", "new", "blood", "vessels", "(6,7).", "The", "role", "of", "angiogenesis", "in", "sustaining", "aninflammatory", "response", "has", "recently", "become", "evident.", "VEGF", "acts", "as", "a", "potent", "chemo-attractant", "for", "leukocytes", "into", "neovascularization", "site", "and", "induces", "endothelial", "cells", "to", "produce", "collagenase.", "VEGF", "has", "also", "been", "implicated", "in", "a", "variety", "of", "chronic", "inflammatory", "Received", "on", "October", "11,", "2011.", "Revised", "on", "October", "28,", "2011.", "Accepted", "on", "November", "3,", "2011.", "CC", "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,", "distribu-", "tion,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "*Corresponding", "Author.", "Tel:", "82-2-2258-6053;", "Fax:", "82-2-599-3589;", "E-mail:", "ckmin@catholic.ac.kr", "Keywords:", "Vascular", "endothelial", "growth", "factors", "(VEGF),", "Allogeneic", "hematopoietic", "stem", "cell", "transplantation,", "Acute", "graft-", "versus-host", "disease,", "VEGF", "blockade,", "dRK6", "368", "IMMUNE", "NETWORK", "http://www.ksimm.or.kr", "Volume", "11", "Number", "6", "December", "2011" ]

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[ "BMC", "Public", "Health", "Study", "protocol", "Peripheral", "Arterial", "Disease", "Study", "(PERART):", "Prevalence", "and", "predictive", "values", "of", "asymptomatic", "peripheral", "arterial", "occlusive", "disease", "related", "to", "cardiovascular", "morbidity", "and", "mortality", "María", "Teresa", "Alzamora*1,2,3,", "José", "Miguel", "Baena-Díez4,", "Marta", "Sorribes5,", "Rosa", "Forés1,", "Pere", "Toran3,", "Marisa", "Vicheto1,", "Guillem", "Pera3,", "María", "Dolores", "Reina6,", "Carlos", "Albaladejo7,", "Judith", "Llussà8,", "Magda", "Bundó9,", "Amparo", "Sancho10,", "Antonio", "Heras1,", "Joan", "Rubiés2,6,", "Juan", "Francisco", "Arenillas11", "for", "the", "PERART", "study", "BioMed", "Central", "Open", "Access", "Address:", "1Primary", "Healthcare", "Centre", "Riu", "Nord-Riu", "Sud,", "Institut", "Català", "de", "la", "Salut,", "Santa", "Coloma", "de", "Gramenet,,", "Spain,", "2Department", "of", "Medicine,", "Universitat", "Autònoma", "de", "Barcelona,", "Spain,", "3Research", "Unit", "Barcelonés", "Nord", "Maresme.", "ICS-IDIAP", "Jordi", "Gol.", "Mataró,", "Spain,", "4Primary", "Healthcare", "Centre", "La", "Marina,", "Institut", "Català", "de", "la", "Salut,", "Barcelona,", "Spain,", "5Primary", "Healthcare", "Centre", "Numància,", "Institut", "Català", "de", "la", "Salut,", "Barcelona,", "Spain,", "6Primary", "Healthcare", "Centre", "Santa", "Coloma", "de", "Gramenet,", "Institut", "Català", "de", "la", "Salut,", "Santa", "Coloma", "de", "Gramenet,", "Spain,", "7Primary", "Healthcare", "Centre", "Llefià,", "Institut", "Català", "de", "la", "Salut", "Badalona,", "Spain,", "8Primary", "Healthcare", "Centre", "Sant", "Roc,", "Institut", "Català", "de", "la", "Salut,", "Badalona,", "Spain,", "9Primary", "Healthcare", "Centre", "Ronda", "Prim,", "Institut", "Català", "de", "la", "Salut,", "Mataró,", "Spain,", "10Primary", "Healthcare", "Centre", "Can", "Mariné,", "Institut", "Català", "de", "la", "Salut,", "Santa", "Coloma", "de", "Gramenet,", "Spain", "and", "11Unitat", "de", "Neurociències.", "Hospital", "Germans", "Trias", "i", "Pujol.", "Institut", "Català", "de", "la", "Salut.", "Badalona,", "Spain", "Email:", "María", "Teresa", "Alzamora*", "-", "mtalzamora.bnm.ics@gencat.net;", "José", "Miguel", "Baena-Díez", "-", "jbaenad@meditex.es;", "Marta", "Sorribes", "-", "martasorribes.pbcn@ics.scs.es;", "Rosa", "Forés", "-", "rfores.bnm.ics@gencat.net;", "Pere", "Toran", "-", "ptoran.bnm.ics@gencat.net;", "Marisa", "Vicheto", "-", "mvicheto@gmail.com;", "Guillem", "Pera", "-", "gpera.bnm.ics@gencat.net;", "María", "Dolores", "Reina", "-", "dreina.bnm.ics@gencat.net;", "Carlos", "Albaladejo", "-", "24270cab@comb.es;", "Judith", "Llussà", "-", "jllussa.bnm.ics@gencat.net;", "Magda", "Bundó", "-", "mbundo.bnm.ics@gencat.net;", "Amparo", "Sancho", "-", "asanchop.bnm.ics@gencat.net;", "Antonio", "Heras", "-", "aheras.bnm.ics@gencat.net;", "Joan", "Rubiés", "-", "jrubiesp@searteriosclerosis.org;", "Juan", "Francisco", "Arenillas", "-", "juanfarenillas@gmail.com", "*", "Corresponding", "author", "Published:", "11", "December", "2007", "BMC", "Public", "Health", "2007,", "7:348", "doi:10.1186/1471-2458-7-348", "This", "article", "is", "available", "from:", "http://www.biomedcentral.com/1471-2458/7/348", "Received:", "22", "August", "2007", "Accepted:", "11", "December", "2007", "©", "2007", "Alzamora", "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", "early", "diagnosis", "of", "atherosclerotic", "disease", "is", "essential", "for", "developing", "preventive", "strategies", "in", "populations", "at", "high", "risk", "and", "acting", "when", "the", "disease", "is", "still", "asymptomatic.", "A", "low", "ankle-", "arm", "index", "(AAI)", "is", "a", "good", "marker", "of", "vascular", "events", "and", "may", "be", "diminished", "without", "presenting", "symptomatology", "(silent", "peripheral", "arterial", "disease).", "The", "aim", "of", "the", "PERART", "study", "(PERipheral", "ARTerial", "disease)", "is", "to", "determine", "the", "prevalence", "of", "peripheral", "arterial", "disease", "(both", "silent", "and", "symptomatic)", "in", "a", "general", "population", "of", "both", "sexes", "and", "determine", "its", "predictive", "value", "related", "to", "morbimortality", "(cohort", "study).", "Methods/Design:", "This", "cross-over,", "cohort", "study", "consists", "of", "2", "phases:", "firstly", "a", "descriptive,", "transversal", "cross-over", "study", "to", "determine", "the", "prevalence", "of", "peripheral", "arterial", "disease,", "and", "secondly,", "a", "cohort", "study", "to", "evaluate", "the", "predictive", "value", "of", "AAI", "in", "relation", "to", "cardiovascular", "morbimortality.", "From", "September", "2006", "to", "June", "2007,", "a", "total", "of", "3,010", "patients", "over", "the", "age", "of", "50", "years", "will", "be", "randomly", "selected", "from", "a", "population", "adscribed", "to", "24", "healthcare", "centres", "in", "the", "province", "of", "Barcelona", "(Spain).", "Page", "1", "of", "7", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Hindawi", "Publishing", "Corporation", "Case", "Reports", "in", "Medicine", "Volume", "2012,", "Article", "ID", "471613,", "4", "pages", "doi:10.1155/2012/471613", "Case", "Report", "Pulmonary", "Blastoma:", "A", "Rare", "Primary", "Lung", "Malignancy", "Mahmoud", "S.", "Alahwal,1", "Iqbal", "H.", "Maniyar,1", "Faiza", "Saleem,1", "and", "Mariam", "Alshiekh2", "1", "Medical", "Oncology,", "Faculty", "of", "Medicine,", "King", "Abdulaziz", "University,", "Jeddah", "22254,", "Saudi", "Arabia", "2", "Faculty", "of", "Medicine,", "King", "Abdulaziz", "University,", "Jeddah", "22254,", "Saudi", "Arabia", "Correspondence", "should", "be", "addressed", "to", "Faiza", "Saleem,", "faizasal@gmail.com", "Received", "17", "July", "2012;", "Accepted", "16", "August", "2012", "Academic", "Editor:", "Ting", "Fan", "Leung", "Copyright", "©", "2012", "Mahmoud", "S.", "Alahwal", "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.", "Pulmonary", "blastoma,", "a", "rare", "primary", "lung", "malignancy,", "is", "considered", "to", "be", "distinct", "from", "other", "lung", "tumors", "based", "on", "pathological", "features,", "clinical", "course,", "and", "prognosis.", "More", "than", "one", "hundred", "cases", "have", "been", "reported", "in", "literature", "highlighting", "an", "interesting", "fact", "about", "their", "distinctive", "biologic", "manner", "from", "histopathological", "features.", "Classic", "pulmonary", "blastoma", "is", "composed", "of", "a", "mixture", "of", "immature", "epithelial", "and", "mesenchymal", "tissue", "resembling", "fetal", "lung", "tissue.", "Surgery", "is", "the", "mainstay", "of", "treatment.", "The", "prognosis", "of", "this", "rare", "malignancy", "is", "poor", "and", "the", "overall", "5-year", "survival", "is", "around", "15%.", "Our", "patient", "presented", "with", "respiratory", "symptoms", "and", "was", "found", "to", "have", "right-sided", "chest", "wall", "mass.", "The", "patient", "underwent", "complete", "surgical", "excision", "followed", "by", "6", "cycles", "of", "platinum-", "based", "chemotherapy.", "The", "patient", "showed", "good", "subjective", "and", "objective", "response", "with", "no", "evidence", "of", "disease", "recurrence.", "We", "report", "this", "rare", "malignancy", "with", "a", "review", "of", "literature,", "and", "the", "potential", "to", "use", "adjuvant", "chemotherapy", "in", "the", "management", "of", "this", "condition.", "1.", "Introduction", "Pulmonary", "blastoma", "(PB)", "is", "classified", "as", "one", "of", "the", "rare", "primary", "lung", "malignancies", "and", "is", "considered", "to", "be", "distinct", "from", "other", "lung", "tumors", "based", "on", "pathological", "features,", "clinical", "course", "and", "prognosis.", "PB", "is", "composed", "of", "a", "mixture", "of", "epithelial", "and", "mesenchymal", "tissues", "resembling", "embryonic", "lung", "tissue.", "Surgery", "is", "the", "standard", "treatment", "and", "the", "efficacy", "of", "adjuvant", "chemotherapy", "and", "radiotherapy", "has", "not", "yet", "been", "established.", "Platinum-based", "chemotherapy", "has", "been", "used", "with", "or", "without", "postoperative", "radiotherapy.", "The", "prognosis", "of", "this", "rare", "tumor", "is", "poor.", "We", "describe", "a", "case", "of", "this", "rare", "pulmonary", "malignancy", "and", "the", "role", "of", "adjuvant", "chemotherapy", "in", "the", "management", "and", "outcome.", "2.", "Case", "Report", "A", "16-year-old", "young", "Egyptian", "female", "presented", "with", "pro-", "gressive", "shortness", "of", "breath", "over", "a", "period", "of", "five", "years.", "The", "dyspnea", "was", "gradual", "in", "onset,", "at", "times", "precipitated", "by", "stress,", "but", "most", "of", "the", "time", "there", "was", "no", "precipitating", "factor.", "It", "was", "associated", "with", "severe", "nonproductive", "cough", "and", "bilateral", "headache.", "There", "was", "no", "significant", "past", "medical", "history.", "There", "was", "no", "history", "of", "fever,", "night", "sweats,", "and", "wheeze", "or", "chest", "pain.", "Also,", "there", "was", "no", "hoarseness", "of", "voice", "or", "hemop-", "tysis.", "The", "patient", "sought", "medical", "advice", "at", "a", "private", "health", "center", "when", "the", "patient’s", "daily", "activities", "gradually", "started", "getting", "affected.", "The", "patient", "was", "prescribed", "Salbutamol", "inhaler", "which", "gave", "her", "temporary", "relief.", "At", "the", "same", "time,", "the", "patient", "was", "diagnosed", "to", "have", "hyperthyroidism", "and", "was", "started", "on", "carbimazole.", "The", "patient", "took", "these", "medications", "for", "about", "4", "weeks", "and", "discontinued", "them", "against", "medical", "advice", "as", "she", "experienced", "lethargy", "and", "easy", "fatigability", "due", "to", "the", "sideeffects", "of", "the", "prescribed", "drugs.", "After", "a", "brief", "period", "of", "relief", "of", "symptoms,", "the", "patient", "again", "started", "to", "have", "dyspnea", "and", "presented", "to", "the", "Cardio-", "thoracic", "Unit", "in", "our", "hospital", "for", "evaluation.", "Baseline", "inves-", "tigations", "were", "done,", "which", "included", "complete", "blood", "count,", "renal", "function", "tests,", "and", "liver", "function", "tests;", "all", "were", "within", "the", "normal", "range.", "Chest", "X-ray", "showed", "a", "well-demarcated", "right", "upper", "lobe", "mass", "close", "to", "hilum", "(Figure", "1).", "Chest", "computed", "tomography", "(CT)", "scan", "showed", "bilateral", "thyroid", "nodules", "and", "a", "large", "well-defined", "heterogeneously", "enhancing", "mass", "measuring", "11", "×", "6", "cm", "with", "a", "central", "hypodensity", "at", "the", "right", "upper", "lobe", "with", "significant", "compression", "to", "the", "superior", "vena", "cava", "(Figure", "2).", "There", "was", "no", "evidence", "of", "significant" ]

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[ "Hindawi", "Publishing", "Corporation", "Thrombosis", "Volume", "2012,", "Article", "ID", "209052,", "6", "pages", "doi:10.1155/2012/209052", "Research", "Article", "Actual", "Situation", "of", "Thromboembolic", "Prophylaxis", "in", "Obesity", "Surgery:", "Data", "of", "Quality", "Assurance", "in", "Bariatric", "Surgery", "in", "Germany", "Christine", "Stroh,1,", "2", "D.", "Luderer,1", "R.", "Weiner,3", "T.", "Horbach,4,", "5", "K.", "Ludwig,6", "F.", "Benedix,7", "Stefanie", "Wolff,7", "C.", "Knoll,8", "H.", "Lippert,2,", "7", "and", "T.", "Manger1,", "2", "1", "Department", "of", "General,", "Abdominal", "and", "Pediatric", "Surgery,", "SRH", "Hospital,", "Straße", "des", "Friedens", "122,", "07548", "Gera,", "Germany", "2", "Institute", "for", "Quality", "Assurance", "in", "Operative", "Medicine,", "Otto-von-Guericke", "University,", "39106", "Magdeburg,", "Germany", "3", "Municipal", "Hospital", "Sachsenhausen,", "Frankfurt/Main,", "Germany", "4", "Friedrich-Alexander", "University,", "91054", "Erlangen-Nuremberg,", "Germany", "5", "Municipal", "Hospital,", "Schwabach,", "Germany", "6", "Municipal", "Hospital,", "Rostock", "Suedstadt,", "Germany", "7", "Otto-von-Guericke", "Universita¨t", "Magdeburg,", "39106", "Magdeburg,", "Germany", "8", "StatConsult,", "39112", "Magdeburg,", "Germany", "Correspondence", "should", "be", "addressed", "to", "Christine", "Stroh,", "christine.stroh@wkg.srh.de", "Received", "18", "March", "2012;", "Revised", "7", "May", "2012;", "Accepted", "7", "May", "2012", "Academic", "Editor:", "Domenico", "Prisco", "Copyright", "©", "2012", "Christine", "Stroh", "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.", "Background.", "Evidence-based", "data", "on", "optimal", "approach", "for", "prophylaxis", "of", "deep", "venous", "thrombosis", "(VTE)", "and", "pulmonary", "embolism", "(PE)", "in", "bariatric", "operations", "is", "discussed.", "Using", "antithrombotic", "prophylaxis", "weight", "adjusted", "the", "risk", "of", "VTE", "and", "its", "complications", "have", "to", "be", "balanced", "with", "the", "increased", "bleeding", "risk.", "Methods.", "Since", "2005", "the", "current", "situation", "for", "bariatric", "surgery", "has", "been", "examined", "by", "quality", "assurance", "study", "in", "Germany.", "As", "a", "prospective", "multicenter", "observational", "study,", "data", "on", "the", "type,", "regimen,", "and", "time", "course", "of", "VTE", "prophylaxis", "were", "documented.", "The", "incidences", "of", "clinically", "diagnosed", "VTE", "or", "PE", "were", "derived", "during", "the", "in-hospital", "course", "and", "follow", "up.", "Results.", "Overall,", "11,835", "bariatric", "procedures", "were", "performed", "between", "January", "2005", "and", "December", "2010.", "Most", "performed", "procedures", "were", "2730", "gastric", "banding", "(GB);", "4901", "Roux-en-Y-gastric", "bypass", "(RYGBP)", "procedures,", "and", "3026", "sleeve", "gastrectomies", "(SG).", "Study", "collective", "includes", "72.5%", "(mean", "BMI", "48.1", "kg/m2)", "female", "and", "27.5%", "(mean", "BMI", "50.5", "kg/m2)", "male", "patients.", "Incidence", "of", "VTE", "was", "0.06%", "and", "of", "PE", "0.08%.", "Conclusion.", "VTE", "prophylaxis", "regimen", "depends", "on", "BMI", "and", "the", "type", "of", "procedure.", "Despite", "the", "low", "incidence", "of", "VTE", "and", "PE", "there", "is", "a", "lack", "of", "evidence.", "Therefore,", "prospective", "randomized", "studies", "are", "necessary", "to", "determine", "the", "optimal", "VTE", "prophylaxis", "for", "bariatric", "surgical", "patients.", "1.", "Introduction", "Obesity", "has", "developed", "into", "an", "epidemic.", "Approximately", "1.7", "billion", "people", "are", "overweight,", "and", "312", "million", "are", "obese", "[1,", "2].", "In", "Germany", "in", "2009,", "60.1%", "of", "male", "and", "42.9%", "of", "female", "population", "were", "overweight", "[3].", "Morbid", "obesity", "is", "associated", "with", "increased", "health", "costs", "and", "an", "increased", "mortality", "risk", "[4,", "5].", "As", "a", "result", "of", "new", "technologies", "with", "lower", "risks", "and", "better", "long-term", "results,", "bariatric", "and", "metabolic", "surgeries", "have", "grown", "in", "popularity", "in", "recent", "years.", "The", "number", "of", "operations", "performed", "is", "rapidly", "increasing.", "However,", "bariatric", "surgery", "is", "associated", "with", "numerous", "peri-", "and", "post-", "operative", "complications.", "Venous", "thromboembolism", "is", "the", "most", "common", "postoperative", "complication.", "Obesity", "needs", "to", "be", "considered", "as", "one", "of", "the", "most", "serious", "factors", "predisposing", "patients", "to", "the", "development", "of", "thrombosis", "and", "pulmonary", "embolism.", "In", "addition,", "the", "risk", "for", "thromboembolism", "in", "metabolic", "surgery", "is", "high,", "and", "its", "detection", "is", "complicated.", "The", "guidelines", "of", "the", "German", "Society", "of", "Surgery", "suggest" ]

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[ "Hindawi", "Publishing", "Corporation", "Advances", "in", "Hematology", "Volume", "2011,", "Article", "ID", "258797,", "6", "pages", "doi:10.1155/2011/258797", "Review", "Article", "Role", "of", "Radiotherapy", "in", "Modern", "Treatment", "of", "Hodgkin’s", "Lymphoma", "Kheng-Wei", "Yeoh", "and", "N.", "George", "Mikhaeel", "Department", "of", "Clinical", "Oncology,", "Guy’s", "and", "St.", "Thomas’", "Hospital,", "London,", "UK", "Correspondence", "should", "be", "addressed", "to", "Kheng-Wei", "Yeoh,", "kwyeoh@doctors.org.uk", "Received", "21", "July", "2010;", "Accepted", "16", "September", "2010", "Academic", "Editor:", "Nelson", "J.", "Chao", "Copyright", "©", "2011", "K.-W.", "Yeoh", "and", "N.", "G.", "Mikhaeel.", "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.", "Hodgkin’s", "Lymphoma", "was", "incurable", "until", "the", "advent", "of", "effective", "therapeutic", "radiation", "around", "the", "first", "half", "of", "the", "20th", "century.", "As", "survival", "rates", "improved,", "the", "long-term", "toxicities", "from", "radiotherapy", "began", "to", "emerge.", "This", "together", "with", "the", "availability", "of", "effective", "chemotherapy", "has", "encouraged", "a", "combined", "modality", "approach", "for", "early-staged", "disease", "and", "the", "omission", "of", "radiotherapy", "in", "advanced-staged", "disease.", "The", "differing", "toxicities", "of", "radiotherapy", "and", "chemotherapy", "has", "promoted", "ongoing", "research", "to", "identify", "the", "utility", "of", "each", "of", "these", "modalities", "in", "the", "modern", "management", "of", "Hodgkin’s", "Lymphoma.", "This", "article", "will", "provide", "a", "critical", "review", "of", "the", "developments", "and", "indications", "for", "modern", "radiotherapy,", "in", "context", "with", "advances", "in", "chemotherapy,", "for", "the", "treatment", "of", "Hodgkin’s", "Lymphoma.", "1.", "Introduction", "During", "the", "first", "half", "of", "the", "20th", "century,", "Hodgkin’s", "Lym-", "phoma", "(HL)", "was", "incurable", "until", "the", "development", "of", "effective", "therapeutic", "radiation", "[1].", "It", "involved", "irradiating", "beyond", "the", "site", "of", "disease", "to", "include", "the", "adjacent", "nodal", "groups,", "the", "so-called", "extended", "field", "radiotherapy", "(EFRT)", "with", "total", "or", "subtotal", "nodal", "irradiation", "[2].", "With", "Radiotherapy", "(RT)", "alone,", "10-year", "relapse-free", "survival", "of", "around", "70%", "had", "been", "achieved", "in", "early-staged", "HL", "[3,", "4].", "However,", "advanced", "stage", "HL", "remained", "less", "curable", "with", "RT", "even", "with", "subtotal", "or", "total", "nodal", "RT", "until", "the", "introduction", "of", "combination", "chemotherapy.", "With", "the", "advent", "of", "effective", "chemotherapy", "regimes", "in", "the", "1980s", "with", "MOPP", "[5]", "and", "ABVD", "[6],", "better", "cure", "rates", "were", "achieved", "in", "advanced", "disease", "establishing", "chemotherapy", "as", "the", "main", "line", "of", "treatment", "in", "advanced", "disease.", "Gradually,", "chemotherapy", "use", "moved", "to", "earlier-stage", "disease,", "initially", "as", "a", "pre-RT", "treatment", "in", "bulky", "mediastinal", "cases", "to", "reduce", "the", "extent", "of", "mediastinal", "RT", "and", "later", "to", "improve", "the", "outcome", "of", "RT", "alone.", "With", "emerging", "reports", "of", "long-term", "toxicities", "from", "EFRT,", "namely", "with", "pulmonary,", "cardiac", "toxicity,", "and", "sec-", "ondary", "malignancies", "[7–13]", "together", "with", "studies", "showing", "that", "limited", "RT", "was", "sufficient", "after", "prior", "chemotherapy,", "combined", "modality", "treatment", "has", "been", "established", "in", "early", "disease.", "More", "recently,", "there", "has", "been", "several", "opinions", "calling", "on", "treating", "early", "stage", "HL", "with", "chemotherapy", "alone", "without", "RT,", "and", "this", "remains", "an", "interesting", "research", "question.", "The", "paper", "below", "will", "aim", "to", "highlight", "the", "developments", "of", "RT", "in", "HL", "treatment,", "with", "specific", "focus", "on", "its", "role", "in", "early,", "advanced,", "and", "relapsed", "disease.", "2.", "Developments", "in", "RT", "2.1.", "Background.", "The", "concept", "of", "RT", "to", "cure", "HL", "by", "Gilbert", "[14]", "was", "implemented", "with", "kilovoltage", "[15]", "and", "later", "with", "megavoltage", "machines", "[1].", "Doses", "of", "up", "to", "4500", "rads", "(1000", "rads/wk)", "were", "commonly", "used", "to", "treat", "extended", "fields", "in", "order", "to", "achieve", "total", "lymphoid", "irradiation", "(TLI).", "This", "included", "mantle", "field,", "inverted-Y", "techniques,", "and", "modifica-", "tions", "to", "include", "splenic", "irradiation,", "delivered", "with", "a", "parallel", "opposed", "technique.", "It", "was", "also", "not", "uncommon", "to", "irradiate", "liver", "and", "lungs", "involved", "with", "disease;", "all", "this", "was", "done", "when", "staging", "laparotomy", "and", "splenectomy", "were", "standard", "practice.", "In", "the", "light", "of", "RT", "toxicities,", "suboptimal", "relapse", "and", "survival", "rates", "together", "with", "the", "introduction", "of", "effective", "chemotherapy,", "the", "impetus", "to", "rationalise", "RT", "delivery", "became" ]

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[ "Baba", "et", "al.", "Radiation", "Oncology", "2010,", "5:81", "http://www.ro-journal.com/content/5/1/81", "R", "E", "S", "E", "A", "R", "C", "H", "Open", "Access", "Clinical", "outcomes", "of", "stereotactic", "body", "radiotherapy", "for", "stage", "I", "non-small", "cell", "lung", "cancer", "using", "different", "doses", "depending", "on", "tumor", "size", "Fumiya", "Baba1,2*,", "Yuta", "Shibamoto1,", "Hiroyuki", "Ogino1,", "Rumi", "Murata1,", "Chikao", "Sugie1,", "Hiromitsu", "Iwata1,", "Shinya", "Otsuka1", ",", "Katsura", "Kosaki1,", "Aiko", "Nagai1,", "Taro", "Murai1,", "Akifumi", "Miyakawa1", "Abstract", "Background:", "The", "treatment", "schedules", "for", "stereotactic", "body", "radiotherapy", "(SBRT)", "for", "lung", "cancer", "vary", "from", "institution", "to", "institution.", "Several", "reports", "have", "indicated", "that", "stage", "IB", "patients", "had", "worse", "outcomes", "than", "stage", "IA", "patients", "when", "the", "same", "dose", "was", "used.", "We", "evaluated", "the", "clinical", "outcomes", "of", "SBRT", "for", "stage", "I", "non-small", "cell", "lung", "cancer", "(NSCLC)", "treated", "with", "different", "doses", "depending", "on", "tumor", "diameter.", "Methods:", "Between", "February", "2004", "and", "November", "2008,", "124", "patients", "with", "stage", "I", "NSCLC", "underwent", "SBRT.", "Total", "doses", "of", "44,", "48,", "and", "52", "Gy", "were", "administered", "for", "tumors", "with", "a", "longest", "diameter", "of", "less", "than", "1.5", "cm,", "1.5-3", "cm,", "and", "larger", "than", "3", "cm,", "respectively.", "All", "doses", "were", "given", "in", "4", "fractions.", "Results:", "For", "all", "124", "patients,", "overall", "survival", "was", "71%,", "cause-specific", "survival", "was", "87%,", "progression-free", "survival", "was", "60%,", "and", "local", "control", "was", "80%,", "at", "3", "years.", "The", "3-year", "overall", "survival", "was", "79%", "for", "85", "stage", "IA", "patients", "treated", "with", "48", "Gy", "and", "56%", "for", "37", "stage", "IB", "patients", "treated", "with", "52", "Gy", "(p", "=", "0.05).", "At", "3", "years,", "cause-specific", "survival", "was", "91%", "for", "the", "former", "group", "and", "79%", "for", "the", "latter", "(p", "=", "0.18),", "and", "progression-free", "survival", "was", "62%", "versus", "54%", "(p", "=", "0.30).", "The", "3-year", "local", "control", "rate", "was", "81%", "versus", "74%", "(p", "=", "0.35).", "The", "cumulative", "incidence", "of", "grade", "2", "or", "3", "radiation", "pneumonitis", "was", "11%", "in", "stage", "IA", "patients", "and", "30%", "in", "stage", "IB", "patients", "(p", "=", "0.02).", "Conclusions:", "There", "was", "no", "difference", "in", "local", "control", "between", "stage", "IA", "and", "IB", "tumors", "despite", "the", "difference", "in", "tumor", "size.", "The", "benefit", "of", "increasing", "the", "SBRT", "dose", "for", "larger", "tumors", "should", "be", "investigated", "further.", "Background", "Stereotactic", "body", "radiotherapy", "(SBRT)", "for", "lung", "tumors", "was", "introduced", "in", "the", "mid", "1990s", "[1],", "and", "it", "has", "been", "performed", "in", "many", "institutions", "as", "a", "new", "treatment", "modality", "for", "stage", "I", "primary", "lung", "cancer", "and", "oligometa-", "static", "lung", "cancer.", "Promising", "clinical", "results", "have", "been", "reported", "despite", "the", "use", "of", "various", "treatment", "protocols", "[2-9].", "According", "to", "a", "recently", "published", "survey", "of", "SBRT", "in", "Japan,", "the", "treatment", "techniques", "and", "schedules", "applied", "for", "SBRT", "for", "lung", "cancer", "varied", "greatly", "from", "institution", "to", "institution", "[10].", "The", "most", "frequently", "used", "*", "Correspondence:", "fbaba@bd5.so-net.ne.jp", "1Department", "of", "Radiology,", "Nagoya", "City", "University", "Graduate", "School", "of", "Medical", "Sciences,", "Nagoya,", "Japan", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "schedule", "was", "48", "Gy", "in", "4", "fractions", "for", "both", "stage", "IA", "and", "IB", "primary", "lung", "cancer", "and", "metastatic", "lung", "cancer.", "As", "a", "result,", "it", "was", "found", "that", "the", "outcomes", "of", "stage", "IB", "patients", "were", "worse", "than", "those", "of", "stage", "IA", "patients", "at", "the", "same", "dose", "[3-5],", "which", "suggests", "that", "SBRT", "doses", "should", "be", "adjusted", "according", "to", "tumor", "size.", "We", "have", "performed", "SBRT", "for", "lung", "tumors", "since", "2004", "and", "changed", "the", "pre-", "scribed", "dose", "depending", "on", "tumor", "diameter.", "In", "this", "study,", "we", "report", "the", "clinical", "outcomes", "of", "SBRT", "performed", "with", "our", "prospective", "hypothesis-driven", "protocol.", "Methods", "Eligibility", "Criteria", "The", "eligibility", "criteria", "were", "as", "follows:", "histologically-", "confirmed", "non-small", "cell", "lung", "cancer", "(NSCLC)", "©", "2010", "Baba", "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.", "Environ.", "Res.", "Public", "Health", "2012,", "9,", "24-32;", "doi:10.3390/ijerph9010024", "OPEN", "ACCESS", "International", "Journal", "of", "Environmental", "Research", "and", "Public", "Health", "ISSN", "1660-4601", "www.mdpi.com/journal/ijerph", "Article", "Essential", "Questions", "on", "Suicide", "Bereavement", "and", "Postvention", "Karl", "Andriessen", "1,*", "and", "Karolina", "Krysinska", "2", "1", "Suicide", "Prevention", "Program", "of", "the", "Flemish", "Community", "Mental", "Health", "Centres,", "9000", "Gent,", "Belgium", "2", "Unit", "for", "Clinical", "Psychology", "Research,", "Faculty", "of", "Psychology", "and", "Educational", "Sciences,", "Catholic", "University", "Leuven,", "3000", "Leuven,", "Belgium;", "E-Mail:", "karolina.krysinska@ppw.kuleuven.be", "*", "Author", "to", "whom", "correspondence", "should", "be", "addressed;", "E-Mail:", "karl.andriessen@pandora.be;", "Tel.:", "+32-9-233-5099.", "Received:", "8", "November", "2011;", "in", "revised", "form:", "12", "December", "2011", "/", "Accepted:", "21", "December", "2011", "/", "Published:", "27", "December", "2011", "Abstract:", "During", "the", "past", "decades", "public", "and", "research", "interest", "in", "postvention,", "i.e.,", "support", "for", "families", "and", "communities", "after", "a", "suicide,", "has", "increased.", "However,", "the", "postvention", "field", "is", "still", "facing", "a", "number", "of", "important", "challenges", "and", "questions.", "This", "article", "aims", "to", "discuss", "a", "series", "of", "essential", "issues", "on", "suicide", "bereavement", "and", "postvention,", "regarding", "the", "current", "state", "of", "the", "art", "and", "future", "developments.", "Who", "is", "a", "suicide", "survivor", "and", "how", "many", "suicide", "survivors", "are", "there?", "Is", "suicide", "bereavement", "different", "from", "other", "types", "of", "bereavement?", "What", "are", "the", "needs", "of", "suicide", "survivors", "and", "what", "is", "postvention", "from", "a", "clinical", "perspective", "and", "from", "a", "public", "health", "perspective?", "Can", "postvention", "be", "prevention?", "With", "this", "last", "question,", "the", "article", "concludes", "with", "a", "series", "of", "recommendations", "in", "order", "to", "strengthen", "the", "potential", "of", "postvention", "as", "prevention.", "Keywords:", "suicide;", "prevention;", "postvention;", "bereavement;", "public", "health;", "policy", "1.", "Introduction", "Any", "discussion", "of", "suicide,", "a", "serious", "public", "health", "problem", "claiming", "globally", "approximately", "one", "million", "victims", "per", "year,", "will", "be", "incomplete", "without", "taking", "into", "consideration", "the", "perspective", "of", "the", "bereaved,", "or", "in", "other", "word,", "the", "suicide", "survivors.", "Their", "number", "is", "significantly", "higher", "than", "the", "number", "of", "suicide", "victims", "and", "some", "of", "the", "survivors", "have", "to", "cope", "with", "serious", "and", "long", "lasting", "psycho-social", "sequelae", "of", "the", "loss,", "including", "increased", "risk", "of", "suicidality.", "Although", "a", "wide", "range", "of" ]

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[ "BMC", "Musculoskeletal", "Disorders", "BioMed", "Central", "3BR2M0e0Cs2eM,ausrccuhlosakerltetiacllDeisorders", "x", "Systemic", "alendronate", "prevents", "resorption", "of", "necrotic", "bone", "during", "revascularization.", "A", "bone", "chamber", "study", "in", "rats", "Jörgen", "Åstrand*1", "and", "Per", "Aspenberg1,2", "Address:", "1Department", "of", "Orthopaedics,", "Lund", "University", "Hospital,", "Lund,", "Sweden", "and", "2Division", "of", "Orthopaedics,", "Department", "of", "Neuroscience", "and", "Locomotion,", "Faculty", "of", "Medicine,", "Linköping", "University,", "Linköping,", "Sweden", "E-mail:", "Jörgen", "Åstrand*", "-", "jorgen.astrand@ort.lu.se;", "Per", "Aspenberg", "-", "Per.Aspenberg@inr.liu.se", "*Corresponding", "author", "Published:", "7", "August", "2002", "BMC", "Musculoskeletal", "Disorders", "2002,", "3:19", "This", "article", "is", "available", "from:", "http://www.biomedcentral.com/1471-2474/3/19", "Received:", "4", "March", "2002", "Accepted:", "7", "August", "2002", "©", "2002", "Åstrand", "and", "Aspenberg;", "licensee", "BioMed", "Central", "Ltd.", "This", "article", "is", "published", "in", "Open", "Access:", "verbatim", "copying", "and", "redistribution", "of", "this", "article", "are", "permitted", "in", "all", "media", "for", "any", "non-commercial", "purpose,", "provided", "this", "notice", "is", "preserved", "along", "with", "the", "article's", "original", "URL.", "Abstract", "Background:", "Avascular", "necrosis", "of", "bone", "(osteonecrosis)", "can", "cause", "structural", "failure", "and", "subsequent", "deformation,", "leading", "to", "joint", "dysfunction", "and", "pain.", "Structural", "failure", "is", "the", "result", "of", "resorption", "of", "necrotic", "bone", "during", "revascularization,", "before", "new", "bone", "has", "formed", "or", "consolidated", "enough", "for", "loadbearing.", "Bone", "resorption", "can", "be", "reduced", "by", "bisphosphonates.", "If", "resorption", "of", "the", "necrotic", "bone", "could", "be", "reduced", "during", "the", "revascularization", "phase", "until", "sufficient", "new", "bone", "has", "formed,", "it", "would", "appear", "that", "structural", "failure", "could", "be", "avoided.", "Methods:", "To", "test", "whether", "resorption", "of", "necrotic", "bone", "can", "be", "prevented,", "structural", "grafts", "were", "subjected", "to", "new", "bone", "ingrowth", "during", "systemic", "bisphosphonate", "treatment", "in", "a", "rat", "model.", "Results:", "In", "rats", "treated", "with", "alendronate", "the", "necrotic", "bone", "was", "not", "resorbed,", "whereas", "it", "was", "almost", "entirely", "resorbed", "in", "the", "controls.", "Conclusion:", "Systemic", "alendronate", "treatment", "prevents", "resorption", "of", "necrotic", "bone", "during", "revascularization.", "In", "patients", "with", "osteonecrosis,", "bisphosphonates", "may", "therefore", "prevent", "collapse", "of", "the", "necrotic", "bone.", "Background", "Osteonecrosis", "is", "caused", "by", "insufficient", "circulation.", "This", "situation", "can", "occur", "after", "trauma", "or", "be", "the", "result", "of", "other", "events", "or", "conditions", "that", "can", "compromise", "circulation,", "such", "as", "corticosteroid", "treatment,", "scuba", "diving,", "sickle", "cell", "anaemia,", "alcoholism", "and", "pregnancy.", "Osteonecrosis", "can", "lead", "to", "structural", "failure,", "with", "subsequent", "collapse", "and", "de-", "formation", "of", "the", "bone", "leading", "to", "joint", "dysfunction", "and", "pain.", "Gardeniers", "[1]", "performed", "a", "series", "of", "experiments,", "where", "a", "section", "of", "the", "femoral", "head", "in", "goats", "was", "removed", "and", "reattached", "using", "bone", "cement.", "The", "cement", "layer", "pre-", "vented", "revascularization,", "which", "was", "verified", "with", "angiog-", "raphy", "and", "histology.", "No", "collapse", "occurred,", "and", "mechanical", "testing", "of", "the", "avascular", "segment", "showed", "no", "weakening", "compared", "to", "vital", "controls.", "However,", "when", "a", "hole", "was", "drilled", "through", "the", "cement", "layer", "in", "a", "second", "op-", "eration,", "revascularization", "ocurred", "and", "collapse", "of", "the", "fem-", "oral", "head", "segment", "followed.", "Mechanical", "testing", "confirmed", "weakening", "of", "the", "revascularized", "segments.", "Others", "have", "confirmed", "that", "necrotic", "bone", "retains", "load", "bearing", "capacity", "[2],", "and", "evidence", "can", "also", "be", "found", "in", "tools", "made", "of", "bone,", "which", "have", "been", "known", "since", "neo-", "lithicum.", "Consequently", "the", "death", "of", "bone", "cells", "per", "se", "does", "not", "cause", "structural", "failure.", "Rather,", "it", "is", "caused", "by", "the", "re-", "sorption", "of", "necrotic", "bone", "[3][1].", "Resorption", "is", "mediated", "Page", "1", "of", "5", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Cellular", "Onc.", "(2011)", "34:3–10", "DOI", "10.1007/s13402-010-0007-3", "ORIGINAL", "PAPER", "Expression", "of", "the", "stem", "cell", "marker", "ALDH1", "in", "BRCA1", "related", "breast", "cancer", "Marise", "R.", "Heerma", "van", "Voss", "&", "Petra", "van", "der", "Groep", "&", "Joost", "Bart", "&", "Elsken", "van", "der", "Wall", "&", "Paul", "J.", "van", "Diest", "Accepted:", "11", "December", "2010", "/", "Published", "online:", "19", "February", "2011", "#", "The", "Author(s)", "2011.", "This", "article", "is", "published", "with", "open", "access", "at", "Springerlink.com", "Abstract", "Introduction", "The", "BRCA1", "protein", "makes", "mammary", "stem", "cells", "differentiate", "into", "mature", "luminal", "and", "myoepithelial", "cells.", "If", "a", "BRCA1", "mutation", "results", "in", "a", "differentiation", "block,", "an", "enlarged", "stem", "cell", "component", "might", "be", "present", "in", "the", "benign", "tissue", "of", "BRCA1", "mutation", "carriers,", "and", "these", "mammary", "stem", "cells", "could", "be", "the", "origin", "of", "BRCA1", "related", "breast", "cancer.", "Since", "ALDH1", "is", "a", "marker", "of", "both", "mammary", "stem", "cells", "and", "breast", "cancer", "stem", "cells,", "we", "compared", "ALDH1", "expression", "in", "malignant", "tissue", "of", "BRCA1", "mutation", "carriers", "to", "non-carriers.", "Methods", "Forty-one", "BRCA1", "related", "breast", "cancers", "and", "41", "age-matched", "sporadic", "breast", "cancers", "were", "immunohisto-", "chemically", "stained", "for", "ALDH1.", "Expression", "in", "epithelium", "and", "stroma", "was", "scored", "and", "compared.", "Results", "Epithelial", "(P=", "0.001)", "and", "peritumoral", "(P=", "0.001)", "ALDH1", "expression", "was", "significantly", "higher", "in", "invasive", "BRCA1", "related", "carcinomas", "compared", "to", "sporadic", "carcino-", "mas.", "Intratumoral", "stromal", "ALDH1", "expression", "was", "similarly", "high", "in", "both", "groups.", "ALDH1", "tumor", "cell", "expression", "was", "an", "independent", "predictor", "of", "BRCA1", "mutation", "status.", "Conclusion", "BRCA1", "related", "breast", "cancers", "showed", "signifi-", "cantly", "more", "frequent", "epithelial", "ALDH1", "expression,", "indi-", "M.", "R.", "Heerma", "van", "Voss", ":", "P.", "J.", "van", "Diest", "(*)", "Department", "of", "Pathology,", "University", "Medical", "Center", "Utrecht,", "PO", "Box", "85500,", "3508", "GA", "Utrecht,", "The", "Netherlands", "e-mail:", "p.j.vandiest@umcutrecht.nl", "P.", "van", "der", "Groep", ":", "E.", "van", "der", "Wall", "Department", "of", "Internal", "Medicine,", "University", "Medical", "Center", "Utrecht,", "Utrecht,", "The", "Netherlands", "J.", "Bart", "Department", "of", "Pathology,", "University", "Medical", "Center", "Groningen,", "Groningen,", "The", "Netherlands", "cating", "that", "these", "hereditary", "tumors", "have", "an", "enlarged", "cancer", "stem", "cell", "component.", "Besides,", "(peritumoral)", "stromal", "ALDH1", "expression", "was", "also", "more", "frequent", "in", "BRCA1", "mutation", "carriers.", "ALDH1", "may", "therefore", "be", "a", "diagnostic", "marker", "and", "a", "therapeutic", "target", "of", "BRCA1", "related", "breast", "cancer.", "Keywords", "Breast", "cancer", ".", "BRCA1", ".", "ALDH1", ".", "Stem", "cells", ".", "Hereditary", "breast", "cancer", "1", "Introduction", "Germline", "mutation", "carriers", "of", "the", "BRCA1", "gene", "locus", "harbor", "a", "high", "cumulative", "risk", "of", "developing", "breast", "and", "ovarian", "cancer", "of", "57%", "and", "40%", "by", "age", "70,", "respectively", "[1].", "BRCA1", "related", "breast", "cancer", "shows", "a", "distinct", "histopatho-", "logical", "and", "immunohistochemical", "phenotype.", "It", "has", "been", "shown", "to", "be", "more", "often", "of", "the", "ductal", "or", "medullary", "types,", "of", "high", "grade", "and", "to", "show", "a", "high", "mitotic", "activity", "index", "(MAI)", "and", "necrosis", "[2–4].", "These", "tumors", "usually", "do", "not", "express", "the", "estrogen", "(ER)", "and", "progesterone", "receptors", "(PR)", "and", "are", "almost", "always", "HER-2/neu", "negative", "(“triple", "negative”)", "[2,", "3].", "At", "the", "gene-expression", "level", "these", "tumors", "cluster", "together", "with", "the", "basal-like", "subgroup", "[5].", "BRCA1", "seems", "to", "play", "an", "important", "role", "in", "DNA", "repair", "in", "a", "common", "pathway", "with", "BRCA2", "[6].", "Increasing", "evidence", "indicates", "that", "BRCA1", "is", "necessary", "for", "mammary", "stem", "cell", "differen-", "tiation,", "a", "function", "that", "could", "explain", "its", "tissue-specificity", "[7–10].", "Stem", "cells", "play", "a", "role", "in", "repopulating", "the", "breast", "at", "several", "points", "in", "the", "human", "female", "lifespan.", "These", "primitive", "cells", "facilitate", "rapid", "expansion", "and", 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[ "JCB:", "Article", "Y", "G", "O", "L", "O", "I", "B", "L", "L", "E", "C", "F", "O", "L", "A", "N", "R", "U", "O", "J", "E", "H", "T", "Rb", "and", "p130", "control", "cell", "cycle", "gene", "silencing", "to", "maintain", "the", "postmitotic", "phenotype", "in", "cardiac", "myocytes", "Patima", "Sdek,1", "Peng", "Zhao,1", "Yaping", "Wang,1", "Chang-jiang", "Huang,2", "Christopher", "Y.", "Ko,1", "Peter", "C.", "Butler,2", "James", "N.", "Weiss,1", "and", "W.", "Robb", "MacLellan1", "1Cardiovascular", "Research", "Laboratory,", "Department", "of", "Medicine", "and", "Department", "of", "Physiology,", "and", "2Larry", "Hillblom", "Islet", "Research", "Center,", "David", "Geffen", "School", "of", "Medicine,", "University", "of", "California,", "Los", "Angeles,", "Los", "Angeles,", "CA", "90095", "T", "soon", "after", "birth.", "Adult", "cardiac", "myocytes", "(ACMs)", "he", "mammalian", "heart", "loses", "its", "regenerative", "potential", "permanently", "exit", "the", "cell", "cycle,", "and", "E2F-dependent", "genes", "are", "stably", "silenced,", "although", "the", "underlying", "mech-", "anism", "is", "unclear.", "Heterochromatin,", "which", "silences", "genes", "in", "many", "biological", "contexts,", "accumulates", "with", "cardiac", "differentiation.", "H3K9me3,", "a", "histone", "methylation", "charac-", "teristic", "of", "heterochromatin,", "also", "increases", "in", "ACMs", "and", "at", "E2F-dependent", "promoters.", "We", "hypothesize", "that", "genes", "relevant", "for", "cardiac", "proliferation", "are", "targeted", "to", "hetero-", "chromatin", "by", "retinoblastoma", "(Rb)", "family", "members", "inter-", "acting", "with", "E2F", "transcription", "factors", "and", "recruiting", "heterochromatin", "protein", "1", "(HP1)", "proteins.", "To", "test", "this", "hypothesis,", "we", "created", "cardiac-specific", "Rb", "and", "p130", "inducible", "double", "knockout", "(IDKO)", "mice.", "IDKO", "ACMs", "showed", "a", "decrease", "in", "total", "heterochromatin,", "and", "cell", "cycle", "genes", "were", "derepressed,", "leading", "to", "proliferation", "of", "ACMs.", "Although", "Rb/p130", "deficiency", "had", "no", "effect", "on", "total", "H3K9me3", "levels,", "recruitment", "of", "HP1-", "to", "promoters", "was", "lost.", "Depleting", "HP1-", "up-regulated", "proliferation-promoting", "genes", "in", "ACMs.", "Thus,", "Rb", "and", "p130", "have", "overlapping", "roles", "in", "maintaining", "the", "postmitotic", "state", "of", "ACMs", "through", "their", "interaction", "with", "HP1-", "to", "direct", "heterochromatin", "formation", "and", "silencing", "of", "proliferation-promoting", "genes.", "Introduction", "Some", "amphibians,", "as", "well", "as", "teleost", "fish,", "have", "a", "robust", "capacity", "to", "regenerate", "their", "hearts", "after", "injury", "throughout", "their", "life", "(Poss", "et", "al.,", "2002).", "Adult", "zebrafish,", "for", "example,", "can", "fully", "regenerate", "their", "heart", "without", "scar", "formation", "after", "up", "to", "20%", "of", "the", "ventri-", "cle", "has", "been", "resected.", "This", "regenerative", "response", "is", "thought", "to", "occur", "primarily", "through", "dedifferentiation", "and", "proliferation", "of", "existing", "myocytes", "(Jopling", "et", "al.,", "2010;", "Kikuchi", "et", "al.,", "2010).", "Recent", "studies", "have", "demonstrated", "that", "the", "embryonic", "mamma-", "lian", "heart", "is", "also", "capable", "of", "mounting", "a", "hyperplastic", "response", "to", "injury", "but", "that", "this", "is", "lost", "rapidly", "after", "birth", "(Drenckhahn", "et", "al.,", "2008;", "Porrello", "et", "al.,", "2011).", "Although", "some", "studies", "have", "sug-", "gested", "that", "the", "adult", "mammalian", "heart", "possesses", "a", "very", "limited", "capacity", "for", "new", "cardiomyocyte", "formation,", "the", "source", "has", "been", "Correspondence", "to", "W.", "Robb", "MacLellan:", "rmaclellan@mednet.ucla.edu", "Abbreviations", "used", "in", "this", "paper:", "ACM,", "adult", "cardiac", "myocyte;", "ANF,", "atrial", "natriuretic", "factor;", "ChIP,", "chromatin", "IP;", "HP1,", "heterochromatin", "protein", "1;", "IDKO,", "inducible", "double", "knockout;", "IP,", "immunoprecipitation;", "ITS,", "insulin-transferrin-", "selenium;", "MCM,", "MerCreMer;", "MHC,", "myosin", "heavy", "chain;", "NI,", "nonionic;", "NRVM,", "neonatal", "rat", "ventricular", "myocyte;", "NS,", "nonspecific;", "PSG,", "penicillin-streptomycin-", "glutamine;", "Rb,", "retinoblastoma;", "TAC,", "trans-aortic", "constriction;", "TAM,", "tamoxifen;", "TLVM,", "time-lapse", "video", "microscopy;", "WT,", "wild", "type.", "The", "Rockefeller", "University", "Press", "$30.00", "J.", "Cell", "Biol.", "Vol.", "194", "No.", "3", "407–423", "www.jcb.org/cgi/doi/10.1083/jcb.201012049", "postulated", "to", "be", "endogenous", "cardiac", "stem", "cells,", "not", "existing", "myocytes", "(Pasumarthi", "and", "Field,", "2002;", "Hsieh", "et", "al.,", "2007;", "Bergmann", "et", "al.,", "2009).", "Thus,", "the", "vast", "majority", "of", "cardiac", "myo-", "cytes", "permanently", "exits", "the", "cell", "cycle", "soon", "after", "birth", "in", "mam-", "mals,", "and,", "when", "adult", "cardiac", "myocytes", "(ACMs)", "are", "subjected", "to", "a", "growth", "stimulus,", "they", "undergo", "an", "increase", "in", "cell", "size", "(hypertrophy)", "but", "do", "not", "proliferate.", "The", "molecular", "basis", "for", "the", "postmitotic", "state", "of", "ACMs", "is", "unknown,", "but", "the", "subset", "of", "E2F-dependent", "genes", "specifically", "involved", "in", "regulating", "G2/M", "and", "cytokinesis", "is", "not", "up-regulated", "after", "growth", "stimuli", "in", "ACMs.", "The", "mechanisms", "that", "irreversibly", "silence", "these", "genes", "are", "un-", "known;", "however,", "stable", "transcriptional", "silencing", "in", "eukaryotic", "cells", "is", "often", "caused", "by", "specific", "histone", "modifications", "that", "result", "in", "heterochromatin", "formation", "around", "a", "gene,", "making", "it", "inacces-", "sible", "to", "transcriptional", "machinery.", "©", "2011", "Sdek", "et", "al.", "This", "article", "is", "distributed", "under", "the", "terms", "of", "an", "Attribution–", "Noncommercial–Share", "Alike–No", "Mirror", "Sites", "license", "for", "the", "first", "six", "months", "after", "the", "pub-", "lication", "date", "(see", "http://www.rupress.org/terms).", "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/).", "JCB", "407" ]

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[ "Ferreira", "et", "al.", "BMC", "Genomics", "2010,", "11:93", "http://www.biomedcentral.com/1471-2164/11/93", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "Comparative", "transcriptome", "analysis", "coupled", "to", "X-ray", "CT", "reveals", "sucrose", "supply", "and", "growth", "velocity", "as", "major", "determinants", "of", "potato", "tuber", "starch", "biosynthesis", "Stephanus", "J", "Ferreira1,", "Melanie", "Senning1,", "Sophia", "Sonnewald1,", "Petra-Maria", "Keßling2,", "Ralf", "Goldstein3,", "Uwe", "Sonnewald1*", "Abstract", "Background:", "Even", "though", "the", "process", "of", "potato", "tuber", "starch", "biosynthesis", "is", "well", "understood,", "mechanisms", "regulating", "biosynthesis", "are", "still", "unclear.", "Transcriptome", "analysis", "provides", "valuable", "information", "as", "to", "how", "genes", "are", "regulated.", "Therefore,", "this", "work", "aimed", "at", "investigating", "transcriptional", "regulation", "of", "starch", "biosynthetic", "genes", "in", "leaves", "and", "tubers", "of", "potato", "plants", "under", "various", "conditions.", "More", "specifically", "we", "looked", "at", "gene", "expression", "diurnally", "in", "leaves", "and", "tubers,", "during", "tuber", "induction", "and", "in", "tubers", "growing", "at", "different", "velocities.", "To", "determine", "velocity", "of", "potato", "tuber", "growth", "a", "new", "method", "based", "on", "X-ray", "Computed", "Tomography", "(X-ray", "CT)", "was", "established.", "Results:", "Comparative", "transcriptome", "analysis", "between", "leaves", "and", "tubers", "revealed", "striking", "similarities", "with", "the", "same", "genes", "being", "differentially", "expressed", "in", "both", "tissues.", "In", "tubers,", "oscillation", "of", "granule", "bound", "starch", "synthase", "(GBSS)", "expression)", "was", "observed", "which", "could", "be", "linked", "to", "sucrose", "supply", "from", "source", "leaves.", "X-ray", "CT", "was", "used", "to", "determine", "time-dependent", "changes", "in", "tuber", "volume", "and", "the", "growth", "velocity", "was", "calculated.", "Although", "there", "is", "not", "a", "linear", "correlation", "between", "growth", "velocity", "and", "expression", "of", "starch", "biosynthetic", "genes,", "there", "are", "significant", "differences", "between", "growing", "and", "non-growing", "tubers.", "Co-expression", "analysis", "was", "used", "to", "identify", "transcription", "factors", "positively", "correlating", "with", "starch", "biosynthetic", "genes", "possibly", "regulating", "starch", "biosynthesis.", "Conclusion:", "Most", "starch", "biosynthetic", "enzymes", "are", "encoded", "by", "gene", "families.", "Co-expression", "analysis", "revealed", "that", "the", "same", "members", "of", "these", "gene", "families", "are", "co-regulated", "in", "leaves", "and", "tubers.", "This", "suggests", "that", "regulation", "of", "transitory", "and", "storage", "starch", "biosynthesis", "in", "leaves", "and", "tubers,", "respectively,", "is", "surprisingly", "similar.", "X-ray", "CT", "can", "be", "used", "to", "monitor", "growth", "and", "development", "of", "belowground", "organs", "and", "allows", "to", "link", "tuber", "growth", "to", "changes", "in", "gene", "expression.", "Comparative", "transcriptome", "analysis", "provides", "a", "useful", "tool", "to", "identify", "transcription", "factors", "possibly", "involved", "in", "the", "regulation", "of", "starch", "biosynthesis.", "Background", "Starch", "is", "not", "only", "the", "most", "important", "carbohydrate", "source", "to", "the", "human", "diet,", "but", "has", "major", "industrial", "applications.", "It", "consists", "of", "two", "major", "fractions,", "amylose", "and", "amylopectin.", "Amylose", "is", "essentially", "a", "linear", "polymer", "of", "glucose", "units", "linked", "with", "alpha", "(1,4)", "bonds", "whilst", "amylopectin", "has", "a", "higher", "percentage", "of", "branched", "alpha", "(1,6)", "bonds.", "Due", "to", "its", "importance,", "crop", "plants", "*", "Correspondence:", "usonne@biologie.uni-erlangen.de", "1Friedrich-Alexander-University", "Erlangen-Nuremberg,", "Department", "of", "Biology,", "Staudtstrasse", "5,", "91058", "Erlangen,", "Germany", "producing", "starch", "in", "large", "quantities", "have", "been", "exten-", "sively", "researched.", "The", "fourth", "most", "important", "crop", "in", "the", "world", "in", "terms", "of", "total", "biomass", "produced", "is", "potato", "and", "this", "is", "due", "to", "its", "starchy", "tuber", "which", "can", "store", "up", "to", "80%", "of", "its", "dry", "weight", "as", "starch", "[1].", "In", "potato", "starch", "is", "either", "accumulated", "transiently", "in", "leaves", "or", "as", "storage", "starch", "in", "tubers.", "In", "leaves", "starch", "is", "synthesised", "in", "the", "chloroplast", "from", "triose-phosphates", "produced", "during", "photosynthesis.", "After", "several", "inter-", "mediate", "steps,", "glucose", "6-phosphate", "is", "converted", "to", "glu-", "cose", "1-phosphate", "by", "the", "enzyme", "phosphoglucomutase", "(PGM).", "Glucose", "1-phosphate,", "along", "with", "ATP", "serves", "as", "©", "2010", "Ferreira", "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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[ "YALE", "JOURNAL", "OF", "BIOLOGY", "AND", "MEDICINE", "80", "(2007),", "pp.", "95-103", "Copyright", "©", "2007.", "REVIEW", "Impact", "of", "Placental", "Plasmodium", "falciparum", "Malaria", "on", "Pregnancy", "and", "Perinatal", "Outcome", "in", "Sub-Saharan", "Africa", "II:", "Effects", "of", "Placental", "Malaria", "on", "Perinatal", "Outcome;", "Malaria", "and", "HIV", "Chigozie", "J.", "Uneke", "Faculty", "of", "Clinical", "Medicine,", "Ebonyi", "State", "University,", "Nigeria", "Placental", "malaria", "is", "recognized", "as", "a", "common", "complication", "of", "malaria", "in", "pregnancy", "in", "areas", "of", "stable", "transmission,", "and,", "as", "a", "consequence,", "serious", "health", "problems", "arise", "for", "the", "mother", "and", "especially", "her", "baby", "[1].", "Although", "malaria", "in", "pregnancy", "is", "a", "major", "factor", "associated", "with", "adverse", "perinatal", "outcome,", "the", "link", "between", "malaria", "and", "perinatal", "morbidity/mortality", "is", "less", "clear", "in", "areas", "with", "stable", "endemic", "malaria", "where", "pregnant", "women", "have", "acquired", "immunity", "[2].", "Histological", "examination", "of", "the", "placenta", "is", "a", "predictor", "of", "fetal", "morbidity,", "as", "well", "as", "being", "the", "most", "sensitive", "detector", "of", "maternal", "infection", "[3].", "Adverse", "perinatal", "outcome", "has", "been", "described", "as", "an", "important", "indicator", "of", "poor", "quality", "of", "obstetric", "care", "and", "social", "development", "[4].", "A", "variety", "of", "adverse", "perinatal", "outcomes", "associ-", "ated", "with", "placental", "malaria", "have", "been", "described,", "including", "low", "birth", "weight,", "preterm", "delivery,", "intrauterine", "growth", "retardation,", "fetal", "anemia,", "congenital", "malaria,", "and", "fetal", "mortality.", "The", "most", "common", "clinical", "features", "in", "80", "percent", "of", "perinatal", "cases", "are", "fever,", "anemia,", "and", "splenomegaly", "[5].", "Other", "signs", "and", "symptoms", "include", "hepatomegaly,", "jaundice,", "regurgitation,", "loose", "stools,", "poor", "feeding,", "and,", "occasionally,", "drowsiness,", "restlessness,", "and", "cyanosis", "also", "can", "be", "seen", "[5,6].", "A", "review", "of", "studies", "that", "investigated", "these", "poor", "fetal", "outcomes", "associated", "with", "placental", "malaria", "in", "sub-Saharan", "Africa", "is", "presented", "here.", "ADVERSE", "OUTCOMES", "OF", "PLACENTAL", "MALARIA", "Congenital", "malaria", "Malaria", "during", "pregnancy", "may", "result", "in", "fetal", "exposure", "to", "malaria", "if", "parasites", "are", "transmitted", "across", "the", "placenta", "and", "could", "re-", "sult", "in", "congenital", "malaria.", "Transplacental", "transmission", "of", "P.", "falciparum", "has", "been", "well", "described,", "and", "the", "reported", "frequency", "of", "this", "event", "in", "babies", "born", "in", "malaria-exposed", "pregnancies", "has", "ranged", "from", "0", "percent", "to", "more", "than", "25", "percent", "[7-11].", "Thus,", "placental", "malaria", "is", "known", "to", "be", "a", "major", "determinant", "To", "whom", "all", "correspondence", "should", "be", "addressed:", "Chigozie", "J.", "Uneke,", "Department", "of", "Med-", "ical", "Microbiology/Parasitology,", "Faculty", "of", "Clinical", "Medicine,", "Ebonyi", "State", "University,", "PMB", "053", "Abakaliki,", "Nigeria.", "Tele:", "234-08038928597;", "Fax:", "234-043221093;", "E-mail:", "unekecj@", "yahoo.com.", "†Abbreviations:", "LBW,", "low", "birth", "weight;", "PTD,", "preterm", "delivery;", "IUGR,", "intrauterine", "growth", "re-", "tardation;", "MTCT,", "mother-to-child", "transmission.", "95" ]

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[ "SY", "Park,", "et", "al", "Ann", "Dermatol", "Vol.", "24,", "No", "1,", "2012", "ORIGINAL", "ARTICLE", "http://dx.doi.org/10.5021/ad.2012.24.1.32", "The", "Prevalence,", "Genotype", "and", "Antimicrobial", "Susceptibility", "of", "High-", "and", "Low-Level", "Mupirocin", "Resistant", "Methicillin-Resistant", "Staphylococcus", "aureus", "Se", "Young", "Park,", "M.D.1,", "Shin", "Moo", "Kim,", "Ph.D.2,", "Seok", "Don", "Park,", "M.D.,", "Ph.D.1,3", "1Department", "of", "Dermatology,", "Wonkwang", "University", "School", "of", "Medicine,", "2Department", "of", "Clinical", "Laboratory", "Science,", "Wonkwang", "Health", "Science", "University,", "3Institute", "of", "Wonkwang", "Medical", "Science,", "Wonkwang", "University", "School", "of", "Medicine,", "Iksan,", "Korea", "Background:", "Mupirocin", "has", "been", "used", "for", "the", "treatment", "of", "skin", "infections", "and", "eradication", "of", "nasal", "carriage", "of", "methicil-", "lin-resistant", "Staphylococcus", "aureus", "(MRSA).", "The", "increased", "use", "of", "this", "antibiotic", "has", "been", "accompanied", "by", "outbreaks", "of", "MRSA", "that", "are", "resistant", "to", "mupirocin.", "Objective:", "This", "study", "aims", "to", "determine", "the", "prevalence,", "genotype", "and", "antimicrobial", "susceptibility", "of", "mupirocin-resistant", "MRSA", "from", "4", "Korean", "hospitals.", "Methods:", "A", "total", "193", "MRSA", "clinical", "isolates", "were", "collected", "from", "four", "university", "hospitals.", "Antimicrobial", "sus-", "ceptibility", "tests,", "including", "mupirocin,", "and", "pulsed-field", "gel", "electrophoresis", "(PFGE)", "pattern", "analysis", "were", "performed.", "Results:", "Overall,", "27", "of", "the", "193", "(14.1%)", "MRSA", "isolates", "were", "resistant", "to", "mupirocin.", "All", "of", "the", "(A)", "hospital", "isolates", "showed", "high-level", "(HL)", "mupirocin", "resistance", "and", "the", "low-level", "(LL)", "mupirocin", "resistant", "strains", "were", "from", "three", "other", "hospitals.", "The", "PFGE", "patterns", "of", "16", "mupirocin-resistant", "isolates", "were", "divided", "into", "5", "clusters", "(1-5),", "and", "the", "nine", "HL", "mupirocin-", "resistant", "isolates", "belonged", "to", "cluster", "1.", "Both", "the", "HL", "and", "LL", "mupirocin-resistant", "MRSA", "isolates", "were", "susceptible", "to", "van-", "comycin", "and", "rifampin,", "but", "they", "were", "resistant", "to", "ciproflo-", "xacin,", "clindamycin", "and", "tetracycline.", "The", "erythromycin", "and", "fusidic", "acid", "resistance", "rates", "were", "different", "between", "the", "HL", "and", "LL", "resistant", "isolates.", "Conclusion:", "HL", "mupirocin-resistant", "isolates", "that", "could", "transfer", "this", "resistance", "to", "other", "bacteria", "Received", "April", "27,", "2011,", "Revised", "July", "5,", "2011,", "Accepted", "for", "publication", "July", "7,", "2011", "Corresponding", "author:", "Seok", "Don", "Park,", "M.D.,", "Ph.D.,", "Department", "of", "Dermatology,", "Wonkwang", "University", "Hospital,", "344-2", "Sinyong-dong,", "Iksan", "570-711,", "Korea.", "Tel:", "82-63-859-1601,", "Fax:", "82-63-842-1895,", "E-mail:", "sdpark@wonkwang.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.", "32", "Ann", "Dermatol", "were", "detected", "and", "these", "isolates", "were", "clonally", "related.", "The", "emergence", "of", "mupirocin", "resistant", "isolates", "emphasizes", "the", "importance", "of", "using", "antibiotics", "judiciously", "and", "carefully", "monitoring", "the", "prevalence", "of", "mupirocin", "resistance.", "(Ann", "Dermatol", "24(1)", "32∼38,", "2012)", "-Keywords-", "Antimicrobial", "susceptibility,", "MRSA,", "Mupirocin,", "Pulsed", "field", "gel", "electrophoresis", "INTRODUCTION", "Mupirocin", "is", "a", "topical", "antibiotic", "that", "was", "originally", "isolated", "from", "Pseudomonas", "fluorescens,", "and", "it", "inhibits", "bacterial", "protein", "synthesis", "by", "competitively", "binding", "to", "isoleucyl-", "tRNA", "synthetase", "(IleS).", "This", "drug", "is", "particularly", "effective", "against", "streptococci", "and", "staphylococci,", "including", "methicil-", "lin-resistant", "Staphylococcus", "aureus", "(MRSA).", "Mupirocin", "is", "one", "of", "the", "most", "popular", "topical", "agents", "used", "for", "the", "treat-", "ment", "of", "skin", "infection", "and", "eradication", "of", "nasal", "carriage", "of", "MRSA1.", "The", "increased", "use", "of", "this", "antibiotic", "has", "been", "accompanied", "by", "outbreaks", "of", "MRSA", "that", "are", "resistant", "to", "mupirocin2.", "The", "mupirocin", "resistant", "strains", "are", "divided", "into", "two", "groups", "depending", "on", "the", "minimum", "inhibitory", "concentra-", "tion", "(MIC)", "against", "mupirocin:", "low-level", "resistance", "(MIC=8", "∼256μg/ml)", "and", "high-level", "resistance", "(MIC＞256μg/", "ml).", "High-level", "mupirocin", "resistant", "strains", "are", "important", "in", "the", "clinical", "field", "because", "they", "are", "able", "to", "transfer", "resistance", "genes", "to", "other", "bacteria", "by", "plasmid", "conjugation,", "conse-", "quently", "protecting", "these", "bacteria", "from", "being", "eradicated", "with", "mupirocin3.", "The", "use", "of", "mupirocin", "ointment", "has", "been", "increasing", "in" ]

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[ "www.jkns.or.kr", "http://dx.doi.org/10.3340/jkns.2012.52.2.80", "J", "Korean", "Neurosurg", "Soc", "52", ":", "80-84,", "2012", "Print", "ISSN", "2005-3711", "On-line", "ISSN", "1598-7876", "Copyright", "©", "2012", "The", "Korean", "Neurosurgical", "Society", "Clinical", "Article", "The", "Meaning", "of", "the", "Prognostic", "Factors", "in", "Ruptured", "Middle", "Cerebral", "Artery", "Aneurysm", "with", "Intracerebral", "Hemorrhage", "Ji", "Woong", "Oh,", "M.D.,1", "Ji-Yong", "Lee,", "M.D.,2", "Myeong", "Sub", "Lee,", "M.D.,3", "Hyen-Ho", "Jung,", "M.D.,1", "Kum", "Whang,", "M.D.;1", "Brain", "Research", "Group", "Departments", "of", "Neurosurgery,1", "Neurology,2", "Radiology,3", "Wonju", "College", "of", "Medicine,", "Yonsei", "University,", "Wonju,", "Korea", "Objective", ":", "This", "study", "analyzed", "the", "relationship", "between", "prognosis", "and", "multiple", "clinical", "factors", "of", "ruptured", "middle", "cerebral", "artery", "(MCA)", "aneurysm", "with", "intracerebral", "hemorrhage", "(ICH),", "to", "aid", "in", "predicting", "the", "results", "of", "surgical", "treatment.", "Methods", ":", "Enrolled", "subjects", "were", "41", "patients", "with", "ruptured", "MCA", "aneurysm", "with", "ICH", "who", "were", "treated", "with", "surgical", "clipping.", "Clinical", "factors", "such", "as", "gender,", "age,", "and", "initial", "Glasgow", "coma", "scale", "were", "assessed", "while", "radiological", "factors", "such", "as", "the", "volume", "and", "location", "of", "hematoma,", "the", "degree", "of", "a", "midline", "shift,", "and", "aneurysm", "size", "were", "considered", "retrospectively.", "Prognosis", "was", "evaluated", "postoperatively", "by", "Glasgow", "outcome", "scale.", "Results", ":", "Age", "and", "prognosis", "were", "correlated", "only", "in", "the", "groups", "with", "ICH", "over", "31", "mL", "or", "ICH", "at", "the", "frontal", "lobe", "or", "sylvian", "fissure.", "When", "initial", "mental", "status", "was", "good,", "only", "patients", "with", "ICH", "on", "the", "temporal", "lobe", "had", "a", "better", "prognosis.", "If", "the", "midline", "shift", "was", "less", "than", "4.5", "mm,", "the", "probability", "of", "better", "prognosis", "was", "95.5%", "(21", "of", "22).", "If", "the", "midline", "shift", "was", "more", "than", "4.5", "mm,", "the", "probability", "of", "poor", "prognosis", "was", "42.1%", "(8", "of", "19).", "Patients", "with", "ICH", "less", "than", "31", "mL", "had", "higher", "survival", "rates,", "whereas", "if", "the", "ICH", "was", "more", "than", "31", "mL,", "41.2%", "(7", "of", "17)", "had", "a", "poor", "clinical", "pathway.", "Conclusion", ":", "Even", "if", "the", "initial", "clinical", "condition", "of", "the", "patient", "was", "not", "promising,", "by", "carefully", "examining", "and", "taking", "into", "account", "all", "factors,", "neuro-", "surgeons", "can", "confidently", "recommend", "surgical", "treatment", "for", "these", "patients.", "Key", "Words", ":", "Ruptured", "middle", "cerebral", "artery", "aneurysm", "·", "Intracerebral", "hemorrhage", "·", "Prognostic", "outcome.", "INTRODUCTION", "Middle", "cerebral", "artery", "(MCA)", "aneurysms", "are", "20%", "of", "saccular", "aneurysms.", "They", "are", "occasionally", "found", "incidentally", "or", "because", "of", "a", "mass", "effect,", "but", "most", "are", "found", "when", "they", "rupture8).", "After", "Dott2)", "treated", "ruptured", "aneurysms", "with", "surgical", "methods,", "many", "treatment", "modalities", "have", "been", "developed", "and", "report-", "ed17).", "When", "MCA", "aneurysms", "rupture,", "approximately", "30-50%", "lead", "to", "a", "subarachnoid", "hemorrhage", "(SAH)", "combined", "with", "an", "intracerebral", "hemorrhage", "(ICH),", "with", "a", "mortality", "rate", "of", "10-", "41%4,16).", "The", "mechanism", "of", "ICH", "developed", "by", "aneurysmal", "rup-", "ture", "is", "still", "controversial", "but", "the", "most", "commonly", "accepted", "hy-", "pothesis", "is", "that", "the", "ICH", "develops", "when", "fibrin,", "hematoma,", "or", "the", "fibrosis", "of", "the", "arachnoid", "membrane", "obstructs", "the", "subarach-", "noid", "space,", "or", "an", "aneurysm", "attached", "to", "the", "pia", "ruptures16).", "These", "ICHs", "are", "a", "risk", "factor", "for", "poor", "prognosis", "and", "surgical", "complica-", "tions", "in", "ruptured", "MCA", "aneurysm", "patients.", "However,", "our", "clini-", "cal", "data", "suggested", "that", "patients", "with", "ruptured", "MCA", "aneurysms", "with", "ICH", "have", "a", "non-classical", "clinical", "course", "that", "requires", "fur-", "ther", "study.", "Therefore,", "authors", "analyzed", "the", "relationship", "between", "multiple", "clinical", "factors", "of", "ruptured", "MCA", "aneurysms", "with", "ICH", "and", "general", "prognosis,", "to", "help", "predict", "the", "results", "of", "surgical", "treatment.", "MATERIALS", "AND", "METHODS", "We", "retrospectively", "reviewed", "68", "patients", "with", "MCA", "aneurysm", "who", "underwent", "neck", "clipping", "after", "aneurysm", "rupture", "between", "January", "2006", "and", "December", "2010.", "We", "excluded", "27", "patients", "who", "did", "not", "have", "accompanying", "ICH.", "The", "remaining", "41", "pa-", "tients", "with", "accompanying", "ICH", "were", "evaluated.", "Aneurysm,", "SAH", "and", "ICH", "were", "diagnosed", "with", "computed", "tomography", "(CT)", "and", "conventional", "cerebral", "angiography.", "Of", "the", "41", "total", "patients,", "27", "were", "evaluated", "with", "preoperative", "angiography", "(Table", "1).", "•", "Received", ":", "February", "15,", "2012", "•", "Revised", ":", "May", "30,", "2012", "•", "Accepted", ":", "August", "19,", "2012", "•", "Address", "for", "reprints", ":", "Kum", "Whang,", "M.D.", "Departments", "of", "Neurosurgery,", "Wonju", "College", "of", "Medicine,", "Yonsei", "University,", "162", "Ilsan-dong,", "Wonju", "220-701,", "Korea", "Tel", ":", "+82-33-741-0593,", "Fax", ":", "+82-33-746-2287,", "E-mail", ":", "whangkum@yonsei.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.", "80" ]

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[ "Hindawi", "Publishing", "Corporation", "Biochemistry", "Research", "International", "Volume", "2012,", "Article", "ID", "369384,", "5", "pages", "doi:10.1155/2012/369384", "Review", "Article", "Role", "of", "Translationally", "Controlled", "Tumor", "Protein", "in", "Cancer", "Progression", "Tim", "Hon", "Man", "Chan,1,", "2", "Leilei", "Chen,1,", "2", "and", "Xin-Yuan", "Guan1,", "2,", "3", "1", "Department", "of", "Clinical", "Oncology,", "Li", "Ka", "Shing", "Faculty", "of", "Medicine,", "The", "University", "of", "Hong", "Kong,", "Hong", "Kong", "2", "State", "Key", "Laboratory", "of", "Liver", "Research,", "The", "University", "of", "Hong", "Kong,", "Hong", "Kong", "3", "State", "Key", "Laboratory", "of", "Oncology", "in", "Southern", "China,", "Sun", "Yat-sen", "University", "Cancer", "Center,", "Guangzhou", "510060,", "China", "Correspondence", "should", "be", "addressed", "to", "Xin-Yuan", "Guan,", "xyguan@hku.hk", "Received", "13", "January", "2012;", "Accepted", "17", "February", "2012", "Academic", "Editor:", "Malgorzata", "Kloc", "Copyright", "©", "2012", "Tim", "Hon", "Man", "Chan", "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.", "Translationally", "controlled", "tumor", "protein", "(TCTP)", "is", "a", "highly", "conserved", "and", "ubiquitously", "expressed", "protein", "in", "all", "eukaryotes—", "highlighting", "its", "important", "functions", "in", "the", "cell.", "Previous", "studies", "revealed", "that", "TCTP", "is", "implicated", "in", "many", "biological", "processes,", "including", "cell", "growth,", "tumor", "reversion,", "and", "induction", "of", "pluripotent", "stem", "cell.", "A", "recent", "study", "on", "the", "solution", "structure", "from", "fission", "yeast", "orthologue", "classifies", "TCTP", "under", "a", "family", "of", "small", "chaperone", "proteins.", "There", "is", "growing", "evidence", "in", "the", "literature", "that", "TCTP", "is", "a", "multifunctional", "protein", "and", "exerts", "its", "biological", "activity", "at", "the", "extracellular", "and", "intracellular", "levels.", "Although", "TCTP", "is", "not", "a", "tumor-specific", "protein,", "our", "research", "group,", "among", "several", "others,", "focused", "on", "the", "role(s)", "of", "TCTP", "in", "cancer", "progression.", "In", "this", "paper,", "we", "will", "summarize", "the", "current", "scientific", "knowledge", "of", "TCTP", "in", "different", "aspects,", "and", "the", "precise", "oncogenic", "mechanisms", "of", "TCTP", "will", "be", "discussed", "in", "detail.", "1.", "Introduction", "Translationally", "controlled", "tumor", "protein", "(TCTP)", "is", "a", "highly", "conserved", "multifunctional", "protein.", "Since", "the", "discovery", "of", "TCTP", "over", "two", "decades", "ago,", "the", "expression", "level", "of", "TCTP", "has", "been", "investigated", "in", "more", "than", "500", "tissues", "and", "cell", "types.", "Expression", "levels", "have", "been", "found", "to", "vary", "by", "nearly", "two", "orders", "of", "magnitude", "between", "different", "types", "of", "tissues", "[1]", "with", "preferential", "expression", "in", "mitotically", "active", "tissues", "[2].", "Two", "mRNA", "transcripts", "have", "been", "reported", "to", "carry", "the", "same", "5", "UTR", "but", "different", "3", "UTR", "using", "alternative", "polyadenylation", "signals.", "The", "solution", "structure", "of", "TCTP", "from", "fission", "yeast", "also", "revealed", "structural", "similarity", "with", "the", "Mss4/Dss4", "protein", "family.", "The", "expression", "of", "TCTP", "is", "highly", "regulated", "both", "at", "transcriptional", "and", "translational", "levels", "in", "addition", "to", "a", "wide", "range", "of", "extracellular", "signals.", "It", "has", "been", "implicated", "in", "many", "cellular", "processes,", "such", "as", "cell", "growth,", "cell", "cycle", "progression,", "apoptosis,", "malignant", "transformation,", "and", "the", "regulation", "of", "pluripotency.", "Although", "TCTP", "is", "not", "a", "tumor-", "specific", "protein,", "the", "downregulation", "of", "TCTP", "was", "found", "in", "tumor", "reversion", "[3].", "Our", "research", "group", "and", "others", "also", "substantiated", "the", "link", "between", "TCTP", "deregulation", "and", "cancer", "progression", "[4–6].", "This", "paper", "will", "mainly", "focus", "on", "the", "biological", "functions", "of", "TCTP", "and", "malignant", "transformation", "induced", "by", "TCTP.", "Furthermore,", "the", "clinical", "implications", "of", "TCTP", "in", "human", "cancers", "will", "also", "be", "discussed.", "2.", "Features", "of", "TCTP", "mRNA", "and", "Protein", "2.1.", "TCTP", "mRNA.", "The", "human", "TPT1", "gene", "coding", "for", "TCTP", "spanning", "about", "4.2", "kb,", "consists", "of", "six", "exons", "and", "five", "introns", "[7].", "Two", "alternative", "polyadenylation", "signals", "at", "3", "UTR", "generated", "two", "mRNA", "transcripts", "that", "differ", "in", "the", "length", "of", "3", "UTR.", "In", "all", "mammalian", "tissues", "tested,", "both", "types", "of", "mRNAs", "are", "expressed", "at", "different", "ratios,", "and", "the", "shorter", "transcript", "is", "usually", "expressed", "more", "abun-", "dantly", "[2].", "Sequence", "analyses", "of", "TCTP", "transcripts", "indi-", "cated", "that", "the", "5", "UTR", "is", "CG-rich", "with", "a", "high", "degree", "of", "secondary", "structure.", "TCTP", "mRNA", "has", "a", "5", "terminal", "oligopyrimidine", "tract", "(5", "TOP),", "which", "is", "a", "signature", "of", "translationally", "controlled", "mRNAs", "[8].", "Although", "AU-rich" ]

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"values", "based", "on", "markers", "is", "a", "very", "active", "area", "of", "research.", "A", "simulated", "dataset", "was", "analyzed", "by", "participants", "of", "the", "QTLMAS", "XIII", "workshop,", "allowing", "a", "comparison", "of", "the", "ability", "of", "different", "methods", "to", "estimate", "genomic", "breeding", "values.", "Methods:", "A", "best", "case", "scenario", "was", "analyzed", "by", "the", "organizers", "where", "QTL", "genotypes", "were", "known.", "Participants", "submitted", "estimated", "breeding", "values", "for", "1000", "unphenotyped", "individuals", "together", "with", "a", "description", "of", "the", "applied", "method(s).", "The", "submitted", "breeding", "values", "were", "evaluated", "for", "correlation", "with", "the", "simulated", "values", "(accuracy),", "rank", "correlation", "of", "the", "best", "10%", "of", "individuals", "and", "error", "in", "predictions.", "Bias", "was", "tested", "by", "regression", "of", "simulated", "on", "estimated", "breeding", "values.", "Results:", "The", "accuracy", "obtained", "from", "the", "best", "case", "scenario", "was", "0.94.", "Six", "research", "groups", "submitted", "19", "sets", "of", "estimated", "breeding", "values.", "Methods", "that", "assumed", "the", "same", "variance", "for", "markers", "showed", "accuracies,", "measured", "as", "correlations", "between", "estimated", "and", "simulated", "values,", "ranging", "from", "0.75", "to", "0.89", "and", "rank", "correlations", "between", "0.58", "and", "0.70.", "Methods", "that", "allowed", "different", "marker", "variances", "showed", "accuracies", "ranging", "from", "0.86", "to", "0.94", "and", "rank", "correlations", "between", "0.69", "and", "0.82.", "Methods", "assuming", "equal", "marker", "variances", "were", "generally", "more", "biased", "and", "showed", "larger", "prediction", "errors.", "Conclusions:", "The", "best", "performing", "methods", "achieved", "very", "high", "accuracies,", "close", "to", "accuracies", "achieved", "in", "a", "best", "case", "scenario", "where", "QTL", "genotypes", "were", "known", "without", "error.", "Methods", "that", "allowed", "different", "marker", "variances", "generally", "outperformed", "methods", "that", "assumed", "equal", "marker", "variances.", "Genomic", "selection", "methods", "performed", "well", "compared", "to", "traditional,", "pedigree", "only,", "methods;", "all", "methods", "showed", "higher", "accuracies", "than", "those", "obtained", "for", "breeding", "values", "estimated", "solely", "on", "pedigree", "relationships.", "Background", "When", "methods", "for", "selection", "based", "on", "many", "markers", "across", "the", "genome,", "or", "genomic", "selection,", "were", "first", "described", "[1]", "the", "application", "of", "genetic", "marker", "data", "in", "plant", "and", "animal", "breeding", "programs", "was", "still", "limited", "[2].", "In", "subsequent", "years", "the", "use", "of", "individual", "markers", "in", "breeding", "programs", "has", "increased", "[3,4].", "With", "the", "avail-", "ability", "of", "assays", "that", "provide", "genotypes", "for", "50,000", "or", "more", "markers", "for", "each", "individual,", "the", "application", "of", "*", "Correspondence:", "john.bastiaansen@wur.nl", "1Animal", "Breeding", "and", "Genomics", "Centre,", "Wageningen", "University,", "Wageningen,", "The", "Netherlands", "genomic", "selection", "has", "started", "to", "take", "hold", "in", "recent", "years.", "Especially", "in", "dairy", "cattle", "the", "use", "of", "genomic", "selec-", "tion", "is", "becoming", "common", "practice", "[5,6].", "In", "other", "spe-", "cies", "the", "application", "of", "genomic", "selection", "is", "being", "considered", "or", "evaluated", "[7-9].", "Methods", "to", "deal", "with", "these", "large", "number", "of", "markers", "in", "breeding", "programs", "were", "first", "proposed", "by", "[1]", "after", "which", "a", "number", "of", "alternatives", "have", "been", "suggested;", "e.g.", "[10,11].", "Most", "methods", "have", "been", "evaluated", "in", "simula-", "tions", "and", "sometimes", "on", "real", "data.", "Analyses", "applying", "genomic", "BLUP", "methodology", "as", "defined", "by", "Meuwissen", "et", "al.[1],", "or", "applying", "Ridge", "Regression", "(RR)", "[12],", "assume", "©", "2010", "Bastiaansen", "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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[ "Shi", "et", "al.", "Journal", "of", "Cardiothoracic", "Surgery", "2012,", "7:64", "http://www.cardiothoracicsurgery.org/content/7/1/64", "C", "A", "S", "E", "R", "E", "P", "O", "R", "T", "Open", "Access", "Rare", "early", "prosthesis", "obstruction", "after", "mitral", "valve", "replacement:", "a", "case", "report", "and", "literature", "review", "Jun", "Shi,", "Zhi-xuan", "Bai,", "Jia", "Hu,", "Ben-gui", "Zhang", "and", "Ying-qiang", "Guo*", "Abstract", "As", "a", "dreadful", "complication", "after", "the", "mechanical", "heart", "valve", "replacement,", "prosthetic", "valve", "obstruction", "caused", "by", "pannus", "formation", "occurs", "increasingly", "with", "time.", "The", "authors", "here", "present", "a", "case", "of", "42-year-old", "woman", "who", "was", "urgently", "admitted", "to", "hospital", "with", "acute", "heart", "failure", "symptoms", "due", "to", "the", "mechanical", "mitral", "valve", "failure", "only", "3", "months", "after", "surgery.", "Transthoracic", "and", "transesophageal", "echocardiography", "demonstrated", "that", "the", "bileaflet", "of", "the", "mitral", "prosthesis", "were", "completely", "immobilized", "with", "only", "a", "small", "transvalvular", "jet", "remained.", "During", "the", "reoperation,", "the", "reason", "of", "the", "prosthetic", "valve", "obstruction", "was", "attributed", "to", "the", "noncircular", "pannus", "ingrowth", "extending", "from", "the", "atrioventricular", "side.", "For", "a", "better", "understanding", "of", "the", "prosthetic", "valve", "dysfunction", "caused", "by", "pannus", "formation,", "the", "authors", "then", "compile", "a", "literature", "review", "to", "briefly", "discuss", "the", "status", "quo", "of", "the", "clinical", "characteristics", "of", "this", "uncommon", "complication.", "Background", "The", "evolving", "design", "and", "biomaterials", "of", "the", "mechanical", "heart", "valves", "have", "greatly", "advanced", "their", "in", "vivo", "hemodynamic", "features", "and", "durability", "over", "decades", "[1].", "However,", "the", "anticipated", "performances", "of", "the", "mechan-", "ical", "prostheses", "are", "still", "compromised", "by", "the", "occurrence", "of", "various", "complications,", "among", "which", "pannus-induced", "prosthetic", "valve", "dysfunction", "(PVD)", "is", "relatively", "uncom-", "mon", "but", "sometimes", "is", "the", "most", "serious", "one", "[2,3].", "In", "par-", "ticular,", "patients", "with", "prosthetic", "valve", "obstruction", "(PVO)", "due", "to", "pannus", "ingrowth", "may", "rapidly", "develop", "hemo-", "dynamic", "deterioration", "and", "crash", "into", "a", "life-threatening", "condition.", "According", "to", "recent", "studies", "[2,4-7],", "the", "prevalence", "of", "pannus", "formation", "in", "aortic", "or", "mit-", "ral", "position", "is", "controversial.", "However,", "pannus", "is", "un-", "doubtedly", "of", "later", "clinical", "onset", "than", "the", "thrombosis,", "which", "is", "mostly", "responsible", "for", "the", "early", "PVD.", "More-", "over,", "the", "duration", "from", "time", "of", "prostheses", "implant-", "ation", "to", "pannus-induced", "PVD", "is", "widely", "variable", "and", "has", "been", "reported", "to", "be", "at", "least", "6", "months", "to", "12", "months,", "during", "which", "an", "ingrowth", "of", "periannular", "tissue", "would", "gradually", "immobilize", "the", "moving", "element", "of", "the", "prostheses", "[6-8].", "Here", "we", "present", "a", "rare", "case", "*", "Correspondence:", "drguoyq@hotmail.com", "Department", "of", "Cardiovascular", "Surgery,", "West", "China", "Hospital,", "Sichuan", "University,", "Cheng", "Du,", "People’s", "Republic", "of", "China", "of", "PVO", "in", "the", "mitral", "position", "caused", "by", "early", "pannus", "formation", "only", "3", "months", "after", "surgery.", "Case", "presentation", "A", "42-year-old", "woman", "was", "admitted", "to", "our", "intensive", "car-", "diac", "care", "unit", "with", "symptoms", "of", "acute", "left", "heart", "failure.", "Three", "months", "prior", "to", "admission,", "she", "underwent", "the", "implantation", "of", "a", "mechanical", "bileaflet", "mitral", "valve", "(25", "mm", "SJM", "Master;", "St.", "Paul,", "MN,", "USA)", "due", "to", "severe", "rheumatic", "valve", "stenosis.", "No", "native", "valve-", "or", "chordal-", "sparing", "procedures", "were", "performed", "during", "the", "replace-", "ment.", "The", "postoperative", "course", "went", "smoothly", "and", "transthoracic", "echocardiography", "(TTE)", "showed", "proper", "functioning", "of", "the", "prosthesis.", "The", "patient", "then", "followed", "adequate", "anticoagulation", "treatment", "with", "wafarin", "and", "the", "international", "normalized", "ratio", "maintained", "above", "2.0.", "No", "episode", "of", "atrial", "fibrillation", "and", "other", "risk", "factors", "for", "thrombus", "formation", "were", "identified.", "One", "week", "before", "this", "admission,", "she", "had", "noticed", "a", "progressive", "physical", "deterioration.", "After", "the", "treatment", "at", "local", "hospital,", "the", "patient", "showed", "no", "signs", "of", "recovery", "and", "finally", "pre-", "sented", "with", "severe", "shortness", "of", "breath", "and", "coughing", "up", "pink,", "foamy", "mucus", "on", "the", "arrival", "of", "our", "hospital.", "On", "admission,", "the", "patient", "was", "conscious", "but", "presented", "with", "marked", "respiratory", "distress.", "Initial", "vital", "signs", "showed", "blood", "pressure", "80/40", "mmHg,", "sinus", "rhythm,", "a", "regular", "pulse", "of", "140", "beats/min", "and", "a", "respiratory", "rate", "of", "40", "breaths/min.", "Auscultation", "of", "the", "chest", "revealed", "©", "2012", "Shi", "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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[ "CELLULAR", "AND", "INFECTION", "MICROBIOLOGY", "The", "influence", "of", "early", "neutrophil-Leishmania", "interactions", "on", "the", "host", "immune", "response", "to", "infection", "Flavia", "L.", "Ribeiro-Gomes", "and", "David", "Sacks*", "Laboratory", "of", "Parasitic", "Diseases,", "National", "Institute", "of", "Allergy", "and", "Infectious", "Diseases,", "National", "Institutes", "of", "Health,", "Bethesda,", "MD,", "USA", "REVIEW", "ARTICLE", "published:", "04", "May", "2012", "doi:", "10.3389/fcimb.2012.00059", "Edited", "by:", "Stephen", "M.", "Beverley,", "Washington", "University", "in", "St.", "Louis,", "USA", "Reviewed", "by:", "Jordi", "Torrelles,", "Ohio", "State", "University,", "USA", "Michael", "L.", "Vasil,", "University", "of", "Colorado", "Medical", "School,", "USA", "*Correspondence:", "David", "Sacks,", "Laboratory", "of", "Parasitic", "Diseases,", "National", "Institute", "of", "Allergy", "and", "Infectious", "Diseases,", "National", "Institutes", "of", "Health,", "4", "Center", "Dr.", "MSC", "0425,", "Bethesda,", "MD", "20892-0425,", "USA.", "e-mail:", "dsacks@nih.gov", "Neutrophils", "are", "the", "first", "cells", "recruited", "to", "the", "dermal", "site", "of", "Leishmania", "infection", "following", "injection", "by", "needle", "or", "sand", "fly", "bite.", "The", "role", "of", "neutrophils", "in", "either", "promoting", "or", "suppressing", "host", "immunity", "remains", "controversial.", "We", "discuss", "the", "events", "driving", "neutrophil", "recruitment,", "their", "interaction", "with", "the", "parasite", "and", "apoptotic", "fate,", "and", "the", "nature", "of", "their", "encounters", "with", "other", "innate", "cells.", "We", "suggest", "that", "the", "influence", "of", "the", "neutrophil", "response", "on", "infection", "outcome", "critically", "depends", "on", "the", "timing", "of", "their", "recruitment", "and", "the", "tissue", "environment", "in", "which", "it", "occurs.", "Keywords:", "neutrophils,", "Leishmania,", "inflammation,", "immune", "response,", "sand", "fly,", "apoptosis,", "dendritic", "cells,", "macrophages", "Neutrophils", "are", "readily", "mobilized", "innate", "immune", "cells", "and", "essen-", "tial", "for", "host", "defense", "against", "a", "variety", "of", "pathogens", "(Kobayashi", "and", "DeLeo,", "2009).", "Patients", "with", "severe", "neutropenia", "or", "chronic", "granulomatous", "disease", "(CGD)", "suffer", "a", "wide", "range", "of", "microbial", "infections", "(Vento", "and", "Cainelli,", "2003;", "Segal,", "2005).", "Neutrophils", "are", "also", "recruited", "during", "acute", "sterile", "inflammation", "where", "they", "con-", "tribute", "to", "tissue", "repair", "(Kim", "et", "al.,", "2006;", "McDonald", "et", "al.,", "2010).", "Given", "their", "potent", "arsenal", "of", "constituents", "used", "for", "host", "defense,", "including", "reactive", "oxygen", "species", "(ROS),", "antimicrobial", "peptides,", "and", "serine", "proteases,", "the", "resolution", "of", "inflammation", "requires", "that", "dying", "neutrophils", "are", "removed", "from", "the", "inflammatory", "site", "by", "other", "phagocytic", "cells,", "such", "as", "macrophages", "and", "dendritic", "cells", "(DCs),", "to", "avoid", "their", "uncontrolled", "release", "of", "injurious", "con-", "tents", "(Segal,", "2005).", "It", "is", "not", "surprising", "that", "any", "imbalance", "in", "the", "recruitment", "and", "removal", "of", "these", "cells", "is", "associated", "with", "numer-", "ous", "pathologies,", "including", "chronic", "infections", "and", "inflammatory", "disorders", "(Kono", "and", "Rock,", "2008).", "Leishmaniasis", "is", "a", "vector-borne", "disease", "caused", "by", "the", "intra-", "cellular", "protozoan", "Leishmania.", "There", "are", "an", "estimated", "2", "million", "new", "cases", "annually", "(1.5", "million", "cases", "of", "cutaneous", "leishmaniasis", "and", "500,000", "cases", "of", "visceral", "leishmaniasis),", "with", "about", "12", "million", "people", "currently", "infected", "(www.who.int/leishmaniasis/burden).", "For", "each", "Leishmania", "species", "studied,", "neutrophils", "have", "been", "found", "recruited", "to", "the", "infection", "site", "following", "the", "delivery", "of", "parasites", "by", "sand", "fly", "bite", "or", "by", "needle", "injection", "(Beil", "et", "al.,", "1992;", "Tacchini-", "Cottier", "et", "al.,", "2000;", "Peters", "et", "al.,", "2008;", "Thalhofer", "et", "al.,", "2011;", "Ribeiro-Gomes", "et", "al.,", "2012).", "Numerous", "in", "vitro", "and", "in", "vivo", "stud-", "ies", "have", "been", "carried", "out", "to", "understand", "the", "role", "of", "neutrophils", "in", "host", "defense", "against", "Leishmaniasis", "(Tacchini-Cottier", "et", "al.,", "2000;", "Ribeiro-Gomes", "et", "al.,", "2004,", "2007;", "Peters", "et", "al.,", "2008,", "2009;", "Charmoy", "et", "al.,", "2010a,b;", "Filardy", "et", "al.,", "2010).", "Because", "of", "the", "het-", "erogeneity", "of", "these", "studies", "in", "terms", "of", "host", "species", "and", "mouse", "strain", "(human,", "dog,", "susceptible,", "or", "resistant", "mice),", "the", "tissue", "source", "and", "site", "of", "recruitment", "(blood,", "peritoneum,", "skin),", "and", "the", "time", "frame", "of", "the", "recruitment", "(hours,", "days,", "weeks)", "the", "impact", "of", "the", "neutrophilic", "response", "on", "promoting", "host", "resistance", "or", "suscep-", "tibility", "to", "Leishmania", "infection", "remains", "a", "matter", "of", "some", "debate.", "In", "keeping", "with", "the", "theme", "of", "this", "volume,", "this", "review", "will", "focus", "on", "the", "early", "events", "driving", "neutrophil", "recruitment,", "and", "their", "fate", "and", "immunologic", "consequences", "following", "Leishmania", "infection", "initiated", "by", "the", "bite", "of", "an", "infected", "sand", "fly", "or", "needle", "inoculation", "in", "the", "skin.", "RECRUITMENT", "The", "first", "observations", "concerning", "the", "early", "recruitment", "of", "neu-", "trophils", "to", "the", "site", "of", "Leishmania", "infection", "were", "made", "by", "Wilson", "et", "al.", "(1987),", "who", "described", "a", "mixed", "neutrophil", "and", "mono-", "cytic", "infiltrate", "within", "1", "h", "following", "intra-dermal", "inoculation", "of", "L.", "donovani", "promastigotes", "in", "hamsters,", "and", "by", "Pompeu", "et", "al.", "(1991)", "and", "Beil", "et", "al.", "(1992),", "who", "described", "the", "predominant", "neutrophilic", "infiltrate", "within", "3", "h", "following", "high", "dose", "subcu-", "taneous", "inoculation", "of", "Leishmania", "amazonensis", "or", "Leishmania", "major", "promastigotes,", "respectively,", "into", "the", "footpad", "of", "BALB/c", "or", "C57Bl/6", "mice.", "Studies", "by", "the", "group", "of", "Laskay", "confirmed", "that", "neu-", "trophils", "were", "the", "first", "leukocyte", "population", "migrating", "to", "the", "site", "of", "L.", "major", "infection", "in", "the", "footpad", "(Muller", "et", "al.,", "2001).", "These", "findings", "have", "more", "recently", "been", "extended", "to", "the", "ear", "dermal", "inoc-", "ulation", "site", "employing", "L.", "major", "(Peters", "et", "al.,", "2008;", "Charmoy", "et", "al.,", "2010a,b;", "Ribeiro-Gomes", "et", "al.,", "2012)", "or", "L.", "infantum", "(Thalhofer", "et", "al.,", "2011).", "A", "recent", "paper", "suggests", "that", "the", "kinet-", "ics", "of", "myeloid", "cell", "recruitment", "to", "the", "L.", "major", "injection", "site", "might", "be", "tissue", "specific,", "as", "neutrophil", "recruitment", "into", "the", "peritoneal", "cavity", "following", "i.p.", "injection", "of", "L.", "major", "was", "preceded", "at", "30", "min", "by", "GR-1+", "monocytes", "(Goncalves", "et", "al.,", "2011).", "Our", "own", "stud-", "ies", "used", "two-photon", "intra-vital", "microscopy", "(2P-IVM)", "to", "confirm", "that", "neutrophils", "are", "the", "first", "cells", "to", "infiltrate", "(within", "30", "min.)", "Frontiers", "in", "Cellular", "and", "Infection", "Microbiology", "www.frontiersin.org", "May", "2012", "|", "Volume", "2", "|", "Article", "59", "|", "1" ]

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[ "Journal", "of", "Chiropractic", "Humanities", "(2009)", "16,", "1–4", "Editorial", "A", "brief", "review", "of", "the", "evolution", "of", "the", "Journal", "of", "Chiropractic", "Humanities:", "a", "journey", "beginning", "in", "1991", "Claire", "Johnson", "DC,", "MSEd⁎", "Professor,", "National", "University", "of", "Health", "Sciences,", "Lombard,", "IL", "Editor,", "Journal", "of", "Chiropractic", "Humanities", "Abstract", "This", "article", "provides", "a", "brief", "review", "of", "the", "history", "and", "origins", "of", "the", "Journal", "of", "Chiropractic", "Humanities.", "The", "reason", "for", "starting", "the", "journal,", "its", "purpose,", "and", "a", "timeline", "from", "1991", "to", "2009", "are", "offered.", "©", "2009", "National", "University", "of", "Health", "Sciences.", "During", "the", "birth", "of", "most", "new", "journals,", "hopes", "are", "high", "but", "the", "future", "is", "uncertain.", "Success", "of", "a", "peer-reviewed", "journal", "requires", "many", "factors.", "Interest", "and", "support", "from", "the", "readers,", "funding", "for", "publication,", "authors", "submitting", "meaningful", "articles,", "a", "willing", "publishing", "company,", "indexing", "systems", "to", "include", "the", "journal,", "and", "an", "infrastructure", "to", "provide", "the", "editorial", "and", "peer-review", "process", "are", "all", "necessary", "to", "ensure", "a", "journal’s", "success.", "In", "the", "early", "years", "of", "chiropractic,", "the", "call", "for", "scholarly", "publication,", "more", "legitimate", "scientific", "research,", "and", "intellectual", "honesty", "had", "been", "demanded", "by", "a", "few", "outspoken", "members", "of", "the", "profession.", "However,", "little", "was", "done", "in", "the", "first", "several", "chiropractic", "decades.", "Watkins", "criticized", "chiropractic", "leaders", "for", "their", "misuse", "and", "misunderstanding", "of", "the", "term", "philosophy.", "Instead", "of", "true", "philosophy", "they", "were", "actually", "promoting", "dogma.", "In", "1944,", "Watkins", "stated,", "“Many", "of", "the", "old", "‘philosophical’", "leaders", "feel", "that", "chiropractic", "is", "doomed", "to", "failure", "as", "a", "‘healing", "movement’", "because", "in", "their", "opinion", "the", "average", "⁎", "200", "E.", "Roosevelt", "Rd.,", "Lombard,", "IL", "60148.", "E-mail", "address:", "cjohnson@nuhs.edu.", "1556-3499/$", "–", "see", "front", "matter", "©", "2009", "National", "University", "of", "Health", "Sciences.", "doi:10.1016/j.echu.2010.02.001", "chiropractor", "has", "‘lost", "the", "faith’", "and", "no", "longer", "fervently", "propounds", "the", "doctrine,", "that", "he", "has", "wandered", "astray", "in", "his", "therapy,", "and", "that", "he", "has", "not", "kept", "chiropractic", "pure", "so", "that", "it", "may", "be", "preserved", "for", "posterity.", "In", "other", "words", "the", "‘philosophical’", "leaders", "regard", "chiropractic", "as", "being", "based", "upon", "doctrine", "rather", "than", "upon", "science.”1", "Keating", "et", "al", "suggested", "that", "those", "in", "the", "chiropractic", "profession", "looked", "to", "medicine’s", "cultural", "success", "due", "to", "its", "scientific", "base", "as", "a", "motivator", "for", "becoming", "more", "scientific.2", "The", "authors", "found", "that", "although", "the", "terms", "research", "and", "science", "were", "used", "in", "chiropractic", "publications,", "these", "terms", "were", "often", "applied", "to", "marketing", "strategies", "and", "only", "rarely", "used", "correctly.", "Though", "there", "seemed", "to", "be", "a", "desire", "for", "legitimate", "research", "and", "philosophical", "discus-", "sion,", "little", "evidence", "for", "these", "were", "found", "in", "the", "first", "half", "of", "the", "chiropractic", "century.", "Demand", "for", "more", "chiropractic", "science,", "research,", "and", "publication", "grew.", "Between", "1970", "and", "1990,", "there", "was", "an", "increased", "interest", "in", "creating", "new", "scientific", "and", "scholarly", "journals", "for", "the", "chiropractic", "profession.", "Some", "in", "the", "profession", "recognized", "a", "need", "for", "chiropractic", "to", "legitimize", "itself", "with", "research", "but", "few", "had", "the", "training" ]

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[ "Zabolotneva", "et", "al.", "Biology", "Direct", "2010,", "5:62", "http://www.biology-direct.com/content/5/1/62", "H", "Y", "P", "O", "T", "H", "E", "S", "I", "S", "Open", "Access", "How", "many", "antiviral", "small", "interfering", "RNAs", "may", "be", "encoded", "by", "the", "mammalian", "genomes?", "Anastasia", "Zabolotneva1,", "Victor", "Tkachev2,", "Felix", "Filatov3,", "Anton", "Buzdin1*", "Abstract", "Background:", "The", "discovery", "of", "RNA", "interference", "phenomenon", "(RNAi)", "and", "understanding", "of", "its", "mechanisms", "has", "revolutionized", "our", "views", "on", "many", "molecular", "processes", "in", "the", "living", "cell.", "Among", "the", "other,", "RNAi", "is", "involved", "in", "silencing", "of", "transposable", "elements", "and", "in", "inhibition", "of", "virus", "infection", "in", "various", "eukaryotic", "organisms.", "Recent", "experimental", "studies", "demonstrate", "few", "cases", "of", "viral", "replication", "suppression", "via", "complementary", "interactions", "between", "the", "mammalian", "small", "RNAs", "and", "viral", "transcripts.", "Presentation", "of", "the", "hypothesis:", "It", "was", "found", "that", ">50%", "of", "the", "human", "genome", "is", "transcribed", "in", "different", "cell", "types", "and", "that", "these", "transcripts", "are", "mainly", "not", "associated", "with", "known", "protein", "coding", "genes,", "but", "represent", "non-", "coding", "RNAs", "of", "unknown", "functions.", "We", "propose", "a", "hypothesis", "that", "mammalian", "DNAs", "encode", "thousands", "RNA", "motifs", "that", "may", "serve", "for", "antiviral", "protection.", "We", "also", "presume", "that", "the", "evolutional", "success", "of", "some", "groups", "of", "genomic", "repeats", "and,", "in", "particular,", "of", "transposable", "elements", "(TEs)", "may", "be", "due", "to", "their", "ability", "to", "provide", "antiviral", "RNA", "motifs", "to", "the", "host", "organism.", "Intense", "genomic", "repeat", "propagation", "into", "the", "genome", "would", "inevitably", "cause", "bidirectional", "transcription", "of", "these", "sequences,", "and", "the", "resulting", "double-stranded", "RNAs", "may", "be", "recognized", "and", "processed", "by", "the", "RNA", "interference", "enzymatic", "machinery.", "Provided", "that", "these", "processed", "target", "motifs", "may", "be", "complementary", "to", "viral", "transcripts,", "fixation", "of", "the", "repeats", "into", "the", "host", "genome", "may", "be", "of", "a", "considerable", "benefit", "to", "the", "host.", "It", "fits", "with", "our", "bioinformatical", "data", "revealing", "thousands", "of", "21-28", "bp", "long", "motifs", "identical", "between", "human", "DNA", "and", "human-pathogenic", "adenoviral", "and", "herpesviral", "genomes.", "Many", "of", "these", "motifs", "are", "transcribed", "in", "human", "cells,", "and", "the", "transcribed", "part", "grows", "proportionally", "to", "their", "lengths.", "Many", "such", "motifs", "are", "included", "in", "human", "TEs.", "For", "example,", "one", "23", "nt-long", "motif", "that", "is", "a", "part", "of", "human", "abundant", "Alu", "retrotransposon,", "shares", "sequence", "identity", "with", "eight", "human", "adenoviral", "genomes.", "Testing", "the", "hypothesis:", "This", "hypothesis", "could", "be", "tested", "on", "various", "mammalian", "species", "and", "viruses", "infecting", "mammalian", "cells.", "Implications", "of", "the", "hypothesis:", "This", "hypothesis", "proposes", "that", "mammalian", "organisms", "may", "use", "their", "own", "genomes", "as", "sources", "of", "thousands", "of", "putative", "interfering", "RNA", "motifs", "that", "can", "be", "recruited", "to", "repress", "intracellular", "pathogens", "like", "proliferating", "viruses.", "Reviewers:", "This", "article", "was", "reviewed", "by", "Eugene", "V.", "Koonin,", "Valerian", "V.", "Dolja", "and", "Yuri", "V.", "Shpakovski.", "Background", "The", "discovery", "of", "RNA", "interference", "(RNAi)", "and", "under-", "standing", "of", "its", "mechanisms", "has", "opened", "a", "new", "era", "in", "molecular", "genetics.", "It", "is", "now", "clear", "that", "very", "small", "com-", "plementary", "RNAs", "may", "modulate", "expression", "of", "large", "genes.", "RNAi", "and", "related", "mechanisms", "may", "interfere", "with", "gene", "expression", "at", "the", "stages", "of", "transcription,", "processing", "*", "Correspondence:", "bu3din@mail.ru", "1Shemyakin-Ovchinnikov", "Institute", "of", "Bioorganic", "Chemistry,", "Russian", "Academy", "of", "Sciences,", "16/10", "Miklukho-Maklaya", "st,", "Moscow", "117997,", "Russia", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "of", "mRNA", "and", "translation", "[1,2].", "They", "may", "alter", "tran-", "script", "stability", "and", "may", "even", "cause", "methylation", "of", "extended", "genomic", "loci", "[3,4].", "RNAi", "is", "a", "very", "conservative", "mechanism", "that", "is", "likely", "to", "be", "active", "in", "almost", "all", "eukar-", "yotic", "taxa.", "This", "phenomenon", "attracts", "growing", "attention", "and", "studying", "RNA", "interference", "is", "probably", "one", "of", "the", "most", "rapidly", "developing", "fields", "of", "modern", "science.", "Known", "RNAi", "pathways", "are", "very", "diverse", "[2]", "and", "many", "new", "mechanisms", "are", "probably", "still", "to", "be", "discovered", "[5].", "A", "fundamental", "step", "of", "RNAi", "is", "the", "basepairing", "of", "the", "two", "interacting", "RNAs.", "The", "resulting", "duplexes,", "that", "may", "©", "2010", "Zabolotneva", "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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[ "Daneault", "et", "al.", "Journal", "of", "Medical", "Case", "Reports", "2011,", "5:449", "http://www.jmedicalcasereports.com/content/5/1/449", "C", "A", "S", "E", "R", "E", "P", "O", "R", "T", "JOURNAL", "OF", "MEDICAL", "CASE", "REPORTS", "Open", "Access", "Changes", "in", "physiological", "tremor", "associated", "with", "an", "epileptic", "seizure:", "a", "case", "report", "Jean-François", "Daneault1,", "Benoit", "Carignan2,", "Maxime", "Robert3", "and", "Christian", "Duval3*", "Abstract", "Introduction:", "Epileptic", "seizures", "are", "associated", "with", "motor,", "sensory,", "somatosensory", "or", "autonomic", "symptoms", "that", "have", "all", "been", "described", "in", "varying", "detail", "over", "the", "years.", "Of", "interest", "in", "the", "present", "report", "is", "a", "case", "of", "normal", "physiological", "tremor,", "which", "to", "date", "has", "never", "been", "evaluated", "prior", "to", "and", "during", "an", "epileptic", "seizure.", "In", "fact,", "there", "is", "only", "anecdotal", "mention", "of", "pre-ictal", "and", "ictal", "changes", "in", "clinically", "noticeable", "tremor", "in", "the", "literature.", "Case", "presentation:", "Our", "patient", "was", "a", "left-handed,", "27-year-old", "Caucasian", "woman", "diagnosed", "seven", "years", "previously", "with", "partial", "epileptic", "seizures,", "secondarily", "generalized.", "Physiological", "tremor", "was", "measured", "simultaneously", "on", "the", "index", "finger", "of", "both", "hands", "of", "our", "patient.", "Electromyography", "as", "well", "as", "heart", "rate", "and", "respiration", "were", "also", "monitored.", "A", "previously", "performed", "electroencephalography", "examination", "revealed", "abnormal", "oscillations", "focalized", "to", "the", "left", "primary", "somatosensory", "cortex.", "She", "was", "also", "diagnosed", "with", "left", "frontal", "neuronal", "heterotopias.", "We", "detected", "subclinical", "changes", "in", "tremor", "characteristics,", "such", "as", "amplitude,", "median", "power", "frequency", "and", "power", "dispersion,", "contralateral", "to", "the", "localization", "of", "epileptic", "activity.", "Tremor", "characteristics", "remained", "relatively", "steady", "ipsilateral", "to", "the", "localization", "of", "the", "epileptic", "activity.", "Conclusions:", "Changes", "in", "physiological", "tremor", "characteristics", "should", "be", "considered", "as", "another", "possible", "pre-ictal", "or", "ictal", "manifestation.", "We", "propose", "that", "the", "network", "associated", "with", "physiological", "tremor", "might", "be", "more", "sensitive", "to", "abnormal", "oscillations", "generated", "within", "the", "central", "nervous", "system", "by", "epileptic", "activity", "from", "certain", "structures.", "Introduction", "Epilepsy", "is", "characterized", "by", "a", "predisposition", "to", "abnor-", "mal", "brain", "activity", "leading", "to", "seizures,", "as", "well", "as", "motor", "and", "non-motor", "symptoms", "[1].", "In", "addition", "to", "motor,", "sensory,", "somatosensory", "or", "autonomic", "symptoms", "that", "can", "be", "encountered", "during", "the", "ictal", "phase", "[2],", "physiolo-", "gical", "changes", "have", "also", "been", "observed", "in", "the", "pre-ictal", "phase.", "In", "some", "cases", "heart", "rate", "variability", "has", "been", "shown", "to", "increase", "in", "the", "minutes", "prior", "to", "the", "clinical", "onset", "of", "seizures", "[3].", "There", "is", "also", "anecdotal", "mention", "of", "pre-ictal", "and", "ictal", "changes", "in", "clinically", "noticeable", "tremor", "[4].", "These", "manifestations", "are", "intimately", "linked", "to", "the", "localization", "of", "the", "seizure", "activity.", "In", "this", "report,", "we", "describe", "the", "case", "of", "an", "epileptic", "patient", "who", "had", "a", "sei-", "zure", "while", "physiological", "tremor", "(PT)", "was", "being", "recorded.", "PT", "is", "commonly", "described", "as", "involuntary", "rhythmical", "oscillations", "with", "sinusoidal", "properties.", "These", "*", "Correspondence:", "duval.christian@uqam.ca", "3Département", "de", "Kinanthropologie,", "Université", "du", "Québec", "à", "Montréal,", "Montréal,", "Québec,", "Canada", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "low-amplitude", "oscillations,", "normally", "less", "than", "0.5", "mm", "[5],", "stem", "from", "mechanical", "properties", "of", "the", "limb", "[6]", "as", "well", "as", "possible", "central", "oscillators", "[7].", "The", "characteris-", "tics", "of", "PT", "have", "been", "extensively", "studied", "by", "our", "group", "[8,9]", "and", "others", "(see", "[10]", "for", "review).", "Case", "presentation", "Our", "patient", "was", "tested", "as", "part", "of", "a", "study", "on", "bilateral", "PT", "[8].", "She", "signed", "the", "institutionally", "approved", "informed", "consent", "form,", "but", "omitted", "to", "inform", "us", "of", "her", "condition", "prior", "to", "testing.", "Detailed", "procedures", "for", "that", "study", "can", "be", "found", "in", "the", "published", "work", "[8],", "and", "are", "described", "in", "brief", "below.", "A", "medical", "history", "for", "our", "patient", "was", "gath-", "ered", "from", "her", "medical", "records.", "She", "was", "a", "left-handed,", "27-year-old", "Caucasian", "woman", "who", "had", "been", "diagnosed", "seven", "years", "previously", "with", "partial", "epileptic", "seizures,", "secondarily", "generalized.", "Her", "medical", "records", "also", "described", "abnormal", "electroencephalography", "(EEG)", "oscil-", "lations", "focalized", "to", "the", "left", "primary", "somatosensory", "cor-", "tex.", "She", "was", "also", "diagnosed", "with", "left", "frontal", "neuronal", "heterotopias.", "Since", "her", "diagnosis,", "her", "symptoms", "had", "©", "2011", "Daneault", "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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[ "TRIALS", "Open", "Access", "Smith", "et", "al.", "Trials", "2012,", "13:60", "http://www.trialsjournal.com/content/13/1/60", "S", "T", "U", "D", "Y", "P", "R", "O", "T", "O", "C", "O", "L", "Acupuncture", "to", "improve", "live", "birth", "rates", "for", "women", "undergoing", "in", "vitro", "fertilization:", "a", "protocol", "for", "a", "randomized", "controlled", "trial", "Caroline", "A", "Smith1*,", "Sheryl", "de", "Lacey2,", "Michael", "Chapman3,", "Julie", "Ratcliffe4,", "Robert", "J", "Norman5,", "Neil", "Johnson6,", "Gavin", "Sacks7,", "Jane", "Lyttleton8", "and", "Clare", "Boothroyd9", "Abstract", "Background:", "IVF", "is", "a", "costly", "treatment", "option", "for", "women,", "their", "partners,", "and", "the", "public.", "Therefore", "new", "therapies", "that", "improve", "reproductive", "and", "health", "outcomes", "are", "highly", "desirable.", "There", "is", "a", "growing", "body", "of", "research", "evaluating", "the", "effect", "of", "acupuncture", "administered", "during", "IVF,", "and", "specifically", "on", "the", "day", "of", "embryo", "transfer", "(ET).", "Many", "trials", "are", "heterogeneous", "and", "results", "inconsistent.", "There", "remains", "insufficient", "evidence", "to", "determine", "if", "acupuncture", "can", "enhance", "live", "birth", "rates", "when", "used", "as", "an", "adjunct", "to", "IVF", "treatment.", "The", "study", "will", "determine", "the", "clinical", "effectiveness", "of", "acupuncture", "with", "improving", "the", "proportion", "of", "women", "undergoing", "IVF", "having", "live", "births.", "Other", "objectives", "include:", "determination", "of", "the", "cost", "effectiveness", "of", "IVF", "with", "acupuncture;", "and", "examination", "of", "the", "personal", "and", "social", "context", "of", "acupuncture", "in", "IVF", "patients,", "and", "examining", "the", "reasons", "why", "the", "acupuncture", "may", "or", "may", "not", "have", "worked.", "Methods:", "We", "will", "conduct", "a", "randomized", "controlled", "trial", "of", "acupuncture", "compared", "to", "placebo", "acupuncture.", "Inclusion", "criteria", "include:", "women", "aged", "less", "than", "43", "years;", "undergoing", "a", "fresh", "IVF", "or", "ICSI", "cycle;", "and", "restricted", "to", "women", "with", "the", "potential", "for", "a", "lower", "live", "birth", "rate", "defined", "as", "two", "or", "more", "previous", "unsuccessful", "ETs;", "and", "unsuccessful", "clinical", "pregnancies", "of", "quality", "embryos", "deemed", "by", "the", "embryologist", "to", "have", "been", "suitable", "for", "freezing", "by", "standard", "criteria.", "Women", "will", "be", "randomized", "to", "acupuncture", "or", "placebo", "acupuncture.", "Treatment", "is", "administered", "on", "days", "6", "to", "8", "of", "the", "stimulated", "cycle", "and", "two", "treatments", "on", "the", "day", "of", "ET.", "A", "non-randomized", "cohort", "of", "women", "not", "using", "acupuncture", "will", "be", "recruited", "to", "the", "study.", "The", "primary", "study", "outcome", "is", "the", "proportion", "of", "women", "reporting", "a", "live", "birth.", "Secondary", "outcomes", "include", "the", "proportion", "of", "women", "reporting", "a", "clinical", "pregnancy", "miscarriage", "prior", "to", "12", "weeks,", "quality", "of", "life,", "and", "self-efficacy.", "The", "sample", "size", "of", "the", "study", "is", "1,168", "women,", "with", "the", "aim", "of", "detecting", "a", "7%", "difference", "in", "live", "births", "between", "groups", "(P", "=", "0.05,", "80%", "power).", "Discussion:", "There", "remains", "a", "need", "for", "further", "research", "to", "add", "significant", "new", "knowledge", "to", "defining", "the", "exact", "role", "of", "certain", "acupuncture", "protocols", "in", "the", "management", "of", "infertility", "requiring", "IVF", "from", "a", "clinical", "and", "cost-effectiveness", "perspective.", "Clinical", "Trial", "Registration:", "Australian", "and", "New", "Zealand", "Clinical", "Trial", "Registry", "ACTRN12611000226909", "*", "Correspondence:", "caroline.smith@uws.edu.au", "1Centre", "for", "Complementary", "Medicine", "Research,", "University", "of", "Western", "Sydney,", "Locked", "Bag,", "1797,", "Penrith", "South,", "DC", "NSW", "2751,", "Australia", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "©", "2012", "Smith", "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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[ "Subcellular", "Localization", "of", "Class", "II", "HDAs", "in", "Arabidopsis", "thaliana", ":", "Nucleocytoplasmic", "Shuttling", "of", "HDA15", "Is", "Driven", "by", "Light", "Malona", "V.", "Alinsug1,", "Fang", "Fang", "Chen1,", "Ming", "Luo1,2,", "Ready", "Tai1,", "Liwen", "Jiang", "3", ",", "Keqiang", "Wu", "1", "*", "1", "Institute", "of", "Plant", "Biology,", "College", "of", "Life", "Science,", "National", "Taiwan", "University,", "Taipei,", "Taiwan,", "2", "Key", "Laboratory", "of", "Plant", "Resources", "Conservation", "and", "Sustainable", "Utilization,", "South", "China", "Botanical", "Garden,", "Chinese", "Academy", "of", "Sciences,", "Guangzhou,", "China,", "3", "School", "of", "Life", "Sciences,", "Centre", "for", "Cell", "and", "Developmental", "Biology,", "The", "Chinese", "University", "of", "Hong", "Kong,", "Shatin,", "New", "Territories,", "Hong", "Kong,", "China", "Abstract", "Class", "II", "histone", "deacetylases", "in", "humans", "and", "other", "model", "organisms", "undergo", "nucleocytoplasmic", "shuttling.", "This", "unique", "functional", "regulatory", "mechanism", "has", "been", "well", "elucidated", "in", "eukaryotic", "organisms", "except", "in", "plant", "systems.", "In", "this", "study,", "we", "have", "paved", "the", "baseline", "evidence", "for", "the", "cytoplasmic", "and", "nuclear", "localization", "of", "Class", "II", "HDAs", "as", "well", "as", "their", "mRNA", "expression", "patterns.", "RT-PCR", "analysis", "on", "the", "different", "vegetative", "parts", "and", "developmental", "stages", "reveal", "that", "Class", "II", "HDAs", "are", "ubiquitously", "expressed", "in", "all", "tissues", "with", "minimal", "developmental", "specificity.", "Moreover,", "stable", "and", "transient", "expression", "assays", "using", "HDA-YFP/GFP", "fusion", "constructs", "indicate", "cytoplasmic", "localization", "of", "HDA5,", "HDA8,", "and", "HDA14", "further", "suggesting", "their", "potential", "for", "nuclear", "transport", "and", "deacetylating", "organellar", "and", "cytoplasmic", "proteins.", "Organelle", "markers", "and", "stains", "confirm", "HDA14", "to", "abound", "in", "the", "mitochondria", "and", "chloroplasts", "while", "HDA5", "localizes", "in", "the", "ER.", "HDA15,", "on", "the", "other", "hand,", "shuttles", "in", "and", "out", "of", "the", "nucleus", "upon", "light", "exposure.", "In", "the", "absence", "of", "light,", "it", "is", "exported", "out", "of", "the", "nucleus", "where", "further", "re-exposition", "to", "light", "treatments", "signals", "its", "nuclear", "import.", "Unlike", "HDA5", "which", "binds", "with", "14-3-3", "proteins,", "HDA15", "fails", "to", "interact", "with", "these", "chaperones.", "Instead,", "HDA15", "relies", "on", "its", "own", "nuclear", "localization", "and", "export", "signals", "to", "navigate", "its", "subcellular", "compartmentalization", "classifying", "it", "as", "a", "Class", "IIb", "HDA.", "Our", "study", "indicates", "that", "nucleocytoplasmic", "shuttling", "is", "indeed", "a", "hallmark", "for", "all", "eukaryotic", "Class", "II", "histone", "deacetylases.", "Citation:", "Alinsug", "MV,", "Chen", "FF,", "Luo", "M,", "Tai", "R,", "Jiang", "L,", "et", "al.", "(2012)", "Subcellular", "Localization", "of", "Class", "II", "HDAs", "in", "Arabidopsis", "thaliana:", "Nucleocytoplasmic", "Shuttling", "of", "HDA15", "Is", "Driven", "by", "Light.", "PLoS", "ONE", "7(2):", "e30846.", "doi:10.1371/journal.pone.0030846", "Editor:", "Qiang", "Wu,", "National", "University", "of", "Singapore,", "Singapore", "Received", "July", "3,", "2011;", "Accepted", "December", "23,", "2011;", "Published", "February", "17,", "2012", "Copyright:", "2012", "Alinsug", "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", "study", "was", "funded", "by", "grants", "from", "the", "National", "Science", "Council", "of", "Taiwan", "(97-2311-B-002-004-MY3,", "98-2628-B-002-016-MY3", "and", "99-2321-B-002-", "027-MY3)", "and", "National", "Taiwan", "University", "(98R0066-36", "and", "99R80840).", "MVA", "is", "supported", "by", "a", "grant", "from", "the", "Democratic", "Pacific", "Union", "graduate", "studies", "program", "and", "research", "fellowship", "from", "NSC.", "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:", "kewu@ntu.edu.tw", "Introduction", "Histone", "acetylation", "has", "been", "known", "to", "induce", "an", "open", "chromatin", "configuration", "leading", "to", "transcriptional", "activation", "while", "deacetylation", "stimulates", "chromatin", "condensation", "triggering", "transcriptional", "quies-", "cence.", "Plant", "histone", "deacetylases", "(HDA", "or", "HDACs)", "are", "classified", "into", "three", "distinct", "families", "namely", "RPD3/HDA1", "superfamily,", "Sirtuin", "family,", "and", "the", "HD2", "family", "which", "is", "unique", "in", "plants", "[1,2,3].", "Twelve", "out", "of", "the", "eighteen", "known", "HDAs", "in", "Arabidopsis", "belong", "to", "the", "RPD3/HDA1-like", "histone", "deacetylase", "superfamily,", "which", "is", "further", "subdivided", "into", "three", "classes", "namely", "Class", "I,", "II,", "and", "IV.", "Recent", "phylogenetic", "studies", "by", "Alinsug", "et", "al.", "[4]", "have", "identified", "HDA10", "and", "HDA17", "in", "addition", "to", "HDA6,", "HDA7,", "HDA9,", "and", "HDA19", "as", "Class", "I", "HDA", "based", "on", "sequence", "homology.", "Although", "HDA8", "and", "HDA14", "are", "only", "represented", "in", "plants,", "they", "exhibit", "higher", "sequence", "similarity", "with", "the", "conserved", "histone", "deacetylase", "domains", "of", "HDA5,", "HDA15,", "and", "HDA18,", "members", "of", "the", "Class", "II", "HDAs", "while", "HDA2", "is", "classified", "as", "Class", "IV.", "Among", "the", "RPD3/HDA1-like", "superfamily", "HDAs", "in", "Arabidop-", "sis,", "HDA6,", "HDA19,", "and", "HDA18", "have", "been", "well", "elucidated", "to", "play", "crucial", "roles", "in", "plant", "development", "and", "environmental", "stress", "response", "and", "display", "tissue-specific", "expression", "[5–11,3].", "HDA6", "is", "the", "most", "extensively", "studied", "plant", "histone", "deacetylase", "acting", "as", "a", "global", "repressor", "involved", "in", "flowering,", "freezing", "tolerance,", "ABA", "and", "salt", "stress", "response,", "senescence,", "repression", "of", "embryonic", "properties,", "JA", "pathway,", "and", "establishment", "of", "nucleolar", "dominance", "[12–16,10].", "Similarly,", "HDA19", "is", "a", "global", "repressor", "in", "embryonic", "and", "flower", "development,", "ABA", "and", "abiotic", "stress", "response,", "light-", "responsive", "gene", "expression,", "JA", "and", "ethylene", "signaling,", "and", "regulates", "basal", "defense", "via", "interaction", "with", "WRKY", "transcription", "factors", "[10,5,6,17,8,18,11].", "HDA18,", "on", "the", "other", "hand,", "had", "been", "implicated", "in", "root", "epidermal", "patterning", "[19].", "Previous", "studies", "by", "Finkemeier", "et", "al.", "[20]", "and", "Wu", "et", "al.", "[21]", "elaborated", "on", "the", "reversible", "acetylation", "of", "cytoplasmic", "proteins", "in", "Arabidopsis", "indicating", "that", "histones", "are", "not", "the", "only", "proteins", "being", "acetylated", "&", "deacetylated.", "A", "substantial", "proportion", "of", "these", "cytoplasmic", "proteins", "are", "involved", "in", "photosynthesis", "and", "central", "metabolism", "where", "the", "deacetylation", "of", "rubisco", "and", "phosphoglyc-", "erate", "kinase", "using", "human", "Sirt3", "lead", "to", "a", "significant", "increase", "in", "their", "catalytic", "activity.", "However,", "the", "use", "of", "human", "Sirt3", "as", "a", "deacetylase", "may", "exhibit", "certain", "specificities", "towards", "plant", "Lys", "acetylation", "sites.", "Thus,", "the", "observed", "potency", "may", "have", "been", "underestimated", "had", "a", "plant", "specific", "deacetylase", "been", "used.", "Unfortunately,", "none", "of", "the", "18", "known", "histone", "deacetylases", "in", "Arabidopsis", "have", "been", "identified", "to", "be", "cytoplasmic", "since", "HDA6", "and", "HDA19", "were", "established", "to", "be", "exclusively", "nuclear.", "In", "rice,", "PLoS", "ONE", "|", "www.plosone.org", "1", "February", "2012", "|", "Volume", "7", "|", "Issue", "2", "|", "e30846" ]

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[ "PAPSS2", "Promotes", "Alkaline", "Phosphates", "Activity", "and", "Mineralization", "of", "Osteoblastic", "MC3T3-E1", "Cells", "by", "Crosstalk", "and", "Smads", "Signal", "Pathways", "Weizhuo", "Wang1*,", "Fang", "Li2,", "Kunzheng", "Wang1,", "Bin", "Cheng1,", "Xiong", "Guo3", "1", "Department", "of", "Orthopedics", "Surgery,", "the", "Second", "Affiliated", "Hospital,", "College", "of", "Medicine,", "Xi’an", "Jiaotong", "University,", "Xi’an,", "Shaanxi,", "People’s", "Republic", "of", "China,", "2", "Department", "of", "Prosthodontics,", "School", "of", "Stomatology,", "The", "Fourth", "Military", "University,", "Xi’an,", "Shaanxi,", "People’s", "Republic", "of", "China,", "3", "Faculty", "of", "Public", "Health,", "College", "of", "Medicine,", "Key", "Laboratory", "of", "Environment", "and", "Gene", "Related", "Diseases", "of", "Ministry", "Education,", "Xi’an", "Jiaotong", "University,", "Xi’an,", "Shaanxi,", "People’s", "Republic", "of", "China", "Abstract", "Several", "studies", "have", "indicated", "that", "PAPSS2", "(39-phosphoadenosine-59-phosphosulfate", "synthetase", "2)", "activity", "is", "important", "to", "normal", "skeletal", "development.", "Mouse", "PAPSS2", "is", "predominantly", "expressed", "during", "the", "formation", "of", "the", "skeleton", "and", "cartilaginous", "elements", "of", "the", "mouse", "embryo", "and", "in", "newborn", "mice.", "However,", "the", "role", "and", "mechanism", "of", "PAPSS2", "in", "bone", "formation", "remains", "largely", "unidentified.", "By", "analyzing", "the", "expression", "pattern", "of", "the", "PAPSS2", "gene,", "we", "have", "found", "that", "PAPSS2", "is", "expressed", "in", "bone", "tissue", "and", "bone", "formation.", "PAPSS2", "transcripts", "increase", "during", "osteoblast", "differentiation", "and", "are", "in", "less", "level", "in", "RANKL-induced", "osteoclast", "like", "cells.", "By", "using", "lentivirus-mediated", "RNA", "interference", "(RNAi)", "technology,", "we", "knocked", "down", "PAPSS2", "expression", "in", "MC3T3-E1", "osteoblast.", "Silencing", "of", "PAPSS2", "expression", "significantly", "decreases", "ALP", "activity", "and", "cell", "mineralization,", "inhibits", "expression", "of", "osteoblast", "marker", "osteopontin", "(OPN)", "and", "collagen", "I.", "Conversely,", "overexpression", "of", "PAPSS2", "promotes", "the", "MC3T3-E1", "to", "differentiate", "into", "osteoblast", "and", "mineralization.", "Moreover,", "compared", "to", "that", "in", "the", "control", "cells,", "the", "mRNA", "level", "and", "protein", "expression", "of", "phosphorylated", "Smad", "2/3,", "which", "is", "a", "key", "transcriptional", "factor", "in", "the", "Smad", "osteoblast", "differentiation", "pathway,", "showed", "significant", "decreases", "in", "PAPSS2-silenced", "cells", "and", "increases", "in", "PAPSS2-", "overexpression", "cells.", "These", "results", "suggest", "that", "PAPSS2", "might", "regulate", "osteoblast", "ALP", "activity", "and", "cell", "mineralization,", "probably", "through", "Smads", "signal", "pathways.", "Citation:", "Wang", "W,", "Li", "F,", "Wang", "K,", "Cheng", "B,", "Guo", "X", "(2012)", "PAPSS2", "Promotes", "Alkaline", "Phosphates", "Activity", "and", "Mineralization", "of", "Osteoblastic", "MC3T3-E1", "Cells", "by", "Crosstalk", "and", "Smads", "Signal", "Pathways.", "PLoS", "ONE", "7(8):", "e43475.", "doi:10.1371/journal.pone.0043475", "Editor:", "Brenda", "Smith,", "Oklahoma", "State", "University,", "United", "States", "of", "America", "Received", "April", "18,", "2012;", "Accepted", "July", "20,", "2012;", "Published", "August", "16,", "2012", "Copyright:", "2012", "Wang", "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", "project", "was", "supported", "by", "the", "Natural", "Scientific", "Fund", "of", "China", "(81001225),", "the", "international", "Co-operative", "Fund", "in", "Xian", "Jiaotong", "University,", "China", "and", "US", "(08143004),", "and", "the", "Fundamental", "Research", "Funds", "for", "the", "Central", "Universities", "(08140003).", "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:", "wangweizhuo@mail.xjtu.edu.cn", "Introduction", "Bone", "is", "a", "mineralized", "tissue", "that", "underlies", "multiple", "mechanical", "and", "metabolic", "functions", "of", "the", "skeleton", "[1,2].", "Formation", "and", "maintenance", "of", "bone", "tissue", "are", "regulated", "in", "a", "sophisticated", "fashion", "by", "bone-forming", "osteoblasts", "and", "bone-resorbing", "osteoclasts.", "Many", "skeletal", "diseases,", "such", "as", "osteoporosis,", "Kashin-Beck", "disease,", "Paget’s", "disease", "of", "the", "bone,", "rheumatoid", "arthritis,", "and", "bone", "metastases", "all", "arise", "from", "an", "imbalance", "in", "the", "relative", "activities", "of", "osteoblasts", "and", "osteoclasts", "[3].", "The", "proliferation", "and", "differentiation", "of", "those", "two", "cell", "types", "are", "controlled", "by", "various", "local", "growth", "factors,", "cytokines", "produced,", "in", "the", "bone", "and", "by", "systemic", "enzymes.", "The", "presence", "of", "PAPS", "(39-phosphoadenosine-59-phosphosulfate)", "is", "a", "prerequisite", "for", "catalytic", "efficiency", "in", "all", "sulfation", "reactions.", "In", "humans,", "PAPS", "is", "synthesized", "from", "ATP", "and", "SO422", "by", "two", "isoforms", "of", "PAPS", "synthetase", "(PAPSS):", "PAPSS1", "and", "PAPSS2.", "The", "PAPSS2", "is", "one", "of", "the", "principal", "enzymes", "required", "for", "the", "sulfation", "of", "extracellular", "matrix", "molecules", "in", "bone", "formation", "and", "other", "tissues", "[4–6].", "A", "truncation", "mutation", "of", "the", "human", "PAPSS2", "gene", "was", "reported", "in", "a", "Pakistani", "family", "suffering", "from", "a", "novel", "form", "of", "spondyloepime-", "taphyseal", "dysplasia", "(SEMD)", "[7,8].", "A", "homozygous", "PAPSS2", "mutation", "(S475X)", "was", "identified", "in", "another", "large", "Pakistani", "family", "affected", "by", "SEMD,", "Pakistani", "type", "[8,9].", "This", "manifested", "as", "disproportionately", "short", "stature", "with", "short,", "bowed", "lower", "limbs,", "enlarged", "knee", "joints,", "kyphoscoliosis,", "and", "generalized", "brachydac-", "tyly", "[7].", "Chondroitin", "6-O-sulfotransferase", "requires", "PAPS", "for", "catalytic", "activity,", "and", "the", "abnormal", "PAPSS2", "gene", "that", "encodes", "chondroitin", "6-O-sulfotransferase", "can", "cause", "SEMD,", "Omani", "type", "[10].", "Humans", "lacking", "normal", "PAPSS2", "activity", "exhibit", "long", "bone", "shortening", "and", "bowing,", "and", "also", "show", "degenerative", "joint", "disease,", "including", "evidence", "of", "knee", "joint", "arthrosis.", "Given", "the", "premature", "development", "of", "degenerative", "knee", "joint", "disease", "in", "the", "mutant", "mice", "and", "other", "similarities", "between", "SEMD", "mice", "and", "human", "lacking", "normal", "PAPSS2", "activity,", "it", "has", "been", "proposed", "that", "this", "mutant", "represents", "a", "model", "of", "human", "PAPSS2", "deficiency-associated", "arthrosis", "[11].", "One", "of", "our", "previous", "studies", "included", "a", "microarray", "analysis", "that", "showed", "some", "correlation", "between", "PAPSS2", "genes", "in", "individuals", "afflicted", "with", "endemic", "knee", "osteoarthritis", "and", "those", "with", "Kashin-", "Beck", "disease", "exhibiting", "shortened", "long", "bones", "and", "enlarged", "knee", "and", "finger", "joints", "[12,13].", "Some", "features", "of", "the", "bone", "phenotype", "in", "the", "endemic", "osteoarthritis", "patient", "resemble", "those", "observed", "in", "SEMD,", "excepting", "that", "the", "changes", "in", "the", "bone", "changes", "were", "milder", "for", "our", "patients", "and", "the", "changes", "in", "the", "epiphyseal", "plates", "of", "the", "long", "bones", "and", "metaphyseal", "changes", "were", "detectable", "in", "our", "patients", "[14,15].", "However,", "the", "absence", "of", "the", "pubertal", "growth", "PLOS", "ONE", "|", "www.plosone.org", "1", "August", "2012", "|", "Volume", "7", "|", "Issue", "8", "|", "e43475" ]

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[ "Regulation", "of", "DNA", "Replication", "Timing", "on", "Human", "Chromosome", "by", "a", "Cell-Type", "Specific", "DNA", "Binding", "Protein", "SATB1", "Masako", "Oda,", "Yutaka", "Kanoh,", "Yoshihisa", "Watanabe,", "Hisao", "Masai*", "Genome", "Dynamics", "Project,", "Department", "of", "Genome", "Medicine,", "Tokyo", "Metropolitan", "Institute", "of", "Medical", "Science,", "Tokyo,", "Japan", "Abstract", "Background:", "Replication", "timing", "of", "metazoan", "DNA", "during", "S-phase", "may", "be", "determined", "by", "many", "factors", "including", "chromosome", "structures,", "nuclear", "positioning,", "patterns", "of", "histone", "modifications,", "and", "transcriptional", "activity.", "It", "may", "be", "determined", "by", "Mb-domain", "structures,", "termed", "as", "‘‘replication", "domains’’,", "and", "recent", "findings", "indicate", "that", "replication", "timing", "is", "under", "developmental", "and", "cell", "type-specific", "regulation.", "Methodology/Principal", "Findings:", "We", "examined", "replication", "timing", "on", "the", "human", "5q23/31", "3.5-Mb", "segment", "in", "T", "cells", "and", "non-T", "cells.", "We", "used", "two", "independent", "methods", "to", "determine", "replication", "timing.", "One", "is", "quantification", "of", "nascent", "replicating", "DNA", "in", "cell", "cycle-fractionated", "stage-specific", "S", "phase", "populations.", "The", "other", "is", "FISH", "analyses", "of", "replication", "foci.", "Although", "the", "locations", "of", "early-", "and", "late-replicating", "domains", "were", "common", "between", "the", "two", "cell", "lines,", "the", "timing", "transition", "region", "(TTR)", "between", "early", "and", "late", "domains", "were", "offset", "by", "200-kb.", "We", "show", "that", "Special", "AT-rich", "sequence", "Binding", "protein", "1", "(SATB1),", "specifically", "expressed", "in", "T-cells,", "binds", "to", "the", "early", "domain", "immediately", "adjacent", "to", "TTR", "and", "delays", "the", "replication", "timing", "of", "the", "TTR.", "Measurement", "of", "the", "chromosome", "copy", "number", "along", "the", "TTR", "during", "synchronized", "S", "phase", "suggests", "that", "the", "fork", "movement", "may", "be", "slowed", "down", "by", "SATB1.", "Conclusions:", "Our", "results", "reveal", "a", "novel", "role", "of", "SATB1", "in", "cell", "type-specific", "regulation", "of", "replication", "timing", "along", "the", "chromosome.", "Citation:", "Oda", "M,", "Kanoh", "Y,", "Watanabe", "Y,", "Masai", "H", "(2012)", "Regulation", "of", "DNA", "Replication", "Timing", "on", "Human", "Chromosome", "by", "a", "Cell-Type", "Specific", "DNA", "Binding", "Protein", "SATB1.", "PLoS", "ONE", "7(8):", "e42375.", "doi:10.1371/journal.pone.0042375", "Editor:", "Marco", "Muzi-Falconi,", "Universita’", "di", "Milano,", "Italy", "Received", "March", "22,", "2012;", "Accepted", "July", "4,", "2012;", "Published", "August", "7,", "2012", "Copyright:", "2012", "Oda", "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", "Grant-in-Aid", "for", "Scientific", "Research", "(A)", "(to", "HM)", "and", "Grant-in-Aid", "for", "Scientific", "Research", "on", "Priority", "Area", "‘‘Chromosome", "Cycle’’", "from", "the", "Ministry", "of", "Education,", "Culture,", "Sports,", "Science,", "and", "Technology", "of", "Japan", "(to", "HM).", "No", "additional", "external", "funding", "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:", "masai-hs@igakuken.or.jp", "Introduction", "DNA", "replication", "occurs", "once", "and", "only", "once", "during", "S", "phase", "of", "cell", "cycle", "[1].", "This", "strict", "regulation", "is", "achieved", "by", "multiple", "layers", "of", "mechanisms.", "Once", "DNA", "replication", "is", "initiated,", "three", "billion", "base-", "pair", "human", "genome", "is", "replicated", "in", "7,8", "hrs", "[2].", "Origins", "on", "the", "eukaryotic", "chromosomes", "can", "be", "classified", "according", "to", "the", "timing", "at", "which", "they", "are", "programmed", "to", "fire", "during", "S", "phase", "[3].", "Studies", "in", "yeasts", "have", "established", "that", "intra-S", "checkpoint", "negatively", "regulates", "the", "firing", "of", "late", "or", "dormant", "origins", "[4].", "This", "is", "also", "the", "case", "in", "mammalian", "cells", "as", "well", "[5–8].", "Other", 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"Issue", "8", "|", "e42375" ]

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[ "Estrogen", "Receptor", "b", "Exerts", "Tumor", "Repressive", "Functions", "in", "Human", "Malignant", "Pleural", "Mesothelioma", "via", "EGFR", "Inactivation", "and", "Affects", "Response", "to", "Gefitinib", "Giulia", "Pinton", "1", ",", "Warren", "Thomas2,", "Paolo", "Bellini1,", "Arcangela", "Gabriella", "Manente1,", "Roberto", "E.", "Favoni3,", "Brian", "J.", "Harvey2,", "Luciano", "Mutti4.,", "Laura", "Moro1*.", "1", "Department", "of", "Chemical,", "Food,", "Pharmaceutical", "and", "Pharmacological", "Sciences,", "Drug", "and", "Food", "Biotechnology", "Center,", "University", "of", "Piemonte", "Orientale", "A.", "Avogadro,", "Novara,", "Italy,", "2", "Department", "of", "Molecular", "Medicine,", "Royal", "College", "of", "Surgeons", "in", "Ireland", "and", "Education", "and", "Research", "Centre,", "Beaumont", "Hospital,", "Dublin,", "Ireland,", "3", "Laboratory", "of", "Experimental", "Pharmacology,", "National", "Cancer", "Institute,", "Genoa,", "Italy,", "4", "Department", "of", "Medicine,", "Local", "Health", "Unit", "11,", "Vercelli,", "Italy", "Abstract", "Background:", "The", "role", "of", "estrogen", "and", "estrogen", "receptors", "in", "oncogenesis", "has", "been", "investigated", "in", "various", "malignancies.", "Recently", "our", "group", "identified", "estrogen", "receptor", "beta", "(ERb)", "expression", "as", "an", "independent", "prognostic", "factor", "in", "the", "progression", "of", "human", "Malignant", "Pleural", "Mesothelioma", "(MMe),", "but", "the", "underlying", "mechanism", "by", "which", "ERb", "expression", "in", "tumors", "determines", "clinical", "outcome", "remains", "largely", "unknown.", "This", "study", "is", "aimed", "at", "investigating", "the", "molecular", "mechanisms", "of", "ERb", "action", "in", "MMe", "cells", "and", "disclosing", "the", "potential", "translational", "implications", "of", "these", "results.", "Methods:", "We", "modulated", "ERb", "expression", "in", "REN", "and", "MSTO-211H", "MMe", "cell", "lines", "and", "evaluated", "cell", "proliferation", "and", "EGF", "receptor", "(EGFR)", "activation.", "Results:", "Our", "data", "indicate", "that", "ERb", "knockdown", "in", "ER", "positive", "cells", "confers", "a", "more", "invasive", "phenotype,", "increases", "anchorage", "independent", "proliferation", "and", "elevates", "the", "constitutive", "activation", "of", "EGFR-coupled", "signal", "transduction", "pathways.", "Conversely,", "re-expression", "of", "ERb", "in", "ER", "negative", "cells", "confers", "a", "more", "epithelioid", "phenotype,", "decreases", "their", "capacity", "for", "anchorage", "independent", "growth", "and", "down-modulates", "proliferative", "signal", "transduction", "pathways.", "We", "identify", "a", "physical", "interaction", "between", "ERb,", "EGFR", "and", "caveolin", "1", "that", "results", "in", "an", "altered", "internalization", "and", "in", "a", "selective", "reduced", "activation", "of", "EGFR-coupled", "signaling,", "when", "ERb", "is", "over-expressed.", "We", "also", "demonstrate", "that", "differential", "expression", "of", "ERb", "influences", "MMe", "tumor", "cell", "responsiveness", "to", "the", "therapeutic", "agent:", "Gefitinib.", "Conclusions:", "This", "study", "describes", "a", "role", "for", "ERb", "in", "the", "modulation", "of", "cell", "proliferation", "and", "EGFR", "activation", "and", "provides", "a", "rationale", "to", "facilitate", "the", "targeting", "of", "a", "subgroup", "of", "MMe", "patients", "who", "would", "benefit", "most", "from", "therapy", "with", "Gefitinib", "alone", "or", "in", "combination", "with", "Akt", "inhibitors.", "Citation:", "Pinton", "G,", "Thomas", "W,", "Bellini", "P,", "Manente", "AG,", "Favoni", "RE,", "et", "al.", "(2010)", "Estrogen", "Receptor", "b", "Exerts", "Tumor", "Repressive", "Functions", "in", "Human", "Malignant", "Pleural", "Mesothelioma", "via", "EGFR", "Inactivation", "and", "Affects", "Response", "to", "Gefitinib.", "PLoS", "ONE", "5(11):", "e14110.", "doi:10.1371/journal.pone.0014110", "Editor:", "Joseph", "Alan", "Bauer,", "Bauer", "Research", "Foundation,", "United", "States", "of", "America", "Received", "July", "6,", "2010;", "Accepted", "October", "22,", "2010;", "Published", "November", "29,", "2010", "Copyright:", "2010", "Pinton", "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", "MARF", "(Mesothelioma", "Applied", "Research", "Foundation),", "Fondazione", "Buzzi", "Unicem", "and", "Higher", "Education", "Authority", "of", "Ireland", "(PRTLI4)", "through", "the", "National", "Biophotonics", "and", "Imaging", "Platform.", "G.", "Pinton", "was", "supported", "by", "a", "PhD", "fellowship", "from", "Progetto", "Lagrange", "(Cassa", "di", "Risparmio", "di", "Torino).", "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:", "moro@pharm.unipmn.it", ".", "These", "authors", "contributed", "equally", "to", "this", "work.", "Introduction", "Malignant", "pleural", "mesothelioma", "(MMe)", "is", "a", "highly", "aggressive", "tumor,", "most", "often", "associated", "with", "asbestos", "exposure,", "although", "a", "role", "for", "SV40", "and", "genetic", "susceptibility", "have", "also", "been", "proposed", "[1].", "The", "delayed", "clinical", "diagnosis", "of", "this", "tumor", "is", "due", "to", "the", "slow", "progression", "of", "the", "malignancy", "[2].", "The", "clinical", "prognosis", "is", "generally", "poor,", "with", "a", "reported", "median", "survival", "from", "presentation", "of", "9–12", "months.", "Several", "clinical", "prognostic", "factors", "have", "been", "tentatively", "correlated", "to", "patient", "survival;", "these", "include", "histological", "type", "(epithelioid,", "sarcomatoid", "or", "biphasic)", "and", "tumor", "grade", "[3,4].", "We", "recently", "published", "data", "demonstrating", "that", "estrogen", "receptor", "beta", "(ERb)", "is", "linked", "with", "better", "prognosis", "in", "MMe", "patients", "and", "is", "likely", "to", "act", "as", "tumor", "repressor", "[5].", "Estrogens", "exert", "their", "biological", "effects", "through", "two", "distinct", "receptors:", "ERa", "and", "ERb.", "The", "ERs", "are", "transcribed", "from", "two", "different", "genes", "and", "display", "specific", "tissue", "expression", "patterns", "as", "well", "as", "distinct", "ligand", "specificities", "even", "though", "both", "bind", "the", "most", "biologically", "active", "estrogen,", "17b-estradiol", "[6].", "This", "is", "confirmed", "by", "the", "fact", "that", "mice", "lacking", "ERb", "(bER", "KO)", "display", "a", "very", "different", "phenotype", "to", "those", "devoid", "of", "ERa", "(aERKO)", "[7–11].", "In", "addition", "to", "ligand", "binding", "ERb", "activity", "and", "sub-cellular", "distribution", "is", "also", "regulated", "through", "its", "post-translational", "modification", "[12,13].", "Evidences", "accumulated", "over", "the", "past", "decade", "describe", "a", "cross-talk", "between", "ERs", "and", "EGFRs", "[14].", "Work", "in", "this", "area", "has", "established", "a", "requirement", "of", "ERs", "for", "some", "EGFR", "actions", "[15,16].", "Recent", "findings", "suggest", "the", "important", "role", "of", "EGFR", "(or", "similar", "receptors)", "for", "estrogen", "signaling", "from", "the", "membrane", "in", "breast", "cancer.", "It", "has", "PLoS", "ONE", "|", "www.plosone.org", "1", "November", "2010", "|", "Volume", "5", "|", "Issue", "11", "|", "e14110" ]

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"http://www.issoonline.com/content/3/1/15", "Received:", "10", "March", "2006", "Accepted:", "22", "June", "2006", "©", "2006", "Qureshi", "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", "Primary", "intra-abdominal", "malignant", "mesenchymal", "tumours", "are", "very", "rare", "and", "there", "are", "not", "many", "cases", "of", "visceral", "malignant", "fibrous", "histiocytoma", "in", "the", "English", "literature.", "We", "report", "a", "new", "case", "of", "abdominal", "malignant", "fibrous", "histiocytoma", "presenting", "as", "abdominal", "pain", "and", "pyrexia", "of", "unknown", "origin", "in", "a", "54", "year", "old", "female", "followed", "by", "a", "brief", "review", "of", "literature.", "Presentation", "with", "pyrexia", "of", "unknown", "origin", "is", "extremely", "rare", "in", "this", "condition.", "Background", "The", "term", "Malignant", "Fibrous", "Histiocytoma", "(MFH)", "was", "originally", "described", "by", "O'Brien", "and", "Stout", "in", "1964", "[1]", "to", "cover", "a", "variety", "of", "pleomorphic", "soft", "tissue", "sarcomas", "derived", "from", "histiocytes", "capable", "of", "fibroblastic", "transfor-", "mation.", "MFH", "is", "a", "common", "sarcoma", "of", "mesenchymal", "ori-", "gin", "affecting", "soft", "tissues", "of", "the", "body,", "especially", "the", "extremities", "and", "retroperitoneum.", "Primary", "intra-abdomi-", "nal", "MFH", "is", "a", "rare", "disease", "and", "few", "cases", "are", "reported", "in", "the", "English", "literature.", "Its", "presentation", "as", "high-grade", "pyrexia", "of", "unknown", "origin", "(PUO)", "is", "extremely", "unusual.", "We", "report", "a", "case", "of", "malignant", "fibrous", "histiocytoma", "affecting", "colon,", "spleen,", "left", "hemi", "diaphragm", "and", "distal", "pancreas", "in", "a", "54", "year", "old", "female,", "who", "presented", "with", "abdominal", "pain", "and", "pyrexia", "of", "unknown", "origin.", "Case", "report", "A", "54", "year", "old", "female", "presented", "to", "our", "surgical", "outpatient", "clinic", "with", "abdominal", "pain", "and", "pyrexia.", "Abdominal", "pain", "was", "of", "recent", "onset", "and", "mainly", "in", "the", "left", "upper", "abdomen", "but", "she", "had", "fever", "for", "at", "least", "6", "months.", "Her", "pyrexia", "was", "high", "grade", "(39.5–40", "C0),", "intermittent,", "and", "most", "common", "in", "the", "early", "morning.", "Clinical", "examination", "revealed", "a", "firm,", "vaguely", "defined,", "tender", "mass", "in", "the", "left", "upper", "quad-", "rant", "of", "the", "abdomen.", "Blood", "results", "showed", "persistently", "high", "ESR", "(>100),", "high", "CRP", "(>240),", "leukocytosis,", "mildly", "raised", "Alkaline", "Phosphatase", "and", "anaemia", "(normochro-", "mic,", "normocytic).", "There", "was", "no", "overt", "source", "of", "infection", "that", "could", "account", "for", "the", "fever.", "Repeated", "blood", "cultures", "did", "not", "yield", "any", "bacterial", "growth.", "NM", "Leukocyte", "HMPAO", "scan", "showed", "no", "convincing", "abnormality", "to", "help", "localise", "an", "infective", "focus.", "There", "was", "no", "improvement", "in", "pyrexia", "after", "treating", "the", "patient", "with", "broad-spectrum", "antibiotics.", "CT", "scan", "of", "the", "abdomen", "was", "performed", "which", "showed", "three", "heterogeneous", "masses", "in", "left", "upper", "abdomen", "relat-", "ing", "to", "splenic", "flexure", "of", "colon,", "pancreatic", "body", "and", "tail", "and", "left", "crus", "of", "the", "diaphragm", "(figure", "1).", "There", "was", "evi-", "dence", "of", "central", "necrosis", "in", "two", "of", "these", "masses.", "A", "trucut", "biopsy", "of", "the", "mass", "was", "performed", "and", "histology", "revealed", "spindle", "cell", "leiomyosarcoma.", "Page", "1", "of", "7", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "ORIGINAL", "RESEARCH", "ARTICLE", "published:", "31", "August", "2012", "doi:", "10.3389/fpsyg.2012.00303", "From", "emotions", "to", "consciousness", "–", "a", "neuro-phenomenal", "and", "neuro-relational", "approach", "Georg", "Northoff", "*", "Mind,", "Brain", "Imaging", "and", "Neuroethics", "Research", "Unit,", "Institute", "of", "Mental", "Health", "Research,", "University", "of", "Ottawa,", "Ottawa,", "ON,", "Canada", "Edited", "by:", "Lihong", "Wang,", "Duke", "University,", "USA", "Reviewed", "by:", "Lihong", "Wang,", "Duke", "University,", "USA", "Mauro", "Adenzato,", "University", "of", "Turin,", "Italy", "*Correspondence:", "Georg", "Northoff", ",", "Mind,", "Brain", "Imaging", "and", "Neuroethics", "Research", "Unit,", "Institute", "of", "Mental", "Health", "Research,", "1145", "Carling", "Avenue,", "Ottawa,", "ON,", "Canada", "K1Z", "7K4.", "e-mail:", "georg.northoff@rohcg.on.ca", "The", "James–Lange", "theory", "considers", "emotional", "feelings", "as", "perceptions", "of", "physiological", "body", "changes.", "This", "approach", "has", "recently", "resurfaced", "and", "modified", "in", "both", "neurosci-", "entific", "and", "philosophical", "concepts", "of", "embodiment", "of", "emotional", "feelings.", "In", "addition", "to", "the", "body,", "the", "role", "of", "the", "environment", "in", "emotional", "feeling", "needs", "to", "be", "considered.", "I", "here", "claim", "that", "the", "environment", "has", "not", "merely", "an", "indirect", "and", "instrumental,", "i.e.,", "modulatory", "role", "on", "emotional", "feelings", "via", "the", "body", "and", "its", "sensorimotor", "and", "vegeta-", "tive", "functions.", "Instead,", "the", "environment", "may", "have", "a", "direct", "and", "non-instrumental,", "i.e.,", "constitutional", "role", "in", "emotional", "feelings.", "This", "implies", "that", "the", "environment", "itself", "is", "con-", "stitutive", "of", "emotional", "feeling", "rather", "than", "the", "bodily", "representation", "of", "the", "environment.", "I", "call", "this", "the", "relational", "concept", "of", "emotional", "feeling.", "The", "present", "paper", "discusses", "recent", "data", "from", "neuroimaging", "that", "investigate", "emotions", "in", "relation", "to", "interoceptive", "processing", "and", "the", "brain’s", "intrinsic", "activity.", "These", "data", "show", "the", "intrinsic", "linkage", "of", "interoceptive", "stimulus", "processing", "to", "both", "exteroceptive", "stimuli", "and", "the", "brain’s", "intrin-", "sic", "activity.", "This", "is", "possible", "only", "if", "the", "differences", "between", "intrinsic", "activity", "and", "intero-", "and", "exteroceptive", "stimuli", "is", "encoded", "into", "neural", "activity.", "Such", "relational", "coding", "makes", "possible", "the", "assignment", "of", "subjective", "and", "affective", "features", "to", "the", "otherwise", "objec-", "tive", "and", "non-affective", "stimulus.", "I", "therefore", "consider", "emotions", "to", "be", "intrinsically", "affec-", "tive", "and", "subjective", "as", "it", "is", "manifest", "in", "emotional", "feelings.", "The", "relational", "approach", "thus", "goes", "together", "with", "what", "may", "be", "described", "as", "neuro-phenomenal", "approach.", "Such", "neuro-", "phenomenal", "approach", "does", "not", "only", "inform", "emotions", "and", "emotional", "feeling", "but", "is", "also", "highly", "relevant", "to", "better", "understand", "the", "neuronal", "mechanisms", "underlying", "consciousness", "in", "general.", "Keywords:", "consciousness,", "emotion,", "emotional", "feeling,", "insula,", "James–Lange", "theory", "INTRODUCTION", "The", "well-known", "James–Lange", "theory", "determined", "feelings", "as", "per-", "ceptions", "of", "physiological", "body", "changes", "in", "the", "autonomic,", "hor-", "monal,", "and", "motor", "systems.", "Once", "we", "become", "aware", "of", "phys-", "iological", "bodily", "changes", "induced", "by", "danger,", "we", "feel", "fear", "and", "subjectively", "experience", "emotional", "feelings.", "James", "(1884,", "p.", "190)", "consequently", "considered", "bodily", "changes", "as", "central", "to", "emo-", "tional", "feelings;", "“we", "feel", "sorry", "because", "we", "cry,", "angry", "because", "we", "strike,", "afraid", "because", "we", "tremble,", "and", "not", "that", "we", "cry,", "strike,", "or", "tremble,", "because", "we", "are", "sorry,", "angry,", "or", "fearful,", "as", "the", "case", "may", "be.”", "Modern", "empirical", "versions", "of", "this", "the-", "ory", "resurface", "in", "current", "neuroscientific", "models", "of", "emotion", "as,", "for", "instance,", "in", "Damasio", "and", "others", "(Damasio,", "1999,", "2010;", "Craig,", "2003,", "2004,", "2005,", "2009,", "2011;", "Bechara,", "2004;", "Niedenthal,", "2007).", "Conceptually,", "the", "embodied", "approach", "to", "emotion", "emphasizes", "the", "crucial", "role", "of", "the", "body", "in", "emotional", "feeling.", "If", "the", "body", "and", "its", "vegetative", "and", "sensorimotor", "function", "play", "a", "crucial", "role", "in", "constituting", "emotional", "feelings,", "the", "body", "can", "no", "longer", "be", "con-", "sidered", "in", "a", "merely", "objective", "way", "but", "rather", "as", "subjective", "and", "experienced", "–", "the", "mere", "Koerper", "as", "objective", "body", "must", "be", "dis-", "tinguished", "from", "the", "lived", "body", "as", "subjectively", "experienced", "body", "in", "emotional", "feeling", "(Colombetti", "and", "Thompson,", "2005,", "2007;", "Colombetti,", "2008)1.", "The", "emphasis", "on", "the", "body", "raises", "the", "question", "for", "the", "role", "of", "the", "environment", "in", "constituting", "emotional", "feelings.", "The", "body", "stands", "in", "direct", "contact", "with", "the", "environment", "via", "its", "sensorimotor", "func-", "tions", "which", "are", "emphasized", "in", "recent", "body-based,", "e.g.,", "embodied", "concepts", "of", "emotional", "feelings", "(see", "Niedenthal", "et", "al.,", "2005;", "Nieden-", "thal,", "2007).", "The", "body", "is", "supposed", "to", "represent", "the", "environment", "in", "sensorimotor", "terms", "and", "it", "is", "these", "bodily", "representations", "that", "are", "considered", "crucial", "in", "constituting", "emotional", "feelings.", "The", "envi-", "ronment", "may", "have", "then", "an", "indirect", "and", "modulatory", "role", "via", "the", "body", "in", "the", "constitution", "of", "the", "emotional", "feelings.", "One", "could", "also", "imagine", "that", "the", "environment", "has", "a", "direct", "and", "constitutive", "role", "in", "emotional", "feeling;", "the", "environment", "may", "then", "1It", "should", "also", "be", "pointed", "out", "that", "feelings", "cannot", "be", "considered", "to", "be", "conscious", "perceptions", "of", "the", "neural", "activity", "in", "those", "brain", "regions", "that", "induce", "emotion", "as", "for", "instance", "LeDoux", "assumes.", "We", "cannot", "become", "conscious", "of", "neural", "activity", "in", "the", "first-order", "emotion", "regions", "(see", "also", "Bennett", "and", "Hacker,", "2003,", "208)", "since", "we", "remain", "principally", "unable", "to", "perceive", "our", "brain’s", "neural", "activity", "as", "such", "which", "I", "recently", "called", "“autoepistemic", "limitation”", "(Northoff,", "2004;", "Northoff", "and", "Musholt,", "2006,", "see", "chapter", "1", "and", "2", "in", "Northoff,", "2011).", "www.frontiersin.org", "August", "2012", "|", "Volume", "3", "|", "Article", "303", "|", "1" ]

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[ "organic", "compounds", "Acta", "Crystallographica", "Section", "E", "Structure", "Reports", "Online", "ISSN", "1600-5368", "Dimethylammonium", "5,5-dimethyl-3-oxo-", "2-(3,3,6,6-tetramethyl-1,8-dioxo-", "2,3,4,5,6,7,8,9-octahydro-1H-xanthen-9-", "yl)cyclohex-1-enolate", "9-(2-hydroxy-4,4-", "dimethyl-6-oxocyclohex-1-enyl)-3,3,6,6-", "tetramethyl-3,4,5,6,7,9-hexahydro-1H-", "xanthene-1,8(2H)-dione", "n-hexane", "hemisolvate", "monohydrate", "Noorhafizah", "Hasanudin,a", "Aisyah", "Saad", "Abdul", "Rahim,a‡", "Salizawati", "Muhamad", "Salhimi,a", "Jia", "Hao", "Gohb§", "and", "Hoong-Kun", "Funb*}", "aSchool", "of", "Pharmaceutical", "Sciences,", "Universiti", "Sains", "Malaysia,", "11800", "USM,", "Penang,", "Malaysia,", "and", "bX-ray", "Crystallography", "Unit,", "School", "of", "Physics,", "Universiti", "Sains", "Malaysia,", "11800", "USM,", "Penang,", "Malaysia", "Correspondence", "e-mail:", "hkfun@usm.my", "Received", "17", "January", "2010;", "accepted", "25", "January", "2010", "Key", "indicators:", "single-crystal", "X-ray", "study;", "T", "=", "100", "K;", "mean", "(C–C)", "=", "0.004", "A˚;", "disorder", "in", "solvent", "or", "counterion;", "R", "factor", "=", "0.052;", "wR", "factor", "=", "0.145;", "data-to-", "parameter", "ratio", "=", "12.5.", "The", "main", "molecule", "of", "the", "title", "compound,", "C2H8N+", "-", "C25H31O5", "C25H32O5", "0.5C6H14", "H2O,", "exists", "as", "two", "crystallo-", "graphically", "independent", "molecules,", "the", "hydroxy", "group", "of", "one", "being", "deprotonated.", "The", "pyran", "rings", "of", "both", "independent", "units", "adopt", "boat", "conformations.", "One", "of", "the", "two", "cyclohexene", "rings", "of", "the", "xanthene", "unit", "adopts", "an", "envelope", "conformation", "whereas", "the", "other", "is", "in", "a", "half-chair", "conformation.", "The", "cyclohexene", "ring", "attached", "to", "the", "xanthene", "unit", "adopts", "an", "envelope", "conformation.", "The", "n-hexane", "solvent", "molecule", "is", "disordered", "about", "a", "crystallographic", "glide", "plane", "and", "the", "symmetry-independent", "components", "are", "again", "disordered", "over", "two", "positions,", "each", "with", "an", "occupancy", "of", "0.25.", "In", "the", "crystal", "structure,", "the", "xanthene", "derivatives", "are", "linked", "by", "O—H", "O,", "N—H", "O", "and", "C—H", "O", "hydrogen", "bonds,", "forming", "a", "three-", "dimensional", "network", "with", "channels", "along", "the", "a", "axis.", "The", "dimethylammonium", "cations", "and", "water", "molecules", "lie", "in", "small", "channels", "and", "are", "linked", "to", "the", "framework", "via", "O—H.", "O", "and", "N—H", "O", "hydrogen", "bonds.", "The", "n-hexane", "solvent", "molecules", "occupy", "large", "channels.", "‡", "Additional", "corresponding", "author:", "aisyah@usm.my.", "§", "Thomson", "Reuters", "ResearcherID:", "C-7576-2009.", "}", "Thomson", "Reuters", "ResearcherID:", "A-3561-2009.", "o470", "Hasanudin", "et", "al.", "Related", "literature", "For", "general", "background", "and", "the", "preparation", "and", "applications", "of", "the", "title", "compound,", "see:", "Ashry", "et", "al.", "(2006);", "Rubinov", "et", "al.", "(1999);", "Saitoh", "et", "al.", "(2006).", "For", "ring", "conformations,", "see:", "Cremer", "&", "Pople", "(1975).", "For", "related", "structures,", "see:", "Jeya-", "kanthan", "et", "al.", "(1999);", "Odabas¸og˘", "lu", "et", "al.", "(2008).", "For", "the", "stability", "of", "the", "temperature", "controller", "used", "for", "the", "data", "collection,", "see:", "Cosier", "&", "Glazer", "(1986).", "Experimental", "Crystal", "data", "C2H8N+", "C25H31O5", "C25H32O5", "-", "0.5C6H14", "H2O", "Mr", "=", "931.20", "Orthorhombic,", "Pna21", "a", "=", "11.2438", "(2)", "A˚", "b", "=", "20.1671", "(3)", "A˚", "c", "=", "23.6474", "(3)", "A˚", "Data", "collection", "Bruker", "SMART", "APEXII", "CCD", "area-detector", "diffractometer", "Absorption", "correction:", "multi-scan", "(SADABS;", "Bruker,", "2009)", "Tmin", "=", "0.963,", "Tmax", "=", "0.984", "Refinement", "R[F", "2", ">", "2", "(F", "2)]", "=", "0.052", "wR(F", "2)", "=", "0.145", "S", "=", "1.03", "8021", "reflections", "640", "parameters", "Table", "1", "Hydrogen-bond", "geometry", "(A˚", ",", ").", "D—H", "A", "O5B—H5OB", "O1W—H2W1", "N1—H1N1", "N1—H2N1", "C4B—H4C", "C12A—H12B", "C12B—H12C", "C18A—H18A", "C26—H26C", "C27—H27B", "O5A", "O4Ai", "O4Aii", "O1W", "O2Ai", "O3Aiii", "O3Biv", "O5B", "O4B", "O3B", "0.82", "0.89", "0.88", "0.87", "0.97", "0.97", "0.97", "0.97", "0.96", "0.96", "1.69", "2.03", "1.94", "2.01", "2.48", "2.41", "2.36", "2.55", "2.42", "2.34", "V", "=", "5362.16", "(14)", "A˚3", "Z", "=", "4", "Mo", "K", "radiation", "=", "0.08", "mm", "1", "T", "=", "100", "K", "0.48", "0.38", "0.20", "mm", "31958", "measured", "reflections", "8021", "independent", "reflections", "6458", "reflections", "with", "I", ">", "2", "(I)", "Rint", "=", "0.040", "19", "restraints", "H-atom", "parameters", "constrained", "max", "=", "0.48", "e", "A˚", "3", "min", "=", "0.28", "e", "A˚", "3", "D", "A", "2.488", "(2)", "2.918", "(3)", "2.755", "(3)", "2.860", "(3)", "3.353", "(4)", "3.261", "(3)", "3.238", "(3)", "3.227", "(3)", "3.244", "(4)", "3.055", "(4)", "163", "175", "155", "167", "150", "146", "150", "126", "144", "131", "D—H", "H", "A", "D—H", "A", "Symmetry", "codes:", "(i)", "x;", "y", "þ", "1;", "z", "þ", "12;", "(ii)", "x", "þ", "12;", "y", "þ", "12;", "z", "þ", "12;", "(iii)", "x", "þ", "21;", "y", "þ", "12;", "z;", "(iv)", "x", "12;", "y", "þ", "23;", "z.", "Data", "collection:", "APEX2", "(Bruker,", "2009);", "cell", "refinement:", "SAINT", "(Bruker,", "2009);", "data", "reduction:", "SAINT;", "program(s)", "used", "to", "solve", "doi:10.1107/S1600536810003107", "Acta", "Cryst.", "(2010).", "E66,", "o470–o471" ]

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[ "World", "J", "Urol", "(2011)", "29:199–204", "DOI", "10.1007/s00345-010-0612-9", "T", "O", "P", "I", "C", "P", "A", "P", "E", "R", "The", "fish-hook", "configuration", "of", "the", "distal", "ureter", "indicates", "bladder", "outlet", "obstruction", "due", "to", "benign", "prostatic", "hyperplasia", "Charalampos", "Mamoulakis", "•", "Thomas", "R.", "W.", "Herrmann", "•", "Klaus", "Ho¨fner", "•", "Matthias", "Oelke", "Received:", "23", "August", "2010", "/", "Accepted:", "30", "October", "2010", "/", "Published", "online:", "16", "November", "2010", "The", "Author(s)", "2010.", "This", "article", "is", "published", "with", "open", "access", "at", "Springerlink.com", "Abstract", "Purpose", "The", "aim", "of", "this", "retrospective", "study", "was", "to", "evaluate", "in", "a", "historical", "series", "of", "patients", "whether", "mor-", "phological", "changes", "of", "the", "urinary", "tract", "imaged", "on", "intra-", "venous", "urography", "(IVU)", "are", "associated", "with", "clinical", "or", "urodynamic", "data.", "Methods", "During", "a", "1-year", "period,", "every", "man", "45", "years", "or", "older", "with", "lower", "urinary", "tract", "symptoms", "suggestive", "of", "benign", "prostatic", "hyperplasia", "was", "systematically", "evaluated", "with", "multi-channel", "computer-urodynamic", "investigation", "and", "IVU.", "Men", "with", "urinary", "retention,", "known", "bladder", "stones", "or", "diverticula,", "severely", "impaired", "renal", "function,", "or", "allergy", "to", "iodine", "contrast", "media", "were", "excluded.", "Structural", "alterations", "of", "the", "urinary", "tract", "were", "correlated", "with", "clinical", "and", "uro-", "dynamic", "data", "using", "logistic", "regression", "analysis.", "Results", "Data", "on", "203", "consecutive", "patients", "were", "available", "for", "analysis.", "Multivariate", "analysis", "demonstrated", "that", "the", "‘‘fish-hook’’", "configuration", "of", "the", "distal", "ureter", "(also", "known", "as", "‘‘hockey-stick’’,", "or", "‘‘J-shaped’’", "ureter)", "was", "the", "only", "sign", "significantly", "associated", "with", "benign", "prostatic", "obstruction", "(BPO)", "(odds-ratio", "3.64;", "95%", "confidence", "interval", "1.69–7.83;", "P", "\\", "0.001).", "The", "sensitivity,", "specificity,", "positive", "and", "negative", "predictive", "values", "of", "the", "‘‘fish-hook’’", "ureter", "C.", "Mamoulakis", "Department", "of", "Urology,", "University", "of", "Crete", "Medical", "School,", "Heraklion,", "Crete,", "Greece", "T.", "R.", "W.", "Herrmann", "K.", "Ho¨fner", "M.", "Oelke", "(&)", "Department", "of", "Urology,", "Hannover", "Medical", "School,", "Carl-Neuberg-Str.", "1,", "30625", "Hannover,", "Germany", "e-mail:", "oelke.matthias@mh-hannover.de", "K.", "Ho¨fner", "Department", "of", "Urology,", "Evangelic", "Hospital,", "Oberhausen,", "Germany", "configuration", "sign", "to", "detect", "BPO", "was", "53,", "76,", "61", "and", "70%,", "respectively.", "Bladder", "trabeculation,", "upper", "urinary", "tract", "dilatation,", "or", "bladder", "base", "elevation", "were", "not", "associated", "with", "BPO,", "detrusor", "overactivity,", "detrusor", "underactivity,", "bladder", "low-compliance", "or", "any", "clinical", "data.", "Conclusions", "The", "‘‘fish-hook’’", "shape", "of", "the", "distal", "ureter(s)", "indicates", "BPO", "and", "may", "be", "a", "result", "of", "prostate", "median", "lobe", "enlargement.", "Keywords", "Benign", "prostatic", "hyperplasia", "Bladder", "outlet", "obstruction", "Fish-hook", "ureter", "Intravenous", "urography", "Lower", "urinary", "tract", "symptoms", "Sensitivity", "Specificity", "Urodynamic", "investigation", "Abbreviations", "BPH", "Benign", "prostatic", "hyperplasia", "BPO", "Benign", "prostatic", "obstruction", "BPE", "Benign", "prostatic", "enlargement", "CI", "Confidence", "interval", "IPP", "Intravesical", "prostatic", "protrusion", "IPSS", "International", "prostate", "symptom", "score", "IVU", "Intravenous", "urography", "LUTS", "Lower", "urinary", "tract", "symptoms", "OR", "Odds", "ratio", "PVR", "Post-void", "residual", "urine", "TRUS", "Transrectal", "ultrasound", "UDI", "Urodynamic", "investigation", "Introduction", "Benign", "prostatic", "hyperplasia", "(BPH)", "is", "the", "term", "used", "to", "describe", "the", "growth", "of", "epithelial,", "muscular", "and/or", "fibrotic", "123" ]

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[ "Leeds", "et", "al.", "BMC", "Research", "Notes", "2011,", "4:317", "http://www.biomedcentral.com/1756-0500/4/317", "P", "R", "O", "J", "E", "C", "T", "N", "O", "T", "E", "Open", "Access", "Intensive", "medical", "student", "involvement", "in", "short-", "term", "surgical", "trips", "provides", "safe", "and", "effective", "patient", "care:", "a", "case", "review", "Ira", "L", "Leeds1*,", "Francis", "X", "Creighton1,", "Matthew", "A", "Wheatley1,2,", "Jana", "B", "Macleod1,3,4,", "Jahnavi", "Srinivasan1,4,", "Marie", "P", "Chery5", "and", "Viraj", "A", "Master1,6", "Abstract", "Background:", "The", "hierarchical", "nature", "of", "medical", "education", "has", "been", "thought", "necessary", "for", "the", "safe", "care", "of", "patients.", "In", "this", "setting,", "medical", "students", "in", "particular", "have", "limited", "opportunities", "for", "experiential", "learning.", "We", "report", "on", "a", "student-faculty", "collaboration", "that", "has", "successfully", "operated", "an", "annual,", "short-term", "surgical", "intervention", "in", "Haiti", "for", "the", "last", "three", "years.", "Medical", "students", "were", "responsible", "for", "logistics", "and", "were", "overseen", "by", "faculty", "members", "for", "patient", "care.", "Substantial", "planning", "with", "local", "partners", "ensured", "that", "trip", "activities", "supplemented", "existing", "surgical", "services.", "A", "case", "review", "was", "performed", "hypothesizing", "that", "such", "trips", "could", "provide", "effective", "surgical", "care", "while", "also", "providing", "a", "suitable", "educational", "experience.", "Findings:", "Over", "three", "week-long", "trips,", "64", "cases", "were", "performed", "without", "any", "reported", "complications,", "and", "no", "immediate", "perioperative", "morbidity", "or", "mortality.", "A", "plurality", "of", "cases", "were", "complex", "urological", "procedures", "that", "required", "surgical", "skills", "that", "were", "locally", "unavailable", "(43%).", "Surgical", "productivity", "was", "twice", "that", "of", "comparable", "peer", "institutions", "in", "the", "region.", "Student", "roles", "in", "patient", "care", "were", "greatly", "expanded", "in", "comparison", "to", "those", "at", "U.S.", "academic", "medical", "centers", "and", "appropriate", "supervision", "was", "maintained.", "Discussion:", "This", "demonstration", "project", "suggests", "that", "a", "properly", "designed", "surgical", "trip", "model", "can", "effectively", "balance", "the", "surgical", "needs", "of", "the", "community", "with", "an", "opportunity", "to", "expose", "young", "trainees", "to", "a", "clinical", "and", "cross-", "cultural", "experience", "rarely", "provided", "at", "this", "early", "stage", "of", "medical", "education.", "Few", "formalized", "programs", "currently", "exist", "although", "the", "experience", "above", "suggests", "the", "rewarding", "potential", "for", "broad-based", "adoption.", "Background", "Historically,", "the", "hierarchical", "nature", "of", "medical", "education", "with", "step-wise", "progression", "to", "greater", "abilities", "and", "responsibilities", "has", "been", "thought", "necessary", "for", "the", "safe", "and", "efficient", "practice", "of", "medical", "care", "within", "the", "aca-", "demic", "learning", "environment.", "Although", "such", "a", "system", "has", "advantages,", "one", "cost", "of", "this", "well-established", "hierar-", "chy", "is", "that", "experiential", "learning", "only", "minimally", "reaches", "those", "further", "down", "the", "chain", "of", "command.", "Medical", "stu-", "dents", "in", "particular", "have", "limited", "clinical", "responsibilities", "and", "therefore", "limited", "opportunities", "for", "direct", "hands-on", "learning", "considered", "by", "some", "to", "be", "the", "superior", "form", "of", "medical", "education", "[1].", "*", "Correspondence:", "ileeds@emory.edu", "1Emory", "University", "School", "of", "Medicine,", "1648", "Pierce", "Drive,", "Atlanta,", "GA", "30322", "USA", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "In", "the", "surgical", "specialties,", "this", "problem", "is", "magnified", "by", "the", "nature", "of", "procedural", "medicine.", "Prior", "studies[2,3]", "have", "demonstrated", "multiple", "systemic", "barriers", "to", "surgical", "skill", "acquisition", "by", "medical", "students.", "Given", "the", "intrinsic", "importance", "of", "technical", "acumen", "and", "repetition-based", "learning", "for", "surgery,[4]", "any", "hierarchy", "that", "limits", "practice", "of", "clinical", "skills", "may", "further", "distance", "the", "medical", "stu-", "dent", "from", "the", "proven", "ideal", "form", "of", "surgical", "skill", "acquisi-", "tion", "-", "routine", "reiteration", "[5,6].", "One", "could", "argue", "that", "the", "rate-limiting", "step", "for", "educa-", "tion", "of", "the", "medical", "student", "is", "not", "the", "student,", "but", "a", "sys-", "tem", "that", "is", "overloaded", "with", "too", "many", "intermediaries.", "Are", "medical", "students", "unable", "to", "work", "more", "indepen-", "dently", "or", "is", "this", "hierarchical", "construct", "more", "a", "matter", "of", "practicality", "than", "absolutely", "necessary", "supervision?", "Such", "inquiry", "applies", "not", "only", "to", "student", "participation", "in", "©", "2010", "Leeds", "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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[ "BMC", "Medical", "Informatics", "and", "Decision", "Making", "Software", "Doublet", "method", "for", "very", "fast", "autocoding", "Jules", "J", "Berman*", "Address:", "Cancer", "Diagnosis", "Program,", "National", "Cancer", "Institute,", "National", "Institutes", "of", "Health,", "Bethesda,", "MD,", "USA", "Email:", "Jules", "J", "Berman*", "-", "bermanj@mail.nih.gov", "*", "Corresponding", "author", "Published:", "15", "September", "2004", "BMC", "Medical", "Informatics", "and", "Decision", "Making", "2004,", "4:16", "doi:10.1186/1472-6947-4-16", "This", "article", "is", "available", "from:", "http://www.biomedcentral.com/1472-6947/4/16", "Received:", "01", "July", "2004", "Accepted:", "15", "September", "2004", "©", "2004", "Berman;", "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:", "Autocoding", "(or", "automatic", "concept", "indexing)", "occurs", "when", "a", "software", "program", "extracts", "terms", "contained", "within", "text", "and", "maps", "them", "to", "a", "standard", "list", "of", "concepts", "contained", "in", "a", "nomenclature.", "The", "purpose", "of", "autocoding", "is", "to", "provide", "a", "way", "of", "organizing", "large", "documents", "by", "the", "concepts", "represented", "in", "the", "text.", "Because", "textual", "data", "accumulates", "rapidly", "in", "biomedical", "institutions,", "the", "computational", "methods", "used", "to", "autocode", "text", "must", "be", "very", "fast.", "The", "purpose", "of", "this", "paper", "is", "to", "describe", "the", "doublet", "method,", "a", "new", "algorithm", "for", "very", "fast", "autocoding.", "Methods:", "An", "autocoder", "was", "written", "that", "transforms", "plain-text", "into", "intercalated", "word", "doublets", "(e.g.", "\"The", "ciliary", "body", "produces", "aqueous", "humor\"", "becomes", "\"The", "ciliary,", "ciliary", "body,", "body", "produces,", "produces", "aqueous,", "aqueous", "humor\").", "Each", "doublet", "is", "checked", "against", "an", "index", "of", "doublets", "extracted", "from", "a", "standard", "nomenclature.", "Matching", "doublets", "are", "assigned", "a", "numeric", "code", "specific", "for", "each", "doublet", "found", "in", "the", "nomenclature.", "Text", "doublets", "that", "do", "not", "match", "the", "index", "of", "doublets", "extracted", "from", "the", "nomenclature", "are", "not", "part", "of", "valid", "nomenclature", "terms.", "Runs", "of", "matching", "doublets", "from", "text", "are", "concatenated", "and", "matched", "against", "nomenclature", "terms", "(also", "represented", "as", "runs", "of", "doublets).", "Results:", "The", "doublet", "autocoder", "was", "compared", "for", "speed", "and", "performance", "against", "a", "previously", "published", "phrase", "autocoder.", "Both", "autocoders", "are", "Perl", "scripts,", "and", "both", "autocoders", "used", "an", "identical", "text", "(a", "170+", "Megabyte", "collection", "of", "abstracts", "collected", "through", "a", "PubMed", "search)", "and", "the", "same", "nomenclature", "(neocl.xml,", "containing", "over", "102,271", "unique", "names", "of", "neoplasms).", "In", "side-by-", "side", "comparison", "on", "the", "same", "computer,", "the", "doublet", "method", "autocoder", "was", "8.4", "times", "faster", "than", "the", "phrase", "autocoder", "(211", "seconds", "versus", "1,776", "seconds).", "The", "doublet", "method", "codes", "0.8", "Megabytes", "of", "text", "per", "second", "on", "a", "desktop", "computer", "with", "a", "1.6", "GHz", "processor.", "In", "addition,", "the", "doublet", "autocoder", "successfully", "matched", "terms", "that", "were", "missed", "by", "the", "phrase", "autocoder,", "while", "the", "phrase", "autocoder", "found", "no", "terms", "that", "were", "missed", "by", "the", "doublet", "autocoder.", "Conclusions:", "The", "doublet", "method", "of", "autocoding", "is", "a", "novel", "algorithm", "for", "rapid", "text", "autocoding.", "The", "method", "will", "work", "with", "any", "nomenclature", "and", "will", "parse", "any", "ascii", "plain-text.", "An", "implementation", "of", "the", "algorithm", "in", "Perl", "is", "provided", "with", "this", "article.", "The", "algorithm,", "the", "Perl", "implementation,", "the", "neoplasm", "nomenclature,", "and", "Perl", "itself,", "are", "all", "open", "source", "materials.", "Background", "Autocoding", "is", "a", "specialized", "form", "of", "machine", "translation.", "The", "general", "idea", "behind", "machine", "translation", "is", "that", "com-", "puters", "have", "the", "patience,", "stamina", "and", "speed", "to", "quickly", "Page", "1", "of", "8", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "CLINICS", "2011;66(7):1177-1182", "CLINICAL", "SCIENCE", "DOI:10.1590/S1807-59322011000700009", "Risk", "of", "herpes", "zoster", "in", "patients", "with", "systemic", "lupus", "erythematosus:", "a", "three-year", "follow-up", "study", "using", "a", "nationwide", "population-based", "cohort", "Hsin-Hua", "Chen,I,II,IV", "Yi-Ming", "Chen,I,II", "Tzeng-Ji", "Chen,II,III", "Joung-Liang", "Lan,I,II,IV,V", "Ching-Heng", "Lin,VI", "Der-Yuan", "ChenI,II,IV,V", "I", "Division", "of", "Allergy,", "Immunology", "and", "Rheumatology,", "Department", "of", "Internal", "Medicine,", "Taichung", "Veterans", "General", "Hospital,", "Taichung,", "Taiwan.", "II", "School", "of", "Medicine,", "National", "Yang-Ming", "University,", "Taipei,", "Taiwan.", "III", "Department", "of", "Family", "Medicine,", "Taipei", "Veterans", "General", "Hospital,", "Taipei,", "Taiwan.", "IV", "School", "of", "Medicine,", "Chung-Shan", "Medical", "University,", "Taichung,", "Taiwan.", "V", "Institute", "of", "Biomedical", "Science,", "Chung-Hsing", "University,", "Taichung,", "Taiwan.", "VI", "Department", "of", "Medical", "Research,", "Taichung", "Veterans", "General", "Hospital,", "Taichung,", "Taiwan.", "OBJECTIVE:", "The", "goal", "of", "the", "present", "study", "was", "to", "estimate", "the", "risk", "ratio", "of", "herpes", "zoster", "among", "systemic", "lupus", "erythematosus", "patients", "after", "disease", "onset", "compared", "with", "a", "cohort", "of", "patients", "without", "systemic", "lupus", "erythematosus", "over", "a", "three-year", "period.", "METHODS:", "A", "nationwide", "population-based", "cohort", "study", "using", "the", "National", "Health", "Insurance", "Research", "Database", "identified", "10,337", "new", "cases", "of", "systemic", "lupus", "erythematosus", "as", "the", "study", "cohort.", "In", "addition,", "62,022", "patients", "without", "systemic", "lupus", "erythematosus,", "who", "were", "matched", "for", "age,", "gender,", "and", "date", "of", "systemic", "lupus", "erythematosus", "diagnosis,", "were", "used", "as", "the", "comparison", "cohort.", "These", "cohorts", "were", "followed-up", "for", "three", "years.", "A", "Cox", "proportional", "hazard", "regression", "was", "performed", "to", "estimate", "the", "risk", "ratio", "of", "herpes", "zoster,", "with", "adjustments", "for", "age,", "gender,", "level", "of", "insurance,", "urbanization", "level,", "geographic", "region,", "comorbid", "medical", "conditions,", "average", "daily", "dosage", "of", "corticosteroids,", "and", "the", "use", "of", "immune-modulation", "agents.", "RESULTS:", "Compared", "to", "patients", "without", "systemic", "lupus", "erythematosus,", "the", "crude", "risk", "ratio", "and", "adjusted", "risk", "ratio", "of", "herpes", "zoster", "among", "systemic", "lupus", "erythematosus", "patients", "were", "7.37", "(95%", "confidence", "interval", "6.75-8.04)", "and", "2.45", "(95%", "confidence", "interval", "1.77-3.40),", "respectively.", "Stratified", "by", "gender,", "the", "adjusted", "risk", "ratio", "of", "herpes", "zoster", "was", "2.10", "(95%", "confidence", "interval", "1.45-2.99)", "in", "women", "and", "7.51", "(95%", "confidence", "interval", "2.89-19.52)", "in", "men.", "Stratified", "by", "age,", "the", "adjusted", "risk", "ratio", "peaked", "in", "systemic", "lupus", "erythematosus", "patients", "who", "were", "aged", "18", "to", "24", "years", "(risk", "ratio", "8.78,", "95%", "confidence", "interval", "3.08-24.97).", "CONCLUSION:", "Based", "on", "nationwide", "population-based", "data,", "there", "is", "an", "increased", "risk", "of", "herpes", "zoster", "in", "systemic", "lupus", "erythematosus", "patients", "compared", "with", "non-systemic", "lupus", "erythematosus", "patients,", "particularly", "among", "males", "and", "patients", "aged", "18", "to", "24", "years.", "Further", "research", "on", "the", "associated", "risk", "factors", "for", "herpes", "zoster", "in", "systemic", "lupus", "erythematosus", "patients", "is", "needed.", "KEYWORDS:", "Herpes", "Zoster;", "Risk;", "Systemic", "Lupus", "Erythematosus;", "Population-Based", "Cohort", "Study;", "Database.", "Chen", "HH,", "Chen", "YM,", "Chen", "TJ,", "Lan", "JL,", "Lin", "CH,", "Chen", "DY.", "Risk", "of", "herpes", "zoster", "in", "patients", "with", "systemic", "lupus", "erythematosus:", "a", "three-year", "follow-up", "study", "using", "a", "nationwide", "population-based", "cohort.", "Clinics.", "2011;66(7):1177-1182.", "Received", "for", "publication", "on", "January", "26,", "2011;", "First", "review", "completed", "on", "February", "25,", "2011;", "Accepted", "for", "publication", "on", "May", "21,", "2011", "E-mail:", "dychen@vghtc.gov.tw", "Tel.:", "886-4-23592525", "ext", "3336", "INTRODUCTION", "Herpes", "zoster", "(HZ)", "is", "characterized", "by", "debilitating", "painful", "vesicular", "eruptions", "in", "a", "dermatomal", "distribution", "that", "are", "caused", "by", "the", "reactivation", "of", "a", "latent", "varicella", "zoster", "virus", "(VZV)", "infection.1", "This", "disease", "is", "commonly", "observed", "in", "the", "elderly,", "in", "immuno-compromised", "hosts,", "and", "in", "patients", "with", "systemic", "lupus", "erythematosus", "(SLE).2-5", "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.", "Cutaneous", "vesicles", "can", "be", "complicated", "by", "a", "bacterial", "super-infection,", "and", "the", "dissemination", "of", "HZ", "may", "be", "life-", "threatening.3", "Post-herpetic", "neuralgia", "in", "the", "affected", "areas", "is", "the", "most", "common", "complication,", "which", "can", "persist", "for", "months", "or", "years.", "The", "incidence", "of", "HZ", "in", "the", "general", "population", "is", "1.2", "to", "4.9", "cases", "per", "1000", "person-years,", "depending", "on", "the", "ethnic", "group.6-7", "The", "reported", "incidence", "of", "HZ", "in", "SLE", "patients", "is", "significantly", "greater", "than", "the", "incidence", "in", "the", "general", "population,", "ranging", "from", "16", "to", "22", "cases", "per", "1000", "patient-years", "in", "large", "cohort", "studies.2-3,8", "The", "greater", "incidence", "of", "HZ", "infection", "in", "SLE", "has", "been", "shown", "to", "be", "related", "to", "abnormal", "T-cell-mediated", "cytotoxi-", "city", "that", "is", "aggravated", "by", "the", "concomitant", "use", "of", "glucocor-", "ticoids", "and", "immuno-suppressants.4,9-10", "Disease", "activity,", "1177" ]

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[ "Research", "|", "Children’s", "Health", "Assessing", "Children’s", "Dietary", "Pesticide", "Exposure:", "Direct", "Measurement", "of", "Pesticide", "Residues", "in", "24-Hr", "Duplicate", "Food", "Samples", "Chensheng", "Lu,1", "Frank", "J.", "Schenck,2", "Melanie", "A.", "Pearson,3", "and", "Jon", "W.", "Wong", "4", "1Exposure,", "Epidemiology,", "and", "Risk", "Program,", "Department", "of", "Environmental", "Health,", "Harvard", "School", "of", "Public", "Health,", "Boston,", "Massachusetts,", "USA;", "2U.S.", "Food", "and", "Drug", "Administration,", "Southeast", "Regional", "Laboratory,", "Atlanta,", "Georgia,", "USA", "(retired);", "3Department", "of", "Environmental", "and", "Occupational", "Health,", "Rollins", "School", "of", "Public", "Health,", "Emory", "University,", "Atlanta,", "Georgia,", "USA;", "4U.S.", "Food", "and", "Drug", "Administration,", "Center", "for", "Food", "Safety", "and", "Applied", "Nutrition,", "College", "Park,", "Maryland,", "USA", "Background", ":", "The", "data", "presented", "here", "are", "a", "response", "to", "calls", "for", "more", "direct", "measurements", "of", "pesticide", "residues", "in", "foods", "consumed", "by", "children", "and", "provide", "an", "opportunity", "to", "compare", "direct", "measures", "of", "pesticide", "residues", "in", "foods", "representing", "actual", "consumption", "with", "those", "reported", "by", "the", "U.S.", "Department", "of", "Agriculture", "Pesticide", "Data", "Program.", "o", "Bjectiv", ":", "We", "measured", "pesticide", "residues", "in", "24-hr", "duplicate", "food", "samples", "collected", "from", "a", "group", "of", "46", "young", "children", "participating", "in", "the", "Children’s", "Pesticide", "Exposure", "Study", "(CPES).", "Methods", ":", "Parents", "were", "instructed", "to", "collect", "24-hr", "duplicate", "food", "samples", "of", "all", "conventional", "fruits,", "vegetables,", "and", "fruit", "juices", "equal", "to", "the", "quantity", "consumed", "by", "their", "children,", "similarly", "prewashed/", "prepared,", "and", "from", "the", "same", "source", "or", "batch.", "Individual", "or", "composite", "food", "items", "were", "analyzed", "for", "organophosphate", "(OP)", "and", "pyrethroid", "insecticide", "residues.", "r", "esult", ":", "We", "collected", "a", "total", "of", "239", "24-hr", "duplicate", "food", "samples", "collected", "from", "the", "46", "CPES", "chil-", "dren.", "We", "found", "14%", "or", "5%", "of", "those", "food", "samples", "contained", "at", "least", "one", "OP", "or", "pyrethroid", "insecti-", "cide,", "respectively.", "We", "measured", "a", "total", "of", "11", "OP", "insecticides,", "at", "levels", "ranging", "from", "1", "to", "387", "ng/g,", "and", "three", "pyrethroid", "insecticides,", "at", "levels", "ranging", "from", "2", "to", "1,133", "ng/g,", "in", "children’s", "food", "samples.", "We", "found", "that", "many", "of", "the", "food", "items", "consumed", "by", "the", "CPES", "children", "were", "also", "on", "the", "list", "of", "the", "most", "contaminated", "food", "commodities", "reported", "by", "the", "Environmental", "Working", "Group.", "c", "onclusi", ":", "The", "frequent", "consumption", "of", "food", "commodities", "with", "episodic", "presence", "of", "pesticide", "residues", "that", "are", "suspected", "to", "cause", "developmental", "and", "neurological", "effects", "in", "young", "children", "sup-", "ports", "the", "need", "for", "further", "mitigation.", "k", "ey", "words", ":", "children’s", "diets,", "dietary", "pesticide", "exposure,", "organophosphate", "pesticides,", "pesticide", "residue,", "pesticide", "risk", "assessment,", "pyrethroid", "insecticides.", "Environ", "Health", "Perspect", "118:1625–1630", "(2010).", "doi:10.1289/ehp.1002044", "[Online", "16", "July", "2010]", "In", "the", "1990s,", "a", "book", "published", "by", "the", "National", "Research", "Council", "(NRC)", "titled", "Pesticides", "in", "the", "Diets", "of", "Infants", "and", "Children", "(NRC", "1993)", "and", "the", "passage", "of", "the", "Food", "Quality", "Protection", "Act", "of", "1996", "(FQPA", "1996)", "were", "hailed", "as", "two", "major", "milestones", "in", "the", "United", "States", "in", "recogniz-", "ing", "the", "need", "for", "systematic", "efforts", "in", "reducing", "pesticide", "exposure", "in", "vulnerable", "populations,", "especially", "infants", "and", "children.", "An", "important", "summary", "statement", "in", "the", "NRC", "report", "declared", "that", "“dietary", "intake", "represents", "the", "major", "source", "of", "pesticide", "exposure", "for", "infants", "and", "children,", "and", "the", "dietary", "exposure", "may", "account", "for", "the", "increased", "pesticide-related", "health", "risks", "in", "chil-", "dren", "compared", "with", "adults.”", "After", "the", "NRC", "report,", "the", "newly", "enacted", "FQPA", "aimed", "to", "fundamentally", "change", "U.S.", "policies", "in", "govern-", "ing", "the", "acceptability", "of", "pesticide", "residues", "in", "foods", "and", "required", "the", "U.S.", "Environmental", "Protection", "Agency", "(EPA)", "to", "assure", "the", "public", "that", "there", "is", "a", "“reasonable", "certainty", "of", "no", "harm”", "from", "pesticide", "exposures", "for", "pregnant", "women,", "infants,", "children,", "and", "other", "vulnerable", "groups.", "Despite", "many", "years", "of", "effort", "in", "implementing", "the", "FQPA,", "monitoring", "and", "managing", "dietary", "pesticide", "exposures", "and", "risks", "are", "still", "an", "ongo-", "ing", "challenge.", "A", "recent", "report", "published", "by", "the", "U.S.", "Office", "of", "Inspector", "General", "(2006)", "has", "stressed", "the", "need", "for", "data-driven", "indicators", "of", "pesticide", "dietary", "exposures/risks.", "The", "data", "presented", "here", "are", "in", "response", "to", "these", "calls", "for", "more", "direct", "measurements", "of", "pes-", "ticide", "residues", "in", "foods", "consumed", "by", "children", "and", "provide", "an", "initial", "assessment", "of", "the", "effects", "of", "the", "U.S.", "EPA’s", "actions", "on", "assessing", "dietary", "pesticide", "risks", "(U.S.", "Office", "of", "the", "Inspector", "General", "2006).", "In", "this", "study,", "we", "measured", "pes-", "ticide", "residues", "in", "24-hr", "duplicate", "foods", "from", "a", "group", "of", "elementary", "school–age", "children", "par-", "ticipating", "in", "the", "Children’s", "Pesticide", "Exposure", "Study", "(CPES).", "In", "addition,", "the", "CPES", "data", "pro-", "vided", "an", "opportunity", "to", "compare", "direct", "mea-", "sures", "of", "pesticide", "residues", "in", "foods", "representing", "actual", "consumption", "with", "measured", "values", "reported", "by", "the", "Pesticide", "Data", "Program", "[PDP;", "U.S.", "Department", "of", "Agriculture", "(USDA)", "2009],", "a", "national", "database", "of", "pesticide", "residues", "found", "on", "foods", "that", "are", "ready", "for", "distribution", "in", "the", "United", "States.", "This", "comparison", "allows", "a", "unique", "examination", "of", "“real-world”", "applicabil-", "ity", "of", "the", "national", "data", "set.", "Materials", "and", "Methods", "Children’s", "Pesticide", "Exposure", "Study.", "CPES", "was", "initially", "conducted", "in", "the", "suburban", "Seattle,", "Washington,", "area", "(CPES-WA)", "from", "summer", "2003", "to", "winter", "2004", "and", "was", "later", "repeated", "in", "Atlanta,", "Georgia", "(CPES-GA),", "in", "2006/2007", "with", "the", "same", "study", "protocol.", "Twenty-three", "children", "3–11", "years", "of", "age", "were", "recruited", "for", "Environmental", "Health", "Perspectives", "•", "volume", "118", "|", "number", "11", "|", "November", "2010", "each", "CPES", "study", "from", "local", "public", "elementary", "schools", "and", "Montessori", "preschools.", "(One", "of", "the", "children", "who", "participated", "in", "CPES-GA", "study", "was", "12", "years", "old", "at", "the", "beginning", "of", "study.)", "Schools", "did", "not", "provide", "any", "assistance", "in", "recruiting", "subjects", "except", "for", "granting", "permis-", "sion", "to", "send", "home", "with", "the", "children", "a", "letter", "and", "a", "fact", "sheet", "describing", "the", "study.", "Families", "that", "were", "interested", "in", "participating", "in", "this", "study", "then", "contacted", "the", "research", "group", "directly.", "A", "screening", "questionnaire", "was", "conducted", "over", "the", "phone", "to", "confirm", "eligibility,", "which", "included", "children", "exclusively", "consuming", "conventional", "(nonorganic)", "diets", "and", "spending", "most", "of", "their", "time", "in", "one", "residence,", "and", "the", "willingness", "of", "parents", "or", "caregivers", "to", "provide", "assistance", "in", "collecting", "specimen", "samples.", "Once", "a", "participant", "was", "enrolled,", "an", "in-house", "appointment", "was", "made", "to", "go", "over", "the", "study", "protocol", "and", "train", "the", "parents/caregivers", "on", "how", "to", "collect", "speci-", "mens", "and", "24-hr", "duplicate", "food", "samples.", "All", "parents", "provided", "written", "informed", "consent,", "and", "all", "children", "provided", "written", "informed", "consent", "(if", "≥", "10", "years", "of", "age)", "or", "oral", "assent", "(<", "10", "years", "of", "age)", "before", "data", "collection", "began.", "A", "ques-", "tionnaire", "was", "also", "administered", "by", "the", "research", "staff", "during", "this", "appointment", "that", "asked", "about", "household", "pesticide", "use", "to", "account", "for", "nondi-", "etary", "sources", "of", "pesticide", "exposure.", "Each", "CPES", "child", "agreed", "to", "participate", "in", "multiple", "consecutive", "days", "of", "sampling", "in", "four", "seasons", "over", "a", "12-month", "period", "(four", "seasons).", "Address", "correspondence", "to", "C.", "Lu,", "401", "Park", "Dr.,", "Landmark", "Center", "West,", "Boston,", "MA", "02215,", "USA.", "Telephone:", "(617)", "998-8811.", "Fax:", "(617)", "384-8728.", "E-mail:", "cslu@hsph.harvard.edu", "We", "thank", "K.", "Toepel,", "R.", "Irish,", "and", "P.", "Sande", "(University", "of", "Washington);", "M.", "Givens,", "C.", "Holbrook,", "D.", "Gregory,", "M.", "Holubar,", "and", "Hui-Mien", "Hsiao", "(Emory", "University);", "and", "K.", "Zhang", "(Food", "and", "Drug", "Administration", "[FDA],", "Center", "for", "Food", "Safety", "and", "Applied", "Nutrition)", "for", "their", "contributions", "in", "the", "Children’s", "Pesticide", "Exposure", "Study.", "This", "work", "was", "supported", "by", "the", "U.S.", "Environmental", "Protection", "Agency", "(EPA)", "under", "the", "Science", "to", "Achieve", "Results", "research", "assistance", "program", "(R-832244", "and", "R-829364).", "The", "content", "of", "this", "publication", "has", "not", "been", "for-", "mally", "reviewed", "by", "the", "U.S.", "EPA", "and", "FDA,", "and", "the", "views", "expressed", "in", "this", "document", "are", "solely", "those", "of", "the", "authors.", "Neither", "the", "U.S.", "EPA", "nor", "the", "FDA", "endorses", "any", "products", "or", "commercial", "services", "men-", "tioned", "in", "this", "publication.", "The", "authors", "declare", "they", "have", "no", "actual", "or", "potential", "competing", "financial", "interests.", "Received", "10", "February", "2010;", "accepted", "16", "July", "2010.", "1625" ]

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[ "Berg", "et", "al.", "Critical", "Care", "2010,", "14:R16", "http://ccforum.com/content/14/1/R16", "R", "E", "S", "E", "A", "R", "C", "H", "Open", "Access", "Cerebral", "net", "exchange", "of", "large", "neutral", "amino", "acids", "after", "lipopolysaccharide", "infusion", "in", "healthy", "humans", "Ronan", "MG", "Berg1*,", "Sarah", "Taudorf1,", "Damian", "M", "Bailey2,", "Carsten", "Lundby3,", "Fin", "Stolze", "Larsen4,", "Bente", "Klarlund", "Pedersen1,3,", "Kirsten", "Møller1,5", "Abstract", "Introduction:", "Alterations", "in", "circulating", "large", "neutral", "amino", "acids", "(LNAAs),", "leading", "to", "a", "decrease", "in", "the", "plasma", "ratio", "between", "branched-chain", "and", "aromatic", "amino", "acids", "(BCAA/AAA", "ratio),", "may", "be", "involved", "in", "sepsis-associated", "encephalopathy.", "We", "hypothesised", "that", "a", "decrease", "in", "the", "BCAA/AAA", "ratio", "occurs", "along", "with", "a", "net", "cerebral", "influx", "of", "the", "neurotoxic", "AAA", "phenylalanine", "in", "a", "human", "experimental", "model", "of", "systemic", "inflammation.", "Methods:", "The", "BCAA/AAA", "ratio,", "the", "cerebral", "delivery,", "and", "net", "exchange", "of", "LNAAs", "and", "ammonia", "were", "measured", "before", "and", "1", "hour", "after", "a", "4-hour", "intravenous", "infusion", "of", "Escherichia", "coli", "lipopolysaccharide", "(LPS)", "in", "12", "healthy", "young", "men.", "Results:", "LPS", "induced", "systemic", "inflammation,", "reduced", "the", "BCAA/AAA", "ratio,", "increased", "the", "cerebral", "delivery", "and", "unidirectional", "influx", "of", "phenylalanine,", "and", "abolished", "the", "net", "cerebral", "influx", "of", "the", "BCAAs", "leucine", "and", "isoleucine.", "Furthermore,", "a", "net", "cerebral", "efflux", "of", "glutamine,", "which", "was", "independent", "of", "the", "cerebral", "net", "exchange", "of", "ammonia,", "was", "present", "after", "LPS", "infusion.", "Conclusions:", "Systemic", "inflammation", "may", "affect", "brain", "function", "by", "reducing", "the", "BCAA/AAA", "ratio,", "thereby", "changing", "the", "cerebral", "net", "exchange", "of", "LNAAs.", "Introduction", "Sepsis-associated", "encephalopathy", "(SAE)", "is", "often", "one", "of", "the", "first", "manifestations", "of", "sepsis", "[1]", "and", "is", "associated", "with", "an", "adverse", "outcome", "[2,3].", "The", "pathogenesis", "of", "SAE", "is", "largely", "unknown,", "although", "several", "potential", "mechan-", "isms", "have", "been", "investigated,", "including", "cerebral", "blood", "flow", "(CBF)", "and", "metabolic", "alterations,", "intracranial", "hyper-", "tension,", "cerebral", "edema,", "disruption", "of", "the", "blood-brain", "barrier", "(BBB),", "neuronal", "degeneration,", "and", "abnormal", "neurotransmitter", "composition", "[4].", "Sepsis", "is", "characterized", "by", "increased", "peripheral", "pro-", "tein", "breakdown,", "notably", "in", "skeletal", "muscle", "[5,6],", "and", "hepatic", "synthesis", "of", "acute-phase", "reactants;", "the", "ensuing", "alterations", "in", "plasma", "amino", "acids", "may", "play", "a", "key", "role", "in", "SAE.", "Thus,", "the", "plasma", "ratio", "between", "branched-", "chain", "and", "aromatic", "amino", "acids", "(BCAAs", "and", "AAAs,", "*", "Correspondence:", "ronan@dadlnet.dk", "1Centre", "of", "Inflammation", "and", "Metabolism,", "Department", "of", "Infectious", "Diseases,", "Rigshospitalet,", "Blegdamsvej", "9,", "2100", "Copenhagen,", "Denmark", "respectively)", "decreases,", "because", "the", "BCAAs", "are", "rapidly", "used", "in", "the", "liver,", "whereas", "phenylalanine", "levels", "increase", "[7-9].", "BCAAs", "and", "AAAs", "belong", "to", "the", "group", "of", "large", "neutral", "amino", "acids", "(LNAAs),", "which", "compete", "for", "the", "same", "saturable", "carrier", "across", "the", "BBB", "[10].", "Hence,", "a", "decrease", "in", "the", "BCAA/AAA", "ratio", "theoreti-", "cally", "implies", "either", "a", "decreased", "availability", "of", "BCAAs", "to", "the", "brain,", "or", "an", "intracerebral", "accumulation", "of", "AAAs,", "both", "of", "which", "may", "profoundly", "affect", "neuronal", "function", "[11].", "At", "present,", "neither", "the", "physiological", "implications", "of", "alterations", "in", "the", "BCAA/AAA", "ratio", "nor", "the", "effects", "of", "systemic", "inflammation", "on", "the", "cerebral", "net", "exchange", "of", "LNAAs", "has", "been", "investigated", "in", "humans.", "Applying", "a", "human", "experimental", "model", "of", "systemic", "inflammation,", "we", "hypothesised", "that", "the", "BCAA/AAA", "ratio", "decreases", "with", "a", "concurrent", "net", "cerebral", "influx", "of", "the", "neurotoxic", "AAA", "phenylalanine,", "and", "that", "this", "attenuates", "the", "net", "cer-", "ebral", "influx", "of", "BCAAs.", "©", "2010", "Berg", "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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[ "Tumor", "Tissue-Derived", "Formaldehyde", "and", "Acidic", "Microenvironment", "Synergistically", "Induce", "Bone", "Cancer", "Pain", "Zhiqian", "Tong", "1", "*", ".", ",", "Wenhong", "Luo2.,", "Yanqing", "Wang3.,", "Fei", "Yang", "1", ",", "Ying", "Han", "1", ",", "Hui", "Li2,", "Hongjun", "Luo", "2", ",", "Bo", "Duan", "4", ",", "Tianle", "Xu", "4", ",", "Qiliang", "Maoying", "3", ",", "Huangying", "Tan5,", "Jun", "Wang", "6", ",", "Hongmei", "Zhao7,", "Fengyu", "Liu1,", "You", "Wan1,8*", "1", "Neuroscience", "Research", "Institute,", "Peking", "University,", "Beijing,", "China,", "2", "The", "Central", "Laboratory,", "Shantou", "University", "Medical", "College,", "Shantou,", "China,", "3", "Department", "of", "Integrative", "Medicine", "and", "Neurobiology,", "State", "Key", "Laboratory", "of", "Medical", "Neurobiology,", "Shanghai", "Medical", "College,", "Fudan", "University,", "Shanghai,", "China,", "4", "Institute", "of", "Neuroscience", "and", "National", "Key", "Laboratory", "of", "Neuroscience,", "Chinese", "Academy", "of", "Sciences,", "Shanghai,", "China,", "5", "Department", "of", "TCM", "Oncology,", "China-Japan", "Friendship", "Hospital,", "Beijing,", "China,", "6", "Department", "of", "Thoratic", "Surgery,", "Peking", "University", "People’s", "Hospital,", "Beijing,", "China,", "7", "Department", "of", "General", "Surgery,", "Peking", "University", "Third", "Hospital,", "Beijing,", "China,", "8", "Key", "Laboratory", "for", "Neuroscience,", "Ministry", "of", "Education/Ministry", "of", "Public", "Health,", "Beijing,", "China", "Abstract", "Background:", "There", "is", "current", "interest", "in", "understanding", "the", "molecular", "mechanisms", "of", "tumor-induced", "bone", "pain.", "Accumulated", "evidence", "shows", "that", "endogenous", "formaldehyde", "concentrations", "are", "elevated", "in", "the", "blood", "or", "urine", "of", "patients", "with", "breast,", "prostate", "or", "bladder", "cancer.", "These", "cancers", "are", "frequently", "associated", "with", "cancer", "pain", "especially", "after", "bone", "metastasis.", "It", "is", "well", "known", "that", "transient", "receptor", "potential", "vanilloid", "receptor", "1", "(TRPV1)", "participates", "in", "cancer", "pain.", "The", "present", "study", "aims", "to", "demonstrate", "that", "the", "tumor", "tissue-derived", "endogenous", "formaldehyde", "induces", "bone", "cancer", "pain", "via", "TRPV1", "activation", "under", "tumor", "acidic", "environment.", "Methodology/Principal", "Findings:", "Endogenous", "formaldehyde", "concentration", "increased", "significantly", "in", "the", "cultured", "breast", "cancer", "cell", "lines", "in", "vitro,", "in", "the", "bone", "marrow", "of", "breast", "MRMT-1", "bone", "cancer", "pain", "model", "in", "rats", "and", "in", "tissues", "from", "breast", "cancer", "and", "lung", "cancer", "patients", "in", "vivo.", "Low", "concentrations", "(1,5", "mM)", "of", "formaldehyde", "induced", "pain", "responses", "in", "rat", "via", "TRPV1", "and", "this", "pain", "response", "could", "be", "significantly", "enhanced", "by", "pH", "6.0", "(mimicking", "the", "acidic", "tumor", "microenvironment).", "Formaldehyde", "at", "low", "concentrations", "(1", "mM", "to", "100", "mM)", "induced", "a", "concentration-dependent", "increase", "of", "[Ca2+]i", "in", "the", "freshly", "isolated", "rat", "dorsal", "root", "ganglion", "neurons", "and", "TRPV1-transfected", "CHO", "cells.", "Furthermore,", "electrophysiological", "experiments", "showed", "that", "low", "concentration", "formaldehyde-elicited", "TRPV1", "currents", "could", "be", "significantly", "potentiated", "by", "low", "pH", "(6.0).", "TRPV1", "antagonists", "and", "formaldehyde", "scavengers", "attenuated", "bone", "cancer", "pain", "responses.", "Conclusions/Significance:", "Our", "data", "suggest", "that", "cancer", "tissues", "directly", "secrete", "endogenous", "formaldehyde,", "and", "this", "formaldehyde", "at", "low", "concentration", "induces", "metastatic", "bone", "cancer", "pain", "through", "TRPV1", "activation", "especially", "under", "tumor", "acidic", "environment.", "Citation:", "Tong", "Z,", "Luo", "W,", "Wang", "Y,", "Yang", "F,", "Han", "Y,", "et", "al.", "(2010)", "Tumor", "Tissue-Derived", "Formaldehyde", "and", "Acidic", "Microenvironment", "Synergistically", "Induce", "Bone", "Cancer", "Pain.", "PLoS", "ONE", "5(4):", "e10234.", "doi:10.1371/journal.pone.0010234", "Editor:", "Hiroaki", "Matsunami,", "Duke", "University,", "United", "States", "of", "America", "Received", "November", "25,", "2009;", "Accepted", "March", "24,", "2010;", "Published", "April", "21,", "2010", "Copyright:", "2010", "Tong", "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", "grants", "from", "the", "National", "Natural", "Science", "Foundation", "of", "China", "(30700206,", "30800332),", "the", "111", "Project", "of", "the", "Ministry", "of", "Education", "of", "China", "(B07001),", "the", "National", "Basic", "Research", "Program", "of", "the", "Ministry", "of", "Science", "and", "Technology", "of", "China", "(2007CB512501)", "and", "Beijing", "Outstanding", "Ph.D.", "Program", "Mentor", "Grant,", "Key", "Project", "of", "Chinese", "Ministry", "of", "Education", "(109003).", "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:", "tzq88666883@sina.com", "(ZT);", "ywan@hsc.pku.edu.cn", "(YW)", 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[ "Fujihara", "et", "al.", "Journal", "of", "Medical", "Case", "Reports", "2012,", "6:268", "http://www.jmedicalcasereports.com/content/6/1/268", "C", "A", "S", "E", "R", "E", "P", "O", "R", "T", "JOURNAL", "OF", "MEDICAL", "CASE", "REPORTS", "Open", "Access", "Endoscopic", "hemostasis", "with", "endoscopic", "mucosal", "resection", "and", "multiple", "synchronous", "early", "gastric", "cancers:", "a", "case", "report", "Shintaro", "Fujihara*,", "Hirohito", "Mori,", "Noriko", "Nishiyama,", "Mitsuyoshi", "Kobayashi,", "Hideki", "Kobara", "and", "Tsutomu", "Masaki", "Abstract", "Introduction:", "Endoscopic", "hemostasis", "for", "severe", "upper", "gastrointestinal", "bleeding", "due", "to", "tumors,", "such", "as", "gastrointestinal", "stromal", "tumors", "and", "malignant", "lymphoma,", "is", "temporarily", "effective.", "However,", "permanent", "hemostasis", "is", "difficult", "in", "many", "cases", "because", "of", "diffuse", "bleeding.", "Case", "presentation:", "A", "60-year-old", "Japanese", "woman", "was", "admitted", "to", "our", "hospital", "with", "hematemesis.", "Endoscopy", "revealed", "multiple", "gastric", "polyps", "and", "fresh", "blood", "in", "her", "stomach.", "One", "of", "the", "gastric", "polyps,", "which", "was", "associated", "with", "oozing", "bleeding,", "was", "found", "near", "the", "anterior", "wall", "of", "the", "lower", "gastric", "body.", "We", "initially", "applied", "hemostatic", "forceps", "and", "argon", "plasma", "coagulation", "over", "the", "tumor", "surface,", "but", "the", "bleeding", "persisted.", "After", "endoscopic", "mucosal", "resection,", "exposed", "vessels", "were", "seen", "at", "the", "base", "of", "the", "mucosal", "resection", "site", "with", "oozing", "bleeding.", "Coagulation", "of", "the", "bleeding", "vessels", "using", "hemostatic", "forceps", "allowed", "successful", "completion", "of", "the", "hemostatic", "procedure.", "Our", "patient", "also", "had", "eight", "synchronous", "gastric", "cancer", "lesions.", "Histological", "examination", "of", "the", "resected", "specimens", "showed", "various", "types", "of", "cancer.", "Conclusion:", "This", "is", "a", "case", "report", "of", "gastric", "cancer", "associated", "with", "eight", "gastric", "cancer", "lesions,", "confirmed", "by", "histology,", "in", "which", "hemostasis", "was", "achieved", "through", "endoscopy.", "Introduction", "Endoscopic", "hemostasis", "for", "severe", "upper", "gastrointestinal", "(GI)", "bleeding", "due", "to", "tumors,", "such", "as", "GI", "stromal", "tumors", "and", "malignant", "lymphoma,", "is", "temporarily", "effective", "[1].", "However,", "permanent", "hemostasis", "is", "difficult", "in", "many", "cases", "because", "of", "diffuse", "bleeding", "[2].", "We", "here", "report", "a", "case", "of", "endoscopic", "hemostasis", "with", "endoscopic", "mucosal", "resection", "(EMR)", "as", "a", "rescue", "therapy", "for", "bleed-", "ing", "of", "a", "malignant", "GI", "tumor", "after", "failed", "conventional", "therapy.", "This", "patient", "also", "had", "multiple", "synchronous", "gastric", "cancers.", "Case", "presentation", "A", "60-year-old", "Japanese", "woman", "was", "admitted", "to", "our", "hospital", "with", "hematemesis.", "She", "had", "no", "history", "of", "GI", "hemorrhage,", "peptic", "ulcer", "disease,", "use", "of", "nonsteroidal", "anti-inflammatory", "drugs,", "excessive", "alcohol", "ingestion,", "or", "*", "Correspondence:", "joshin@med.kagawa-u.ac.jp", "Department", "of", "Gastroenterology", "and", "Neurology,", "Kagawa", "University,", "Faculty", "of", "Medicine,", "1750-1", "Ikenobe,", "Miki-cho,", "Kita-gun,", "Kagawa", "Prefecture", "761-0793,", "Japan", "chronic", "liver", "disease.", "She", "had", "no", "other", "medical", "problems", "and", "was", "taking", "no", "medications.", "On", "presentation,", "her", "abdomen", "was", "soft,", "nontender,", "and", "nondistended", "with", "normal", "bowel", "sounds.", "Her", "hemoglobin", "level", "was", "8.5g/dL.", "Contrast-enhanced", "com-", "puted", "tomography", "(CT)", "revealed", "multiple", "lesions", "in", "her", "stomach.", "Hematologic", "tests", "revealed", "a", "total", "peripheral", "3", "white", "cell", "count", "of", "14,400/mm", ".", "Biochemical", "tests", "yielded", "elevated", "serum", "blood", "nitrogen", "(30.7mg/dL),", "decreased", "total", "protein", "(3.8g/dL),", "and", "decreased", "serum", "albumin", "(2.0mg/dL).", "Endoscopy", "revealed", "multiple", "gastric", "polyps", "and", "fresh", "blood", "in", "her", "stomach.", "One", "of", "the", "gastric", "polyps,", "which", "was", "associated", "with", "oozing", "bleeding,", "was", "found", "near", "the", "anterior", "wall", "of", "the", "lower", "gastric", "body.", "Hemostatic", "for-", "ceps", "(Coagrasper,", "FD-410LR;", "Olympus,", "Tokyo,", "Japan)", "were", "initially", "applied", "over", "the", "tumor", "surface,", "but", "because", "the", "bleeding", "persisted,", "argon", "plasma", "coagulation", "(APC)", "was", "performed", "around", "the", "bleeding", "site.", "Mucosal", "oozing", "continued", "after", "failed", "APC", "and", "the", "application", "of", "the", "hemostatic", "forceps", "(Figure", "1).", "©", "2012", "Fujihara", "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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[ "Available", "online", "http://arthritis-research.com/content/6/4/147", "Commentary", "Phosphatidylserine", "receptor", "and", "apoptosis:", "consequences", "of", "a", "non-ingested", "meal", "Marina", "Botto", "Rheumatology", "Section,", "Eric", "Bywaters", "Centre,", "Faculty", "of", "Medicine,", "Imperial", "College,", "London,", "UK", "Corresponding", "author:", "Marina", "Botto", "(e-mail:", "m.botto@imperial.ac.uk)", "Received:", "8", "Mar", "2004", "Revisions", "requested:", "5", "Apr", "2004", "Revisions", "received:", "19", "Apr", "2004", "Accepted:", "28", "Apr", "2004", "Published:", "4", "Jun", "2004", "Arthritis", "Res", "Ther", "2004,", "6:147-150", "(DOI", "10.1186/ar1191)", "©", "2004", "BioMed", "Central", "Ltd", "Abstract", "Apoptosis,", "a", "physiological", "process", "of", "controlled", "cell", "death,", "is", "essential", "during", "embryonic", "development", "and", "for", "the", "maintenance", "of", "tissue", "homeostasis.", "In", "recent", "years", "the", "view", "has", "emerged", "that", "dying", "cells", "can", "provide", "specific", "signals", "that", "enable", "recruitment", "and", "recognition", "by", "phagocytes.", "Exposure", "of", "phosphatidylserine,", "the", "best", "characterized", "of", "such", "signals,", "allows", "safe", "clearance", "of", "apoptotic", "waste", "without", "induction", "of", "inflammation.", "Here", "I", "re-examine", "some", "of", "the", "arguments", "that", "underpin", "the", "importance", "of", "these", "clearance", "mechanisms", "in", "light", "of", "recent", "observations", "from", "an", "animal", "model", "that", "lacks", "the", "receptor", "specific", "for", "phosphatidylserine.", "Keywords:", "apoptosis,", "autoimmunity,", "inflammation,", "phagocytosis", "Introduction", "Apoptosis", "is", "an", "active", "process", "of", "cell", "suicide", "that", "leads", "to", "ordered", "destruction", "of", "the", "cells", "and", "their", "safe", "disposal", "by", "professional", "(macrophages", "and", "immature", "dendritic", "cells)", "and", "nonprofessional", "(such", "as", "fibroblasts", "and", "epithelial", "cells)", "phagocytes", "[1].", "The", "removal", "of", "apoptotic", "cells", "is", "the", "final", "step", "and", "perhaps", "the", "ultimate", "objective", "of", "the", "apoptotic", "programme.", "When", "apoptosis", "was", "initially", "described", "by", "Kerr", "and", "coworkers", "[2],", "the", "phenomenon", "of", "programmed", "cell", "death", "was", "greeted", "with", "a", "striking", "lack", "of", "interest.", "It", "has", "now", "become", "apparent", "that", "the", "process", "is", "ubiquitous", "and", "plays", "a", "key", "role", "in", "many", "fundamental", "biological", "events,", "including", "embryonic", "development,", "normal", "tissue", "homeostasis,", "development", "of", "the", "immune", "system", "and", "resolution", "of", "inflammation.", "In", "addition,", "apoptotic", "cells", "are", "a", "potential", "source", "of", "self-antigens", "[3],", "and", "defective", "clearance", "of", "cell", "corpses", "has", "recently", "been", "implicated", "in", "the", "pathogenesis", "of", "autoimmune", "diseases", "[4].", "Although", "enormous", "progress", "has", "been", "made", "in", "our", "understanding", "of", "the", "molecular", "mechanisms", "of", "apoptosis,", "the", "events", "that", "lead", "to", "clearance", "of", "apoptotic", "cells", "are", "still", "undefined.", "However,", "it", "has", "become", "increasingly", "clear", "that", "in", "vivo", "apoptosis", "and", "engulfment", "are", "not", "distinct", "events,", "PS", "=", "phosphatidylserine;", "PSR", "=", "phosphatidylserine", "receptor.", "but", "rather", "are", "two", "linked", "stages", "in", "the", "same", "process.", "Cells", "dying", "by", "apoptosis", "provide", "both", "‘recruitment’", "and", "‘eat", "me’", "signals", "to", "scavenger", "cells,", "facilitating", "their", "own", "uptake", "[5].", "The", "best", "studied", "of", "these", "signals", "is", "exposure", "of", "phosphatidylserine", "(PS),", "a", "phospholipid", "that", "is", "normally", "limited", "to", "the", "inner", "leaflet", "of", "the", "plasma", "membrane", "bilayer.", "Although", "it", "has", "been", "well", "established", "that", "PS", "exposure", "on", "apoptotic", "cells", "is", "critically", "required", "for", "their", "proper", "uptake,", "the", "identification", "of", "a", "single", "dominant", "receptor", "that", "is", "capable", "of", "recognizing", "and", "removing", "the", "apoptotic", "cells", "has", "remained", "controversial.", "Is", "a", "phosphatidylserine-specific", "receptor", "required", "for", "safe", "clearance", "of", "dying", "cells?", "Many", "receptors", "and", "soluble", "ligands", "have", "been", "proposed", "to", "mediate", "the", "recognition", "and", "uptake", "of", "apoptotic", "cells.", "These", "include", "lectin-like", "molecules,", "scavenger", "receptors,", "CD14,", "the", "thrombospondin", "receptor", "CD36,", "the", "vitronectin", "receptor", "CD51/CD61,", "the", "oxidized", "low-density", "lipoprotein", "receptor", "CD68,", "the", "low-density", "lipoprotein", "receptor", "related", "protein", "(LRP1,", "known", "as", "CD91)", "and", "annexins", "[6].", "Some", "receptors", "recognize", "apoptotic", "cells", "in", "the", "early", "phase", "of", "cell", "death,", "whereas", "others,", "which", "recognize", "later", "stages", "of", "the", "process,", "act", "as", "backup", "systems.", "Some", "147" ]

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[ "Journal", "of", "Cardiovascular", "Magnetic", "Resonance", "Research", "Infarct", "evolution", "in", "man", "studied", "in", "patients", "with", "first-time", "coronary", "occlusion", "in", "comparison", "to", "different", "species", "-", "implications", "for", "assessment", "of", "myocardial", "salvage", "Erik", "Hedström1,", "Henrik", "Engblom1,", "Fredrik", "Frogner2,", "Karin", "Åström-Olsson3,", "Hans", "Öhlin2,", "Stefan", "Jovinge2", "and", "Håkan", "Arheden*1", "BioMed", "Central", "Open", "Access", "Address:", "1Department", "of", "Clinical", "Physiology,", "Lund", "University", "Hospital,", "SE-221", "85", "Lund,", "Sweden,", "2Department", "of", "Cardiology,", "Lund", "University", "Hospital,", "SE-221", "85", "Lund,", "Sweden", "and", "3Department", "of", "Cardiology,", "Sahlgrenska", "Hospital,", "SE-413", "45", "Gothenburg,", "Sweden", "Email:", "Erik", "Hedström", "-", "erik.hedstrom@med.lu.se;", "Henrik", "Engblom", "-", "henrik.engblom@med.lu.se;", "Fredrik", "Frogner", "-", "fredrik.frogner@skane.se;", "Karin", "Åström-Olsson", "-", "karin.astrom-olsson@vgregion.se;", "Hans", "Öhlin", "-", "hans.ohlin@skane.se;", "Stefan", "Jovinge", "-", "stefan.jovinge@med.lu.se;", "Håkan", "Arheden*", "-", "hakan.arheden@med.lu.se", "*", "Corresponding", "author", "Published:", "23", "September", "2009", "Journal", "of", "Cardiovascular", "Magnetic", "Resonance", "2009,", "11:38", "doi:10.1186/1532-429X-11-38", "This", "article", "is", "available", "from:", "http://www.jcmr-online.com/content/11/1/38", "Received:", "13", "May", "2009", "Accepted:", "23", "September", "2009", "©", "2009", "Hedström", "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", "time", "course", "of", "infarct", "evolution,", "i.e.", "how", "fast", "myocardial", "infarction", "(MI)", "develops", "during", "coronary", "artery", "occlusion,", "is", "well", "known", "for", "several", "species,", "whereas", "no", "direct", "evidence", "exists", "on", "the", "evolution", "of", "MI", "size", "normalized", "to", "myocardium", "at", "risk", "(MaR)", "in", "man.", "Despite", "the", "lack", "of", "direct", "evidence,", "current", "literature", "often", "refers", "to", "the", "\"golden", "hour\"", "as", "the", "time", "during", "which", "myocardial", "salvage", "can", "be", "accomplished", "by", "reperfusion", "therapy.", "Therefore,", "the", "aim", "of", "the", "present", "study", "was", "to", "investigate", "how", "duration", "of", "myocardial", "ischemia", "affects", "infarct", "evolution", "in", "man", "in", "relation", "to", "previous", "animal", "data.", "Consecutive", "patients", "with", "clinical", "signs", "of", "acute", "myocardial", "ischemia", "were", "screened", "and", "considered", "for", "enrollment.", "Particular", "care", "was", "taken", "to", "assure", "uniformity", "of", "the", "patients", "enrolled", "with", "regard", "to", "old", "MI,", "success", "of", "revascularization,", "collateral", "flow,", "release", "of", "biochemical", "markers", "prior", "to", "intervention", "etc.", "Sixteen", "patients", "were", "ultimately", "included", "in", "the", "study.", "Myocardium", "at", "risk", "was", "assessed", "acutely", "by", "acute", "Myocardial", "Perfusion", "Single", "photon", "emission", "computed", "tomography", "(MPS)", "and", "by", "T2", "imaging", "(T2-STIR)", "cardiovascular", "magnetic", "resonance", "(CMR)", "after", "one", "week", "in", "10", "of", "the", "16", "patients.", "Infarct", "size", "was", "measured", "by", "late", "gadolinium", "enhancement", "(LGE)", "at", "one", "week.", "Results:", "The", "time", "to", "reach", "50%", "MI", "of", "the", "MaR", "(T50)", "was", "significantly", "shorter", "in", "pigs", "(37", "min),", "rats", "(41", "min)", "and", "dogs", "(181", "min)", "compared", "to", "humans", "(288", "min).", "There", "was", "no", "significant", "difference", "in", "T50", "when", "using", "MPS", "compared", "to", "T2-STIR", "(p", "=", "0.53)", "for", "assessment", "of", "MaR", "(288", "±", "23", "min", "vs", "310", "±", "22", "min,", "T50", "±", "standard", "error).", "The", "transmural", "extent", "of", "MI", "increased", "progressively", "as", "the", "duration", "of", "ischemia", "increased", "(R2", "=", "0.56,", "p", "<", "0.001).", "Conclusion:", "This", "is", "the", "first", "study", "to", "provide", "direct", "evidence", "of", "the", "time", "course", "of", "acute", "myocardial", "infarct", "evolution", "in", "relation", "to", "MaR", "in", "man", "with", "first-time", "MI.", "Infarct", "evolution", "in", "man", "is", "significantly", "slower", "than", "in", "pigs,", "rats", "and", "dogs.", "Furthermore,", "infarct", "evolution", "assessments", "in", "man", "are", "similar", "when", "using", "MPS", "acutely", "and", "T2-STIR", "one", "week", "later", "for", "determination", "of", "MaR,", "which", "significantly", "facilitates", "future", "clinical", "trials", "of", "cardioprotective", "therapies", "in", "acute", "coronary", "syndrome", "by", "the", "use", "of", "CMR.", "Page", "1", "of", "10", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "W140–W144", "Nucleic", "Acids", "Research,", "2008,", "Vol.", "36,", "Web", "Server", "issue", "doi:10.1093/nar/gkn253", "Published", "online", "8", "May", "2008", "OREST:", "the", "online", "resource", "for", "EST", "analysis", "Brigitte", "Waegele1,*,", "Thorsten", "Schmidt2,", "H.", "Werner", "Mewes1,2", "and", "Andreas", "Ruepp1", "1Institute", "for", "Bioinformatics", "and", "Systems", "Biology", "(MIPS),", "Helmholtz", "Zentrum", "M", "u¨nchen", "-", "German", "Research", "Center", "for", "Environmental", "Health", "(GmbH),", "Ingolsta¨", "dter", "Landstraße", "1,", "D-85764", "Neuherberg", "and", "2Chair", "of", "Genome-oriented", "Bioinformatics,", "Technische", "Universita¨", "t", "M", "u¨nchen,", "Life", "and", "Food", "Science", "Center", "Weihenstephan,", "Am", "Forum", "1,", "D-85354", "Freising-Weihenstephan,", "Germany", "Received", "January", "31,", "2008;", "Revised", "April", "10,", "2008;", "Accepted", "April", "20,", "2008", "ABSTRACT", "The", "generation", "of", "expressed", "sequence", "tag", "(EST)", "libraries", "offers", "an", "affordable", "approach", "to", "investi-", "gate", "organisms,", "if", "no", "genome", "sequence", "is", "available.", "OREST", "(http://mips.gsf.de/genre/proj/orest/index.", "html)", "is", "a", "server-based", "EST", "analysis", "pipeline,", "which", "allows", "the", "rapid", "analysis", "of", "large", "amounts", "of", "ESTs", "or", "cDNAs", "from", "mammalia", "and", "fungi.", "In", "order", "to", "assign", "the", "ESTs", "to", "genes", "or", "proteins", "OREST", "maps", "DNA", "sequences", "to", "reference", "datasets", "of", "gene", "products", "and", "in", "a", "second", "step", "to", "complete", "genome", "sequences.", "Mapping", "against", "genome", "sequences", "recovers", "additional", "13%", "of", "EST", "data,", "which", "otherwise", "would", "escape", "further", "analysis.", "To", "enable", "functional", "analysis", "of", "the", "datasets,", "ESTs", "are", "functionally", "annotated", "using", "the", "hierarchical", "FunCat", "annotation", "scheme", "as", "well", "as", "GO", "annotation", "terms.", "OREST", "also", "allows", "to", "predict", "the", "association", "of", "gene", "products", "and", "diseases", "by", "Morbid", "Map", "(OMIM)", "classification.", "A", "statistical", "analysis", "of", "the", "results", "of", "the", "dataset", "is", "possible", "with", "the", "included", "PROMPT", "software,", "which", "provides", "information", "about", "enrich-", "ment", "and", "depletion", "of", "functional", "and", "disease", "annotation", "terms.", "OREST", "was", "successfully", "applied", "for", "the", "identification", "and", "functional", "characterization", "of", "more", "than", "3000", "EST", "sequences", "of", "the", "common", "marmoset", "monkey", "(Callithrix", "jacchus)", "as", "part", "of", "an", "international", "collaboration.", "INTRODUCTION", "In", "spite", "of", "considerable", "genome", "sequencing", "efforts", "during", "the", "last", "years", "there", "is", "still", "a", "large", "number", "of", "poorly", "characterized", "organisms,", "which", "serve", "as", "models", "for", "the", "investigation", "of", "different", "phenotypes", "and", "diseases.", "Sequencing", "of", "cDNA", "libraries", "offers", "a", "low-cost", "approach", "to", "obtain", "information", "about", "the", "protein-coding", "genes", "of", "these", "organisms.", "End-sequencing", "of", "cDNA", "clones", "with", "standard", "primers", "results", "in", "expressed", "sequence", "tag", "(EST)", "libraries", "with", "up", "to", "thousands", "of", "DNA", "fragments.", "The", "dbEST", "at", "the", "NCBI", "(1),", "one", "of", "the", "largest", "resources,", "contains", "more", "than", "48", "000", "000", "EST", "sequences", "from", "1500", "organisms.", "In", "addition,", "EST", "data", "are", "used", "to", "validate", "gene", "models", "on", "genome", "sequences,", "to", "analyse", "results", "from", "proteome", "experiments", "and", "to", "construct", "organism-specific", "microarrays", "(2).", "High-throughput", "in", "silico", "analysis", "of", "thousands", "of", "EST", "sequences", "for", "the", "identification", "of", "corresponding", "gene", "products", "and", "associated", "information", "requires", "an", "auto-", "mated", "EST", "analysis", "tool", "which", "should", "fulfil", "several", "requirements:", "(i)", "it", "should", "be", "designed", "in", "a", "way", "that", "it", "can", "be", "operated", "without", "in-depth", "bioinformatics", "skills;", "(ii)", "it", "should", "allow", "the", "analysis", "of", "ESTs", "from", "organisms", "with", "different", "phylogenetic", "background;", "(iii)", "the", "tool", "has", "to", "identify", "gene", "products", "that", "correspond", "to", "ESTs", "with", "high", "accuracy;", "(iv)", "in", "order", "to", "provide", "the", "user", "with", "a", "primary", "characterisation", "about", "the", "dataset", "there", "is", "a", "demand", "of", "a", "systematic", "functional", "annotation", "of", "the", "dataset", "and", "(v)", "statistics", "about", "functional", "characteristics", "that", "are", "significantly", "over-", "or", "under-represented", "within", "the", "dataset.", "There", "are", "a", "number", "of", "EST", "processing", "systems", "existing", "like", "ESTAnnotator", "(3),", "ESTAP", "(4),", "ESTExplorer", "(5),", "PartiGene", "(6)", "or", "EST2uni", "(7).", "However,", "many", "of", "the", "existing", "tools", "require", "local", "installation", "and", "maintenance", "of", "the", "latest", "versions", "of", "the", "tools", "and", "databases.", "This", "hampers", "an", "immediate", "analysis", "for", "occasional", "users", "and", "requires", "investments", "for", "disc", "requirements,", "database", "installation", "and", "administration.", "Here,", "we", "present", "OREST", "(Figure", "1),", "a", "web-based", "EST", "analysis", "pipeline", "for", "gene", "assignment", "and", "systematic", "func-", "tional", "annotation", "of", "large", "amounts", "of", "DNA", "sequences.", "OREST", "allows", "mapping", "of", "user", "data", "to", "the", "fungal", "model", "organism", "Saccharomyces", "cerevisiae", "as", "well", "as", "to", "several", "mammalian", "datasets.", "Automated", "functional", "assignment", "of", "the", "gene", "products", "can", "be", "performed", "via", "FunCat", "or", "GO", "annotation", "schemes.", "Mapping", "to", "the", "human", "dataset", "predicts", "also", "the", "association", "of", "the", "ESTs", "with", "diseases.", "Over-", "und", "under-represented", "features", "from", "functional", "annotation", "and", "disease", "relevance", "are", "obtained", "through", "a", "statistical", "analysis.", "Advantage", "and", "usability", "of", "the", "OREST", "EST", "analysis", "pipeline", "has", "been", "shown", "in", "a", "*To", "whom", "correspondence", "should", "be", "addressed.", "Tel:", "+49", "89", "3187", "3640;", "Fax:", "+49", "89", "3187", "3585;", "Email:", "brigitte.waegele@helmholtz-muenchen.de", "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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[ "Tropical", "Medicine", "and", "Health", "Vol.", "39", "No.", "4", "Supplement,", "2011,", "pp.", "17-27", "doi:10.2149/tmh.2011-S04", "Copyright", "2011", "by", "The", "Japanese", "Society", "of", "Tropical", "Medicine", "Review", "TMH", "9", "Dengue", "Vectors", "and", "their", "Spatial", "Distribution", "Yukiko", "Higa", "Published", "online", "25", "August,", "2011", "17", "©", "20A1b1stJraapcat:neTsheeSdoicsiteritbyuotifonTroofpdiceanlguMeevdeicctionres,", "Ae.", "aegypti", "and", "Ae.", "albopictus,", "is", "affected", "by", "climatic", "factors.", "In", "addition,", "since", "their", "life", "cycles", "are", "well", "adapted", "to", "the", "human", "environment,", "environmental", "changes", "resulting", "from", "human", "activity", "such", "as", "urbanization", "exert", "a", "great", "impact", "on", "vector", "distribution.", "The", "different", "responses", "of", "Ae.", "aegypti", "and", "Ae", "albopictus", "to", "various", "environments", "result", "in", "a", "difference", "in", "spatial", "distribution", "along", "north-south", "and", "urban-rural", "gradients,", "and", "between", "the", "indoors", "and", "outdoors.", "In", "the", "north-south", "gradient,", "climate", "associated", "with", "survival", "is", "an", "important", "factor", "in", "spatial", "distribution.", "In", "the", "urban-rural", "gradient,", "different", "distribution", "reflects", "a", "difference", "in", "adult", "niches", "and", "is", "modified", "by", "geographic", "and", "human", "factors.", "The", "direct", "response", "of", "the", "two", "species", "to", "the", "environment", "around", "houses", "is", "related", "to", "different", "spatial", "distribution", "indoors", "and", "outdoors.", "Dengue", "viruses", "circulate", "mainly", "between", "human", "and", "vector", "mosquitoes,", "and", "the", "vector", "presence", "is", "a", "limiting", "factor", "of", "transmission.", "Therefore,", "spatial", "distribution", "of", "dengue", "vectors", "is", "a", "significant", "concern", "in", "the", "epidemiology", "of", "the", "disease.", "Current", "technologies", "such", "as", "GIS,", "satellite", "imagery", "and", "statistical", "models", "allow", "researchers", "to", "predict", "the", "spatial", "distribution", "of", "vectors", "in", "the", "changing", "environment.", "Although", "it", "is", "difficult", "to", "confirm", "the", "actual", "effect", "of", "environ-", "mental", "and", "climate", "changes", "on", "vector", "abundance", "and", "vector-borne", "diseases,", "environmental", "changes", "caused", "by", "humans", "and", "human", "behavioral", "changes", "due", "to", "climate", "change", "can", "be", "expected", "to", "exert", "an", "impact", "on", "dengue", "vectors.", "Longitudinal", "monitoring", "of", "dengue", "vectors", "and", "viruses", "is", "therefore", "necessary.", "Key", "words:", "Aedes", "aegypti,", "Aedes", "albopictus,", "spatial,", "distribution,", "environment,", "dengue", "INTRODUCTION", "Humans", "have", "experienced", "dengue", "fever", "(DF)", "since", "ancient", "times.", "Dengue-like", "illness", "was", "already", "described", "in", "Chinese", "literature", "in", "992", "[1].", "Since", "the", "early", "20th", "century", "when", "experiments", "showed", "that", "dengue", "virus", "was", "trans-", "mitted", "by", "Aedes", "aegypti", "(L.),", "a", "great", "number", "of", "studies", "on", "the", "relationship", "between", "Ae.", "aegypti", "and", "DF", "have", "been", "conducted", "[2].", "Although", "there", "are", "several", "potential", "dengue", "vectors,", "the", "field", "isolation", "of", "viruses", "and", "epidemiological", "evidence", "clearly", "show", "that", "Ae.", "aegypti", "and", "Ae.", "albopictus", "are", "responsible", "for", "the", "majority", "of", "dengue", "transmission", "[1].", "Aedes", "albopictus", "(Skuse),", "better", "known", "as", "the", "“Asian", "tiger", "mosquito”,", "originates", "in", "Orient", "and", "serves", "as", "a", "second-", "ary", "vector", "of", "DF", "[2].", "This", "species", "feeds", "on", "humans", "in", "gardens,", "parks", "and", "bushes", "around", "human", "dwellings", "in", "the", "daytime", "and", "is", "very", "common", "in", "Japan", "and", "other", "Asian", "countries.", "After", "Ae.", "albopictus", "was", "recognized", "to", "be", "a", "vector", "of", "DF", "in", "1931", "and", "dengue", "virus", "was", "isolated", "from", "Ae.", "albopictus", "caught", "in", "the", "wild,", "many", "scientists", "have", "taken", "an", "interest", "in", "this", "species", "as", "well", "as", "Ae.", "aegypti", "[2].", "There", "is", "a", "wealth", "of", "studies", "on", "the", "distribution,", "mor-", "phology,", "genetics,", "biology", "and", "ecology", "of", "these", "two", "major", "dengue", "vectors", "due", "to", "their", "great", "medical", "importance.", "However,", "the", "dengue", "vector", "situation", "has", "completely", "changed", "since", "the", "1980’s.", "World", "geographic", "distribution", "of", "Ae.", "albopictus", "has", "dramatically", "shifted", "as", "a", "result", "of", "intro-", "duction", "of", "the", "species", "from", "Orient", "to", "New", "World,", "Europe", "and", "Africa", "by", "frequent", "used", "tire", "transportations", "[3].", "In", "addition,", "recent", "uncontrolled", "urbanization", "in", "developing", "countries", "and", "global", "warming,", "which", "influence", "vector", "mosquitoes", "and", "exert", "an", "impact", "on", "vector-borne", "diseases,", "have", "become", "topics", "of", "concern", "among", "scientists.", "Frequent", "movement", "of", "people", "by", "aircraft", "has", "resulted", "in", "a", "further", "introduction", "of", "vector", "mosquitoes", "to", "new", "places.", "Ae.", "aegypti", "and", "Ae.", "albopictus", "were", "collected", "from", "aircraft", "arriving", "at", "Changi", "International", "Airport", "in", "Singapore", "[4].", "Such", "vector", "movement", "will", "increase", "the", "risk", "of", "newly", "emerging", "vector-", "borne", "diseases.", "Not", "only", "the", "expansion", "of", "dengue", "vector", "distribution", "but", "also", "behavioral", "changes", "of", "Ae.", "aegypti", "and", "Ae.", "albopictus", "are", "currently", "reported.", "Ae.", "aegypti,", "which", "usually", "breeds", "in", "artificial", "containers", "in", "houses,", "was", "found", "Department", "of", "Vector", "Ecology", "and", "Environment,", "Institute", "of", "Tropical", "Medicine", "(NEKKEN),", "Nagasaki", "University,", "Sakamoto", "1-12-4,", "Nagasaki", "city,", "Nagasaki", "852-8523,", "Japan", "Tel:", "+81-95-819-7811", "Fax:", "+81-95-819-7812", "E-mail:", "yukko@nagasaki-u.ac.jp" ]

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[ "Perspective", "Too", "Much", "Cleavage", "of", "Cyclin", "E", "Promotes", "Breast", "Tumorigenesis", "Keith", "R.", "Loeb1,2,3*,", "Xueyan", "Chen1", "1", "Department", "of", "Laboratory", "Medicine,", "University", "of", "Washington", "School", "of", "Medicine,", "Seattle,", "Washington,", "United", "States", "of", "America,", "2", "Department", "of", "Pathology,", "University", "of", "Washington", "School", "of", "Medicine,", "Seattle,", "Washington,", "United", "States", "of", "America,", "3", "Division", "of", "Clinical", "Research,", "Fred", "Hutchinson", "Cancer", "Research", "Center,", "Seattle,", "Washington,", "United", "States", "of", "America", "Cyclin", "E,", "together", "with", "cyclin-depen-", "dent", "kinase", "2", "(CDK2),", "functions", "as", "a", "gatekeeper", "to", "promote", "G1/S", "transitions", "and", "the", "initiation", "of", "DNA", "replication.", "In", "normal", "cells,", "cyclin", "E–associated", "kinase", "activity", "is", "exquisitely", "regulated,", "with", "ac-", "tivity", "being", "limited", "to", "a", "brief", "time", "interval", "between", "late", "G1", "and", "early", "S", "phase.", "Human", "cancers", "frequently", "exhibit", "dereg-", "ulated", "cyclin", "E–associated", "kinase", "activity", "resulting", "from", "overexpression", "of", "cyclin", "E", "and", "loss", "of", "cyclin-dependent", "kinase", "inhi-", "bition", "(via", "p53", "mutations)", "promoting", "genetic", "instability", "and", "cell", "proliferation", "[1].", "Increased", "levels", "of", "cyclin", "E", "correlate", "with", "tumorigenesis", "and", "are", "a", "poor", "prog-", "nostic", "indicator", "independent", "of", "prolifera-", "tion", "rate,", "suggesting", "that", "cyclin", "E’s", "role", "in", "tumorigenesis", "is", "not", "limited", "to", "promoting", "increased", "cell", "proliferation", "[2,3].", "By", "elim-", "inating", "regulatory", "constraints", "using", "p53", "null", "cells,", "we", "and", "others", "have", "shown", "that", "overexpression", "or", "endogenous", "expression", "of", "stabilizing", "mutant", "forms", "of", "cyclin", "E", "can", "lead", "to", "hyperproliferation,", "genetic", "insta-", "bility,", "and", "malignancy", "in", "cell", "culture", "and", "murine", "models", "[4,5].", "Normal", "cells", "sup-", "press", "the", "effects", "of", "excess/stabilized", "cyclin", "E", "via", "the", "G1/S", "checkpoint", "involving", "the", "p53/p21", "pathway.", "Five", "isoforms", "of", "cyclin", "E,", "ranging", "in", "size", "from", "33", "to", "44", "kDa,", "have", "been", "identified", "in", "tumors", "over-expressing", "cyclin", "E.", "These", "low", "molecular", "weight", "forms", "of", "cyclin", "E", "(LMW-E)", "are", "generated", "through", "post-", "translational", "cleavage", "of", "full-length", "cyclin", "E", "by", "the", "elastase", "family", "of", "serine", "proteases", "in", "tumor", "cells", "[6,7].", "In", "comparison", "to", "full-", "length", "cyclin", "E", "(50", "kDa),", "LMW-E", "forms", "are", "uniquely", "expressed", "in", "tumor", "cells,", "exhibit", "enhanced", "CDK2-associated", "kinase", "activity,", "have", "increased", "affinity", "for", "CDK2", "[7–9],", "and", "exhibit", "decreased", "inhibition", "by", "CDK2", "inhibitors,", "p21", "and", "p27", "(Figure", "1)", "[10,11].", "Ectopic", "expression", "of", "LMW-E", "isoforms", "promotes", "cell", "proliferation,", "ge-", "netic", "instability,", "centrosome", "amplification,", "and", "malignancy", "[12,13].", "In", "addition,", "clinical", "studies", "have", "shown", "that", "high", "LMW-E", "is", "strongly", "associated", "with", "poor", "survival", "in", "breast", "cancer", "[2],", "colorectal", "cancer", "[14,15],", "ovarian", "cancer", "[16],", "and", "melanomas", "[17].", "Given", "its", "unique", "prop-", "erties", "and", "distinct", "function", "in", "human", "cancers,", "targeting", "LMW-E", "could", "have", "important", "therapeutic", "implications.", "The", "study", "by", "Duong", "et", "al.", "in", "this", "issue", "of", "PLoS", "Genetics", "[18]", "convincingly", "uncovers", "the", "tumorigenic", "potential", "of", "LMW-E.", "The", "authors", "used", "three", "different", "model", "sys-", "tems—3D", "acinar", "cultures,", "xenograft", "trans-", "plantation,", "and", "transgenic", "mice—to", "show", "that", "overexpression", "of", "LMW-E", "is", "sufficient", "to", "induce", "aberrant", "acinar", "morphogenesis", "in", "culture", "and", "mammary", "tumors", "in", "mice", "(Figure", "1).", "When", "grown", "on", "Matrigel,", "immortalized", "human", "mammary", "epithelial", "cells", "(hMECs)", "expressing", "LMW-E", "exhibit", "large", "misshapen", "multiacinar", "structures", "resulting", "from", "defective", "growth", "arrest", "and", "apoptosis", "that", "mimic", "morphologic", "features", "of", "breast", "carcinomas.", "Further,", "ectopic", "expression", "of", "LMW-E", "in", "immor-", "talized", "hMECs", "promotes", "tumorigenesis", "in", "xenografts", "and", "transgenic", "mice", "to", "a", "much", "greater", "extent", "than", "full-length", "cyclin", "E.", "Consistent", "with", "the", "reports", "by", "Akli", "et", "al.", "and", "Nanos-Webb", "et", "al.,", "tumorigenesis", "associated", "with", "LMW-E", "is", "dependent", "on", "CDK2", "[19,20].", "Furthermore,", "in", "vivo", "passaging", "of", "tumor", "cells", "increases", "the", "expression", "of", "LMW-E,", "suggesting", "that", "LMW-E", "provides", "a", "selective", "growth", "ad-", "vantage", "to", "the", "tumor.", "Duong", "et", "al.", "also", "took", "advantage", "of", "a", "proteomic", "analysis", "termed", "reverse-phase", "protein", "array", "assay", "(RPPA)", "to", "examine", "protein", "expression", "patterns", "in", "cultured", "tumor", "cells", "and", "in", "breast", "tumors", "expressing", "high", "LMW-E", "levels.", "Their", "analyses", "revealed", "that", "multi-", "ple", "components", "of", "the", "b-RAF-ERK1/2-", "mTOR", "pathway", "are", "elevated", "in", "these", "cells.", "Activation", "of", "the", "b-RAF-ERK1/2-", "mTOR", "pathway", "normally", "promotes", "cell", "division", "and", "cell", "survival.", "Consistent", "with", "this,", "the", "authors", "observed", "that", "endogenous", "cyclin", "E", "levels", "are", "also", "increased", "in", "cells", "expressing", "high", "LMW-E,", "indicative", "of", "the", "existence", "of", "a", "positive", "feedback", "loop", "that", "promotes", "cell", "proliferation.", "Both", "high", "LMW-E", "levels", "and", "up-regulation", "of", "the", "b-RAF-ERK1/2-mTOR", "signaling", "path-", "way", "are", "associated", "with", "poor", "survival,", "suggesting", "functional", "correlation", "of", "these", "events", "in", "aggressive", "tumors.", "Importantly,", "the", "authors", "demonstrated", "that", "combina-", "tion", "therapy", "targeting", "LMW-E/CDK2", "and", "the", "b-RAF-ERK1/2-mTOR", "pathway", "has", "a", "synergistic", "effect", "in", "abrogating", "the", "tumorigenic", "effect", "of", "LMW-E.", "Thus,", "the", "identification", "of", "these", "downstream", "regula-", "tors", "may", "provide", "novel", "biomarkers", "and/or", "potential", "therapeutic", "targets", "for", "LMW-E–", "expressing", "tumors.", "The", "report", "that", "LMW-E", "potentiates", "tumorigenesis", "in", "three", "independent", "model", "systems", "associated", "with", "activation", "of", "the", "b-", "RAF-ERK1/2-mTOR", "pathway", "is", "intrigu-", "ing.", "However,", "there", "are", "many", "important", "questions", "about", "the", "role", "of", "LMW-E", "in", "tumorigenesis", "that", "need", "to", "be", "addressed.", "1)", "What", "is", "the", "functional", "relationship", "be-", "tween", "LMW-E", "and", "full-length", "cyclin", "E?", "In", "each", "tumor", "model", "reported", "by", "Duong", "et", "al.,", "the", "effect", "was", "examined", "by", "over-", "expressing", "LMW-E", "in", "a", "background", "of", "endogenous", "full-length", "cyclin", "E.", "Further,", "the", "authors", "show", "that", "ectopic", "expression", "of", "LMW-E", "in", "transplanted", "xenografts", "trig-", "gers", "tumor", "evolution", "and", "results", "in", "increased", "levels", "of", "endogenous", "cyclin", "E.", "Thus,", "the", "contribution", "of", "endogenous", "full-", "Citation:", "Loeb", "KR,", "Chen", "X", "(2012)", "Too", "Much", "Cleavage", "of", "Cyclin", "E", "Promotes", "Breast", "Tumorigenesis.", "PLoS", "Genet", "8(3):", "e1002623.", "doi:10.1371/journal.pgen.1002623", "Editor:", "Marshall", "S.", "Horwitz,", "University", "of", "Washington,", "United", "States", "of", "America", "Published", "March", "29,", "2012", "Copyright:", "2012", "Loeb,", "Chen.", "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:", "The", "authors", "received", "no", "specific", "funding", "for", "this", "article.", "Competing", "Interests:", "The", "authors", "have", "declared", "that", "no", "competing", "interests", "exist.", "*", "E-mail:", "kloeb@fhcrc.org", "PLoS", "Genetics", "|", "www.plosgenetics.org", "1", "March", "2012", "|", "Volume", "8", "|", "Issue", "3", "|", "e1002623" ]

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[ "Fornaro", "Annals", "of", "General", "Psychiatry", "2011,", "10:5", "http://www.annals-general-psychiatry.com/content/10/1/5", "P", "R", "I", "M", "A", "R", "Y", "R", "E", "S", "E", "A", "R", "C", "H", "Open", "Access", "Switching", "from", "serotonin", "reuptake", "inhibitors", "to", "agomelatine", "in", "patients", "with", "refractory", "obsessive-compulsive", "disorder:", "a", "3", "month", "follow-up", "case", "series", "Michele", "Fornaro", "Abstract", "Background:", "Serotonin", "reuptake", "inhibitors", "(SRIs)", "currently", "represent", "the", "cornerstone", "of", "obsessive-compulsive", "disorder", "(OCD)", "pharmacotherapy.", "However,", "OCD", "is", "characterized", "by", "high", "rates", "of", "partial", "and/or", "absent", "response", "to", "standard,", "recommended", "treatments,", "often", "prompting", "pharmacological", "and", "non-pharmacological", "augmentation", "or", "switching", "of", "strategies.", "Agomelatine,", "a", "novel", "melatonin", "agonist", "and", "selective", "serotonin", "antagonist", "(MASSA)", "antidepressant", "approved", "for", "major", "depressive", "disorder", "(MDD)", "has", "recently", "been", "additionally", "proposed", "as", "a", "treatment", "for", "anxiety", "disorders", "such", "as", "social", "anxiety", "disorder", "(SAD)", "and", "panic", "disorder", "(PD),", "but", "not", "yet", "OCD.", "Nonetheless,", "agomelatine", "may", "have", "a", "role", "in", "the", "management", "of", "OCD,", "essentially", "due", "to", "its", "anxiolytic", "5-", "hydroxytryptamine", "(HT)2C", "blockade", "action,", "while", "melatonin", "(MT)1", "and", "MT2", "modulation", "might", "contribute", "to", "circadian", "rhythm", "restoration", "if", "impaired.", "Methods:", "This", "case", "series", "reports", "the", "outcome", "of", "six", "patients", "with", "or", "without", "comorbid", "mood", "and/or", "other", "anxiety", "disorders", "who", "were", "treated", "with", "SRIs", "at", "adequate", "doses", "for", "at", "least", "8", "weeks,", "showing", "partial", "or", "no", "response.", "Patients", "were", "then", "switched", "to", "agomelatine", "50", "mg/day,", "and", "followed", "up", "for", "12", "weeks.", "Results:", "Three", "out", "of", "six", "patients,", "in", "particular", "those", "with", "relevant", "circadian", "rhythm", "subjective", "impairment,", "showed", "a", "Yale-Brown", "Obsessive", "Compulsive", "Scale", "(Y-BOCS)", "score", "reduction", "of", "≥35%.", "No", "relevant", "side", "effects", "were", "observed,", "but", "initial,", "transient,", "self-remitting", "dizziness", "in", "one", "patient", "and", "weight", "gain", "in", "another", "were", "seen.", "Conclusions:", "Although", "clinical", "confounding", "factors", "(subthreshold", "bipolarity", "and", "eventually", "the", "presence", "of", "impaired", "circadian", "rhythms)", "and", "methodological", "boundaries", "(lack", "of", "control", "and", "neurophysiological", "recording,", "tiny", "sample", "size", "and", "short", "follow-up)", "limit", "the", "validity", "of", "this", "preliminary", "observation,", "it", "does", "indicate", "agomelatine", "may", "have", "a", "role", "in", "some", "SRI-refractory", "OCD", "cases,", "thus", "prompting", "the", "validity", "of", "investigation", "by", "further", "controlled", "studies,", "even", "for", "drug-naïve", "OCD", "patients.", "Introduction", "Obsessive-compulsive", "disorder", "(OCD)", "is", "a", "common", "con-", "dition", "that", "affects", "individuals", "of", "all", "ages.", "This", "disorder", "has", "been", "listed", "as", "one", "of", "the", "10", "most", "disabling", "illnesses", "by", "the", "World", "Health", "Organization", "[1],", "while", "the", "National", "Comorbidity", "Survey", "Replication", "indicated", "that", "OCD", "is", "the", "anxiety", "disorder", "with", "the", "highest", "percentage", "(50.6%)", "of", "serious", "cases", "[2].", "Approximately", "2%", "to", "3%", "of", "the", "world’s", "population", "will", "suffer", "from", "OCD", "at", "some", "point", "Correspondence:", "Dott.Fornaro@gmail.com", "University", "of", "Genova,", "Department", "of", "Psychiatry,", "Genoa,", "Italy", "in", "their", "lives", "[3],", "and", "it", "has", "been", "estimated", "that", "most", "individuals", "with", "OCD", "spend", "an", "average", "of", "17", "years", "before", "receiving", "an", "appropriate", "diagnosis", "and", "treatment", "for", "their", "illness", "[4].", "Additionally,", "OCD", "usually", "exhibits", "a", "waxing", "and", "waning", "course,", "frequently", "increasing", "in", "severity", "when", "left", "untreated,", "which", "causes", "unnecessary", "pain", "to", "those", "afflicted", "and", "to", "their", "families.", "Hence,", "the", "need", "for", "appropriate", "management", "is", "imperative.", "Although", "serotonin", "reuptake", "inhibitors", "(SRIs),", "includ-", "ing", "the", "widely", "prescribed", "selective", "SRIs", "(SSRIs),", "are", "con-", "sidered", "the", "cornerstone", "of", "pharmacological", "treatment", "of", "©", "2011", "Fornaro;", "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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[ "Hepat", "Mon.2012;12(7):430-436.", "DOI:", "10.5812/hepatmon.6170", "KOWSAR", "www.HepatMon.com", "Treatment", "Response", "and", "Tolerability", "of", "Pegylated", "Interferon-α", "Plus", "Ribavirin", "Combination", "Therapy", "in", "Elderly", "Patients", "(≥", "65", "years)", "With", "Chronic", "Hepatitis", "C", "in", "Korea", "Hyeong", "Il", "Kim", "1,", "In", "Hee", "Kim", "1*,", "Byung", "Jun", "Jeon", "1,", "Seok", "Lee", "1,", "Seong", "Hun", "Kim", "1,", "Sang", "Wook", "Kim", "1,", "Seung", "Ok", "Lee", "1,", "Soo", "Teik", "Lee", "1,", "Dae", "Ghon", "Kim", "1", "1", "Department", "of", "Internal", "Medicine,", "Chonbuk", "National", "University", "Medical", "School", "and", "Hospital,", "Jeonju,", "Jeonbuk,", "South", "Korea", "A", "R", "T", "I", "C", "L", "E", "I", "N", "F", "O", "A", "B", "S", "T", "R", "A", "C", "T", "Article", "type:", "Original", "Article", "Article", "history:", "Received:", "27", "Apr", "2012", "Revised:", "07", "May", "2012", "Accepted:", "17", "May", "2012", "Keywords:", "Chronic", "Hepatitis", "C", "Ribavirin", "Korea", "Background:", "The", "prevalence", "of", "hepatitis", "C", "virus", "(HCV)", "infections", "in", "elderly", "patients", "has", "been", "increasing", "in", "a", "number", "of", "countries.", "A", "few", "reports", "concerning", "pegylated", "interferon-α", "(PEG-IFN-α)-based", "combination", "treatment", "in", "elderly", "chronic", "hepatitis", "C", "(CHC)", "patients", "have", "been", "published,", "with", "slightly", "different", "treatment", "outcomes.", "Objectives:", "We", "investigated", "the", "treatment", "response", "and", "safety", "of", "PEG-IFN-α", "plus", "ribavirin", "combination", "therapy", "in", "elderly", "patients", "with", "CHC.", "Patients", "and", "Methods:", "Among", "a", "total", "of", "181", "treatment-naïve", "CHC", "patients", "(60", "patients", "with", "genotype", "1,", "121", "patients", "with", "genotype", "2", "or", "3),", "38", "were", "aged", "≥", "65", "years", "(defined", "as", "the", "elderly", "group)", "and", "143", "were", "aged", "<", "65", "years", "(defined", "as", "the", "non-elderly", "group).", "Results:", "The", "overall", "sustained", "virologic", "response", "(SVR)", "was", "lower", "in", "the", "elderly", "group", "than", "in", "the", "non-elderly", "group,", "but", "it", "was", "not", "significantly", "different", "(65.8", "%vs.", "76.2", "%,", "P", "=", "0.15).", "In", "a", "subgroup", "analysis,", "among", "patients", "with", "genotype", "1,", "the", "elderly", "group", "had", "a", "significantly", "lower", "SVR", "rate", "than", "the", "non-elderly", "group", "(30.8", "%", "vs.", "66.0", "%,", "P", "=", "0.03).", "However,", "the", "SVR", "rate", "in", "patients", "with", "HCV", "genotype", "2", "or", "3", "was", "comparable", "between", "the", "two", "groups", "(84.0", "%", "vs.", "81.3", "%,", "P", "=", "0.85).", "HCV", "genotype", "was", "significantly", "associated", "with", "SVR", "in", "the", "elderly", "patients", "(genotype", "1", "vs.", "2", "or", "3,", "odds", "ratio:", "0.18,", "95%", "confidence", "interval:", "0.000-0.869,", "P", "=", "0.03).", "The", "incidence", "of", "premature", "discontinuation", "of", "treatment", "(21.1", "%", "vs.", "9.1", "%,", "P", "=", "0.05)", "and", "dose", "modification", "(52.6", "%", "vs.", "31.5", "%;", "P", "=", "0.02)", "due", "mainly", "to", "adverse", "events", "or", "laboratory", "abnor-", "malities,", "were", "higher", "in", "the", "elderly", "group", "than", "in", "the", "non-elderly", "group.", "Conclusions:", "PEG-IFN-α", "plus", "ribavirin", "combination", "therapy", "might", "be", "considered", "for", "elder-", "ly", "CHC", "patients,", "especially", "for", "genotype", "2", "or", "3,", "with", "vigilant", "monitoring", "of", "adverse", "events.", "Copyright", "c", "2012", "Kowsar", "Corp.", "All", "rights", "reserved.", "Implication", "for", "health", "policy/practice/research/medical", "education:", "The", "care", "of", "older", "patients", "with", "chronic", "hepatitis", "C", "(CHC)", "is", "one", "of", "the", "most", "important", "issues", "confronted", "by", "physicians.", "The", "results", "of", "this", "study", "suggest", "that", "PEG-IFN-α", "plus", "ribavirin", "combination", "therapy", "might", "be", "considered", "for", "elderly", "chronic", "hepatitis", "C", "pa-", "tients,", "especially", "for", "genotype", "2", "or", "3,", "with", "vigilant", "monitoring", "of", "adverse", "events.", "Please", "cite", "this", "paper", "as:", "Kim", "HI,", "Kim", "IH,", "Jeon", "BJ,", "Lee", "S,", "Kim", "SH,", "Kim", "SW,", "et", "al.", "Treatment", "Response", "and", "Tolerability", "of", "Pegylated", "Interferon-α", "Plus", "Ribavirin", "Combination", "Therapy", "in", "Elderly", "Patients", "(≥", "65", "years)", "With", "Chronic", "Hepatitis", "C", "in", "Korea.", "Hepat", "Mon.", "2012;12(7):", "430-6.", "DOI:", "10.5812/", "hepatmon.6170", "*", "Corresponding", "author:", "In", "Hee", "Kim,", "Department", "of", "Internal", "Medi-", "cine,", "Chonbuk", "National", "University", "Medical", "School", "and", "Hospital,", "634-18", "Keumam-dong,", "Dukjin-gu,", "Jeonju,", "Jeonbuk", "561-712,", "South", "Korea.", "Tel:", "+82-", "632501677,", "Fax:", "+82-632541609,", "E-mail:", "ihkimmd@jbnu.ac.kr", "DOI:", "10.5812/hepatmon.6170", "Copyright", "c", "2012", "Kowsar", "Corp.", "All", "rights", "reserved." ]

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[ "MOLECULAR", "NEUROSCIENCE", "Drug-evoked", "plasticity:", "do", "addictive", "drugs", "reopen", "a", "critical", "period", "of", "postnatal", "synaptic", "development?", "Camilla", "Bellone", "1*", "and", "Christian", "Lüscher", "1,2", "1", "Medical", "Faculty,", "Department", "of", "Basic", "Neurosciences,", "University", "of", "Geneva,", "Geneva,", "Switzerland", "2", "Clinic", "of", "Neurology,", "Department", "of", "Clinical", "Neurosciences,", "Geneva", "University", "Hospital,", "Geneva,", "Switzerland", "REVIEW", "ARTICLE", "published:", "15", "June", "2012", "doi:", "10.3389/fnmol.2012.00075", "Edited", "by:", "R.", "Suzanne", "Zukin,", "Albert", "Einstein", "College", "of", "Medicine,", "USA", "Reviewed", "by:", "Carlo", "Sala,", "CNR", "Institute", "of", "Neuroscience,", "Italy", "Enrico", "Tongiorgi,", "University", "of", "Trieste,", "Italy", "*Correspondence:", "Camilla", "Bellone,", "Medical", "Faculty,", "Department", "of", "Basic", "Neuroscience,", "University", "of", "Geneva,", "1,", "Michel-Servet,", "1211", "Geneve,", "Switzerland.", "e-mail:", "camilla.bellone@unige.ch", "As", "in", "other", "parts", "of", "the", "central", "nervous", "system", "(CNS)", "of", "the", "mouse,", "glutamatergic", "synapses", "onto", "dopamine", "(DA)", "neurons", "in", "the", "ventral", "tegmental", "area", "(VTA)", "mature", "postnatally.", "At", "birth", "many", "AMPA", "receptors", "(AMPARs)", "lack", "GluA2R", "subunit", "and", "most", "NMDARs", "contain", "the", "GluN2B", "subunit.", "Within", "2", "weeks", "these", "receptors", "are", "replaced", "with", "GluA2-", "and", "GluN2A-", "containing", "AMPARs", "and", "NMDARs,", "respectively.", "Recent", "data", "suggest", "that", "a", "single", "injection", "of", "cocaine", "(or", "another", "drug", "of", "addiction)", "triggers", "glutamate", "receptor", "redistribution", "with", "the", "reappearance", "of", "the", "subunits", "typically", "present", "in", "immature", "synapses,", "as", "if", "addictive", "drugs", "reopen", "the", "developmental", "critical", "period.", "Here", "we", "review", "the", "experimental", "evidence", "for", "this", "hypothesis", "and", "discuss", "the", "implications", "for", "circuit", "function.", "Keywords:", "CP-AMPARs,", "VTA,", "addictive", "drugs,", "postnatal", "development", "INTRODUCTION", "Fast", "excitatory", "synaptic", "transmission", "in", "the", "mammalian", "central", "nervous", "system", "(CNS)", "is", "mediated", "predominantly", "by", "ionotropic", "glutamate", "receptors", "of", "the", "AMPA-", "and", "NMDA-type.", "These", "recep-", "tors", "are", "composed", "of", "different", "subunits", "that", "determine", "the", "bio-", "physical", "and", "trafficking", "properties", "of", "the", "channel.", "Depending", "on", "the", "particular", "subunit", "composition", "of", "the", "ionotropic", "receptors", "both", "synaptic", "transmission", "and", "synaptic", "plasticity", "can", "vary", "con-", "siderably.", "The", "AMPA", "receptors", "(AMPARs)", "are", "the", "workhorses", "of", "fast", "excitatory", "transmission", "in", "the", "CNS.", "They", "are", "tetrameric", "receptor", "assemblies", "of", "GluA1–4", "subunits,", "which", "are", "differently", "expressed", "in", "the", "brain", "and", "are", "encoded", "by", "separate", "genes", "(Hollmann", "and", "Heinemann,", "1994;", "Kato", "et", "al.,", "2008;", "Traynelis", "et", "al.,", "2010).", "The", "subunits", "that", "are", "predominantly", "expressed", "in", "the", "CNS", "are", "the", "GluA1", "and", "GluA2", "subunits", "and", "the", "major-", "ity", "of", "receptors", "at", "the", "synapse", "are", "heteromers", "incorporating", "both.", "The", "GluA2", "subunit", "is", "critical", "in", "determining", "the", "proper-", "ties", "of", "AMPARs;", "the", "presence", "of", "an", "arginine", "(R)", "residue", "in", "its", "pore", "membrane", "domain,", "introduced", "by", "post-translational", "edit-", "ing,", "renders", "the", "receptor", "impermeable", "to", "Ca2+", "(CI-AMPARs)", "and", "therefore", "results", "in", "a", "linear", "current-voltage", "(I–V)", "curve", "that", "reverses", "at", "0", "mV.", "Conversely,", "when", "the", "GluA2", "subunit", "is", "absent,", "the", "receptors", "are", "Ca2+-permeable", "(CP-AMPARs)", "and", "the", "I–V", "curve", "becomes", "inwardly", "rectifying", "because", "the", "currents", "at", "positive", "potentials", "are", "inhibited", "by", "endogenous", "polyamines", "(Donevan", "and", "Rogawski,", "1995;", "Liu", "and", "Zukin,", "2007)", "and", "because", "the", "unitary", "current", "is", "larger.", "Many", "reversible", "post-translational", "modifications", "of", "both", "GluA1", "and", "GluA2", "subunits", "regulate", "AMPAR", "expression", "and", "function;", "among", "them", "subunit", "phosphorylation", "as", "well", "as", "palmitoylation", "and", "ubiquitination", "have", "been", "shown", "to", "modu-", "late", "both", "biophysical", "properties", "and", "receptor", "trafficking", "(Lu", "and", "Roche,", "2011).", "How", "this", "post-translational", "modification", "affects", "the", "trafficking", "of", "AMPARs", "in", "a", "subunit-specific", "manner,", "and", "how", "this", "determines", "synaptic", "plasticity,", "remains", "elusive.", "Tight", "control", "of", "CP-AMPAR", "expression", "ensures", "that", "the", "majority", "of", "cells", "in", "the", "brain", "contain", "CI-AMPARs", "(Shin", "et", "al.,", "2005).", "Although", "the", "CP-AMPARs", "may", "mediate", "excitotoxicity", "associated", "with", "different", "neurological", "disorders", "(Liu", "and", "Zukin,", "2007)", "it", "has", "been", "shown", "that", "these", "receptors", "also", "play", "an", "impor-", "tant", "role", "in", "synaptic", "plasticity", "(Plant", "et", "al.,", "2006;", "Adesnik", "and", "Nicoll,", "2007).", "Moreover", "there", "are", "several", "synapses", "in", "which", "CP-", "AMPARs", "are", "developmentally", "expressed,", "in", "contrast", "to", "the", "adult", "where", "CP-AMPARs", "are", "mainly", "found", "on", "GABAegic", "interneurons", "(Goldberg", "et", "al.,", "2003).", "Because", "of", "their", "characteristics,", "the", "CP-", "AMPARs", "confer", "novel", "properties", "to", "the", "synapses", "where", "they", "are", "expressed", "and", "their", "specific", "role", "in", "synaptic", "function", "as", "well", "as", "synaptic", "plasticity", "is", "beginning", "to", "be", "elucidated.", "NMDARs", "are", "heteromeric", "receptors", "containing", "GluN1", "as", "an", "obligatory", "subunit.", "GluN1", "is", "expressed", "both", "in", "the", "neonatal", "as", "well", "as", "the", "adult", "brain.", "Two", "other", "NMDAR", "subunits", "exist:", "GluN2", "and", "GluN3", "(Moriyoshi", "et", "al.,", "1991;", "Traynelis", "et", "al.,", "2010).", "Given", "that", "they", "each", "can", "be", "expressed", "in", "distinct", "subunit", "isoforms", "(e.g.,", "GluN2A/2B)", "their", "combination", "gives", "rise", "to", "multiple", "func-", "tionally", "distinct", "NMDARs", "(Paoletti,", "2011).", "It", "has", "been", "shown", "that", "NMDAR", "subunit", "composition", "is", "developmentally", "regulated;", "at", "many", "synapses", "GluN2B", "is", "the", "predominant", "isoform", "during", "the", "first", "2", "postnatal", "weeks", "(Monyer", "et", "al.,", "1994).", "The", "GluN2A", "isoform", "gradually", "increases", "after", "birth", "while", "the", "GluN2B", "and", "GluN2D", "expression", "progressively", "decrease.", "This", "developmental", "switch", "results", "in", "a", "change", "in", "the", "kinetics", "and", "subunit-specific", "modulation", "of", "NMDAR", "currents.", "The", "GluN3", "family", "can", "be", "expressed", "as", "two", "isoforms", "(GluN3A", "and", "GluN3B)", "that", "arise", "from", "two", "different", "genes", "that", "have", "different", "expression", "pro-", "files.", "GluN3A", "is", "mainly", "expressed", "during", "early", "postnatal", "life", "and", "Frontiers", "in", "Molecular", "Neuroscience", "www.frontiersin.org", "June", "2012", "|", "Volume", "5", "|", "Article", "75", "|", "1" ]

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[ "BioPsychoSocial", "Medicine", "Research", "Altered", "autonomic", "nervous", "system", "activity", "as", "a", "potential", "etiological", "factor", "of", "premenstrual", "syndrome", "and", "premenstrual", "dysphoric", "disorder", "Tamaki", "Matsumoto*1,", "Takahisa", "Ushiroyama2,", "Tetsuya", "Kimura3,", "Tatsuya", "Hayashi3", "and", "Toshio", "Moritani3", "BioMed", "Central", "Open", "Access", "Address:", "1Department", "of", "Health", "Science,", "International", "Buddhist", "University,", "3-2-1", "Gakuenmae,", "Habikino,", "Osaka,", "583-8501,", "Japan,", "2Department", "of", "Nursing,", "Aino", "Gakuin", "College,", "Ibaragi,", "Osaka,", "Japan", "and", "3Graduate", "School", "of", "Human", "and", "Environmental", "Studies,", "Kyoto", "University,", "Kyoto,", "Japan", "Email:", "Tamaki", "Matsumoto*", "-", "tamaki@shitennoji.ac.jp;", "Takahisa", "Ushiroyama", "-", "t-ushiroyama@ns-t.aino.ac.jp;", "Tetsuya", "Kimura", "-", "kimura@mmg.mbox.media.kyoto-u.ac.jp;", "Tatsuya", "Hayashi", "-", "tatsuya@kuhp.kyoto-u.ac.jp;", "Toshio", "Moritani", "-", "t.moritani@neuro.mbox.media.kyoto-u.ac.jp", "*", "Corresponding", "author", "Published:", "20", "December", "2007", "BioPsychoSocial", "Medicine", "2007,", "1:24", "doi:10.1186/1751-0759-1-24", "This", "article", "is", "available", "from:", "http://www.bpsmedicine.com/content/1/1/24", "Received:", "25", "September", "2007", "Accepted:", "20", "December", "2007", "©", "2007", "Matsumoto", "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:", "Premenstrual", "syndrome", "(PMS)", "encompasses", "a", "wide", "variety", "of", "cyclic", "and", "recurrent", "physical,", "emotional,", "and", "behavioral", "symptoms", "occurring", "during", "the", "late", "luteal", "phase", "of", "the", "menstrual", "cycle", "and", "abating", "shortly", "following", "the", "beginning", "of", "menses.", "Although", "PMS", "is", "widely", "recognized,", "its", "etiopathogenesis", "is", "not", "yet", "understood.", "The", "present", "study", "investigates", "whether", "the", "activity", "of", "the", "autonomic", "nervous", "system,", "which", "plays", "a", "vital", "role", "in", "orchestrating", "physiological", "homeostasis", "within", "the", "human", "body,", "is", "altered", "during", "the", "menstrual", "cycle", "of", "women", "with", "different", "degrees", "of", "premenstrual", "symptomatology.", "Methods:", "Sixty-two", "women", "in", "their", "20s", "to", "40s", "with", "regular", "menstrual", "cycles", "participated", "in", "this", "study.", "All", "subjects", "were", "examined", "during", "the", "follicular", "and", "late", "luteal", "phases.", "Cycle", "phase", "was", "determined", "by", "the", "onset", "of", "menstruation", "and", "oral", "temperature", "and", "was", "verified", "by", "concentrations", "of", "ovarian", "hormones,", "estrone,", "and", "pregnanediol", "in", "a", "urine", "sample", "taken", "early", "in", "the", "morning.", "Autonomic", "nervous", "system", "activity", "was", "assessed", "by", "means", "of", "heart-rate", "variability", "(HRV)", "power", "spectral", "analysis", "during", "supine", "rest.", "The", "Menstrual", "Distress", "Questionnaire", "was", "used", "to", "evaluate", "physical,", "emotional,", "and", "behavioral", "symptoms", "accompanying", "the", "menstrual", "cycle", "of", "the", "subjects.", "The", "subjects", "were", "categorized", "in", "three", "groups,", "Control,", "PMS,", "and", "premenstrual", "dysphoric", "disorder", "(PMDD)", "groups,", "depending", "on", "the", "severity", "of", "premenstrual", "symptomatology.", "Results:", "No", "intramenstrual", "cycle", "difference", "in", "any", "of", "the", "parameters", "of", "HRV", "was", "found", "in", "the", "Control", "group,", "which", "had", "no", "or", "a", "small", "increase", "in", "premenstrual", "symptoms.", "In", "contrast,", "Total", "power", "and", "high", "frequency", "power,", "which", "reflect", "overall", "autonomic", "and", "parasympathetic", "nerve", "activity,", "respectively,", "significantly", "decreased", "in", "the", "late", "luteal", "phase", "from", "the", "follicular", "phase", "in", "the", "PMS", "group.", "As", "for", "the", "PMDD", "group,", "which", "had", "more", "severe", "symptoms", "premenstrually,", "heart-rate", "fluctuation", "as", "well", "as", "all", "components", "of", "the", "power", "spectrum", "of", "HRV", "were", "markedly", "decreased", "regardless", "of", "the", "menstrual", "cycle", "compared", "to", "those", "of", "the", "other", "two", "groups.", "Conclusion:", "Several", "theories", "have", "been", "proposed", "to", "explain", "the", "underlying", "mechanisms", "of", "PMS", "with", "its", "complex", "web", "of", "bio-", "psycho-social", "factors.", "Although", "causes", "and", "consequences", "continue", "to", "elude,", "the", "present", "study", "provides", "intriguing", "and", "novel", "findings", "that", "the", "altered", "functioning", "of", "the", "autonomic", "nervous", "system", "in", "the", "late", "luteal", "phase", "could", "be", "associated", "with", "diverse", "psychosomatic", "and", "behavioral", "symptoms", "appearing", "premenstrually.", "In", "addition,", "when", "symptoms", "become", "more", "severe", "(as", "seen", "in", "women", "with", "PMDD),", "the", "sympathovagal", "function", "might", "be", "more", "depressed", "regardless", "of", "the", "menstrual", "cycle.", "Page", "1", "of", "8", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Journal", "of", "Medical", "Case", "Reports", "BioMed", "Central", "Case", "report", "Severe", "heparin-induced", "thrombocytopenia:", "when", "the", "obvious", "is", "not", "obvious,", "a", "case", "report", "Graham", "M", "Cormack", "and", "Larry", "J", "Kaufman*", "Open", "Access", "Address:", "Department", "of", "Medicine,", "University", "of", "Hawaii,", "and", "St.", "Francis", "Medical", "Center,", "Honolulu,", "HI,", "USA", "Email:", "Graham", "M", "Cormack", "-", "grahamcormack@hotmail.com;", "Larry", "J", "Kaufman*", "-", "bjammin@hawaii.rr.com", "*", "Corresponding", "author", "Published:", "30", "April", "2007", "Journal", "of", "Medical", "Case", "Reports", "2007,", "1:13", "doi:10.1186/1752-1947-1-13", "This", "article", "is", "available", "from:", "http://www.jmedicalcasereports.com/content/1/1/13", "Received:", "18", "December", "2006", "Accepted:", "30", "April", "2007", "©", "2007", "Cormack", "and", "Kaufman;", "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", "Thrombocytopenia", "commonly", "occurs", "in", "hospitalized", "patients,", "particularly", "critically", "ill", "patients.", "We", "present", "an", "exemplifying", "case", "of", "severe", "heparin-induced", "thrombocytopenia", "(HIT)", "in", "an", "effort", "to", "solidify", "its", "high", "priority", "in", "the", "differential", "diagnosis", "of", "thrombocytopenia.", "A", "75-year-old", "female", "underwent", "cardiac", "surgery", "with", "intraaortic", "balloon", "pump", "(IABP)", "placement.", "A", "platelet", "count", "drop", "to", "25", "×", "10(9)/L", "by", "the", "third", "postoperative", "day", "was", "attributed", "to", "the", "IABP,", "which", "was", "removed.", "Her", "thrombocytopenia", "remained", "refractory", "to", "multiple", "platelet", "transfusions", "over", "several", "days.", "Right", "hand", "cyanosis", "then", "developed,", "attributed", "to", "a", "right", "radial", "arterial", "catheter,", "which", "was", "removed.", "All", "toes", "and", "fingers", "then", "showed", "severe", "ischemic", "changes.", "Ten", "days", "after", "the", "initial", "platelet", "count", "drop,", "a", "critical", "care", "specialist", "new", "to", "the", "treating", "team", "suspected", "HIT.", "Heparin", "exposure", "was", "stopped", "and", "argatroban", "was", "initiated.", "A", "HIT", "antibody", "test", "was", "subsequently", "strongly", "positive.", "The", "patients", "thrombocytopenia", "gradually", "resolved.", "No", "additional", "thromboses", "occurred", "during", "a", "27-day", "intensive", "care", "unit", "stay.", "This", "case", "underscores", "the", "need", "for", "vigilance", "in", "suspecting", "HIT", "in", "patients", "with", "thrombocytopenia", "and", "recent", "heparin", "exposure.", "To", "avoid", "catastrophic", "outcomes", "in", "such", "patients,", "heparin", "should", "be", "stopped", "and", "alternative", "anticoagulation", "should", "be", "initiated,", "at", "least", "until", "HIT", "is", "excluded.", "Background", "Thrombocytopenia", "is", "a", "common", "finding", "in", "hospitalized", "patients,", "particularly", "critically", "ill", "patients,", "with", "readily", "plausible", "causes", "including", "disseminated", "intravascular", "coagulation,", "dilution", "from", "blood", "transfusions,", "continu-", "ous", "venovenous", "hemodialysis", "(CVVHD),", "liver", "disease", "with", "hypersplenism,", "and", "certain", "medications.", "Physicians", "should", "be", "vigilant", "in", "excluding", "the", "more", "dangerous", "causes", "of", "thrombocytopenia.", "For", "example,", "heparin-induced", "thrombocytopenia", "(HIT)", "warrants", "serious", "consideration", "because", "it", "is", "a", "potentially", "devastating,", "yet", "underdiag-", "nosed,", "complication", "of", "one", "of", "the", "most", "commonly", "pre-", "scribed", "medications", "worldwide.", "Approximately", "one", "trillion", "units", "of", "heparin", "are", "adminis-", "tered", "to", "12", "million", "patients", "per", "year", "in", "the", "United", "States", "[1].", "HIT", "is", "caused", "by", "antibodies", "to", "a", "complex", "of", "heparin", "and", "platelet", "factor", "4", "that", "activate", "platelets,", "resulting", "in", "release", "of", "procoagulant", "microparticles,", "thrombocytope-", "nia,", "excessive", "thrombin", "generation,", "and", "frequently", "thrombosis", "[2].", "HIT", "occurs", "in", "approximately", "0.5%", "of", "patients", "with", "occult", "exposure", "to", "heparin", "(e.g.,", "catheter", "flushes),", "0.1%–1%", "of", "patients", "treated", "with", "low-molecu-", "lar-weight", "heparin", "[3],", "and", "3%–5%", "of", "patients", "receiving", "unfractionated", "heparin", "[4].", "Although", "these", "are", "small", "per-", "centages,", "the", "ubiquitous", "use", "of", "heparin", "puts", "an", "extremely", "large", "number", "of", "patients", "at", "risk.", "Page", "1", "of", "5", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Hindawi", "Publishing", "Corporation", "Case", "Reports", "in", "Medicine", "Volume", "2012,", "Article", "ID", "659104,", "5", "pages", "doi:10.1155/2012/659104", "Case", "Report", "Adrenal", "Cortex-Sparing", "Surgery", "for", "Bilateral", "Multiple", "Pheochromocytomas", "in", "a", "Patient", "with", "Von", "Hippel-Lindau", "Disease", "Tarık", "Esen,1,", "2", "O¨", "mer", "Acar,2", "Ahmet", "Tefekli,2", "Ahmet", "Musaog˘lu,2", "I˙zzet", "Rozanes,3", "and", "Ali", "Emre4", "1", "School", "of", "Medicine,", "Ko¸c", "University,", "34450", "Istanbul,", "Turkey", "2", "Department", "of", "Urology,", "VKF", "American", "Hospital,", "34365", "Istanbul,", "Turkey", "3", "Department", "of", "Radiology,", "VKF", "American", "Hospital,", "34365", "Istanbul,", "Turkey", "4", "Department", "of", "General", "Surgery,", "VKF", "American", "Hospital,", "34365", "Istanbul,", "Turkey", "Correspondence", "should", "be", "addressed", "to", "O¨", "mer", "Acar,", "omer", "acar", "@hotmail.com", "Received", "22", "June", "2012;", "Revised", "18", "September", "2012;", "Accepted", "24", "September", "2012", "Academic", "Editor:", "Chin-Jung", "Wang", "Copyright", "©", "2012", "Tarık", "Esen", "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.", "Pheochromocytomas", "can", "be", "a", "part", "of", "familial", "neoplastic", "syndromes,", "in", "which", "case", "they", "tend", "to", "be", "multiple", "and", "involve", "both", "adrenal", "glands.", "Therefore,", "sparing", "adrenocortical", "function", "represents", "a", "major", "concern", "while", "dealing", "with", "these", "hereditary", "lesions.", "Herein,", "we", "describe", "the", "clinical", "characteristics", "and", "the", "management", "strategy", "of", "a", "patient", "with", "von", "Hippel-Lindau", "(VHL)", "disease", "who", "had", "multiple,", "bilateral", "pheochromocytomas", "as", "well", "as", "bilateral", "renal", "masses,", "pancreatic", "masses,", "and", "a", "paracaval", "mass.", "Only", "a", "portion", "of", "the", "left", "adrenal", "gland", "has", "remained", "in", "situ", "after", "two", "consecutive", "open", "surgeries", "and", "a", "percutaneous", "radiofrequency", "ablation", "which", "have", "been", "performed", "to", "treat", "the", "various", "components", "of", "this", "syndrome.", "No", "adrenal", "or", "extra-", "adrenal", "pheochromocytoma", "recurrences", "have", "been", "detected", "during", "a", "follow-up", "period", "of", "more", "than", "2", "years.", "Pancreatic", "and", "adrenal", "functions", "were", "normal", "throughout", "the", "postoperative", "period", "and", "never", "necessitated", "any", "replacement", "therapy.", "Adrenal", "cortex-", "sparing", "surgery", "is", "a", "valid", "option", "for", "VHL", "disease", "patients", "who", "present", "with", "synchronous", "bilateral", "adrenal", "pheochromocytomas.", "1.", "Introduction", "Adrenal", "surgery", "has", "gained", "popularity", "throughout", "the", "world", "most", "probably", "because", "of", "the", "increased", "radiologic", "detection", "of", "small,", "solid,", "asymptomatic", "adrenal", "masses.", "These", "inci-", "dentalomas", "are", "mostly", "small", "in", "size", "and", "nonfunctioning.", "However,", "surgery", "is", "needed", "either", "because", "of", "the", "size", "or", "the", "hormone-producing", "nature", "of", "the", "lesion,", "in", "at", "least", "15%", "of", "the", "cases", "[1].", "Adrenal", "surgery", "has", "been", "accepted", "as", "a", "total", "adrenal", "resection", "per", "definition.", "In", "a", "patient", "with", "unilateral", "disease", "and", "a", "healthy", "contralateral", "adrenal", "gland,", "this", "is", "mostly", "not", "a", "problem.", "Yet", "the", "radiologic", "presence", "of", "the", "contralateral", "gland", "is", "not", "necessarily", "an", "evidence", "for", "healthy", "function.", "Moreover,", "adrenal", "masses", "are", "common", "and", "mostly", "bilateral", "and/or", "multiple", "in", "patients", "with", "hereditary", "syndromes,", "where", "a", "bilateral", "adrenalectomy", "could", "have", "devastating", "side", "effects", "either", "with", "the", "resulting", "adrenal", "insufficiency", "or", "the", "need", "for", "life-long", "hormonal", "replacement", "[2].", "Recently,", "the", "concept", "of", "partial", "adrenalectomy", "is", "intro-", "duced", "for", "the", "above-mentioned", "reasons", "and", "prompted", "us", "to", "report", "a", "case", "where", "a", "staged", "cortex-sparing", "adrenal", "surgery", "was", "done", "in", "a", "patient", "with", "von", "Hippel-Lindau", "(VHL)", "disease", "and", "successfully", "eliminated", "multiple", "bilateral", "pheochromocytomas", "without", "causing", "adrenal", "insufficiency.", "2.", "Case", "Report", "A", "31-year-old,", "otherwise", "healthy,", "young", "male", "patient", "pre-", "sented", "with", "incidentally", "detected", "bilateral", "small", "solid", "renal", "and", "adrenal", "masses,", "a", "cystic", "mass", "at", "the", "head", "of", "the", "pancreas,", "and", "a", "paracaval", "mass.", "The", "patient", "defined", "no", "relevant", "family", "history", "and", "had", "no", "obvious", "symptoms.", "Physical", "examination", "findings", "(including", "serial", "blood", "pressure", "measurements)" ]

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[ "Xhabija", "et", "al.", "Cardiovascular", "Ultrasound", "2010,", "8:44", "http://www.cardiovascularultrasound.com/content/8/1/44", "C", "A", "S", "E", "R", "E", "P", "O", "R", "T", "CARDIOVASCULAR", "ULTRASOUND", "Open", "Access", "Gerbode", "defect", "following", "endocarditis", "and", "misinterpreted", "as", "severe", "pulmonary", "arterial", "hypertension", "Nereida", "Xhabija1*,", "Edvin", "Prifti1,", "Iris", "Allajbeu2,", "Fatmir", "Sula1", "Abstract", "A", "Gerbode", "-type", "defect", "is", "a", "ventricular", "septal", "defect", "communicating", "directly", "between", "the", "left", "ventricle", "and", "right", "atrium.", "It", "is", "usually", "congenital,", "but", "rarely", "is", "acquired,", "as", "a", "complication", "of", "endocarditis.", "This", "can", "be", "anatomically", "possible", "because", "the", "normal", "tricuspid", "valve", "is", "more", "apically", "displaced", "than", "the", "mitral", "valve.", "However,", "identification", "of", "an", "actual", "communication", "is", "often", "extremely", "difficult,", "so", "a", "careful", "and", "meticulous", "echocardiogram", "should", "be", "done", "in", "order", "to", "prevent", "echocardiographic", "misinterpretation", "of", "this", "defect", "as", "pulmonary", "arterial", "hypertension.", "The", "large", "systolic", "pressure", "gradient", "between", "the", "left", "ventricle", "and", "the", "right", "atrium", "would", "expectedly", "result", "in", "a", "high", "velocity", "systolic", "Doppler", "flow", "signal", "in", "right", "atrium", "and", "it", "can", "be", "sometimes", "mistakably", "diagnosed", "as", "tricus-", "pid", "regurgitant", "jet", "simulating", "pulmonary", "arterial", "hypertension.", "We", "present", "a", "rare", "case", "of", "young", "woman,", "with", "endocarditis", "who", "presented", "with", "severe", "pulmonary", "arterial", "hyper-", "tension.", "The", "preoperative", "diagnosis", "of", "left", "ventricle", "to", "right", "atrial", "communication", "(acquired", "Gerbode", "defect)", "was", "suspected", "initially", "by", "echocardiogram", "and", "confirmed", "at", "the", "time", "of", "the", "surgery.", "A", "point", "of", "interest,", "apart", "from", "the", "diagnostic", "problem,", "was", "the", "explanation", "for", "its", "mechanism", "and", "presentation.", "The", "probability", "of", "a", "bacterial", "etiology", "of", "the", "defect", "is", "high", "in", "this", "case.", "Introduction", "Gerbode’s", "defect", "is", "a", "rare", "form", "of", "VSD", "that", "allows", "for", "communication", "between", "the", "LV", "and", "RA.", "Two", "types", "of", "LV-to-RA", "communication", "are", "described:", "supravalvular", "and", "infravalvular,", "depending", "on", "whether", "the", "defect", "in", "the", "membranous", "septum", "is", "above", "or", "below", "the", "tricuspid", "valve", "[1,2].", "Although", "the", "majority", "appears", "to", "attribute", "the", "Gerbode", "defect", "to", "congenital", "origins,", "there", "have", "been", "publication", "in", "the", "past", "that", "have", "credited", "the", "defect’s", "formation", "secondary", "to", "bacterial", "endocarditis,", "especially", "supravalvular", "form", "[3].", "We", "present", "a", "case", "of", "our", "patient", "with", "this", "uncommon", "complication", "of", "endocarditis,", "simulating", "severe", "pulmon-", "ary", "hypertension.", "Case", "report", "A", "41", "year", "old", "lady,", "from", "Kosovo,", "was", "referred", "to", "our", "hospital", "for", "severe", "pulmonary", "arterial", "hypertension", "and", "a", "*", "Correspondence:", "nereidaxh@yahoo.fr", "1Department", "of", "Cardiology", "and", "Cardiac-Surgery,", "American", "Hospital,", "Department", "of", "Cardiology,", "Tirana,", "Albania", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "mass", "in", "right", "atrium", "suspected", "for", "vegetation.", "About", "one", "month", "before,", "she", "presented", "to", "the", "ER", "of", "her", "local", "hospi-", "tal", "with", "pyrexia", "and", "malaise.", "She", "was", "given", "medication", "and", "nutrition", "through", "the", "right", "internal", "jugular", "site", "for", "a", "few", "days", "since", "her", "peripheral", "venous", "system", "was", "unavail-", "able.", "Cardiology", "was", "consulted", "because", "her", "blood", "culture", "grew", "methacilin", "sensitive", "Staphylococcus", "aureus", "and", "she", "had", "persistent", "fever,", "despite", "antibiotics", "treatment.", "At", "that", "time", "the", "echocardiogram", "was", "interpreted", "as", "following:", "normal", "valves", "and", "cardiac", "chambers,", "but", "a", "mobile", "mass", "consistent", "with", "vegetation", "in", "right", "atrium", "was", "present.", "The", "tricuspid", "regurgitation", "was", "considered", "mild-", "to-", "moderate", "with", "estimated", "pulmonary", "arterial", "systolic", "pres-", "sure", "about", "80-90", "mmHg", "(figure", "1A).", "At", "the", "time", "of", "her", "presentation", "she", "had", "a", "40", "grade", "fever", "and", "complained", "of", "fatigue", "and", "palpitation.", "A", "3/6", "systolic", "murmur", "over", "the", "left", "precordium", "was", "audible,", "while", "pulmonary", "auscultation", "was", "negative.", "Her", "C-reactive", "pro-", "tein,", "white", "cell", "count", "and", "erythrocyte", "sedimentation", "rate", "were", "elevated,", "Hb", "level", "was", "9.6", "and", "D-dimer", "was", "very", "high", "(3088", "ng/ml).", "An", "electrocardiogram", "revealed", "sinus", "tachycardia", "with", "right", "bundle", "branch", "block.", "©", "2010", "Xhabija", "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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[ "Protein", "Kinase", "A", "Binds", "and", "Activates", "Heat", "Shock", "Factor", "1", "Ayesha", "Murshid1,", "Shiuh-Dih", "Chou1,", "Thomas", "Prince1,", "Yue", "Zhang", "1", ",", "Ajit", "Bharti2,", "Stuart", "K.", "Calderwood", "1", "*", "1", "Molecular", "and", "Cellular", "Radiation", "Oncology,", "Beth", "Israel", "Deaconess", "Medical", "Center,", "Harvard", "Medical", "School,", "Boston,", "Massachusetts,", "United", "States", "of", "America,", "2", "Stress", "Response", "Center,", "Boston", "University", "Medical", "Center,", "Boston,", "Massachusetts,", "United", "States", "of", "America", "Abstract", "Background:", "Many", "inducible", "transcription", "factors", "are", "regulated", "through", "batteries", "of", "posttranslational", "modifications", "that", "couple", "their", "activity", "to", "inducing", "stimuli.", "We", "have", "studied", "such", "regulation", "of", "Heat", "Shock", "Factor", "1", "(HSF1),", "a", "key", "protein", "in", "control", "of", "the", "heat", "shock", "response,", "and", "a", "participant", "in", "carcinogenisis,", "neurological", "health", "and", "aging.", "As", "the", "mechanisms", "involved", "in", "the", "intracellular", "regulation", "of", "HSF1", "in", "good", "health", "and", "its", "dysregulation", "in", "disease", "are", "still", "incomplete", "we", "are", "investigating", "the", "role", "of", "posttranslational", "modifications", "in", "such", "regulation.", "Methodology/Principal", "Findings:", "In", "a", "proteomic", "study", "of", "HSF1", "binding", "partners,", "we", "have", "discovered", "its", "association", "with", "the", "pleiotropic", "protein", "kinase", "A", "(PKA).", "HSF1", "binds", "avidly", "to", "the", "catalytic", "subunit", "of", "PKA,", "(PKAca)", "and", "becomes", "phosphorylated", "on", "a", "novel", "serine", "phosphorylation", "site", "within", "its", "central", "regulatory", "domain", "(serine", "320", "or", "S320),", "both", "in", "vitro", "and", "in", "vivo.", "Intracellular", "PKAca", "levels", "and", "phosphorylation", "of", "HSF1", "at", "S320", "were", "both", "required", "for", "HSF1", "to", "be", "localized", "to", "the", "nucleus,", "bind", "to", "response", "elements", "in", "the", "promoter", "of", "an", "HSF1", "target", "gene", "(hsp70.1)", "and", "activate", "hsp70.1", "after", "stress.", "Reduction", "in", "PKAca", "levels", "by", "small", "hairpin", "RNA", "led", "to", "HSF1", "exclusion", "from", "the", "nucleus,", "its", "exodus", "from", "the", "hsp70.1", "promoter", "and", "decreased", "hsp70.1", "transcription.", "Likewise,", "null", "mutation", "of", "HSF1", "at", "S320", "by", "alanine", "substitution", "for", "serine", "led", "to", "an", "HSF1", "species", "excluded", "from", "the", "nucleus", "and", "deficient", "in", "hsp70.1", "activation.", "Conclusions:", "These", "findings", "of", "PKA", "regulation", "of", "HSF1", "through", "S320", "phosphorylation", "add", "to", "our", "knowledge", "of", "the", "signaling", "networks", "converging", "on", "this", "factor", "and", "may", "contribute", "to", "elucidating", "its", "complex", "roles", "in", "the", "stress", "response", "and", "understanding", "HSF1", "dysregulation", "in", "disease.", "Citation:", "Murshid", "A,", "Chou", "S-D,", "Prince", "T,", "Zhang", "Y,", "Bharti", "A,", "et", "al.", "(2010)", "Protein", "Kinase", "A", "Binds", "and", "Activates", "Heat", "Shock", "Factor", "1.", "PLoS", "ONE", "5(11):", "e13830.", "doi:10.1371/journal.pone.0013830", "Editor:", "Mikhail", "V.", "Blagosklonny,", "Roswell", "Park", "Cancer", "Institute,", "United", "States", "of", "America", "Received", "June", "2,", "2010;", "Accepted", "October", "18,", "2010;", "Published", "November", "9,", "2010", "Copyright:", "2010", "Murshid", "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:", "Studies", "were", "supported", "by", "NIH", "research", "grants", "2RO1CA047407", "and", "RO1CA077465.", "These", "are", "peer-reviewed", "National", "Institutes", "of", "Health", "RO-1", "grants", "intended", "to", "investigate", "the", "role", "of", "cell", "signaling", "in", "the", "heat", "shock/stress", "response.", "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:", "scalderw@bidmc.harvard.edu", "Introduction", "HSF1", "is", "a", "primary", "regulator", "of", "the", "heat", "shock", "response", "and", "a", "factor", "in", "a", "number", "of", "human", "pathologies", "including", "cancer", "and", "neurodegenerative", "diseases", "[1,2,3,4,5].", "Curiously,", "although", "both", "diseases", "are", "associated", "with", "advancing", "age,", "HSF1", "loses", "activity", "in", "the", "progression", "of", "neurodegenerative", "diseases", "while", "being", "activated", "in", "cancer", "[1,2,6].", "It", "would", "seem", "apparent", "therefore", "that", "understanding", "the", "molecular", "basis", "of", "HSF1", "up-", "and", "down-", "regulation", "in", "disease", "would", "provide", "valuable", "insights.", "HSF1", "belongs", "to", "the", "multi-gene", "HSF", "family", "present", "in", "all", "eukaryotes", "[7].", "Initial", "studies", "were", "carried", "out", "on", "the", "single", "HSF", "gene", "of", "the", "yeast", "S.", "cereviseae", "[8].", "These", "studies", "indicated", "that,", "unique", "among", "transcription", "factors", "HSF", "undergoes", "trimer", "formation", "on", "activation", "and", "that", "such", "oligomerization", "governs", "binding", "to", "the", "heat", "shock", "elements", "(HSE)", "on", "the", "promoters", "of", "heat", "shock", "protein", "(HSP)", "genes", "[9,10].", "The", "findings", "in", "yeast", "were", "confirmed", "in", "mammalian", "cells", "in", "which", "trimerization", "was", "shown", "to", "be", "a", "requirement", "for", "binding", "to", "HSP", "promoters", "[7].", "Another", "unusual", "feature", "associated", "with", "HSF", "is", "that", "trimerization", "and", "binding", "to", "HSE", "can", "be", "dissociated", "from", "trans-activation", "in", "studies", "carried", "out", "both", "in", "vitro", "and", "in", "vivo;", "DNA", "binding", "alone", "is", "evidently", "insufficient", "to", "drive", "transcription", "and", "other,", "binding", "independent", "processes", "are", "involved", "[11,12,13,14].", "Early", "studies", "suggested", "that", "these", "may", "include", "posttranslational", "modification", "of", "HSF1", "[10,13,15].", "Indeed", "yeast", "HSF", "and", "mammalian", "HSF1", "appear", "to", "undergo", "heavy", "phosphorylation", "on", "serine", "and", "threonine", "residues", "when", "activated", "[10,15,16].", "In", "addition", "intracellular", "HSF1", "under-", "goes", "other", "modifications", "such", "as", "sumoylation", "and", "acetylation", "after", "stress", "[17].", "Alterations", "in", "HSF1", "phosphorylation", "appear", "to", "be", "important", "in", "the", "‘‘second", "step’’", "of", "HSF1", "activation", "and", "stress", "and", "trans-activation", "of", "HSP", "genes", "can", "be", "inhibited", "by", "kinase", "inhibitors,", "while", "inactive", "HSF1", "trimers", "can", "be", "rendered", "active", "in", "vivo", "by", "exposure", "to", "phosphatase", "inhibitors", "[14].", "The", "sites", "of", "HSF1", "phosphorylation", "have", "been", "studied", "by", "phosphopeptide", "mapping", "and", "a", "partial", "list", "of", "such", "sites", "exists.", "HSF1", "is", "known", "to", "be", "phosphorylated", "on", "serines", "residues", "at", "121,", "230,", "303,", "307,", "326,", "363", "[16,18,19,20,21,22,23].", "The", "role", "of", "these", "sites", "in", "HSP", "transcrip-", "tion", "have", "been", "attributed", "mainly", "by", "point", "mutation", "studies", "and", "these", "experiments", "suggest", "that", "phosphorylation", "of", "serine", "121,", "303,", "307,", "or", "363", "can", "inhibit", "HSP", "transcription", "[16,18,24,25].", "S230", "and", "S326", "are", "the", "only", "currently", "known", "phosphorylation", "sites", "associated", "with", "stimulation", "of", "transcription", "by", "HSF1.", "In", "addition,", "the", "regulatory", "mechanisms", "through", "which", "these", "posttranslational", "PLoS", "ONE", "|", "www.plosone.org", "1", "November", "2010", "|", "Volume", "5", "|", "Issue", "11", "|", "e13830" ]

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[ "organic", "compounds", "Acta", "Crystallographica", "Section", "E", "Structure", "Reports", "Online", "ISSN", "1600-5368", "N-[Amino(azido)methylidene]-4-methyl-", "benzenesulfonamide", "Ayyaz", "Mahmood,", "Islam", "Ullah", "Khan,*", "Muhammad", "Nadeem", "Arshad‡", "and", "Jamil", "Ahmed", "Materials", "Chemistry", "Laboratory,", "Department", "of", "Chemistry,", "GC", "University,", "Lahore", "54000,", "Pakistan", "Correspondence", "e-mail:", "iukhan@gcu.edu.pk", "Received", "29", "June", "2011;", "accepted", "6", "July", "2011", "Key", "indicators:", "single-crystal", "X-ray", "study;", "T", "=", "296", "K;", "mean", "(C–C)", "=", "0.003", "A˚;", "R", "factor", "=", "0.035;", "wR", "factor", "=", "0.107;", "data-to-parameter", "ratio", "=", "17.1.", "In", "the", "title", "molecule,", "C8H10N5O2S,", "the", "amino(azido)methyl", "and", "p-toluenesulfonyl", "moieties", "are", "inclined", "almost", "at", "right", "angles", "with", "respect", "to", "each", "other,", "making", "a", "dihedral", "angle", "of", "83.49", "(6)", ".", "An", "intramolecular", "N—H", "O", "hydrogen", "bond", "gives", "rise", "to", "the", "formation", "of", "six-membered", "ring", "with", "graph-set", "motif", "S(6).", "In", "the", "crystal,", "intermolecular", "N—H", "O", "hydrogen", "bonding", "is", "responsible", "for", "the", "formation", "of", "dimers", "about", "inversion", "centers,", "which", "are", "linked", "through", "another", "N—", "H", "O", "interaction", "along", "the", "b", "axis.", "Related", "literature", "For", "the", "synthesis,", "see:", "Arshad", "et", "al.", "(2009).", "For", "the", "biological", "activity", "of", "sulfonamides,", "see:", "Moree", "et", "al.", "(1991);", "Arshad", "et", "al.", "(2008);", "Gennarti", "et", "al.", "(1994).", "For", "related", "structures,", "see:", "Denny", "et", "al.", "(1980);", "Mu¨", "ller", "&", "Ba¨", "rnighausen", "(1970).", "For", "graph-", "set", "notation,", "see:", "Bernstein", "et", "al.", "(1995).", "Experimental", "Crystal", "data", "C8H9N5O2S", "Mr", "=", "239.26", "Triclinic,", "P1", "a", "=", "6.8986", "(2)", "A˚", "b", "=", "7.2146", "(2)", "A˚", "c", "=", "11.3771", "(3)", "A˚", "=", "92.244", "(1)", "=", "93.615", "(1)", "=", "110.505", "(1)", "V", "=", "528.18", "(3)", "A˚3", "Z", "=", "2", "Mo", "K", "radiation", "=", "0.30", "mm", "1", "T", "=", "296", "K", "0.34", "0.17", "0.17", "mm", "Data", "collection", "Bruker", "APEXII", "CCD", "diffractometer", "8664", "measured", "reflections", "Refinement", "R[F2", ">", "2", "(F2)]", "=", "0.031", "wR(F2)", "=", "0.088", "S", "=", "1.09", "2549", "reflections", "152", "parameters", "Table", "1", "Hydrogen-bond", "geometry", "(A˚", ",", ").", "D—H", "A", "N2—H2N", "N2—H3N", "N2—H2N", "O2i", "O1ii", "O2", "D—H", "0.80", "(2)", "0.89", "(2)", "0.80", "(2)", "H", "A", "2.24", "(2)", "2.08", "(2)", "2.34", "(2)", "Symmetry", "codes:", "(i)", "x", "þ", "2;", "y;", "z;", "(ii)", "x;", "y", "1;", "z.", "2549", "independent", "reflections", "2343", "reflections", "with", "I", ">", "2", "(I)", "Rint", "=", "0.020", "H", "atoms", "treated", "by", "a", "mixture", "of", "independent", "and", "constrained", "refinement", "max", "=", "0.30", "e", "A˚", "3", "min", "=", "0.29", "e", "A˚", "3", "D", "A", "2.9459", "(16)", "2.9481", "(15)", "2.8862", "(16)", "D—H", "A", "148", "(2)", "164", "(2)", "127", "(2)", "Data", "collection:", "APEX2", "(Bruker,", "2007);", "cell", "refinement:", "SAINT", "(Bruker,", "2007);", "data", "reduction:", "SAINT;", "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);", "software", "used", "to", "prepare", "material", "for", "publication:", "WinGX", "(Farrugia,", "1999).", "The", "authors", "acknowledge", "the", "Higher", "Education", "Commis-", "sion", "of", "Pakistan", "for", "the", "purchase", "of", "the", "diffractometer", "under", "the", "grant", "to", "strengthen", "the", "Materials", "Chemistry", "Laboratory", "at", "GC", "University,", "Lahore,", "and", "thank", "Dr", "Sohail", "Anjum", "Shehzad", "for", "helpful", "discussions.", "Supplementary", "data", "and", "figures", "for", "this", "paper", "are", "available", "from", "the", "IUCr", "electronic", "archives", "(Reference:", "PV2426).", "References", "Arshad,", "M.", "N.,", "Khan,", "I.", "U.", "&", "Zia-ur-Rehman,", "M.", "(2008).", "Acta", "Cryst.", "E64,", "o2283–o2284.", "Arshad,", "M.", "N.,", "Tahir,", "M.", "N.,", "Khan,", "I.", "U.,", "Siddiqui,", "W.", "A.", "&", "Shafiq,", "M.", "(2009).", "Acta", "Cryst.", "E65,", "o281.", "Bernstein,", "J.,", "Davis,", "R.", "E.,", "Shimoni,", "L.", "&", "Chang,", "N.-L.", "(1995).", "Angew.", "Chem.", "Int.", "Ed.", "Engl.", "34,", "1555–1573.", "Bruker", "(2007).", "SADABS,", "APEX2", "and", "SAINT.", "Bruker", "AXS", "Inc.,", "Madison,", "Wisconsin,", "USA.", "Denny,", "G.", "H.,", "Crageo,", "E.", "J.", "Jr", "&", "Rooney,", "C.", "S.", "(1980).", "J.", "Org.", "Chem.", "E45,", "1662–", "1665.", "Farrugia,", "L.", "J.", "(1997).", "J.", "Appl.", "Cryst.", "30,", "565.", "Farrugia,", "L.", "J.", "(1999).", "J.", "Appl.", "Cryst.", "32,", "837–838.", "Gennarti,", "C.,", "Salom,", "B.,", "Potenza,", "D.", "&", "Williams,", "A.", "(1994).", "Angew.", "Chem.", "Int.", "Ed.", "Engl.", "33,", "2067–2069.", "Moree,", "W.", "J.,", "Van", "der", "Marel,", "G.", "A.", "&", "Liskamp,", "R.", "M.", "(1991).", "Tetrahedron", "Lett.", "32,", "409–411.", "Mu¨", "ller,", "U.", "&", "B", "a¨rnighausen,", "H.", "(1970).", "Acta", "Cryst.", "B26,", "1671–1679.", "Sheldrick,", "G.", "M.", "(2008).", "Acta", "Cryst.", "A64,", "112–122.", "‡", "X-ray", "Diffraction", "and", "Physical", "Laboratory,", "Department", "of", "Physics,", "School", "of", "Physical", "Sciences,", "University", "of", "the", "Punjab,", "Quaid-e-Azam", "Campus,", "Lahore", "54590,", "Pakistan.", "o2140", "Mahmood", "et", "al.", "doi:10.1107/S1600536811026973", "Acta", "Cryst.", "(2011).", "E67,", "o2140" ]

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[ "HUMAN", "NEUROSCIENCE", "Repetition", "enhancement", "and", "perceptual", "processing", "of", "visual", "word", "form", "Karine", "Lebreton", "1,2,3,4*†,", "Nicolas", "Villain", "1,2,3,4†,", "Gaël", "Chételat", "1,2,3,4,", "Brigitte", "Landeau", "1,2,3,4,", "Mohamed", "L.", "Seghier", "5,6,", "François", "Lazeyras", "5,", "Francis", "Eustache", "1,2,3,4", "and", "Vicente", "Ibanez", "7", "1", "INSERM,", "U1077,", "Caen,", "France", "2", "Université", "de", "Caen", "Basse-Normandie,", "UMR-S1077,", "Caen,", "France", "3", "Ecole", "Pratique", "des", "Hautes", "Etudes,", "UMR-S1077,", "Caen,", "France", "4", "CHU", "de", "Caen,", "U1077,", "Caen,", "France", "5", "Department", "of", "Radiology,", "University", "Hospitals", "of", "Geneva,", "Geneva,", "Switzerland", "6", "Wellcome", "Trust", "Centre", "for", "Neuroimaging,", "Institute", "of", "Neurology,", "UCL,", "London,", "UK", "7", "Psychiatric", "Neuroimaging", "Unit,", "Division", "of", "Neuropsychiatry,", "Department", "of", "Psychiatry,", "University", "Hospitals", "of", "Geneva,", "Geneva,", "Switzerland", "ORIGINAL", "RESEARCH", "ARTICLE", "published:", "12", "July", "2012", "doi:", "10.3389/fnhum.2012.00206", "Edited", "by:", "David", "Bartrés-Faz,", "University", "of", "Barcelona,", "Spain", "Reviewed", "by:", "Arun", "Bokde,", "Ludwig-Maximilian", "University,", "Germany", "Alfonso", "Barrós-Loscertales,", "Universitat", "Jaume", "I,", "Spain", "*Correspondence:", "Karine", "Lebreton,", "Unité", "de", "Recherche", "U1077,", "GIP", "Cyceron,", "Bd", "H.", "Becquerel,", "BP", "5229,", "Caen", "Cedex,", "14074,", "France.", "e-mail:", "lebreton@cyceron.fr", "†These", "authors", "contributed", "equally", "to", "this", "work.", "The", "current", "study", "investigated", "the", "cerebral", "basis", "of", "word", "perceptual", "repetition", "priming", "with", "fMRI", "during", "a", "letter", "detection", "task", "that", "manipulated", "the", "familiarity", "of", "perceptual", "word", "form", "and", "the", "number", "of", "repetitions.", "Some", "neuroimaging", "studies", "have", "reported", "increases,", "instead", "of", "decreases,", "in", "brain", "activations", "(called", "“repetition", "enhancement”)", "associated", "with", "repetition", "priming", "of", "unfamiliar", "stimuli", "which", "have", "been", "interpreted", "as", "the", "creation", "of", "new", "perceptual", "representations", "for", "unfamiliar", "items.", "According", "to", "this", "interpretation,", "several", "repetitions", "of", "unfamiliar", "items", "would", "then", "be", "necessary", "for", "the", "repetition", "priming", "to", "occur,", "a", "hypothesis", "not", "explicitly", "tested", "in", "prior", "studies.", "In", "the", "present", "study,", "using", "a", "letter", "detection", "task", "on", "briefly", "flashed", "words,", "we", "explored", "the", "effect", "of", "familiarity", "on", "brain", "response", "for", "word", "visual", "perceptual", "priming", "using", "both", "words", "with", "usual", "(i.e.,", "familiar)", "and", "unusual", "(i.e.,", "unfamiliar)", "font,", "presented", "up", "to", "four", "times", "for", "stimuli", "with", "unusual", "font.", "This", "allows", "potential", "changes", "in", "the", "brain", "responses", "for", "unfamiliar", "items", "to", "be", "assessed", "over", "several", "repetitions,", "i.e.,", "repetition", "enhancement", "to", "suppression.", "Our", "results", "reveal", "significant", "increases", "of", "activity", "in", "the", "bilateral", "occipital", "areas", "related", "to", "repetition", "of", "words", "in", "both", "familiar", "and", "unfamiliar", "conditions.", "Our", "findings", "support", "the", "sharpening", "hypothesis,", "showing", "a", "lack", "of", "cerebral", "economy", "with", "repetition", "when", "the", "task", "requires", "the", "processing", "of", "all", "word", "features,", "whatever", "the", "familiarity", "of", "the", "material,", "and", "emphasize", "the", "influence", "of", "the", "nature", "of", "stimuli", "processing", "on", "its", "neuronal", "manifestation.", "Keywords:", "priming,", "fMRI,", "repetition", "suppression,", "repetition", "enhancement,", "sharpening,", "visual", "processing", "INTRODUCTION", "Priming", "is", "generally", "defined", "as", "an", "improvement", "or", "a", "change", "in", "the", "identification,", "production", "or", "classification", "of", "a", "stimulus", "as", "a", "result", "of", "a", "prior", "encounter", "with", "the", "same", "or", "a", "similar", "stimulus", "(Tulving", "and", "Schacter,", "1990;", "Schacter", "and", "Buckner,", "1998;", "Wiggs", "and", "Martin,", "1998;", "Henson,", "2003;", "Schacter", "et", "al.,", "2007).", "It", "rep-", "resents", "an", "implicit", "form", "of", "memory", "which", "occurs", "even", "in", "the", "absence", "of", "conscious", "remembering", "and", "it", "may", "reflect", "a", "memory", "system", "distinct", "from", "explicit", "memory", "(Graf", "and", "Schacter,", "1985;", "Gabrieli,", "1998;", "Henson,", "2003).", "From", "a", "multi-system", "memory", "point", "of", "view,", "two", "kinds", "of", "repetition", "priming", "have", "been", "distin-", "guished,", "depending", "on", "two", "distinct", "memory", "systems:", "perceptual", "and", "conceptual", "(or", "semantic)", "priming.", "Perceptual", "priming", "(the", "focus", "of", "the", "present", "study)", "is", "based", "on", "the", "perceptual", "or", "phys-", "ical", "representations", "of", "stimuli", "and", "is", "thought", "to", "depend", "on", "a", "perceptual", "representation", "system", "or", "perceptual", "memory,", "which", "stores", "and", "processes", "perceptual,", "but", "not", "semantic,", "features", "of", "items", "(Tulving", "and", "Schacter,", "1990;", "Tulving,", "1995;", "Eustache", "and", "Desgranges,", "2008).", "Perceptual", "repetition", "priming", "is", "often", "assessed", "using", "identification", "tasks", "of", "degraded", "items", "or", "briefly", "flashed", "stimuli", "which", "are", "supposed", "to", "further", "solicit", "the", "perceptual", "mem-", "ory", "(Brown", "et", "al.,", "1996;", "Berry", "et", "al.,", "1997;", "Lebreton", "et", "al.,", "2001;", "Gagnepain", "et", "al.,", "2008,", "2011).", "This", "repetition-based", "processing", "facilitation", "has", "been", "asso-", "ciated", "with", "reductions", "in", "neural", "activity", "when", "an", "experience", "is", "repeated.", "Several", "functional", "neuroimaging", "studies", "have", "con-", "sistently", "revealed", "a", "decrease", "in", "haemodynamic", "responses", "for", "repeated", "(primed)", "relative", "to", "unrepeated", "(unprimed)", "stimuli.", "This", "repetition-based", "neural", "change", "has", "been", "assigned", "numer-", "ous", "terms", "such", "as", "adaptation,", "repetition", "suppression", "or", "neural", "priming", "(for", "review", "see", "Grill-Spector", "et", "al.,", "2006),", "and", "has", "been", "observed", "within", "a", "set", "of", "specific", "cortical", "regions", "(Schacter", "et", "al.,", "1998,", "2004,", "2007;", "Schacter", "and", "Badgaiyan,", "2001;", "Henson,", "2003),", "depending", "on", "the", "type", "of", "stimulus", "(visual", "or", "auditory", "word,", "object,", "face,", "symbol.", ".", ".)", "and", "on", "the", "nature", "of", "representations", "across", "different", "stages", "of", "a", "processing", "stream", "(perceptual", "or", "con-", "ceptual).", "For", "example,", "repetition-related", "reductions", "associated", "with", "perceptual", "behavioral", "priming", "were", "reported", "in", "brain", "areas", "that", "are", "significantly", "active", "for", "novel", "items", "(or", "for", "the", "first", "pre-", "sentation", "of", "item),", "and", "that", "are", "known", "to", "be", "involved", "in", "early", "Frontiers", "in", "Human", "Neuroscience", "www.frontiersin.org", "July", "2012", "|", "Volume", "6", "|", "Article", "206", "|", "1" ]

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[ "Latexin", "Is", "Down-Regulated", "in", "Hematopoietic", "Malignancies", "and", "Restoration", "of", "Expression", "Inhibits", "Lymphoma", "Growth", "Yi", "Liu2,", "Dianna", "Howard1,", "Kyle", "Rector2,", "Carol", "Swiderski1,", "Jason", "Brandon3,", "Lawrence", "Schook4,", "Jayesh", "Mehta5,", "J.", "Scott", "Bryson1,3,", "Subbarao", "Bondada3,", "Ying", "Liang", "1", "*", "1", "Department", "of", "Internal", "Medicine,", "University", "of", "Kentucky", "College", "of", "Medicine,", "Lexington,", "Kentucky,", "United", "States", "of", "America,", "2", "Department", "of", "Physiology,", "University", "of", "Kentucky", "College", "of", "Medicine,", "Lexington,", "Kentucky,", "United", "States", "of", "America,", "3", "Department", "of", "Microbiology,", "Immunology", "and", "Molecular", "Genetics,", "University", "of", "Kentucky", "College", "of", "Medicine,", "Lexington,", "Kentucky,", "United", "States", "of", "America,", "4", "Department", "of", "Animal", "Sciences,", "University", "of", "Illinois,", "Urbana,", "Illinois,", "United", "States", "of", "America,", "5", "Department", "of", "Medicine,", "The", "Feinberg", "School", "of", "Medicine,", "Northwestern", "University,", "Chicago,", "Illinois,", "United", "States", "of", "America", "Abstract", "Latexin", "is", "a", "negative", "regulator", "of", "hematopoietic", "stem", "cell", "number", "in", "mice.", "Its", "dysregulated", "expression", "in", "other", "tumors", "led", "us", "to", "hypothesize", "that", "latexin", "may", "have", "tumor", "suppressor", "properties", "in", "hematological", "malignancies.", "We", "found", "that", "latexin", "was", "down-regulated", "in", "a", "variety", "of", "leukemia", "and", "lymphoma", "cell", "lines", "as", "well", "as", "in", "CD34+", "cells", "from", "the", "blood", "and", "marrow", "of", "patients", "with", "these", "malignancies.", "5-aza-29-deoxycytodine", "treatment", "and", "bisulfite", "sequencing", "revealed", "hypermethylation", "of", "latexin", "promoter", "in", "tumor", "cells.", "Retrovirus-mediated", "latexin", "overexpression", "in", "A20", "mouse", "lymphoma", "cells", "inhibited", "their", "in", "vitro", "growth", "by", "16", "fold", "and", "in", "vivo", "tumor", "volume", "by", "2", "fold.", "Latexin", "caused", "growth", "inhibition", "of", "lymphoma", "cells", "by", "significantly", "increasing", "apoptosis", "through", "the", "down-regulation", "of", "anti-apoptotic", "genes", "Bcl-2", "and", "Pim-2.", "The", "molecular", "mechanism", "underlying", "latexin-mediated", "tumor", "inhibition", "was", "not", "through", "its", "canonical", "carboxypeptidase", "inhibitor", "activity.", "These", "results", "are", "consistent", "with", "a", "tumor", "suppressor", "role", "for", "latexin", "and", "suggest", "that", "latexin", "may", "have", "clinical", "efficacy", "in", "the", "treatment", "of", "malignancies.", "Citation:", "Liu", "Y,", "Howard", "D,", "Rector", "K,", "Swiderski", "C,", "Brandon", "J,", "et", "al.", "(2012)", "Latexin", "Is", "Down-Regulated", "in", "Hematopoietic", "Malignancies", "and", "Restoration", "of", "Expression", "Inhibits", "Lymphoma", "Growth.", "PLoS", "ONE", "7(9):", "e44979.", "doi:10.1371/journal.pone.0044979", "Editor:", "Ilya", "Ulasov,", "University", "of", "Chicago,", "United", "States", "of", "America", "Received", "April", "30,", "2012;", "Accepted", "August", "16,", "2012;", "Published", "September", "27,", "2012", "Copyright:", "2012", "Liu", "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", "American", "Cancer", "Society", "ACS178898", "(to", "YL)", "and", "BD", "Biosciences", "Research", "Grant", "Award", "(to", "YL)", "and", "the", "support", "of", "The", "Edward", "P.", "Evans", "Foundation.", "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:", "ying.liang@uky.edu", "Introduction", "Both", "solid", "and", "liquid", "tumors", "are", "now", "understood", "to", "originate", "from", "the", "malignant", "transformation", "of", "resident", "adult", "stem", "and", "progenitor", "cells.", "[1,2]", "Nowhere", "is", "this", "paradigm", "better", "established", "than", "in", "leukemia,", "yet", "events", "causing", "neoplastic", "conversion", "remain", "poorly", "understood.", "[3]", "We", "identified", "latexin", "(Lxn)", "as", "a", "novel,", "homeostatic", "regulator", "of", "the", "size", "of", "the", "hematopoietic", "stem", "cell", "population", "in", "mice.", "[4]", "The", "stem", "cell", "pool", "size", "was", "inversely", "related", "to", "quantitative", "Lxn", "expression", "at", "both", "the", "levels", "of", "transcript", "and", "protein.", "We", "found", "that", "population", "size", "was", "influenced", "by", "Lxn", "in", "a", "stem", "cell-autonomous", "manner,", "and", "acting", "through", "the", "concerted", "mechanisms", "of", "self-renewal", "and", "apoptosis,", "which", "were", "decreased", "and", "increased,", "respectively,", "by", "Lxn", "abundance.", "[4]", "Thus,", "Lxn", "acts", "as", "a", "brake", "on", "the", "expansion", "of", "stem", "cell", "population.", "Unrestrained", "stem", "cell", "expansion", "carries", "with", "it", "the", "risk", "of", "mutations,", "genomic", "instability", "and", "carcinogenesis.", "We", "therefore", "hypothesized", "that", "Lxn", "expression", "patterns", "in", "stem", "and", "progenitor", "cells", "may", "act", "as", "a", "tumor", "suppressor", "by", "inhibiting", "stem", "and", "progenitor", "cell", "proliferation,", "influencing", "the", "crucial", "steps", "toward", "malignancy.", "Lxn", "was", "primarily", "studied", "in", "the", "nervous", "system,", "involving", "the", "specification", "of", "cortical", "brain", "regions", "during", "development", "[5,6,7,8,9],", "as", "well", "as", "the", "speed", "of", "nerve", "transmission", "in", "adult", "peripheral", "nervous", "systems", "[10].", "Lxn", "was", "found", "to", "be", "involved", "in", "the", "inflammatory", "response", "in", "macrophages", "owing", "to", "its", "paired", "cystatin-like", "domains", "[11].", "It", "was", "detected", "in", "mast", "cells", "associated", "with", "a", "unique", "type", "of", "intracellular", "granule", "distinct", "from", "histamine-", "containing", "secretory", "granules", "and", "lysosomes", "[12].", "Lxn", "has", "about", "30%", "sequence", "homology,", "but", "much", "greater", "structural", "homology,", "with", "tazarotene-induced", "gene", "1", "(TIG1)", "(or", "retinoic", "acid", "receptor", "responder", "1,", "RARRES1),", "whose", "expression", "was", "down-regulated", "in", "an", "extensive", "list", "of", "tumor", "types", "in", "humans.", "[11,13,14,15,16].", "Lxn", "and", "TIG1", "are", "closely", "linked", "genetically", "and", "may", "represent", "members", "of", "a", "family", "of", "functionally", "related", "genes.", "Moreover,", "Lxn", "was", "reported", "to", "be", "a", "TNF-responsive", "gene", "in", "human", "papillovirus-infected", "keratinocytes,", "suggesting", "that", "it", "may", "contrib-", "ute", "to", "TNF-mediated", "suppression", "of", "cervical", "cancer", "development", "[17].", "A", "recent", "report", "revealed", "that", "Lxn", "was", "down-regulated", "in", "patients", "with", "gastric", "carcinomas,", "and", "overexpression", "or", "knock-", "down", "of", "Lxn", "inhibited", "or", "stimulated", "tumor", "growth", "respectively", "[18].", "Decreased", "or", "absent", "Lxn", "expression", "was", "observed", "in", "several", "human", "leukemia", "and", "lymphoma", "cell", "lines", "[19],", "as", "well", "as", "in", "malignant", "melanoma", "patients.", "[20]", "However,", "there", "is", "still", "lack", "of", "direct", "evidence", "for", "the", "cause-effect", "relationship", "between", "Lxn", "and", "hematopoietic", "malignancy.", "Gene", "silencing,", "especially", "of", "tumor", "suppressors,", "and", "inappro-", "priate", "gene", "activation,", "especially", "of", "oncogenes,", "are", "common", "PLOS", "ONE", "|", "www.plosone.org", "1", "September", "2012", "|", "Volume", "7", "|", "Issue", "9", "|", "e44979" ]

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[ "O", "R", "I", "G", "I", "N", "A", "L", "R", "E", "S", "E", "A", "R", "C", "H", "Impairment", "of", "small", "airways", "in", "COPD", "patients", "with", "frequent", "exacerbations", "and", "effects", "of", "treatment", "with", "tiotropium", "Cristoforo", "Incor", "vaia1", "Gian", "Galeazzo", "Riario-", "Sforza1", "Chiara", "Pravettoni1", "Mona-Rita", "Yacoub2", "Franco", "Frati3", "1Pulmonary", "Rehabilitation", "Unit,", "ICP", "Hospital,", "Milan,", "Italy;", "2Allergy", "and", "Rheumatology", "Unit,", "IRCCS", "San", "Raffaele", "Hospital,", "Milan,", "Italy;", "3Institute", "of", "Pediatrics,", "Department", "of", "Medical", "and", "Surgical", "specialty", "and", "Public", "Health,", "University", "of", "Perugia,", "Policlinico", "Monteluce,", "Perugia,", "Italy", "Correspondence:", "Cristoforo", "Incorvaia", "Viale", "Molise", "69,", "20137", "Milano,", "Italy", "Tel/Fax", "+39", "2", "5513852", "Email", "cristoforo.incorvaia@fastwebnet.it", "Abstract:", "Disease", "exacerbations", "are", "an", "important", "aspect", "of", "COPD,", "because", "they", "affect", "its", "course", "and", "are", "associated", "with", "higher", "lung", "function", "decline.", "On", "the", "other", "hand,", "data", "obtained", "by", "biopsies", "have", "demonstrated", "that", "the", "progression", "of", "COPD", "is", "related", "to", "an", "increasing", "impairment", "of", "small", "airways.", "We", "sought", "to", "evaluate", "the", "small", "airway", "impairment", "(FEF25–75)", "in", "two", "groups", "of", "COPD", "patients", "(each", "group", "had", "37", "subjects)", "in", "relation", "to", "the", "frequency", "of", "exacerbations", "and", "the", "effective-", "ness", "of", "treatment", "with", "tiotropium", "bromide", "on", "the", "small", "airway", "impairment.", "The", "mean", "number", "of", "exacerbations", "was", "3.6/year", "and", "1.38/year", "in", "frequent", "and", "in", "infrequent", "exacerbators,", "respectively", "(p", "0.001).", "The", "mean", "value", "of", "FEF25–75", "at", "baseline", "was", "624", "mL", "and", "865", "mL", "in", "frequent", "and", "in", "infrequent", "exacerbators", "respectively", "(p", "=", "0.002).", "The", "changes", "in", "respiratory", "parameters", "ver-", "sus", "baseline", "showed", "increases", "in", "mean", "FEV1,", "FVC,", "and", "FEF25–75", "in", "both", "groups", "but", "only", "the", "increase", "in", "FEF25–75", "in", "frequent", "exacerbators", "was", "statistically", "significantly", "(p", "=", "0.013).", "During", "the", "3-month", "period", "of", "the", "study", "the", "mean", "number", "of", "exacerbations", "was", "0.66", "in", "frequent", "and", "0.12", "in", "infrequent", "exacerbators.", "These", "findings", "indicate", "that", "COPD", "patients", "with", "frequent", "exacerbations", "have", "a", "higher", "impairment", "of", "small", "airways.", "Treatment", "with", "tiotropium", "in", "COPD", "subjects", "with", "frequent", "exacerbations", "proved", "to", "be", "effective", "in", "improving", "small", "airway", "impairment.", "Keywords:", "COPD,", "exacerbations,", "small", "airways,", "FEF25–75,", "tiotropium", "Introduction", "Chronic", "obstructive", "pulmonary", "disease", "(COPD)", "is", "a", "major", "health", "problem.", "It", "is", "char-", "acterized", "by", "a", "progressive", "impairment", "of", "lung", "function", "(Barnes", "2000)", "and", "leads", "to", "inability", "and", "mortality,", "which", "are", "projected", "to", "increase", "their", "burden", "in", "future", "(Murray", "and", "Lopez", "1997).", "This", "makes", "the", "treatment", "strategies", "for", "COPD", "very", "important,", "cur-", "rently", "stated", "as", "mainly", "smoking", "cessation,", "drug", "therapy,", "and", "pulmonary", "rehabilitation", "(Sutherland", "and", "Cherniak", "2004).", "An", "important", "aspect", "of", "COPD", "is", "the", "exacerbations,", "which", "occur", "regardless", "of", "the", "stage", "of", "disease", "according", "to", "GOLD", "classification", "(Pauwels", "et", "al", "2004;", "Rabe", "et", "al", "2007),", "and", "is", "currently", "defined", "as", "“...", "a", "sustained", "worsening", "of", "the", "patient’s", "symptoms", "from", "his", "or", "her", "usual", "stable", "state", "that", "is", "beyond", "normal", "day", "to", "day", "variations,", "and", "is", "acute", "in", "onset.", "Commonly", "reported", "symptoms", "are", "worsening", "breathlessness,", "cough,", "increased", "sputum", "production", "and", "change", "in", "sputum", "color.", "The", "change", "in", "these", "symptoms", "often", "necessitates", "a", "change", "in", "medication.”", "(The", "National", "Collaborating", "Centre", "for", "Chronic", "Conditions", "2004).", "Exacerbations", "clearly", "affect", "the", "course", "of", "the", "disease,", "since", "their", "frequency", "is", "related", "to", "lung", "function", "decline", "(Donaldson", "et", "al", "2002).", "In", "particular,", "data", "obtained", "by", "biopsies", "demonstrated", "that", "the", "progression", "of", "COPD", "is", "associated", "with", "an", "increasing", "impairment", "of", "small", "airways", "which", "is", "strongly", "related", "to", "infiltration", "of", "inflammatory", "cells", "in", "airways", "walls", "and", "accumulation", "of", "exudate", "in", "the", "lumen", "(Hogg", "et", "al", "2004).", "International", "Journal", "of", "COPD", "2008:3(1)", "123–126", "©", "2008", "Incorvaia", "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.", "123" ]

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[ "Martin", "et", "al.", "BMC", "Bioinformatics", "2010,", "11:91", "http://www.biomedcentral.com/1471-2105/11/91", "S", "O", "F", "T", "W", "A", "R", "E", "Open", "Access", "BisoGenet:", "a", "new", "tool", "for", "gene", "network", "building,", "visualization", "and", "analysis", "Alexander", "Martin,", "Maria", "E", "Ochagavia,", "Laya", "C", "Rabasa,", "Jamilet", "Miranda,", "Jorge", "Fernandez-de-Cossio,", "Ricardo", "Bringas*", "Abstract", "Background:", "The", "increasing", "availability", "and", "diversity", "of", "omics", "data", "in", "the", "post-genomic", "era", "offers", "new", "perspectives", "in", "most", "areas", "of", "biomedical", "research.", "Graph-based", "biological", "networks", "models", "capture", "the", "topology", "of", "the", "functional", "relationships", "between", "molecular", "entities", "such", "as", "gene,", "protein", "and", "small", "compounds", "and", "provide", "a", "suitable", "framework", "for", "integrating", "and", "analyzing", "omics-data.", "The", "development", "of", "software", "tools", "capable", "of", "integrating", "data", "from", "different", "sources", "and", "to", "provide", "flexible", "methods", "to", "reconstruct,", "represent", "and", "analyze", "topological", "networks", "is", "an", "active", "field", "of", "research", "in", "bioinformatics.", "Results:", "BisoGenet", "is", "a", "multi-tier", "application", "for", "visualization", "and", "analysis", "of", "biomolecular", "relationships.", "The", "system", "consists", "of", "three", "tiers.", "In", "the", "data", "tier,", "an", "in-house", "database", "stores", "genomics", "information,", "protein-protein", "interactions,", "protein-DNA", "interactions,", "gene", "ontology", "and", "metabolic", "pathways.", "In", "the", "middle", "tier,", "a", "global", "network", "is", "created", "at", "server", "startup,", "representing", "the", "whole", "data", "on", "bioentities", "and", "their", "relationships", "retrieved", "from", "the", "database.", "The", "client", "tier", "is", "a", "Cytoscape", "plugin,", "which", "manages", "user", "input,", "communication", "with", "the", "Web", "Service,", "visualization", "and", "analysis", "of", "the", "resulting", "network.", "Conclusion:", "BisoGenet", "is", "able", "to", "build", "and", "visualize", "biological", "networks", "in", "a", "fast", "and", "user-friendly", "manner.", "A", "feature", "of", "Bisogenet", "is", "the", "possibility", "to", "include", "coding", "relations", "to", "distinguish", "between", "genes", "and", "their", "products.", "This", "feature", "could", "be", "instrumental", "to", "achieve", "a", "finer", "grain", "representation", "of", "the", "bioentities", "and", "their", "relationships.", "The", "client", "application", "includes", "network", "analysis", "tools", "and", "interactive", "network", "expansion", "capabilities.", "In", "addition,", "an", "option", "is", "provided", "to", "allow", "other", "networks", "to", "be", "converted", "to", "BisoGenet.", "This", "feature", "facilitates", "the", "integration", "of", "our", "software", "with", "other", "tools", "available", "in", "the", "Cytoscape", "platform.", "BisoGenet", "is", "available", "at", "http://bio.cigb.edu.cu/", "bisogenet-cytoscape/.", "Background", "Network", "representation", "of", "relationships", "among", "biomole-", "cules", "is", "an", "intensive", "field", "of", "research", "of", "in", "silico", "System", "Biology.", "New", "models", "for", "data", "integration,", "standard", "spe-", "cifications", "for", "data", "exchange", "and", "the", "development", "of", "new", "tools", "for", "data", "visualization", "and", "analysis", "are", "crucial", "and", "represent", "one", "of", "the", "most", "challenging", "tasks", "for", "bioinformaticians.", "Data", "repositories", "such", "as", "NCBI’s", "Entrez", "Gene[1]", "and", "Ensembl[2]", "maintain", "annotation", "on", "whole", "genomes,", "including", "sequences,", "gene", "location,", "transcripts,", "classifi-", "cation", "and", "links", "to", "several", "external", "databases.", "Data", "retrieved", "from", "high-throughput", "experiments", "and", "litera-", "ture", "are", "available", "from", "several", "databases,", "such", "as,", "DIP", "*", "Correspondence:", "bringas@cigb.edu.cu", "Center", "for", "Genetic", "Engineering", "and", "Biotechnology,", "PO", "BOX", "6162,", "Havana,", "Cuba", "[3],", "BIND[4],", "HPRD[5],", "BioGRID[6],", "MINT[7]", "and", "Intact[8],", "which", "represent", "the", "major", "repositories", "of", "pro-", "tein-protein", "interacions", "from", "multiple", "organisms.", "On", "the", "other", "hand", "databases", "like", "KEGG[9],", "Reactome[10],", "BioCyc[11],", "NCI", "Nature", "PID[12]", "and", "others", "provide", "information", "on", "both", "metabolic", "and", "signaling", "pathways.", "These", "databanks", "can", "be", "seen", "as", "repositories", "of", "biological", "entities", "and", "their", "functional", "relations.", "As", "the", "amount", "of", "biological", "data", "increase,", "software", "tools", "able", "to", "visualize", "biological-meaningful", "abstract", "representations", "of", "these", "data", "at", "different", "levels", "of", "details", "are", "valuable", "to", "biologists.", "Graph-based", "model", "has", "shown", "to", "be", "a", "convenient", "model", "for", "representing", "the", "global", "picture", "of", "protein-pro-", "tein", "interactions,", "transcription", "regulation,", "metabolic", "data", "and", "gene", "co-expression.", "In", "this", "model,", "bio-entities", "are", "represented", "as", "nodes", "in", "a", "graph,", "and", "functional", "relations", "©", "2010", "Martin", "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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[ "PLoS", "BIOLOGY", "Expanding", "the", "Neuron’s", "Calcium", "Signaling", "Repertoire:", "Intracellular", "Calcium", "Release", "via", "Voltage-Induced", "PLC", "and", "IP3R", "Activation", "Stefanie", "Ryglewski1,", "Hans", "J.", "Pflueger1,", "Carsten", "Duch2*", "1", "Institute", "of", "Biology/Neurobiology,", "Free", "University", "of", "Berlin,", "Berlin,", "Germany,", "2", "School", "of", "Life", "Sciences,", "Arizona", "State", "University,", "Tempe,", "Arizona,", "United", "States", "of", "America", "Neuronal", "calcium", "acts", "as", "a", "charge", "carrier", "during", "information", "processing", "and", "as", "a", "ubiquitous", "intracellular", "messenger.", "Calcium", "signals", "are", "fundamental", "to", "numerous", "aspects", "of", "neuronal", "development", "and", "plasticity.", "Specific", "and", "independent", "regulation", "of", "these", "vital", "cellular", "processes", "is", "achieved", "by", "a", "rich", "bouquet", "of", "different", "calcium", "signaling", "mechanisms", "within", "the", "neuron,", "which", "either", "can", "operate", "independently", "or", "may", "act", "in", "concert.", "This", "study", "demonstrates", "the", "existence", "of", "a", "novel", "calcium", "signaling", "mechanism", "by", "simultaneous", "patch", "clamping", "and", "calcium", "imaging", "from", "acutely", "isolated", "central", "neurons.", "These", "neurons", "possess", "a", "membrane", "voltage", "sensor", "that,", "independent", "of", "calcium", "influx,", "causes", "G-protein", "activation,", "which", "subsequently", "leads", "to", "calcium", "release", "from", "intracellular", "stores", "via", "phospholipase", "C", "and", "inositol", "1,4,5-trisphosphate", "receptor", "activation.", "This", "allows", "neurons", "to", "monitor", "activity", "by", "intracellular", "calcium", "release", "without", "relying", "on", "calcium", "as", "the", "input", "signal", "and", "opens", "up", "new", "insights", "into", "intracellular", "signaling,", "developmental", "regulation,", "and", "information", "processing", "in", "neuronal", "compartments", "lacking", "calcium", "channels.", "Citation:", "Ryglewski", "S,", "Pflueger", "HJ,", "Duch", "C", "(2007)", "Expanding", "the", "neuron’s", "calcium", "signaling", "repertoire:", "Intracellular", "calcium", "release", "via", "voltage-induced", "PLC", "and", "IP3R", "activation.", "PLoS", "Biol", "5(4):", "e66.", "doi:10.1371/journal.pbio.0050066", "Introduction", "Neuronal", "calcium", "plays", "a", "dual", "role", "as", "a", "charge", "carrier", "and", "as", "an", "intracellular", "messenger.", "Calcium", "signals", "regulate", "various", "developmental", "processes,", "such", "as", "migration", "in", "the", "central", "nervous", "system", "(CNS)", "[1],", "growth-cone", "behavior", "[2],", "dendritic", "development", "[3,4],", "and", "synaptogenesis", "[5],", "but", "calcium", "is", "also", "involved", "in", "apoptosis", "[6],", "and", "it", "regulates", "neurotransmitter", "release", "and", "membrane", "excitability", "[7].", "How", "can", "one", "ubiquitous", "intracellular", "messenger", "regulate", "so", "many", "different", "vital", "processes", "in", "parallel,", "but", "independently?", "The", "answer", "lies", "in", "the", "versatility", "of", "the", "calcium", "signaling", "mechanisms", "in", "terms", "of", "amplitude", "and", "spatiotemporal", "patterning", "within", "a", "neuron", "[8],", "and", "the", "present", "study", "adds", "a", "novel", "mechanism", "to", "the", "bouquet", "of", "neuronal", "calcium", "signals.", "The", "neuronal", "plasma", "membrane", "contains", "numerous", "voltage-operated", "(VOCs),", "receptor-operated", "(ROCs)", "and", "store-operated", "(SOCs)", "calcium", "channels", "carrying", "out", "differ-", "ent", "functions", "in", "different", "parts", "of", "the", "cell.", "For", "example,", "in", "vertebrate", "neurons,", "N-", "and", "P/Q-type", "VOCs", "trigger", "vesicle", "fusion", "at", "synaptic", "terminals,", "whereas", "L-type", "VOCs", "are", "located", "proximally", "to", "provide", "calcium", "signals", "regulating", "gene", "tran-", "scription.", "Structural", "plasticity", "of", "dendrites", "and", "filopodia", "is", "mediated", "via", "calcium", "influx", "through", "VOCs", "and", "ROCs", "and", "also", "by", "local", "release", "from", "internal", "stores", "[5,9].", "Internal", "calcium", "stores", "are", "held", "within", "the", "membrane", "system", "of", "the", "endoplasmic", "reticulum", "(ER).", "Release", "from", "the", "ER", "is", "mediated", "by", "the", "inositol", "1,4,5-trisphosphate", "receptor", "(IP3R)", "and", "the", "ryanodine", "receptor", "(RYR)", "families,", "both", "of", "which", "depend", "on", "the", "concentration", "of", "free", "intracellular", "calcium", "([Ca2þ]i", "[10]).", "The", "patterns", "of", "calcium", "signals", "depend", "on", "the", "distributions", "of", "the", "calcium", "entry", "mechanisms", "and", "calcium-binding", "proteins", "within", "a", "specific", "neuronal", "compartment", "[8].", "Calcium", "buffers,", "such", "as", "parvalbumin", "and", "calbindin,", "can", "locally", "confine", "calcium", "signals", "even", "to", "individual", "synapses", "[11].", "Calcium-sensing", "proteins", "translate", "elevation", "or", "even", "tempo-", "ral", "patterns", "in", "[Ca2þ]i", "into", "diverse", "cellular", "processes", "[7,12].", "In", "summary,", "different", "spatiotemporal", "distributions", "of", "calcium", "signals,", "buffers,", "and", "sensors", "in", "various", "neuronal", "compartments", "allow", "distinct", "calcium", "signals", "to", "be", "assigned", "separately", "to", "specific", "cellular", "processes.", "Conversely,", "multiple", "calcium", "signals", "can", "act", "as", "coincidence", "detectors", "[13].", "Never-", "theless,", "to", "date,", "no", "mechanism", "is", "known", "by", "which", "a", "neuron", "can", "monitor", "its", "own", "activity", "by", "ER", "calcium", "release", "in", "the", "absence", "of", "both", "metabotropic", "receptor", "activation", "and", "calcium", "influx", "from", "the", "extracellular", "space.", "Consequently,", "influx", "and", "store", "activation", "are", "thought", "to", "be", "irrevocably", "linked,", "such", "that", "they", "neither", "operate", "independently", "from", "each", "other,", "nor", "work", "in", "concert", "for", "coincidence", "detection.", "In", "the", "present", "study,", "we", "use", "well-characterized", "and", "identified", "insect", "central", "neurons,", "the", "dorsal", "unpaired", "median", "(DUM)", "neurons,", "as", "a", "model", "to", "analyze", "a", "novel", "calcium-release", "mechanism", "in", "neurons.", "DUM", "neurons", "are", "among", "the", "best-", "studied", "insect", "neurons", "that", "can", "be", "individually", "identified", "in", "culture", "[14,15].", "Therefore,", "they", "are", "well", "suited", "for", "pharmaco-", "logical", "analysis", "of", "cellular", "signaling", "mechanisms.", "We", "demon-", "strate", "the", "existence", "of", "a", "novel", "voltage-dependent,", "but", "not", "Academic", "Editor:", "Nick", "C.", "Spitzer,", "University", "of", "California", "San", "Diego,", "United", "States", "of", "America", "Received", "July", "28,", "2006;", "Accepted", "December", "29,", "2006;", "Published", "March", "6,", "2007", "Copyright:", "2007", "Ryglewski", "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.", "Abbreviations:", "[Ca2þ]i,", "free", "intracellular", "calcium;", "DUM,", "dorsal", "unpaired", "median;", "ER,", "endoplasmic", "reticulum;", "IP3R,", "inositol", "1,4,5-trisphosphate", "receptor;", "PLC,", "phospho-", "lipase", "C;", "RYR,", "ryanodine", "receptor;", "VOC,", "voltage-operated", "calcium", "channel", "*", "To", "whom", "correspondence", "should", "be", "addressed.", "E-mail:", "carsten.duch@asu.edu", "PLoS", "Biology", "|", "www.plosbiology.org", "0818", "April", "2007", "|", "Volume", "5", "|", "Issue", "4", "|", "e66" ]

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[ "Int", "Urogynecol", "J", "(2011)", "22:557–561", "DOI", "10.1007/s00192-010-1353-4", "ORIGINAL", "ARTICLE", "Technique", "of", "anterior", "colporrhaphy:", "a", "Dutch", "evaluation", "Ellen", "J.", "M.", "Lensen", "&", "Jackie", "A.", "Stoutjesdijk", "&", "Mariella", "I.", "J.", "Withagen", "&", "Kirsten", "B.", "Kluivers", "&", "Mark", "E.", "Vierhout", "Received:", "7", "October", "2010", "/", "Accepted:", "16", "December", "2010", "/", "Published", "online:", "25", "February", "2011", "#", "The", "Author(s)", "2011.", "This", "article", "is", "published", "with", "open", "access", "at", "Springerlink.com", "Abstract", "Introduction", "and", "hypothesis", "To", "evaluate", "the", "variation", "in", "techniques", "of", "anterior", "colporrhaphy", "among", "members", "of", "the", "Dutch", "Urogynecologic", "Society.", "Methods", "A", "questionnaire", "evaluating", "the", "technique", "of", "anterior", "colporrhaphy,", "preoperative", "and", "postoperative", "care,", "and", "use", "of", "the", "POP-Q", "score", "was", "sent", "out", "by", "e-mail.", "Results", "One", "hundred", "thirty-three", "completed", "questionnaires", "were", "received.", "The", "response", "rate", "was", "65%.", "There", "are", "large", "variations", "in", "incisions,", "use", "of", "hydrodissection,", "method", "of", "plication,", "and", "excision", "of", "redundant", "vaginal", "epithelium.", "The", "urinary", "catheter", "was", "generally", "removed", "on", "day", "2", "after", "surgery", "and", "the", "vaginal", "pack", "on", "day", "1.", "Less", "than", "half", "of", "the", "respondents", "used", "the", "POP-Q", "score", "routinely.", "Conclusions", "Dutch", "gynecologists", "use", "a", "variety", "of", "surgical", "techniques", "to", "operate", "on", "a", "cystocele.", "This", "suggests", "that", "there", "is", "no", "widely", "accepted", "opinion", "on", "the", "best", "surgical", "approach.", "The", "lack", "of", "differentiation", "between", "central", "and", "lateral", "defects", "is", "striking", "and", "in", "contrast", "with", "the,", "mostly,", "American", "literature.", "Keywords", "Anterior", "colporrhaphy", ".", "Cystocele", ".", "Pelvic", "organ", "prolapse", ".", "POP-Q", "E.", "J.", "M.", "Lensen", ":", "J.", "A.", "Stoutjesdijk", "Obstetrics", "and", "Gynecology,", "Canisius-Wilhelmina", "Hospital,", "Nijmegen,", "Netherlands", "M.", "I.", "J.", "Withagen", ":", "K.", "B.", "Kluivers", ":", "M.", "E.", "Vierhout", "Obstetrics", "and", "Gynecology,", "UMC", "St.", "Radboud,", "Nijmegen,", "Netherlands", "E.", "J.", "M.", "Lensen", "(*)", "Kersenlaan", "45,", "5345", "JL", "Oss,", "The", "Netherlands", "e-mail:", "ellen@lensen.nu", "Abbreviations", "AUGS", "American", "Urogynecologic", "Society", "POP", "Pelvic", "organ", "prolapse", "POP-Q", "Pelvic", "organ", "prolapse", "quantification", "Introduction", "Pelvic", "organ", "prolapse", "(POP)", "is", "known", "to", "affect", "up", "to", "50%", "of", "women", "with", "a", "lifetime", "risk", "of", "undergoing", "surgery", "for", "POP", "or", "incontinence", "of", "11%", "[1].", "Recurrence", "rates", "after", "surgery", "are", "high", "and", "especially", "anterior", "vaginal", "wall", "prolapse", "is", "known", "to", "recur", "frequently,", "with", "recurrence", "rates", "following", "anterior", "colporrhaphy", "anywhere", "between", "0%", "and", "92%", "[2].", "To", "prevent", "recurrence", "of", "a", "cystocele", "after", "repair,", "different", "techniques", "have", "been", "used,", "for", "example", "paravaginal", "repair", "(abdominal", "or", "vaginal),", "ultralateral", "anterior", "colporrha-", "phy,", "and", "the", "use", "of", "different", "grafts", "and", "meshes.", "All", "these", "different", "techniques,", "except", "the", "use", "of", "grafts,", "have", "had", "disappointing", "results", "to", "date.", "Studies", "comparing", "techniques", "have", "shown", "no", "differences", "in", "the", "risk", "of", "recurrence", "[3].", "In", "2008,", "Shippey", "described", "a", "survey", "of", "the", "American", "Urogynecologic", "Society", "(AUGS)", "members", "of", "the", "contem-", "porary", "approaches", "to", "cystocele", "repair", "[4].", "Their", "research", "mainly", "compared", "the", "differences", "between", "generalist", "and", "fellowship-trained", "urogynecologists.", "Since", "a", "number", "of", "Dutch", "studies", "also", "showed", "comparable", "poor", "anatomical", "outcome", "of", "anterior", "colporrhaphy,", "we", "decided", "to", "evaluate", "the", "variation", "in", "techniques", "of", "anterior", "colporraphy", "among", "members", "of", "the", "Dutch", "Urogynecologic", "Society", "in", "an", "attempt", "to", "get", "more", "insight", "in", "the", "variation", "of", "techniques", "and", "potentially", "find", "a", "reason", "for", "the", "high", "recurrence", "[5,", "6]." ]

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[ "HUMAN", "NEUROSCIENCE", "Is", "analogical", "reasoning", "just", "another", "measure", "of", "executive", "functioning?", "GENERAL", "COMMENTARY", "published:", "20", "September", "2010", "doi:", "10.3389/fnhum.2010.00180", "Lindsey", "Engle", "Richland1*", "and", "Robert", "G.", "Morrison", "2", "1", "Department", "of", "Education,", "University", "of", "California,", "Irvine,", "CA,", "USA", "2", "Department", "of", "Psychology,", "Loyola", "University", "Chicago,", "Chicago,", "IL,", "USA", "*Correspondence:", "l.e.richland@uci.edu", "A", "commentary", "on", "Deficits", "in", "analogical", "reasoning", "in", "adoles", "-", "cents", "with", "traumatic", "brain", "injury.", "by", "Krawczyk,", "D.", "C.,", "Hanten,", "G.,", "Wilde,", "E.", "A.,", "Li,", "X.,", "Schnelle,", "K.", "P.,", "Merkley,", "T.", "L.,", "Vasquez,", "A.", "C.,", "Cook,", "L.", "G.,", "McClelland,", "M.,", "Chapman,", "S.", "B.,", "and", "Levin,", "H.", "S.", "(2010).", "Front.", "Hum.", "Neurosci.4:62.", "doi:", "10.3389/", "fnhum.2010.00062", "The", "present", "paper", "by", "Krawczyk", "et", "al.", "(2010)", "adds", "to", "a", "growing", "list", "of", "studies", "that", "have", "shown", "analogical", "reasoning", "to", "be", "critically", "dependent", "on", "what", "is", "known", "as", "executive", "functioning", "in", "the", "neuropsychological", "lit-", "erature,", "and", "working", "memory", "in", "the", "cogni-", "tive", "(neuro)science", "literature.", "Specifically,", "analogy", "requires", "the", "maintenance,", "manipu-", "lation,", "and", "selective", "activation", "(or", "inhibi-", "tion)", "of", "mental", "representations", "to", "identify,", "map", "correspondences,", "and", "draw", "inferences", "about", "higher-order", "similarity", "relationships", "(e.g.,", "Waltz", "et", "al.,", "2000;", "Morrison", "et", "al.,", "2004;", "Bunge", "et", "al.,", "2005,", "2009;", "Morrison,", "2005;", "Green", "et", "al.,", "2006;", "Cho", "et", "al.,", "2007,", "2010;", "Krawczyk", "et", "al.,", "2008;", "Morrison", "and", "Cho,", "2008).", "Consistent", "with", "this,", "popula-", "tions", "with", "limited", "executive", "functioning", "resources", "have", "shown", "reduced", "analogy", "performance", "when", "required", "to", "integrate", "multiple", "relations", "and/or", "inhibit", "featural", "distractors", "in", "favor", "of", "relational", "similar-", "ity", "(e.g.,", "TBI", "adolescents:", "Krawczyk", "et", "al.,", "2010;", "children:", "Richland", "et", "al.,", "2006,", "2010;", "Wright", "et", "al.,", "2008;", "Thibaut", "et", "al.,", "2010;", "older", "adults:", "Viskontas", "et", "al.,", "2004;", "and", "brain", "damaged", "adults:", "Morrison", "et", "al.,", "2004;", "Krawczyk", "et", "al.,", "2008).", "So", "is", "analogical", "reasoning", "simply", "another", "measure", "of", "execu-", "tive", "function?", "Analogy", "is", "pervasive", "in", "everyday", "learn-", "ing", "and", "discovery.", "Importantly", "it", "allows", "us", "to", "make", "sense", "of", "and", "make", "inferences", "about", "new", "situations", "and", "information", "with", "respect", "to", "things", "we", "already", "know", "and", "understand", "(Holyoak", "and", "Thagard,", "1995;", "Dunbar", "and", "Blanchette,", "2001).", "Thus,", "theories", "of", "the", "development", "of", "analogy", "in", "children", "have", "frequently", "focused", "on", "rela-", "tional", "knowledge", "as", "a", "necessary", "precondi-", "tion", "for", "analogy", "(Rattermann", "and", "Gentner,", "1998;", "Goswami,", "2001).", "The", "importance", "of", "relational", "knowledge", "may", "also", "be", "seen", "in", "patients", "with", "damage", "to", "the", "temporal", "lobe.", "Morrison", "et", "al.", "(2004)", "and", "Krawczyk", "et", "al.", "(2008)", "and", "colleagues", "have", "previously", "found", "that", "patients", "with", "broad", "damage", "to", "anterior", "temporal", "lobe,", "an", "area", "associated", "with", "semantic", "knowledge,", "have", "difficulty", "with", "both", "verbal", "and", "visual", "analogies", "in", "spite", "of", "having", "preserved", "executive", "func-", "tions;", "however,", "the", "patterns", "of", "deficit", "are", "different", "than", "those", "of", "patients", "with", "dam-", "age", "to", "prefrontal", "cortex", "and", "their", "associated", "executive", "dysfunction.", "These", "findings", "are", "consistent", "with", "the", "current", "paper’s", "finding", "that", "cortical", "differences", "in", "both", "prefrontal", "and", "temporal", "regions", "were", "associated", "with", "lower", "analogy", "performance.", "We", "have", "recently", "begun", "to", "explore", "how", "executive", "functions", "and", "relational", "knowl-", "edge,", "and", "their", "underlying", "brain", "networks,", "may", "work", "together", "in", "the", "service", "of", "anal-", "ogy.", "In", "one", "study,", "Richland", "et", "al.", "(2010),", "we", "exploited", "cross-cultural", "differences", "in", "relational", "knowledge", "and", "discovered", "a", "dissociation", "between", "the", "ability", "to", "inhibit", "featural", "distractors", "and", "integrate", "relations", "in", "analogy,", "two", "functions", "associated", "with", "executive", "functions", "which", "have", "traditionally", "correlated", "in", "studies", "of", "analogy", "(see", "Cho", "et", "al.,", "2010", "for", "an", "exception", "using", "neu-", "roimaging).", "Using", "a", "computational", "model", "of", "analogy", "we", "offered", "an", "explanation", "of", "the", "results,", "suggesting", "that", "more", "advanced", "relational", "knowledge", "structures", "reduce", "the", "demands", "for", "executive", "functions", "in", "analogy", "(Morrison", "et", "al.,", "in", "press).", "Thus,", "prefrontal", "and", "temporal", "networks", "work", "together", "in", "analogy", "and", "the", "development", "or", "advanced", "functioning", "on", "one", "area", "affect", "demands", "on", "the", "other.", "In", "fact,", "we", "have", "also", "shown", "via", "modeling", "that", "the", "development", "of", "such", "advanced", "relational", "knowledge", "networks", "themselves", "may", "be", "dependent", "on", "executive", "functions", "(Doumas", "et", "al.,", "2010).", "Thus,", "analogy", "is", "not", "simply", "another", "measure", "of", "executive", "functions,", "rather", "it", "is", "a", "whole", "brain", "activity,", "that", "is", "a", "profound", "test", "of", "our", "ability", "to", "think", "in", "everyday", "life,", "and", "as", "such", "is", "an", "excellent", "measure", "to", "evalu-", "ate", "the", "impact", "of", "traumatic", "brain", "injury", "on", "patients’", "ability", "to", "function.", "RRfescne", "Bunge,", "S.", "A.,", "Wendelken,", "C.,", "Badre,", "D.,", "and", "Wagner,", "A.", "D.", "(2005).", "Analogical", "reasoning", "and", "prefrontal", "cor-", "tex:", "evidence", "for", "separable", "retrieval", "and", "integration", "mechanisms.", "Cereb.", "Cortex", "15,", "239–249.", "Bunge,", "S.", "A.,", "Wendelken,", "C.,", "and", "Helskog,", "E.", "H.", "(2009).", "Left,", "but", "not", "right,", "rostrolateral", "prefrontal", "cortex", "meets", "a", "stringent", "test", "of", "the", "relational", "integration", "hypothesis.", "Neuroimage", "46,", "338–342.", "Cho,", "S.,", "Holyoak,", "K.", "J.,", "and", "Cannon,", "T.", "D.", "(2007).", "Analogical", "reasoning", "in", "working", "memory:", "resources", "shared", "among", "relational", "integration,", "interference", "resolution,", "and", "maintenance.", "Mem.", "Cognit.", "35,", "1445–1455.", "Cho,", "S.,", "Moody,", "T.", "D.,", "Fernandino,", "L.,", "Mumford,", "J.", "A.,", "Poldrack,", "R.", "A.,", "Cannon,", "T.", "D.,", "Knowlton,", "B.", "J.,", "and", "Holyoak,", "K.", "J.", "(2010).", "Common", "and", "dis-", "sociable", "prefrontal", "loci", "associated", "with", "component", "mechanisms", "of", "analogical", "reasoning.", "Cereb.", "Cortex", "20,", "524–533.", "Dunbar,", "K.,", "and", "Blanchette,", "I.", "(2001).", "The", "in", "vivo/in", "vitro", "approach", "to", "cognition:", "the", "case", "of", "analogy.", "Trends", "Cogn.", "Sci.", "5,", "335–339.", "Doumas,", "L.", "A.", "A.,", "Morrison,", "R.", "G.,", "&", "Richland,", "L.", "E.", "(2010).“Differences", "in", "development", "of", "analogy", "across", "cultures:", "a", "computational", "account,”", "in", "Proceedings", "of", "the", "32nd", "Annual", "Conference", "of", "the", "Cognitive", "Science", "Society,", "Portland,", "Oregon.", "Goswami,", "U.", "(2001).“Analogical", "reasoning", "in", "children,”", "in", "The", "Analogical", "mind:", "Perspectives", "from", "Cognitive", "Science,", "eds.", "D.", "Gentner,", "K.", "J.", "Holyoak,", "and", "B.", "N.", "Kokinov", "(Cambridge,", "MA:", "MIT", "Press),", "437–470.", "Green,A.", "E.,", "Fugelsang,", "J.A.,", "Kraemer,", "D.", "J.", "M.,", "Shamosh,", "N.", "A.,", "and", "Dunbar,", "K.", "N.", "(2006).", "Frontopolar", "cortex", "mediates", "abstract", "integration", "in", "analogy.", "Brain", "Res.", "1096,", "125–137.", "Holyoak,", "K.", "J.,", "and", "Thagard,", "P.", "(1995).", "Mental", "Leaps:", "Analogy", "in", "Creative", "Thought.", "Cambridge,", "MA:", "The", "MIT", "Press.", "Krawczyk,", "D.", "C.,", "Hanten,", "G.,Wilde,", "E.A.,", "Li,", "X.,", "Schnelle,", "K.", "P.,", "Merkley,", "T.", "L.,", "Vasquez,", "A.", "C.,", "Cook,", "L.", "G.,", "Frontiers", "in", "Human", "Neuroscience", "www.frontiersin.org", "September", "2010", "|", "Volume", "4", "|", "Article", "180", "|", "1" ]

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[ "Olangir", "r", "e", "hcraes", "a", "r", "elcit", "published:", "11", "March", "2011", "doi:", "10.3389/fphys.2011.00010", "The", "driving", "force", "of", "the", "Na+/Ca2+-exchanger", "during", "metabolic", "inhibition", "Antonius", "Baartscheer*,", "Cees", "A.", "Schumacher,", "Ruben", "Coronel", "and", "Jan", "W.T.", "Fiolet", "Experimental", "Cardiology,", "Heart", "Failure", "Research", "Center,", "Academic", "Medical", "Center,", "University", "of", "Amsterdam,", "Amsterdam,", "Netherlands", "Edited", "by:", "Marcel", "V.", "D.", "Heyden,", "University", "Medical", "Center,", "Netherlands", "Reviewed", "by:", "Teun", "P.", "De", "Boer,", "University", "Medical", "Center", "Utrecht,", "Netherlands", "Gudrun", "Antoons,", "Katholieke", "Unversiteit", "Leuven,", "Belgium", "YukiomiTsuji,", "Nagoya", "University,", "Japan", "*Correspondence:", "Antonius", "Baartscheer,", "Experimental", "Cardiology,", "Heart", "failure", "Research", "Center,", "Academic", "Medical", "Center,", "University", "of", "Amsterdam,", "Room", "K2-104,", "1105", "AZ,", "Amsterdam,", "Netherlands.", "e-mail:", "a.baartscheer@amc.uva.nl", "Objective:", "Metabolic", "inhibition", "causes", "a", "decline", "in", "mechanical", "performance", "and,", "if", "prolonged,", "myocardial", "contracture", "and", "cell", "death.The", "decline", "in", "mechanical", "performance", "is", "mainly", "due", "to", "altered", "intracellular", "calcium", "handling,", "which", "is", "under", "control", "of", "the", "Na+/Ca2+-exchanger", "(NCX)", "The", "driving", "force", "of", "the", "NCX", "(∆", "Gncx)", "determines", "the", "activity", "of", "NCX.", "The", "aim", "of", "this", "study", "was", "to", "describe", "the", "relation", "between", "∆", "Gncx", "and", "calcium", "homeostasis", "during", "metabolic", "inhibition.", "Methods:", "In", "left", "ventricular", "rabbit", "myocytes,", "during", "metabolic", "inhibition", "(2", "mmol/L", "sodium", "cyanide),", "sodium", "([Na+]i),", "calcium", "([Ca2+]i),", "and", "action", "potentials", "were", "determined", "with", "SBFI,", "indo-", "1,", "and", "the", "patch", "clamp", "technique.", "Changes", "of", "∆", "Gncx", "were", "calculated.", "Results:", "During", "metabolic", "inhibition:", "The", "first", "8", "min", "[Na+]i", "remained", "constant,", "systolic", "calcium", "decreased", "from", "532", "±", "28", "to", "82", "±", "13", "nM,", "diastolic", "calcium", "decreased", "from", "121", "±", "12", "to", "36", "±", "10", "nM", "and", "the", "sarcoplasmic", "reticulum", "(SR)", "calcium", "content", "was", "depleted", "for", "85", "±", "3%.", "After", "8", "min", "[Na+]i", "and", "diastolic", "calcium", "started", "to", "increase", "to", "30", "±", "1.3", "mmol/L", "and", "500", "±", "31", "nM", "after", "30", "min", "respectively.The", "action", "potential", "duration", "shortened", "biphasically.", "In", "the", "first", "5", "min", "it", "shortened", "from", "225", "±", "12", "to", "153", "±", "11", "ms", "and", "remained", "almost", "constant", "until", "it", "shortened", "again", "after", "10", "min.", "After", "14", "min", "action", "potential", "and", "calcium", "transients", "disappeared", "due", "to", "unexcitability", "of", "the", "myocytes.", "This", "resulted", "in", "an", "increased", "of", "the", "time", "average", "of", "∆", "Gncx", "from", "6.2", "±", "0.2", "to", "7.7", "±", "0.3", "kJ/mol", "during", "the", "first", "3", "min,", "where", "after", "it", "decreased", "and", "became", "negative", "after", "about", "15", "min.", "Conclusion:", "Metabolic", "inhibition", "caused", "an", "early", "increase", "of", "∆", "Gncx", "caused", "by", "shortening", "of", "the", "action", "potential.The", "increase", "of", "∆", "Gncx", "contributed", "to", "decrease", "of", "diastolic", "calcium,", "calcium", "transient", "amplitude,", "SR", "calcium", "content,", "and", "contractility.", "The", "increase", "of", "diastolic", "calcium", "started", "after", "∆", "Gncx", "became", "lower", "than", "under", "aerobic", "conditions.", "Keywords:", "Na/Ca-exchanger,", "myocytes,", "calcium,", "sodium,", "action", "potential,", "metabolic", "inhibition,", "SR,", "driving", "force", "Incudortt", "Io", "n", "The", "sarcolemmal", "Na+/Ca2+-exchanger", "(NCX)", "is", "a", "passive", "ion", "transport", "mechanism,", "which", "directly", "couples", "transmembrane", "movements", "of", "Ca2+", "to", "reciprocal", "movements", "of", "Na+", "with", "a", "stoi-", "chiometric", "ratio", "of", "three", "sodium", "per", "calcium", "(Reeves", "and", "Hale,", "1984).", "The", "direction", "of", "action", "(forward", "mode,", "Ca2+", "efflux", "or", "reversed", "mode,", "Ca2+", "influx)", "depends", "on", "the", "driving", "force", "of", "NCX", "(∆", "Gncx).", "A", "passive", "transporter", "such", "as", "NCX", "must", "be", "out", "of", "ther-", "modynamic", "equilibrium", "in", "order", "to", "operate.", "This", "requires", "a", "non-", "zero", "driving", "force", "and", "the", "continuous", "input", "of", "metabolic", "energy.", "The", "energy", "required", "to", "maintain", "a", "non-equilibrium", "state", "is", "pro-", "vided", "by", "the", "Na+/K+-ATPase,", "which", "channels", "metabolic", "energy", "derived", "from", "ATP", "hydrolysis", "into", "the", "trans-sarcolemmal", "electro-", "chemical", "potential", "differences", "of", "sodium.", "Therefore,", "NCX", "is", "indi-", "rectly", "under", "thermodynamic", "control", "of", "myocardial", "metabolism", "and", "the", "phosphorylation", "potential,", "∆", "GATP", "(Fiolet", "et", "al.,", "1984).", "The", "∆", "Gncx", "can", "be", "calculated", "from", "the", "difference", "of", "three", "times", "the", "trans-sarcolemmal", "electrochemical", "potential", "of", "sodium", "and", "once", "that", "of", "calcium", "(Chapman", "et", "al.,", "1983;", "Fiolet", "et", "al.,", "1995).", "Thus,", "measurement", "of", "concentration", "gradients", "of", "the", "respective", "ions", "and", "membrane", "potential", "allows", "calculation", "of", "∆", "Gncx.", "Under", "physiological", "resting", "conditions", "in", "cardiac", "myocytes", "the", "reversal", "potential", "of", "NCX", "is", "about", "−20", "mV.", "Therefore,", "at", "a", "resting", "membrane", "potential", "of", "−90", "mV", "∆", "Gncx", "deviates", "70", "mV", "from", "thermodynamic", "equilibrium,", "corresponding", "to", "a", "free", "energy", "of", "about", "7", "kJ/mol", "(Bers", "et", "al.,", "1988;", "Barry", "and", "Bridge,", "1993).", "This", "favors", "transport", "of", "calcium", "coupled", "to", "inward", "transport", "of", "sodium.", "However,", "in", "dynamic", "conditions,", "such", "as", "during", "electrical", "stimulation,", "∆", "Gncx", "continuously", "changes", "due", "to", "changes", "of", "membrane", "potential", "and", "[Ca2+]i", "and", "even", "operates", "in", "reversed", "mode", "(calcium", "influx)", "for", "a", "short", "period", "after", "the", "upstroke", "of", "the", "action", "potential", "(Despa", "et", "al.,", "2002;", "Baartscheer", "et", "al.,", "2003a).", "Nevertheless,", "it", "is", "unanimously", "agreed", "that", "the", "NCX", "is", "the", "main", "pathway", "for", "Ca2+", "extrusion", "from", "ventricular", "myocytes", "(Noble", "et", "al.,", "1991;", "Egger", "and", "Niggli,", "1999;", "Bers,", "2001;", "Weber", "et", "al.,", "2002)", "and", "contributes", "to", "contraction", "by", "regulating", "the", "overall", "calcium", "balance", "(Mullins,", "1979;", "Barry", "and", "Bridge,", "1993).", "In", "pathophysiological", "conditions", "in", "which", "myocardial", "metab-", "olism", "is", "disturbed,", "such", "as", "ischemia", "and", "anoxia,", "∆", "Gncx", "must", "adapt", "to", "reduced", "metabolic", "energy", "derived", "from", "ATP", "hydroly-", "sis", "(∆", "GATP),", "which", "influence", "[Ca2+]i", "homeostasis", "and", "contractil-", "ity", "(Fiolet", "et", "al.,", "1984;", "Baartscheer", "et", "al.,", "2003b).", "Indeed,", "It", "has", "been", "shown", "that", "during", "metabolic", "inhibition", "∆", "Gncx", "is", "shifted", "toward", "more", "reversed", "and", "less", "forward", "mode", "resulting", "in", "an", "increase", "of", "[Ca2+]i", "(Boston", "et", "al.,", "1998;", "Sugishita", "et", "al.,", "2001;", "Ju", "and", "Allen,", "2005;", "Barry", "et", "al.,", "2009).", "www.frontiersin.org", "March", "2011", "|", "Volume", "2", "|", "Article", "10", "|", "1" ]

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[ "Clin", "Transl", "Oncol", "(2012)", "14:606–612", "DOI", "10.1007/s12094-012-0843-x", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "A", "randomized", "phase", "II", "study", "to", "compare", "oxaliplatin", "plus", "5-fluorouracil", "and", "leucovorin", "(FOLFOX4)", "versus", "oxaliplatin", "plus", "raltitrexed", "(TOMOX)", "as", "first-line", "chemotherapy", "for", "advanced", "colorectal", "cancer", "Cristina", "Gravalos", "•", "Antonieta", "Salut", "•", "Carlos", "Garc´ıa-Giro´", "n", "•", "Roc´ıo", "Garc´ıa-Carbonero", "•", "Ana", "Isabel", "Le", "o´n", "•", "Isabel", "Sevilla", "•", "Joan", "Maurel", "•", "Beatriz", "Esteban", "•", "Eduardo", "Garc´ıa-Rico", "•", "Adolfo", "Murias", "•", "Herna´", "n", "Corte´s-Funes", "Received:", "28", "March", "2011", "/", "Accepted:", "14", "November", "2011", "/", "Published", "online:", "19", "July", "2012", "The", "Author(s)", "2012.", "This", "article", "is", "published", "with", "open", "access", "at", "Springerlink.com", "Abstract", "Introduction", "The", "aim", "of", "this", "study", "was", "to", "compare", "TOMOX", "versus", "FOLFOX4", "as", "first-line", "treatment", "of", "advanced", "colorectal", "cancer", "(CRC).", "Materials", "and", "methods", "191", "chemotherapy-na¨ıve", "patients", "were", "randomized", "to", "receive", "TOMOX", "or", "FOLFOX4.", "Patients", "were", "evaluated", "every", "3", "months", "and", "chemotherapy", "C.", "Gravalos", "(&)", "H.", "Corte´s-Funes", "Medical", "Oncology", "Department,", "University", "Hospital", "12", "de", "Octubre,", "Avda.", "de", "Andaluc´ıa", "s/n", "Km", "5.400,", "28041", "Madrid,", "Spain", "e-mail:", "cgravalos@telefonica.net", "A.", "Salut", "Hospital", "Arnau", "de", "la", "Villanova,", "Lleida,", "Spain", "C.", "Garc´ıa-Giro´n", "Hospital", "General", "Yagu¨e,", "Burgos,", "Spain", "R.", "Garc´ıa-Carbonero", "Hospital", "Severo", "Ochoa,", "Legane´s,", "Spain", "A.", "I.", "Leo´n", "Fundacio´n", "Jime´nez", "D´ıaz,", "Madrid,", "Spain", "I.", "Sevilla", "Hospital", "Virgen", "de", "la", "Victoria,", "Ma´laga,", "Spain", "J.", "Maurel", "Hospital", "Clinic", "i", "Provincial,", "Barcelona,", "Spain", "B.", "Esteban", "Hospital", "General", "de", "Segovia,", "Segovia,", "Spain", "E.", "Garc´ıa-Rico", "Hospital", "de", "Monteprincipe,", "Madrid,", "Spain", "A.", "Murias", "Hospital", "Insular", "de", "Las", "Palmas,", "Gran", "Canaria,", "Spain", "123", "was", "continued", "until", "disease", "progression", "or", "unacceptable", "toxicity.", "Overall", "response", "rate", "was", "the", "primary", "endpoint.", "Results", "183", "patients", "were", "included", "in", "the", "intent-to-treat", "analysis", "(92", "TOMOX", "and", "91", "FOLFOX4).", "Overall", "response", "rate", "was", "45.6", "and", "36.3", "%", "(p", "=", "0.003)", "for", "TOMOX", "and", "FOLFOX4,", "respectively.", "No", "statistically", "significant", "dif-", "ferences", "were", "observed", "in", "overall", "survival", "(15.6", "and", "17.2", "months;", "p", "=", "0.475);", "progression-free", "survival", "(7.7", "and", "8.7", "months;", "p", "=", "0.292),", "and", "response", "duration", "(6.4", "and", "7.6", "months;", "p", "=", "0.372)", "for", "TOMOX", "and", "FOLFOX4,", "respectively.", "Grades", "3", "and", "4", "neutropenia", "(p", "\\", "0.0001)", "and", "leukopenia", "(p", "=", "0.028)", "were", "more", "common", "with", "the", "FOLFOX4", "regimen,", "while", "hepatic", "disorders", "and", "asthenia", "were", "higher", "in", "TOMOX", "group", "(p", "=", "ns).", "There", "were", "two", "treatment-related", "deaths", "in", "the", "FOLFOX4", "arm", "and", "one", "in", "the", "TOMOX", "arm.", "Quality", "of", "life", "analysis", "based", "on", "the", "SF-", "36", "revealed", "differences", "between", "the", "two", "regimens", "for", "physical", "and", "mental", "composite", "scores", "after", "6", "weeks,", "and", "for", "body", "pain", "and", "emotional", "role", "functioning", "after", "6", "and", "12", "weeks;", "all", "of", "these", "favored", "the", "FOLFOX4", "arm", "(p", "B", "0.05).", "Conclusions", "TOMOX", "and", "FOLFOX4", "seem", "to", "have", "similar", "efficacy", "and", "are", "well", "tolerated", "in", "the", "first-line", "treatment", "for", "advanced", "CRC", "with", "different", "profiles", "of", "toxicity.", "The", "convenient", "TOMOX", "regimen", "may", "offer", "an", "alternative", "to", "fluoropyrimidine-based", "regimens.", "Colorectal", "cancer", "Raltitrexed", "Oxaliplatin", "Keywords", "Fluorouracil", "Introduction", "Colorectal", "cancer", "(CRC)", "is", "the", "second", "most", "prevalent", "cancer", "worldwide,", "with", "more", "than", "1", "million", "new", "cases" ]

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[ "Bai", "et", "al.", "Journal", "of", "Animal", "Science", "and", "Biotechnology", "2012,", "3:8", "http://www.jasbsci.com/content/3/1/8", "R", "E", "V", "I", "E", "W", "JOURNAL", "OF", "ANIMAL", "SCIENCE", "AND", "BIOTECHNOLOGY", "Open", "Access", "Current", "status", "and", "future", "perspectives", "for", "sequencing", "livestock", "genomes", "Yongsheng", "Bai1*,", "Maureen", "Sartor1,2", "and", "James", "Cavalcoli1", "Abstract", "Only", "in", "recent", "years,", "the", "draft", "sequences", "for", "several", "agricultural", "animals", "have", "been", "assembled.", "Assembling", "an", "individual", "animal’s", "entire", "genome", "sequence", "or", "specific", "region(s)", "of", "interest", "is", "increasingly", "important", "for", "agricultural", "researchers", "to", "perform", "genetic", "comparisons", "between", "animals", "with", "different", "performance.", "We", "review", "the", "current", "status", "for", "several", "sequenced", "agricultural", "species", "and", "suggest", "that", "next", "generation", "sequencing", "(NGS)", "technology", "with", "decreased", "sequencing", "cost", "and", "increased", "speed", "of", "sequencing", "can", "benefit", "agricultural", "researchers.", "By", "taking", "advantage", "of", "advanced", "NGS", "technologies,", "genes", "and", "chromosomal", "regions", "that", "are", "more", "labile", "to", "the", "influence", "of", "environmental", "factors", "could", "be", "pinpointed.", "A", "more", "long", "term", "goal", "would", "be", "addressing", "the", "question", "of", "how", "animals", "respond", "at", "the", "molecular", "and", "cellular", "levels", "to", "different", "environmental", "models", "(e.g.", "nutrition).", "Upon", "revealing", "important", "genes", "and", "gene-environment", "interactions,", "the", "rate", "of", "genetic", "improvement", "can", "also", "be", "accelerated.", "It", "is", "clear", "that", "NGS", "technologies", "will", "be", "able", "to", "assist", "animal", "scientists", "to", "efficiently", "raise", "animals", "and", "to", "better", "prevent", "infectious", "diseases", "so", "that", "overall", "costs", "of", "animal", "production", "can", "be", "decreased.", "Keywords:", "livestock", "genomes,", "next-generation", "sequencing", "technology,", "nutrition", "1.", "Current", "Status", "of", "Domestic", "Animal", "Reference", "Sequences", "As", "the", "new", "genomics", "era", "matures,", "with", "large-scale", "gen-", "ome", "research", "and", "the", "development", "of", "sophisticated", "bioinformatics", "tools", "that", "can", "be", "applied", "to", "the", "agricul-", "tural", "field,", "agricultural", "researchers", "should", "take", "advan-", "tage", "of", "and", "benefit", "from", "new", "sequencing", "and", "mapping", "technologies.", "In", "recent", "years,", "the", "genomes", "of", "several", "domesticated", "livestock", "animals", "(chicken,", "pig,", "cow,", "sheep,", "and", "horse)", "have", "been", "partially", "or", "completely", "sequenced.", "In", "this", "review,", "we", "first", "examine", "the", "current", "sequencing", "status", "for", "several", "sequenced", "agricultural", "spe-", "cies.", "Next,", "we", "discuss", "the", "different", "platforms", "used", "for", "genome", "sequencing,", "tools", "available", "for", "mapping", "sequences", "to", "the", "genome,", "and", "several", "additional", "applica-", "tions", "for", "which", "next", "generation", "sequencing", "can", "be", "used.", "We", "also", "list", "tools", "available", "for", "analyzing", "data", "from", "these", "additional", "applications.", "*", "Correspondence:", "ybai@umich.edu", "1Center", "for", "Computational", "Medicine", "and", "Bioinformatics", "and", "Department", "of", "Computational", "Medicine", "and", "Bioinformatics,", "The", "University", "of", "Michigan,", "100", "Washtenaw", "Ave.,", "2017", "Palmer", "Commons,", "Ann", "Arbor,", "Michigan", "48109-2218,", "USA", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "Due", "to", "the", "high", "recombination", "rate", "of", "its", "micro-chro-", "mosomes,", "the", "chicken", "is", "an", "ideal", "model", "for", "studying", "genetic", "linkage", "[1].", "The", "chicken", "genome", "sequence", "of", "Red", "Junglefowl", "(RJF)", "was", "the", "first", "livestock", "species", "to", "be", "sequenced.", "The", "first", "draft", "of", "the", "chicken", "genome", "was", "built", "from", "an", "assembly", "with", "6.6-fold", "whole-genome", "shotgun", "coverage,", "although", "sex", "chromosomes", "were", "poorly", "annotated", "in", "the", "initial", "assembly", "[1,2].", "The", "updated", "version", "of", "NCBI", "build", "2.1", "was", "released", "recently", "with", "a", "significant", "improvement", "on", "the", "annotation", "of", "the", "sex", "chromosomes.", "Roughly", "2.8", "million", "SNPs", "for", "chicken", "were", "identified", "[1,3,4]", "between", "the", "base", "(wild", "type)", "RJF", "sequence", "assembly", "and", "a", "partial", "genome", "scan", "of", "three", "chicken", "breeds:", "a", "female", "layer", "(White", "Leghorn);", "a", "male", "broiler", "(Cornish);", "and", "a", "female", "Silkie.", "A", "moderate", "den-", "sity", "(60", "k)", "Illumina", "SNP", "BeadChip", "for", "commercial", "chicken", "(broilers", "and", "layers)", "containing", "352,303", "SNPs", "was", "designed", "and", "additional", "SNPs", "not", "covered", "by", "the", "current", "chicken", "genome", "assembly", "(Gallus_gallus-2.1)", "were", "identified", "and", "selected", "recently", "[5].", "The", "BBSRC", "ChickenEST", "Database", "(http://www.chick.manchester.ac.", "uk/)", "provides", "the", "most", "comprehensive", "database", "[6,7]", "of", "ESTs/cDNAs", "for", "the", "chicken", "genome.", "Chicken", "Varia-", "tion", "Database", "(ChickVD)", "(http://chicken.genomics.org.", "©", "2012", "Bai", "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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"unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Background:", "How", "novel", "morphological", "traits", "originate", "and", "diversify", "represents", "a", "major", "frontier", "in", "evolutionary", "biology.", "Horned", "beetles", "are", "emerging", "as", "an", "increasingly", "popular", "model", "system", "to", "explore", "the", "genetic,", "developmental,", "and", "ecological", "mechanisms,", "as", "well", "as", "the", "interplay", "between", "them,", "in", "the", "genesis", "of", "novelty", "and", "diversity.", "The", "horns", "of", "beetles", "originate", "during", "a", "rapid", "growth", "phase", "during", "the", "prepupal", "stage", "of", "larval", "development.", "Differential", "growth", "during", "this", "period", "is", "either", "implicitly", "or", "explicitly", "assumed", "to", "be", "the", "sole", "mechanism", "underlying", "differences", "in", "horn", "expression", "within", "and", "between", "species.", "Here", "I", "focus", "on", "male", "horn", "dimorphisms,", "a", "phenomenon", "at", "the", "center", "of", "many", "studies", "in", "behavioral", "ecology", "and", "evolutionary", "development,", "and", "quantify", "the", "relative", "contributions", "of", "a", "previously", "ignored", "developmental", "process,", "pupal", "remodeling,", "to", "the", "expression", "of", "male", "dimorphism", "in", "three", "horned", "beetle", "species.", "Results:", "Prepupal", "growth", "is", "not", "the", "only", "determinant", "of", "differences", "in", "male", "horn", "expression.", "Instead,", "following", "their", "initial", "prepupal", "growth", "phase,", "beetles", "may", "be", "extensively", "remodeled", "during", "the", "subsequent", "pupal", "stage", "in", "a", "sex", "and", "size-dependent", "manner.", "Specifically,", "male", "dimorphism", "in", "the", "three", "Onthophagus", "species", "studied", "here", "was", "shaped", "not", "at", "all,", "partly", "or", "entirely", "by", "such", "pupal", "remodeling", "rather", "than", "differential", "growth,", "suggesting", "that", "pupal", "remodeling", "is", "phylogenetically", "widespread,", "evolutionarily", "labile,", "and", "developmentally", "flexible.", "Conclusion:", "This", "study", "is", "the", "first", "to", "document", "that", "male", "dimorphism", "in", "horned", "beetles", "is", "the", "product", "of", "two", "developmentaly", "dissociated", "processes:", "prepupal", "growth", "and", "pupal", "remodeling.", "More", "generally,", "adult", "morphology", "alone", "appears", "to", "provide", "few", "clues,", "if", "any,", "as", "to", "the", "relative", "contributions", "of", "both", "processes", "to", "the", "expression", "of", "alternative", "male", "morphs,", "underscoring", "the", "importance", "of", "developmental", "studies", "in", "efforts", "aimed", "at", "understanding", "the", "evolution", "of", "adult", "diversity", "patterns.", "Background", "Phenotypic", "diversity", "is", "produced", "by", "changes", "in", "ontoge-", "netic", "processes", "occurring", "at", "earlier", "developmental", "stages.", "Such", "changes", "may", "be", "brought", "about", "by", "allelic", "differences", "among", "individuals,", "differences", "in", "ontogenetic", "environ-", "ment,", "or", "as", "is", "probably", "the", "case", "for", "the", "majority", "of", "pheno-", "typic", "traits,", "both.", "Evolutionary", "biologists", "are", "accustomed", "to", "deducing", "ontogenetic", "properties", "based", "on", "ontogenetic", "outputs", "rather", "than", "by", "studying", "development", "as", "a", "process.", "For", "example,", "the", "degree", "of", "fluctuating", "asymmetry", "between", "paired", "adult", "structures", "has", "been", "assumed", "by", "many", "studies", "to", "be", "indicative", "of", "degree", "of", "developmental", "instability", "and", "integration", "[1-3],", "even", "though", "few", "studies", "made", "the", "effort", "to", "investigate", "the", "developmental", "underpinnings", "of", "asym-", "Page", "1", "of", "12", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Hindawi", "Publishing", "Corporation", "Journal", "of", "Lipids", "Volume", "2011,", "Article", "ID", "575840,", "9", "pages", "doi:10.1155/2011/575840", "Review", "Article", "Lipid", "Abnormalities", "and", "Cardiometabolic", "Risk", "in", "Patients", "with", "Overt", "and", "Subclinical", "Thyroid", "Disease", "Melpomeni", "Peppa,1", "Grigoria", "Betsi,1", "and", "George", "Dimitriadis2", "1", "Endocrine", "Unit,", "Second", "Department", "of", "Internal", "Medicine-Propaedeutic,", "Research", "Institute", "and", "Diabetes", "Center,", "Athens", "University", "Medical", "School,", "Attikon", "University", "Hospital,", "Athens,", "Greece", "2", "Second", "Department", "of", "Internal", "Medicine-Propaedeutic,", "Research", "Institute", "and", "Diabetes", "Center,", "Athens", "University", "Medical", "School,", "Attikon", "University", "Hospital,", "Athens,", "Greece", "Correspondence", "should", "be", "addressed", "to", "Melpomeni", "Peppa,", "molypepa@otenet.gr", "Received", "3", "May", "2011;", "Revised", "17", "May", "2011;", "Accepted", "17", "May", "2011", "Academic", "Editor:", "Angeliki", "Chroni", "Copyright", "©", "2011", "Melpomeni", "Peppa", "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.", "Dyslipidemia", "is", "a", "common", "finding", "in", "patients", "with", "thyroid", "disease,", "explained", "by", "the", "adverse", "effects", "of", "thyroid", "hormones", "in", "almost", "all", "steps", "of", "lipid", "metabolism.", "Not", "only", "overt", "but", "also", "subclinical", "hypo-", "and", "hyperthyroidism,", "through", "different", "mechanisms,", "are", "associated", "with", "lipid", "alterations,", "mainly", "concerning", "total", "and", "LDL", "cholesterol", "and", "less", "often", "HDL", "cholesterol,", "triglycerides,", "lipoprotein", "(a),", "apolipoprotein", "A1,", "and", "apolipoprotein", "B.", "In", "addition", "to", "quantitative,", "qualitative", "alterations", "of", "lipids", "have", "been", "also", "reported,", "including", "atherogenic", "and", "oxidized", "LDL", "and", "HDL", "particles.", "In", "thyroid", "disease,", "dyslipidemia", "coexists", "with", "various", "metabolic", "abnormalities", "and", "induce", "insulin", "resistance", "and", "oxidative", "stress", "via", "a", "vice-vicious", "cycle.", "The", "above", "associations", "in", "combination", "with", "the", "thyroid", "hormone", "induced", "hemodynamic", "alterations,", "might", "explain", "the", "increased", "risk", "of", "coronary", "artery", "disease,", "cerebral", "ischemia", "risk,", "and", "angina", "pectoris", "in", "older,", "and", "possibly", "ischemic", "stroke", "in", "younger", "patients", "with", "overt", "or", "subclinical", "hyperthyroidism.", "1.", "Introduction", "Thyroid", "disease,", "namely", "hypothyroidism", "and", "hyperthyroid-", "ism,", "constitutes", "the", "most", "common", "endocrine", "abnormality", "in", "recent", "years,", "diagnosed", "either", "in", "subclinical", "or", "clinical", "form.", "According", "to", "the", "6-year", "duration", "NHANES", "III", "Study,", "the", "prevalence", "of", "hypothyroidism", "was", "4.6%", "(0.3%", "clinical", "and", "4.3%", "subclinical)", "and", "of", "hyperthyroidism", "1.3%", "(0.5%", "clinical", "and", "0.7%", "subclinical),", "in", "population", "aged", "at", "least", "12", "years,", "showing", "an", "age", "and", "sex", "dependence", "[1].", "Thyroid", "disease", "is", "associated", "with", "various", "metabolic", "ab-", "normalities,", "due", "to", "the", "effects", "of", "thyroid", "hormones", "on", "nearly", "all", "major", "metabolic", "pathways.", "Thyroid", "hormones", "regulate", "the", "basal", "energy", "expenditure", "through", "their", "effect", "on", "protein,", "carbohydrate,", "and", "lipid", "metabolism.", "This", "might", "be", "a", "direct", "effect", "or", "an", "indirect", "effect", "by", "modification", "of", "other", "regulatory", "hormones", "such", "as", "insulin", "or", "catecholamines", "[2].", "Dyslipi-", "demia", "is", "a", "common", "metabolic", "abnormality", "in", "patients", "with", "thyroid", "disease,", "either", "in", "the", "overt", "or", "subclinical", "forms", "of", "the", "disease,", "and", "constitutes", "the", "end", "result", "of", "the", "effect", "of", "thyroid", "hormones", "in", "all", "aspects", "of", "lipid", "metabolism", "leading", "to", "var-", "ious", "quantitative", "and/or", "qualitative", "changes", "of", "triglycerides,", "phospholipids,", "cholesterol,", "and", "other", "lipoproteins", "[3].", "In", "thyroid", "disease,", "dyslipidemia", "and", "the", "coexisting", "met-", "abolic", "abnormalities,", "in", "combination", "with", "the", "thyroid", "hor-", "mone-induced", "hemodynamic", "alterations,", "explain", "the", "high", "risk", "for", "cardiovascular", "disease", "[4–7].", "2.", "Effects", "of", "Thyroid", "Hormones", "on", "Lipid", "Metabolism", "Thyroid", "hormones", "influence", "all", "aspects", "of", "lipid", "metabolism", "including", "synthesis,", "mobilization,", "and", "degradation", "[3].", "Thy-", "roid", "hormones", "stimulate", "cholesterol", "synthesis", "by", "inducing", "3-hydroxy-3-methyl-glutaryl", "coenzyme", "A", "reductase", "in", "the", "liver", "[8].", "Thyroid", "hormones", "affect", "lipoprotein", "lipase", "activity", "and", "thus,", "the", "hydrolysis", "of", "triglycerides", "into", "very-low,", "density", "lipoprotein", "(VLDL)", "and", "chylomicrons", "into", "fatty" ]

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[ "Knee", "Surg", "Sports", "Traumatol", "Arthrosc", "(2007)", "15:465–471", "DOI", "10.1007/s00167-006-0275-7", "A", "N", "K", "L", "E", "The", "distal", "fascicle", "of", "the", "anterior", "inferior", "tibiofibular", "ligament", "as", "a", "cause", "of", "tibiotalar", "impingement", "syndrome:", "a", "current", "concepts", "review", "Michel", "P.", "J.", "van", "den", "Bekerom", "Æ", "Eric", "E.", "J.", "Raven", "Received:", "12", "August", "2006", "/", "Accepted:", "11", "December", "2006", "/", "Published", "online:", "20", "January", "2007", "Springer-Verlag", "2007", "Abstract", "Impingement", "syndromes", "of", "the", "ankle", "in-", "volve", "either", "osseous", "or", "soft", "tissue", "impingement", "and", "can", "be", "anterior,", "anterolateral,", "or", "posterior.", "Ankle", "impingement", "syndromes", "are", "painful", "conditions", "caused", "by", "the", "friction", "of", "joint", "tissues,", "which", "are", "both", "the", "cause", "and", "the", "effect", "of", "altered", "joint", "biomechanics.", "The", "distal", "fascicle", "of", "the", "anterior", "inferior", "tibiofibular", "ligament", "(AITFL)", "is", "possible", "cause", "of", "anterior", "impingement.", "The", "objective", "of", "this", "article", "was", "to", "review", "the", "literature", "concerning", "the", "anatomy,", "pathogenesis,", "symptoms", "and", "treatment", "of", "the", "AITFL", "impingement", "and", "finally", "to", "formulate", "treatment", "recommendations.", "The", "AITFL", "starts", "from", "the", "distal", "tibia,", "5", "mm", "in", "average", "above", "the", "articular", "surface,", "and", "descends", "obliquely", "between", "the", "adjacent", "margins", "of", "the", "tibia", "and", "fibula,", "anterior", "to", "the", "syndesmosis", "to", "the", "anterior", "aspect", "of", "the", "lateral", "malleolus.", "The", "incidence", "of", "the", "accessory", "fascicle", "differs", "very", "widely", "in", "the", "several", "studies.", "The", "presence", "of", "the", "distal", "fascicle", "of", "the", "AITFL", "and", "also", "the", "contact", "with", "the", "anterolateral", "talus", "is", "probably", "a", "normal", "find-", "ing.", "It", "may", "become", "pathological,", "due", "to", "anatomical", "variations", "and/or", "anterolateral", "instability", "of", "the", "ankle", "resulting", "from", "an", "anterior", "talofibular", "ligament", "injury.", "When", "observed", "during", "an", "ankle", "arthroscopy,", "the", "sur-", "geon", "should", "look", "for", "the", "criteria", "described", "to", "decide", "whether", "it", "is", "pathological", "and", "considering", "resection", "M.", "P.", "J.", "van", "den", "Bekerom", "E.", "E.", "J.", "Raven", "Department", "of", "Orthopaedic", "Surgery,", "Gelre", "Hospitals,", "Apeldoorn,", "The", "Netherlands", "M.", "P.", "J.", "van", "den", "Bekerom", "(&)", "Department", "of", "Surgery", "and", "Traumatology,", "Gelre", "Hospitals,", "Location", "Lukas,", "P.O.", "Box", "9014,", "7300", "Apeldoorn,", "The", "Netherlands", "e-mail:", "Bekerom@gmail.com", "of", "the", "distal", "fascicle.", "The", "presence", "of", "the", "AITFL", "and", "the", "contact", "with", "the", "talus", "is", "a", "normal", "finding.", "An", "impingement", "of", "the", "AITFL", "can", "result", "from", "an", "ana-", "tomical", "variant", "or", "anteroposterior", "instability", "of", "the", "ankle.", "The", "diagnosis", "of", "ligamentous", "impingement", "in", "the", "anterior", "aspect", "of", "the", "ankle", "should", "be", "considered", "in", "patients", "who", "have", "chronic", "ankle", "pain", "in", "the", "antero-", "lateral", "aspect", "of", "the", "ankle", "after", "an", "inversion", "injury", "and", "have", "a", "stable", "ankle,", "normal", "plain", "radiographs,", "and", "isolated", "point", "tenderness", "on", "the", "anterolateral", "aspect", "of", "the", "talar", "dome", "and", "in", "the", "anteroinferior", "tibiofibular", "ligament.", "The", "impingement", "syndrome", "can", "be", "treated", "arthroscopically.", "Keywords", "Ankle", "Impingement", "syndrome", "Anterior", "inferior", "tibiofibular", "ligament", "Accessory", "fascicle", "Introduction", "Impingement", "syndromes", "of", "the", "ankle", "involve", "either", "osseous", "or", "soft", "tissue", "impingement", "and", "can", "be", "anterior,", "anterolateral,", "or", "posterior", "[5,", "25].", "Ankle", "impingement", "syndromes", "are", "painful", "conditions", "caused", "by", "the", "friction", "of", "joint", "tissues,", "which", "are", "both", "the", "cause", "and", "the", "effect", "of", "altered", "joint", "biomechanics", "[14].", "The", "leading", "causes", "of", "impingement", "lesions", "are", "post-traumatic", "ankle", "injuries,", "usually", "ankle", "sprains,", "resulting", "in", "chronic", "ankle", "pain", "[33].", "According", "to", "the", "ISAKOS", "definition,", "anterior", "ankle", "impingement", "is", "a", "pain", "syndrome", "char-", "acterised", "by", "anterior", "ankle", "pain", "on", "activity.", "Recurrent", "dorsiflexion", "is", "often", "the", "cause.", "On", "investigation,", "there", "is", "pain", "on", "palpation", "at", "the", "antero/medial", "and/or", "ante-", "rolateral", "aspect", "of", "the", "ankle", "joint.", "Some", "swelling", "and/", "123" ]

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[ "Theme", "and", "Variations", "in", "the", "Evolutionary", "Pathways", "to", "Virulence", "of", "an", "RNA", "Plant", "Virus", "Species", "Agn", "e`s", "Pinel-Galzi1,", "Mbolarinosy", "Rakotomalala2,", "Emmanuel", "Sangu3,", "Fatogoma", "Sorho4,", "Zakaria", "Kanyeka3,", "Oumar", "Traor", "e´5,", "Drissa", "Se´", "r", "e´m", "e´5,", "Nils", "Poulicard1,", "Yvonne", "Rabenantoandro6,", "Yacouba", "Se´", "r", "e´4,", "Gnissa", "Konat", "e´5,", "Alain", "Ghesquie`", "re7,", "Euge´", "nie", "He´", "brard1,", "Denis", "Fargette1*", "1", "Institut", "de", "Recherche", "pour", "le", "De´veloppement", "(IRD),", "UMR", "RPB,", "Montpellier,", "France,", "2", "Centre", "National", "de", "la", "Recherche", "Applique´e", "au", "De´veloppement", "Rural", "(FOFIFA),", "Mahajanga,", "Madagascar,", "3", "Botany", "Department,", "Dar", "es", "Salaam", "University,", "Dar", "es", "Salaam,", "Tanzania,", "4", "Africa", "Rice", "Center", "(WARDA),", "Cotonou,", "Be´nin,", "5", "Institut", "de", "l’Environnement", "et", "de", "Recherches", "Agricoles", "(INERA),", "Laboratoire", "de", "Biotechnologie", "et", "de", "Virologie", "Ve´ge´tale,", "Kamboinse´,", "Ouagadougou,", "Burkina", "Faso,", "6", "Centre", "National", "de", "la", "Recherche", "Applique´e", "au", "De´veloppement", "Rural", "(FOFIFA),", "Antananarivo,", "Madagascar,", "7", "Institut", "de", "Recherche", "pour", "le", "De´veloppement", "(IRD),", "UMR", "GDP,", "Montpellier,", "France", "The", "diversity", "of", "a", "highly", "variable", "RNA", "plant", "virus", "was", "considered", "to", "determine", "the", "range", "of", "virulence", "substitutions,", "the", "evolutionary", "pathways", "to", "virulence,", "and", "whether", "intraspecific", "diversity", "modulates", "virulence", "pathways", "and", "propensity.", "In", "all,", "114", "isolates", "representative", "of", "the", "genetic", "and", "geographic", "diversity", "of", "Rice", "yellow", "mottle", "virus", "(RYMV)", "in", "Africa", "were", "inoculated", "to", "several", "cultivars", "with", "eIF(iso)4G-mediated", "Rymv1-2", "resistance.", "Altogether,", "41", "virulent", "variants", "generated", "from", "ten", "wild", "isolates", "were", "analyzed.", "Nonconservative", "amino", "acid", "replacements", "at", "five", "positions", "located", "within", "a", "stretch", "of", "15", "codons", "in", "the", "central", "region", "of", "the", "79-aa-long", "protein", "VPg", "were", "associated", "with", "virulence.", "Virulence", "substitutions", "were", "fixed", "predominantly", "at", "codon", "48", "in", "most", "strains,", "whatever", "the", "host", "genetic", "background", "or", "the", "experimental", "conditions.", "There", "were", "one", "major", "and", "two", "isolate-specific", "mutational", "pathways", "conferring", "virulence", "at", "codon", "48.", "In", "the", "prevalent", "mutational", "pathway", "I,", "arginine", "(AGA)", "was", "successively", "displaced", "by", "glycine", "(GGA)", "and", "glutamic", "acid", "(GAA).", "Substitutions", "in", "the", "other", "virulence", "codons", "were", "displaced", "when", "E48", "was", "fixed.", "In", "the", "isolate-specific", "mutational", "pathway", "II,", "isoleucine", "(ATA)", "emerged", "and", "often", "later", "coexisted", "with", "valine", "(GTA).", "In", "mutational", "pathway", "III,", "arginine,", "with", "the", "specific", "S2/S3", "strain", "codon", "usage", "AGG,", "was", "displaced", "by", "tryptophane", "(TGG).", "Mutational", "pathway", "I", "never", "arose", "in", "the", "widely", "spread", "West", "African", "S2/S3", "strain", "because", "G48", "was", "not", "infectious", "in", "the", "S2/S3", "genetic", "context.", "Strain", "S2/S3", "least", "frequently", "overcame", "resistance,", "whereas", "two", "geographically", "localized", "variants", "of", "the", "strain", "S4", "had", "a", "high", "propensity", "to", "virulence.", "Codons", "49", "and", "26", "of", "the", "VPg,", "under", "diversifying", "selection,", "are", "candidate", "positions", "in", "modulating", "the", "genetic", "barriers", "to", "virulence.", "The", "theme", "and", "variations", "in", "the", "evolutionary", "pathways", "to", "virulence", "of", "RYMV", "illustrates", "the", "extent", "of", "parallel", "evolution", "within", "a", "highly", "variable", "RNA", "plant", "virus", "species.", "Citation:", "Pinel-Galzi", "A,", "Rakotomalala", "M,", "Sangu", "E,", "Sorho", "F,", "Kanyeka", "Z,", "et", "al.", "(2007)", "Theme", "and", "variations", "in", "the", "evolutionary", "pathways", "to", "virulence", "of", "an", "RNA", "plant", "virus", "species.", "PLoS", "Pathog", "3(11):", "e180.", "doi:10.1371/journal.ppat.0030180", "Introduction", "Parallel", "evolution", "is", "the", "evolution", "of", "similar", "or", "identical", "features", "independently", "in", "related", "lineages", "when", "subjected", "to", "similar", "selection", "pressures", "[1,2].", "Parallel", "evolution", "has", "been", "reported", "extensively", "both", "in", "natural", "isolates", "and", "in", "exper-", "imental", "populations", "of", "many", "microbes,", "most", "often", "viruses", "[2–", "4],", "but", "also", "bacteria", "[5],", "yeast", "[6],", "and", "protozoa", "[7].", "With", "viruses,", "similar", "amino", "acid", "replacements", "often", "occurred", "in", "immune", "or", "antiviral", "escape", "variants.", "This", "is", "usually", "inter-", "preted", "as", "the", "fixation", "of", "a", "mutation", "with", "a", "beneficial", "effect.", "However,", "differences", "in", "founding", "genotypes", "may", "result", "in", "divergent", "evolutionary", "trajectories", "[5].", "So,", "patterns", "of", "adaptation", "to", "selective", "constraints", "may", "also", "be", "dependent", "on", "intraspecific", "polymorphisms.", "This", "is", "well", "documented", "for", "HIV", "resistance", "to", "antiretroviral", "agents,", "where", "pathways", "of", "viral", "evolution", "towards", "drug", "resistance", "may", "proceed", "through", "distinct", "steps", "and", "at", "different", "rates", "among", "different", "HIV", "subtypes", "[8,9].", "The", "objective", "of", "this", "article", "is", "to", "assess", "the", "extent", "of", "parallel", "evolution", "in", "a", "highly", "variable", "RNA", "plant", "virus", "species.", "Then,", "the", "diversity", "of", "Rice", "yellow", "mottle", "virus", "(RYMV)", "was", "considered", "to", "determine", "the", "range", "of", "virulence", "substitutions,", "to", "reconstruct", "the", "evolutionary", "pathways", "to", "virulence,", "and", "to", "test", "whether", "intraspecific", "diversity", "modu-", "lates", "virulence", "pathways", "and", "propensity.", "The", "breakdown", "of", "host", "plant", "resistance", "is", "a", "well-docu-", "mented", "case", "of", "virus", "adaptation", "[10].", "Translation", "initiation", "factors", "of", "the", "eIF4E", "and", "eIF4G", "families", "are", "major", "determi-", "nants", "of", "recessive", "resistance", "to", "plant", "viruses", "[11,12].", "Several", "studies", "showed", "that", "one", "or", "a", "few", "amino", "acid", "substitutions", "in", "the", "genome-linked", "viral", "protein", "VPg", "are", "independently", "responsible", "for", "virulence", "(see", "[12]", "for", "a", "recent", "review).", "In", "Editor:", "Edward", "C.", "Holmes,", "The", "Pennsylvania", "State", "University,", "United", "States", "of", "America", "Received", "June", "11,", "2007;", "Accepted", "October", "12,", "2007;", "Published", "November", "23,", "2007", "Copyright:", "2007", "Pinel-Galzi", "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.", "Abbreviations:", "NIL,", "nearly", "isogenic", "line;", "ORF,", "open", "reading", "frame;", "PI,", "protease", "inhibitor;", "RYMV,", "Rice", "yellow", "mottle", "virus", "*", "To", "whom", "correspondence", "should", "be", "addressed.", "E-mail:", "Denis.Fargette@mpl.ird.fr", "PLoS", "Pathogens", "|", "www.plospathogens.org", "1761", "November", "2007", "|", "Volume", "3", "|", "Issue", "11", "|", "e180" ]

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[ "BMC", "Genomics", "Research", "article", "The", "trypanosome", "transcriptome", "is", "remodelled", "during", "differentiation", "but", "displays", "limited", "responsiveness", "within", "life", "stages", "V", "Lila", "Koumandou,", "Senthil", "Kumar", "A", "Natesan,", "Tatiana", "Sergeenko", "and", "Mark", "C", "Field*", "BioMed", "Central", "Open", "Access", "Address:", "The", "Molteno", "Building,", "Department", "of", "Pathology,", "University", "of", "Cambridge,", "Tennis", "Court", "Road,", "Cambridge,", "CB2", "1QP,", "UK", "Email:", "V", "Lila", "Koumandou", "-", "vk219@cam.ac.uk;", "Senthil", "Kumar", "A", "Natesan", "-", "ska23@mole.bio.cam.ac.uk;", "Tatiana", "Sergeenko", "-", "ts329@cam.ac.uk;", "Mark", "C", "Field*", "-", "mcf34@cam.ac.uk", "*", "Corresponding", "author", "Published:", "23", "June", "2008", "BMC", "Genomics", "2008,", "9:298", "doi:10.1186/1471-2164-9-298", "This", "article", "is", "available", "from:", "http://www.biomedcentral.com/1471-2164/9/298", "Received:", "3", "March", "2008", "Accepted:", "23", "June", "2008", "©", "2008", "Koumandou", "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:", "Trypanosomatids", "utilise", "polycistronic", "transcription", "for", "production", "of", "the", "vast", "majority", "of", "protein-coding", "mRNAs,", "which", "operates", "in", "the", "absence", "of", "gene-specific", "promoters.", "Resolution", "of", "nascent", "transcripts", "by", "polyadenylation", "and", "trans-splicing,", "together", "with", "specific", "rates", "of", "mRNA", "turnover,", "serve", "to", "generate", "steady", "state", "transcript", "levels", "that", "can", "differ", "in", "abundance", "across", "several", "orders", "of", "magnitude", "and", "can", "be", "developmentally", "regulated.", "We", "used", "a", "targeted", "oligonucleotide", "microarray,", "representing", "the", "strongly", "developmentally-regulated", "T.", "brucei", "membrane", "trafficking", "system", "and", "~10%", "of", "the", "Trypanosoma", "brucei", "genome,", "to", "investigate", "both", "between-stage,", "or", "differentiation-dependent,", "transcriptome", "changes", "and", "within-stage", "flexibility", "in", "response", "to", "various", "challenges.", "Results:", "6%", "of", "the", "gene", "cohort", "are", "developmentally", "regulated,", "including", "several", "small", "GTPases,", "SNAREs,", "vesicle", "coat", "factors", "and", "protein", "kinases", "both", "consistent", "with", "and", "extending", "previous", "data.", "Therefore", "substantial", "differentiation-dependent", "remodeling", "of", "the", "trypanosome", "transcriptome", "is", "associated", "with", "membrane", "transport.", "Both", "the", "microarray", "and", "qRT-PCR", "were", "then", "used", "to", "analyse", "transcriptome", "changes", "resulting", "from", "specific", "gene", "over-expression,", "knockdown,", "altered", "culture", "conditions", "and", "chemical", "stress.", "Firstly,", "manipulation", "of", "Rab5", "expression", "results", "in", "co-ordinate", "changes", "to", "clathrin", "protein", "expression", "levels", "and", "endocytotic", "activity,", "but", "no", "detectable", "changes", "to", "steady-state", "mRNA", "levels,", "which", "indicates", "that", "the", "effect", "is", "mediated", "post-transcriptionally.", "Secondly,", "knockdown", "of", "clathrin", "or", "the", "variant", "surface", "glycoprotein", "failed", "to", "perturb", "transcription.", "Thirdly,", "exposure", "to", "dithiothreitol", "or", "tunicamycin", "revealed", "no", "evidence", "for", "a", "classical", "unfolded", "protein", "response,", "mediated", "in", "higher", "eukaryotes", "by", "transcriptional", "changes.", "Finally,", "altered", "serum", "levels", "invoked", "little", "transcriptome", "alteration", "beyond", "changes", "to", "expression", "of", "ESAG6/7,", "the", "transferrin", "receptor.", "Conclusion:", "While", "trypanosomes", "regulate", "mRNA", "abundance", "to", "effect", "the", "major", "changes", "accompanying", "differentiation,", "a", "given", "differentiated", "state", "appears", "transcriptionally", "inflexible.", "The", "implications", "of", "the", "absence", "of", "a", "transcriptome", "response", "in", "trypanosomes", "for", "both", "virulence", "and", "models", "of", "life", "cycle", "progression", "are", "discussed.", "Page", "1", "of", "28", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Hindawi", "Publishing", "Corporation", "Oxidative", "Medicine", "and", "Cellular", "Longevity", "Volume", "2012,", "Article", "ID", "428010,", "11", "pages", "doi:10.1155/2012/428010", "Review", "Article", "Mechanism", "of", "Oxidative", "Stress", "in", "Neurodegeneration", "Sonia", "Gandhi", "and", "Andrey", "Y.", "Abramov", "Department", "of", "Molecular", "Neuroscience,", "UCL", "Institute", "of", "Neurology,", "Queen", "Square,", "London", "WC1N", "3BG,", "UK", "Correspondence", "should", "be", "addressed", "to", "Andrey", "Y.", "Abramov,", "a.abramov@ucl.ac.uk", "Received", "13", "December", "2011;", "Accepted", "14", "March", "2012", "Academic", "Editor:", "Krzysztof", "Ksiazek", "Copyright", "©", "2012", "S.", "Gandhi", "and", "A.", "Y.", "Abramov.", "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.", "Biological", "tissues", "require", "oxygen", "to", "meet", "their", "energetic", "demands.", "However,", "the", "consumption", "of", "oxygen", "also", "results", "in", "the", "generation", "of", "free", "radicals", "that", "may", "have", "damaging", "effects", "on", "cells.", "The", "brain", "is", "particularly", "vulnerable", "to", "the", "effects", "of", "reactive", "oxygen", "species", "due", "to", "its", "high", "demand", "for", "oxygen,", "and", "its", "abundance", "of", "highly", "peroxidisable", "substrates.", "Oxidative", "stress", "is", "caused", "by", "an", "imbalance", "in", "the", "redox", "state", "of", "the", "cell,", "either", "by", "overproduction", "of", "reactive", "oxygen", "species,", "or", "by", "dysfunction", "of", "the", "antioxidant", "systems.", "Oxidative", "stress", "has", "been", "detected", "in", "a", "range", "of", "neurodegenerative", "disease,", "and", "emerging", "evidence", "from", "in", "vitro", "and", "in", "vivo", "disease", "models", "suggests", "that", "oxidative", "stress", "may", "play", "a", "role", "in", "disease", "pathogenesis.", "However,", "the", "promise", "of", "antioxidants", "as", "novel", "therapies", "for", "neurodegenerative", "diseases", "has", "not", "been", "borne", "out", "in", "clinical", "studies.", "In", "this", "review,", "we", "critically", "assess", "the", "hypothesis", "that", "oxidative", "stress", "is", "a", "crucial", "player", "in", "common", "neurodegenerative", "disease", "and", "discuss", "the", "source", "of", "free", "radicals", "in", "such", "diseases.", "Furthermore,", "we", "examine", "the", "issues", "surrounding", "the", "failure", "to", "translate", "this", "hypothesis", "into", "an", "effective", "clinical", "treatment.", "1.", "Introduction", "1.1.", "Oxidative", "Stress", "and", "Neurodegeneration.", "It", "has", "been", "long", "recognised", "that", "oxidative", "stress", "may", "be", "important", "in", "the", "aeti-", "ology", "of", "a", "variety", "of", "late", "onset", "neurodegenerative", "diseases.", "Aging", "has", "been", "established", "as", "the", "most", "important", "risk", "factor", "for", "the", "common", "neurodegenerative", "diseases,", "Alzheimer’s", "disease", "(AD),", "and", "Parkinson’s", "disease", "(PD).", "Most", "theories", "of", "aging", "centre", "are", "on", "the", "idea", "that", "cumulative", "oxidative", "stress", "leads", "to", "mitochondrial", "mutations,", "mitochondrial", "dysfunc-", "tion,", "and", "oxidative", "damage", "[1].", "However,", "as", "the", "role", "of", "ROS", "becomes", "increasingly", "recognised", "in", "aging", "and", "age-related", "diseases,", "a", "number", "of", "controversies", "begin", "to", "emerge", "in", "this", "field.", "Is", "oxidative", "stress", "an", "epiphenomenon", "of", "dysfunctional", "and", "dying", "neurons,", "or", "does", "oxidative", "stress", "itself", "cause", "the", "dysfunctionality/death", "of", "neurons?", "How", "does", "a", "global", "event", "such", "as", "oxidative", "stress", "result", "in", "the", "selective", "neuronal", "vulnerability", "seen", "in", "most", "neurodegenerative", "diseases?", "And", "finally,", "if", "oxidative", "stress", "is", "truly", "fundamental", "to", "pathogenesis", "then", "why", "has", "the", "use", "of", "antioxidant", "therapy", "been", "thus", "far", "largely", "unsuccessful", "in", "such", "diseases?", "In", "order", "to", "address", "these", "questions,", "we", "first", "outline", "the", "definition", "of", "oxidative", "stress", "and", "show", "how", "ROS", "is", "generated", "in", "the", "human", "brain", "(Box", "1),", "as", "well", "as", "the", "antioxidant", "defence", "mechanisms", "that", "exist", "to", "counteract", "it", "(Box", "2).", "We", "present", "the", "evidence", "that", "oxidative", "stress", "can", "be", "found", "in", "ne-", "urodegenerative", "disease.", "Next", "we", "address", "the", "issue", "of", "whe-", "ther", "oxidative", "stress", "is", "truly", "pathogenic", "in", "disease", "models.", "In", "order", "to", "prove", "a", "crucial", "of", "ROS,", "it", "is", "necessary", "to", "observe", "oxidative", "stress", "as", "an", "early", "event", "in", "the", "disease", "process,", "and", "to", "further", "demonstrate", "that", "inhibition", "of", "ROS", "production", "is", "able", "to", "prevent", "the", "pathogenic", "process.", "We", "describe", "the", "evidence", "from", "animal", "and", "cellular", "models", "of", "the", "role", "of", "ROS", "in", "the", "major", "neurodegenerative", "diseases.", "We", "present", "hypotheses", "for", "the", "interplay", "between", "oxidative", "stress", "and", "selective", "cell", "death.", "Finally", "we", "study", "the", "rationale", "for", "the", "use", "of", "antioxidant", "therapy", "and", "the", "outcome", "of", "its", "use", "in", "human", "disease.", "Although", "oxidative", "stress", "has", "been", "implicated", "in", "a", "range", "of", "chronic", "neurodegenerative", "disorders,", "including", "Alzheimer’s", "disease,", "Parkinson’s", "disease,", "Huntington’s", "dis-", "ease,", "and", "Amyotrophic", "Lateral", "Sclerosis,", "the", "two", "commonest", "of", "these", "diseases,", "AD", "and", "PD,", "will", "be", "discussed", "in", "detail" ]

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[ "W540–W543", "Nucleic", "Acids", "Research,", "2005,", "Vol.", "33,", "Web", "Server", "issue", "doi:10.1093/nar/gki478", "YASS:", "enhancing", "the", "sensitivity", "of", "DNA", "similarity", "search", "Laurent", "Noe´", "*", "and", "Gregory", "Kucherov", "LORIA/INRIA-Lorraine,", "615", "rue", "du", "Jardin", "Botanique,", "54602", "Villers-les-Nancy,", "France", "Received", "March", "23,", "2005;", "Accepted", "April", "15,", "2005", "ABSTRACT", "YASS", "is", "a", "DNA", "local", "alignment", "tool", "based", "on", "an", "effi-", "cient", "and", "sensitive", "filtering", "algorithm.", "It", "applies", "transition-constrained", "seeds", "to", "specify", "the", "most", "probable", "conserved", "motifs", "between", "homologous", "sequences,", "combined", "with", "a", "flexible", "hit", "criterion", "used", "to", "identify", "groups", "of", "seeds", "that", "are", "likely", "to", "exhibit", "significant", "alignments.", "A", "web", "interface", "(http://www.loria.fr/projects/YASS/)", "is", "available", "to", "upload", "input", "sequences", "in", "fasta", "format,", "query", "the", "program", "and", "visualize", "the", "results", "obtained", "in", "several", "forms", "(dot-plot,", "tabular", "output", "and", "others).", "A", "stan-", "dalone", "version", "is", "available", "for", "download", "from", "the", "web", "page.", "INTRODUCTION", "Modern", "bioinformatics", "relies", "heavily", "on", "alignment", "programs", "and", "motif", "discovery", "tools,", "and", "numerous", "comparative", "genomics", "projects", "need", "ever", "more", "precise", "and", "faster", "tools", "for", "comparing", "two", "or", "several", "genomic", "sequences", "with", "differ-", "ent", "resolutions.", "Except", "for", "small", "sequences,", "the", "exact", "local", "alignment", "algo-", "rithm", "of", "Smith", "and", "Waterman", "(1)", "is", "not", "frequently", "used,", "and", "most", "alignments", "are", "obtained", "using", "heuristic", "alignment", "tools", "such", "as", "FASTA", "(2),", "FLASH", "(3),", "BLAST", "(4,5),", "BLASTZ", "(6)", "and", "PatternHunter", "(7,8).", "All", "these", "methods", "introduce", "a", "trade-", "off", "between", "two", "competing", "parameters:", "selectivity", "(or", "speci-", "ficity)", "directly", "affecting", "the", "speed", "of", "the", "algorithm", "and", "sensitivity", "affecting", "its", "precision", "(i.e.", "the", "number", "of", "relevant", "alignments", "missed).", "Achieving", "a", "good", "trade-off", "between", "sens-", "itivity", "and", "selectivity", "is", "the", "key", "issue", "in", "local", "alignment", "tools.", "The", "recently", "introduced", "spaced", "seeds", "technique", "(7,8)", "allows", "an", "increase", "in", "sensitivity", "without", "loss", "in", "selectivity.", "This", "innovation", "triggered", "various", "studies", "(9–15)", "related", "to", "the", "usage,", "design", "and", "generalizations", "of", "spaced", "seeds.", "In", "this", "note,", "we", "present", "YASS", "(Yet", "Another", "Similarity", "Searcher)—a", "new", "software", "for", "computing", "local", "alignments", "of", "two", "DNA", "sequences—and", "its", "web", "server", "(http://yass.", "loria.fr/interface.php).", "Compared", "with", "other", "tools,", "YASS", "is", "based", "on", "two", "innovations.", "The", "first", "is", "a", "new", "spaced", "seed", "model", "called", "transition-constrained", "seeds", "that", "takes", "advantage", "of", "statistical", "properties", "of", "real", "genomic", "sequences.", "The", "second", "feature", "is", "a", "new", "statistically", "founded", "hit", "criterion", "that", "controls", "the", "formation", "of", "groups", "of", "closely", "located", "seeds", "that", "are", "likely", "to", "belong", "to", "the", "same", "alignment.", "An", "implementation", "of", "these", "improvements,", "reported", "here,", "provides", "a", "fast", "and", "sensitive", "tool", "for", "local", "alignment", "of", "large", "genomic", "sequences.", "DESCRIPTION", "Web", "interface", "The", "main", "user", "input", "(Figure", "1A)", "consists", "of", "one", "or", "two", "sequences", "in", "fasta", "format", "either", "chosen", "from", "a", "predefined", "database", "or", "uploaded", "to", "the", "web", "server.", "Once", "sequences", "have", "been", "selected,", "the", "user", "can", "run", "the", "program", "right", "away", "with", "all", "other", "parameters", "set", "by", "default.", "Alternatively,", "the", "user", "can", "set", "other", "parameters", "such", "as", "the", "scoring", "matrix", "or", "gap", "penalties", "(preselected", "matrices", "are", "pro-", "posed),", "and", "specify", "the", "DNA", "strain", "to", "be", "processed", "(direct,", "complementary", "or", "both).", "The", "user", "can", "also", "choose", "to", "display", "complete", "alignments", "rather", "than", "only", "alignment", "positions.", "More", "advanced", "parameters", "are", "available", "for", "expert", "users.", "For", "example,", "the", "right", "choice", "of", "the", "seed", "pattern", "can", "increase", "the", "search", "sensitivity", "considerably", "provided", "that", "some", "knowledge", "of", "target", "alignments", "is", "available", "(10–14).", "The", "web", "interface", "provides", "a", "preselection", "of", "seeds", "including", "three", "transition-constrained", "seeds,", "one", "providing", "a", "good", "perform-", "ance", "compromise", "between", "coding", "and", "non-coding", "sequences,", "and", "the", "other", "two", "tuned", "respectively", "for", "non-coding", "and", "coding", "regions.", "The", "accompanying", "Hedera", "program", "(http://", "www.loria.fr/projects/YASS/hedera.html)", "is", "also", "provided", "for", "advanced", "users", "in", "order", "to", "design", "new", "seed", "patterns", "according", "to", "different", "probabilistic", "models", "of", "alignments", "(15).", "Finally,", "the", "user", "can", "specify", "some", "statistical", "parameters", "of", "target", "alignments,", "such", "as", "the", "assumed", "substitution", "rate", "or", "indel", "rate.", "These", "parameters", "control", "the", "hit", "criterion,", "i.e.", "the", "rules", "for", "grouping", "together", "closely", "located", "seeds", "to", "detect", "similarities.", "*To", "whom", "correspondence", "should", "be", "addressed.", "Tel:", "+33", "3", "83", "59", "30", "11;", "Fax:", "+33", "3", "83", "27", "83", "19;", "Email:", "Laurent.Noe@loria.fr", "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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[ "Acta", "Neuropathol", "(2011)", "122:293–311", "DOI", "10.1007/s00401-011-0834-y", "O", "R", "I", "G", "I", "N", "A", "L", "P", "A", "P", "E", "R", "Vascular", "b-amyloid", "and", "early", "astrocyte", "alterations", "impair", "cerebrovascular", "function", "and", "cerebral", "metabolism", "in", "transgenic", "arcAb", "mice", "Mario", "Merlini", "•", "Eric", "P.", "Meyer", "•", "Alexandra", "Ulmann-Schuler", "•", "Roger", "M.", "Nitsch", "Received:", "10", "December", "2010", "/", "Revised:", "11", "April", "2011", "/", "Accepted:", "4", "May", "2011", "/", "Published", "online:", "19", "June", "2011", "The", "Author(s)", "2011.", "This", "article", "is", "published", "with", "open", "access", "at", "Springerlink.com", "Abstract", "Cerebrovascular", "lesions", "related", "to", "congophilic", "amyloid", "angiopathy", "(CAA)", "often", "accompany", "deposition", "of", "b-amyloid", "(Ab)", "in", "Alzheimer’s", "disease", "(AD),", "leading", "to", "disturbed", "cerebral", "blood", "flow", "and", "cognitive", "dysfunction,", "posing", "the", "question", "how", "cerebrovascular", "pathology", "con-", "tributes", "to", "the", "pathology", "of", "AD.", "To", "address", "this", "question,", "we", "characterised", "the", "morphology,", "biochemistry", "and", "func-", "tionality", "of", "brain", "blood", "vessels", "in", "transgenic", "arctic", "b-amyloid", "(arcAb)", "mice", "expressing", "human", "amyloid", "pre-", "cursor", "protein", "(APP)", "with", "both", "the", "familial", "AD-causing", "Swedish", "and", "Arctic", "mutations;", "these", "mice", "are", "characterised", "by", "strong", "CAA", "pathology.", "Mice", "were", "analysed", "at", "early,", "mid", "and", "late-stage", "pathology.", "Expression", "of", "the", "glucose", "transporter", "GLUT1", "at", "the", "blood–brain", "barrier", "(BBB)", "was", "significantly", "decreased", "and", "paralleled", "by", "impaired", "in", "vivo", "blood-to-brain", "glucose", "transport", "and", "reduced", "cerebral", "lac-", "tate", "release", "during", "neuronal", "activation", "from", "mid-stage", "pathology", "onwards.", "Reductions", "in", "astrocytic", "GLUT1", "and", "lactate", "transporters,", "as", "well", "as", "retraction", "of", "astrocyte", "end-", "feet", "and", "swelling", "consistent", "with", "neurovascular", "uncoupling,", "preceded", "wide-spread", "b-amyloid", "plaque", "pathology.", "We", "M.", "Merlini", "(&)", "R.", "M.", "Nitsch", "(&)", "Division", "of", "Psychiatry", "Research,", "University", "of", "Zu¨rich,", "August", "Forel-Strasse", "1,", "8008", "Zurich,", "Switzerland", "e-mail:", "mario.merlini@gladstone.ucsf.edu", "R.", "M.", "Nitsch", "e-mail:", "nitsch@bli.uzh.ch", "E.", "P.", "Meyer", "A.", "Ulmann-Schuler", "Institute", "of", "Molecular", "Life", "Sciences,", "University", "of", "Zu¨rich,", "Winterthurerstrasse", "190,", "8057", "Zurich,", "Switzerland", "Present", "Address:", "M.", "Merlini", "Gladstone", "Institute", "of", "Neurological", "Disease,", "1650", "Owens", "Street,", "San", "Francisco,", "CA", "94158,", "USA", "show", "that", "CAA", "at", "later", "disease", "stages", "is", "accompanied", "by", "severe", "morphological", "alterations", "of", "brain", "blood", "vessels", "including", "stenoses,", "BBB", "leakages", "and", "the", "loss", "of", "vascular", "smooth", "muscle", "cells", "(SMCs).", "Together,", "our", "data", "establish", "that", "cerebrovascular", "and", "astrocytic", "pathology", "are", "paralleled", "by", "impaired", "cerebral", "metabolism", "in", "arcAb", "mice,", "and", "that", "astrocyte", "alterations", "occur", "already", "at", "premature", "stages", "of", "pathology,", "suggesting", "that", "astrocyte", "dysfunction", "can", "con-", "tribute", "to", "early", "behavioural", "and", "cognitive", "impairments", "seen", "in", "these", "mice.", "Keywords", "Alzheimer’s", "disease", "Congophilic", "amyloid", "angiopathy", "Cerebral", "glucose", "metabolism", "Astrocytes", "Introduction", "Vascular", "accumulation", "of", "b-amyloid", "(Ab)", "results", "in", "con-", "gophilic", "amyloid", "angiopathy", "(CAA),", "a", "vascular", "lesion", "diagnosed", "as", "part", "of", "b-amyloid", "pathology", "in", "up", "to", "90%", "of", "post-mortem", "brains", "with", "a", "neuropathological", "diagnosis", "of", "Alzheimer’s", "disease", "(AD)", "[57].", "CAA", "is", "associated", "with", "a", "plethora", "of", "abnormalities", "and", "malfunctioning", "of", "the", "cere-", "brovasculature", "[6,", "15,", "40,", "49,", "52,", "64]", "including", "ruptures", "of", "the", "vessel", "walls", "causing", "microhaemorrhages", "and", "lesions", "of", "the", "blood–brain", "barrier", "(BBB),", "resulting", "in", "inflammation,", "vascular", "oedema", "and", "uncontrolled", "influx", "of", "peripheral", "blood", "components", "into", "the", "brain", "parenchyma", "[65].", "As", "a", "result", "of", "CAA,", "vascular", "basement", "membranes", "(VBM)", "thicken", "and", "smooth", "muscle", "cells", "(SMC)", "degenerate,", "jointly", "leading", "to", "impaired", "cerebral", "blood", "flow", "(CBF)", "[15,", "18,", "40].", "Physiological", "functions", "of", "the", "cerebral", "vasculature", "are", "compromised", "early,", "possibly", "even", "preceding", "the", "onset", "of", "AD", "pathology", "including", "the", "onset", "of", "CAA,", "and", "raising", "the", "123" ]

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"included", "in", "current", "guidelines.", "Methods:", "A", "guideline", "implementability", "framework", "was", "developed", "by", "reviewing", "the", "implementation", "science", "literature.", "We", "then", "examined", "whether", "guidelines", "included", "these,", "or", "additional", "implementability", "elements.", "Data", "were", "extracted", "from", "publicly", "available", "high", "quality", "guidelines", "reflecting", "primary", "and", "institutional", "care,", "reviewed", "independently", "by", "two", "individuals,", "who", "through", "discussion", "resolved", "conflicts,", "then", "by", "the", "research", "team.", "Results:", "The", "final", "implementability", "framework", "included", "22", "elements", "organized", "in", "the", "domains", "of", "adaptability,", "usability,", "validity,", "applicability,", "communicability,", "accommodation,", "implementation,", "and", "evaluation.", "Data", "were", "extracted", "from", "20", "guidelines", "on", "the", "management", "of", "diabetes,", "hypertension,", "leg", "ulcer,", "and", "heart", "failure.", "Most", "contained", "a", "large", "volume", "of", "graded,", "narrative", "evidence,", "and", "tables", "featuring", "complementary", "clinical", "information.", "Few", "contained", "additional", "features", "that", "could", "improve", "guideline", "use.", "These", "included", "alternate", "versions", "for", "different", "users", "and", "purposes,", "summaries", "of", "evidence", "and", "recommendations,", "information", "to", "facilitate", "interaction", "with", "and", "involvement", "of", "patients,", "details", "of", "resource", "implications,", "and", "instructions", "on", "how", "to", "locally", "promote", "and", "monitor", "guideline", "use.", "There", "were", "no", "consistent", "trends", "by", "guideline", "topic.", "Conclusions:", "Numerous", "opportunities", "were", "identified", "by", "which", "guidelines", "could", "be", "modified", "to", "support", "various", "types", "of", "decision", "making", "by", "different", "users.", "New", "governance", "structures", "may", "be", "required", "to", "accommodate", "development", "of", "guidelines", "with", "these", "features.", "Further", "research", "is", "needed", "to", "validate", "the", "proposed", "framework", "of", "guideline", "implementability,", "develop", "methods", "for", "preparing", "this", "information,", "and", "evaluate", "how", "inclusion", "of", "this", "information", "influences", "guideline", "use.", "Background", "Guidelines", "are", "syntheses", "of", "best", "available", "evidence", "that", "support", "decision", "making", "by", "clinicians,", "managers,", "and", "policy", "makers", "about", "the", "organization", "and", "delivery", "of", "healthcare,", "but", "continue", "to", "be", "underused.", "Numerous", "population-based", "studies", "demonstrate", "low", "compliance", "with", "guidelines", "produced", "by", "prominent", "government", "and", "professional", "agencies", "for", "chronic", "and", "acute", "conditions", "[1-7].", "It", "has", "been", "proposed", "that", "for", "a", "condition", "such", "as", "cancer,", "a", "third", "of", "cases", "could", "be", "prevented,", "another", "*", "Correspondence:", "anna.gagliardi@uhnresearch.ca", "1Departments", "of", "Surgery;", "and", "Department", "of", "Health", "Policy,", "Management", "and", "Evaluation;", "and", "Institute", "of", "Medical", "Science,", "Faculty", "of", "Medicine,", "University", "of", "Toronto,", "Toronto,", "Ontario,", "Canada", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "third", "cured,", "and", "the", "remainder", "effectively", "treated", "if", "management", "consistently", "complied", "with", "existing", "guide-", "lines", "[8].", "Thus,", "it", "is", "imperative", "that", "we", "better", "implement", "guidelines.", "Many", "existing", "implementation", "strategies", "have", "limited", "effectiveness", "and", "are", "not", "routinely", "applied", "outside", "of", "experimental", "research", "due", "to", "their", "cost", "and", "complexity", "[9-18].", "As", "a", "result", "many", "guidelines", "are", "passively", "distrib-", "uted", "[19-21].", "Surveys", "of", "international", "guideline", "develo-", "pers", "found", "that", "few", "developers", "implemented", "their", "own", "guidelines,", "had", "dedicated", "implementation", "staff,", "or", "evalu-", "ated", "use", "of", "their", "guidelines,", "and", "many", "believed", "that", "tar-", "get", "users", "should", "be", "responsible", "for", "implementation", "[22-25].", "Accountability", "for", "guideline", "implementation", "may", "differ", "by", "jurisdiction", "and", "organization", "depending", "©", "2011", "Gagliardi", "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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[ "Dynamic", "Medicine", "Research", "A", "new", "evaluation", "method", "for", "+Gz", "tolerance", "with", "loratadine", "by", "using", "a", "near-infrared", "spectroscopy", "Akihiko", "Onozawa†,", "Azusa", "Kikukawa†", "and", "Yoshinori", "Miyamoto*", "BioMed", "Central", "Open", "Access", "Address:", "Aeromedical", "Laboratory,", "Japan", "Air", "Self-Defense", "Force,", "Tachikawa,", "Tokyo,", "Japan", "Email:", "Akihiko", "Onozawa", "-", "akihikoonozawa@ybb.ne.jp;", "Azusa", "Kikukawa", "-", "kikukawa4232@inet.asdf.mod.go.jp;", "Yoshinori", "Miyamoto*", "-", "ymiyamo@rivo.mediatti.net", "*", "Corresponding", "author", "†Equal", "contributors", "Published:", "28", "January", "2008", "Dynamic", "Medicine", "2008,", "7:3", "doi:10.1186/1476-5918-7-3", "This", "article", "is", "available", "from:", "http://www.dynamic-med.com/content/7/1/3", "Received:", "19", "October", "2007", "Accepted:", "28", "January", "2008", "©", "2008", "Onozawa", "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:", "Loratadine", "(Claritin®),", "an", "over", "the", "counter", "antihistamine", "in", "U.S.", "and", "UK,", "is", "acceptable", "for", "use", "without", "adverse", "side", "effects", "by", "aircrew", "with", "mild", "or", "moderate", "allergic", "or", "other", "situations", "requiring", "an", "antihistamine.", "Although", "+Gz", "(head", "to", "foot", "direction)", "tolerance", "testing", "for", "aircrew", "with", "loratadine", "has", "not", "been", "documented", "in", "the", "published", "literature,", "it", "is", "commonly", "accepted", "that", "loratadine", "dose", "not", "effect", "+Gz", "tolerance.", "The", "purpose", "of", "this", "study", "was", "to", "offer", "and", "validate", "a", "new", "evaluation", "method", "for", "+Gz", "tolerance", "testing", "with", "loratadine", "by", "using", "a", "near-infrared", "spectroscopy", "(NIRS).", "Methods:", "A", "double-blind,", "placebo-controlled,", "randomized,", "crossover", "protocol", "was", "used", "to", "administer", "10", "mg", "of", "loratadine", "or", "placebo", "in", "nine", "healthy", "subjects.", "The", "subjects", "didn't", "wear", "anti-G", "suit.", "The", "+Gz", "exposure", "profiles", "consisted", "of,", "in", "series,", "a", "gradual", "onset", "ran", "(0.1", "G·sec-1)", "to", "the", "subject's", "visual", "end-point", "(peripheral", "light", "loss)", "or", "loss", "of", "consciousness", "(GLOC),", "and", "rapid", "onset", "run", "(1.0", "G·sec-1)", "to", "the", "subject's", "same", "end-point.", "In", "this", "study,", "G-level", "tolerance", "was", "defined", "as", "the", "+Gz", "level", "at", "visual", "end-point", "and/or", "at", "GLOC.", "As", "a", "subject's", "G-duration", "tolerance,", "we", "measured", "the", "total", "time", "(seconds)", "during", "rapid", "onset", "run.", "Otherwise,", "to", "confirm", "the", "effect", "of", "loratadine", "on", "+Gz", "tolerance,", "we", "measured", "the", "cerebral", "NIRS", "variables", "(hemoglobin", "concentration", "changes", "and", "tissue", "oxygenation", "index)", "as", "a", "new", "quantitative", "method", "for", "+Gz", "tolerance", "during", "a", "centrifuge", "experiments.", "Results:", "No", "significant", "differences", "were", "observed", "in", "+Gz", "tolerance", "(+Gz", "level,", "duration", "time", "and", "NIRS", "variables)", "between", "subjects", "taking", "loratadine", "and", "placebo.", "Conclusion:", "Our", "results", "demonstrate", "that", "loratadine", "has", "no", "detectable", "effect", "on", "+Gz", "tolerance", "by", "using", "a", "new", "method", "with", "cerebral", "NIRS", "variables", "and", "the", "traditional", "method", "with", "+Gz", "level", "and", "duration", "time.", "This", "study", "represents", "the", "first", "use", "of", "a", "quantitative", "parameter", "such", "as", "cerebral", "NIRS", "variables", "to", "assess", "the", "effects", "of", "a", "drug", "on", "acceleration", "tolerance.", "Background", "Older", "first-generation", "antihistamines,", "such", "as", "diphenhy-", "dramine", "and", "chlorpheniramine,", "are", "unsuitable", "for", "use", "by", "aircrew", "during", "flight", "duties", "due", "to", "their", "well-documented", "sedating", "side", "effects.", "Loratadine", "(Claritin®)", "is", "a", "newer,", "sec-", "ond-generation", "antihistamine", "available", "over-the-counter", "Page", "1", "of", "7", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Gatherer", "BMC", "Systems", "Biology", "2010,", "4:22", "http://www.biomedcentral.com/1752-0509/4/22", "C", "O", "R", "R", "E", "S", "P", "O", "N", "D", "E", "N", "C", "E", "Open", "Access", "So", "what", "do", "we", "really", "mean", "when", "we", "say", "that", "systems", "biology", "is", "holistic?", "Derek", "Gatherer", "Abstract", "Background:", "An", "old", "debate", "has", "undergone", "a", "resurgence", "in", "systems", "biology:", "that", "of", "reductionism", "versus", "holism.", "At", "least", "35", "articles", "in", "the", "systems", "biology", "literature", "since", "2003", "have", "touched", "on", "this", "issue.", "The", "histories", "of", "holism", "and", "reductionism", "in", "the", "philosophy", "of", "biology", "are", "reviewed,", "and", "the", "current", "debate", "in", "systems", "biology", "is", "placed", "in", "context.", "Results:", "Inter-theoretic", "reductionism", "in", "the", "strict", "sense", "envisaged", "by", "its", "creators", "from", "the", "1930s", "to", "the", "1960s", "is", "largely", "impractical", "in", "biology,", "and", "was", "effectively", "abandoned", "by", "the", "early", "1970s", "in", "favour", "of", "a", "more", "piecemeal", "approach", "using", "individual", "reductive", "explanations.", "Classical", "holism", "was", "a", "stillborn", "theory", "of", "the", "1920s,", "but", "the", "term", "survived", "in", "several", "fields", "as", "a", "loose", "umbrella", "designation", "for", "various", "kinds", "of", "anti-reductionism", "which", "often", "differ", "markedly.", "Several", "of", "these", "different", "anti-reductionisms", "are", "on", "display", "in", "the", "holistic", "rhetoric", "of", "the", "recent", "systems", "biology", "literature.", "This", "debate", "also", "coincides", "with", "a", "time", "when", "interesting", "arguments", "are", "being", "proposed", "within", "the", "philosophy", "of", "biology", "for", "a", "new", "kind", "of", "reductionism.", "Conclusions:", "Engaging", "more", "deeply", "with", "these", "issues", "should", "sharpen", "our", "ideas", "concerning", "the", "philosophy", "of", "systems", "biology", "and", "its", "future", "best", "methodology.", "As", "with", "previous", "decisive", "moments", "in", "the", "history", "of", "biology,", "only", "those", "theories", "that", "immediately", "suggest", "relatively", "easy", "experiments", "will", "be", "winners.", "Introduction", "An", "old", "debate", "has", "made", "a", "surprising,", "or", "perhaps", "not", "so", "surprising,", "reappearance", "in", "systems", "biology:", "that", "of", "reductionism", "versus", "holism.", "Surprising:", "in", "the", "sense", "that", "the", "mainstream", "of", "molecular", "biology", "has", "for", "at", "least", "30", "years", "been", "relatively", "uninterested", "in", "the", "matter,", "content", "with", "a", "compromise", "that", "allows", "lab", "work", "to", "proceed", "without", "too", "much", "philosophical", "agonizing.", "Unsurprising:", "in", "that", "general", "systems", "theory", "has", "churned", "with", "the", "debate", "for", "nearly", "75", "years.", "Once", "systems", "theory", "met", "molecular", "biology,", "it", "was", "probably", "only", "a", "matter", "of", "time", "before", "the", "controversy", "went", "pandemic.", "At", "least", "35", "arti-", "cles", "in", "the", "systems", "biology", "literature", "from", "2003", "to", "the", "early", "part", "of", "2009", "touched", "on", "this", "issue", "[1-35].", "How-", "ever,", "much", "confusion", "is", "apparent", "in", "the", "variation", "in", "what", "is", "understood", "by", "the", "term", "holistic,", "and", "also", "from", "overstatements", "as", "to", "the", "degree", "that", "“traditional”", "mole-", "cular", "biology", "is", "truly", "reductionist.", "Some", "of", "the", "systems", "biology", "articles", "give", "the", "impression", "that", "this", "is", "the", "first", "Correspondence:", "d.gatherer@mrcvu.gla.ac.uk", "MRC", "Virology", "Unit,", "Institute", "of", "Virology,", "University", "of", "Glasgow,", "Church", "Street,", "Glasgow", "G11", "5JR,", "UK", "time", "this", "argument", "has", "arisen,", "but", "we", "have", "been", "here", "before", "on", "several", "occasions.", "The", "reductionist-holist", "debate", "emerged", "in", "biology", "in", "the", "1920s", "out", "of", "the", "ear-", "lier", "disputes", "between", "mechanists", "and", "vitalists,", "and", "between", "neo-Darwinians", "and", "neo-Lamarckians,", "although", "it", "should", "not", "be", "thought", "that", "all", "the", "corresponding", "terms", "on", "the", "left", "or", "right", "sides", "of", "each", "pair", "are", "in", "any", "way", "necessarily", "equivalent.", "One", "would", "not", "expect", "any", "aspiring", "modern", "holist", "within", "the", "systems", "biology", "com-", "munity", "to", "be", "a", "vitalist", "or", "a", "neo-Lamarckian.", "Neverthe-", "less,", "broadly", "speaking,", "it", "is", "possible", "to", "see", "general", "continuities", "that", 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[ "Acta", "Crystallographica", "Section", "E", "Structure", "Reports", "Online", "ISSN", "1600-5368", "4-[1-(4-Hydroxy-3-methoxybenzyl)-1H-", "benzimidazol-2-yl]-2-methoxyphenol", "Zuo-an", "Xiao,*", "Tao", "Gao,", "Fa-jun", "Huang", "and", "Ting-ting", "Jiang", "School", "of", "Chemical", "Engineering", "and", "Food", "Science,", "Xiangfan", "University,", "Xiangfan", "441053,", "People’s", "Republic", "of", "China", "Correspondence", "e-mail:", "blueice8250@yahoo.com.cn", "Received", "17", "October", "2011;", "accepted", "23", "October", "2011", "Key", "indicators:", "single-crystal", "X-ray", "study;", "T", "=", "298", "K;", "mean", "(C–C)", "=", "0.002", "A˚;", "R", "factor", "=", "0.058;", "wR", "factor", "=", "0.154;", "data-to-parameter", "ratio", "=", "17.7.", "In", "the", "title", "molecule,", "C22H20N2O4,", "the", "dihedral", "angles", "between", "the", "benzimidazole", "ring", "system", "and", "the", "benzene", "rings", "are", "44.26", "(2)", "and", "82.91", "(2)", ".", 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"organic", "compounds", "=", "0.09", "mm", "1", "T", "=", "298", "K", "Data", "collection", "Bruker", "SMART", "CCD", "diffractometer", "Absorption", "correction:", "multi-scan", "(SADABS;", "Sheldrick,", "1996)", "Tmin", "=", "0.966,", "Tmax", "=", "0.983", "Refinement", "R[F", "2", ">", "2", "(F", "2)]", "=", "0.058", "wR(F", "2)", "=", "0.154", "S", "=", "1.06", "4625", "reflections", "261", "parameters", "Table", "1", "Hydrogen-bond", "geometry", "(A˚", ",", ").", "D—H", "A", "O4—H4A", "O1—H1A", "O4—H4A", "O1—H1A", "C15—H15B", "O3", "O2", "N2i", "O4ii", "O4iii", "D—H", "0.89", "(2)", "0.85", "(3)", "0.89", "(2)", "0.85", "(3)", "0.97", "0.20", "0.20", "0.20", "mm", "14067", "measured", "reflections", "4625", "independent", "reflections", "3718", "reflections", "with", "I", ">", "2", "(I)", "Rint", "=", "0.064", "H", "atoms", "treated", "by", "a", "mixture", "of", "independent", "and", "constrained", "refinement", "max", "=", "0.30", "e", "A˚", "3", "min", "=", "0.23", "e", "A˚", "3", "H", "A", "2.25", "(2)", "2.22", "(3)", "1.90", "(2)", "2.07", "(3)", "2.59", "D", "A", "2.6598", "(18)", "2.6631", "(18)", "2.7671", "(18)", "2.7934", "(17)", "3.402", "(2)", "D—H", "A", "108.0", "(18)", "113", "(2)", "165", "(2)", "143", "(2)", "141", "Symmetry", "codes:", "(i)", "x", "þ", "1;", "y", "þ", "12;", "z", "þ", "12;", "(ii)", "x;", "y", "þ", "21;", "z", "12.", "x", "þ", "2;", "y", "12;", "z", "þ", "32;", "(iii)", "Data", "collection:", "SMART", "(Bruker,", "2001);", "cell", "refinement:", "SAINT", "(Bruker,", "2001);", "data", "reduction:", "SAINT;", "program(s)", "used", "to", "solve", "structure:", "SHELXS97", "(Sheldrick,", "2008);", "program(s)", "used", "to", "refine", "structure:", "SHELXL97", "(Sheldrick,", "2008);", "molecular", "graphics:", "PLATON", "(Spek,", "2009);", "software", "used", "to", "prepare", "material", "for", "publication:", "SHELXTL", "(Sheldrick,", "2008).", "The", "authors", "are", "grateful", "to", "the", "Science", "Technology", "Research", "Programme", "of", "the", "Education", "Office", "of", "Hubei", "Province", "(grant", "No.", "Q20092503)", "for", "financial", "support.", "Supplementary", "data", "and", "figures", "for", "this", "paper", "are", "available", "from", "the", "IUCr", "electronic", "archives", "(Reference:", "LH5356).", "References", "Bruker", "(2001).", "SAINT", "and", "SMART.", "Bruker", "AXS", "Inc.,", "Madison,", "Wisconsin,", "USA.", "Li,", "J.,", "Meng,", "X.-G.", "&", "Liao,", "Z.-R.", "(2005).", "Acta", "Cryst.", "E61,", "o3421–o3423.", "Liu,", "Y.-C.,", "Ma,", "J.-F.,", "Hu,", "N.-H.", "&", "Jia,", "H.-Q.", "(2003).", "Acta", "Cryst.", "E59,", "m361–", "m363.", "Santoro,", "S.", "W.,", "Joyce,", "G.", "F.,", "Sakthivel,", "K.,", "Gramatikova,", "S.", "&", "Barbas,", "C.", "F.", "(2000).", "J.", "Am.", "Chem.", "Soc.", "122,", "2433–2439.", "Sheldrick,", "G.", "M.", "(1996).", "SADABS.", "University", "of", "Go¨", "ttingen,", "Germany.", "Sheldrick,", "G.", "M.", "(2008).", "Acta", "Cryst.", "A64,", "112–122.", "Spek,", "A.", "L.", "(2009).", "Acta", "Cryst.", "D65,", "148–155.", "Sundberg,", "R.", "J.,", "Yilmaz,", "I.", "&", "Mente,", "D.", "C.", "(1977).", "Inorg.", "Chem.", "16,", "1470–1476.", "Xi,", "Y.,", "Jiang,", "M.,", "Li,", "J.,", "Wang,", "C.,", "Yan,", "J.-F.", "&", "Zhang,", "F.-X.", "(2006).", "Acta", "Chim.", "Sin.", "64,", "1183–1188.", "Acta", "Cryst.", "(2011).", "E67,", "o3087", "doi:10.1107/S1600536811043935", "Xiao", "et", "al.", "o3087" ]

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[ "BMC", "Psychiatry", "Research", "article", "The", "factor", "structure", "and", "reliability", "of", "the", "Illness", "Attitude", "Scales", "in", "a", "student", "and", "a", "patient", "sample", "Alexander", "Crössmann*", "and", "Paul", "Pauli", "Address:", "Department", "of", "Psychology", "I,", "University", "of", "Wuerzburg,", "Marcusstr.", "9-11,", "97070", "Wuerzburg,", "Germany", "Email:", "Alexander", "Crössmann*", "-", "alexander@croessmann.org;", "Paul", "Pauli", "-", "pauli@psychologie.uni-wuerzburg.de", "*", "Corresponding", "author", "BioMed", "Central", "Open", "Access", "Published:", "26", "October", "2006", "BMC", "Psychiatry", "2006,", "6:46", "doi:10.1186/1471-244X-6-46", "This", "article", "is", "available", "from:", "http://www.biomedcentral.com/1471-244X/6/46", "Received:", "05", "May", "2006", "Accepted:", "26", "October", "2006", "©", "2006", "Crössmann", "and", "Pauli;", "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", "Illness", "Attitude", "Scales", "(IAS),", "designed", "by", "Kellner", "in", "1986,", "assesses", "fears,", "beliefs,", "and", "attitudes", "associated", "with", "hypochondriasis", "and", "abnormal", "illness", "behaviour.", "However,", "its", "factor", "structure", "is,", "especially", "for", "translations", "of", "the", "IAS,", "not", "sufficiently", "explored.", "Thus,", "the", "present", "Study", "aimed", "to", "analyse", "the", "factor", "structure", "of", "the", "IAS", "in", "a", "German", "student", "and", "a", "patient", "population", "using", "exploratory", "factor", "analysis.", "Methods:", "A", "mixed", "student", "(N", "=", "296)", "and", "a", "mixed", "patient", "(N", "=", "130)", "sample", "completed", "the", "IAS.", "The", "data", "was", "submitted", "to", "principal", "components", "analyses", "(PCA)", "with", "subsequent", "oblique", "rotations.", "From", "identified", "factor", "structures,", "scales", "were", "derived", "and", "submitted", "to", "reliability", "analyses", "as", "well", "as", "to", "a", "preliminary", "validity", "analysis.", "Results:", "The", "PCA", "revealed", "a", "four-factor", "solution", "in", "the", "student", "sample:", "(1)", "fear", "of", "illness", "and", "death;", "(2)", "treatment", "experience;", "(3)", "hypochondriacal", "beliefs;", "and", "(4)", "effect", "of", "symptoms.", "In", "the", "patient", "sample,", "the", "data", "was", "best", "explained", "by", "a", "two-factor", "solution:", "(1)", "health", "related", "anxiety", "and", "(2)", "effect", "of", "symptoms", "and", "treatment", "experience.", "All", "scales", "reached", "good", "to", "acceptable", "reliability", "coefficients.", "The", "scales", "derived", "from", "the", "student", "sample", "and", "those", "derived", "from", "the", "patient", "sample", "were", "able", "to", "distinguish", "between", "pain", "patients", "and", "a", "matched", "group", "of", "normal", "controls.", "Conclusion:", "Our", "data", "suggests", "that", "the", "IAS", "is", "in", "student", "samples", "best", "represented", "by", "a", "four", "factor-solution", "and", "in", "patient", "samples", "by", "a", "two-factor-solution.", "Background", "Hypochondriasis", "as", "described", "in", "DSM-IV", "is", "a", "mental", "dis-", "order", "characterized", "by", "excessive", "fear", "of", "or", "preoccupation", "with", "a", "serious", "illness,", "despite", "medical", "testing", "and", "reassur-", "ance", "to", "the", "contrary", "[1].", "In", "primary", "care", "users", "its", "preva-", "lence", "is", "estimated", "at", "3%", "[2].", "The", "disorder", "can", "significantly", "interfere", "with", "an", "individual's", "functioning", "and", "can", "be", "very", "costly", "to", "the", "health", "care", "system", "when", "it", "results", "in", "high", "lev-", "els", "of", "medical", "services", "utilization.", "To", "detect", "hypochon-", "driasis", "in", "an", "early", "stage,", "it", "is", "very", "important", "that", "self-report", "questionnaires", "are", "developed", "and", "thoroughly", "evaluated.", "One", "of", "the", "most", "popular", "self-report", "measures", "of", "hypo-", "chondriasis", "is", "the", "Illness", "Attitude", "Scales", "(IAS)", "by", "Kellner", "[3].", "The", "questionnaire,", "which", "consists", "of", "29", "self-rated", "items,", "is", "designed", "to", "measure", "abnormal", "illness", "behaviour", "and", "hypochondriasis.", "Twenty-seven", "items", "are", "answered", "on", "a", "five-point", "scale,", "two", "items", "are", "answered", "differently.", "For", "24", "of", "the", "27", "items,", "the", "steps", "of", "the", "scale", "are", "labelled:", "Page", "1", "of", "7", "(page", "number", "not", "for", "citation", "purposes)" ]

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1042, 235, 1054 ], [ 742, 1042, 757, 1056 ] ]

[ "Diagnosis", "of", "Recurrent", "Uterine", "Cervical", "Cancer:", "Computed", "Tomography", "versus", "Positron", "Emission", "Tomography", "Dong", "Hee", "Park,", "MD1", "Kie", "Hwan", "Kim,", "MD1", "Sang", "Yoon", "Park,", "MD2", "Byung", "Hee", "Lee,", "MD1", "Chang", "Woon", "Choi,", "MD3", "Soo", "Yil", "Chin,", "MD1", "Index", "words:", "Uterine", "neoplasms,", "CT", "Uterine", "neoplasms,", "radionuclide", "studies", "Positron", "emission", "tomography", "(PET),", "comparative", "studies", "Korean", "J", "Radiol", "2000;1", ":51-55", "Received", "October", "13,", "1999;", "accepted", "after", "revision", "January", "6,", "2000.", "Departments", "of", "1Diagnostic", "Radiology,", "2Obstetrics", "and", "Gynecology,", "and", "3Nuclear", "Medicine,", "Korea", "Cancer", "Center", "Hospital.", "Address", "reprint", "requests", "to:", "Dong", "Hee", "Park,", "MD,", "Department", "of", "Diagnostic", "Radiology,", "Korea", "Cancer", "Center", "Hospital,", "215-4,", "Gongneung-Dong,", "Nowon-Gu,", "Seoul", "139-240,", "Korea.", "Telephone:", "(822)", "974-2501", "Fax:", "(822)", "972-3093", "Objective:", "To", "determine", "the", "accuracy", "of", "CT", "and", "positron", "emission", "tomogra-", "phy", "(PET)", "in", "the", "diagnosis", "of", "recurrent", "uterine", "cervical", "cancer.", "Materials", "and", "Methods:", "Imaging", "findings", "of", "CT", "and", "PET", "in", "36", "patients", "(mean", "age,", "53", "years)", "in", "whom", "recurrent", "uterine", "cervical", "cancer", "was", "suspected", "were", "analyzed", "retrospectively.", "Between", "October", "1997", "and", "May", "1998,", "they", "had", "under-", "gone", "surgery", "and/or", "radiation", "therapy.", "Tumor", "recurrence", "was", "confirmed", "by", "pathologic", "examination", "or", "follow-up", "studies.", "Results:", "In", "detecting", "recurrent", "uterine", "cervical", "cancer,", "the", "sensitivity,", "specifici-", "ty,", "and", "accuracy", "of", "CT", "were", "77.8%,", "83.3%,", "and", "80.5%,", "respectively,", "while", "for", "PET,", "the", "corresponding", "figures", "were", "100%,", "94.4%,", "and", "97.2%.", "The", "Chi-square", "test", "revealed", "no", "significant", "difference", "in", "specificity", "(p", "=", ".2888),", "but", "significant", "dif-", "ferences", "in", "sensitivity", "(p", "=", ".0339)", "and", "accuracy", "(p", "=", ".0244).", "Conclusion:", "PET", "proved", "to", "be", "a", "reliable", "screening", "method", "for", "detecting", "recur-", "rent", "uterine", "cervical", "cancer,", "but", "to", "determine", "the", "anatomical", "localization", "of", "recur-", "rent", "tumors,", "and", "thus", "decide", "an", "adequate", "treatment", "plan,", "CT", "was", "eventually", "needed.", "T", "he", "recurrence", "rate", "of", "uterine", "cervical", "cancer", "is", "reported", "to", "be", "6.5%", "after", "surgery", "and", "26.2%", "after", "radiation", "therapy", "alone", "(1).", "Radiological", "studies", "such", "as", "intravenous", "urography", "(IVU),", "US,", "CT,", "and", "MR", "imaging", "are", "used", "to", "detect", "recurrent", "cervical", "cancer", "(2).", "It", "is", "difficult,", "however,", "for", "these", "imaging", "modali-", "ties", "to", "differentiate", "recurrent", "tumor", "from", "postoperative", "or", "radiation", "fibrosis,", "and", "to", "de-", "tect", "metastatic", "normal-sized", "lymph", "nodes", "and", "extrapelvic", "metastases", "(2", "7).", "Since", "Di", "Chiro", "et", "al.", "(8)", "first", "used", "it", "to", "detect", "recurrent", "brain", "tumors,", "positron", "emis-", "sion", "tomography", "(PET),", "the", "diagnostic", "modality", "which", "makes", "use", "of", "increased", "glycoly-", "sis", "in", "tumor", "cells,", "has", "been", "used", "to", "detect", "recurrent", "tumors", "in", "many", "organs.", "To", "our", "knowledge,", "no", "report", "has", "described", "the", "diagnosis", "of", "recurrent", "cervical", "cancer", "using", "PET.", "The", "purpose", "of", "this", "study", "is", "to", "compare", "the", "accuracy", "of", "CT", "with", "that", "of", "PET", "in", "the", "detection", "of", "recurrent", "cervical", "cancer.", "MATERIALS", "AND", "METHODS", "Among", "patients", "with", "uterine", "cervical", "cancer", "who", "had", "undergone", "initial", "treatment", "between", "October", "1997", "and", "May", "1998,", "CT", "and", "PET", "were", "performed", "in", "36", "in", "whom", "recurrence", "was", "clinically", "suspected.", "As", "initial", "treatment,", "13", "patients", "had", "undergone", "surgery", "alone,", "14", "radiation", "therapy", "alone,", "and", "nine", "surgery", "and", "postoperative", "radia-", "tion", "therapy.", "Recurrence", "was", "suspected", "on", "the", "basis", "of", "increased", "levels", "of", "serum", "squa-", "Korean", "J", "Radiol", "1(1),", "March", "2000", "51" ]

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[ "Guerrero", "et", "al.", "International", "Journal", "of", "Emergency", "Medicine", "2012,", "5:4", "http://www.intjem.com/content/5/1/4", "C", "A", "S", "E", "R", "E", "P", "O", "R", "T", "Open", "Access", "The", "role", "of", "perfusion", "CT", "in", "identifying", "stroke", "mimics", "in", "the", "emergency", "room:", "a", "case", "of", "status", "epilepticus", "presenting", "with", "perfusion", "CT", "alterations", "Waldo", "R", "Guerrero*,", "Haitham", "Dababneh", "and", "Stephan", "Eisenschenk", "Abstract", "Emergency", "medicine", "physicians", "are", "often", "faced", "with", "the", "challenging", "task", "of", "differentiating", "true", "acute", "ischemic", "strokes", "from", "stroke", "mimics.", "We", "present", "a", "case", "that", "was", "initially", "diagnosed", "as", "acute", "stroke.", "However,", "perfusion", "CT", "and", "EEG", "eventually", "led", "to", "the", "final", "diagnosis", "of", "status", "epilepticus.", "This", "case", "further", "asserts", "the", "role", "of", "CT", "perfusion", "in", "the", "evaluation", "of", "patients", "with", "stroke", "mimics", "in", "the", "emergency", "room", "setting.", "Background", "The", "differentiation", "between", "stroke", "and", "seizure", "can", "be", "a", "clinically", "arduous", "task", "for", "both", "emergency", "medicine", "physicians", "and", "neurologists", "[1,2].", "Patients", "with", "diseases", "that", "mimic", "stroke", "account", "for", "one-fifth", "of", "patients", "with", "brain", "attacks", "[1].", "Imaging", "may", "therefore", "be", "critical", "in", "making", "a", "diagnosis", "in", "the", "acute", "setting.", "Seizure", "is", "one", "condition", "that", "can", "mimic", "a", "stroke.", "Commonly,", "patients", "with", "Todd’s", "paralysis", "or", "those", "with", "nonconvulsive", "status", "epilepticus", "can", "be", "clinically", "indistinct", "from", "those", "with", "acute", "stroke.", "Further", "complicating", "the", "clinical", "scenario,", "seizure", "may", "also", "be", "a", "presenting", "sign", "of", "stroke", "[3].", "Recently", "the", "time", "frame", "for", "standard", "treatment", "of", "acute", "stroke", "with", "IV", "tissue", "plasminogen", "activator", "was", "expanded", "from", "3", "h", "to", "4.5", "h", "from", "ictus", "onset", "[4].", "Although", "this", "extension", "of", "time", "is", "supported", "by", "the", "American", "Heart", "Association,", "it", "is", "not", "FDA", "approved", "and", "comes", "with", "a", "different", "set", "of", "relative", "contraindica-", "tions.", "Intravenous", "thrombolytics", "are", "not", "without", "the", "risk", "of", "complications,", "including", "intracranial", "hemorrhage", "[5].", "Non-contrast", "CT", "(NCCT)", "of", "the", "head", "is", "the", "current", "gold", "standard", "in", "excluding", "intracranial", "hemorrhage", "prior", "to", "administration", "of", "intravenous", "thrombolysis.", "However,", "NCCT", "has", "a", "limited", "role", "in", "differentiating", "those", "patients", "with", "stroke", "from", "those", "with", "seizure.", "*", "Correspondence:", "waldo.guerrero@neurology.ufl.edu", "Department", "of", "Neurology,", "College", "of", "Medicine,", "University", "of", "Florida,", "1601", "Archer", "Road", "Gainesville,", "32610-0236", "FL,", "USA", "Although", "current", "guidelines", "advocate", "only", "NCCT", "as", "the", "imaging", "modality", "of", "choice", "in", "the", "initial", "evaluation", "of", "acute", "stroke,", "this", "case", "illustrates", "the", "importance", "of", "CT", "perfusion", "studies", "in", "the", "radiographic", "evaluation", "of", "brain", "attack", "patients", "in", "order", "to", "avoid", "misdiagnosis", "and", "inad-", "vertent", "treatment", "of", "non-stroke", "patients", "with", "thrombo-", "lytic", "therapy.", "Furthermore,", "whereas", "hypoperfusion", "related", "to", "strokes", "has", "been", "widely", "investigated", "by", "CT-", "perfusion", "imaging", "[6,7],", "this", "case", "demonstrates", "the", "hyperperfusion", "state", "often", "seen", "on", "perfusion", "CT", "in", "emergency", "room", "patients", "with", "epilepsy.", "We", "describe", "an", "interesting", "case", "of", "a", "patient", "presenting", "to", "the", "Shands", "Hospital", "at", "the", "University", "of", "Florida", "emergency", "room", "with", "a", "homonymous", "hemianopsia", "and", "alterations", "on", "perfusion", "CT", "related", "to", "hyperglycemia-induced", "occipital", "status", "epilepticus.", "Case", "presentation", "A", "72-year-old", "man", "with", "a", "past", "medical", "history", "signifi-", "cant", "for", "diabetes", "mellitus", "type", "2", "presented", "to", "the", "Shands", "Hospital", "at", "the", "University", "of", "Florida", "emergency", "room", "with", "sudden", "onset", "of", "visual", "changes.", "The", "patient", "had", "noted", "that", "he", "would", "miss", "objects", "when", "reaching", "for", "them", "at", "home.", "He", "also", "noted", "black", "and", "red", "spots", "and", "prisms", "in", "his", "vision.", "There", "was", "no", "previous", "history", "of", "seizures.", "His", "risk", "factors", "for", "stroke", "included", "his", "age,", "dia-", "betes", "type", "2,", "as", "well", "as", "tobacco", "use.", "The", "NIH", "Stroke", "Scale", "score", "on", "presentation", "was", "2", "with", "a", "complete", "left", "©", "2012", "Guerrero", "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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[ "INTEGRATIVE", "NEUROSCIENCE", "GENERAL", "COMMENTARY", "published:", "18", "May", "2009", "doi:", "10.3389/neuro.07.006.2009", "Retina", "or", "visual", "cortex?The", "site", "of", "phosphene", "induction", "by", "transcranial", "alternating", "current", "stimulation", "Caspar", "M.", "Schwiedrzik*", "Department", "of", "Neurophysiology,", "Max", "Planck", "Institute", "for", "Brain", "Research,", "Frankfurt", "am", "Main,", "Germany", "*Correspondence:", "schwiedrzik@mpih-frankfurt.mpg.de", "A", "commentary", "on", "Frequency-dependent", "electrical", "stimula-", "tion", "of", "the", "visual", "cortex.", "Kanai,", "R.,", "Chaieb,", "L.,", "Antal,", "A.,", "Walsh,", "V.,", "and", "Paulus,", "W.", "(2008).", "Curr.", "Biol.", "18,", "1839–1843.", "Since", "the", "first", "descriptions", "of", "oscillatory", "synchrony", "in", "the", "cortex,", "a", "plethora", "of", "stud-", "ies", "have", "provided", "empirical", "evidence", "for", "correlations", "between", "cortical", "oscillations", "and", "perception,", "attention,", "and", "other", "cog-", "nitive", "functions", "(Tallon-Baudry,", "2009).", "However,", "it", "has", "remained", "difficult", "to", "obtain", "causal", "evidence", "for", "a", "role", "of", "oscil-", "latory", "synchrony", "in", "cortical", "processing.", "Recent", "developments", "in", "noninvasive", "brain", "stimulation", "techniques", "might", "constitute", "a", "new", "approach", "to", "this", "problem", "(Thut", "and", "Miniussi,", "2009).", "In", "a", "recent", "paper", "employ-", "ing", "such", "a", "technique,", "Kanai", "et", "al.", "(2008)", "report", "that", "the", "visibility", "of", "phosphenes", "elicited", "by", "transcranial", "alternating", "cur-", "rent", "stimulation", "(tACS)", "depends", "on", "the", "frequency", "of", "stimulation.", "Specifically,", "at", "a", "frequency", "of", "about", "20", "Hz", "the", "lowest", "intensity", "was", "needed", "to", "produce", "periph-", "eral", "phosphenes.", "Furthermore,", "when", "the", "eyes", "of", "the", "subjects", "were", "closed,", "this", "opti-", "mum", "frequency", "shifted", "to", "a", "frequency", "of", "about", "10", "Hz.", "Interestingly,", "these", "stimula-", "tion", "frequencies", "seem", "to", "correspond", "to", "the", "well", "known", "beta", "(12–30", "Hz)", "and", "alpha", "(8–12", "Hz)", "frequency", "bands", "in", "the", "electro-", "encephalogram", "(EEG),", "and", "alpha", "power", "in", "the", "EEG", "indeed", "increases", "when", "subjects", "close", "their", "eyes.", "Based", "on", "these", "ostensible", "similarities,", "the", "authors", "concluded", "that", "“the", "frequency", "dependency", "is", "caused", "by", "inter-", "actions", "with", "ongoing", "oscillatory", "activity", "in", "the", "stimulated", "cortex”,", "and", "that", "“tACS", "can", "be", "used", "as", "a", "noninvasive", "tool", "for", "establish-", "ing", "a", "causal", "link", "between", "rhythmic", "cortical", "activities", "and", "their", "functions”.", "If", "this", "were", "the", "case,", "tACS", "would", "poten-", "tially", "be", "an", "interesting", "tool", "to", "inquire", "the", "causal", "role", "of", "oscillatory", "synchrony", "in", "cor-", "tical", "processing.", "However,", "previously", "pub-", "lished", "evidence", "renders", "the", "interpretation", "that", "tACS", "interacts", "directly", "with", "cortical", "activity", "questionable:", "It", "has", "been", "suggested", "that", "peripheral", "phosphenes", "as", "observed", "by", "Kanai", "et", "al.", "(2008)", "are", "elicited", "on", "the", "level", "of", "the", "retina,", "and", "not", "in", "cortical", "structures.", "The", "first", "successful", "attempts", "to", "stimulate", "the", "visual", "system", "by", "alternating", "current", "(AC)", "were", "already", "introduced", "in", "the", "first", "half", "of", "the", "last", "century", "by", "one", "of", "the", "pioneers", "of", "the", "EEG,", "Rohracher", "(1935).", "He", "described", "that", "peripheral", "phosphenes", "could", "reliably", "be", "elicited", "by", "AC", "stimulation", "with", "differ-", "ent", "electrode", "configurations", "on", "the", "head.", "The", "most", "consistent", "finding", "was", "a", "frequency", "optimum", "in", "the", "beta", "range", "(15–20", "Hz),", "irrespective", "of", "electrode", "arrangement.", "This", "finding", "corresponds", "well", "to", "the", "more", "recent", "results", "of", "Kanai", "et", "al.", "(2008),", "which", "were", "obtained", "only", "with", "a", "fronto-occipital", "mon-", "tage.", "Based", "on", "the", "result", "that", "the", "intensity", "needed", "to", "elicit", "phosphenes", "increased", "with", "distance", "from", "the", "eye,", "Rohracher", "concluded", "that", "the", "most", "likely", "site", "of", "stimulation", "was", "the", "retina", "(although", "he", "also", "considered", "an", "effect", "of", "AC", "stimulation", "on", "the", "cortex).", "A", "few", "years", "later,", "Schwarz", "(1947)", "showed", "that", "the", "intensity", "needed", "to", "elicit", "phos-", "phenes", "by", "AC", "stimulation", "depends", "on", "the", "adaptational", "state", "of", "the", "eye.", "The", "initial", "adjustment", "of", "retinal", "sensitivity", "to", "back-", "ground", "illumination", "only", "takes", "fractions", "of", "a", "second", "(Meister", "and", "Berry,", "1999),", "thus", "5", "s", "of", "eyes", "closed", "as", "in", "Kanai", "et", "al.", "(2008)", "can", "be", "considered", "a", "case", "of", "dark", "adaptation.", "During", "dark", "adaptation,", "the", "susceptibility", "to", "AC", "stimulation", "shifts", "to", "lower", "frequencies", "(see", "Figure", "1).", "These", "findings", "were", "replicated", "by", "Meyer-Schwickerath", "and", "Magun", "(1951),", "and", "expanded", "to", "the", "field", "of", "color", "vision", "by", "Motokawa", "and", "Ebe", "(1952).", "More", "definite", "proof", "that", "the", "site", "of", "stimulation", "was", "indeed", "the", "retina", "was", "obtained", "by", "Brindley", "(1955).", "Brindley", "used", "conjunctival", "electrodes", "which", "render", "volume", "conduction", "to", "the", "occipital", "cortex", "highly", "unlikely.", "More", "importantly,", "he", "FIGURE", "1", "|", "In", "his", "experiments,", "Schwarz", "(1947)", "varied", "the", "duration", "of", "dark", "adaptation", "and", "the", "frequency", "of", "alternating", "current", "stimulation.", "Without", "dark", "adaptation,", "a", "clear", "frequency", "optimum", "is", "seen", "at", "20", "Hz,", "whereas", "differing", "durations", "of", "dark", "adaptation", "shift", "this", "optimum", "to", "lower", "frequencies", "(10", "Hz)", "(adapted", "from", "Schwarz,", "1947,", "with", "kind", "permission", "from", "Springer", "Science", "+", "Business", "Media).", "Frontiers", "in", "Integrative", "Neuroscience", "www.frontiersin.org", "April", "2009", "|", "Volume", "3", "|", "Article", "6", "|", "1" ]

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[ "Ann", "Dermatol", "Vol.", "23,", "Suppl.", "2,", "2011", "CASE", "REPORT", "Linear", "Focal", "Elastosis", "Following", "Striae", "Distensae", "http://dx.doi.org/10.5021/ad.2011.23.S2.S141", "Linear", "Focal", "Elastosis", "Following", "Striae", "Distensae:", "Further", "Evidence", "of", "Keloidal", "Repair", "Process", "in", "the", "Pathogenesis", "of", "Linear", "Focal", "Elastosis", "Jin", "Seob", "Jeong,", "M.D.,", "Ji", "Yeoun", "Lee,", "M.D.,", "Mi", "Kyeong", "Kim,", "M.D.1,", "Tae", "Young", "Yoon,", "M.D.", "Departments", "of", "Dermatology", "and", "1Internal", "Medicine,", "School", "of", "Medicine", "and", "Medical", "Research", "Institute,", "Chungbuk", "National", "University,", "Cheongju,", "Korea", "Linear", "focal", "elastosis", "(LFE)", "is", "a", "rare", "dermal", "elastosis", "characterized", "by", "hypertrophic", "yellowish", "linear", "plaques", "and", "increased", "abnormal", "elastic", "tissues", "in", "the", "lumbosacral", "area.", "Although", "the", "pathogenesis", "of", "this", "disorder", "remains", "unknown,", "it", "may", "be", "associated", "with", "keloidal", "repair", "process", "(KRP)", "of", "elastic", "tissues", "in", "striae", "distensae", "(SD),", "because", "there", "have", "been", "some", "reported", "cases", "of", "LFE", "accompanied", "by", "SD.", "We", "herein", "report", "a", "14-year-old", "boy", "with", "LFE", "following", "SD", "in", "the", "lumbar", "region.", "Our", "case", "supports", "the", "hypothesis", "of", "KRP", "in", "the", "pathogenesis", "of", "LFE.", "Immunohistochemical", "study", "for", "transforming", "growth", "factor-beta", "(TGF-β)", "was", "negative.", "Therefore,", "we", "assume", "that", "the", "pathogenesis", "of", "KRP", "in", "LFE", "is", "different", "from", "that", "of", "keloid", "development,", "which", "is", "the", "TGF-", "β", "signaling", "pathway.", "(Ann", "Dermatol", "23(S2)", "S141∼S143,", "2011)", "-Keywords-", "Keloidal", "repair", "process,", "Linear", "focal", "elastosis,", "Striae", "dis-", "tensae,", "Transforming", "growth", "factor-beta", "Received", "January", "22,", "2010,", "Revised", "May", "13,", "2010,", "Accepted", "for", "publication", "July", "14,", "2010", "Corresponding", "author:", "Tae", "Young", "Yoon,", "M.D.,", "Department", "of", "Derma-", "tology,", "School", "of", "Medicine", "and", "Medical", "Research", "Institute,", "Chungbuk", "National", "University,", "52", "Naesoodong-ro,", "Heungdeok-gu,", "Cheongju", "361-763,", "Korea.", "Tel:", "82-43-269-6369,", "Fax:", "82-43-266-1698,", "E-mail:", "tyyoon@chungbuk.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.", "INTRODUCTION", "Since", "Burket", "et", "al.1", "described", "three", "white", "elderly", "men", "with", "palpable", "yellow", "lines", "on", "their", "back", "and", "named", "the", "disorder,", "linear", "focal", "elastosis", "(LFE),", "in", "1989,", "many", "cases", "of", "LFE", "have", "been", "reported.", "It", "usually", "occurs", "in", "the", "lumbosacral", "area,", "characterized", "by", "hypertrophic", "yellowish", "linear", "bands", "and", "an", "increase", "of", "abnormal", "elastic", "tissues2.", "Although", "the", "pathogenesis", "of", "LFE", "remains", "unknown,", "it", "may", "be", "associated", "with", "keloidal", "repair", "process", "(KRP)", "of", "elastic", "tissue", "in", "striae", "distensae", "(SD),", "because", "some", "cases", "of", "LFE", "have", "presented", "with", "features", "of", "SD3-5.", "Several", "cases", "of", "LFE,", "including", "two", "cases", "of", "LFE", "with", "SD,", "have", "been", "reported", "since", "we", "first", "reported", "two", "patients", "with", "LFE", "in", "the", "Korean", "dermatologic", "literature6-8.", "We", "herein", "report", "a", "14-year-old", "boy", "with", "LFE", "following", "SD", "in", "the", "same", "region.", "Our", "case", "supports", "the", "hypothesis", "of", "KRP", "in", "the", "patho-", "genesis", "of", "LFE.", "Additionally,", "in", "order", "to", "elucidate", "the", "role", "of", "transforming", "growth", "factor-beta", "(TGF-β)", "in", "the", "patho-", "genesis", "of", "LFE,", "we", "performed", "immunohistochemical", "study", "for", "TGF-β.", "　", "CASE", "REPORT", "A", "14-year-old", "Korean", "boy", "presented", "with", "a", "2-year", "history", "of", "asymptomatic", "multiple", "horizontal", "linear", "lesions", "on", "his", "lumbar", "area.", "His", "familial", "and", "personal", "histories", "were", "unremarkable,", "and", "he", "did", "not", "take", "any", "significant", "medi-", "cations", "such", "as", "steroids.", "He", "denied", "any", "history", "of", "trauma", "on", "his", "lumbar", "area,", "obesity,", "rapid", "growth,", "and", "systemic", "illness.", "He", "recalled", "that", "the", "hypertrophic", "lesions", "arose", "from", "the", "atrophic", "bands,", "and", "the", "atrophic", "bands", "on", "the", "upper", "back", "occurred", "recently.", "Physical", "examination", "revealed", "several", "palpable", "hypertrophic", "yellowish", "bands", "Vol.", "23,", "Suppl.", "2,", "2011", "S141" ]

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[ "Zintl", "et", "al.", "Veterinary", "Research", "2011,", "42:7", "http://www.veterinaryresearch.org/content/42/1/7", "R", "E", "S", "E", "A", "R", "C", "H", "VETERINARY", "RESEARCH", "Open", "Access", "Babesias", "of", "red", "deer", "(Cervus", "elaphus)", "in", "Ireland", "Annetta", "Zintl1,", "Eugene", "J", "Finnerty2,", "Thomas", "M", "Murphy3,", "Theo", "de", "Waal1,", "Jeremy", "S", "Gray2*", "Abstract", "Blood", "samples", "were", "obtained", "from", "38", "wild", "red", "deer", "(Cervus", "elaphus)", "at", "two", "sites", "in", "Ireland", "and", "subjected", "to", "PCR", "analysis", "of", "the", "18S", "rRNA", "gene", "followed", "by", "sequencing.", "Two", "fragments", "of", "the", "18S", "rRNA", "gene", "were", "generated", "by", "two", "different", "PCR", "protocols", "and", "subsequent", "sequencing", "suggested", "that", "at", "least", "six", "of", "the", "deer", "were", "infected", "by", "a", "babesia", "that,", "in", "those", "loci,", "is", "indistinguishable", "from", "Babesia", "divergens,", "an", "important", "tick-borne", "pathogen", "of", "cattle", "and", "of", "zoonotic", "significance.", "Additionally,", "a", "B.", "odocoilei-like", "parasite", "was", "detected", "in", "three", "samples", "and", "a", "babesia", "that", "did", "not", "match", "any", "sequences", "in", "the", "GenBank", "database", "was", "found", "in", "five", "samples.", "Neither", "B.", "capreoli", "nor", "B.", "venatorum", "(EU1)", "were", "found.", "There", "have", "been", "several", "reports", "of", "B.", "divergens", "occurring", "in", "deer", "species,", "including", "red", "deer,", "roe", "deer", "(Capreolus", "capreolus)", "and", "reindeer", "(Rangifer", "tarandus).", "However,", "in", "view", "of", "recent", "re-sequencing", "of", "bovine-origin", "samples", "deposited", "previously", "in", "GenBank,", "it", "is", "unlikely", "that", "any", "of", "these", "sequences", "from", "deer", "are", "B.", "divergens.", "The", "present", "study", "describes", "the", "only", "deer", "piroplasm", "detected", "so", "far", "that", "shows", "complete", "identity", "with", "B.", "divergens,", "in", "just", "over", "half", "of", "the", "18S", "rRNA", "gene.", "The", "entire", "gene", "of", "this", "deer", "parasite", "should", "be", "analysed", "and", "transmission", "experiments", "undertaken", "before", "the", "infectivity", "of", "B.", "divergens", "for", "red", "deer", "can", "be", "confirmed.", "Introduction", "There", "has", "been", "considerable", "recent", "interest", "in", "the", "iden-", "tity", "of", "Babesia", "spp.", "in", "deer,", "because", "of", "concerns", "about", "the", "health", "of", "endangered", "host", "species", "such", "as", "chamois", "(Rupicapra", "r.", "rupicapra)", "[1]", "and", "also", "because", "of", "the", "possibility", "of", "deer", "acting", "as", "reservoirs", "for", "important", "cat-", "tle", "parasites", "such", "as", "Babesia", "divergens", "[2].", "Earlier", "stu-", "dies", "on", "red", "(Cervus", "elaphus)", "and", "sika", "(C.", "nippon)", "deer", "babesias", "in", "Europe", "suggested", "that", "they", "were", "morpholo-", "gically", "and", "antigenically", "indistinguishable", "from", "B.", "diver-", "gens,", "but", "were", "not", "transmissible", "to", "splenectomised", "calves.", "They", "were", "therefore", "tentatively", "identified", "as", "B.", "capreoli", "[3,4],", "which", "was", "first", "observed", "in", "roe", "deer", "(Capreolus", "capreolus)", "[5].", "With", "the", "advent", "of", "molecular", "taxonomy", "based", "on", "analysis", "of", "DNA", "sequences,", "several", "authors", "described", "parasites", "in", "roe,", "red", "or", "reindeer", "as", "B.", "divergens", "or", "B.", "divergens-like", "[2,6-12].", "These", "authors", "based", "their", "conclusions", "on", "18S", "rRNA", "gene", "sequence", "alignment,", "but", "none", "of", "their", "samples", "showed", "100%", "simi-", "larity", "with", "B.", "divergens", "sequences", "of", "bovine", "origin", "in", "GenBank.", "Resequencing", "of", "the", "18S", "rRNA", "gene", "from", "the", "same", "strains", "of", "B.", "divergens", "originally", "deposited", "in", "Gen-", "Bank", "showed", "that", "all", "were", "in", "fact", "identical", "and", "that", "*", "Correspondence:", "Jeremy.gray@ucd.ie", "2UCD", "School", "of", "Biology", "and", "Environmental", "Science,", "University", "College", "Dublin,", "Ireland", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "there", "were", "errors", "in", "the", "original", "sequences", "(Slemenda", "et", "al.,", "unpublished,", "cited", "in", "[13]).", "This", "suggests", "that", "parasites", "showing", "less", "than", "100%", "similarity", "for", "this", "gene", "should", "not", "be", "designated", "B.", "divergens", "and", "to", "date", "there", "are", "no", "studies", "showing", "that", "B.", "divergens", "occurs", "naturally", "in", "ruminant", "hosts", "other", "than", "cattle.", "An", "opportunity", "to", "re-examine", "this", "situation", "arose", "dur-", "ing", "a", "serosurvey", "of", "deer", "parasites", "in", "free-ranging", "wild", "Irish", "deer.", "Blood", "samples", "from", "38", "red", "deer", "from", "two", "National", "Parks", "in", "different", "geographical", "locations", "were", "analysed", "by", "two", "PCR", "protocols", "targeting", "the", "18S", "rRNA", "gene,", "and", "the", "products", "then", "sequenced", "and", "aligned", "for", "identification", "purposes.", "Materials", "and", "methods", "Blood", "samples", "were", "collected", "from", "red", "deer", "shot", "by", "the", "National", "Parks", "and", "Wildlife", "Service", "as", "part", "of", "the", "seaso-", "nal", "cull", "in", "Glenveagh", "(n", "=", "27)", "and", "Killarney", "(n", "=", "11)", "(Figure", "1).", "From", "each", "animal", "3", "to", "4", "mL", "whole", "blood", "were", "collected", "into", "EDTA.", "Following", "centrifugation", "and", "removal", "of", "plasma,", "the", "packed", "cell", "component", "was", "stored", "at", "-20°C.", "DNA", "was", "subsequently", "extracted", "from", "thawed", "and", "mixed", "100", "mg", "packed", "cells", "of", "each", "sample", "using", "the", "High", "Pure", "PCR", "Template", "Preparation", "Kit", "(Roche,", "Burgess", "Hill,", "UK).", "A", "nested", "PCR", "protocol", "was", "used", "initially", "to", "screen", "all", "samples", "(protocol", "I).", "The", "positive", "samples", "were", "then", "additionally", "analysed", "using", "a", "©", "2011", "Zintl", "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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[ "Time-Dependent", "Effect", "of", "Refrigeration", "on", "Viscosity", "and", "Conversion", "Kinetics", "of", "Dental", "Adhesive", "Resins", "André", "L", "Faria-e-Silvaa", "Evandro", "Pivab", "Rafael", "R", "Moraesb", "AbstrAct", "Objectives:", "This", "study", "evaluated", "the", "effect", "of", "refrigeration", "at", "4oC", "and", "post-refrigeration", "times", "(immediate,", "5,", "10,", "15,", "or", "20", "min)", "on", "the", "viscosity", "and", "conversion", "kinetics", "of", "adhesive", "bonding", "resins.", "Methods:", "Scotchbond", "Dual-Cure", "(3M", "ESPE)", "and", "Clearfil", "SE", "Bond", "(Kuraray)", "were", "tested.", "Control", "samples", "were", "kept", "at", "25oC", "for", "24", "h.", "At", "each", "post-refrigeration", "time,", "the", "temperature", "was", "checked", "with", "a", "K-type", "thermocouple.", "Viscosity", "measurements", "as", "a", "function", "of", "temperature", "were", "performed", "using", "a", "cone-plate", "viscometer.", "Real-time", "polymerization", "was", "monitored", "by", "infrared", "spectroscopy.", "Degree", "of", "conversion", "(DC)", "was", "calculated", "for", "each", "second", "during", "polymerization,", "and", "the", "rate", "of", "po-", "lymerization", "analyzed.", "Data", "were", "separately", "submitted", "to", "two-way", "ANOVA", "and", "Tukey’s", "test", "(P<.05).", "Results:", "Clearfil", "presented", "faster", "increase", "in", "temperature", "after", "exposure", "to", "room", "temperature", "than", "Scotchbond.", "A", "continuous", "decrease", "in", "viscosity", "(Pa.s)", "was", "observed", "for", "both", "Scotchbond", "(0.49,", "0.34,", "0.30,", "0.26,", "0.23,", "0.23)", "and", "Clearfil", "(0.38,", "0.37,", "0.34,", "0.25,", "0.24,", "0.22).", "For", "Scotchbond,", "higher", "final", "DC", "was", "detected", "for", "the", "control", "(62.7%)", "compared", "with", "the", "immediate", "(53.3%)", "and", "5", "min", "(54.7%)", "groups.", "For", "Clearfil,", "the", "control", "sample", "(81.4%)", "showed", "higher", "DC", "than", "all", "refrigerated", "groups", "(68.8–", "69.5%).", "Clearfil", "always", "showed", "significantly", "higher", "DC", "than", "Scotchbond.", "Conclusions:", "Refrigeration", "presented", "a", "significant", "time-", "and", "material-dependent", "effect", "on", "the", "viscosity", "and", "polymerization", "kinetics", "of", "the", "bonding", "resins.", "Under", "clinical", "conditions,", "adhesive", "agents", "should", "be", "removed", "from", "the", "refrigerator", "at", "least", "20", "min", "before", "being", "used.", "(Eur", "J", "Dent", "2010;4:150-", "155)", "Key", "words:", "Bonding", "resins;", "Degree", "of", "conversion;", "Polymerization", "kinetics;", "Refrigeration;", "Viscosity.", "a", "Professor,", "Department", "of", "Dentistry,", "School", "of", "Dentistry,", "State", "University", "of", "Montes", "Claros,", "MG,", "Brasil.", "b", "Department", "of", "Restorative", "Dentistry,", "School", "of", "Dentistry,", "Federal", "University", "of", "Pelotas,", "RS,", "Brasil.", "Corresponding", "author:", "Prof.", "André", "L.", "Faria-e-Silva", "Department", "of", "Dentistry,", "School", "of", "Dentistry", "State", "Uni-", "versity", "of", "Montes", "Claros,", "MG,", "Brazil", "Campus", "Universi-", "tário", "Prof.", "Darcy", "Ribeiro,", "Vila", "Mauricéia", "Montes", "Claros,", "MG,", "Brasil", "-", "39401-089", "Phone/Fax:", "+55", "38", "3229.8284", "E-mail:", "andrelfsilva@hotmail.com", "IntroductIon", "The", "main", "goal", "of", "the", "adhesion", "of", "restoratives", "materials", "to", "dental", "hard", "tissues", "is", "to", "obtain", "high", "bond", "strengths", "and", "a", "satisfactory,", "long-lasting", "seal.1-3", "Over", "the", "last", "decade,", "a", "number", "of", "inves-", "tigations", "have", "reported", "that", "several", "factors", "might", "interfere", "with", "the", "bonding", "ability", "of", "adhesive", "sys-", "tems", "to", "enamel", "or", "dentin,", "including", "the", "adhesion", "strategy,4", "conditioning", "time,5", "solvent", "removal", "method,6,7", "thickness", "of", "the", "adhesive", "layer,8", "and", "even", "the", "environmental", "humidity.9,10", "150", "European", "Journal", "of", "Dentistry" ]

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[ "Background:", "Material/Methods:", "Results:", "Conclusions:", "O", "R", "I", "G", "I", "N", "A", "L", "A", "R", "T", "I", "C", "L", "E", "The", "hyperdense", "posterior", "cerebral", "artery", "sign", "in", "CT", "is", "related", "to", "larger", "ischemic", "lesion", "volume", "Wojciech", "Ambrosius1,2,", "Varsha", "Gupta1,", "Radoslaw", "Kazmierski3,", "Agnieszka", "Hellmann2,", "GuoYu", "Qian1,", "Wieslaw", "L.", "Nowinski1", "1", "Biomedical", "Imaging", "Lab,", "Agency", "for", "Science", "Technology", "and", "Research,", "Singapore", "2", "Department", "of", "Neurology", "Poznań", "University", "of", "Medical", "Sciences,", "Poznań,", "Poland", "3", "Department", "of", "Neurology", "and", "Cerebrovascular", "Disorders,", "Poznań", "University", "of", "Medical", "Sciences,", "L.", "Bierkowski", "Hospital,", "Poznań,", "Poland", "Author’s", "address:", "Wojciech", "Ambrosius,", "Department", "of", "Neurology,", "Poznan", "University", "of", "Medical", "Sciences,", "Przybyszewskiego", "49", "Str.,", "60-645,", "Poznań,", "Poland,", "e-mail:", "wambrosius@ump.edu.pl", "Source", "of", "support:", "This", "study", "is", "a", "part", "of", "the", "joined", "Singaporean-Polish", "project", "focused", "on", "development", "of", "the", "computer-", "aided", "decision", "support", "system", "for", "assessment", "of", "thrombolytic", "therapy", "in", "acute", "ischemic", "stroke", "in", "Emergency", "Department", "funded", "by", "Agency", "for", "Science,", "Technology", "and", "Research,", "Singapore", "and", "Ministry", "of", "Science", "and", "Higher", "Education,", "Poland", "(project", "no.", "072-134", "0049)", "Summary", "Hyperdensity", "of", "the", "middle", "cerebral", "artery", "(MCA)", "on", "unenhanced", "CT", "is", "a", "recognized", "sign", "associated", "with", "brain’s", "early", "ischemia.", "The", "number", "of", "studies", "which", "showed", "a", "hyperdense", "posterior", "cerebral", "artery", "(HPCA)", "sign", "in", "posterior", "circulation", "infarct", "is", "relatively", "small.", "We", "investigated", "the", "prevalence", "of", "the", "HPCA", "sign,", "correlations", "with", "ischemic", "lesion", "volume,", "and", "stroke", "risk", "factors.", "We", "also", "determined", "the", "association", "with", "prothrombotic", "and", "inflammatory", "markers", "which", "have", "not", "been", "studied", "before.", "In", "the", "group", "of", "376", "patients", "with", "a", "first", "acute", "stroke", "consecutively", "admitted", "to", "Emergency", "Department,", "early", "signs", "of", "brain", "infarction", "were", "visible", "in", "221", "(58%)", "cases.", "Fifty", "five", "(25%)", "subjects", "had", "ischemic", "lesions", "in", "the", "brain", "supplied", "by", "the", "posterior", "circulation.", "We", "analyzed", "the", "unenhanced", "CT", "scans,", "calculated", "the", "density", "of", "the", "posterior", "cerebral", "arteries,", "infarct", "volume,", "and", "assessed", "the", "relation", "of", "the", "HPCA", "sign", "to", "other", "factors.", "The", "HPCA", "sign", "appeared", "on", "CT", "scans", "of", "12", "(22%)", "patients", "with", "evidence", "of", "the", "posterior", "circulation", "infarct.", "The", "density", "(in", "Hounsfield", "units)", "of", "the", "affected", "PCA", "was", "46.5", "comparing", "to", "20.2", "of", "an", "intact", "vessel", "(p<0.0001).", "The", "stroke", "volume", "was", "larger", "when", "the", "HPCA", "sign", "was", "observed", "(medians:", "17.6", "vs.", "4.3", "cm3,", "p=0.02);", "in", "multivariate", "analysis", "this", "association", "was", "still", "significant", "(OR=1.07;", "95%", "CI,", "0.99–1.13).", "The", "C-reactive", "protein", "and", "fibrinogen", "levels", "were", "significantly", "higher", "(p=0.02", "for", "both", "factors)", "in", "patients", "with", "the", "HPCA", "sign", "in", "the", "univariate", "analysis.", "The", "HPCA", "may", "be", "considered", "as", "an", "additional", "marker", "of", "early", "brain", "infarct,", "especially", "with", "large", "lesion", "volume.", "Signature:", "©", "Pol", "J", "Radiol,", "2011;", "76(2):", "13-17", "Received:", "2011.04.12", "Accepted:", "2011.05.11", "Key", "words:", "stroke", "•", "imaging", "•", "computed", "tomography", "•", "hyperdense", "artery", "sign", "PDF", "file:", "http://www.polradiol.com/fulltxt.php?ICID=881814", "Background", "Visualization", "of", "acute", "signs", "of", "ischemic", "stroke", "is", "still", "a", "challenging", "aspect", "of", "neuroimaging.", "Every", "year", "new", "sophisticated", "imaging", "methods", "are", "introduced", "and", "their", "results", "are", "published", "showing", "brain", "ischemic", "lesions", "much", "more", "accurately.", "Most", "of", "these", "trials", "employ", "MRI", "techni-", "ques", "[1,2].", "Practically,", "in", "routine", "emergency", "neurological", "13" ]

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[ "Upsala", "Journal", "of", "Medical", "Sciences.", "2011;", "116:", "285–288", "CASE", "REPORT", "Recurrent", "dislocation", "of", "the", "patella", "accompanying", "hypotrochlea", "of", "the", "femur", "and", "malalignment", "of", "the", "patella", "AKIRA", "HORIKAWA1,", "HIROYUKI", "KODAMA1,", "NAOHISA", "MIYAKOSHI2,", "SHIN", "YAMADA2", "&", "SEIYA", "MIYAMOTO3", "1South", "Akita", "Orthopedic", "Clinic,", "Seiwakai,", "96-2", "Kaidousita,", "Syowa-Ookubo,", "Katagami", "018-1401,", "Japan,", "2Department", "of", "Orthopedic", "Surgery,", "Akita", "University", "Graduate", "School", "of", "Medicine,", "1-1-1", "Hondo,", "Akita", "010-8543,", "Japan,", "and", "3Department", "of", "Orthopedic", "Surgery,", "Nakadori", "General", "Hospital,", "3-15", "Minamidoori-Misono,", "Akita", "010-8577,", "Japan", "Abstract", "This", "case", "report", "describes", "a", "rare", "case", "of", "recurrent", "dislocation", "of", "the", "patella", "which", "was", "accompanied", "with", "trochlear", "dysplasia", "and", "malalignment", "of", "the", "patella", "in", "a", "15-year-old", "girl.", "She", "complained", "of", "hemoarthrosis", "and", "recurrent", "patellar", "dislocation", "in", "the", "early", "knee", "flexion", "phase.", "Plain", "radiography", "and", "computed", "tomography", "(CT)", "showed", "patellar", "malalignment", "(quadriceps", "angle", "20", ")", "and", "severe", "dysplasia", "of", "the", "trochlea", "of", "the", "femur", "(sulcus", "angle", "170", ").", "Surgery", "was", "performed,", "consisting", "of", "trochleoplasty", "in", "addition", "to", "proximal", "and", "distal", "realignment.", "Trochleoplasty", "was", "undertaken", "using", "a", "modified", "Dejour", "technique.", "After", "surgery,", "the", "patient", "complained", "of", "joint", "contracture.", "Arthroscopic", "release", "of", "fibrous", "tissue", "relieved", "symptoms", "and", "obtained", "normal", "range", "of", "motion", "without", "patellar", "dislocation.", "Postoperative", "radiography", "and", "CT", "demonstrated", "improvement", "of", "the", "quadriceps", "angle", "(10", ")", "and", "sulcus", "angle", "(140", ").", "Key", "words:", "Dislocations,", "knee,", "patella", "Introduction", "Although", "biomechanics", "and", "surgical", "treatments", "have", "been", "examined", "for", "recurrent", "dislocation", "of", "the", "patella,", "few", "studies", "have", "reported", "on", "the", "combination", "of", "troch-", "lear", "dysplasia", "and", "recurrent", "patellar", "instability.", "In", "addi-", "tion,", "treatment", "methods", "have", "only", "been", "reported", "in", "a", "few", "cases.", "We", "present", "herein", "a", "case", "with", "successful", "surgical", "outcomes", "for", "the", "treatment", "of", "recurrent", "dislocation", "of", "the", "patella", "with", "trochlear", "dysplasia", "and", "malalignment", "of", "the", "patella.", "Case", "report", "A", "15-year-old", "girl", "who", "had", "complained", "of", "recurrent", "patellar", "dislocation", "for", "more", "than", "5", "years", "presented", "with", "left", "knee", "hemoarthrosis.", "Physical", "examination", "revealed", "patellar", "dislocation", "at", "slight", "knee", "flexion", "of", "approximately", "30", "that", "was", "easily", "reduced", "without", "pain.", "No", "signs", "of", "apprehension,", "joint", "laxities,", "or", "sys-", "tematic", "disease", "were", "observed.", "Plain", "radiography", "showed", "a", "lateralized", "tibial", "tubercle", "with", "increased", "quad-", "riceps", "angle", "(Q", "angle)", "of", "20", "and", "dysplasia", "of", "the", "trochlea", "as", "defined", "by", "the", "‘crossing", "sign’", "(1)", "without", "patella", "alta.", "Computed", "tomography", "(CT)", "also", "demon-", "strated", "marked", "trochleodysplasia", "of", "the", "femur,", "with", "a", "sulcus", "angle", "of", "170", "(Figure", "1).", "Arthroscopic", "examination", "showed", "a", "flat,", "hypoplastic", "trochlea", "of", "the", "femur", "and", "frequent", "patellar", "dislocation", "with", "knee", "motion.", "Surgery", "consisted", "of", "trochleoplasty,", "followed", "by", "proximal", "and", "distal", "realignment.", "Tro-", "chleoplasty", "was", "performed", "as", "a", "modified", "Dejour", "tech-", "nique", "(2).", "This", "technique", "involved:", "1)", "shaving", "of", "the", "subchondral", "bone;", "2)", "making", "an", "incision", "from", "the", "aspect", "of", "the", "groove", "to", "the", "anterior", "femoral", "cortex;", "3)", "cutting", "a", "subchondral", "trench;", "4)", "undermining", "the", "flap", "to", "allow", "collapse", "of", "the", "osteochondral", "flap;", "5)", "impaction", "using", "finger", "pressure;", "and", "6)", "fixation", "of", "Correspondence:", "Akira", "Horikawa,", "MD,", "South", "Akita", "Orthopedic", "Clinic,", "Seiwakai,", "96-2", "Kaidousita,", "Syowa-Ookubo,", "Katagami", "018-1401,", "Japan.", "E-mail:", "horikawa@virgo.interq.or.jp", "(Received", "19", "February", "2011;", "accepted", "8", "June", "2011)", "ISSN", "0300-9734", "print/ISSN", "2000-1967", "online", "2011", "Informa", "Healthcare", "DOI:", "10.3109/03009734.2011.596291" ]

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[ "y", "g", "o", "l", "o", "i", "s", "y", "h", "P", "l", "a", "r", "e", "n", "e", "G", "f", "o", "l", "a", "n", "r", "u", "o", "J", "e", "h", "T", "A", "R", "T", "I", "C", "L", "E", "EF", "hands", "at", "the", "N-lobe", "of", "calmodulin", "are", "required", "for", "both", "SK", "channel", "gating", "and", "stable", "SK–calmodulin", "interaction", "Weiyan", "Li,", "David", "B.", "Halling,", "Amelia", "W.", "Hall,", "and", "Richard", "W.", "Aldrich", "Section", "of", "Neurobiology,", "Center", "for", "Learning", "and", "Memory,", "The", "University", "of", "Texas", "at", "Austin,", "Austin,", "TX", "78712", "Small", "conductance", "calcium-activated", "potassium", "(SK)", "channels", "respond", "to", "intracellular", "Ca2+", "via", "constitutively", "asso-", "ciated", "calmodulin", "(CaM).", "Previous", "studies", "have", "proposed", "a", "modular", "design", "for", "the", "interaction", "between", "CaM", "and", "SK", "channels.", "The", "C-lobe", "and", "the", "linker", "of", "CaM", "are", "thought", "to", "regulate", "the", "constitutive", "binding,", "whereas", "the", "N-lobe", "binds", "Ca2+", "and", "gates", "SK", "channels.", "However,", "we", "found", "that", "coexpression", "of", "mutant", "CaM", "(E/Q)", "where", "the", "N-lobe", "has", "only", "one", "functional", "EF", "hand", "leads", "to", "rapid", "rundown", "of", "SK", "channel", "activity,", "which", "can", "be", "recovered", "with", "exogenously", "applied", "wild-type", "(WT),", "but", "not", "mutant,", "CaM.", "Our", "results", "suggest", "that", "the", "mutation", "at", "the", "N-lobe", "EF", "hand", "disrupts", "the", "stable", "interaction", "between", "CaM", "and", "SK", "channel", "subunits,", "such", "that", "mutant", "CaM", "dissociates", "from", "the", "channel", "complex", "when", "the", "inside", "of", "the", "membrane", "is", "exposed", "to", "CaM-free", "solution.", "The", "disruption", "of", "the", "stable", "interaction", "does", "not", "directly", "result", "from", "the", "loss", "of", "Ca2+-binding", "capacity", "because", "SK", "channels", "and", "WT", "CaM", "can", "stably", "interact", "in", "the", "absence", "of", "Ca2+.", "These", "findings", "question", "a", "previous", "conclusion", "that", "CaM", "where", "the", "N-lobe", "has", "only", "one", "functional", "EF", "hand", "can", "stably", "support", "the", "gating", "of", "SK", "channels.", "They", "cannot", "be", "explained", "by", "the", "current", "model", "of", "modular", "interaction", "between", "CaM", "and", "SK", "channels,", "and", "they", "imply", "a", "role", "for", "N-lobe", "EF", "hand", "residues", "in", "binding", "to", "the", "channel", "subunits.", "Additionally,", "we", "found", "that", "a", "potent", "enhancer", "for", "SK", "channels,", "3-oxime-6,7-dichloro-1H-indole-2,3-dione", "(NS309),", "enables", "the", "recovery", "of", "channel", "activity", "with", "CaM", "(E/Q),", "sug-", "gesting", "that", "NS309", "stabilizes", "the", "interaction", "between", "CaM", "and", "SK", "channels.", "CaM", "(E/Q)", "can", "regulate", "Ca2+-depen-", "dent", "gating", "of", "SK", "channels", "in", "the", "presence", "of", "NS309,", "but", "with", "a", "lower", "apparent", "Ca2+", "affinity", "than", "WT", "CaM.", "I", "N", "T", "R", "O", "D", "U", "C", "T", "I", "O", "N", "By", "responding", "to", "elevated", "intracellular", "Ca2+", "concentra-", "tion,", "small", "conductance", "calcium-activated", "potassium", "(SK;", "KCa2,", "KCNN)", "channels", "play", "critical", "roles", "in", "regulat-", "ing", "neuronal", "excitability", "(Stocker", "et", "al.,", "1999),", "hor-", "mone", "release", "(Tse", "and", "Hille,", "1992),", "and", "smooth", "muscle", "tone", "(Doughty", "et", "al.,", "1999;", "Herrera", "et", "al.,", "2000).", "SK", "channel", "subunits", "do", "not", "directly", "bind", "Ca2+", "but", "detect", "Ca2+", "concentration", "via", "associated", "calmodulin", "(CaM)", "(Xia", "et", "al.,", "1998).", "Different", "from", "many", "other", "CaM-interact-", "ing", "proteins", "that", "only", "bind", "with", "Ca2+-loaded", "CaM", "(Yam-", "niuk", "and", "Vogel,", "2004),", "SK", "channels", "are", "constitutively", "associated", "with", "CaM,", "even", "in", "the", "absence", "of", "Ca2+", "(Xia", "et", "al.,", "1998).", "This", "intimate", "association", "likely", "enables", "the", "fast", "activation", "of", "SK", "channels", "in", "response", "to", "Ca2+", "as", "es-", "sential", "for", "their", "physiological", "functions", "(Xia", "et", "al.,", "1998).", "CaM", "consists", "of", "two", "globular", "domains", "(the", "C-", "and", "N-lobe)", "connected", "by", "a", "flexible", "linker.", "Each", "lobe", "con-", "tains", "two", "EF", "hand", "structures", "that", "serve", "as", "the", "Ca2+-binding", "sites.", "Structural,", "functional,", "and", "biochemical", "studies", "on", "SK", "channel–CaM", "complexes", "have", "suggested", "a", "modular", "mechanism", "for", "the", "molecular", "interaction", "between", "SK", "channels", "and", "CaM.", "The", "C-lobe", "and", "the", "linker", "of", "CaM", "are", "thought", "to", "be", "responsible", "for", "the", "constitutive", "asso-", "ciation", "between", "CaM", "and", "SK", "channels,", "but", "C-lobe", "EF", "hands", "do", "not", "bind", "Ca2+.", "On", "the", "other", "hand,", "the", "N-lobe", "of", "CaM", "is", "considered", "not", "involved", "in", "the", "constitutive", "bind-", "ing,", "but", "EF", "hands", "in", "the", "N-lobe", "bind", "Ca2+", "and", "gate", "SK", "channels", "(Xia", "et", "al.,", "1998;", "Keen", "et", "al.,", "1999;", "Schumacher", "et", "al.,", "2001;", "Li", "and", "Aldrich,", "2009).", "A", "thorough", "understanding", "of", "the", "activation", "mecha-", "nism", "for", "SK", "channels", "is", "not", "yet", "available,", "partly", "result-", "ing", "from", "the", "fact", "that", "each", "SK", "channel", "complex", "has", "up", "to", "four", "CaM", "molecules,", "each", "with", "at", "least", "two", "Ca2+-bind-", "ing", "sites", "(EF", "hands)", "that", "likely", "bind", "Ca2+", "cooperatively", "(Xia", "et", "al.,", "1998;", "Keen", "et", "al.,", "1999).", "The", "contribution", "of", "individual", "EF", "hands", "to", "the", "opening", "of", "SK", "channels", "has", "been", "difficult", "to", "evaluate.", "To", "establish", "a", "quantitative", "framework", "for", "the", "characterization", "of", "the", "coupling", "be-", "tween", "Ca2+", "binding", "and", "channel", "activation,", "it", "is", "useful", "to", "study", "SK", "channels", "associated", "with", "CaMs", "in", "which", "only", "one", "of", "the", "N-lobe", "EF", "hands", "binds", "Ca2+.", "A", "previous", "study", "suggested", "that", "when", "one", "of", "the", "EF", "hands", "at", "the", "N-lobe", "of", "CaM", "loses", "its", "Ca2+-binding", "capacity", "by", "mutation,", "CaM", "can", "still", "stably", "support", "SK", "channel", "gating,", "albeit", "with", "a", "reduced", "apparent", "affinity", "for", "Ca2+", "(Keen", "et", "al.,", "1999).", "This", "mutation", "in", "CaM", "would", "greatly", "reduce", "the", "com-", "plexity", "of", "the", "SK", "channel", "gating", "scheme;", "therefore,", "we", "Correspondence", "to", "Richard", "W.", "Aldrich:", "raldrich@­mail.utexas.edu", "Abbreviations", "used", "in", "this", "paper:", "CaM,", "calmodulin;", "NS309,", "3-oxime-6,7-", "dichloro-1H-indole-2,3-dione;", "SK,", "small", "conductance", "calcium-activated", "potassium;", "WT,", "wild-type.", "©", "2009", "Li", "et", "al.", "This", "article", "is", "distributed", "under", "the", "terms", "of", "an", "Attribution–Noncommer-", "cial–Share", "Alike–No", "Mirror", "Sites", "license", "for", "the", "first", "six", "months", "after", "the", "publication", "date", "(see", "http://www.jgp.org/misc/terms.shtml).", "After", "six", "months", "it", "is", "available", "under", "a", "Creative", "Commons", "License", "(Attribution–Noncommercial–Share", "Alike", "3.0", "Unported", "license,", "as", "de-", "scribed", "at", "http://creativecommons.org/licenses/by-nc-sa/3.0/).", "The", "Rockefeller", "University", "Press", "$30.00", "J.", "Gen.", "Physiol.", "Vol.", "134", "No.", "4", "281–293", "www.jgp.org/cgi/doi/10.1085/jgp.200910295", "281" ]

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[ "Psychon", "Bull", "Rev", "(2011)", "18:364–370", "DOI", "10.3758/s13423-010-0044-y", "When", "bicycle", "pump", "is", "harder", "to", "read", "than", "bicycle", "bell:", "effects", "of", "parsing", "cues", "in", "first", "and", "second", "language", "compound", "reading", "Kristin", "Lemhöfer", "&", "Dirk", "Koester", "&", "Robert", "Schreuder", "Published", "online:", "5", "January", "2011", "#", "The", "Author(s)", "2010.", "This", "article", "is", "published", "with", "open", "access", "at", "Springerlink.com", "Abstract", "Reading", "and", "understanding", "morphologically", "com-", "plex", "words", "can", "sometimes", "be", "a", "particular", "challenge", "to", "nonnative", "speakers.", "For", "example,", "compound", "words", "consist", "of", "multiple", "free", "morphemes,", "oftentimes", "without", "explicit", "marking", "of", "the", "morpheme", "boundaries.", "In", "a", "lexical", "decision", "task,", "we", "investigated", "compound", "reading", "in", "native", "and", "nonnative", "speakers", "of", "Dutch.", "The", "compounds", "differed", "in", "that", "the", "letter", "bigram", "that", "formed", "the", "morpheme", "boundary", "could", "or", "could", "not", "occur", "within", "a", "Dutch", "morpheme,", "thus", "providing", "an", "orthotactic", "cue", "as", "to", "the", "position", "of", "the", "morpheme", "boundary.", "Native", "and", "nonnative", "speakers", "responded", "faster", "to", "compounds", "that", "contained", "such", "an", "orthotactic", "cue.", "Additional", "analyses", "showed", "that", "although", "native", "speakers", "used", "this", "cue", "for", "long,", "but", "not", "for", "short", "compounds,", "no", "such", "word", "length", "modulation", "was", "observed", "for", "nonnative", "speakers.", "It", "is", "suggested", "that", "orthotactic", "parsing", "cues", "are", "used", "during", "compound", "reading", "and", "possibly", "even", "more", "so", "in", "nonnative", "speakers.", "Keywords", "Visual", "word", "recognition", ".", "compound", "reading", ".", "Orthotactic", "parsing", "cues", ".", "Second", "language", "speakers", "Learning", "a", "second", "language", "(L2)", "can", "be", "a", "tedious", "enterprise,", "and", "each", "language", "has", "its", "own", "hurdles", "that", "Electronic", "supplementary", "material", "The", "online", "version", "of", "this", "article", "(doi:10.3758/s13423-010-0044-y)", "contains", "supplementary", "material,", "which", "is", "available", "to", "authorized", "users.", "K.", "Lemhöfer", "(*)", ":", "R.", "Schreuder", "Donders", "Institute", "for", "Brain,", "Cognition,", "and", "Behaviour", "-", "Centre", "for", "Cognition,", "Radboud", "University", "Nijmegen,", "P.O.", "Box", "9104,", "6500", "HE", "Nijmegen,", "The", "Netherlands", "e-mail:", "k.lemhofer@donders.ru.nl", "D.", "Koester", "Cognitive", "Interaction", "Technology", "-", "Center", "of", "Excellence,", "University", "of", "Bielefeld,", "Bielefeld,", "Germany", "make", "life", "hard", "for", "nonnative", "speakers.", "In", "languages", "such", "as", "Dutch", "or", "German,", "for", "instance,", "reading", "compounds", "(words", "with", "more", "than", "one", "free", "morpheme,", "such", "as", "doghouse)", "can", "be", "problematic,", "because", "they", "are", "written", "without", "interspa-", "ces", "or", "hyphens.", "An", "extreme", "example", "from", "German", "is", "Selbstbedienungskontoauszugsdrucker", "(“self-service", "printer", "for", "account", "statements”),", "but", "even", "in", "two-constituent", "compounds,", "it", "can", "be", "difficult", "to", "identify", "the", "constituent", "boundary.", "In", "the", "Dutch", "example", "fiets-pomp", "(“bicycle", "pump”;", "hyphens", "are", "included", "only", "to", "indicate", "constituent", "boundaries),", "the", "location", "of", "the", "boundary", "does", "not", "follow", "from", "orthotactic", "constraints—that", "is,", "from", "the", "rules", "spec-", "ifying", "which", "letter", "sequences", "are", "well", "formed", "for", "a", "given", "language.", "The", "incorrect", "parsing", "*fiet-spomp", "also", "results", "in", "two", "legal", "and", "pronounceable", "letter", "strings", "and", "can", "thus", "not", "be", "rejected", "immediately.", "In", "contrast,", "in", "fiets-bel", "(“bicycle", "bell”),", "the", "morpheme", "boundary", "is", "easier", "to", "detect,", "since", "the", "bigram", "“sb”", "cannot", "occur", "within", "Dutch", "morphemes.", "Whether", "or", "not", "orthotactic", "parsing", "cues", "such", "as", "the", "legality", "of", "the", "boundary", "bigram", "are", "used", "in", "compound", "processing", "is", "not", "only", "unknown", "for", "L2", "speakers,", "it", "has", "also", "rarely", "been", "investigated", "in", "native", "speakers.", "Of", "course,", "not", "only", "nonnative,", "but", "also", "native", "Dutch", "readers", "might", "be", "slowed", "down", "when", "orthotactic", "cues", "that", "indicate", "the", "boundary", "are", "missing.", "The", "few", "studies", "on", "effects", "of", "orthotactic", "boundary", "cues", "in", "native", "speakers", "have", "yielded", "controversial", "results.", "Taft", "and", "Forster", "(1976)", "used", "nonwords", "with", "clear", "(e.g.,", "bonchmip)", "versus", "unclear", "constituent", "boundaries", "(e.g.,", "glicerax)", "in", "lexical", "decision", "and", "found", "no", "effect", "of", "boundary", "type.", "However,", "rejecting", "nonwords", "might", "involve", "quite", "different", "mecha-", "nisms", "than", "word", "recognition.", "Libben", "(1994)", "showed", "that", "parsing", "preferences", "for", "novel", "English", "compounds", "with", "ambiguous", "parsings", "(e.g.,", "busheater)", "are", "influenced", "by", "orthographic", "factors.", "In", "a", "study", "using", "eye-movement", "measures", "during", "sentence", "reading,", "Bertram,", "Pollatsek," ]

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[ "y", "g", "o", "l", "o", "i", "s", "y", "h", "P", "l", "a", "r", "e", "n", "e", "G", "f", "o", "l", "a", "n", "r", "u", "o", "J", "e", "h", "T", "A", "R", "T", "I", "C", "L", "E", "Inhibition", "of", "KCa2.2", "and", "KCa2.3", "channel", "currents", "by", "protonation", "of", "outer", "pore", "histidine", "residues", "Samuel", "J.", "Goodchild,1", "Cedric", "Lamy,2", "Vincent", "Seutin,2", "and", "Neil", "V.", "Marrion1", "1Department", "of", "Physiology", "and", "Pharmacology,", "School", "of", "Medical", "Sciences,", "University", "of", "Bristol,", "Bristol", "BS8", "1TD,", "England,", "UK", "2Laboratory", "of", "Pharmacology,", "Giga-Neurosciences,", "University", "of", "Liège,", "4000", "Liège,", "Belgium", "Ion", "channels", "are", "often", "modulated", "by", "changes", "in", "extracellular", "pH,", "with", "most", "examples", "resulting", "from", "shifts", "in", "the", "ionization", "state", "of", "histidine", "residue(s)", "in", "the", "channel", "pore.", "The", "application", "of", "acidic", "extracellular", "solution", "inhib-", "ited", "expressed", "KCa2.2", "(SK2)", "and", "KCa2.3", "(SK3)", "channel", "currents,", "with", "KCa2.3", "(pIC50", "of", "6.8)", "being", "approximately", "fourfold", "more", "sensitive", "than", "KCa2.2", "(pIC50", "of", "6.2).", "Inhibition", "was", "found", "to", "be", "voltage", "dependent,", "resulting", "from", "a", "shift", "in", "the", "affinity", "for", "the", "rectifying", "intracellular", "divalent", "cation(s)", "at", "the", "inner", "mouth", "of", "the", "selectivity", "filter.", "The", "inhibition", "by", "extracellular", "protons", "resulted", "from", "a", "reduction", "in", "the", "single-channel", "conductance,", "without", "signifi-", "cant", "changes", "in", "open-state", "kinetics", "or", "open", "probability.", "KCa2.2", "and", "KCa2.3", "subunits", "both", "possess", "a", "histidine", "residue", "in", "their", "outer", "pore", "region", "between", "the", "transmembrane", "S5", "segment", "and", "the", "pore", "helix,", "with", "KCa2.3", "also", "exhibiting", "an", "additional", "histidine", "residue", "between", "the", "selectivity", "filter", "and", "S6.", "Mutagenesis", "revealed", "that", "the", "outer", "pore", "histi-", "dine", "common", "to", "both", "channels", "was", "critical", "for", "inhibition.", "The", "greater", "sensitivity", "of", "KCa2.3", "currents", "to", "protons", "arose", "from", "the", "additional", "histidine", "residue", "in", "the", "pore,", "which", "was", "more", "proximal", "to", "the", "conduction", "pathway", "and", "in", "the", "electrostatic", "vicinity", "of", "the", "ion", "conduction", "pathway.", "The", "decrease", "of", "channel", "conductance", "by", "extracellular", "protons", "was", "mimicked", "by", "mutation", "of", "the", "outer", "pore", "histidine", "in", "KCa2.2", "to", "an", "asparagine", "residue.", "These", "data", "sug-", "gest", "that", "local", "interactions", "involving", "the", "outer", "turret", "histidine", "residues", "are", "crucial", "to", "enable", "high", "conductance", "openings,", "with", "protonation", "inhibiting", "current", "by", "changing", "pore", "shape.", "I", "N", "T", "R", "O", "D", "U", "C", "T", "I", "O", "N", "The", "KCa2.2", "(SK2)", "and", "KCa2.3", "(SK3)", "potassium", "channels", "are", "characterized", "by", "their", "activation", "by", "intracellular", "calcium", "(Ca2+;", "half-maximal", "activation", "of", "0.3–0.7", "µM),", "voltage", "independence,", "and", "small", "single-channel", "con-", "ductance", "of", "10–20", "pS", "(Köhler", "et", "al.,", "1996;", "Hirschberg", "et", "al.,", "1998;", "Xia", "et", "al.,", "1998).", "Because", "of", "the", "distinct", "spatial", "distribution", "of", "the", "channel", "subtypes", "in", "the", "mammalian", "brain", "and", "their", "involvement", "in", "the", "genera-", "tion", "of", "afterhyperpolarization", "currents,", "there", "has", "been", "considerable", "interest", "in", "developing", "subtype-selective", "pharmacological", "tools", "to", "study", "these", "channels", "(Stocker", "and", "Pedarzani,", "2000;", "Shakkottai", "et", "al.,", "2001;", "Sailer", "et", "al.,", "2002,", "2004;", "Stocker", "et", "al.,", "2004;", "Dilly", "et", "al.,", "2005).", "The", "predicted", "pore", "regions", "of", "KCa2.2", "and", "KCa2.3", "display", "high", "sequence", "homology.", "Each", "channel", "subunit", "pos-", "sesses", "a", "histidine", "(H)", "residue", "that", "is", "predicted", "to", "reside", "within", "the", "extracellular-facing", "region", "of", "the", "outer", "pore", "(H337", "in", "KCa2.2", "and", "H491", "in", "KCa2.3).", "In", "addition,", "the", "KCa2.3", "subunit", "exhibits", "an", "additional", "H", "(H522)", "that", "is", "seen", "as", "asparagine", "(N368)", "in", "KCa2.2.", "Histidine", "residues", "in", "channels’", "outer", "pore", "regions", "have", "been", "reported", "to", "be", "proton", "interaction", "sites", "that", "mediate", "inhibition", "of", "currents.", "For", "example,", "proton-induced", "inhibition", "is", "ob-", "V.", "Seutin", "and", "N.V.", "Marrion", "contributed", "equally", "to", "this", "paper.", "Correspondence", "to", "Neil", "V.", "Marrion:", "N.V.Marrion@­bris.ac.uk", "Abbreviation", "used", "in", "this", "paper:", "GHK,", "Goldman-Hodgkin-Katz.", "The", "Rockefeller", "University", "Press", "$30.00", "J.", "Gen.", "Physiol.", "Vol.", "134", "No.", "4", "295–308", "www.jgp.org/cgi/doi/10.1085/jgp.200910252", "served", "for", "several", "different", "potassium", "channels,", "includ-", "ing", "the", "voltage-gated", "Shaker-like", "plant", "channel", "ATK3", "(Geiger", "et", "al.,", "2002),", "Kv1.5", "(Steidl", "and", "Yool,", "1999;", "Jäger", "and", "Grissmer,", "2001;", "Kehl", "et", "al.,", "2002),", "Kv1.4", "(Claydon", "et", "al.,", "2000),", "Kv7.2/7.3", "(Prole", "et", "al.,", "2003),", "K2P2.1", "(Cohen", "et", "al.,", "2008),", "and", "the", "inward-rectifying", "channel", "Kir2.3", "(Coulter", "et", "al.,", "1995;", "Ureche", "et", "al.,", "2008).", "Several", "mechanisms", "have", "been", "proposed", "to", "explain", "this", "inhi-", "bition.", "For", "example,", "Kv1.5", "macroscopic", "current", "block", "is", "mediated", "through", "modifying", "gating", "and", "enhancing", "inactivation", "without", "any", "effect", "on", "single-channel", "con-", "ductance", "(Kwan", "et", "al.,", "2006).", "Macroscopic", "inhibition", "of", "both", "ATK3", "and", "Kir2.3", "channel", "currents", "resulted", "from", "a", "reduction", "in", "single-channel", "conductance", "(Coulter", "et", "al.,", "1995;", "Geiger", "et", "al.,", "2002),", "whereas", "inhibition", "of", "Kv7.2/7.3", "heteromeric", "channel", "currents", "resulted", "from", "both", "effects", "on", "gating", "and", "single-channel", "conductance", "(Prole", "et", "al.,", "2003).", "We", "demonstrate", "that", "macroscopic", "KCa2.2", "and", "KCa2.3", "current", "is", "inhibited", "by", "extracellular", "protons,", "with", "KCa2.3", "being", "more", "sensitive.", "Inhibition", "resulted", "from", "a", "reduc-", "tion", "in", "single-channel", "conductance", "and,", "in", "particular", "for", "KCa2.3,", "a", "shift", "of", "inward", "rectification.", "We", "show", "that", "©", "2009", "Goodchild", "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.jgp.org/misc/terms.shtml).", "After", "six", "months", "it", "is", "available", "under", "a", "Cre-", "ative", "Commons", "License", "(Attribution–Noncommercial–Share", "Alike", "3.0", "Unported", "license,", "as", "described", "at", "http://creativecommons.org/licenses/by-nc-sa/3.0/).", "295" ]

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[ "DISPATCH", "CLINICAL", "STUDIES", "Atypical", "SARS", "and", "Escherichia", "coli", "Bacteremia", "Thuan", "Tong", "Tan,*", "Ban", "Hock", "Tan,*", "Asok", "Kurup,*", "Lynette", "Lin", "Ean", "Oon,*", "Derrick", "Heng,*", "Su", "Yun", "Se", "Thoe,*", "Xin", "Lai", "Bai,*", "Kwai", "Peng", "Chan,*", "and", "Ai", "Ee", "Ling*", "We", "describe", "a", "patient", "with", "severe", "acute", "respiratory", "syndrome", "(SARS)", "whose", "clinical", "symptoms", "were", "masked", "by", "Escherichia", "coli", "bacteremia.", "SARS", "developed", "in", "a", "clus-", "ter", "of", "healthcare", "workers", "who", "had", "contact", "with", "this", "patient.", "SARS", "was", "diagnosed", "when", "a", "chest", "infiltrate", "developed", "and", "when", "the", "patient’s", "brother", "was", "hospitalized", "with", "acute", "respiratory", "failure.", "We", "highlight", "problems", "in", "atypical", "cases", "and", "offer", "infection", "control", "suggestions.", "Srecognized", "condition.", "In", "early", "March", "2003,", "the", "World", "evere", "acute", "respiratory", "syndrome", "(SARS)", "is", "a", "newly", "Health", "Organization", "(WHO)", "issued", "case", "definitions", "for", "SARS", "(1).", "In", "most", "studies,", "the", "clinical", "syndrome", "includes", "fever", "in", "100%", "of", "patients", "(2–4).", "Other", "common", "clinical", "features", "include", "chills", "and", "rigors", "(73%),", "myalgia", "(60%),", "and", "cough", "(>50%).", "Some", "patients", "initially", "thought", "to", "have", "SARS", "have", "been", "excluded", "when", "tests", "showed", "other", "caus-", "es", "(5).", "We", "report", "a", "patient", "whose", "coexisting", "conditions", "masked", "the", "diagnosis", "of", "SARS,", "leading", "to", "a", "cluster", "of", "sus-", "pect", "and", "probable", "cases.", "Case", "Report", "A", "59-year-old", "Chinese", "man", "was", "admitted", "on", "March", "24,", "2003,", "to", "the", "Singapore", "General", "Hospital.", "He", "had", "previous-", "ly", "been", "hospitalized", "in", "Tan", "Tock", "Seng", "Hospital,", "the", "hospi-", "tal", "in", "which", "the", "first", "SARS", "outbreak", "in", "Singapore", "occurred", "(6),", "from", "March", "5", "to", "March", "20", "for", "diabetic", "nephropathy.", "The", "patient", "had", "multiple", "coexisting", "conditions", "includ-", "ing", "ischemic", "heart", "disease", "with", "atrial", "fibrillation,", "previous", "stroke", "with", "scar", "epilepsy,", "diabetes", "mellitus", "with", "nephropa-", "thy", "(creatinine", "242", "µ", "mol/L),", "and", "peripheral", "vascular", "dis-", "ease.", "He", "was", "not", "on", "steroids", "or", "traditional", "medications.", "Clinical", "signs", "and", "symptoms", "were", "melena", "and", "dizzi-", "ness.", "He", "was", "pale,", "temperature", "was", "36.5°C,", "blood", "pressure", "was", "126/70", "mm", "Hg,", "and", "pulse", "rate", "was", "110/min.", "Chest", "examination", "was", "normal,", "and", "the", "abdomen", "was", "soft.", "Rectal", "examination", "showed", "melena.", "The", "patient", "also", "had", "a", "sloughy", "right", "heel", "ulcer.", "Laboratory", "values", "are", "shown", "in", "the", "Table.", "Antral", "gastritis", "was", "diagnosed", "on", "gastroscopy.", "*Singapore", "General", "Hospital,", "Singapore", "Colonoscopy", "and", "barium", "enema", "were", "unsuccessful", "because", "of", "excessive", "fecal", "residue.", "The", "patient", "had", "a", "temperature", "spike", "(38.4°C)", "on", "March", "26,", "and", "intravenous", "(IV)", "amoxicillin/clavulanic", "acid", "was", "started.", "His", "temperature", "spiked", "again", "(38.8°C)", "on", "March", "28.", "The", "source", "of", "sepsis", "was", "thought", "to", "be", "the", "necrotic", "heel", "ulcer;", "wound", "débridement", "was", "performed", "on", "March", "30.", "The", "fever", "persisted", "from", "March", "28", "until", "April", "2.", "Blood", "cultures", "drawn", "on", "March", "28", "isolated", "E.", "coli", "of", "intermedi-", "ate", "sensitivity", "to", "amoxicillin/clavulanic", "acid.", "Further", "eval-", "uation", "for", "the", "source", "of", "bacteremia", "included", "urinalysis,", "which", "indicated", "a", "leukocyte", "count", "of", "4", "and", "erythrocyte", "count", "of", "165.", "Ultrasonography", "showed", "a", "2.8-cm", "abscess", "at", "the", "midpole", "of", "the", "right", "kidney.", "Urine", "culture", "yielded", "mixed", "bacteria", "growth.", "The", "patient’s", "medication", "was", "changed", "to", "IV", "ceftriaxone", "(to", "which", "the", "organism", "was", "sus-", "ceptible)", "on", "April", "1.", "Tissue", "cultures", "from", "the", "necrotic", "heel", "yielded", "Pseudomonas", "aeruginosa", "sensitive", "only", "to", "imipenem.", "Although", "fever", "was", "lower", "after", "1", "day", "of", "ceftri-", "axone,", "the", "patient’s", "medication", "was", "switched", "to", "IV", "imipenem", "on", "April", "2.", "He", "remained", "afebrile", "thereafter.", "On", "April", "1", "(6", "days", "after", "the", "patient’s", "first", "spike", "of", "tem-", "perature),", "three", "healthcare", "workers", "from", "the", "ward", "into", "which", "he", "had", "first", "been", "admitted", "became", "febrile.", "At", "this", "time,", "physicians", "were", "notified", "that", "the", "patient", "was", "on", "a", "surveillance", "program", "for", "SARS.", "He", "was", "transferred", "from", "the", "general", "surgical", "ward", "to", "an", "isolation", "room,", "and", "health-", "care", "workers", "used", "a", "combination", "of", "airborne,", "contact,", "and", "droplet", "precautions.", "His", "clinical", "course", "was", "scrutinized", "for", "evidence", "of", "SARS.", "Despite", "the", "positive", "contact", "history,", "he", "did", "not", "have", "any", "respiratory", "symptoms.", "Three", "chest", "x-rays", "performed", "on", "days", "1,", "5,", "and", "7", "of", "hospitalization", "were", "nor-", "mal", "(Figure", "1A,", "B,", "and", "C).", "The", "fever", "could", "have", "been", "attributed", "to", "the", "E.", "coli", "bacteremia", "because", "it", "subsided", "after", "the", "patient’s", "antimicrobial", "drug", "was", "changed", "to", "an", "appropriate", "one.", "Over", "the", "subsequent", "days,", "16", "healthcare", "workers", "from", "the", "two", "wards", "where", "this", "patient", "was", "treated", "became", "febrile.", "On", "day", "11", "of", "hospitalization", "(April", "3,", "14", "days", "after", "the", "patient’s", "last", "day", "in", "Tan", "Tock", "Seng", "Hospital),", "an", "ill-", "defined", "air", "space", "shadow", "was", "noted", "in", "the", "right", "lower", "zone", "Emerging", "Infectious", "Diseases", "•", "www.cdc.gov/eid", "•", "Vol.", "10,", "No.", "2,", "February", "2004", "349" ]

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[ "Pearls", "Five", "Questions", "on", "Prion", "Diseases", "Adriano", "Aguzzi*,", "Caihong", "Zhu", "Institute", "of", "Neuropathology,", "University", "Hospital", "of", "Zu¨", "rich,", "Zu¨", "rich,", "Switzerland", "Introduction", "Prion", "diseases", "are", "characterized", "by", "deposition", "of", "PrPSc,", "a", "misfolded", "and", "aggregated", "isoform", "of", "the", "host-encoded", "cellular", "prion", "protein", "(PrPC),", "within", "the", "central", "nervous", "system", "(CNS)", "and", "other", "organs.", "Here", "we", "review", "the", "current", "knowledge", "on", "five", "issues", "relevant", "to", "prion", "diseases:", "(1)", "how", "do", "prions", "enter", "the", "body,", "(2)", "how", "do", "prions", "reach", "the", "central", "nervous", "system,", "(3)", "how", "do", "prions", "damage", "the", "CNS,", "(4)", "do", "mammals", "have", "an", "antiprion", "defense", "system,", "and", "(5)", "how", "can", "the", "prion", "problem", "be", "resolved", "for", "good.", "How", "Do", "Prions", "Enter", "the", "Body?", "Most", "cases", "of", "human", "prion", "disease", "occur", "for", "unknown", "reasons,", "and", ".20", "mutations", "in", "the", "prion", "gene", "(PRNP)", "may", "lead", "to", "inherited", "prion", "disease.", "In", "other", "instances,", "prion", "diseases", "are", "contracted", "by", "exposure", "to", "prion", "infectivity.", "Save", "for", "direct", "brain", "exposure", "by", "neurosurgery,", "prions", "typically", "enter", "the", "body", "through", "extraneural", "pathways.", "This", "raises", "the", "intriguing", "question", "of", "how", "a", "mere", "protein", "aggregate", "can", "trespass", "mucosal", "barriers,", "circumvent", "innate", "and", "adaptive", "immunity,", "and", "travel", "across", "the", "blood–brain", "barrier", "to", "eventually", "provoke", "brain", "disease.", "Oral", "Uptake", "There", "is", "no", "doubt", "that", "prion", "infections", "can", "be", "efficaciously", "transmitted", "under", "both", "natural", "and", "human-made", "conditions.", "While", "some", "aspects", "of", "the", "natural", "transmission", "of", "scrapie", "and", "chronic", "wasting", "disease", "(CWD)", "remain", "unexplained,", "oral", "transmission", "of", "prions", "has", "caused", "large", "epidemics", "and", "epizootics.", "Kuru,", "a", "human", "prion", "disease", "transmitted", "through", "ritual", "cannibalism,", "has", "afflicted", "the", "Fore", "people", "of", "Northern", "Papua", "New", "Guinea", "at", "extraordinarily", "high", "rates.", "Bovine", "spongiform", "encephalopathy", "(BSE),", "which", "has", "killed", "more", "than", "280,000", "cattle", "worldwide,", "is", "a", "prion", "disease", "caused", "by", "the", "feeding", "of", "recycled", "prion-infected", "foodstuff", "to", "cattle", "[1].", "In", "turn,", "variant", "Creutzfeldt-", "Jacob", "Disease", "(vCJD),", "which", "has", "claimed", "over", "200", "victims,", "appears", "to", "be", "caused", "by", "consumption", "of", "BSE-contaminated", "beef", "products", "[2].", "Parenteral", "Uptake", "Prions", "can", "also", "enter", "the", "body", "via", "parenteral", "uptake.", "Most", "worryingly,", "vCJD", "has", "been", "transmitted", "from", "subclinically", "vCJD-", "infected", "donors", "to", "recipients", "of", "transfused", "non-leukocyte-reduced", "red", "cells", "and", "of", "purified", "factor", "VIII", "preparations", "[3].", "By", "far", "the", "largest", "incident", "involving", "iatrogenic", "prion", "transmission", "involved", "human", "pituitary", "hormones.", "Before", "the", "advent", "of", "recombinant", "DNA", "technology,", "growth", "hormone", "(used", "to", "treat", "dwarfism)", "and", "fertility", "hormones", "were", "recovered", "from", "human", "cadaveric", "pituitary", "glands.", "The", "prevalence", "of", "subclinically", "CJD-affected", "donors,", "probably", "coupled", "with", "brain-tissue", "contamination", "of", "pituitary", "extracts,", "led", "to", "over", "160", "prion", "deaths", "in", "mostly", "young", "recipients.", "Experimentally,", "the", "parenteral", "route", "of", "prion", "transmission", "is", "very", "effective", "and,", "e.g.,", "intraperitoneal", "(i.p)", "inoculation", "of", "prions", "to", "laboratory", "animals", "is", "a", "widely", "used", "route", "for", "studies", "of", "peripheral", "prion", "replication", "and", "neuroinvasion.", "Intracerebral", "Administration", "The", "most", "efficient", "way", "of", "prion", "transmission", "is", "intracerebral", "(i.c)", "administration.", "This", "is", "not", "unexpected,", "since", "the", "brain", "is", "the", "main", "target", "of", "prion", "toxicity", "and", "administration", "to", "the", "brain", "bypasses", "all", "natural", "barriers", "to", "prion", "neuroinvasion,", "such", "as", "the", "innate", "and", "adaptive", "immune", "system,", "as", "well", "as", "the", "blood–brain", "barrier.", "Several", "iatrogenic", "CJD", "(iCJD)", "transmissions", "occurred", "via", "neurosurgery", "and", "dura", "mater", "grafts.", "These", "cases", "were", "particularly", "tragic", "for", "all", "those", "involved", "because", "they", "were", "inadvertently", "caused", "by", "medical", "personnel", "and", "represented", "an", "untoward", "effect", "of", "the", "intent", "to", "treat", "other", "ailments.", "Some", "of", "the", "first", "well-", "documented", "instances", "of", "intracerebral", "prion", "transmission", "to", "humans", "occurred", "in", "Zu¨", "rich", "in", "the", "1970s", "[4].", "Electrodes", "were", "used", "for", "stereotactic", "electroencephalographic", "(EEG)", "recordings", "in", "a", "CJD", "patient,", "and", "reused", "after", "sterilization", "with", "ethanol", "and", "formaldehyde", "vapors—a", "procedure", "that", "reliably", "inactivates", "viruses", "and", "bacteria,", "but", "is", "ineffective", "against", "prions.", "This", "resulted", "in", "fatal", "prion", "transmission", "to", "two", "young", "patients.", "The", "infectivity", "on", "these", "electrodes", "was", "later", "confirmed", "by", "transmission", "of", "CJD", "to", "a", "chimpanzee.", "Aerosols", "Prion", "transmission", "is", "usually", "not", "considered", "to", "be", "airborne", "like", "influenza", "or", "chicken", "pox.", "But", "we", "and", "others", "recently", "have", "found", "that", "prions", "can", "also", "be", "efficiently", "transmitted", "to", "mice", "through", "aerosols", "[5,6].", "Although", "aerosol-transmitted", "prions", "have", "never", "been", "found", "under", "natural", "conditions,", "this", "finding", "highlights", "the", "necessity", "of", "revising", "the", "current", "prion-related", "biosafety", "guidelines", "and", "health", "standards", "in", "diagnostic", "and", "scientific", "laboratories", "being", "potentially", "confronted", "with", "prion-", "infected", "materials.", "Citation:", "Aguzzi", "A,", "Zhu", "C", "(2012)", "Five", "Questions", "on", "Prion", "Diseases.", "PLoS", "Pathog", "8(5):", "e1002651.", "doi:10.1371/journal.ppat.1002651", "Editor:", "Heather", "True-Krob,", "Washington", "University", "School", "of", "Medicine,", "United", "States", "of", "America", "Published", "May", "3,", "2012", "Copyright:", "2012", "Aguzzi,", "Zhu.", "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", "funded", "by", "European", "Research", "Council", "(ERC)", "Advanced", "Grant", "to", "Adriano", "Aguzzi", "(#", "250356),", "by", "the", "Swiss", "National", "Science", "Foundation", "(#", "3100A0-125927/1),", "the", "Center", "of", "Transgenesis", "Expertise", "of", "the", "National", "Center", "of", "Competence", "in", "Research", "‘‘Neural", "Plasticity", "and", "Repair’’,", "by", "a", "Sinergia", "grant", "from", "Swiss", "National", "Science", "Foundation", "(#", "CRSI33_125073),", "by", "an", "unrestricted", "grant", "of", "the", "Novartis", "Research", "Foundation,", "and", "by", "the", "European", "Union", "Framework", "7", "programs", "PRIORITY", "(#", "222887),", "LUPAS", "(#", "242098)", "and", "NeuriNox", "(#", "278611).", "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:", "adriano.aguzzi@usz.ch", "PLoS", "Pathogens", "|", "www.plospathogens.org", "1", "May", "2012", "|", "Volume", "8", "|", "Issue", "5", "|", "e1002651" ]

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[ "Endow", "and", "Hallen", "BMC", "Cell", "Biology", "2011,", "12:1", "http://www.biomedcentral.com/1471-2121/12/1", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "Anastral", "spindle", "assembly", "and", "g-tubulin", "in", "Drosophila", "oocytes", "Sharyn", "A", "Endow*,", "Mark", "A", "Hallen", "Abstract", "Background:", "Anastral", "spindles", "assemble", "by", "a", "mechanism", "that", "involves", "microtubule", "nucleation", "and", "growth", "from", "chromatin.", "It", "is", "still", "uncertain", "whether", "g-tubulin,", "a", "microtubule", "nucleator", "essential", "for", "mitotic", "spindle", "assembly", "and", "maintenance,", "plays", "a", "role.", "Not", "only", "is", "the", "requirement", "for", "g-tubulin", "to", "form", "anastral", "Drosophila", "oocyte", "meiosis", "I", "spindles", "controversial,", "but", "its", "presence", "in", "oocyte", "meiosis", "I", "spindles", "has", "not", "been", "demonstrated", "and", "is", "uncertain.", "Results:", "We", "show,", "for", "the", "first", "time,", "using", "a", "bright", "GFP", "fusion", "protein", "and", "live", "imaging,", "that", "the", "Drosophila", "maternally-expressed", "gTub37C", "is", "present", "at", "low", "levels", "in", "oocyte", "meiosis", "I", "spindles.", "Despite", "this,", "we", "find", "that", "formation", "of", "bipolar", "meiosis", "I", "spindles", "does", "not", "require", "functional", "gTub37C,", "extending", "previous", "findings", "by", "others.", "Fluorescence", "photobleaching", "assays", "show", "rapid", "recovery", "of", "gTub37C", "in", "the", "meiosis", "I", "spindle,", "similar", "to", "the", "cytoplasm,", "indicating", "weak", "binding", "by", "gTub37C", "to", "spindles,", "and", "fits", "of", "a", "new,", "potentially", "more", "accurate", "model", "for", "fluorescence", "recovery", "yield", "kinetic", "parameters", "consistent", "with", "transient,", "diffusional", "binding.", "Conclusions:", "The", "FRAP", "results,", "together", "with", "its", "mutant", "effects", "late", "in", "meiosis", "I,", "indicate", "that", "gTub37C", "may", "perform", "a", "role", "subsequent", "to", "metaphase", "I,", "rather", "than", "nucleating", "microtubules", "for", "meiosis", "I", "spindle", "formation.", "Weak", "binding", "to", "the", "meiosis", "I", "spindle", "could", "stabilize", "pre-existing", "microtubules", "or", "position", "g-tubulin", "for", "function", "during", "meiosis", "II", "spindle", "assembly,", "which", "follows", "rapidly", "upon", "oocyte", "activation", "and", "completion", "of", "the", "meiosis", "I", "division.", "Background", "Anastral", "spindles", "assemble", "without", "centrosomes", "by", "a", "pathway", "that", "is", "still", "not", "fully", "understood.", "In", "particular,", "the", "mechanism", "by", "which", "microtubule", "nucleation", "occurs", "has", "not", "been", "well", "defined.", "Although", "chromatin", "has", "been", "shown", "to", "play", "an", "essential", "role", "[1],", "the", "involvement", "of", "the", "microtubule", "nucleator,", "g-tubulin,", "is", "still", "an", "open", "question.", "g-Tubulin", "localizes", "to", "centrosomes", "and", "other", "microtubule", "organizing", "centers", "in", "mitosis", "and", "is", "essential", "for", "nucleating", "microtubules", "in", "organisms", "as", "diverse", "as", "yeast,", "Drosophila,", "Xenopus,", "humans,", "and", "higher", "plants", "[2-5].", "g-Tubulin", "is", "also", "found", "on", "spindle", "microtubules,", "where", "it", "has", "been", "proposed", "to", "nucleate", "microtubules", "for", "spindle", "maintenance", "by", "functioning", "in", "a", "chromatin-", "mediated", "nucleation", "pathway", "that", "augments", "the", "domi-", "nant", "pathway", "of", "nucleation", "by", "centrosomes", "[6,7].", "g-Tubulin", "is", "present", "in", "cells", "as", "a", "large", "ring", "complex,", "gTuRC,", "comprising", "12-13", "g-tubulin", "molecules", "associated", "*", "Correspondence:", "endow@duke.edu", "Department", "of", "Cell", "Biology", "and", "Structural", "Biology", "&", "Biophysics", "Program,", "Duke", "University", "with", "as", "many", "as", "~7-8", "other", "proteins", "[8,9].", "gTuRC", "forms", "from", "a", "small", "complex,", "gTuSC,", "consisting", "of", "g-tubulin", "bound", "to", "two", "other", "proteins", "[10-12].", "The", "mechanism", "by", "which", "gTuRC", "nucleates", "microtubules", "is", "uncertain", "-", "it", "could", "serve", "as", "a", "ring-like", "template", "for", "a", "12-or", "13-", "protofilament", "microtubule", "[13,14]", "or,", "alternatively,", "a/b", "tubulin", "dimers", "could", "assemble", "onto", "an", "end", "of", "the", "large", "ring", "complex", "to", "form", "individual", "protofilaments", "[15].", "Although", "g-tubulin", "is", "believed", "to", "play", "a", "central", "role", "in", "mitotic", "spindle", "assembly", "and", "maintenance", "in", "many", "organisms,", "its", "role", "in", "anastral", "spindles", "that", "lack", "centro-", "somes", "is", "less", "certain.", "Analysis", "of", "mutants", "that", "affect", "the", "Drosophila", "oocyte-", "and", "early", "embryo-specific", "gTub37C", "[16]", "has", "led", "to", "the", "conclusion", "that", "g-tubulin", "plays", "an", "essential", "role", "in", "nucleating", "microtubules", "for", "anastral", "oocyte", "meiosis", "I", "(MI)", "spindle", "assembly", "[17].", "Conflict-", "ingly,", "another", "study", "of", "the", "same", "mutants", "concluded", "that", "g-tubulin", "is", "not", "required", "for", "oocyte", "MI", "spindle", "forma-", "tion", "[18].", "Moreover,", "attempts", "by", "several", "groups", "to", "stain", "oocyte", "MI", "spindles", "using", "anti-gTub37C", "antibodies", "have", "©", "2011", "Endow", "and", "Hallen;", "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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"clinical", "features", "for", "some", "of", "these", "diseases,", "indicate", "that", "common", "pathways", "may", "contribute", "to", "pathology.", "Multiple", "mechanisms,", "mediated", "by", "both", "expanded", "homopolymeric", "proteins", "and", "expanded", "repeat", "RNA,", "have", "been", "identified", "by", "the", "use", "of", "model", "systems,", "that", "may", "account", "for", "shared", "pathology.", "The", "use", "of", "such", "animal", "models", "enables", "identification", "of", "distinct", "pathways", "and", "their", "‘molecular", "hallmarks’", "that", "can", "be", "used", "to", "determine", "the", "contribution", "of", "each", "pathway", "in", "human", "pathology.", "Here", "we", "characterise", "a", "tergite", "disruption", "phenotype", "in", "adult", "flies,", "caused", "by", "ubiquitous", "expression", "of", "either", "untranslated", "CUG", "or", "CAG", "expanded", "repeat", "RNA.", "Using", "the", "tergite", "phenotype", "as", "a", "quantitative", "trait", "we", "define", "a", "new", "genetic", "system", "in", "which", "to", "examine", "‘hairpin’", "repeat", "RNA-mediated", "cellular", "perturbation.", "Further", "experiments", "use", "this", "system", "to", "examine", "whether", "pathways", "involving", "Muscleblind", "sequestration", "or", "Dicer", "processing,", "which", "have", "been", "shown", "to", "mediate", "repeat", "RNA-", "mediated", "pathology", "in", "other", "model", "systems,", "contribute", "to", "cellular", "perturbation", "in", "this", "model.", "Citation:", "Lawlor", "KT,", "O’Keefe", "LV,", "Samaraweera", "SE,", "van", "Eyk", "CL,", "Richards", "RI", "(2012)", "Ubiquitous", "Expression", "of", "CUG", "or", "CAG", "Trinucleotide", "Repeat", "RNA", "Causes", "Common", "Morphological", "Defects", "in", "a", "Drosophila", "Model", "of", "RNA-Mediated", "Pathology.", "PLoS", "ONE", "7(6):", "e38516.", "doi:10.1371/journal.pone.0038516", "Editor:", "Diego", "E.", "Rincon-Limas,", "University", "of", "Florida,", "United", "States", "of", "America", "Received", "February", "9,", "2012;", "Accepted", "May", "8,", "2012;", "Published", "June", "8,", "2012", "Copyright:", "2012", "Lawlor", "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", "Australian", "Postgraduate", "Awards", "(to", "KTL,", "SES", "and", "CLvE);", "a", "National", "Health", "and", "Medical", "Research", "Council", "Peter", "Doherty", "Fellowship", "(fellowship", "number", "207830", "to", "LVO);", "project", "grants", "from", "the", "National", "Health", "and", "Medical", "Research", "Council", "(grant", "numbers", "453674,", "627183", "to", "RIR", "and", "LVO);", "and", "the", "Australian", "Research", "Council", "Special", "Research", "Centre", "for", "the", "Molecular", "Genetics", "of", "Development.", "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:", "robert.richards@adelaide.edu.au", "Introduction", "The", "expansion", "of", "polymorphic", "repeat", "sequences", "(dynamic", "mutation)", "is", "responsible", "for", "over", "20", "human", "diseases,", "including", "Huntington’s", "disease", "(HD),", "myotonic", "dystrophy", "and", "several", "types", "of", "spinocerebellar", "ataxia", "(SCA)", "[1–3].", "In", "all", "cases", "affected", "individuals", "inherit", "a", "repeat", "number", "that", "exceeds", "a", "pathogenic", "threshold.", "Increased", "disease", "severity", "and", "earlier", "age-of-onset", "are", "correlated", "with", "repeat", "length", "expansion,", "which", "occurs", "within", "successive", "generations", "[1–3].", "Expansion", "is", "associated", "with", "loss", "of", "repeat-containing", "gene", "function", "and", "recessive", "inheritance", "in", "a", "few", "cases", "[4,5],", "however", "the", "majority", "of", "diseases", "appear", "to", "be", "caused", "by", "dominant,", "repeat-mediated", "mechanisms.", "As", "well", "as", "a", "shared", "genetic", "basis,", "many", "diseases", "show", "similar", "clinical", "features,", "including", "late", "onset", "neurodegeneration", "and", "movement", "disorder,", "highlighting", "the", "possibility", "that", "common", "pathways", "contribute", "to", "pathology", "in", "most,", "if", "not", "all", "cases", "of", "dominantly", "inherited", "dynamic", "mutation", "[1–3,6].", "In", "diseases", "including", "HD", "and", "some", "types", "of", "SCA,", "expanded", "CAG", "trinucleotide", "repeats", "are", "found", "within", "a", "coding", "region,", "producing", "an", "expanded", "polyglutamine", "tract", "within", "the", "final", "protein", "[2].", "Polyglutamine", "is", "able", "to", "cause", "pathology", "through", "multiple", "possible", "pathways,", "including", "gain-of-function", "interactions", "inherent", "to", "the", "expanded", "protein", "tract", "and", "alterations", "to", "normal", "protein", "function", "[3,7,8].", "Nevertheless,", "polyglutamine", "protein-", "mediated", "pathology", "is", "not", "able", "to", "account", "for", "diseases", "where", "repeats", "are", "unable", "to", "encode", "polyglutamine,", "due", "to", "the", "repeat", "sequence", "composition", "and/or", "presence", "of", "the", "repeat", "tract", "within", "non-coding", "regions", "of", "the", "associated", "gene.", "This", "class", "of", "‘untranslated’", "repeat", "diseases", "share", "similar", "repeat", "sequences,", "pathogenic", "thresholds", "and", "clinical", "features", "with", "the", "‘polygluta-", "mine’", "diseases", "and", "includes", "myotonic", "dystrophy", "type", "1", "(DM1)", "and", "2", "(DM2),", "Huntington’s", "disease-like-2", "(HDL-2),", "fragile", "X", "tremor/", "ataxia", "syndrome", "(FXTAS)", "and", "SCA8,", "10", "and", "12.", "In", "these", "diseases,", "gain-of-function", "properties", "of", "the", "expanded", "repeat", "RNA", "transcript", "appear", "to", "be", "responsible", "for", "dominant", "pathology", "[9–11].", "Since", "repeat-containing", "RNA", "is", "present", "whether", "repeats", "are", "coding", "or", "non-coding,", "it", "may", "also", "represent", "a", "common", "contributor", "to", "all", "the", "dominant", "expanded", "repeat", "diseases.", "Studies", "have", "reported", "the", "ability", "of", "repeat", "RNA", "to", "cause", "pathology", "in", "animal", "and", "cellular", "model", "systems,", "via", "multiple,", "and", "likely", "distinct", "pathways", "[12–21].", "Pathology", "due", "to", "expanded", "repeat", "RNA", "was", "first", "attributed", "in", "DM1,", "caused", "by", "a", "non-coding", "CUG", "repeat", "within", "the", "39UTR", "of", "the", "dystrophia", "myotonica-protein", "kinase", "(DMPK)", "gene,", "and", "DM2,", "caused", "by", "a", "non-coding", "CCUG", "repeat", "within", "an", "intron", "of", "ZNF9", "(now", "called", "CNBP)", "[22,23].", "Expanded", "repeat", "RNA", "transcripts", "form", "a", "‘hairpin’", "secondary", "structure,", "which", "is", "able", "to", "bind", "and", "sequester", "specific", "RNA-binding", "proteins", "[24–26].", "The", "most", "extensively", "characterised", "of", "these", "is", "Muscleblind-like", "1", "(MBNL-1),", "which", "is", "PLoS", "ONE", "|", "www.plosone.org", "1", "June", "2012", "|", "Volume", "7", "|", "Issue", "6", "|", "e38516" ]

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[ "Liguori", "et", "al.", "BMC", "Microbiology", "2010,", "10:19", "http://www.biomedcentral.com/1471-2180/10/19", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "Microbiological", "quality", "of", "drinking", "water", "from", "dispensers", "in", "Italy", "Giorgio", "Liguori,", "Ivan", "Cavallotti,", "Antonio", "Arnese,", "Ciro", "Amiranda,", "Daniela", "Anastasi,", "Italo", "F", "Angelillo*", "Abstract", "Background:", "Water", "coolers", "are", "popular", "in", "office", "buildings", "and", "commercial", "stores", "and", "the", "quality", "of", "this", "source", "of", "drinking", "water", "has", "the", "potential", "to", "cause", "waterborne", "outbreaks,", "especially", "in", "sensitive", "and", "immunocompromised", "subjects.", "The", "aim", "of", "this", "study", "was", "to", "determine", "the", "quality", "of", "water", "plumbed", "in", "coolers", "from", "commercial", "stores", "in", "comparison", "with", "tap", "water", "in", "Italy.", "Methods:", "For", "each", "sample,", "microbial", "parameters", "and", "chemical", "indicators", "of", "contamination", "were", "evaluated", "and", "information", "about", "the", "date", "of", "installation,", "time", "since", "last", "ordinary", "and", "extraordinary", "maintenance", "of", "water", "coolers", "was", "collected.", "Results:", "In", "all", "samples", "the", "chemical", "parameters", "(nitrite,", "ammonium,", "free", "active", "chlorine", "residual)", "did", "not", "exceed", "the", "reference", "values", "of", "the", "drinking", "water", "regulation;", "the", "pH", "value", "in", "86.8%", "samples", "of", "the", "carbonated", "waters", "was", "lower", "than", "the", "reference", "limit.", "The", "microbiological", "results", "indicated", "that", "the", "bacteria", "count", "at", "22°C", "and", "37°C", "was", "higher", "than", "the", "required", "values", "in", "71%", "and", "81%", "for", "the", "non-carbonated", "water", "and", "in", "86%", "and", "88%", "for", "the", "carbonated", "one,", "respectively.", "Enterococcus", "spp.", "and", "Escherichia", "coli", "were", "not", "detected", "in", "any", "of", "the", "water", "samples.", "Pseudomonas", "aeruginosa", "was", "found", "in", "only", "one", "sample", "of", "the", "tap", "water", "and", "in", "28.9%", "and", "23.7%", "of", "the", "non-", "carbonated", "and", "carbonated", "water", "samples,", "respectively.", "No", "statistically", "significant", "differences", "in", "bacterial", "counts", "at", "22°C", "and", "37°C", "have", "been", "found", "between", "the", "non-carbonated", "and", "carbonated", "water", "from", "the", "sampled", "coolers", "in", "relation", "with", "the", "time", "since", "the", "last", "filter", "was", "substituted.", "The", "bacteriological", "quality", "of", "tap", "water", "was", "superior", "to", "that", "of", "non-carbonated", "and", "carbonated", "water", "from", "coolers.", "Conclusion:", "The", "results", "emphasize", "the", "importance", "of", "adopting", "appropriate", "routinely", "monitoring", "system", "in", "order", "to", "prevent", "or", "to", "diminish", "the", "chances", "of", "contamination", "of", "this", "water", "source.", "Background", "It", "is", "well", "known", "that", "the", "quality", "and", "safety", "of", "the", "drink-", "ing", "water", "continues", "to", "be", "an", "important", "public", "health", "issue", "[1,2],", "because", "its", "contamination", "has", "been", "fre-", "quently", "described", "as", "responsible", "for", "the", "transmission", "of", "infectious", "diseases", "that", "have", "caused", "serious", "illnesses", "and", "associated", "mortality", "worldwide", "[3-6].", "Clearly,", "point-of-", "use", "water", "quality", "is", "a", "critical", "public", "health", "indicator", "[2].", "Over", "the", "past", "decade,", "there", "has", "been", "a", "markedly", "increase", "in", "the", "consumption", "of", "water", "derived", "from", "dif-", "ferent", "sources", "in", "place", "of", "tap", "water", "for", "drinking", "use", "in", "many", "regions", "of", "the", "world.", "One", "of", "these", "alternative", "sources", "is", "the", "water", "from", "dispensers,", "which", "is", "popular", "mainly", "in", "office", "buildings", "and", "commercial", "stores,", "that", "*", "Correspondence:", "italof.angelillo@unina2.it", "Department", "of", "Public,", "Clinical", "and", "Preventive", "Medicine,", "Second", "University", "of", "Naples,", "Naples,", "Italy", "are", "often", "presented", "as", "systems", "that", "are", "able", "to", "improve", "some", "characteristics", "of", "water", "and", "easy", "to", "use", "and", "to", "maintain.", "However,", "concerns", "have", "been", "sometimes", "raised", "about", "the", "quality", "of", "this", "source", "due", "to", "its", "poten-", "tial", "to", "cause", "waterborne", "outbreaks", "associated", "with", "drinking", "water,", "particularly", "in", "sensitive", "and", "immuno-", "compromised", "populations", "[2].", "International", "drinking", "water-quality", "monitoring", "pro-", "grams", "have", "been", "established", "in", "order", "to", "prevent", "or", "to", "reduce", "the", "risk", "of", "contracting", "water", "related", "infections.", "In", "Italy,", "the", "water", "for", "human", "consumption,", "including", "the", "water", "coming", "from", "dispensers,", "according", "to", "the", "Eur-", "opean", "Community", "Directive", "guidelines,", "is", "required", "to", "be", "free", "from", "any", "pathogenic", "microorganism", "as", "well", "as", "che-", "mical", "contaminations,", "which", "may", "be", "hazardous", "to", "the", "human", "health", "[7,8].", "©", "2010", "Liguori", "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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"reflected", "by", "the", "high", "incidence", "of", "arrhythmias", "in", "cardiac", "sodium", "channelopathies,", "i.e.,", "arrhythmogenic", "diseases", "in", "patients", "with", "mutations", "in", "SCN5A,", "the", "gene", "responsible", "for", "the", "pore-forming", "ion-", "conducting", "α-subunit,", "or", "in", "genes", "that", "encode", "the", "ancillary", "β-subunits", "or", "regulatory", "proteins", "of", "the", "cardiac", "sodium", "channel.", "While", "clinical", "and", "genetic", "studies", "have", "laid", "the", "foundation", "for", "our", "understanding", "of", "cardiac", "sodium", "channe-", "lopathies", "by", "establishing", "links", "between", "arrhythmogenic", "diseases", "and", "mutations", "in", "genes", "that", "encode", "various", "subunits", "of", "the", "cardiac", "sodium", "channel,", "biophysical", "studies", "(particularly", "in", "heterologous", "expression", "systems", "and", "transgenic", "mouse", "models)", "have", "provided", "insights", "into", "the", "mechanisms", "by", "which", "INa", "dysfunction", "causes", "disease", "in", "such", "channelopathies.", "It", "is", "now", "recognized", "that", "mutations", "that", "increase", "INa", "delay", "cardiac", "repolarization,", "prolong", "action", "potential", "duration,", "and", "cause", "long", "QT", "syndrome,", "while", "mutations", "that", "reduce", "INa", "decrease", "cardiac", "excitability,", "reduce", "electrical", "conduction", "velocity,", "and", "Grant", "support", "Dr.", "Tan", "was", "supported", "by", "the", "Netherlands", "Organization", "for", "Scientific", "Research", "(NWO,", "grant", "ZonMW", "Vici", "918.86.616).", "A.", "S.", "Amin", ":", "A.", "Asghari-Roodsari", "Heart", "Failure", "Research", "Center,", "Academic", "Medical", "Center,", "University", "of", "Amsterdam,", "Amsterdam,", "the", "Netherlands", "H.", "L.", "Tan", "(*)", "Department", "of", "Cardiology,", "Heart", "Failure", "Research", "Center,", "Academic", "Medical", "Center,", "University", "of", "Amsterdam,", "Room", "K2-109,", "Meibergdreef", "9,", "Amsterdam,", "1105", "AZ,", "the", "Netherlands", "e-mail:", "h.l.tan@amc.nl", "induce", "Brugada", "syndrome,", "progressive", "cardiac", "conduction", "disease,", "sick", "sinus", "syndrome,", "or", "combinations", "thereof.", "Recently,", "mutation-induced", "INa", "dysfunction", "was", "also", "linked", "to", "dilated", "cardiomyopathy,", "atrial", "fibrillation,", "and", "sudden", "infant", "death", "syndrome.", "This", "review", "describes", "the", "structure", "and", "function", "of", "the", "cardiac", "sodium", "channel", "and", "its", "various", "subunits,", "summarizes", "major", "cardiac", "sodium", "channelopathies", "and", "the", "current", "knowledge", "concerning", "their", "genetic", "back-", "ground", "and", "underlying", "molecular", "mechanisms,", "and", "discusses", "recent", "advances", "in", "the", "discovery", "of", "mutation-specific", "therapies", "in", "the", "management", "of", "these", "channelopathies.", "Keywords", "Arrhythmia", ".", "Action", "potential", ".", "Cardiac", "electrophysiology", ".", "Cardiomyocyte", ".", "Ion", "channels", "Introduction", "Cardiac", "sodium", "channels", "are", "transmembrane", "proteins", "that", "are", "located", "in", "the", "sarcolemma", "of", "atrial", "and", "ventricular", "myocytes", "and", "the", "Purkinje", "fibers.", "They", "enable", "a", "large", "and", "rapid", "influx", "of", "sodium", "ions", "(sodium", "current;", "INa)", "during", "the", "rapid", "upstroke", "(phase", "0)", "of", "the", "cardiac", "action", "potential.", "INa", "underlies", "the", "initiation", "and", "propagation", "of", "action", "potentials,", "and,", "by", "doing", "so,", "it", "determines", "cardiac", "excitability", "and", "conduction", "velocity", "of", "electrical", "stimuli", "through", "the", "heart", "(Fig.", "1a,", "b)", "[9].", "To", "a", "lesser", "extent,", "cardiac", "sodium", "channels", "are", "also", "present", "in", "the", "sinoatrial", "node", "and", "the", "atrioventric-", "ular", "node,", "where", "they", "contribute", "to", "pacemaker", "activity", "[45].", "The", "importance", "of", "sodium", "channels", "for", "normal", "electrical", "activity", "of", "the", "heart", "is", "emphasized", "in", "arrhythmogenic", "diseases", "caused", "by", "inherited", "or", "de", "novo", "(mostly", "heterozy-", "gous)", "mutations", "in", "SCN5A,", "the", "gene", "that", "encodes", "the", "cardiac", "sodium", "channel", "(“cardiac", "sodium", "channelopathies”).", "These", "diseases", "include", "long", "QT", "syndrome", "type", "3", "(LQT-3),", "Brugada" ]

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